Sample records for fluid migration pathways

  1. Gas Migration Processes through the Gas Hydrate Stability Zone at Four-Way Closure Ridge Offshore SW Taiwan

    NASA Astrophysics Data System (ADS)

    Kunath, P.; Chi, W. C.; Berndt, C.; Liu, C. S.

    2016-12-01

    We have used 3D P-Cable seismic data from Four-Way-Closure Ridge, a NW-SE trending anticlinal ridge within the lower slope domain of accretionary wedge, to investigate the geological constraints influencing the fluid migration pattern in the shallow marine sediments. In the seismic data, fluid migration feature manifests itself as high reflection layers of dipping strata, which originate underneath a bottom simulating reflector (BSR) and extend towards the seafloor. Shoaling of the BSR near fluid migration pathways indicates a focused fluid flux, perturbing the temperature field. Furthermore, seafloor video footage confirmed the presence of recent methane seepage above seismically imaged fluid migration pathways. We plan to test two hypotheses for the occurrence of these fluid migration pathways: 1) the extensional regime under the anticlinal ridge crest caused the initiation of localized fault zones, acting as fluid conduits in the gas hydrate stability zone (GHSZ). 2) sediment deformation induced by focused fluid flow and massive growth and dissolution of gas hydrate, similar to processes controlling the evolution of pockmarks on the Nigerian continental margin. We suggest that these processes may be responsible for the formation of a massive hydrate core in the crest of the anticline, as inferred from other geophysical datasets. Triggering process for fluid migration cannot be clearly defined. However, the existence of blind thrust faults may help to advect deep-seated fluids. This may be augmented by biogenic production of shallow gas underneath the ridge, where the excess of gas enables the coexistence of gas, water, and gas hydrate within the GHSZ. Fluid migration structures may exists because of the buoyancy of gas-bearing fluids. This study shows a potential model on how gas-bearing fluids migrate upward towards structural highs, which might occur in other anticlinal structures around the world. Keywords: P-Cable, gas-hydrate, fluid flow, fault-related fold, methane seepage

  2. Hydraulic fracturing fluid migration in the subsurface: A review and expanded modeling results

    NASA Astrophysics Data System (ADS)

    Birdsell, Daniel T.; Rajaram, Harihar; Dempsey, David; Viswanathan, Hari S.

    2015-09-01

    Understanding the transport of hydraulic fracturing (HF) fluid that is injected into the deep subsurface for shale gas extraction is important to ensure that shallow drinking water aquifers are not contaminated. Topographically driven flow, overpressured shale reservoirs, permeable pathways such as faults or leaky wellbores, the increased formation pressure due to HF fluid injection, and the density contrast of the HF fluid to the surrounding brine can encourage upward HF fluid migration. In contrast, the very low shale permeability and capillary imbibition of water into partially saturated shale may sequester much of the HF fluid, and well production will remove HF fluid from the subsurface. We review the literature on important aspects of HF fluid migration. Single-phase flow and transport simulations are performed to quantify how much HF fluid is removed via the wellbore with flowback and produced water, how much reaches overlying aquifers, and how much is permanently sequestered by capillary imbibition, which is treated as a sink term based on a semianalytical, one-dimensional solution for two-phase flow. These simulations include all of the important aspects of HF fluid migration identified in the literature review and are performed in five stages to faithfully represent the typical operation of a hydraulically fractured well. No fracturing fluid reaches the aquifer without a permeable pathway. In the presence of a permeable pathway, 10 times more fracturing fluid reaches the aquifer if well production and capillary imbibition are not included in the model.

  3. 3D seismic detection of shallow faults and fluid migration pathways offshore Southern Costa Rica: Application of neural-network meta-attributes

    NASA Astrophysics Data System (ADS)

    Kluesner, J. W.; Silver, E. A.; Nale, S. M.; Bangs, N. L.; McIntosh, K. D.

    2013-12-01

    We employ a seismic meta-attribute workflow to detect and analyze probable faults and fluid-pathways in 3D within the sedimentary section offshore Southern Costa Rica. During the CRISP seismic survey in 2011 we collected an 11 x 55 km grid of 3D seismic reflection data and high-resolvability EM122 multibeam data, with coverage extending from the incoming plate to the outer-shelf. We mapped numerous seafloor seep indicators, with distributions ranging from the lower-slope to ~15 km landward of the shelf break [Kluesner et al., 2013, G3, doi:10.1002/ggge.20058; Silver et al., this meeting]. We used the OpendTect software package to calculate meta-attribute volumes from the 3D seismic data in order to detect and visualize seismic discontinuities in 3D. This methodology consists of dip-steered filtering to pre-condition the data, followed by combining a set of advanced dip-steered seismic attributes into a single object probability attribute using a user-trained neural-network pattern-recognition algorithm. The parameters of the advanced seismic attributes are set for optimal detection of the desired geologic discontinuity (e.g. faults or fluid-pathways). The product is a measure of probability for the desired target that ranges between 0 and 1, with 1 representing the highest probability. Within the sedimentary section of the CRISP survey the results indicate focused fluid-migration pathways along dense networks of intersecting normal faults with approximately N-S and E-W trends. This pattern extends from the middle slope to the outer-shelf region. Dense clusters of fluid-migration pathways are located above basement highs and deeply rooted reverse faults [see Bangs et al., this meeting], including a dense zone of fluid-pathways imaged below IODP Site U1413. In addition, fault intersections frequently show an increased signal of fluid-migration and these zones may act as major conduits for fluid-flow through the sedimentary cover. Imaged fluid pathways root into high-backscatter pockmarks and mounds on the seafloor, which are located atop folds and clustered along intersecting fault planes. Combining the fault and fluid-pathway attribute volumes reveals qualitative first order information on fault seal integrity within the CRISP survey region, highlighting which faults and/or fault sections appear to be sealing or leaking within the sedimentary section. These results provide 3D insight into the fluid-flow behavior offshore southern Costa Rica and suggest that fluids escaping through the deeper crustal rocks are predominantly channeled along faults in the sedimentary cover, especially at fault intersections.

  4. Drilling into a present-day migration pathway for hydrocarbons within a fault zone conduit in the Eugene Island 330 field, offshore Louisiana

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Anderson, R.N.

    1995-11-01

    Within the Global Basins Research Network, we have developed 4-D seismic analysis techniques that, when integrated with pressure and temperature mapping, production history, geochemical monitoring, and finite element modeling, allow for the imaging of active fluid migration in the subsurface. We have imaged fluid flow pathways that are actively recharging shallower hydrocarbon reservoirs in the Eugene Island 330 field, offshore Louisiana. The hydrocarbons appear to be sourcing from turbidite stacks within the salt-withdrawal mini-basin buried deep within geopressure. Fault zone conduits provide transient migration pathways out of geopressure. To accomplish this 4-D imaging, we use multiple 3-D seismic surveys donemore » several years apart over the same blocks. 3-D volume processing and attribute analysis algorithms are used to identify significant seismic amplitude interconnectivity and changes over time that result from active fluid migration. Pressures and temperatures are then mapped and modeled to pro- vide rate and timing constraints for the fluid movement. Geochemical variability observed in the shallow reservoirs is attributed to the mixing of new with old oils. The Department of Energy has funded an industry cost-sharing project to drill into one of these active conduits in Eugene Island Block 330. Active fluid flow was encountered within the fault zone in the field demonstration experiment, and hydrocarbons were recovered. The active migration events connecting shallow reservoirs to deep sourcing regions imply that large, heretofore undiscovered hydrocarbon reserves exist deep within geopressures along the deep continental shelf of the northern Gulf of Mexico.« less

  5. Numerical modeling of fracking fluid migration through fault zones and fractures in the North German Basin

    NASA Astrophysics Data System (ADS)

    Pfunt, Helena; Houben, Georg; Himmelsbach, Thomas

    2016-09-01

    Gas production from shale formations by hydraulic fracturing has raised concerns about the effects on the quality of fresh groundwater. The migration of injected fracking fluids towards the surface was investigated in the North German Basin, based on the known standard lithology. This included cases with natural preferential pathways such as permeable fault zones and fracture networks. Conservative assumptions were applied in the simulation of flow and mass transport triggered by a high pressure boundary of up to 50 MPa excess pressure. The results show no significant fluid migration for a case with undisturbed cap rocks and a maximum of 41 m vertical transport within a permeable fault zone during the pressurization. Open fractures, if present, strongly control the flow field and migration; here vertical transport of fracking fluids reaches up to 200 m during hydraulic fracturing simulation. Long-term transport of the injected water was simulated for 300 years. The fracking fluid rises vertically within the fault zone up to 485 m due to buoyancy. Progressively, it is transported horizontally into sandstone layers, following the natural groundwater flow direction. In the long-term, the injected fluids are diluted to minor concentrations. Despite the presence of permeable pathways, the injected fracking fluids in the reported model did not reach near-surface aquifers, either during the hydraulic fracturing or in the long term. Therefore, the probability of impacts on shallow groundwater by the rise of fracking fluids from a deep shale-gas formation through the geological underground to the surface is small.

  6. Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells

    PubMed Central

    Howes, Mark T.; Kirkham, Matthew; Riches, James; Cortese, Katia; Walser, Piers J.; Simpson, Fiona; Hill, Michelle M.; Jones, Alun; Lundmark, Richard; Lindsay, Margaret R.; Hernandez-Deviez, Delia J.; Hadzic, Gordana; McCluskey, Adam; Bashir, Rumasia; Liu, Libin; Pilch, Paul; McMahon, Harvey; Robinson, Phillip J.; Hancock, John F.; Mayor, Satyajit

    2010-01-01

    Although the importance of clathrin- and caveolin-independent endocytic pathways has recently emerged, key aspects of these routes remain unknown. Using quantitative ultrastructural approaches, we show that clathrin-independent carriers (CLICs) account for approximately three times the volume internalized by the clathrin-mediated endocytic pathway, forming the major pathway involved in uptake of fluid and bulk membrane in fibroblasts. Electron tomographic analysis of the 3D morphology of the earliest carriers shows that they are multidomain organelles that form a complex sorting station as they mature. Proteomic analysis provides direct links between CLICs, cellular adhesion turnover, and migration. Consistent with this, CLIC-mediated endocytosis of key cargo proteins, CD44 and Thy-1, is polarized at the leading edge of migrating fibroblasts, while transient ablation of CLICs impairs their ability to migrate. These studies provide the first quantitative ultrastructural analysis and molecular characterization of the major endocytic pathway in fibroblasts, a pathway that provides rapid membrane turnover at the leading edge of migrating cells. PMID:20713605

  7. Secondary migration and leakage of methane from a major tight-gas system

    NASA Astrophysics Data System (ADS)

    Wood, James M.; Sanei, Hamed

    2016-11-01

    Tight-gas and shale-gas systems can undergo significant depressurization during basin uplift and erosion of overburden due primarily to the natural leakage of hydrocarbon fluids. To date, geologic factors governing hydrocarbon leakage from such systems are poorly documented and understood. Here we show, in a study of produced natural gas from 1,907 petroleum wells drilled into a Triassic tight-gas system in western Canada, that hydrocarbon fluid loss is focused along distinct curvilinear pathways controlled by stratigraphic trends with superior matrix permeability and likely also structural trends with enhanced fracture permeability. Natural gas along these pathways is preferentially enriched in methane because of selective secondary migration and phase separation processes. The leakage and secondary migration of thermogenic methane to surficial strata is part of an ongoing carbon cycle in which organic carbon in the deep sedimentary basin transforms into methane, and ultimately reaches the near-surface groundwater and atmosphere.

  8. Secondary migration and leakage of methane from a major tight-gas system

    PubMed Central

    Wood, James M.; Sanei, Hamed

    2016-01-01

    Tight-gas and shale-gas systems can undergo significant depressurization during basin uplift and erosion of overburden due primarily to the natural leakage of hydrocarbon fluids. To date, geologic factors governing hydrocarbon leakage from such systems are poorly documented and understood. Here we show, in a study of produced natural gas from 1,907 petroleum wells drilled into a Triassic tight-gas system in western Canada, that hydrocarbon fluid loss is focused along distinct curvilinear pathways controlled by stratigraphic trends with superior matrix permeability and likely also structural trends with enhanced fracture permeability. Natural gas along these pathways is preferentially enriched in methane because of selective secondary migration and phase separation processes. The leakage and secondary migration of thermogenic methane to surficial strata is part of an ongoing carbon cycle in which organic carbon in the deep sedimentary basin transforms into methane, and ultimately reaches the near-surface groundwater and atmosphere. PMID:27874012

  9. Modeling Studies to Constrain Fluid and Gas Migration Associated with Hydraulic Fracturing Operations

    NASA Astrophysics Data System (ADS)

    Rajaram, H.; Birdsell, D.; Lackey, G.; Karra, S.; Viswanathan, H. S.; Dempsey, D.

    2015-12-01

    The dramatic increase in the extraction of unconventional oil and gas resources using horizontal wells and hydraulic fracturing (fracking) technologies has raised concerns about potential environmental impacts. Large volumes of hydraulic fracturing fluids are injected during fracking. Incidents of stray gas occurrence in shallow aquifers overlying shale gas reservoirs have been reported; whether these are in any way related to fracking continues to be debated. Computational models serve as useful tools for evaluating potential environmental impacts. We present modeling studies of hydraulic fracturing fluid and gas migration during the various stages of well operation, production, and subsequent plugging. The fluid migration models account for overpressure in the gas reservoir, density contrast between injected fluids and brine, imbibition into partially saturated shale, and well operations. Our results highlight the importance of representing the different stages of well operation consistently. Most importantly, well suction and imbibition both play a significant role in limiting upward migration of injected fluids, even in the presence of permeable connecting pathways. In an overall assessment, our fluid migration simulations suggest very low risk to groundwater aquifers when the vertical separation from a shale gas reservoir is of the order of 1000' or more. Multi-phase models of gas migration were developed to couple flow and transport in compromised wellbores and subsurface formations. These models are useful for evaluating both short-term and long-term scenarios of stray methane release. We present simulation results to evaluate mechanisms controlling stray gas migration, and explore relationships between bradenhead pressures and the likelihood of methane release and transport.

  10. Pathway from subducting slab to surface for melt and fluids beneath Mount Rainier.

    PubMed

    McGary, R Shane; Evans, Rob L; Wannamaker, Philip E; Elsenbeck, Jimmy; Rondenay, Stéphane

    2014-07-17

    Convergent margin volcanism originates with partial melting, primarily of the upper mantle, into which the subducting slab descends. Melting of this material can occur in one of two ways. The flow induced in the mantle by the slab can result in upwelling and melting through adiabatic decompression. Alternatively, fluids released from the descending slab through dehydration reactions can migrate into the hot mantle wedge, inducing melting by lowering the solidus temperature. The two mechanisms are not mutually exclusive. In either case, the buoyant melts make their way towards the surface to reside in the crust or to be extruded as lava. Here we use magnetotelluric data collected across the central state of Washington, USA, to image the complete pathway for the fluid-melt phase. By incorporating constraints from a collocated seismic study into the magnetotelluric inversion process, we obtain superior constraints on the fluids and melt in a subduction setting. Specifically, we are able to identify and connect fluid release at or near the top of the slab, migration of fluids into the overlying mantle wedge, melting in the wedge, and transport of the melt/fluid phase to a reservoir in the crust beneath Mt Rainier.

  11. Pathway from subducting slab to surface for melt and fluids beneath Mount Rainier

    NASA Astrophysics Data System (ADS)

    McGary, R. Shane; Evans, Rob L.; Wannamaker, Philip E.; Elsenbeck, Jimmy; Rondenay, Stéphane

    2014-07-01

    Convergent margin volcanism originates with partial melting, primarily of the upper mantle, into which the subducting slab descends. Melting of this material can occur in one of two ways. The flow induced in the mantle by the slab can result in upwelling and melting through adiabatic decompression. Alternatively, fluids released from the descending slab through dehydration reactions can migrate into the hot mantle wedge, inducing melting by lowering the solidus temperature. The two mechanisms are not mutually exclusive. In either case, the buoyant melts make their way towards the surface to reside in the crust or to be extruded as lava. Here we use magnetotelluric data collected across the central state of Washington, USA, to image the complete pathway for the fluid-melt phase. By incorporating constraints from a collocated seismic study into the magnetotelluric inversion process, we obtain superior constraints on the fluids and melt in a subduction setting. Specifically, we are able to identify and connect fluid release at or near the top of the slab, migration of fluids into the overlying mantle wedge, melting in the wedge, and transport of the melt/fluid phase to a reservoir in the crust beneath Mt Rainier.

  12. Evidence for natural molecular hydrogen seepage associated with Carolina bays (surficial, ovoid depressions on the Atlantic Coastal Plain, Province of the USA)

    NASA Astrophysics Data System (ADS)

    Zgonnik, Viacheslav; Beaumont, Valérie; Deville, Eric; Larin, Nikolay; Pillot, Daniel; Farrell, Kathleen M.

    2015-12-01

    A study of soil gases was made in North Carolina (USA) in and around morphological depressions called "Carolina bays." This type of depression is observed over the Atlantic coastal plains of the USA, but their origin remains debated. Significant concentrations of molecular hydrogen (H2) were detected, notably around the bays. These measurements suggest that Carolina bays are the surficial expression of fluid flow pathways for hydrogen gas moving from depth to the surface. The potential mechanisms of H2 production and transport and the geological controls on the fluid migration pathways are discussed, with reference to the hypothesis that Carolina bays are the result of local collapses caused by the alteration of rock along the deep pathways of H2 migrating towards the surface. The present H2 seepages are comparable to those in similar structures previously observed in the East European craton.

  13. Fluid inclusions in calcite filled opening fractures of the Serra Alta Formation reveal paleotemperatures and composition of diagenetic fluids percolating Permian shales of the Paraná Basin

    NASA Astrophysics Data System (ADS)

    Teixeira, C. A. S.; Sawakuchi, A. O.; Bello, R. M. S.; Nomura, S. F.; Bertassoli, D. J.; Chamani, M. A. C.

    2018-07-01

    The thermal and diagenetic evolution of shale units has received renewed focus because of their emergence as unconventional hydrocarbon reservoirs. The Serra Alta Formation (SAF) is a Permian shale unit of the Paraná Basin, which is the largest South American cratonic basin. The SAF stands out as a pathway for aqueous fluids and hydrocarbon migration from the Irati organic-rich shales to the Pirambóia fluvial-eolian sandstone reservoirs. Vertical NNW and NNE opening fractures would be the main pathways for the migration of buried pore waters and aqueous fluids, besides the input of meteoric water. These fractures would be associated to the reactivation of basement discontinuities such as the Jacutinga (NE) and Guapiara (NW) faults. Thus, vertical NNE and NNW associated fractures would represent the main pathways for fluid migration in the studied area. The vertical calcite filled opening fractures from SAF record moderately low salinity (0-4.5 wt % of NaCl eq.) aqueous fluids, suggesting the input of meteoric water in the buried fracture system. Eutectic melting temperatures at -52±5 °C indicate an H2O + NaCl + CaCl2 system with CaCl2 or MgCl2 in solution. Homogenization temperatures recorded in fluid inclusion assemblages (FIAs) of calcite filled opening fractures indicate that the SAF in the studied area reached temperatures above 200 °C, suitable for generation of gaseous hydrocarbons. The recorded paleotemperatures point to a thermal peak associated with Serra Geral volcanic event during the Early Cretaceous, with the thermal effect of volcanic rock cap possibly overcoming the effect of intrusive igneous bodies. The detection of methane in SAF shale pores indicates conditions for hydrocarbon generation. However, additionally studies are necessary to confirm the thermogenic and/or biogenic origin of the methane within the SAF.

  14. Fluid pathways from mantle wedge up to forearc seafloor in the coseismic slip area of the 2011 Tohoku earthquake

    NASA Astrophysics Data System (ADS)

    Park, J. O.; Tsuru, T.; Fujie, G.; Kagoshima, T.; Sano, Y.

    2017-12-01

    A lot of fluids at subduction zones are exchanged between the solid Earth and ocean, affecting the earthquake and tsunami generation. New multi-channel seismic reflection and sub-bottom profiling data reveal normal and reverse faults as the fluid pathways in the coseismic slip area of the 2011 Tohoku earthquake (M9.0). Based on seismic reflection characteristics and helium isotope anomalies, we recognize variations in fluid pathways (i.e., faults) from the mantle wedge up to forearc seafloor in the Japan Trench margin. Some fluids are migrated from the mantle wedge along plate interface and then normal or reverse faults cutting through the overriding plate. Others from the mantle wedge are migrated directly up to seafloor along normal faults, without passing through the plate interface. Locations of the normal faults are roughly consistent with aftershocks of the 2011 Tohoku earthquake, which show focal mechanism of normal faulting. It is noticeable that landward-dipping normal faults developing down into Unit C (Cretaceous basement) from seafloor are dominant in the middle slope region where basal erosion is inferred to be most active. A high-amplitude, reverse-polarity reflection of the normal faults within Unit C suggests that the fluids are locally trapped along the faults in high pore pressures. The 2011 Tohoku mainshock and subsequent aftershocks could lead the pre-existing normal faults to be reactive and more porous so that the trapped fluids are easily transported up to seafloor through the faults. Elevated fluid pressures can decrease the effective normal stress for the fault plane, allowing easier slip of the landward-dipping normal fault and also enhancing its tsunamigenic potential.

  15. Influence of mantle viscosity structure and mineral grain size on fluid migration pathways in the mantle wedge.

    NASA Astrophysics Data System (ADS)

    Cerpa, N. G.; Wada, I.; Wilson, C. R.; Spiegelman, M. W.

    2016-12-01

    We develop a 2D numerical porous flow model that incorporates both grain size distribution and matrix compaction to explore the fluid migration (FM) pathways in the mantle wedge. Melt generation for arc volcanism is thought to be triggered by slab-derived fluids that migrate into the hot overlying mantle and reduce its melting temperature. While the narrow location of the arcs relative to the top of the slab ( 100±30 km) is a robust observation, the release of fluids is predicted to occur over a wide range of depth. Reconciling such observations and predictions remains a challenge for the geodynamic community. Fluid transport by porous flow depends on the permeability of the medium which in turn depends on fluid fraction and mineral grain size. The grain size distribution in the mantle wedge predicted by laboratory derived laws was found to be a possible mechanism to focusing of fluids beneath the arcs [Wada and Behn, 2015]. The viscous resistance of the matrix to the volumetric strain generates compaction pressure that affects fluid flow and can also focus fluids towards the arc [Wilson et al, 2014]. We thus have developed a 2D one-way coupled Darcy's-Stokes flow model (solid flow independent of fluid flow) for the mantle wedge that combines both effects. For the solid flow calculation, we use a kinematic-dynamic approach where the system is driven by the prescribed slab velocity. The solid rheology accounts for both dislocation and diffusion creep and we calculate the grain size distribution following Wada and Behn [2015]. In our fluid flow model, the permeability of the medium is grain size dependent and the matrix bulk viscosity depends on solid shear viscosity and fluid fraction. The fluid influx from the slab is imposed as a boundary condition at the base of the mantle wedge. We solve the discretized governing equations using the software package TerraFERMA. Applying a range of model parameter values, including slab age, slab dip, subduction rate, and fluid influx, we quantify the combined effects of grain size and compaction on fluid flow paths.

  16. Numerical Simulation of Potential Groundwater Contaminant Pathways from Hydraulically Fractured Oil Shale in the Nevada Basin and Range Province

    NASA Astrophysics Data System (ADS)

    Rybarski, S.; Pohll, G.; Pohlmann, K.; Plume, R.

    2014-12-01

    In recent years, hydraulic fracturing (fracking) has become an increasingly popular method for extraction of oil and natural gas from tight formations. Concerns have been raised over a number of environmental risks associated with fracking, including contamination of groundwater by fracking fluids, upwelling of deep subsurface brines, and methane migration. Given the potentially long time scale for contaminant transport associated with hydraulic fracturing, numerical modeling remains the best practice for risk assessment. Oil shale in the Humboldt basin of northeastern Nevada has now become a target for hydraulic fracturing operations. Analysis of regional and shallow groundwater flow is used to assess several potential migration pathways specific to the geology and hydrogeology of this basin. The model domain in all simulations is defined by the geologic structure of the basin as determined by deep oil and gas well bores and formation outcrops. Vertical transport of gaseous methane along a density gradient is simulated in TOUGH2, while fluid transport along faults and/or hydraulic fractures and lateral flow through more permeable units adjacent to the targeted shale are modeled in FEFLOW. Sensitivity analysis considers basin, fault, and hydraulic fracturing parameters, and results highlight key processes that control fracking fluid and methane migration and time scales under which it might occur.

  17. Creep cavitation can establish a dynamic granular fluid pump in ductile shear zones.

    PubMed

    Fusseis, F; Regenauer-Lieb, K; Liu, J; Hough, R M; De Carlo, F

    2009-06-18

    The feedback between fluid migration and rock deformation in mid-crustal shear zones is acknowledged as being critical for earthquake nucleation, the initiation of subduction zones and the formation of mineral deposits. The importance of this poorly understood feedback is further highlighted by evidence for shear-zone-controlled advective flow of fluids in the ductile lower crust and the recognition that deformation-induced grain-scale porosity is a key to large-scale geodynamics. Fluid migration in the middle crust cannot be explained in terms of classical concepts. The environment is considered too hot for a dynamic fracture-sustained permeability as in the upper crust, and fluid pathways are generally too deformed to be controlled by equilibrium wetting angles that apply to hotter, deeper environments. Here we present evidence that mechanical and chemical potentials control a syndeformational porosity generation in mid-crustal shear zones. High-resolution synchrotron X-ray tomography and scanning electron microscopy observations allow us to formulate a model for fluid migration in shear zones where a permeable porosity is dynamically created by viscous grain-boundary sliding, creep cavitation, dissolution and precipitation. We propose that syndeformational fluid migration in our 'granular fluid pump' model is a self-sustained process controlled by the explicit role of the rate of entropy production of the underlying irreversible mechanical and chemical microprocesses. The model explains fluid transfer through the middle crust, where strain localization in the creep regime is required for plate tectonics, the formation of giant ore deposits, mantle degassing and earthquake nucleation. Our findings provide a key component for the understanding of creep instabilities in the middle crust.

  18. Fluid source inferred from strontium isotopes in pore fluid and carbonate recovered during Expedition 337 off Shimokita, Japan

    NASA Astrophysics Data System (ADS)

    Hong, W.; Moen, N.; Haley, B. A.

    2013-12-01

    IODP Expedition 337 was designed to understand the relationship between a deep-buried (2000 meters below seafloor) hydrocarbon reservoir off the Shimokita peninsula (Japan), and the microbial community that this carbon reservoir sustains at such depth. Understanding sources and pathways of flow of fluids that carry hydrocarbons, nutrients, and other reduced components is of particular interest to fulfilling the expedition objectives, since this migrating fluid supports microbial activity not only of the deep-seated communities but also to the shallow-dwelling organisms. To this aim, the concentration and isotopic signature of Sr can be valuable due to that it is relatively free from biogenic influence and pristine in terms of drill fluid contamination. From the pore water Sr profile, concentration gradually increases from 1500 to 2400 mbsf. The depth where highest Sr concentration is observed corresponds to the depths where couple layers of carbonate were observed. Such profile suggests an upward-migrating fluid carries Sr from those deep-seated carbonate layers (>2400 mbsf) to shallower sediments. To confirm this inference, pore water, in-situ formation fluid, and carbonate samples were analyzed for Sr isotopes to investigate the fluid source.

  19. Spatial and Temporal Characteristics of Historical Oil and Gas Wells in Pennsylvania: Implications for New Shale Gas Resources.

    PubMed

    Dilmore, Robert M; Sams, James I; Glosser, Deborah; Carter, Kristin M; Bain, Daniel J

    2015-10-20

    Recent large-scale development of oil and gas from low-permeability unconventional formations (e.g., shales, tight sands, and coal seams) has raised concern about potential environmental impacts. If left improperly sealed, legacy oil and gas wells colocated with that new development represent a potential pathway for unwanted migration of fluids (brine, drilling and stimulation fluids, oil, and gas). Uncertainty in the number, location, and abandonment state of legacy wells hinders environmental assessment of exploration and production activity. The objective of this study is to apply publicly available information on Pennsylvania oil and gas wells to better understand their potential to serve as pathways for unwanted fluid migration. This study presents a synthesis of historical reports and digital well records to provide insights into spatial and temporal trends in oil and gas development. Areas with a higher density of wells abandoned prior to the mid-20th century, when more modern well-sealing requirements took effect in Pennsylvania, and areas where conventional oil and gas production penetrated to or through intervals that may be affected by new Marcellus shale development are identified. This information may help to address questions of environmental risk related to new extraction activities.

  20. Modeling the migration of fluids in subduction zones

    NASA Astrophysics Data System (ADS)

    Spiegelman, M.; Wilson, C. R.; van Keken, P. E.; Hacker, B. R.

    2010-12-01

    Fluids play a major role in the formation of arc volcanism and the generation of continental crust. Progressive dehydration reactions in the downgoing slab release fluids to the hot overlying mantle wedge, causing flux melting and the migration of melts to the volcanic front. While the qualitative concept is well established the quantitative details of fluid release and especially that of fluid migration and generation of hydrous melting in the wedge is still poorly understood. Here we present new models of the fluid migration through the mantle wedge for subduction zones that span the spectrum of arcs worldwide. We focus on the flow of water and use an existing set of high resolution thermal and metamorphic models (van Keken et al., JGR, in review) to predict the regions of water release from the sediments, upper and lower crust, and upper most mantle. We use this water flux as input for the fluid migration calculation based on new finite element models built on advanced computational libraries (FEniCS/PETSc) for efficient and flexible solution of coupled multi-physics problems. The first generation of these models solves for the evolution of porosity and fluid-pressure/flux throughout the slab and wedge given solid flow, viscosity and thermal fields from the existing thermal models. Fluid flow in the new models depends on both permeability and the rheology of the slab-wedge system as interaction with rheological variability can induce additional pressure gradients that affect the fluid flow pathways. We will explore the sensitivity of fluid flow paths for a range of subduction zones and fluid flow parameters with emphasis on variability of the location of the volcanic arc with respect to flow paths and expected degrees of hydrous melting which can be estimated given a variety of wet-melting parameterizations (e.g. Katz et al, 2003, Kelley et al, 2010). The current models just include dehydration reactions but work continues on the next generation of models which will include both dehydration and hydration reactions as well as parameterized flux melting in a consistent reactive-flow framework. We have also begun work on re-implementing the solid-flow thermal calculations in FEniCS/PETSc which are open-source libraries in preparation for developing a fully coupled fluid-solid dynamics models for exploring subduction zone processes

  1. Permeability anisotropy of serpentinite and fluid pathways in a subduction zone

    NASA Astrophysics Data System (ADS)

    Katayama, I.; Kawano, S.; Okazaki, K.

    2011-12-01

    Subduction zones are the only sites where water is transported into the Earth's deep interior. Although the fluid released into the mantle wedge is generally believed to ascend under buoyancy, it is possible that fluid movement is influenced by anisotropic permeability in localized shear zones. The mantle rocks at the plate interface of a subducting slab are subjected to non-coaxial stress and commonly develop a strong foliation. Indeed, the existence of foliated serpentinite is indicated by strong seismic anisotropy in the forearc mantle wedge (e.g., Katayama et al., 2009; Bezacier et al., 2010). Therefore, fluid pathways in the mantle wedge may be controlled by the preferred orientation of highly anisotropic minerals. In this study, we measured the permeability of highly foliated natural serpentinite, in directions parallel and perpendicular to the foliation, and we discuss the influence of permeability anisotropy on fluid flow in subduction zones. The permeability was measured by an intra-vessel deformation and fluid flow apparatus housed at Hiroshima University. In the measurements, we used nitrogen gas as a pore fluid and maintained constant pore pressure during the measurements (Pp < 6 MPa). The obtained gas permeability was then converted to intrinsic permeability using the Klinkenberg effect, which is known to be insensitive to the type of pore fluid. Under low confining pressure, all the experiments show similar permeability, in the order of 10-19 m2. However, permeability anisotropy appears under high confining pressures, with the specimens oriented parallel to the foliation having higher permeability than those oriented normal to the foliation. At a confining pressure of 50 MPa, the difference in permeability between the samples with contrasting orientations reaches several orders of magnitude, possibly reflecting the pore tortuosity of the highly sheared serpentinite, as indicated by the Kozeny-Carman relation. The present experimental data show that the highly foliated serpentinites have a marked permeability anisotropy: consequently, fluid migration is strongly influenced by the orientation of the foliation in the mantle wedge. Serpentine forms in the mantle wedge because of the infiltration of water expelled from the subducting plate, above which deformation is concentrated in a relatively thin layer (e.g., Hilairet and Reynard, 2009). In such a case, the water released from the subducting plate migrates along the plate interface. The total flux of fluid expelled from the subducting plate would be expected to result in a thick layer of serpentinized mantle, if the water migrates vertically in the mantle wedge. However, geophysical observations, including seismic tomography and reflection data, have shown that the serpentinized layer is limited to a narrow zone above the subducting plate. These data are consistent with our hypothesis that fluid tends to migrate within the highly sheared serpentinite layer, along the plate interface, rather than vertically upward.

  2. 3D Chirp Sonar Images on Fluid Migration Pathways and Their Implications on Seafloor Stability East of the Fangliao Submarine Canyon Offshore SW Taiwan

    NASA Astrophysics Data System (ADS)

    Lu, Y. W.; Liu, C. S.; Su, C. C.; Hsu, H. H.; Chen, Y. H.

    2015-12-01

    This study utilizes both chirp sonar images and coring results to investigate the unstable seafloor strata east of the Fangliao Submarine Canyon offshore southwestern Taiwan. We have constructed 3D chirp sonar images from a densely surveyed block to trace the attitude of an acoustic transparent layer and features caused by fluid activities. Based on the distribution of this transparent layer and fluid-related features, we suggest that this transparent layer forms a pathway for fluid migration which induces fluid-related characters such as acoustic blanking and fluid chimneys in the 3D chirp sonar images. Cored seafloor samples are used in this study to investigate the sediment compositions. The 210Pb activity profiles of the cores show oscillating and unsteady values at about 20~25 cm from core top. The bulk densities of the core samples in the same section (about 20~25 cm from core top) give values lower than those at deeper parts of the cores. These results indicate that the water content is much higher in the shallow sediments than in the deeper strata. From core sample analyses, we deduce that the local sediments are disturbed by liquefaction. From the analyses of 3D chirp sonar images and core data, we suggest that the seafloor east of the Fangliao Submarine Canyon is in an unstable condition, if disturbed by earthquakes, submarine landslides and gravity flows could be easily triggered and cause some geohazards, like breaking submarine cables during the 2006 Pingtung earthquake event.

  3. Numerical Model of Hydraulic Fracturing Fluid Transport in the Subsurface with Pressure Transient, Density Effects, and Imbibition

    NASA Astrophysics Data System (ADS)

    Birdsell, D.; Rajaram, H.; Dempsey, D.; Viswanathan, H.

    2014-12-01

    Understanding the transport of hydraulic fracturing (HF) fluid that is injected into the deep subsurface for shale gas extraction is important to ensure that shallow drinking water aquifers are not contaminated from an environmental and public health perspective and to understand formation damage from an oil and gas production perspective. Upward pressure gradients, permeable pathways such as faults or improperly abandoned wellbores, and the density contrast of the HF fluid to the surrounding brine encourages upward HF fluid migration. In contrast, the very low shale permeability and the imbibition of water into partially-saturated shale may sequester much of the HF fluid. Using the Finite Element Heat and Mass Transfer Code (FEHM), single-phase flow and transport simulations are performed to quantify how much HF fluid is removed via the wellbore as flowback and produced water and how much reaches overlying aquifers; imbibition is calculated with a semi-analytical one-dimensional solution and treated as a sink term. The travel time for HF fluid to reach the shallow aquifers is highly dependent on the amount of water imbibed and the suction applied to the well. If imbibition rates and suction are small, the pressure transient due to injection and the density contrast allows rapid upward plume migration at early times. The density contrast diminishes considerably within tens to hundreds of years as mixing occurs. We present estimates of HF fluid migration to shallow aquifers during the first 1,000 years after hydraulic fracturing begins for ranges of subsurface properties.

  4. Methane fluxes, microbes and carbonate mounds: insights from asin modelling of the porcupine basin, ireland

    NASA Astrophysics Data System (ADS)

    Naeth, J.; di Primio, R.; Schäfer, R. G.; Horsfield, B.

    2003-04-01

    Our broad task has been to investigate the origin and growth of large carbonate mounds within the Porcupine Basin offshore Ireland. Specifically, the project aims at determining the timing and magnitude of chemical degradation and physical redistribution processes which are likely to have played a key role in the formation of carbonate mounds. We addressed these issues using 2D basin modelling the results of which were used for map-based migration modelling. The overall sedimentary basin architecture of the basin facilitates up-dip fluid migration towards the western, eastern and especially the northern margins of the basin. Potential fluid migration pathways are available through a variety of stratal surfaces, unconformities, faults and detachments. The spatial association of deep water carbonate mounds with underlying fluid pathways is compatible with the provision of a basin-derived nutrient source (e.g. hydrocarbons). Numerical simulations lie at the centre of the investigation using three seismic lines covering the Hovland-Magellan mound area in the northern part of the basin and the Belgica mound area in the western part. The calibration of the thermal history was performed by iteratively using putative heat-flow scenarios in compliance with the known geologic evolution of the basin, present-day temperatures, organic maturity parameters, overpressure occurrence and assigned lithologies. After optimisation of the model, the generation and migration history of potential source units were modelled using, inter alia, the source richness and quality assignments referred to above and kinetic parameters of hydrocarbon generation determined experimentally. The results achieved indicate that: bullet hydrocarbon generation and expulsion is currently taking place in the vicinity of the mound locations bullet stratigraphic pinch outs and shallow structural closures underly most mounds bullet a high temporal and spatial resolution of the latest Tertiary and Quaternary events in combination with accurate paleo-water depth reconstructions are of critical importance for recognition of leakage pathways leading to the sea floor bullet the onset of carbonate mound growth coincides with the predicted timing of maximum thermogenic methane fluxes to the sea floor

  5. Chemical Evidence for Episodic Growth of a Fibrous Antitaxial Calcite Vein From Externally Derived Fluid

    NASA Astrophysics Data System (ADS)

    Barker, S. L.; Cox, S. F.; Eggins, S. M.; Gagan, M. K.

    2005-12-01

    Fibrous, massive and crustiform textured quartz and calcite veins occur within a deformed limestone-shale sequence at Taemas, in the Lachlan Fold Belt, eastern New South Wales, Australia. Stable isotope analyses of veins and host rock indicate that these veins formed from upwardly migrating, externally derived fluids. High spatial resolution (100 μm) analyses reveal per mil scale variations of stable C and O isotope ratios, and radiogenic Sr isotope ratios in a 1.5 cm thick, fibrous, antitaxial-growth calcite vein. LA-ICP-MS analyses (30 μm resolution) demonstrate significant variations in Fe, Mn, Sr, REE and Eu/Eu* parallel to the long axes of fibres. Stable and radiogenic isotopic ratio variations, and trace and REE concentration changes correlate with different cathodoluminesence zones, and slight changes in fibre orientation and thickness. The covariance of calcite textures and chemistry indicate that this fibrous vein grew episodically. Moreover, calcite in this vein was precipitated from externally derived fluid, which underwent variable fluid-rock interaction, and had a fluctuating oxidation state. This fibrous, antitaxial growth vein likely formed from fluid that migrated along fracture-controlled flow pathways.

  6. Diagenetic variation at the lamina scale in lacustrine organic-rich shales: Implications for hydrocarbon migration and accumulation

    NASA Astrophysics Data System (ADS)

    Liang, Chao; Cao, Yingchang; Liu, Keyu; Jiang, Zaixing; Wu, Jing; Hao, Fang

    2018-05-01

    Lacustrine carbonate-rich shales are well developed within the Mesozoic-Cenozoic strata of the Bohai Bay Basin (BBB) of eastern China and across southeast Asia. Developing an understanding of the diagenesis of these shales is essential to research on mass balance, diagenetic fluid transport and exchange, and organic-inorganic interactions in black shales. This study investigates the origin and distribution of authigenic minerals and their diagenetic characteristics, processes, and pathways at the scale of lacustrine laminae within the Es4s-Es3x shale sequence of the BBB. The research presented in this study is based on thin sections, field emission scanning electron microscope (FESEM) and SEM-catholuminescence (CL) observations of well core samples combined with the use of X-ray diffraction (XRD), energy dispersive spectroscopy, electron microprobe analysis, and carbon and oxygen isotope analyses performed using a laser microprobe mass spectrometer. The dominant lithofacies within the Es4s-Es3x sequence are a laminated calcareous shale (LCS-1) and a laminated clay shale (LCS-2). The results of this study show that calcite recrystallization1 is the overarching diagenetic process affecting the LCS-1, related to acid generation from organic matter (OM) thermal evolution. This evolutionary transition is the key factor driving the diagenesis of this lithofacies, while the transformation of clay minerals is the main diagenetic attribute of the LCS-2. Diagenetic differences occur within different laminae and at variable locations within the same lamina level, controlled by variations in mineral composition and the properties of laminae interfaces. The diagenetic fluid migration scale is vertical and responses (dissolution and replacement) are limited to individual laminae, between zero and 100 μm in width. In contrast, the dominant migration pathway for diagenetic fluid is lateral, along the abrupt interfaces between laminae boundaries, which leads to the vertical transmission of diagenetic responses. The recrystallization boundaries between calcite laminae act as the main migration pathways for the expulsion of hydrocarbons from these carbonate-rich lacustrine shales. However, because the interaction between diagenetic fluids and the shales themselves is limited to the scale of individual lamina, this system is normally closed. The occurrence of abnormal pressure fractures can open the diagenetic system, however, and cause interactions to occur throughout laminae; in particular, the closed-open (C-O) diagenetic process at this scale is critical to this shale interval. Multi-scale C-O systems are ubiquitous and episodic ranging from the scale of laminae to the whole basin. Observations show that such small-scale systems are often superimposed onto larger ones to constitute the complex diagenetic system seen within the BBB combining fluid transport, material and energy exchange, and solid-liquid and organic-inorganic interactions.

  7. Soliton-mediated conduit flow: Deep Hawaiian magma migration

    NASA Astrophysics Data System (ADS)

    Ryan, M.; Stanley, B.

    2006-12-01

    Solitons have first-order attributes that include shape- and volume-conserving packets of fluid that migrate with characteristic wavelengths, amplitudes, wave numbers, and pulse durations. For ascent in dike-like magma- filled fractures, the soliton pulse duration is directly proportional to the conduit wall region viscosity and inversely proportional to the density contrast that drives the flow. Second-order effects that modify pathways include heat loss to conduit wall rocks, and progressive crystallization episodes along conduit walls. Long-lived (and intermediate duration) historical eruption episodes of Kilauea volcano, Hawai'i, include the 1959 Kilauea summit series at Kilauea Iki, the 1969-1974 series at Mauna Ulu and the 1983-to-present series at Pu'u `O'o-Kupaianaha. For each locale, the eruptions display a variable time-series in their erupted volumes, as well as fountain heights and vent flow rates. Inter-episode repose periods, however, often show broad regularity over extended periods. We suggest that these dynamics represent serendipitous windows into the characteristic system dynamics of deep magma migration beneath Hawai'i: all made possible by the chance clearance of mechanical obstructions allowing virtually open-system behavior. The rhythmic `beat' of eruptive episodes within a long-lived series (and their roughly regular repose periods) arise directly from the soliton migration mechanism. For non-summit locales such as Mauna Ulu and Pu'u `O'o-Kupaianaha, the fluid contents of the sub-caldera reservoir and the shallow molten rift zone core modulate the observed intrusion- eruption dynamics as volumetric displacements transmit down-rift the pressure pulses first felt beneath Halemaumau and the summit caldera. Analytic calculations of wave speed, wave length, batch volume, parcel shapes and repose periods reveal the dependence on material properties appropriate for Kilauea intrusions and eruptions. Analogue laboratory experiments using stiff mixtures of gelatin as the matrix `fluid' and dyed aqueous solutions as the injected phase, reveal that the injections exhibit soliton-like ascent modes: independent packets of fluid rise along vertical fractures with bulbous noses and slender tails that thin with depth and increasing confining pressures. Spatially-varying azimuths of principal stress components ( ) result in systematic rotations of the ascent pathway as the rising soliton rotates to reestablish an orthogonal relationship with the minimum compressive stress component ( ) orientation. These rotations in ascent pathway orientation are appropriate for the inferred transitions from the upper mantle, through the oceanic crust and into Kilauea's volcanic shield and laterally extensive East Rift Zone and Southwest Rift Zone.

  8. Insights on fluid-rock interaction evolution during deformation from fracture network geochemistry at reservoir-scale

    NASA Astrophysics Data System (ADS)

    Beaudoin, Nicolas; Koehn, Daniel; Lacombe, Olivier; Bellahsen, Nicolas; Emmanuel, Laurent

    2015-04-01

    Fluid migration and fluid-rock interactions during deformation is a challenging problematic to picture. Numerous interplays, as between porosity-permeability creation and clogging, or evolution of the mechanical properties of rock, are key features when it comes to monitor reservoir evolution, or to better understand seismic cycle n the shallow crust. These phenomenoms are especially important in foreland basins, where various fluids can invade strata and efficiently react with limestones, altering their physical properties. Stable isotopes (O, C, Sr) measurements and fluid inclusion microthermometry of faults cement and veins cement lead to efficient reconstruction of the origin, temperature and migration pathways for fluids (i.e. fluid system) that precipitated during joints opening or faults activation. Such a toolbox can be used on a diffuse fracture network that testifies the local and/or regional deformation history experienced by the rock at reservoir-scale. This contribution underlines the advantages and limits of geochemical studies of diffuse fracture network at reservoir-scale by presenting results of fluid system reconstruction during deformation in folded structures from various thrust-belts, tectonic context and deformation history. We compare reconstructions of fluid-rock interaction evolution during post-deposition, post-burial growth of basement-involved folds in the Sevier-Laramide American Rocky Mountains foreland, a reconstruction of fluid-rock interaction evolution during syn-depostion shallow detachment folding in the Southern Pyrenean foreland, and a preliminary reconstruction of fluid-rock interactions in a post-deposition, post-burial development of a detachment fold in the Appenines. Beyond regional specification for the nature of fluids, a common behavior appears during deformation as in every fold, curvature-related joints (related either to folding or to foreland flexure) connected vertically the pre-existing stratified fluid system. The lengthscale of the migration and the nature of invading fluids during these connections is different in every studied example, and can be related to the tectonic nature of the fold, along with the burial depth at the time of deformation. Thus, to decipher fluid-fracture relationships provides insights to better reconstruct the mechanisms of deformation at reservoir-scale.

  9. Natural flows of H2-rich fluids in the ophiolites of Oman and the Philippines: Tectonic control of migration pathways and associated diagenetic processes

    NASA Astrophysics Data System (ADS)

    Deville, E. P.; Prinzhofer, A.; Vacquand, C.; Chavagnac, V.; Monnin, C.; Ceuleneer, G.; Arcilla, C. A.

    2009-12-01

    We compare the geological environments of sites of emission of natural hydrogen in the Oman ophiolite and the Zambales ophiolite (Luzon, Philippines). The genesis of natural H2 results from the interaction between ultrabasic rocks and aqueous solutions circulating in deep fracture networks, by oxidation of metals (Fe2+, Mn2+) and reduction of water, probably under high temperature conditions. This process generates very reducing conditions capable of destabilizing other molecules (notably reduction of deep CO2 being transformed into CH4 by Fisher-Tropsch type reactions). Nitrogen is also commonly associated to the H2-rich fluids. H2 flows are associated with the expulsion of hyperalkaline waters rich in ions OH- and Ca2+ and characterized by high pH (between 11 and 12). Most alkaline springs are found in the vicinity of major faults and/or lithological discontinuities like the basal thrust plane of the ophiolites and the peridotite-gabbro contact (Moho). Within the fracture networks, gas and water separate probably at shallow depth, i.e. close to the top of the upper aquifer level. Locally high flows of gas migrate vertically through fracture pathways and they are able to inflame spontaneously on the surface. Aqueous fluids tends to migrate laterally in the fracture network toward the creeks where most of the hyperalkaline springs are found. This water circulation induces a chain of diagenetic reactions starting in the fracture systems and continuing at the surface where it leads to the precipitation of calcite, aragonite, brucite and more rarely portlandite. This chain of diagenetic reactions is associated with the capture of the atmospheric CO2 during the precipitation of carbonates.

  10. Modeling the Migration of Fluids in Subduction Zones

    NASA Astrophysics Data System (ADS)

    Wilson, C. R.; Spiegelman, M.; Van Keken, P. E.; Vrijmoed, J. C.; Hacker, B. R.

    2011-12-01

    Fluids play a major role in the formation of arc volcanism and the generation of continental crust. Progressive dehydration reactions in the downgoing slab release fluids to the hot overlying mantle wedge, causing flux melting and the migration of melts to the volcanic front. While the qualitative concept is well established, the quantitative details of fluid release and especially that of fluid migration and generation of hydrous melting in the wedge is still poorly understood. Here we present new models of the fluid migration through the mantle wedge for subduction zones. We use an existing set of high resolution metamorphic models (van Keken et al, 2010) to predict the regions of water release from the sediments, upper and lower crust, and upper most mantle. We use this water flux as input for the fluid migration calculation based on new finite element models built on advanced computational libraries (FEniCS/PETSc) for efficient and flexible solution of coupled multi-physics problems. The first generation of one-way coupled models solves for the evolution of porosity and fluid-pressure/flux throughout the slab and wedge given solid flow, viscosity and thermal fields from separate solutions to the incompressible Stokes and energy equations in the mantle wedge. These solutions are verified by comparing to previous benchmark studies (van Keken et al, 2008) and global suites of thermal subduction models (Syracuse et al, 2010). Fluid flow depends on both permeability and the rheology of the slab-wedge system as interaction with rheological variability can induce additional pressure gradients that affect the fluid flow pathways. These non-linearities have been shown to explain laboratory-scale observations of melt band orientation in labratory experiments and numerical simulations of melt localization in shear bands (Katz et al 2006). Our second generation of models dispense with the pre-calculation of incompressible mantle flow and fully couple the now compressible system of mantle and fluid flow equations, introducing complex feedbacks between the rheology, temperature, permeability, strain rate and porosity. Using idealized subduction zone geometries we investigate the effects of this non-linearity and explore the sensitivity of fluid flow paths for a range of fluid flow parameters with emphasis on variability of the location of the volcanic arc with respect to flow paths. We also estimate the expected degrees of hydrous melting using a variety of wet-melting parameterizations (e.g., Katz et al, 2003, Kelley et al, 2010). The current models only include dehydration reactions but work continues on the next generation of models which will include both dehydration and hydration reactions as well as parameterized flux melting in a consistent reactive-flow framework.

  11. Geochemical evidence for possible natural migration of Marcellus Formation brine to shallow aquifers in Pennsylvania

    PubMed Central

    Warner, Nathaniel R.; Jackson, Robert B.; Darrah, Thomas H.; Osborn, Stephen G.; Down, Adrian; Zhao, Kaiguang; White, Alissa; Vengosh, Avner

    2012-01-01

    The debate surrounding the safety of shale gas development in the Appalachian Basin has generated increased awareness of drinking water quality in rural communities. Concerns include the potential for migration of stray gas, metal-rich formation brines, and hydraulic fracturing and/or flowback fluids to drinking water aquifers. A critical question common to these environmental risks is the hydraulic connectivity between the shale gas formations and the overlying shallow drinking water aquifers. We present geochemical evidence from northeastern Pennsylvania showing that pathways, unrelated to recent drilling activities, exist in some locations between deep underlying formations and shallow drinking water aquifers. Integration of chemical data (Br, Cl, Na, Ba, Sr, and Li) and isotopic ratios (87Sr/86Sr, 2H/H, 18O/16O, and 228Ra/226Ra) from this and previous studies in 426 shallow groundwater samples and 83 northern Appalachian brine samples suggest that mixing relationships between shallow ground water and a deep formation brine causes groundwater salinization in some locations. The strong geochemical fingerprint in the salinized (Cl > 20 mg/L) groundwater sampled from the Alluvium, Catskill, and Lock Haven aquifers suggests possible migration of Marcellus brine through naturally occurring pathways. The occurrences of saline water do not correlate with the location of shale-gas wells and are consistent with reported data before rapid shale-gas development in the region; however, the presence of these fluids suggests conductive pathways and specific geostructural and/or hydrodynamic regimes in northeastern Pennsylvania that are at increased risk for contamination of shallow drinking water resources, particularly by fugitive gases, because of natural hydraulic connections to deeper formations. PMID:22778445

  12. Geochemical evidence for possible natural migration of Marcellus Formation brine to shallow aquifers in Pennsylvania.

    PubMed

    Warner, Nathaniel R; Jackson, Robert B; Darrah, Thomas H; Osborn, Stephen G; Down, Adrian; Zhao, Kaiguang; White, Alissa; Vengosh, Avner

    2012-07-24

    The debate surrounding the safety of shale gas development in the Appalachian Basin has generated increased awareness of drinking water quality in rural communities. Concerns include the potential for migration of stray gas, metal-rich formation brines, and hydraulic fracturing and/or flowback fluids to drinking water aquifers. A critical question common to these environmental risks is the hydraulic connectivity between the shale gas formations and the overlying shallow drinking water aquifers. We present geochemical evidence from northeastern Pennsylvania showing that pathways, unrelated to recent drilling activities, exist in some locations between deep underlying formations and shallow drinking water aquifers. Integration of chemical data (Br, Cl, Na, Ba, Sr, and Li) and isotopic ratios ((87)Sr/(86)Sr, (2)H/H, (18)O/(16)O, and (228)Ra/(226)Ra) from this and previous studies in 426 shallow groundwater samples and 83 northern Appalachian brine samples suggest that mixing relationships between shallow ground water and a deep formation brine causes groundwater salinization in some locations. The strong geochemical fingerprint in the salinized (Cl > 20 mg/L) groundwater sampled from the Alluvium, Catskill, and Lock Haven aquifers suggests possible migration of Marcellus brine through naturally occurring pathways. The occurrences of saline water do not correlate with the location of shale-gas wells and are consistent with reported data before rapid shale-gas development in the region; however, the presence of these fluids suggests conductive pathways and specific geostructural and/or hydrodynamic regimes in northeastern Pennsylvania that are at increased risk for contamination of shallow drinking water resources, particularly by fugitive gases, because of natural hydraulic connections to deeper formations.

  13. Mega-pockmarks surrounding IODP Site U1414: Insights from the CRISP 3D seismic survey

    NASA Astrophysics Data System (ADS)

    Nale, S. M.; Kluesner, J. W.; Silver, E. A.; Bangs, N. L.; McIntosh, K. D.; Ranero, C. R.

    2013-12-01

    Visualization of neural network meta-attribute analyses reveals fluid migration pathways associated with mega-pockmarks within the CRISP 3D seismic volume offshore southern Costa Rica, near site U1414 of IODP Expedition 344. A 245km2 field of mega-pockmarks was imaged on the Cocos Ridge using EM122 multibeam bathymetry, backscatter and 3D seismic reflection aboard R/V Marcus G. Langseth during the 2011 CRISP seismic survey. We utilize the OpendTect software package to calculate supervised neural network meta-attributes within the 3D seismic volume, in order to detect and visualize probable faults and fluid-migration pathways within the sedimentary section of the incoming Cocos plate [see Kluesner et al., this meeting]. Pockmarks imaged within the 3D volume near the trench commonly show a two-tier structure with upper pockmarks located above the steep walls of deeper, older pockmarks. The latter appear to truncate surrounding strata, including widespread high-amplitude reverse polarity reflectors (RPRs), interpreted as trapping horizons. In addition, RPRs are also truncated by positive polarity crosscutting reflections (CCRs), most of which form the base and sides of lens-like structures below the RPRs that are frequently located next to imaged pockmarks. Site U1414 intersects one of these lens-like structures and this appears to correlate to a sharp density and porosity swing observed at ~255 mbsf. In addition, preliminary geochemical analyses from site U1414 show evidence of lateral fluid flow through sediments below the RPR [Expedition 344 Scientists, 2013]. Thus, we interpret the 3D lens-like structures to be pockets of trapped gas and/or over-pressured fluid. Based on 3D imaging we propose a 3-stage pockmark evolution: (1) Overpressure and blowout along RPRs, resulting in pockmark formation, (2) sustained seepage along pockmark walls, resulting in preferential deposition near the center of the pockmark, and (3) rapid burial as pockmarks near the trench axis. On the seafloor, small high-backscatter mounds are found near the walls of a subset of pockmarks, suggesting recent or active seafloor seepage. Further geochemical analyses are needed to determine the source of fluid/gas migration associated with the pockmark structures.

  14. Trapping and migration of methane associated with the gas hydrate stability zone at the Blake Ridge Diapir: New insights from seismic data

    USGS Publications Warehouse

    Taylor, M.H.; Dillon, William P.; Pecher, I.A.

    2000-01-01

    The Blake Ridge Diapir is the southernmost of a line of salt diapirs along the Carolina trough. Diapirs cause faulting of the superjacent sediments, creating pathways for migration of fluids and gas to the seafloor. We analyzed reflection seismic data from the Blake Ridge Diapir, which is located in a region with known abundant gas hydrate occurrence. A striking feature in these data is a significant shallowing of the base of gas hydrate stability (BGHS) over the center of the diapir. The seafloor is warped up by about 100 m above the diapir, from about 2300 m to about 2200 m. The BGHS, as indicated by a bottom simulating reflection (BSR), is about 4.5 s off the flanks of the diapir, rising to about 4.15 s at the center. Above the diapir, a fault system appears to rise vertically from the BGHS to about 0.05 s below the seafloor (40-50 m); it then diverges into several steeply dipping faults that breach the seafloor and cover an area ~700 m in diameter. Other secondary faults diverge from the main fault or emerge directly from the BGHS near the crest of the diapir. Gas and other fluids may migrate upward through the faults. We performed complex trace analysis to compare the reflection strength and instantaneous frequency along individual reflections. A low-frequency anomaly over the center of the diapir indicates high seismic attenuation. This is interpreted to be caused by migration of fluids (probably methane) along fault pathways. The migration of gas (i.e. probably mainly methane) through the gas hydrate stability zone is not yet understood. We speculate that pore fluids in the faults may be too warm and too salty to form gas hydrate, even at depths where gas hydrate is stable away from the diapir. Alternatively, gas hydrates may seal the fault walls such that water supply is too low to transform all the gas into gas hydrates. The shallowing of the BSR may reflect increased heatflow above the diapir either caused by the high thermal conductivity of the underlying salt or by advective heat transport along with fluids. High pore water salinity shifts the gas hydrate stability to lower temperatures and may also play a significant role in BSR shallowing. We, therefore, investigated the possible effect of pore water salinity on shallowing of the BSR. We found that BSR shallowing may theoretically be entirely caused by increased salinity over the diapir, although geologically this would not be reasonable. This observation demonstrates the potential importance of pore water salinity for lateral variations of BSR depths, in particular, above salt structures: (C) 2000 Elsevier Science B.V.

  15. Failure of cap-rock seals as determined from mechanical stratigraphy, stress history, and tensile-failure analysis of exhumed analogs

    DOE PAGES

    Petrie, E. S.; Evans, J. P.; Bauer, S. J.

    2014-11-01

    In this study, the sedimentologic and tectonic histories of clastic cap rocks and their inherent mechanical properties control the nature of permeable fractures within them. The migration of fluid through mm- to cm-scale fracture networks can result in focused fluid flow allowing hydrocarbon production from unconventional reservoirs or compromising the seal integrity of fluid traps. To understand the nature and distribution of subsurface fluid-flow pathways through fracture networks in cap-rock seals we examine four exhumed Paleozoic and Mesozoic seal analogs in Utah. We combine these outcrop analyses with subsidence analysis, paleoloading histories, and rock-strength testing data in modified Mohr–Coulomb–Griffith analysesmore » to evaluate the effects of differential stress and rock type on fracture mode.« less

  16. Fracture Propagation, Fluid Flow, and Geomechanics of Water-Based Hydraulic Fracturing in Shale Gas Systems and Electromagnetic Geophysical Monitoring of Fluid Migration

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, Jihoon; Um, Evan; Moridis, George

    2014-12-01

    We investigate fracture propagation induced by hydraulic fracturing with water injection, using numerical simulation. For rigorous, full 3D modeling, we employ a numerical method that can model failure resulting from tensile and shear stresses, dynamic nonlinear permeability, leak-off in all directions, and thermo-poro-mechanical effects with the double porosity approach. Our numerical results indicate that fracture propagation is not the same as propagation of the water front, because fracturing is governed by geomechanics, whereas water saturation is determined by fluid flow. At early times, the water saturation front is almost identical to the fracture tip, suggesting that the fracture is mostlymore » filled with injected water. However, at late times, advance of the water front is retarded compared to fracture propagation, yielding a significant gap between the water front and the fracture top, which is filled with reservoir gas. We also find considerable leak-off of water to the reservoir. The inconsistency between the fracture volume and the volume of injected water cannot properly calculate the fracture length, when it is estimated based on the simple assumption that the fracture is fully saturated with injected water. As an example of flow-geomechanical responses, we identify pressure fluctuation under constant water injection, because hydraulic fracturing is itself a set of many failure processes, in which pressure consistently drops when failure occurs, but fluctuation decreases as the fracture length grows. We also study application of electromagnetic (EM) geophysical methods, because these methods are highly sensitive to changes in porosity and pore-fluid properties due to water injection into gas reservoirs. Employing a 3D finite-element EM geophysical simulator, we evaluate the sensitivity of the crosswell EM method for monitoring fluid movements in shaly reservoirs. For this sensitivity evaluation, reservoir models are generated through the coupled flow-geomechanical simulator and are transformed via a rock-physics model into electrical conductivity models. It is shown that anomalous conductivity distribution in the resulting models is closely related to injected water saturation, but not closely related to newly created unsaturated fractures. Our numerical modeling experiments demonstrate that the crosswell EM method can be highly sensitive to conductivity changes that directly indicate the migration pathways of the injected fluid. Accordingly, the EM method can serve as an effective monitoring tool for distribution of injected fluids (i.e., migration pathways) during hydraulic fracturing operations« less

  17. Seismic variability and structural controls on fluid migration in Northern Oklahoma

    NASA Astrophysics Data System (ADS)

    Lambert, C.; Keranen, K. M.; Stevens, N. T.

    2016-12-01

    The broad region of seismicity in northern Oklahoma encompasses distinct structural settings; notably, the area contains both high-length, high-offset faults bounding a major structural uplift (the Nemaha uplift), and also encompasses regions of distributed, low-length, low-offset faults on either side of the uplift. Seismicity differs between these structural settings in mode of migration, rate, magnitude, and mechanism. Here we use our catalog from 2015-2016, acquired using a dense network of 55 temporary broadband seismometers, complemented by data from 40+ regional stations, including the IRIS Wavefields stations. We compare seismicity between these structural settings using precise earthquake locations, focal mechanism solutions, and body-wave tomography. Within and along the dominant Nemaha uplift, earthquakes rarely occur on one of the primary uplift-bounding faults. Earthquakes instead occur within the uplift on isolated, discrete faults, and migrate gradually along these faults at 20-30 m/day. The regions peripheral to the uplift hosted the majority of earthquakes within the year, on multiple series of frequently unmapped, densely-spaced, subparallel faults. We did not detect a similar slow migration along these faults. Earthquakes instead occurred via progressive failure of individual segments along a fault, or jumped abruptly from one fault to another nearby. Mechanisms in both regions are dominantly strike-slip, with the interpreted dominant fault plane orientation rotating from N100E in the Wavefields area (west of the uplift) to N50E (within the uplift). We interpret that the distinct variation in seismicity may result from the variation in fault density and length between the uplift and the surrounding regions. Seismic velocity within the upper basement of the uplift is lower than the velocity on either side, possibly indicative of enhanced fracturing within the uplift, as seen in the Nemaha uplift to the north. The fracturing, along with the large faults, may create fluid pathways that facilitate pressure diffusion. Conversely, outside of the uplift, the numerous small-offset faults that are reactivated appear to be less efficient fluid pathways, inhibiting pressure diffusion and resulting in a higher seismicity rate.

  18. Imaging the internal structure of fluid upflow zones with detailed digital Parasound echosounder surveys

    NASA Astrophysics Data System (ADS)

    Spiess, V.; Zuehlsdorff, L.; von Lom-Keil, H.; Schwenk, T.

    2001-12-01

    Sites of venting fluids both with continuous and episodic supply often reveal complex surface and internal structures, which are difficult to image and cause problems to transfer results from local sampling towards a structural reconstruction and a quantification of (average) flux rates. Detailed acoustic and seismic surveys would be required to retrieve this information, but also an appropriate environment, where fluid migration can be properly imaged from contrasts to unaffected areas. Hemipelagic sediments are most suitable, since typically reflectors are coherent and of low lateral amplitude variation and structures are continuous over distances much longer than the scale of fluid migration features. During RV Meteor Cruise M473 and RV Sonne Cruise SO 149 detailed studies were carried out in the vicinity of potential fluid upflow zones in the Lower Congo Basin at 5oS in 3000 m water depth and at the Northern Cascadia Margin in 1000 m water depth. Unexpected sampling of massive gas hydrates from the sea floor as well as of carbonate concretions, shell fragments and different liveforms indicated active fluid venting in a typically hemipelagic realm. The acoustic signature of such zones includes columnar blanking, pockmark depressions at the sea floor, association with small offset faults (< 1m). A dedicated survey with closely spaced grid lines was carried out with the Parasound sediment echosounder (4 kHz), which data were digitally acquired with the ParaDigMA System for further processing and display, to image the spatial structure of the upflow zones. Due to the high data density amplitudes and other acoustic properties could be investigated in a 3D volume and time slices as well as reflector surfaces were analyzed. Pronounced lateral variations of reflection amplitudes within a complex pattern indicate potential pathways for fluid/gas migration and occurrences of near-surface gas hydrate deposits, which may be used to trace detailed surface evidence from side scan sonar imaging down to depth and support dedicated sampling.

  19. Mevastatin ameliorates sphingosine 1‐phosphate‐induced COX‐2/PGE2‐dependent cell migration via FoxO1 and CREB phosphorylation and translocation

    PubMed Central

    Hsu, Chih‐Kai; Lin, Chih‐Chung; Hsiao, Li‐Der

    2015-01-01

    Background and Purpose Sphingosine 1‐phosphate (S1P), an important inflammatory mediator, has been shown to regulate COX‐2 production and promote various cellular responses such as cell migration. Mevastatin, an inhibitor of 3‐hydroxy‐3‐methylglutaryl‐CoA reductase (HMG‐CoA), effectively inhibits inflammatory responses. However, the mechanisms underlying S1P‐evoked COX‐2‐dependent cell migration, which is modulated by mevastatin in human tracheal smooth muscle cells (HTSMCs) remain unclear. Experimental Approach The expression of COX‐2 was determined by Western blotting, real time‐PCR and promoter analyses. The signalling molecules were investigated by pretreatment with respective pharmacological inhibitors or transfection with siRNAs. The interaction between COX‐2 promoter and transcription factors was determined by chromatin immunoprecipitation assay. Finally, the effect of mevastatin on HTSMC migration and leukocyte counts in BAL fluid and COX‐2 expression induced by S1P was determined by a cell migration assay, cell counting and Western blot. Key Results S1P stimulated mTOR activation through the Nox2/ROS and PI3K/Akt pathways, which can further stimulate FoxO1 phosphorylation and translocation to the cytosol. We also found that S1P induced CREB activation and translocation via an mTOR‐independent signalling pathway. Finally, we showed that pretreatment with mevastatin markedly reduced S1P‐induced cell migration and COX‐2/PGE2 production via a PPARγ‐dependent signalling pathway. Conclusions and Implications Mevastatin attenuates the S1P‐induced increased expression of COX‐2 and cell migration via the regulation of FoxO1 and CREB phosphorylation and translocation by PPARγ in HTSMCs. Mevastatin could be beneficial for prevention of airway inflammation in the future. PMID:26359950

  20. Cap rock efficiency of geothermal systems in fold-and-thrust belts: Evidence from paleo-thermal and structural analyses in Rosario de La Frontera geothermal area (NW Argentina)

    NASA Astrophysics Data System (ADS)

    Maffucci, R.; Corrado, S.; Aldega, L.; Bigi, S.; Chiodi, A.; Di Paolo, L.; Giordano, G.; Invernizzi, C.

    2016-12-01

    Cap rock characterization of geothermal systems is often neglected despite fracturing may reduce its efficiency and favours fluid migration. We investigated the siliciclastic cap rock of Rosario de La Frontera geothermal system (NW Argentina) in order to assess its quality as a function of fracture patterns and related thermal alteration. Paleothermal investigations (XRD on fine-grained fraction of sediments, organic matter optical analysis and fluid inclusions on veins) and 1D thermal modelling allowed us to distinguish the thermal fingerprint associated to sedimentary burial from that related to fluid migration. The geothermal system is hosted in a Neogene N-S anticline dissected by high angle NNW- and ENE-striking faults. Its cap rock can be grouped into two quality categories: rocks acting as good insulators, deformed by NNW-SSE and E-W shear fractures, NNE-SSW gypsum- and N-S-striking calcite-filled veins that developed during the initial stage of anticline growth. Maximum paleo-temperatures (< 60 °C) were experienced during deposition to folding phases. rocks acting as bad insulators, deformed by NNW-SSE fault planes and NNW- and WNW-striking sets of fractures associated to late transpressive kinematics. Maximum paleo-temperatures higher than about 115 °C are linked to fluid migration from the reservoir to surface (with a reservoir top at maximum depths of 2.5 km) along fault damage zones. This multi-method approach turned out to be particularly useful to trace the main pathways of hot fluids and can be applied in blind geothermal systems where either subsurface data are scarce or surface thermal anomalies are lacking.

  1. Recent progress of particle migration in viscoelastic fluids.

    PubMed

    Yuan, Dan; Zhao, Qianbin; Yan, Sheng; Tang, Shi-Yang; Alici, Gursel; Zhang, Jun; Li, Weihua

    2018-02-13

    Recently, research on particle migration in non-Newtonian viscoelastic fluids has gained considerable attention. In a viscoelastic fluid, three dimensional (3D) particle focusing can be easily realized in simple channels without the need for any external force fields or complex microchannel structures compared with that in a Newtonian fluid. Due to its promising properties for particle precise focusing and manipulation, this field has been developed rapidly, and research on the field has been shifted from fundamentals to applications. This review will elaborate the recent progress of particle migration in viscoelastic fluids, especially on the aspect of applications. The hydrodynamic forces on the micro/nano particles in viscoelastic fluids are discussed. Next, we elaborate the basic particle migration in viscoelasticity-dominant fluids and elasto-inertial fluids in straight channels. After that, a comprehensive review on the applications of viscoelasticity-induced particle migration (particle separation, cell deformability measurement and alignment, particle solution exchange, rheometry-on-a-chip and others) is presented; finally, we thrash out some perspectives on the future directions of particle migration in viscoelastic fluids.

  2. Asymmetry of Radial and Symmetry of Tangential Neuronal Migration Pathways in Developing Human Fetal Brains

    PubMed Central

    Miyazaki, Yuta; Song, Jae W.; Takahashi, Emi

    2016-01-01

    The radial and tangential neural migration pathways are two major neuronal migration streams in humans that are critical during corticogenesis. Corticogenesis is a complex process of neuronal proliferation that is followed by neuronal migration and the formation of axonal connections. Existing histological assessments of these two neuronal migration pathways have limitations inherent to microscopic studies and are confined to small anatomic regions of interest (ROIs). Thus, little evidence is available about their three-dimensional (3-D) fiber pathways and development throughout the entire brain. In this study, we imaged and analyzed radial and tangential migration pathways in the whole human brain using high-angular resolution diffusion MR imaging (HARDI) tractography. We imaged ten fixed, postmortem fetal (17 gestational weeks (GW), 18 GW, 19 GW, three 20 GW, three 21 GW and 22 GW) and eight in vivo newborn (two 30 GW, 34 GW, 35 GW and four 40 GW) brains with no neurological/pathological conditions. We statistically compared the volume of the left and right radial and tangential migration pathways, and the volume of the radial migration pathways of the anterior and posterior regions of the brain. In specimens 22 GW or younger, the volume of radial migration pathways of the left hemisphere was significantly larger than that of the right hemisphere. The volume of posterior radial migration pathways was also larger when compared to the anterior pathways in specimens 22 GW or younger. In contrast, no significant differences were observed in the radial migration pathways of brains older than 22 GW. Moreover, our study did not identify any significant differences in volumetric laterality in the tangential migration pathways. These results suggest that these two neuronal migration pathways develop and regress differently, and radial neuronal migration varies regionally based on hemispheric and anterior-posterior laterality, potentially explaining regional differences in the amount of excitatory neurons that migrate along the radial scaffold. PMID:26834572

  3. Analogue modelling of caprock failure and sediment mobilisation due to pore fluid overpressure in shallow reservoirs

    NASA Astrophysics Data System (ADS)

    Warsitzka, Michael; Kukowski, Nina; May, Franz

    2017-04-01

    Injection of CO2 in geological formations may cause excess pore fluid pressure by enhancing the fluid volume in the reservoir rock and by buoyancy-driven flow. If sediments in the reservoir and the caprock are undercompacted, pore fluid overpressure can lead to hydro-fractures in the caprock and fluidisation of sediments. Eventually, these processes trigger the formation of pipe structures, gas chimneys, gas domes or sand injections. Generally, such structures serve as high permeable pathways for fluid migration through a low-permeable seal layer and have to be considered in risk assessment or modelling of caprock integrity of CO2 storage sites. We applied scaled analogue experiments to characterise and quantify mechanisms determining the onset and migration of hydro-fractures in a low-permeable, cohesive caprock and fluidisation of unconsolidated sediments of the reservoir layer. The caprock is simulated by different types of cohesive powder. The reservoir layer consists of granulates with small particle density. Air injected through the base of the experiment and additionally through a single needle valve reaching into the analogue material is applied to generate fluid pressure within the materials. With this procedure, regional fluid pressure increase or a point-like local fluid pressure increase (e.g. injection well), respectively, can be simulated. The deformation in the analogue materials is analysed with a particle tracking imaging velocimetry technique. Pressure sensors at the base of the experiment and in the needle valve record the air pressure during an experimental run. The structural evolution observed in the experiments reveal that the cohesive cap rock first forms a dome-like anticline. Extensional fractures occur at the hinges of the anticline. A further increase of fluid pressure causes a migration of this fractures towards the surface, which is followed by intrusion of reservoir material into the fractures and the collapse of the anticline. The breakthrough of the fractures at the surface is accompanied by a significant drop of air pressure at the base of the analogue materials. The width of the dome shaped uplift is narrower and the initiating fluid pressure in the needle valve is lower, if the fluid pressure at the base of the experiment is larger. The experimental outcomes help to evaluate if the injection of CO2 into a reservoir potentially provokes initiation or reactivation of fractures and sediment mobilisation structures.

  4. Assessment of brine migration along vertical pathways due to CO2 injection

    NASA Astrophysics Data System (ADS)

    Kissinger, Alexander; Class, Holger

    2016-04-01

    Global climate change, shortage of resources and the growing usage of renewable energy sources has lead to a growing demand for the utilization of subsurface systems which may create conflicts with essential public interests such as water supply from aquifers. For example, brine migration into potential drinking water aquifers due to the injection of CO2 into deep saline aquifers is perceived as a potential threat resulting from the Carbon Capture and Storage Technology (CCS). In this work, we focus on the large scale impacts of CO2 storage on brine migration but the methodology and the obtained results may also apply to other fields like waste water disposal, where large amounts of fluid are injected into the subsurface. We consider a realistic (but not real) on-shore site in the North German Basin with characteristic geological features. In contrast to modeling on the reservoir scale, the spatial scale in this work is much larger in both vertical and lateral direction, since the regional hydrogeology is considered as well. Structures such as fault zones, hydrogeological windows in the Rupelian clay or salt wall flanks are considered as potential pathways for displaced fluids into shallow systems and their influence needs to be taken into account. Simulations on this scale always require a compromise between the accuracy of the description of the relevant physical processes, data availability and computational resources. Therefore, we test different model simplifications and discuss them with respect to the relevant physical processes and the expected data availability. The simplifications in the models are concerned with the role of salt-induced density differences on the flow, with injection of brine (into brine) instead of CO2 into brine, and with simplifying the geometry of the site.

  5. Fluids in crustal deformation: Fluid flow, fluid-rock interactions, rheology, melting and resources

    NASA Astrophysics Data System (ADS)

    Lacombe, Olivier; Rolland, Yann

    2016-11-01

    Fluids exert a first-order control on the structural, petrological and rheological evolution of the continental crust. Fluids interact with rocks from the earliest stages of sedimentation and diagenesis in basins until these rocks are deformed and/or buried and metamorphosed in orogens, then possibly exhumed. Fluid-rock interactions lead to the evolution of rock physical properties and rock strength. Fractures and faults are preferred pathways for fluids, and in turn physical and chemical interactions between fluid flow and tectonic structures, such as fault zones, strongly influence the mechanical behaviour of the crust at different space and time scales. Fluid (over)pressure is associated with a variety of geological phenomena, such as seismic cycle in various P-T conditions, hydrofracturing (including formation of sub-horizontal, bedding-parallel veins), fault (re)activation or gravitational sliding of rocks, among others. Fluid (over)pressure is a governing factor for the evolution of permeability and porosity of rocks and controls the generation, maturation and migration of economic fluids like hydrocarbons or ore forming hydrothermal fluids, and is therefore a key parameter in reservoir studies and basin modeling. Fluids may also help the crust partially melt, and in turn the resulting melt may dramatically change the rheology of the crust.

  6. 75 FR 260 - Airworthiness Directives; Empresa Brasileira de Aeronautica S.A. (EMBRAER) Model ERJ 170...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-05

    ..., migration of flammable vapors and fluids to middle electronic bay may occur, which then could lead to an..., migration of flammable vapors and fluids to middle electronic bay may occur, which then could lead to an... assembly, migration of flammable vapors and fluids to middle electronic bay may occur, which then could...

  7. Tectonic impact on the dynamics of CO2-rich fluid migration in Utah

    NASA Astrophysics Data System (ADS)

    Nadine, E. Z.; Jean Luc, F.; Remy, D.; Battani, A.; Olivier, V.

    2009-12-01

    With the objective to rank the first order parameters acting in the long term CO2 storage, IFP is developing an integrated study based on the analytical results around the natural silici-clastic analogue of the Colorado Plateau in Utah. What are the dominant parameters which governed the fluid/gas migration in front of the Sevier fold-and-thrust Belt, particularly the CO2-enriched ones? Several sites have been investigated in Utah and Idaho provinces; in the Colorado Plateau, East and in front of the Sevier fold-and-thrust belt, as well as in the Basin & Range geological province North and South West of Salt Lake city (Sevier basin). As a first site selection, three distinct structural provinces have been analysed depending on their seal/reservoir characteristics for confinement: the Green River leaking area (Utah), where large WNW-ESE faults (Salt Wash, Little Wash F...) show several water, oil and gas (CO2, HC) seepages; the Basin & Range province (Utah & Idaho provinces) where low-angle normal faults are seismically active (leaking locally); and the Canyonlands zone (Utah), south of the Moab fault, where the system is well confined. The migration pathways used by composite gas and particularly CO2-enriched fluids (in the Green River area) combined with a reducing agent are locally easily recognisable by the bleaching effect where some reservoir levels or the faults pathways have been flushed. The architecture of the paleo and active fluid migration network can thus be mapped. As a second selective ranking, natural gas have been sampled either from oil/gas producing wells in the Moab area and Ferron Valley, or from natural seepages along leaking fault sections or from geysers along the Green-River fault system. The results, based on noble gas isotope analyses (Battani et al, AGU fall meeting 2009) show that 3 distinct provinces can be "isolated", either marked by the occurrence of mantle-derived CO2, or mixed mantle/crustal CO2 signature of varying ratio. How to explain the existence of these distinct provinces? Is it due to the physical properties of the reservoirs, to the evolution of the fracture and fault patterns changing through time in connection with paleostress fields, to the occurrence of a thick salt pillow in the Moab area which has driven the tectonic style and played as local seal, to the shale sealing properties when PCO2 increased at depth to the physical phase of the CO2 during migration or storage (dissolved, super-critical or gas), or finally to the seismic cyclicity. A possible strong linkage between the seismicity and the volcanic activity, corresponding to large CO2-rich gas expel, have been investigated. In order to constrain the architecture of the deep buried reservoirs and traps we analyzed the deformation through analogue models, the models have been acquired with X-Ray tomography at IFP. These parameters have been analysed for the three investigated areas, allowing to propose an integrated model of the local circulation and/or storage of the CO2-enriched fluid for each area.

  8. Numerical modeling of fracking fluid and methane migration through fault zones in shale gas reservoirs

    NASA Astrophysics Data System (ADS)

    Taherdangkoo, Reza; Tatomir, Alexandru; Sauter, Martin

    2017-04-01

    Hydraulic fracturing operation in shale gas reservoir has gained growing interest over the last few years. Groundwater contamination is one of the most important environmental concerns that have emerged surrounding shale gas development (Reagan et al., 2015). The potential impacts of hydraulic fracturing could be studied through the possible pathways for subsurface migration of contaminants towards overlying aquifers (Kissinger et al., 2013; Myers, 2012). The intent of this study is to investigate, by means of numerical simulation, two failure scenarios which are based on the presence of a fault zone that penetrates the full thickness of overburden and connect shale gas reservoir to aquifer. Scenario 1 addresses the potential transport of fracturing fluid from the shale into the subsurface. This scenario was modeled with COMSOL Multiphysics software. Scenario 2 deals with the leakage of methane from the reservoir into the overburden. The numerical modeling of this scenario was implemented in DuMux (free and open-source software), discrete fracture model (DFM) simulator (Tatomir, 2012). The modeling results are used to evaluate the influence of several important parameters (reservoir pressure, aquifer-reservoir separation thickness, fault zone inclination, porosity, permeability, etc.) that could affect the fluid transport through the fault zone. Furthermore, we determined the main transport mechanisms and circumstances in which would allow frack fluid or methane migrate through the fault zone into geological layers. The results show that presence of a conductive fault could reduce the contaminant travel time and a significant contaminant leakage, under certain hydraulic conditions, is most likely to occur. Bibliography Kissinger, A., Helmig, R., Ebigbo, A., Class, H., Lange, T., Sauter, M., Heitfeld, M., Klünker, J., Jahnke, W., 2013. Hydraulic fracturing in unconventional gas reservoirs: risks in the geological system, part 2. Environ Earth Sci 70, 3855-3873. Myers, T., 2012. Potential contaminant pathways from hydraulically fractured shale to aquifers. Groundwater, 50(6), 872-882. Reagan, M.T., Moridis, G.J., Keen, N.D., Johnson, J.N., 2015. Numerical simulation of the environmental impact of hydraulic fracturing of tight/shale gas reservoirs on near-surface groundwater: Background, base cases, shallow reservoirs, short-term gas, and water transport. Water Resources Research 51, 2543-2573. Tatomir, A., 2012. From Discrete to Continuum Concepts of Flow in Fractured Porous Media. Stuttgart University: University of Stuttgart.

  9. Slab melting beneath the Cascade Arc driven by dehydration of altered oceanic peridotite

    NASA Astrophysics Data System (ADS)

    Walowski, K. J.; Wallace, P. J.; Hauri, E. H.; Wada, I.; Clynne, M. A.

    2015-05-01

    Water is returned to Earth’s interior at subduction zones. However, the processes and pathways by which water leaves the subducting plate and causes melting beneath volcanic arcs are complex; the source of the water--subducting sediment, altered oceanic crust, or hydrated mantle in the downgoing plate--is debated; and the role of slab temperature is unclear. Here we analyse the hydrogen-isotope and trace-element signature of melt inclusions in ash samples from the Cascade Arc, where young, hot lithosphere subducts. Comparing these data with published analyses, we find that fluids in the Cascade magmas are sourced from deeper parts of the subducting slab--hydrated mantle peridotite in the slab interior--compared with fluids in magmas from the Marianas Arc, where older, colder lithosphere subducts. We use geodynamic modelling to show that, in the hotter subduction zone, the upper crust of the subducting slab rapidly dehydrates at shallow depths. With continued subduction, fluids released from the deeper plate interior migrate into the dehydrated parts, causing those to melt. These melts in turn migrate into the overlying mantle wedge, where they trigger further melting. Our results provide a physical model to explain melting of the subducted plate and mass transfer from the slab to the mantle beneath arcs where relatively young oceanic lithosphere is subducted.

  10. Slab melting beneath the Cascades Arc driven by dehydration of altered oceanic peridotite

    USGS Publications Warehouse

    Walowski, Kristina J; Wallace, Paul J.; Hauri, E.H.; Wada, I.; Clynne, Michael A.

    2015-01-01

    Water is returned to Earth’s interior at subduction zones. However, the processes and pathways by which water leaves the subducting plate and causes melting beneath volcanic arcs are complex; the source of the water—subducting sediment, altered oceanic crust, or hydrated mantle in the downgoing plate—is debated; and the role of slab temperature is unclear. Here we analyse the hydrogen-isotope and trace-element signature of melt inclusions in ash samples from the Cascade Arc, where young, hot lithosphere subducts. Comparing these data with published analyses, we find that fluids in the Cascade magmas are sourced from deeper parts of the subducting slab—hydrated mantle peridotite in the slab interior—compared with fluids in magmas from the Marianas Arc, where older, colder lithosphere subducts. We use geodynamic modelling to show that, in the hotter subduction zone, the upper crust of the subducting slab rapidly dehydrates at shallow depths. With continued subduction, fluids released from the deeper plate interior migrate into the dehydrated parts, causing those to melt. These melts in turn migrate into the overlying mantle wedge, where they trigger further melting. Our results provide a physical model to explain melting of the subducted plate and mass transfer from the slab to the mantle beneath arcs where relatively young oceanic lithosphere is subducted.

  11. Investigation of particle lateral migration in sample-sheath flow of viscoelastic fluid and Newtonian fluid.

    PubMed

    Yuan, Dan; Zhang, Jun; Yan, Sheng; Peng, Gangrou; Zhao, Qianbin; Alici, Gursel; Du, Hejun; Li, Weihua

    2016-08-01

    In this work, particle lateral migration in sample-sheath flow of viscoelastic fluid and Newtonian fluid was experimentally investigated. The 4.8-μm micro-particles were dispersed in a polyethylene oxide (PEO) viscoelastic solution, and then the solution was injected into a straight rectangular channel with a deionised (DI) water Newtonian sheath flow. Micro-particles suspended in PEO solution migrated laterally to a DI water stream, but migration in the opposite direction from a DI water stream to a PEO solution stream or from one DI water stream to another DI water stream could not be achieved. The lateral migration of particles depends on the viscoelastic properties of the sample fluids. Furthermore, the effects of channel length, flow rate, and PEO concentration were studied. By using viscoelastic sample flow and Newtonian sheath flow, a selective particle lateral migration can be achieved in a simple straight channel, without any external force fields. This particle lateral migration technique could be potentially used in solution exchange fields such as automated cell staining and washing in microfluidic platforms, and holds numerous biomedical applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. The acute neutrophil response mediated by S100 alarmins during vaginal Candida infections is independent of the Th17-pathway.

    PubMed

    Yano, Junko; Kolls, Jay K; Happel, Kyle I; Wormley, Floyd; Wozniak, Karen L; Fidel, Paul L

    2012-01-01

    Vulvovaginal candidiasis (VVC) caused by Candida albicans affects a significant number of women during their reproductive ages. Clinical observations revealed that a robust vaginal polymorphonuclear neutrophil (PMN) migration occurs in susceptible women, promoting pathological inflammation without affecting fungal burden. Evidence to date in the mouse model suggests that a similar acute PMN migration into the vagina is mediated by chemotactic S100A8 and S100A9 alarmins produced by vaginal epithelial cells in response to Candida. Based on the putative role for the Th17 response in mucosal candidiasis as well as S100 alarmin induction, this study aimed to determine whether the Th17 pathway plays a role in the S100 alarmin-mediated acute inflammation during VVC using the experimental mouse model. For this, IL-23p19(-/-), IL-17RA(-/-) and IL-22(-/-) mice were intravaginally inoculated with Candida, and vaginal lavage fluids were evaluated for fungal burden, PMN infiltration, the presence of S100 alarmins and inflammatory cytokines and chemokines. Compared to wild-type mice, the cytokine-deficient mice showed comparative levels of vaginal fungal burden and PMN infiltration following inoculation. Likewise, inoculated mice of all strains with substantial PMN infiltration exhibited elevated levels of vaginal S100 alarmins in both vaginal epithelia and secretions in the vaginal lumen. Finally, cytokine analyses of vaginal lavage fluid from inoculated mice revealed equivalent expression profiles irrespective of the Th17 cytokine status or PMN response. These data suggest that the vaginal S100 alarmin response to Candida does not require the cells or cytokines of the Th17 lineage, and therefore, the immunopathogenic inflammatory response during VVC occurs independently of the Th17-pathway.

  13. The Acute Neutrophil Response Mediated by S100 Alarmins during Vaginal Candida Infections Is Independent of the Th17-Pathway

    PubMed Central

    Yano, Junko; Kolls, Jay K.; Happel, Kyle I.; Wormley, Floyd; Wozniak, Karen L.; Fidel, Paul L.

    2012-01-01

    Vulvovaginal candidiasis (VVC) caused by Candida albicans affects a significant number of women during their reproductive ages. Clinical observations revealed that a robust vaginal polymorphonuclear neutrophil (PMN) migration occurs in susceptible women, promoting pathological inflammation without affecting fungal burden. Evidence to date in the mouse model suggests that a similar acute PMN migration into the vagina is mediated by chemotactic S100A8 and S100A9 alarmins produced by vaginal epithelial cells in response to Candida. Based on the putative role for the Th17 response in mucosal candidiasis as well as S100 alarmin induction, this study aimed to determine whether the Th17 pathway plays a role in the S100 alarmin-mediated acute inflammation during VVC using the experimental mouse model. For this, IL-23p19−/−, IL-17RA−/− and IL-22−/− mice were intravaginally inoculated with Candida, and vaginal lavage fluids were evaluated for fungal burden, PMN infiltration, the presence of S100 alarmins and inflammatory cytokines and chemokines. Compared to wild-type mice, the cytokine-deficient mice showed comparative levels of vaginal fungal burden and PMN infiltration following inoculation. Likewise, inoculated mice of all strains with substantial PMN infiltration exhibited elevated levels of vaginal S100 alarmins in both vaginal epithelia and secretions in the vaginal lumen. Finally, cytokine analyses of vaginal lavage fluid from inoculated mice revealed equivalent expression profiles irrespective of the Th17 cytokine status or PMN response. These data suggest that the vaginal S100 alarmin response to Candida does not require the cells or cytokines of the Th17 lineage, and therefore, the immunopathogenic inflammatory response during VVC occurs independently of the Th17-pathway. PMID:23050010

  14. Submarine gas seepage in a mixed contractional and shear deformation regime: Cases from the Hikurangi oblique-subduction margin

    NASA Astrophysics Data System (ADS)

    Plaza-Faverola, Andreia; Pecher, Ingo; Crutchley, Gareth; Barnes, Philip M.; Bünz, Stefan; Golding, Thomas; Klaeschen, Dirk; Papenberg, Cord; Bialas, Joerg

    2014-02-01

    Gas seepage from marine sediments has implications for understanding feedbacks between the global carbon reservoir, seabed ecology, and climate change. Although the relationship between hydrates, gas chimneys, and seafloor seepage is well established, the nature of fluid sources and plumbing mechanisms controlling fluid escape into the hydrate zone and up to the seafloor remain one of the least understood components of fluid migration systems. In this study, we present the analysis of new three-dimensional high-resolution seismic data acquired to investigate fluid migration systems sustaining active seafloor seepage at Omakere Ridge, on the Hikurangi subduction margin, New Zealand. The analysis reveals at high resolution, complex overprinting fault structures (i.e., protothrusts, normal faults from flexural extension, and shallow (<1 km) arrays of oblique shear structures) implicated in fluid migration within the gas hydrate stability zone in an area of 2 × 7 km. In addition to fluid migration systems sustaining seafloor seepage on both sides of a central thrust fault, the data show seismic evidence for subseafloor gas-rich fluid accumulation associated with proto-thrusts and extensional faults. In these latter systems fluid pressure dissipation through time has been favored, hindering the development of gas chimneys. We discuss the elements of the distinct fluid migration systems and the influence that a complex partitioning of stress may have on the evolution of fluid flow systems in active subduction margins.

  15. Gas and porewater composition of shallow sediments in the Tuaheni Basin, New Zealand

    NASA Astrophysics Data System (ADS)

    Rose, P. S.; Coffin, R. B.; Yoza, B.; Boyd, T. J.; Crutchley, G. J.; Mountjoy, J. J.; Pecher, I. A.

    2015-12-01

    Seismic profiles collected during previous investigations on the Hikurangi Margin, off the North Island, New Zealand showed bottom simulating reflectors (BSRs), which are generally indicative of the presence of free gas. Further, double BSRs clearly identified in the Tuaheni Basin were hypothesized to result from differences in gas composition and fluid migration. During a cruise on the RV Tangaroa in June 2015 (TAN 1508) additional seismic data were collected and used to identify piston coring targets. Coring locations were selected to sample around BSR pinch-outs and possible fluid migration pathways to determine gas composition and flux. Shallow sediments collected in June 2015 in the Tuaheni Basin had relatively low sediment headspace CH4 concentrations (6000ppm. Higher molecular weight alkanes were not detected in the sediment headspace gas at any location. Sediment porewater sulfate, chloride and sulfide concentrations will be presented with CH4concentration profiles and geophysical data.

  16. Microchemical evidence for episodic growth of antitaxial veins during fracture-controlled fluid flow

    NASA Astrophysics Data System (ADS)

    Barker, Shaun L. L.; Cox, Stephen F.; Eggins, Stephen M.; Gagan, Michael K.

    2006-10-01

    The mechanism by which syntectonic hydrothermal veins form is widely debated, with some workers suggesting that certain vein textures are related to specific fluid flow regimes. Central to the debate is whether vein formation involves advective fluid flow, or occurs by local diffusion of material from the surrounding wall rock. To address this issue, we integrated textural observations and microchemical analyses of a hydrothermal vein from the Lachlan Orogen, southeast Australia, to reveal information about vein growth history, changes in fluid chemistry, and the evolution of fluid flow pathways during vein growth. The study area is part of a regional-scale fault-fracture network in an interbedded limestone-shale sequence, which formed at depths of ˜ 5-10 km (˜ 150-200 °C) during late Devonian crustal shortening. This integrated approach demonstrates that the zonation of textures, Sr isotopes, stable isotopes (C, O), and trace and rare earth elements is distinctly asymmetrical about the median growth-line of the vein. δ 18O values in vein calcite (17.0-18.8‰, VSMOW) are lower than those in surrounding unaltered limestones (23-25‰, VSMOW), and vary systematically across the vein. In contrast, δ 13C values are relatively constant across most of the vein, but become markedly depleted ( ca. 4‰) immediately adjacent to the wall rock. This strong depletion in δ 13C was probably caused by the influx of more oxidised fluids during the latest stages of vein growth. Strontium isotope ratios ( 87Sr/ 86Sr) vary between 0.70912 and 0.70931 across the vein. Abrubt changes in 87Sr/ 86Sr, δ 18O, Ce/Ce *, Eu/Eu * and trace element concentrations indicate that vein growth was accompanied by stepwise changes in the fluid flow pathway and consequent variations in fluid chemistry. Taken together, our findings are not consistent with growth of fibrous antitaxial veins by diffusional transfer of material from the surrounding wall rock. Instead, they suggest that externally sourced fluids migrated along episodically changing fracture-controlled flow pathways. This has implications for the dynamics of crustal permeability and mineralisation.

  17. Inertial migration of elastic particles in a pressure-driven power-law fluid

    NASA Astrophysics Data System (ADS)

    Bowie, Samuel; Alexeev, Alexander

    2016-11-01

    Using three-dimensional computer simulations, we study the cross-stream migration of deformable particles in a channel filled with a non-Newtonian fluid driven by a pressure gradient. Our numerical approach integrates lattice Boltzmann method and lattice spring method in order to model fluid structural interactions of the elastic particle and the surrounding power fluid in the channel. The particles are modeled as elastic shells filled with a viscous fluid that are initially spherical. We focus on the regimes where the inertial effects cannot be neglected and cause cross-stream drift of particles. We probe the flow with different power law indexes including both the shear thickening and thinning fluids. We also examine migration of particles of with different elasticity and relative size. To isolate the non-Newtonian effects on particle migration, we compare the results with the inertial migration results found in the case where the channel is filled with a simple Newtonian fluid. The results can be useful for applications requiring high throughput separation, sorting, and focusing of both synthetic particles and biological cells in microfluidic devices. Financial support provided by National Science Foundation (NSF) Grant No. CMMI1538161.

  18. Sediment-hosted micro-disseminated gold mineralization constrained by basin paleo-topographic highs in the Youjiang basin, South China

    NASA Astrophysics Data System (ADS)

    Liu, Jianming; Ye, Jie; Ying, Hanlong; Liu, Jiajun; Zheng, Minghua; Gu, Xuexiang

    2002-06-01

    The Youjiang basin is a Devonian-Triassic rift basin on the southern margin of the Yangtze Craton in South China. Strong syndepositional faulting defined the basin-and-range style paleo-topography that further developed into isolated carbonate platforms surrounded by siliciclastic filled depressions. Finally, thick Triassic siliciclastic deposits covered the platforms completely. In the Youjiang basin, numerous sediment-hosted, micro-disseminated gold (SMG) deposits occur mainly in Permian-Triassic chert and siliciclastic rocks. SMG ores are often auriferous sedimentary rocks with relatively low sulfide contents and moderate to weak alteration. Similar to Carlin-type gold ores in North America, SMG ores in the Youjiang basin are characterized by low-temperature mineral assemblages of pyrite, arsenopyrite, realgar, stibnite, cinnabar, marcasite, chalcedony and carbonate. Most of the SMG deposits are remarkably distributed around the carbonate platforms. Accordingly, there are platform-proximal and platform-distal SMG deposits. Platform-proximal SMG deposits often occur in the facies transition zone between the underlying platform carbonate rocks and the overlying siliciclastic rocks with an unconformity (often a paleo-karst surface) in between. In the ores and hostrocks there are abundant synsedimentary-syndiagenetic fabrics such as lamination, convolute bedding, slump texture, soft-sediment deformation etc. indicating submarine hydrothermal deposition and syndepositional faulting. Numerous fluid-escape and liquefaction fabrics imply strong fluid migration during sediment basin evolution. Such large-scale geological and fabric evidence implies that SMG ores were formed during basin evolution, probably in connection with basinal fluids. It is well known that basinal fluids (especially sediment-sourced fluids) will migrate generally (1) upwards, (2) towards basin margins or basin topographic highs, (3) and from thicker towards thinner deposits during basin evolution. The isolated carbonate platform (as a basin paleo-high) and related syndepositional fault system, together with the unconformity-related facies succession, may have controlled the migration pathway of ore-forming basinal fluids and subsequently determined the location of SMG deposits in the Youjiang basin. Unlike Carlin-type gold deposits, SMG mineralization in the Youjiang basin may represent an integral aspect of the dynamic evolution of extensional basins along divergent continental margins.

  19. T-Lymphocytes Traffic into the Brain across the Blood-CSF Barrier: Evidence Using a Reconstituted Choroid Plexus Epithelium

    PubMed Central

    Strazielle, Nathalie; Creidy, Rita; Malcus, Christophe; Boucraut, José; Ghersi-Egea, Jean-François

    2016-01-01

    An emerging concept of normal brain immune surveillance proposes that recently and moderately activated central memory T lymphocytes enter the central nervous system (CNS) directly into the cerebrospinal fluid (CSF) via the choroid plexus. Within the CSF space, T cells inspect the CNS environment for cognate antigens. This gate of entry into the CNS could also prevail at the initial stage of neuroinflammatory processes. To actually demonstrate T cell migration across the choroidal epithelium forming the blood-CSF barrier, an in vitro model of the rat blood-CSF barrier was established in an “inverse” configuration that enables cell transmigration studies in the basolateral to apical, i.e. blood/stroma to CSF direction. Structural barrier features were evaluated by immunocytochemical analysis of tight junction proteins, functional barrier properties were assessed by measuring the monolayer permeability to sucrose and the active efflux transport of organic anions. The migratory behaviour of activated T cells across the choroidal epithelium was analysed in the presence and absence of chemokines. The migration pathway was examined by confocal microscopy. The inverse rat BCSFB model reproduces the continuous distribution of tight junction proteins at cell margins, the restricted paracellular permeability, and polarized active transport mechanisms, which all contribute to the barrier phenotype in vivo. Using this model, we present experimental evidence of T cell migration across the choroidal epithelium. Cell migration appears to occur via a paracellular route without disrupting the restrictive barrier properties of the epithelial interface. Apical chemokine addition strongly stimulates T cell migration across the choroidal epithelium. The present data provide evidence for the controlled migration of T cells across the blood-CSF barrier into brain. They further indicate that this recruitment route is sensitive to CSF-borne chemokines, extending the relevance of this migration pathway to neuroinflammatory and neuroinfectious disorders which are typified by elevated chemokine levels in CSF. PMID:26942913

  20. T-Lymphocytes Traffic into the Brain across the Blood-CSF Barrier: Evidence Using a Reconstituted Choroid Plexus Epithelium.

    PubMed

    Strazielle, Nathalie; Creidy, Rita; Malcus, Christophe; Boucraut, José; Ghersi-Egea, Jean-François

    2016-01-01

    An emerging concept of normal brain immune surveillance proposes that recently and moderately activated central memory T lymphocytes enter the central nervous system (CNS) directly into the cerebrospinal fluid (CSF) via the choroid plexus. Within the CSF space, T cells inspect the CNS environment for cognate antigens. This gate of entry into the CNS could also prevail at the initial stage of neuroinflammatory processes. To actually demonstrate T cell migration across the choroidal epithelium forming the blood-CSF barrier, an in vitro model of the rat blood-CSF barrier was established in an "inverse" configuration that enables cell transmigration studies in the basolateral to apical, i.e. blood/stroma to CSF direction. Structural barrier features were evaluated by immunocytochemical analysis of tight junction proteins, functional barrier properties were assessed by measuring the monolayer permeability to sucrose and the active efflux transport of organic anions. The migratory behaviour of activated T cells across the choroidal epithelium was analysed in the presence and absence of chemokines. The migration pathway was examined by confocal microscopy. The inverse rat BCSFB model reproduces the continuous distribution of tight junction proteins at cell margins, the restricted paracellular permeability, and polarized active transport mechanisms, which all contribute to the barrier phenotype in vivo. Using this model, we present experimental evidence of T cell migration across the choroidal epithelium. Cell migration appears to occur via a paracellular route without disrupting the restrictive barrier properties of the epithelial interface. Apical chemokine addition strongly stimulates T cell migration across the choroidal epithelium. The present data provide evidence for the controlled migration of T cells across the blood-CSF barrier into brain. They further indicate that this recruitment route is sensitive to CSF-borne chemokines, extending the relevance of this migration pathway to neuroinflammatory and neuroinfectious disorders which are typified by elevated chemokine levels in CSF.

  1. Gas-controlled seafloor doming on Opouawe Bank, offshore New Zealand

    NASA Astrophysics Data System (ADS)

    Koch, Stephanie; Berndt, Christian; Bialas, Joerg; Haeckel, Matthias; Crutchley, Gareth; Papenberg, Cord; Klaeschen, Dirk; Greinert, Jens

    2015-04-01

    The process of gas accumulation and subsequent sediment doming appears to be a precursory process in the development of methane seep sites on Opouawe Bank and might be a common characteristic for gas seeps in general. Seabed domes appear as unimpressive topographic highs with diameters ranging from 10-1000 m and exhibit small vertical displacements and layer thickness in comparison to their width. The dome-like uplift of the sediments results from an increase in pore pressure caused by gas accumulation in near-seabed sediments. In this context sediment doming is widely discussed to be a precursor of pockmark formation. Our results suggest that by breaching of domed seafloor sediments a new seep site can develop and contrary to ongoing discussion does not necessarily lead to the formation of pockmarks. There are clear differences in individual gas migration structures that indicate a progression through different evolutionary stages, which range from channeled gas flow and associated seismic blanking, to gas trapping beneath relatively low-permeability horizons, and finally overpressure accumulation and doming. We present high resolution sub-bottom profiler (Parasound) and 2D multichannel seismic data from Opouawe Bank, an accretionary ridge at the Hikurangi Margin, offshore New Zealand's North Island. Beneath this bank, methane migrates along stratigraphic pathways from a maximum source depth of 1500-2100 mbsf (meter below seafloor) towards active cold seeps at the seafloor. We show that, in the shallow sediment of the upper 100 mbsf, this primary migration mechanism changes into a process of gas accumulation leading to sediment doming. Modeling the height of the gas column necessary to create different dome geometries, shows that doming due to gas accumulation is feasible and consistent with field observations. The well-stratified, sub-horizontal strata that exist beneath Opouawe Bank provide favorable conditions for this type of seep development because shallow sub-vertical gas migration is forced to traverse sedimentary layering in the absence of faults that might otherwise have provided more efficient gas migration pathways. Thus, gas has to generate its own migration pathways through the progressive process of doming and breaking through the strata. The data from offshore New Zealand document that shallow sediment doming does not have to be associated with seafloor pockmarks and that models in which fluid migration through soft sediments necessarily culminates in pockmark formations are not applicable everywhere.

  2. Structural controls on the hydrogeology of the Costa Rica subduction thrust NW of the Osa Peninisula (Invited)

    NASA Astrophysics Data System (ADS)

    Bangs, N. L.; McIntosh, K. D.; Silver, E. A.; Kluesner, J.; Ranero, C. R.

    2013-12-01

    Three-dimensional seismic reflection data from the Costa Rica margin NW of the Osa peninsula have enabled us to map the subduction megathrust from the trench to ~12 km subseafloor beneath the shelf. The subduction thrust has a large, abrupt downdip transition in seismic reflection amplitude from very high to low amplitude 6 km subseafloor beneath the upper slope. This transition broadly corresponds with an increase in concentration of microseismic earthquakes potentially due to a significant increase in plate coupling (Bangs et al., 2012, AGU Fall Meeting, T13A-2587), thus linking seismic reflection amplitude to fluid content and mechanical coupling along the fault. A detailed look at the overriding plate reflectivity shows numerous high-amplitude, continuous seismic reflections through the upper plate, many of which are clearly reversed-polarity from the seafloor reflection and are thus likely active fluid conduits through the overriding margin wedge, the slope cover sediment, and the seafloor. Broadly, the structural grain of the margin wedge trends E-W and dips landward across the lower slope and onto the shelf, presumably due to stress imparted by subducting ridges. However, directly above the abrupt high-to-low plate-boundary reflection amplitude transition, structures within the overlying margin wedge reverse dip, steepen, and change strike to an ESE direction. Within this zone we interpret a set of parallel reflections with small offsets and reverse-polarity as high-angle reverse faults that act as fluid conduits leading directly into shallow fluid migration systems described by Bangs et al., 2012 (AGU Fall Meeting, T13A-2587) and Kluesner et al. [this meeting]. The coincidence between the plate-boundary reflection amplitude patterns and the change in structure implies that the fluid migration pathways that drain the plate interface are locally disrupted by overriding plate structure in two possible ways: 1) by focusing up dip fluid migration along the plate interface into a thinner but richer fluid zone along the subduction thrust, or 2) by creating a more direct, nearly vertical route along high-angle reverse faults through the overlying margin wedge to the seafloor (possibly shortened by a factor of two) and draining deeper portions of the plate-boundary more efficiently.

  3. Real-time Microseismic Processing for Induced Seismicity Hazard Detection

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Matzel, Eric M.

    Induced seismicity is inherently associated with underground fluid injections. If fluids are injected in proximity to a pre-existing fault or fracture system, the resulting elevated pressures can trigger dynamic earthquake slip, which could both damage surface structures and create new migration pathways. The goal of this research is to develop a fundamentally better approach to geological site characterization and early hazard detection. We combine innovative techniques for analyzing microseismic data with a physics-based inversion model to forecast microseismic cloud evolution. The key challenge is that faults at risk of slipping are often too small to detect during the site characterizationmore » phase. Our objective is to devise fast-running methodologies that will allow field operators to respond quickly to changing subsurface conditions.« less

  4. Could Fluid Seeps Originate from the Seismogenic Zone? Evidence from Southern Costa Rica

    NASA Astrophysics Data System (ADS)

    Silver, E. A.; Kluesner, J. W.; Nale, S. M.; Bangs, N. L.; McIntosh, K. D.; Ranero, C. R.; Tryon, M. D.; Spinelli, G. A.; Rathburn, T.; von Huene, R.

    2013-12-01

    The prevailing conceptual model of convergent margin hydrogeology is one in which fluid sourced from porosity loss and dehydration reactions seaward of the updip limit of the seismogenic zone reach the seafloor via relatively low angle splay faults that act as high permeability conduits through an otherwise nearly impermeable upper plate [e.g., Lauer and Saffer, GRL, 39:L13604, 2012; Saffer and Tobin, Ann. Rev. Earth Planet. Sci., 39:157-186, 2011]. Interpretation of newly acquired 3D seismic reflection data and high resolvability multibeam and backscatter data, showing evidence for abundant potential fluid seeps sourced beneath the sediment cover and farther landward than previously thought possible, may require reevaluation of this concept. Kluesner et al. [2013, G3, doi:10.1002/ggge.20058], identified 160 potential fluid seeps in an 11 km wide swath off southern Costa Rica, based on pockmarks and high backscatter mounds, each showing subsurface indicators of fluid migration in the seismic data. Approximately half of these potential seeps are on the outer continental shelf; these are landward of the updip limit of the seismogenic zone, as estimated by both the transition from high to low reflectivity of the plate boundary and the intersection of the 150°C isotherm with the plate boundary [Ranero et al., 2008, G3, doi:10.1029/2007GC001679; Bangs et al., 2012, AGU Fall Meeting, T13A-2587; Bangs et al., this meeting]. We have mapped high probability fluid pathways beneath these potential seeps, based on seismic meta-attribute volumes calculated using user-trained neural network algorithms [Kluesner et al., this meeting]. The mapped fluid pathways are high-angle through the sedimentary section, and they root into basement highs and basement faults. Fluids could originate along the plate interface, where potential sources and pathways are known (Mid-slope sites: Hensen et al., 2004, Geology, 32:201-204), or above or below the interface, although sources from these regions have not been reported. They could travel near vertical paths through the crustal rocks, or along a landward-dipping path, because the seismic data show landward dips but not seaward dips. If the fluids do come from the plate interface, they originate in the seismogenic zone. This inference can be tested by geochemical study of the outer shelf fluid seeps, where such sampling has not yet occurred.

  5. Changes in migration mode of brine and supercritical CO2 in imbibition process under steady flow state of very slow fluid velocities

    NASA Astrophysics Data System (ADS)

    Kogure, Tetsuya; Zhang, Yi; Nishizawa, Osamu; Xue, Ziqiu

    2018-05-01

    Relative permeability curves and flow mechanisms of CO2 and brine in Berea sandstone were investigated during a two-phase flow imbibition process, where CO2 saturation in the rock decreased from 55 per cent to 9 per cent by stepwise decrease of CO2/brine injection ratios. Total fluid flow velocity was 4.25 × 10-6 m/s, corresponding to the capillary number of order ˜10-8 for CO2 flow. The relative permeability curves showed a slight hysteresis compared to those during the drainage process. Local CO2 saturation and the differential pressure showed temporal fluctuations when the average differential pressure showed constant values or very small trends. The fluctuations in local CO2 saturation correlate with local porosity distributions. The differential pressure between the inlet and outlet ends showed the largest fluctuation when the CO2/brine ratio equals to one. A final brine-only injection resulted in more CO2 trapped within low porosity zones. These results suggest important roles of ganglion dynamics in the low flow rate ranges, where fluid pathways undergo repetitive brine snap-off and coalescence of CO2 ganglia that causes morphological changes in distributions of CO2 pathways.

  6. Evolution of fracture and fault-controlled fluid pathways in carbonates of the Albanides fold-thrust belt

    USGS Publications Warehouse

    Graham, Wall B.R.; Girbacea, R.; Mesonjesi, A.; Aydin, A.

    2006-01-01

    The process of fracture and fault formation in carbonates of the Albanides fold-thrust belt has been systematically documented using hierarchical development of structural elements from hand sample, outcrop, and geologic-map scales. The function of fractures and faults in fluid migration was elucidated using calcite cement and bitumen in these structures as a paleoflow indicator. Two prefolding pressure-solution and vein assemblages were identified: an overburden assemblage and a remote tectonic stress assemblage. Sheared layer-parallel pressure-solution surfaces of the overburden assemblage define mechanical layers. Shearing of mechanical layers associated with folding resulted in the formation of a series of folding assemblage fractures at different orientations, depending on the slip direction of individual mechanical layers. Prefolding- and folding-related fracture assemblages together formed fragmentation zones in mechanical layers and are the sites of incipient fault localization. Further deformation along these sites was accommodated by rotation and translation of fragmented rock, which formed breccia and facilitated fault offset across multiple mechanical layers. Strike-slip faults formed by this process are organized in two sets in an apparent conjugate pattern. Calcite cement and bitumen that accumulated along fractures and faults are evidence of localized fluid flow along fault zones. By systematic identification of fractures and faults, their evolution, and their fluid and bitumen contents, along with subsurface core and well-log data, we identify northeast-southwest-trending strike-slip faults and the associated structures as dominant fluid pathways in the Albanides fold-thrust belt. Copyright ?? 2006. The American Association of Petroleum Geologists. All rights reserved.

  7. Reactive transport of CO2-rich fluids in simulated wellbore interfaces: Experiments and models exploring behaviour on length scales of 1 to 6 m

    NASA Astrophysics Data System (ADS)

    Wolterbeek, T. K. T.; Raoof, A.; Peach, C. J.; Spiers, C. J.

    2016-12-01

    Defects present at casing-cement interfaces in wellbores constitute potential pathways for CO2 to migrate from geological storage systems. It is essential to understand how the transport properties of such pathways evolve when penetrated by CO2-rich fluids. While numerous studies have explored this problem at the decimetre length-scale, the 1-10-100 m scales relevant for real wellbores have received little attention. The present work addresses the effects of long-range reactive transport on a length scale of 1-6 m. This is done by means of a combined experimental and modelling study. The experimental work consisted of flow-through tests, performed on cement-filled steel tubes, 1-6 m in length, containing artificially debonded cement-interfaces. Four tests were performed, at 60-80 °C, imposing flow-through of CO2-rich fluid at mean pressures of 10-15 MPa, controlling the pressure difference at 0.12-4.8 MPa, while measuring flow-rate. In the modelling work, we developed a numerical model to explore reactive transport in CO2-exposed defects on a similar length scale. The formulation adopted incorporates fluid flow, advective and diffusive solute transport, and CO2-cement chemical reactions. Our results show that long-range reactive transport strongly affects the permeability evolution of CO2-exposed defects. In the experiments, sample permeability decreased by 2-4 orders, which microstructural observations revealed was associated with downstream precipitation of carbonates, possibly aided by migration of fines. The model simulations show precipitation in initially open defects produces a sharp decrease in flow rate, causing a transition from advection to diffusion-dominated reactive transport. While the modelling results broadly reproduce the experimental observations, it is further demonstrated that non-uniformity in initial defect aperture has a profound impact on self-sealing behaviour and system permeability evolution on the metre scale. The implication is that future reactive transport models and wellbore scale analyses must include defects with variable aperture in order to obtain reliable upscaling relations.

  8. Seismic texture and amplitude analysis of large scale fluid escape pipes using time lapses seismic surveys: examples from the Loyal Field (Scotland, UK)

    NASA Astrophysics Data System (ADS)

    Maestrelli, Daniele; Jihad, Ali; Iacopini, David; Bond, Clare

    2016-04-01

    Fluid escape pipes are key features of primary interest for the analysis of vertical fluid flow and secondary hydrocarbon migration in sedimentary basin. Identified worldwide (Løset et al., 2009), they acquired more and more importance as they represent critical pathways for supply of methane and potential structure for leakage into the storage reservoir (Cartwright & Santamarina, 2015). Therefore, understanding their genesis, internal characteristics and seismic expression, is of great significance for the exploration industry. Here we propose a detailed characterization of the internal seismic texture of some seal bypass system (e.g fluid escape pipes) from a 4D seismic survey (released by the BP) recently acquired in the Loyal Field. The seal by pass structure are characterized by big-scale fluid escape pipes affecting the Upper Paleogene/Neogene stratigraphic succession in the Loyal Field, Scotland (UK). The Loyal field, is located on the edge of the Faroe-Shetland Channel slope, about 130 km west of Shetland (Quadrants 204/205 of the UKCS) and has been recently re-appraised and re developed by a consortium led by BP. The 3D detailed mapping analysis of the full and partial stack survey (processed using amplitude preservation workflows) shows a complex system of fluid pipe structure rooted in the pre Lista formation and developed across the paleogene and Neogene Units. Geometrical analysis show that pipes got diameter varying between 100-300 m and a length of 500 m to 2 km. Most pipes seem to terminate abruptly at discrete subsurface horizons or in diffuse termination suggesting multiple overpressured events and lateral fluid migration (through Darcy flows) across the overburden units. The internal texture analysis of the large pipes, (across both the root and main conduit zones), using near, medium and far offset stack dataset (processed through an amplitude preserved PSTM workflow) shows a tendency of up-bending of reflection (rather than pulls up artefacts) affected by large scale fracture (semblance image) and seem consistent with a suspended mud/sand mixture non-fluidized fluid flow. Near-Middle-Far offsets amplitude analysis confirms that most of the amplitude anomalies within the pipes conduit and terminus are only partly related to gas. An interpretation of the possible texture observed is proposed with a discussion of the noise and artefact induced by resolution and migration problems. Possible hypothetical formation mechanisms for those Pipes are discussed.

  9. Constraints on Upward Migration of Hydraulic Fracturing Fluid and Brine

    PubMed Central

    Flewelling, Samuel A; Sharma, Manu

    2014-01-01

    Recent increases in the use of hydraulic fracturing (HF) to aid extraction of oil and gas from black shales have raised concerns regarding potential environmental effects associated with predictions of upward migration of HF fluid and brine. Some recent studies have suggested that such upward migration can be large and that timescales for migration can be as short as a few years. In this article, we discuss the physical constraints on upward fluid migration from black shales (e.g., the Marcellus, Bakken, and Eagle Ford) to shallow aquifers, taking into account the potential changes to the subsurface brought about by HF. Our review of the literature indicates that HF affects a very limited portion of the entire thickness of the overlying bedrock and therefore, is unable to create direct hydraulic communication between black shales and shallow aquifers via induced fractures. As a result, upward migration of HF fluid and brine is controlled by preexisting hydraulic gradients and bedrock permeability. We show that in cases where there is an upward gradient, permeability is low, upward flow rates are low, and mean travel times are long (often >106 years). Consequently, the recently proposed rapid upward migration of brine and HF fluid, predicted to occur as a result of increased HF activity, does not appear to be physically plausible. Unrealistically high estimates of upward flow are the result of invalid assumptions about HF and the hydrogeology of sedimentary basins. PMID:23895673

  10. MiR-9-5p promotes MSC migration by activating β-catenin signaling pathway.

    PubMed

    Li, Xianyang; He, Lihong; Yue, Qing; Lu, Junhou; Kang, Naixin; Xu, Xiaojing; Wang, Huihui; Zhang, Huanxiang

    2017-07-01

    Mesenchymal stem cells (MSCs) have the potential to treat various tissue damages, but the very limited number of cells that migrate to the damaged region strongly restricts their therapeutic applications. Full understanding of mechanisms regulating MSC migration will help to improve their migration ability and therapeutic effects. Increasing evidence shows that microRNAs play important roles in the regulation of MSC migration. In the present study, we reported that miR-9-5p was upregulated in hepatocyte growth factor -treated MSCs and in MSCs with high migration ability. Overexpression of miR-9-5p promoted MSC migration, whereas inhibition of endogenous miR-9-5p decreased MSC migration. To elucidate the underlying mechanism, we screened the target genes of miR-9-5p and report for the first time that CK1α and GSK3β, two inhibitors of β-catenin signaling pathway, were direct targets of miR-9-5p in MSCs and that overexpression of miR-9-5p upregulated β-catenin signaling pathway. In line with these data, inhibition of β-catenin signaling pathway by FH535 decreased the miR-9-5p-promoted migration of MSCs, while activation of β-catenin signaling pathway by LiCl rescued the impaired migration of MSCs triggered by miR-9-5p inhibitor. Furthermore, the formation and distribution of focal adhesions as well as the reorganization of F-actin were affected by the expression of miR-9-5p. Collectively, these results demonstrate that miR-9-5p promotes MSC migration by upregulating β-catenin signaling pathway, shedding light on the optimization of MSCs for cell replacement therapy through manipulating the expression level of miR-9-5p. Copyright © 2017 the American Physiological Society.

  11. Tanshinone IIA inhibits AGEs-induced proliferation and migration of cultured vascular smooth muscle cells by suppressing ERK1/2 MAPK signaling.

    PubMed

    Lu, Ming; Luo, Ying; Hu, Pengfei; Dou, Liping; Huang, Shuwei

    2018-01-01

    Vascular smooth muscle cells (VSMCs) play a key role in the pathogenesis of diabetic vascular disease. Our current study sought to explore the effects of tanshinone IIA on the proliferation and migration of VSMCs induced by advanced glycation end products (AGEs). In this study, we examined the effects of tanshinone IIA by cell proliferation assay and cell migration assay. And we explored the underlying mechanism by Western blotting. AGEs significantly induced the proliferation and migration of VSMCs, but treatment with tanshinone IIA attenuated these effects. AGEs could increase the activity of the ERK1/2 and p38 pathways but not the JNK pathway. Treatment with tanshinone IIA inhibited the AGEs-induced activation of the ERK1/2 pathway but not the p38 pathway. Tanshinone IIA inhibits AGEs-induced proliferation and migration of VSMCs by suppressing the ERK1/2 MAPK signaling pathway.

  12. Hypogene caves of the central Appalachian Shenandoah Valley in Virginia

    USGS Publications Warehouse

    Doctor, Daniel H.; Orndorff, Wil

    2017-01-01

    Several caves in the Shenandoah Valley in Virginia show evidence for early hypogenic conduit development with later-enhanced solution under partly confined phreatic conditions guided by geologic structures. Many (but not all) of these caves have been subsequently invaded by surface waters as a result of erosion and exhumation. Those not so affected are relict phreatic caves, bearing no relation to modern drainage patterns. Field and petrographic evidence shows that carbonate rocks hosting certain relict phreatic caves were dolomitized and/or silicified by early hydrothermal fluid migration in zones that served to locally enhance rock porosity, thus providing preferential pathways for later solution by groundwater flow, and making the surrounding bedrock more resistant to surficial weathering to result in caves that reside within isolated hills on the land surface. Features suggesting that deep phreatic processes dominated the development of these relict caves include (1) cave passage morphologies indicative of ascending fluids, (2) cave plans of irregular pattern, reflecting early maze or anastomosing development, (3) a general lack of cave breakdown and cave streams or cave stream deposits, and (4) calcite wall and pool coatings within isolated caves intersecting the local water table, and within unroofed caves at topographic locations elevated well above the local base level. Episodes of deep karstification were likely separated by long periods of geologic time, encompassing multiple phases of sedimentary fill and excavation within caves, and reflect a complex history of deep fluid migration that set the stage for later shallow speleogenesis that continues today.

  13. Fiber length and orientation prevent migration in fluid filters

    NASA Technical Reports Server (NTRS)

    Reiman, P. A.

    1966-01-01

    Stainless steel fiber web filter resists fiber migration which causes contamination of filtered fluids. This filter is capable of holding five times more particulate matter before arbitrary cutoff pressure drop and shows excellent retention in fuel flow at high rates.

  14. Modeling the Buildup of Annular Pressure in Cased and Uncased Annuli of Faulty Wellbores

    NASA Astrophysics Data System (ADS)

    Lackey, G.; Rajaram, H.

    2017-12-01

    Structurally sound wellbores are essential to oil and gas production, natural gas storage, and carbon dioxide sequestration operations. Wellbore integrity is easily assessed at the wellhead by the presence of pressure or gas flow in the outer annuli of a well, as it indicates the uncontrolled vertical migration of fluids outside the production casing. This phenomenon is typically referred to as sustained casing pressure (SCP), sustained annular pressure, or surface casing vent flow. Of particular concern is the buildup of pressure in the surface casing annulus. If the surface casing is sealed at the wellhead and cement is not brought into the bottom of the casing, annular pressure that builds induces gas migration when the fluid and entry pressure of the formation at the bottom of the surface casing is exceeded. Multiple incidents of stray gas migration from oil and gas operations have contaminated water wells in Colorado, Pennsylvania, and Ohio through this mechanism. Natural gas escaping the #25 Standard Senson well at the Aliso Gas storage facility in California, the largest accidental release of greenhouse gases in US history, also followed this pathway. Previous studies have modeled the buildup of SCP in faulty wells with fully-cased annuli that are isolated from the surrounding formation. However, the majority of onshore oil and gas wells in the US are constructed with uncased outermost annuli that are hydraulically connected to the surrounding subsurface. In this study, we adapt current approaches of modeling SCP to include the regulation of annular liquid level by formation fluid pressure, dissolution of gas into the annular liquids, the transport of aqueous gas by crossflow into deep formations, and gas migration away from the well, when the entry pressure of the formations or fractures along the uncased annulus is exceeded, to compare the buildup behavior of SCP in both uncased and fully-cased annuli. We consider well construction and subsurface geology representative of the Wattenberg Field in Colorado and interpret observations of sustained casing pressure collected by the Colorado Oil and Gas Conservation Commission. We demonstrate that the potential negative consequences of integrity loss are much greater for an uncased well than for fully-cased well.

  15. Cell-line-specific stimulation of tumor cell aggressiveness by wound healing factors - a central role for STAT3.

    PubMed

    Ekblad, Lars; Lindgren, Gustaf; Persson, Emma; Kjellén, Elisabeth; Wennerberg, Johan

    2013-01-25

    Local recurrence is a major factor affecting survival after treatment for head and neck squamous cell carcinoma (HNSCC). It is possible that the normal processes involved in wound healing after surgical removal of a primary tumor can boost the regrowth of residual cancer cells, thereby contributing to the recurrent growth. In this work, we collected human wound fluids and used them to investigate the effect of wound healing factors on HNSCC cell lines in vitro. Wound fluids were collected from thyroidectomized patients diagnosed with benign disease and were included in assays of cell proliferation, migration, cell scattering, and invasion. The involvement of intracellular signaling pathways and membrane receptors were investigated by western blotting and the inclusion of specific inhibitors. One out of four cell lines was greatly stimulated in proliferation, migration, cell scattering, and invasion by the addition of wound fluid as compared with addition of fetal bovine or human serum. These effects were accompanied by a sharp increase in activation of signal transducer and activator of transcription 3 (STAT3). Inhibition of STAT3 activation abolished the wound fluid response, showing that STAT3 plays an important role in the wound healing response. Several of the observed phenotypic changes were epithelial-to-mesenchymal transition (EMT)-like, but the appropriate changes were not seen in any of the EMT markers investigated. The involvement of c-Met or epidermal growth factor receptor family members was excluded, while the interleukin-6 receptor was found to be partly responsible for the activation of STAT3. In conclusion, we found cell-line-specific effects of wound healing factors on HNSCC, setting the stage for therapy development and predictive opportunities.

  16. Measurements of fluid transport by controllable vertical migrations of plankton

    NASA Astrophysics Data System (ADS)

    Houghton, Isabel A.; Dabiri, John O.

    2016-11-01

    Diel vertical migration of zooplankton has been proposed to be a significant contributor to local and possibly large-scale fluid transport in the ocean. However, studies of this problem to date have been limited to order-of-magnitude estimates based on first principles and a small number of field observations. In this work, we leverage the phototactic behavior of zooplankton to stimulate controllable vertical migrations in the laboratory and to study the associated fluid transport and mixing. Building upon a previous prototype system, a laser guidance system induces vertical swimming of brine shrimp (Artemia salina) in a 2.1 meter tall, density-stratified water tank. The animal swimming speed and spacing during the controlled vertical migration is characterized with video analysis. A schlieren imaging system is utilized to visualize density perturbations to a stable stratification for quantification of fluid displacement length scales and restratification timescales. These experiments can add to our understanding of the dynamics of active particles in stratified flows. NSF and US-Israel Binational Science Foundation.

  17. Exploring the Climate Change, Migration and Conflict Nexus.

    PubMed

    Burrows, Kate; Kinney, Patrick L

    2016-04-22

    The potential link between climate change, migration, and conflict has been widely discussed and is increasingly viewed by policy makers as a security issue. However, considerable uncertainty remains regarding the role that climate variability and change play among the many drivers of migration and conflict. The overall objective of this paper is to explore the potential pathways linking climate change, migration and increased risk of conflict. We review the existing literature surrounding this issue and break the problem into two components: the links between climate change and migration, and those between migration and conflict. We found a large range of views regarding the importance of climate change as a driver for increasing rates of migration and subsequently of conflict. We argue that future research should focus not only on the climate-migration-conflict pathway but also work to understand the other pathways by which climate variability and change might exacerbate conflict. We conclude by proposing five questions to help guide future research on the link between climate change, migration, and conflict.

  18. Exploring the Climate Change, Migration and Conflict Nexus

    PubMed Central

    Burrows, Kate; Kinney, Patrick L.

    2016-01-01

    The potential link between climate change, migration, and conflict has been widely discussed and is increasingly viewed by policy makers as a security issue. However, considerable uncertainty remains regarding the role that climate variability and change play among the many drivers of migration and conflict. The overall objective of this paper is to explore the potential pathways linking climate change, migration and increased risk of conflict. We review the existing literature surrounding this issue and break the problem into two components: the links between climate change and migration, and those between migration and conflict. We found a large range of views regarding the importance of climate change as a driver for increasing rates of migration and subsequently of conflict. We argue that future research should focus not only on the climate-migration-conflict pathway but also work to understand the other pathways by which climate variability and change might exacerbate conflict. We conclude by proposing five questions to help guide future research on the link between climate change, migration, and conflict. PMID:27110806

  19. Distribution and Characteristics of Seafloor Seepage Features in the Active Margin Offshore of SW Taiwan

    NASA Astrophysics Data System (ADS)

    Chen, T. T.; Hsu, H. H.; Liu, C. S.; Su, C. C.; Paull, C. K.; Chen, Y. H.; Caress, D. W.; Gwiazda, R.; Lundsten, E. M.

    2017-12-01

    In the active margin offshore of southwest (SW) Taiwan, west-vergent imbricated thrusts, folds and dipping strata are the main structural features. This is also the area where gas hydrates are widely distributed beneath the seafloor. Fluids from deep strata may migrate upwards along porous dipping layers or faults and then vent out to form seafloor seepage features in many of the gas hydrate prospects. A joint survey was conducted in May 2017 using MBARI mapping AUV and miniROV to investigate the seafloor seepage features. Numerous comet-shaped depressions (CSD) are mapped along flanks of several anticlinal ridges, and four carbonate mounds around CSD are observed from the ultra-high-resolution (1-m lateral resolution) bathymetry data collected by AUV. Samples of the carbonate mounds were collected by the mini-ROV, and their mineral compositions contain dolomite and ankerite. The AUV collected chirp sonar profiles and previously collected surface ship multichannel seismic reflection profiles across these seafloor features show that potential fluid migration pathways connect free gas trapped below the base of gas hydrate stability zone and the seafloor in the vicinity of these features. Our study suggests that the CSD could be an indicator of seafloor seepage and may be distribution widely in the active margin setting.

  20. A lateral signalling pathway coordinates shape volatility during cell migration

    PubMed Central

    Zhang, Liang; Luga, Valbona; Armitage, Sarah K.; Musiol, Martin; Won, Amy; Yip, Christopher M.; Plotnikov, Sergey V.; Wrana, Jeffrey L.

    2016-01-01

    Cell migration is fundamental for both physiological and pathological processes. Migrating cells usually display high dynamics in morphology, which is orchestrated by an integrative array of signalling pathways. Here we identify a novel pathway, we term lateral signalling, comprised of the planar cell polarity (PCP) protein Pk1 and the RhoGAPs, Arhgap21/23. We show that the Pk1–Arhgap21/23 complex inhibits RhoA, is localized on the non-protrusive lateral membrane cortex and its disruption leads to the disorganization of the actomyosin network and altered focal adhesion dynamics. Pk1-mediated lateral signalling confines protrusive activity and is regulated by Smurf2, an E3 ubiquitin ligase in the PCP pathway. Furthermore, we demonstrate that dynamic interplay between lateral and protrusive signalling generates cyclical fluctuations in cell shape that we quantify here as shape volatility, which strongly correlates with migration speed. These studies uncover a previously unrecognized lateral signalling pathway that coordinates shape volatility during productive cell migration. PMID:27226243

  1. Tanshinone IIA inhibits AGEs-induced proliferation and migration of cultured vascular smooth muscle cells by suppressing ERK1/2 MAPK signaling

    PubMed Central

    Lu, Ming; Luo, Ying; Hu, Pengfei; Dou, Liping; Huang, Shuwei

    2018-01-01

    Objective(s): Vascular smooth muscle cells (VSMCs) play a key role in the pathogenesis of diabetic vascular disease. Our current study sought to explore the effects of tanshinone IIA on the proliferation and migration of VSMCs induced by advanced glycation end products (AGEs). Materials and Methods: In this study, we examined the effects of tanshinone IIA by cell proliferation assay and cell migration assay. And we explored the underlying mechanism by Western blotting. Results: AGEs significantly induced the proliferation and migration of VSMCs, but treatment with tanshinone IIA attenuated these effects. AGEs could increase the activity of the ERK1/2 and p38 pathways but not the JNK pathway. Treatment with tanshinone IIA inhibited the AGEs-induced activation of the ERK1/2 pathway but not the p38 pathway. Conclusion: Tanshinone IIA inhibits AGEs-induced proliferation and migration of VSMCs by suppressing the ERK1/2 MAPK signaling pathway. PMID:29372041

  2. Dual role for DOCK7 in tangential migration of interneuron precursors in the postnatal forebrain.

    PubMed

    Nakamuta, Shinichi; Yang, Yu-Ting; Wang, Chia-Lin; Gallo, Nicholas B; Yu, Jia-Ray; Tai, Yilin; Van Aelst, Linda

    2017-12-04

    Throughout life, stem cells in the ventricular-subventricular zone generate neuroblasts that migrate via the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into local interneurons. Although progress has been made toward identifying extracellular factors that guide the migration of these cells, little is known about the intracellular mechanisms that govern the dynamic reshaping of the neuroblasts' morphology required for their migration along the RMS. In this study, we identify DOCK7, a member of the DOCK180-family, as a molecule essential for tangential neuroblast migration in the postnatal mouse forebrain. DOCK7 regulates the migration of these cells by controlling both leading process (LP) extension and somal translocation via distinct pathways. It controls LP stability/growth via a Rac-dependent pathway, likely by modulating microtubule networks while also regulating F-actin remodeling at the cell rear to promote somal translocation via a previously unrecognized myosin phosphatase-RhoA-interacting protein-dependent pathway. The coordinated action of both pathways is required to ensure efficient neuroblast migration along the RMS. © 2017 Nakamuta et al.

  3. Dual role for DOCK7 in tangential migration of interneuron precursors in the postnatal forebrain

    PubMed Central

    Yang, Yu-Ting; Yu, Jia-Ray; Tai, Yilin

    2017-01-01

    Throughout life, stem cells in the ventricular–subventricular zone generate neuroblasts that migrate via the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into local interneurons. Although progress has been made toward identifying extracellular factors that guide the migration of these cells, little is known about the intracellular mechanisms that govern the dynamic reshaping of the neuroblasts’ morphology required for their migration along the RMS. In this study, we identify DOCK7, a member of the DOCK180-family, as a molecule essential for tangential neuroblast migration in the postnatal mouse forebrain. DOCK7 regulates the migration of these cells by controlling both leading process (LP) extension and somal translocation via distinct pathways. It controls LP stability/growth via a Rac-dependent pathway, likely by modulating microtubule networks while also regulating F-actin remodeling at the cell rear to promote somal translocation via a previously unrecognized myosin phosphatase–RhoA–interacting protein-dependent pathway. The coordinated action of both pathways is required to ensure efficient neuroblast migration along the RMS. PMID:29089377

  4. Vaginal Migration of Ventriculoperitoneal Shunt Catheter and Cerebrospinal Fluid Leak as a Complication of Hysterectomy.

    PubMed

    Houten, John K; Smith, Shiela; Schwartz, Amit Y

    2017-08-01

    Ventriculoperitoneal (VP) shunting is a common neurosurgical procedure to treat hydrocephalus that diverts cerebrospinal fluid from the cerebral ventricles to the peritoneal cavity for reabsorption. The distal catheter may potentially migrate through any potential or iatrogenic opening in the peritoneal cavity. Increasingly successfully management of childhood hydrocephalus and adult-onset conditions leading to hydrocephalus, such as subarachnoid hemorrhage, is leading many adult female patients harboring VP shunts needing to undergo hysterectomy. Hysterectomy creates a potential defect though which a VP shunt catheter may migrate. It is not known whether the hysterectomy cuff closure technique may affect the likelihood of distal catheter migration though the repair site. We report the case of a 38-year-old woman with a VP shunt who underwent laparoscopic hysterectomy via an open vaginal cuff technique who subsequently presented with vaginal cerebrospinal fluid leakage secondary to migration of the distal shunt catheter through the hysterectomy cuff. Vaginal migration of the distal VP shunt catheter is a possible complication of hysterectomy. The authors postulate that an open cuff hysterectomy closure technique may increase the risk of catheter migration, an issue that may be better understood with further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Migration Pathways of Thalamic Neurons and Development of Thalamocortical Connections in Humans Revealed by Diffusion MR Tractography.

    PubMed

    Wilkinson, Molly; Kane, Tara; Wang, Rongpin; Takahashi, Emi

    2017-12-01

    The thalamus plays an important role in signal relays in the brain, with thalamocortical (TC) neuronal pathways linked to various sensory/cognitive functions. In this study, we aimed to see fetal and postnatal development of the thalamus including neuronal migration to the thalamus and the emergence/maturation of the TC pathways. Pathways from/to the thalami of human postmortem fetuses and in vivo subjects ranging from newborns to adults with no neurological histories were studied using high angular resolution diffusion MR imaging (HARDI) tractography. Pathways likely linked to neuronal migration from the ventricular zone and ganglionic eminence (GE) to the thalami were both successfully detected. Between the ventricular zone and thalami, more tractography pathways were found in anterior compared with posterior regions, which was well in agreement with postnatal observations that the anterior TC segment had more tract count and volume than the posterior segment. Three different pathways likely linked to neuronal migration from the GE to the thalami were detected. No hemispheric asymmetry of the TC pathways was quantitatively observed during development. These results suggest that HARDI tractography is useful to identify multiple differential neuronal migration pathways in human brains, and regional differences in brain development in fetal ages persisted in postnatal development. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Passive non-linear microrheology for determining extensional viscosity

    NASA Astrophysics Data System (ADS)

    Hsiao, Kai-Wen; Dinic, Jelena; Ren, Yi; Sharma, Vivek; Schroeder, Charles M.

    2017-12-01

    Extensional viscosity is a key property of complex fluids that greatly influences the non-equilibrium behavior and processing of polymer solutions, melts, and colloidal suspensions. In this work, we use microfluidics to determine steady extensional viscosity for polymer solutions by directly observing particle migration in planar extensional flow. Tracer particles are suspended in semi-dilute solutions of DNA and polyethylene oxide, and a Stokes trap is used to confine single particles in extensional flows of polymer solutions in a cross-slot device. Particles are observed to migrate in the direction transverse to flow due to normal stresses, and particle migration is tracked and quantified using a piezo-nanopositioning stage during the microfluidic flow experiment. Particle migration trajectories are then analyzed using a second-order fluid model that accurately predicts that migration arises due to normal stress differences. Using this analytical framework, extensional viscosities can be determined from particle migration experiments, and the results are in reasonable agreement with bulk rheological measurements of extensional viscosity based on a dripping-onto-substrate method. Overall, this work demonstrates that non-equilibrium properties of complex fluids can be determined by passive yet non-linear microrheology.

  7. Relationship between karstification and burial dolomitization in Permian platform carbonates (Lower Khuff - Oman)

    NASA Astrophysics Data System (ADS)

    Beckert, Julia; Vandeginste, Veerle; John, Cédric M.

    2016-08-01

    Large breccia fabrics associated with karst constitute an important structure in massive limestone successions. The dimensions and shapes of breccia structures are controlled by the initial fracture pattern of the limestone and preferential pathways of the karstifying fluids, but subsequently breccia fabrics can also govern the migration of later fluids. Therefore, breccias are highly relevant features to capture for reservoir characterisation. Outcrop analogues for Lower Khuff units in the Middle East present in the Central Oman Mountains reveal brecciated fabrics up to 10s of metres in diameter. These brecciated units are closely associated with dolomite bodies of late diagenetic origin. Based on an integrated set of data, the breccias are interpreted as collapsed karst cavities either formed by meteoric or hypogenic fluids. The exact origin of the fluids could not be constrained due to an overprint by later dolomitizing fluids. Based on the composition of the clasts and matrix in the breccias, two dolomitization events are interpreted to have affected the succession, one prior to (early diagenetic [ED] dolomite) and one after brecciation (late diagenetic [DT2] dolomite). Dolomite of shallow burial origin (ED dolomite) was only observed as clasts within breccia and is much more frequent than late diagenetic (medium to deep burial) dolomite clasts. Thus, the timing of the brecciation and collapse is assumed to postdate shallow burial early diagenetic dolomitization. Late diagenetic replacive dolomite (DT2 dolomite) forms 90% of the matrix in the breccia fabrics with the exception of a small area that was not affected by dolomitization, but is rarely present as clasts. Stable isotope measurements [δ18O: - 2.5‰ to - 6‰ VPDB and δ13C: 2.9‰ to 4.8‰ VPDB] suggest a burial origin for the late diagenetic dolomite potentially with the participation of hydrothermal fluids. The dolomitized matrix indicates a migration of late dolomitizing fluids subsequent to or postdating the collapse of the karstic cavities. Thus, early karstification processes seem to have played a big role in controlling subsequent loci of late dolomitization in the Oman Mountains, and potentially in other similar settings elsewhere.

  8. The Golgi in Cell Migration: Regulation by Signal Transduction and Its Implications for Cancer Cell Metastasis

    PubMed Central

    Millarte, Valentina; Farhan, Hesso

    2012-01-01

    Migration and invasion are fundamental features of metastatic cancer cells. The Golgi apparatus, an organelle involved in posttranslational modification and sorting of proteins, is widely accepted to regulate directional cell migration. In addition, mounting evidence suggests that the Golgi is a hub for different signaling pathways. In this paper we will give an overview on how polarized secretion and microtubule nucleation at the Golgi regulate directional cell migration. We will review different signaling pathways that signal to and from the Golgi. Finally, we will discuss how these signaling pathways regulate the role of the Golgi in cell migration and invasion. We propose that by identifying regulators of the Golgi, we might be able to uncover unappreciated modulators of cell migration. Uncovering the regulatory network that orchestrates cell migration is of fundamental importance for the development of new therapeutic strategies against cancer cell metastasis. PMID:22623902

  9. Correlation between deep fluids, tremor and creep along the central San Andreas fault

    USGS Publications Warehouse

    Becken, M.; Ritter, O.; Bedrosian, P.A.; Weckmann, U.

    2011-01-01

    The seismicity pattern along the San Andreas fault near Parkfield and Cholame, California, varies distinctly over a length of only fifty kilometres. Within the brittle crust, the presence of frictionally weak minerals, fault-weakening high fluid pressures and chemical weakening are considered possible causes of an anomalously weak fault northwest of Parkfield. Non-volcanic tremor from lower-crustal and upper-mantle depths is most pronounced about thirty kilometres southeast of Parkfield and is thought to be associated with high pore-fluid pressures at depth. Here we present geophysical evidence of fluids migrating into the creeping section of the San Andreas fault that seem to originate in the region of the uppermost mantle that also stimulates tremor, and evidence that along-strike variations in tremor activity and amplitude are related to strength variations in the lower crust and upper mantle. Interconnected fluids can explain a deep zone of anomalously low electrical resistivity that has been imaged by magnetotelluric data southwest of the Parkfield-Cholame segment. Near Cholame, where fluids seem to be trapped below a high-resistivity cap, tremor concentrates adjacent to the inferred fluids within a mechanically strong zone of high resistivity. By contrast, subvertical zones of low resistivity breach the entire crust near the drill hole of the San Andreas Fault Observatory at Depth, northwest of Parkfield, and imply pathways for deep fluids into the eastern fault block, coincident with a mechanically weak crust and the lower tremor amplitudes in the lower crust. Fluid influx to the fault system is consistent with hypotheses of fault-weakening high fluid pressures in the brittle crust.

  10. How does the architecture of a fault system controls magma upward migration through the crust?

    NASA Astrophysics Data System (ADS)

    Iturrieta, P. C.; Cembrano, J. M.; Stanton-Yonge, A.; Hurtado, D.

    2017-12-01

    The orientation and relative disposition of adjacent faults locally disrupt the regional stress field, thus enhancing magma flow through previous or newly created favorable conduits. Moreover, the brittle-plastic transition (BPT), due to its stronger rheology, governs the average state of stress of shallower portions of the fault system. Furthermore, the BPT may coincide with the location of transient magma reservoirs, from which dikes can propagate upwards into the upper crust, shaping the inner structure of the volcanic arc. In this work, we examine the stress distribution in strike-slip duplexes with variable geometry, along with the critical fluid overpressure ratio (CFOP), which is the minimum value required for individual faults to fracture in tension. We also determine the stress state disruption of the fault system when a dike is emplaced, to answer open questions such as: what is the nature of favorable pathways for magma to migrate? what is the architecture influence on the feedback between fault system kinematics and magma injection? To this end, we present a 3D coupled hydro-mechanical finite element model of the continental lithosphere, where faults are represented as continuum volumes with an elastic-plastic rheology. Magma flow upon fracturing is modeled through non-linear Stoke's flow, coupling solid and fluid equilibrium. A non-linear sensitivity analysis is performed in function of tectonic, rheology and geometry inputs, to assess which are the first-order factors that governs the nature of dike emplacement. Results show that the CFOP is heterogeneously distributed in the fault system, and within individual fault segments. Minimum values are displayed near fault intersections, where local kinematics superimpose on regional tectonic loading. Furthermore, when magma is transported through a fault segment, the CFOP is now minimized in faults with non-favorable orientations. This suggests that these faults act as transient pathways for magma to continue migrating upwards, which may explain the heterogeneity of seismicity patterns in volcano-tectonic seismic swarms. Likewise, once magma is injected, the consequent disruption of the stress field enhances the slip of faults which are not favorably oriented to the regional tectonic loading.

  11. CoCl2 , a mimic of hypoxia, enhances bone marrow mesenchymal stem cells migration and osteogenic differentiation via STAT3 signaling pathway.

    PubMed

    Yu, Xin; Wan, Qilong; Cheng, Gu; Cheng, Xin; Zhang, Jing; Pathak, Janak L; Li, Zubing

    2018-06-16

    Mesenchymal stem cells homing and migration is a crucial step during bone fracture healing. Hypoxic environment in fracture site induces bone marrow mesenchymal stem cells (BMSCs) migration, but its mechanism remains unclear. Our previous study and studies by other groups have reported the involvement of signal transducer and activator of transcription 3 (STAT3) pathway in cell migration. However, the role of STAT3 pathway in hypoxia-induced cell migration is still unknown. In this study, we investigated the role of STAT3 signaling in hypoxia-induced BMSCs migration and osteogenic differentiation. BMSCs isolated from C57BL/6 male mice were cultured in the presence of cobalt chloride (CoCl 2 ) to simulate intracellular hypoxia. Hypoxia enhanced BMSCs migration, and upregulated cell migration related gene expression i.e., metal-loproteinase (MMP) 7, MMP9 and C-X-C motif chemokine receptor 4. Hypoxia enhanced the phosphorylation of STAT3, and cell migration related proteins: c-jun n-terminal kinase (JNK), focal of adhesion kinase (FAK), extracellular regulated protein kinases and protein kinase B 1/2 (ERK1/2). Moreover, hypoxia enhanced expression of osteogenic differentiation marker. Inhibition of STAT3 suppressed the hy-poxia-induced BMSCs migration, cell migration related signaling molecules phos-phorylation, and osteogenic differentiation related gene expression. In conclusion, our result indicates that hypoxia-induced BMSCs migration and osteogenic differentiation is via STAT3 phosphorylation and involves the cooperative activity of the JNK, FAK and MMP9 signaling pathways. This article is protected by copyright. All rights reserved.

  12. Thrombin-induced Migration and Matrix Metalloproteinase-9 Expression Are Regulated by MAPK and PI3K Pathways in C6 Glioma Cells

    PubMed Central

    Kim, Jiyoung; Lee, Jae-Won; Kim, Song-In; Choi, Yong-Joon; Lee, Won-Ki; Jeong, Myung-Ja; Cha, Sang-Hoon; Lee, Hee Jae; Chun, Wanjoo

    2011-01-01

    Glioblastoma multiforme is one of the most common and aggressive tumors in central nervous system. It often possesses characteristic necrotic lesions with hemorrhages, which increase the chances of exposure to thrombin. Thrombin has been known as a regulator of MMP-9 expression and cancer cell migration. However, the effects of thrombin on glioma cells have not been clearly understood. In the present study, influences of thrombin on glioma cell migration were examined using Boyden chamber migration assay and thrombin-induced changes in MMP-9 expression were measured using zymography, semi-quantitative RT-PCR, and Western blotting. Furthermore, underlying signaling pathways by which thrombin induces MMP-9 expression were examined. Thrombin-induced migration and MMP-9 expression were significantly potentiated in the presence of wortmannin, a PI3K inhibitor, whereas MAPK inhibitors suppressed thrombin-induced migration and MMP-9 expression in C6 glioma cells. The present data strongly demonstrate that MAPK and PI3K pathways evidently regulate thrombin-induced migration and MMP-9 expression of C6 glioma cells. Therefore, the control of these pathways might be a beneficial therapeutic strategy for treatment of invasive glioblastoma multiforme. PMID:21994479

  13. Emergence and migration of trunk neural crest cells in a snake, the California Kingsnake (Lampropeltis getula californiae)

    PubMed Central

    2010-01-01

    Background The neural crest is a group of multipotent cells that emerges after an epithelial-to-mesenchymal transition from the dorsal neural tube early during development. These cells then migrate throughout the embryo, giving rise to a wide variety derivatives including the peripheral nervous system, craniofacial skeleton, pigment cells, and endocrine organs. While much is known about neural crest cells in mammals, birds, amphibians and fish, relatively little is known about their development in non-avian reptiles like snakes and lizards. Results In this study, we show for the first time ever trunk neural crest migration in a snake by labeling it with DiI and immunofluorescence. As in birds and mammals, we find that early migrating trunk neural crest cells use both a ventromedial pathway and an inter-somitic pathway in the snake. However, unlike birds and mammals, we also observed large numbers of late migrating neural crest cells utilizing the inter-somitic pathway in snake. Conclusions We found that while trunk neural crest migration in snakes is very similar to that of other amniotes, the inter-somitic pathway is used more extensively by late-migrating trunk neural crest cells in snake. PMID:20482793

  14. Emergence and migration of trunk neural crest cells in a snake, the California Kingsnake (Lampropeltis getula californiae).

    PubMed

    Reyes, Michelle; Zandberg, Katrina; Desmawati, Iska; de Bellard, Maria E

    2010-05-18

    The neural crest is a group of multipotent cells that emerges after an epithelial-to-mesenchymal transition from the dorsal neural tube early during development. These cells then migrate throughout the embryo, giving rise to a wide variety derivatives including the peripheral nervous system, craniofacial skeleton, pigment cells, and endocrine organs. While much is known about neural crest cells in mammals, birds, amphibians and fish, relatively little is known about their development in non-avian reptiles like snakes and lizards. In this study, we show for the first time ever trunk neural crest migration in a snake by labeling it with DiI and immunofluorescence. As in birds and mammals, we find that early migrating trunk neural crest cells use both a ventromedial pathway and an inter-somitic pathway in the snake. However, unlike birds and mammals, we also observed large numbers of late migrating neural crest cells utilizing the inter-somitic pathway in snake. We found that while trunk neural crest migration in snakes is very similar to that of other amniotes, the inter-somitic pathway is used more extensively by late-migrating trunk neural crest cells in snake.

  15. Focused fluid-flow processes through high-quality bathymetric, 2D seismic and Chirp data from the southern parts of the Bay of Biscay, France

    NASA Astrophysics Data System (ADS)

    Baudon, Catherine; Gillet, Hervé; Cremer, Michel

    2013-04-01

    High-quality bathymetric, 2D seismic and Chirp data located in the southern parts of the Bay of Biscay, France, collected by the University of Bordeaux 1 (Cruises ITSAS 2, 2001; PROSECAN 3, 2006 and SARGASS, 2010) have recently been compiled. The survey area widely covers the Capbreton Canyon, which lies on the boundary between two major structural zones: the Aquitanian passive margin to the North, and the Basque-Cantabrian margin to the South which corresponds to the offshore Pyrenean front. The dataset revealed a large number of key seafloor features potentially associated with focused fluid-flow processes and subsurface sediment-remobilization. Focused fluid migration through sub-seabed sediments is a common phenomenon on continental margins worldwide and has widespread implications from both industrial and fundamental perspectives, from seafloor marine environmental issues to petroleum exploration and hazard assessments. Our study analyses the relationships between seafloor features, deeper structures and fluid migration through the Plio-Quaternary sedimentary pile. The geometrical characteristics, mechanisms of formation and kinematics of four main groups of seabed features have been investigated. (i) A 150km2 field of pockmarks can be observed on the Basque margin. These features are cone-shaped circular or elliptical depressions that are either randomly distributed as small pockmarks (diameter < 20m) or aligned in trains of large pockmarks (ranging from 200 to 600m in diameter) along shallow troughs leading downstream to the Capbreton Canyon. Seismic data show that most pockmarks reach the seabed through vertically staked V-shaped features but some are buried and show evidence of lateral migration through time. (ii) A second field of widely-spaced groups of pockmarks pierce the upper slope of the Aquitanian margin. These depressions are typically a few hundred meters in diameter and seem to be preferentially located in the troughs or on the stoss sides of sediment waves. (iii) Several trains of small circular depressions are distributed along narrow channels that are up to 70 km in length and run downslope the south-western sides of the marginal Landes Plateau. (iv) The dataset also revealed isolated mega-pockmarks located on the Landes Plateau. These 1,5km-wide circular depressions exhibit a convex upward central part and show no evidence of underlying structure nor fluid migration pathways. However, collapsed strata within the infill sediments suggest that the structure is related to fluid expulsion. Interestingly, our results show that the base level of initiation for many of these features corresponds to a transition in seismic facies that is also marked by a seismic unconformity. This boundary can be interpreted as reflecting drastic changes in the sedimentary record related to an important transition in climatic cycles (i.e. base of Quaternary or Mid Pleistocene Revolution) and/or changes in the Mediterranean Outflow Water (bottom current).

  16. Mechano-growth factor induces migration of rat mesenchymal stem cells by altering its mechanical properties and activating ERK pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wu, Jiamin; Wu, Kewen; Lin, Feng

    2013-11-08

    Highlights: •MGF induced the migration of rat MSC in a concentration-dependent manner. •MGF enhanced the mechanical properties of rMSC in inducing its migration. •MGF activated the ERK 1/2 signaling pathway of rMSC in inducing its migration. •rMSC mechanics may synergy with ERK 1/2 pathway in MGF-induced rMSC migration. -- Abstract: Mechano-growth factor (MGF) generated by cells in response to mechanical stimulation has been identified as a mechano effector molecule, playing a key role in regulating mesenchymal stem cell (MSC) function, including proliferation and migration. However, the mechanism(s) underlying how MGF-induced MSC migration occurs is still unclear. In the present study,more » MGF motivated migration of rat MSCs (rMSCs) in a concentration-dependent manner and optimal concentration of MGF at 50 ng/mL (defined as MGF treatment in this paper) was demonstrated. Notably, enhancement of mechanical properties that is pertinent to cell migration, such as cell traction force and cell stiffness were found to respond to MGF treatment. Furthermore, MGF increased phosphorylation of extracellular signal-regulated kinase (ERK), ERK inhibitor (i.e., PD98059) suppressed ERK phosphorylation, and abolished MGF-induced rMSC migration were found, demonstrating that ERK is involved molecule for MGF-induced rMSC migration. These in vitro evidences of MGF-induced rMSC migration and its direct link to altering rMSC mechanics and activating the ERK pathway, uncover the underlying biomechanical and biological mechanisms of MGF-induced rMSC migration, which may help find MGF-based application of MSC in clinical therapeutics.« less

  17. Biogenic methane leakage on the Aquitaine Shelf: fluid system characterization from source to emission

    NASA Astrophysics Data System (ADS)

    Michel, Guillaume; Dupré, Stéphanie; Baltzer, Agnès; Imbert, Patrice; Ehrhold, Axel; Battani, Anne; Deville, Eric

    2017-04-01

    The recent discovery of biogenic methane emissions associated with methane-derived authigenic carbonate mounds along the Aquitaine Shelf edge offshore SW France (140 to 220 m water depth) questions about the initiation and temporal evolution of this fluid system (80 km N-S and 8 km E-W). Based on a multi-data study (including multibeam echosounder, subbottom profiler, single channel sparker seismic, 80 traces air gun seismic data and well cuttings and logs), different scenarii are proposed for the organic matter source levels and migration pathways of the methane. Several evidence of the presence of gas are observed on seismic data and interpreted to be linked to the biogenic system. Single channel sparker seismic lines exhibit an acoustic blanking (between 75-100 ms TWT below seafloor and the first multiple) below the present-day seepage area and westwards up to 8 km beyond the shelf-break. An air gun seismic line exhibits chaotic reflections along 8 km below the seepage area from the seabed down to 700 ms TWT below seafloor. Based on 1) the local geothermal gradient about 26 °C/km and 2) the window for microbial methanogenesis ranging from 4 to 56 °C, the estimation of the bottom limit for biogenic generation window is about 1.5 km below seafloor. Cuttings from 3 wells of the area within the methanogenesis window show average TOC (Total Organic Carbon) of 0.5 %; however, one well shows some coal levels with 30-35 % TOC in the Oligocene between 1490 and 1540 m below seafloor. Geochemical analysis on crushed cuttings evidenced heavy hydrocarbons up to mid-Paleogene, while shallower series did not evidence any. In the first scenario, we propose that methane is sourced from the Neogene prograding system. The 0.5% average TOC is sufficient to generate a large volume of methane over the thickness of this interval (up to 1 km at the shelf break area). In the second scenario, methane would be sourced from the Oligocene coals; however their spatial extension with regard to available data is too limited to supply the gas system along 80 km from north to south. The third scenario corresponds to methane production in the early Paleogene and Cretaceous source levels; but evidence for heavy hydrocarbons is not consistent with the isotopic signatures of the gases seeping at the seabed. The first scenario is therefore the most coherent one even if the TOC is relatively low in the Neogene formations. Regarding the fluid system geometry and the associated source level position, migration pathways may involve 1) upslope migration from the base of the Neogene clinoforms, 2) sub-vertical migration through faults and fractures at the shelf edge, and 3) groundwater circulation from onshore forcing methane migration westward through hydrodynamism. The PhD thesis of Guillaume Michel as well as the oceanographic expeditions Gazcogne1 (http://dx.doi.org/10.17600/13020070) and Gazcogne2 (http://dx.doi.org/10.17600/13030090) are co-funded by TOTAL and IFREMER as part of the PAMELA (Passive Margin Exploration Laboratories) scientific project.

  18. Surface wettability of plasma SiOx:H nanocoating-induced endothelial cells' migration and the associated FAK-Rho GTPases signalling pathways

    PubMed Central

    Shen, Yang; Wang, Guixue; Huang, Xianliang; Zhang, Qin; Wu, Jiang; Tang, Chaojun; Yu, Qingsong; Liu, Xiaoheng

    2012-01-01

    Vascular endothelial cell (EC) adhesion and migration are essential processes in re-endothelialization of implanted biomaterials. There is no clear relationship and mechanism between EC adhesion and migration behaviour on surfaces with varying wettabilities. As model substrates, plasma SiOx:H nanocoatings with well-controlled surface wettability (with water contact angles in the range of 98.5 ± 2.3° to 26.3 ± 4.0°) were used in this study to investigate the effects of surface wettability on cell adhesion/migration and associated protein expressions in FAK-Rho GTPases signalling pathways. It was found that EC adhesion/migration showed opposite behaviour on the hydrophilic and hydrophobic surfaces (i.e. hydrophobic surfaces promoted EC migration but were anti-adhesions). The number of adherent ECs showed a maximum on hydrophilic surfaces, while cells adhered to hydrophobic surfaces exhibited a tendency for cell migration. The focal adhesion kinase (FAK) inhibitor targeting the Y-397 site of FAK could significantly inhibit cell adhesion/migration, suggesting that EC adhesion and migration on surfaces with different wettabilities involve (p)FAK and its downstream signalling pathways. Western blot results suggested that the FAK-Rho GTPases signalling pathways were correlative to EC migration on hydrophobic plasma SiOx:H surfaces, but uncertain to hydrophilic surfaces. This work demonstrated that surface wettability could induce cellular behaviours that were associated with different cellular signalling events. PMID:21715399

  19. Assessment of brine migration risks along vertical pathways due to CO2 injection

    NASA Astrophysics Data System (ADS)

    Kissinger, Alexander; Class, Holger

    2015-04-01

    Global climate change, shortage of resources and the growing usage of renewable energy sources has lead to a growing demand for the utilization of subsurface systems. Among these competing uses are Carbon Capture and Storage (CCS), geothermal energy, nuclear waste disposal, 'renewable' methane or hydrogen storage as well as the ongoing production of fossil resources like oil, gas and coal. Additionally, these technologies may also create conflicts with essential public interests such as water supply. For example, the injection of CO2 into the subsurface causes an increase in pressure reaching far beyond the actual radius of influence of the CO2 plume, potentially leading to large amounts of displaced salt water. In this work we focus on the large scale impacts of CO2 storage on brine migration but the methodology and the obtained results may also apply to other fields like waste water disposal, where large amounts of fluid are injected into the subsurface. In contrast to modeling on the reservoir scale the spatial scale required for this work is much larger in both vertical and lateral direction, as the regional hydrogeology has to be considered. Structures such as fault zones, hydrogeological windows in the Rupelian clay or salt domes are considered as potential pathways for displaced fluids into shallow systems and their influence has to be taken into account. We put the focus of our investigations on the latter type of scenario, since there is still a poor understanding of the role that salt diapirs would play in CO2 storage projects. As there is hardly any field data available on this scale, we compare different levels of model complexity in order to identify the relevant processes for brine displacement and simplify the modeling process wherever possible, for example brine injection vs. CO2 injection, simplified geometries vs. the complex formation geometry and the role of salt induced density differences on flow. Further we investigate the impact of the displaced brine due to CO2 injection and compare it to the natural fluid exchange between shallow and deep aquifers in order to asses possible damage.

  20. Basin-scale hydrogeologic modeling

    NASA Astrophysics Data System (ADS)

    Person, Mark; Raffensperger, Jeff P.; Ge, Shemin; Garven, Grant

    1996-02-01

    Mathematical modeling of coupled groundwater flow, heat transfer, and chemical mass transport at the sedimentary basin scale has been increasingly used by Earth scientists studying a wide range of geologic processes including the formation of excess pore pressures, infiltration-driven metamorphism, heat flow anomalies, nuclear waste isolation, hydrothermal ore genesis, sediment diagenesis, basin tectonics, and petroleum generation and migration. These models have provided important insights into the rates and pathways of groundwater migration through basins, the relative importance of different driving mechanisms for fluid flow, and the nature of coupling between the hydraulic, thermal, chemical, and stress regimes. The mathematical descriptions of basin transport processes, the analytical and numerical solution methods employed, and the application of modeling to sedimentary basins around the world are the subject of this review paper. The special considerations made to represent coupled transport processes at the basin scale are emphasized. Future modeling efforts will probably utilize three-dimensional descriptions of transport processes, incorporate greater information regarding natural geological heterogeneity, further explore coupled processes, and involve greater field applications.

  1. Climate change-related migration and infectious disease.

    PubMed

    McMichael, Celia

    2015-01-01

    Anthropogenic climate change will have significant impacts on both human migration and population health, including infectious disease. It will amplify and alter migration pathways, and will contribute to the changing ecology and transmission dynamics of infectious disease. However there has been limited consideration of the intersections between migration and health in the context of a changing climate. This article argues that climate-change related migration - in conjunction with other drivers of migration - will contribute to changing profiles of infectious disease. It considers infectious disease risks for different climate-related migration pathways, including: forced displacement, slow-onset migration particularly to urban-poor areas, planned resettlement, and labor migration associated with climate change adaptation initiatives. Migration can reduce vulnerability to climate change, but it is critical to better understand and respond to health impacts - including infectious diseases - for migrant populations and host communities.

  2. Association of Wnt1-inducible signaling pathway protein-1 with the proliferation, migration and invasion in gastric cancer cells.

    PubMed

    Jia, Shuqin; Qu, Tingting; Feng, Mengmeng; Ji, Ke; Li, Ziyu; Jiang, Wenguo; Ji, Jiafu

    2017-06-01

    Wnt1-inducible signaling pathway protein-1 is a cysteine-rich protein that belongs to the CCN family, which has been implicated in mediating the occurrence and progression through distinct molecular mechanisms in several tumor types. However, the association of Wnt1-inducible signaling pathway protein-1 with gastric cancer and the related molecular mechanisms remain to be elucidated. Therefore, this study aimed to clarify the biological role of Wnt1-inducible signaling pathway protein-1 in the proliferation, migration, and invasion in gastric cancer cells and further investigated the associated molecular mechanism on these biological functions. We first detected the expression level of Wnt1-inducible signaling pathway protein-1 in gastric cancer, and the reverse transcription polymerase chain reaction have shown that Wnt1-inducible signaling pathway protein-1 expression levels were upregulated in gastric cancer tissues. The expression of Wnt1-inducible signaling pathway protein-1 in gastric cancer cell lines was also detected by quantitative real-time polymerase chain reaction and Western blotting. Furthermore, two gastric cancer cell lines with high expression of Wnt1-inducible signaling pathway protein-1 were selected to explore the biological function of Wnt1-inducible signaling pathway protein-1 in gastric cancer. Function assays indicated that knockdown of Wnt1-inducible signaling pathway protein-1 suppressed cell proliferation, migration, and invasion in BGC-823 and AGS gastric cancer cells. Further investigation of mechanisms suggested that cyclinD1 was identified as one of Wnt1-inducible signaling pathway protein-1 related genes to accelerate proliferation in gastric cancer cells. In addition, one pathway of Wnt1-inducible signaling pathway protein-1 induced migration and invasion was mainly through the enhancement of epithelial-to-mesenchymal transition progression. Taken together, our findings presented the first evidence that Wnt1-inducible signaling pathway protein-1 was upregulated in gastric cancer and acted as an oncogene by promoting proliferation, migration, and invasion in gastric cancer cells.

  3. Self-induced seismicity due to fluid circulation along faults

    NASA Astrophysics Data System (ADS)

    Aochi, Hideo; Poisson, Blanche; Toussaint, Renaud; Rachez, Xavier; Schmittbuhl, Jean

    2014-03-01

    In this paper, we develop a system of equations describing fluid migration, fault rheology, fault thickness evolution and shear rupture during a seismic cycle, triggered either by tectonic loading or by fluid injection. Assuming that the phenomena predominantly take place on a single fault described as a finite permeable zone of variable width, we are able to project the equations within the volumetric fault core onto the 2-D fault interface. From the basis of this `fault lubrication approximation', we simulate the evolution of seismicity when fluid is injected at one point along the fault to model-induced seismicity during an injection test in a borehole that intercepts the fault. We perform several parametric studies to understand the basic behaviour of the system. Fluid transmissivity and fault rheology are key elements. The simulated seismicity generally tends to rapidly evolve after triggering, independently of the injection history and end when the stationary path of fluid flow is established at the outer boundary of the model. This self-induced seismicity takes place in the case where shear rupturing on a planar fault becomes dominant over the fluid migration process. On the contrary, if healing processes take place, so that the fluid mass is trapped along the fault, rupturing occurs continuously during the injection period. Seismicity and fluid migration are strongly influenced by the injection rate and the heterogeneity.

  4. PM2.5 promotes human bronchial smooth muscle cell migration via the sonic hedgehog signaling pathway.

    PubMed

    Ye, Xiuqin; Hong, Wei; Hao, Binwei; Peng, Gongyong; Huang, Lingmei; Zhao, Zhuxiang; Zhou, Yumin; Zheng, Mengning; Li, Chenglong; Liang, Chunxiao; Yi, Erkang; Pu, Jinding; Li, Bing; Ran, Pixin

    2018-03-02

    The contribution of airway remodeling in chronic obstructive pulmonary disease (COPD) has been well documented, with airway smooth muscle cell proliferation and migration playing a role in the remodeling process. Here, we aimed to verify the effects of fine particulate matter (PM2.5) on human bronchial smooth muscle cell (HBSMC) migration and to explore the underlying signaling pathways. HBSMC apoptosis, proliferation and migration were measured using flow cytometry, cell counting and transwell migration assays, respectively. The role of the hedgehog pathway in cell migration was assessed by western blotting to measure the expression of Sonic hedgehog (Shh), Gli1 and Snail. Furthermore, siRNA was used to knock down Gli1 or Snail expression. PM2.5 induced HBSMC apoptosis in a dose-dependent manner, although certain concentrations of PM2.5 did not induce HBSMC proliferation or apoptosis. Interestingly, cell migration was stimulated by PM2.5 doses far below those that induced apoptosis. Additional experiments revealed that these PM2.5 doses enhanced the expression of Shh, Gli1 and Snail in HBSMCs. Furthermore, PM2.5-induced cell migration and protein expression were enhanced by recombinant Shh and attenuated by cyclopamine. Similar results were obtained by knocking down Gli1 or Snail. These findings suggest that PM2.5, which may exert its effects through the Shh signaling pathway, is necessary for the migration of HBSMCs. These data define a novel role for PM2.5 in airway remodeling in COPD.

  5. Estimating the gas hydrate recovery prospects in the western Black Sea basin based on the 3D multiphase flow of fluid and gas components within highly permeable paleo-channel-levee systems

    NASA Astrophysics Data System (ADS)

    Burwicz, Ewa; Zander, Timo; Rottke, Wolf; Bialas, Joerg; Hensen, Christian; Atgin, Orhan; Haeckel, Matthias

    2017-04-01

    Gas hydrate deposits are abundant in the Black Sea region and confirmed by direct observations as well as geophysical evidence, such as continuous bottom simulating reflectors (BSRs). Although those gas hydrate accumulations have been well-studied for almost two decades, the migration pathways of methane that charge the gas hydrate stability zone (GHSZ) in the region are unknown. The aim of this study is to explore the most probable gas migration scenarios within a three-dimensional finite element grid based on seismic surveys and available basin cross-sections. We have used the commercial software PetroMod(TM) (Schlumberger) to perform a set of sensitivity studies that narrow the gap between the wide range of sediment properties affecting the multi-phase flow in porous media. The high-resolution model domain focuses on the Danube deep-sea fan and associated buried sandy channel-levee systems whereas the total extension of the model domain covers a larger area of the western Black Sea basin. Such a large model domain allows for investigating biogenic as well as thermogenic methane generation and a permeability driven migration of the free phase of methane on a basin scale to confirm the hypothesis of efficient methane migration into the gas hydrate reservoir layers by horizontal flow along the carrier beds.

  6. Interactions of UNC-34 Enabled With Rac GTPases and the NIK Kinase MIG-15 in Caenorhabditis elegans Axon Pathfinding and Neuronal Migration

    PubMed Central

    Shakir, M. Afaq; Gill, Jason S.; Lundquist, Erik A.

    2006-01-01

    Many genes that affect axon pathfinding and cell migration have been identified. Mechanisms by which these genes and the molecules they encode interact with one another in pathways and networks to control developmental events are unclear. Rac GTPases, the cytoskeletal signaling molecule Enabled, and NIK kinase have all been implicated in regulating axon pathfinding and cell migration. Here we present evidence that, in Caenorhabditis elegans, three Rac GTPases, CED-10, RAC-2, and MIG-2, define three redundant pathways that each control axon pathfinding, and that the NIK kinase MIG-15 acts in each Rac pathway. Furthermore, we show that the Enabled molecule UNC-34 defines a fourth partially redundant pathway that acts in parallel to Rac/MIG-15 signaling in axon pathfinding. Enabled and the three Racs also act redundantly to mediate AQR and PQR neuronal cell migration. The Racs and UNC-34 Ena might all control the formation of actin-based protrusive structures (lamellipodia and filopodia) that mediate growth cone outgrowth and cell migration. MIG-15 does not act with the three Racs in execution of cell migration. Rather, MIG-15 affects direction of PQR neuronal migration, similar to UNC-40 and DPY-19, which control initial Q cell polarity, and Wnt signaling, which acts later to control Q cell-directed migration. MIG-2 Rac, which acts with CED-10 Rac, RAC-2 Rac, and UNC-34 Ena in axon pathfinding and cell migration, also acts with MIG-15 in PQR directional migration. PMID:16204220

  7. Fluid-Faulting Interactions Examined Though Massive Waveform-Based Analyses of Earthquake Swarms in Volcanic and Tectonic Settings: Mammoth Mountain, Long Valley, Lassen, and Fillmore, California Swarms, 2014-2015

    NASA Astrophysics Data System (ADS)

    Shelly, D. R.; Ellsworth, W. L.; Prejean, S. G.; Hill, D. P.; Hardebeck, J.; Hsieh, P. A.

    2015-12-01

    Earthquake swarms, sequences of sustained seismicity, convey active subsurface processes that sometimes precede larger tectonic or volcanic episodes. Their extended activity and spatiotemporal migration can often be attributed to fluid pressure transients as migrating crustal fluids (typically water and CO2) interact with subsurface structures. Although the swarms analyzed here are interpreted to be natural in origin, the mechanisms of seismic activation likely mirror those observed for earthquakes induced by industrial fluid injection. Here, we use massive-scale waveform correlation to detect and precisely locate 3-10 times as many earthquakes as included in routine catalogs for recent (2014-2015) swarms beneath Mammoth Mountain, Long Valley Caldera, Lassen Volcanic Center, and Fillmore areas of California, USA. These enhanced catalogs, with location precision as good as a few meters, reveal signatures of fluid-faulting interactions, such as systematic migration, fault-valve behavior, and fracture mesh structures, not resolved in routine catalogs. We extend this analysis to characterize source mechanism similarity even for very small newly detected events using relative P and S polarity estimates. This information complements precise locations to define fault complexities that would otherwise be invisible. In particular, although swarms often consist of groups of highly similar events, some swarms contain a population of outliers with different slip and/or fault orientations. These events highlight the complexity of fluid-faulting interactions. Despite their different settings, the four swarms analyzed here share many similarities, including pronounced hypocenter migration suggestive of a fluid pressure trigger. This includes the July 2015 Fillmore swarm, which, unlike the others, occurred outside of an obvious volcanic zone. Nevertheless, it exhibited systematic westward and downdip migration on a ~1x1.5 km low-angle, NW-dipping reverse fault at midcrustal depth.

  8. Methane hydrate induced permeability modification for multiphase flow in unsaturated porous media

    NASA Astrophysics Data System (ADS)

    Seol, Yongkoo; Kneafsey, Timothy J.

    2011-08-01

    An experimental study was performed using X-ray computed tomography (CT) scanning to capture three-dimensional (3-D) methane hydrate distributions and potential discrete flow pathways in a sand pack sample. A numerical study was also performed to develop and analyze empirical relations that describe the impacts of hydrate accumulation habits within pore space (e.g., pore filling or grain cementing) on multiphase fluid migration. In the experimental study, water was injected into a hydrate-bearing sand sample that was monitored using an X-ray CT scanner. The CT images were converted into numerical grid elements, providing intrinsic sample data including porosity and phase saturations. The impacts of hydrate accumulation were examined by adapting empirical relations into the flow simulations as additional relations governing the evolution of absolute permeability of hydrate bearing sediment with hydrate deposition. The impacts of pore space hydrate accumulation habits on fluid migration were examined by comparing numerical predictions with experimentally measured water saturation distributions and breakthrough curves. A model case with 3-D heterogeneous initial conditions (hydrate saturation, porosity, and water saturation) and pore body-preferred hydrate accumulations best captured water migration behavior through the hydrate-bearing sample observed in the experiment. In the best matching model, absolute permeability in the hydrate bearing sample does not decrease significantly with increasing hydrate saturation until hydrate saturation reaches about 40%, after which it drops rapidly, and complete blockage of flow through the sample can occur as hydrate accumulations approach 70%. The result highlights the importance of permeability modification due to hydrate accumulation habits when predicting multiphase flow through high-saturation, reservoir quality hydrate-bearing sediments.

  9. Optimum swimming pathways of fish spawning migrations in rivers

    USGS Publications Warehouse

    McElroy, Brandon; DeLonay, Aaron; Jacobson, Robert

    2012-01-01

    Fishes that swim upstream in rivers to spawn must navigate complex fluvial velocity fields to arrive at their ultimate locations. One hypothesis with substantial implications is that fish traverse pathways that minimize their energy expenditure during migration. Here we present the methodological and theoretical developments necessary to test this and similar hypotheses. First, a cost function is derived for upstream migration that relates work done by a fish to swimming drag. The energetic cost scales with the cube of a fish's relative velocity integrated along its path. By normalizing to the energy requirements of holding a position in the slowest waters at the path's origin, a cost function is derived that depends only on the physical environment and not on specifics of individual fish. Then, as an example, we demonstrate the analysis of a migration pathway of a telemetrically tracked pallid sturgeon (Scaphirhynchus albus) in the Missouri River (USA). The actual pathway cost is lower than 105 random paths through the surveyed reach and is consistent with the optimization hypothesis. The implication—subject to more extensive validation—is that reproductive success in managed rivers could be increased through manipulation of reservoir releases or channel morphology to increase abundance of lower-cost migration pathways.

  10. A Simple Geotracer Compositional Correlation Analysis Reveals Oil Charge and Migration Pathways

    NASA Astrophysics Data System (ADS)

    Yang, Yunlai; Arouri, Khaled

    2016-03-01

    A novel approach, based on geotracer compositional correlation analysis is reported, which reveals the oil charge sequence and migration pathways for five oil fields in Saudi Arabia. The geotracers utilised are carbazoles, a family of neutral pyrrolic nitrogen compounds known to occur naturally in crude oils. The approach is based on the concept that closely related fields, with respect to filling sequence, will show a higher carbazole compositional correlation, than those fields that are less related. That is, carbazole compositional correlation coefficients can quantify the charge and filling relationships among different fields. Consequently, oil migration pathways can be defined based on the established filling relationships. The compositional correlation coefficients of isomers of C1 and C2 carbazoles, and benzo[a]carbazole for all different combination pairs of the five fields were found to vary extremely widely (0.28 to 0.94). A wide range of compositional correlation coefficients allows adequate differentiation of separate filling relationships. Based on the established filling relationships, three distinct migration pathways were inferred, with each apparently being charged from a different part of a common source kitchen. The recognition of these charge and migration pathways will greatly aid the search for new accumulations.

  11. A Simple Geotracer Compositional Correlation Analysis Reveals Oil Charge and Migration Pathways

    PubMed Central

    Yang, Yunlai; Arouri, Khaled

    2016-01-01

    A novel approach, based on geotracer compositional correlation analysis is reported, which reveals the oil charge sequence and migration pathways for five oil fields in Saudi Arabia. The geotracers utilised are carbazoles, a family of neutral pyrrolic nitrogen compounds known to occur naturally in crude oils. The approach is based on the concept that closely related fields, with respect to filling sequence, will show a higher carbazole compositional correlation, than those fields that are less related. That is, carbazole compositional correlation coefficients can quantify the charge and filling relationships among different fields. Consequently, oil migration pathways can be defined based on the established filling relationships. The compositional correlation coefficients of isomers of C1 and C2 carbazoles, and benzo[a]carbazole for all different combination pairs of the five fields were found to vary extremely widely (0.28 to 0.94). A wide range of compositional correlation coefficients allows adequate differentiation of separate filling relationships. Based on the established filling relationships, three distinct migration pathways were inferred, with each apparently being charged from a different part of a common source kitchen. The recognition of these charge and migration pathways will greatly aid the search for new accumulations. PMID:26965479

  12. A Simple Geotracer Compositional Correlation Analysis Reveals Oil Charge and Migration Pathways.

    PubMed

    Yang, Yunlai; Arouri, Khaled

    2016-03-11

    A novel approach, based on geotracer compositional correlation analysis is reported, which reveals the oil charge sequence and migration pathways for five oil fields in Saudi Arabia. The geotracers utilised are carbazoles, a family of neutral pyrrolic nitrogen compounds known to occur naturally in crude oils. The approach is based on the concept that closely related fields, with respect to filling sequence, will show a higher carbazole compositional correlation, than those fields that are less related. That is, carbazole compositional correlation coefficients can quantify the charge and filling relationships among different fields. Consequently, oil migration pathways can be defined based on the established filling relationships. The compositional correlation coefficients of isomers of C1 and C2 carbazoles, and benzo[a]carbazole for all different combination pairs of the five fields were found to vary extremely widely (0.28 to 0.94). A wide range of compositional correlation coefficients allows adequate differentiation of separate filling relationships. Based on the established filling relationships, three distinct migration pathways were inferred, with each apparently being charged from a different part of a common source kitchen. The recognition of these charge and migration pathways will greatly aid the search for new accumulations.

  13. From migration to settlement: the pathways, migration modes and dynamics of neurons in the developing brain

    PubMed Central

    HATANAKA, Yumiko; ZHU, Yan; TORIGOE, Makio; KITA, Yoshiaki; MURAKAMI, Fujio

    2016-01-01

    Neuronal migration is crucial for the construction of the nervous system. To reach their correct destination, migrating neurons choose pathways using physical substrates and chemical cues of either diffusible or non-diffusible nature. Migrating neurons extend a leading and a trailing process. The leading process, which extends in the direction of migration, determines navigation, in particular when a neuron changes its direction of migration. While most neurons simply migrate radially, certain neurons switch their mode of migration between radial and tangential, with the latter allowing migration to destinations far from the neurons’ site of generation. Consequently, neurons with distinct origins are intermingled, which results in intricate neuronal architectures and connectivities and provides an important basis for higher brain function. The trailing process, in contrast, contributes to the late stage of development by turning into the axon, thus contributing to the formation of neuronal circuits. PMID:26755396

  14. Climate change-related migration and infectious disease

    PubMed Central

    McMichael, Celia

    2015-01-01

    Anthropogenic climate change will have significant impacts on both human migration and population health, including infectious disease. It will amplify and alter migration pathways, and will contribute to the changing ecology and transmission dynamics of infectious disease. However there has been limited consideration of the intersections between migration and health in the context of a changing climate. This article argues that climate-change related migration - in conjunction with other drivers of migration – will contribute to changing profiles of infectious disease. It considers infectious disease risks for different climate-related migration pathways, including: forced displacement, slow-onset migration particularly to urban-poor areas, planned resettlement, and labor migration associated with climate change adaptation initiatives. Migration can reduce vulnerability to climate change, but it is critical to better understand and respond to health impacts – including infectious diseases - for migrant populations and host communities. PMID:26151221

  15. Temporal and spatial variation in porosity and compaction pressure for the viscoelastic slab

    NASA Astrophysics Data System (ADS)

    Morishige, M.; Van Keken, P. E.

    2017-12-01

    Fluid is considered to play key roles in subduction zones. It triggers various types of earthquakes by elevating pore-fluid pressure or forming hydrous minerals, and it also facilitates magma genesis by lowering the solidus temperatures of mantle and crustal rocks. Several previous numerical studies have worked on how fluid migrates and how porosity changes in time and space, but our knowledge of the fluid behavior remains limited. In this presentation, we demonstrate the detailed fluid behavior in the slab. The main features of this study are that (1) viscoelasticity is included, and that (2) fluid flow toward the inner part of the slab is also considered. We construct 2D and 3D finite element models for viscoelastic slab based on a theory of two-phase flow, which allows us to treat the movement of rock- and fluid- phases simultaneously. We solve the equations for porosity and compaction pressure which is defined as the pressure difference in between the two phases. Fluid source is fixed in time and space, and a uniform slab velocity is imposed for the whole model domain. There are several important parameters affecting the fluid behavior which includes bulk viscosity, bulk modulus, permeability, and fluid viscosity. Among these we fix bulk modulus and change the other parameters to investigate their effects on fluid migration. We find that when bulk viscosity is relatively high, elasticity is dominant and large amount of fluid is trapped in and around the fluid source. In addition, fluid migrates along the fluid source when relatively high ratio of permeability to fluid viscosity is assumed. Fluid generally moves with the slab when the ratio of permeability to fluid viscosity is low. One interesting feature is that in some cases porosity increases also in the deeper part of the fluid source due to the diffusion of compaction pressure. It suggests that the effects of resistance to volume change can be an alternative mechanism to effectively hydrate the inner part in the slab. In 3D, we find that fluid migrates in the maximum-dip direction of the slab. It leads to a fluid focusing where the slab bends away from the trench and it results in the increase in porosity and compaction pressure there. This finding may be useful to explain the observed along-arc variation in short-term slow slip events and the upper plane of double seismic zone.

  16. Spatiotemporal distribution of low-frequency earthquakes in Southwest Japan: Evidence for fluid migration and magmatic activity

    NASA Astrophysics Data System (ADS)

    Yu, Zhiteng; Zhao, Dapeng; Niu, Xiongwei; Li, Jiabiao

    2018-01-01

    Low-frequency earthquakes (LFEs) in the lower crust and uppermost mantle are widely observed in Southwest Japan, and they occur not only along the subducting Philippine Sea (PHS) slab interface but also beneath active arc volcanoes. The volcanic LFEs are still not well understood because of their limited quantities and less reliable hypocenter locations. In this work, seismic tomography is used to determine detailed three-dimensional (3-D) P- and S-wave velocity (Vp and Vs) models of the crust and upper mantle beneath Southwest Japan, and then the obtained 3-D Vp and Vs models are used to relocate the volcanic LFEs precisely. The results show that the volcanic LFEs can be classified into two types: pipe-like and swarm-like LFEs, and both of them are located in or around zones of low-velocity and high-Poisson's ratio anomalies in the crust and uppermost mantle beneath the active volcanoes. The pipe-like LFEs may be related to the fluid migration from the lower crust or the uppermost mantle, whereas the swarm-like LFEs may be related to local magmatic activities or small magma chambers. The number of LFEs sometimes increases sharply before or after a nearby large crustal earthquake which may cause cracks and fluid migration. The spatiotemporal distribution of the LFEs may indicate the track of migrating fluids. As compared with the tectonic LFEs along the PHS slab interface, the volcanic LFEs are more sensitive to fluid migration and local magmatic activities. High pore pressures play an important role in triggering both types of LFEs in Southwest Japan.

  17. Method for identifying subsurface fluid migration and drainage pathways in and among oil and gas reservoirs using 3-D and 4-D seismic imaging

    DOEpatents

    Anderson, R.N.; Boulanger, A.; Bagdonas, E.P.; Xu, L.; He, W.

    1996-12-17

    The invention utilizes 3-D and 4-D seismic surveys as a means of deriving information useful in petroleum exploration and reservoir management. The methods use both single seismic surveys (3-D) and multiple seismic surveys separated in time (4-D) of a region of interest to determine large scale migration pathways within sedimentary basins, and fine scale drainage structure and oil-water-gas regions within individual petroleum producing reservoirs. Such structure is identified using pattern recognition tools which define the regions of interest. The 4-D seismic data sets may be used for data completion for large scale structure where time intervals between surveys do not allow for dynamic evolution. The 4-D seismic data sets also may be used to find variations over time of small scale structure within individual reservoirs which may be used to identify petroleum drainage pathways, oil-water-gas regions and, hence, attractive drilling targets. After spatial orientation, and amplitude and frequency matching of the multiple seismic data sets, High Amplitude Event (HAE) regions consistent with the presence of petroleum are identified using seismic attribute analysis. High Amplitude Regions are grown and interconnected to establish plumbing networks on the large scale and reservoir structure on the small scale. Small scale variations over time between seismic surveys within individual reservoirs are identified and used to identify drainage patterns and bypassed petroleum to be recovered. The location of such drainage patterns and bypassed petroleum may be used to site wells. 22 figs.

  18. Method for identifying subsurface fluid migration and drainage pathways in and among oil and gas reservoirs using 3-D and 4-D seismic imaging

    DOEpatents

    Anderson, Roger N.; Boulanger, Albert; Bagdonas, Edward P.; Xu, Liqing; He, Wei

    1996-01-01

    The invention utilizes 3-D and 4-D seismic surveys as a means of deriving information useful in petroleum exploration and reservoir management. The methods use both single seismic surveys (3-D) and multiple seismic surveys separated in time (4-D) of a region of interest to determine large scale migration pathways within sedimentary basins, and fine scale drainage structure and oil-water-gas regions within individual petroleum producing reservoirs. Such structure is identified using pattern recognition tools which define the regions of interest. The 4-D seismic data sets may be used for data completion for large scale structure where time intervals between surveys do not allow for dynamic evolution. The 4-D seismic data sets also may be used to find variations over time of small scale structure within individual reservoirs which may be used to identify petroleum drainage pathways, oil-water-gas regions and, hence, attractive drilling targets. After spatial orientation, and amplitude and frequency matching of the multiple seismic data sets, High Amplitude Event (HAE) regions consistent with the presence of petroleum are identified using seismic attribute analysis. High Amplitude Regions are grown and interconnected to establish plumbing networks on the large scale and reservoir structure on the small scale. Small scale variations over time between seismic surveys within individual reservoirs are identified and used to identify drainage patterns and bypassed petroleum to be recovered. The location of such drainage patterns and bypassed petroleum may be used to site wells.

  19. Gas injection to inhibit migration during an in situ heat treatment process

    DOEpatents

    Kuhlman, Myron Ira; Vinegar; Harold J.; Baker, Ralph Sterman; Heron, Goren

    2010-11-30

    Methods of treating a subsurface formation are described herein. Methods for treating a subsurface treatment area in a formation may include introducing a fluid into the formation from a plurality of wells offset from a treatment area of an in situ heat treatment process to inhibit outward migration of formation fluid from the in situ heat treatment process.

  20. Method for inverting reflection trace data from 3-D and 4-D seismic surveys and identifying subsurface fluid and pathways in and among hydrocarbon reservoirs based on impedance models

    DOEpatents

    He, W.; Anderson, R.N.

    1998-08-25

    A method is disclosed for inverting 3-D seismic reflection data obtained from seismic surveys to derive impedance models for a subsurface region, and for inversion of multiple 3-D seismic surveys (i.e., 4-D seismic surveys) of the same subsurface volume, separated in time to allow for dynamic fluid migration, such that small scale structure and regions of fluid and dynamic fluid flow within the subsurface volume being studied can be identified. The method allows for the mapping and quantification of available hydrocarbons within a reservoir and is thus useful for hydrocarbon prospecting and reservoir management. An iterative seismic inversion scheme constrained by actual well log data which uses a time/depth dependent seismic source function is employed to derive impedance models from 3-D and 4-D seismic datasets. The impedance values can be region grown to better isolate the low impedance hydrocarbon bearing regions. Impedance data derived from multiple 3-D seismic surveys of the same volume can be compared to identify regions of dynamic evolution and bypassed pay. Effective Oil Saturation or net oil thickness can also be derived from the impedance data and used for quantitative assessment of prospective drilling targets and reservoir management. 20 figs.

  1. Method for inverting reflection trace data from 3-D and 4-D seismic surveys and identifying subsurface fluid and pathways in and among hydrocarbon reservoirs based on impedance models

    DOEpatents

    He, Wei; Anderson, Roger N.

    1998-01-01

    A method is disclosed for inverting 3-D seismic reflection data obtained from seismic surveys to derive impedance models for a subsurface region, and for inversion of multiple 3-D seismic surveys (i.e., 4-D seismic surveys) of the same subsurface volume, separated in time to allow for dynamic fluid migration, such that small scale structure and regions of fluid and dynamic fluid flow within the subsurface volume being studied can be identified. The method allows for the mapping and quantification of available hydrocarbons within a reservoir and is thus useful for hydrocarbon prospecting and reservoir management. An iterative seismic inversion scheme constrained by actual well log data which uses a time/depth dependent seismic source function is employed to derive impedance models from 3-D and 4-D seismic datasets. The impedance values can be region grown to better isolate the low impedance hydrocarbon bearing regions. Impedance data derived from multiple 3-D seismic surveys of the same volume can be compared to identify regions of dynamic evolution and bypassed pay. Effective Oil Saturation or net oil thickness can also be derived from the impedance data and used for quantitative assessment of prospective drilling targets and reservoir management.

  2. The Fat-like Cadherin CDH-4 Acts Cell-Non-Autonomously in Anterior-Posterior Neuroblast Migration

    PubMed Central

    Sundararajan, Lakshmi; Norris, Megan L.; Schöneich, Sebastian; Ackley, Brian D.; Lundquist, Erik A.

    2014-01-01

    Directed migration of neurons is critical in the normal and pathological development of the brain and central nervous system. In C. elegans, the bilateral Q neuroblasts, QR on the right and QL on the left, migrate anteriorly and posteriorly, respectively. Initial protrusion and migration of the Q neuroblasts is autonomously controlled by the transmembrane proteins UNC-40/DCC, PTP-3/LAR, and MIG-21. As QL migrates posteriorly, it encounters and EGL-20/Wnt signal that induces MAB-5/Hox expression that drives QL descendant posterior migration. QR migrates anteriorly away from EGL-20/Wnt and does not activate MAB-5/Hox, resulting in anterior QR descendant migration. A forward genetic screen for new mutations affecting initial Q migrations identified alleles of cdh-4, which caused defects in both QL and QR directional migration similar to unc-40, ptp-3, and mig-21. Previous studies showed that in QL, PTP-3/LAR and MIG-21 act in a pathway in parallel to UNC-40/DCC to drive posterior QL migration. Here we show genetic evidence that CDH-4 acts in the PTP-3/MIG-21 pathway in parallel to UNC-40/DCC to direct posterior QL migration. In QR, the PTP-3/MIG-21 and UNC-40/DCC pathways mutually inhibit each other, allowing anterior QR migration. We report here that CDH-4 acts in both the PTP-3/MIG-21 and UNC-40/DCC pathways in mutual inhibition in QR, and that CDH-4 acts cell-non-autonomously. Interaction of CDH-4 with UNC-40/DCC in QR but not QL represents an inherent left-right asymmetry in the Q cells, the nature of which is not understood. We conclude that CDH-4 might act as a permissive signal for each Q neuroblast to respond differently to anterior-posterior guidance information based upon inherent left-right asymmetries in the Q neuroblasts. PMID:24954154

  3. Regional hydrogeology and hydrochemistry of deep formation waters in the Williston Basin (Canada-USA): implications for fluid migration in the basin

    NASA Astrophysics Data System (ADS)

    Rostron, B. J.

    2010-12-01

    The regional groundwater flow-system in the Williston Basin (Canada-USA) is one of the best examples of a mega-scale confined aquifer-system in the world. With its well-defined recharge and discharge areas separated by approximately 1000 km horizontal and 1 km vertical distance, the basin is an ideal natural laboratory to study regional groundwater flow and hydrochemistry. Springs and shallow water wells in the recharge and discharge areas, along with deeper oil and gas wells, allow for detailed mapping of formation-pressures. Further, these wells provide access for sampling and geochemical analyses of formation waters along flow paths. Basin-scale hydrogeological and hydrochemical mapping combined with newly obtained geochemical and isotopic data from more than 2000 wells across the basin provide new insights into the present and paleohydrogeology of the basin. Results indicate: 1) the hydrogeology and hydrochemistry of the basin must be mapped on hydrogeological (not political) boundaries; 2) many aquifers have similar water chemistries, yet unique isotopic fingerprints; 3) stable isotope distributions provide insight(s) into regional fluid flow patterns; 4) analysis of bromine concentrations and stable isotopic compositions provide evidence that at least some of the brine in the basin owes its origin to evaporated seawater and not just dissolved evaporites as previously thought; 5) regional patterns of stable isotopes and halogens can be used to trace different flow "events" in the basin's history; 6) calcium-rich brines in the center of the basin may be associated with relict calcium-rich seawaters; 7) hydrocarbon migration pathways have been variably impacted by evolving hydrodynamic conditions; and 8) there is strong evidence of past glacially-driven recharge in the current discharge area of the basin. These observations show that the hydrogeology and hydrochemistry of the basin is more complex than previously thought. Portions of the basin appear to respond rapidly to changes in boundary conditions including: the recharge areas; midline areas that have experienced extensive salt dissolution; and present discharge areas that appear to show evidence of glacially-driven recharge. Other portions of the basin appear to have had little to no fluid-flow despite being continuous and highly-permeable. Mixing, and not depth, appears to control water compositions. Insights gained from regional hydrogeology and hydrochemical provide an improved understanding the present and past mega-scale fluid migration in the Williston Basin.

  4. Heparanase induced by advanced glycation end products (AGEs) promotes macrophage migration involving RAGE and PI3K/AKT pathway

    PubMed Central

    2013-01-01

    Background Advanced glycation end products (AGEs), inflammatory-associated macrophage migration and accumulation are crucial for initiation and progression of diabetic vascular complication. Enzymatic activity of heparanase (HPA) is implicated strongly in dissemination of metastatic tumor cells and cells of the immune system. In addition, HPA enhances the phosphorylation of selected signaling molecules including AKT pathway independent of enzymatic activity. However, virtually nothing is presently known the role of HPA during macrophage migration exposed to AGEs involving signal pathway. Methods These studies were carried out in Ana-1 macrophages. Macrophage viability was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays. HPA and AKT protein expression in macrophages are analysed by Western blotting and HPA mRNA expression by real time quantitative RT-PCR. Release of HPA was determined by ELISA. Macrophage migration was assessed by Transwell assays. Results HPA protein and mRNA were found to be increased significantly in AGEs-treated macrophages. Pretreatment with anti-HPA antibody which recognizes the nonenzymatic terminal of HPA prevented AGEs-induced AKT phosphorylation and macrophage migration. LY294002 (PI3k/AKT inhibitor) inhibited AGEs-induced macrophage migration. Furthermore, pretreatment with anti-receptor for advanced glycation end products (RAGE) antibody attenuated AGEs-induced HPA expression, AKT phosphorylation and macrophage migration. Conclusions These data indicate that AGEs-induced macrophage migration is dependent on HPA involving RAGE-HPA-PI3K/AKT pathway. The nonenzymatic activity of HPA may play a key role in AGEs-induced macrophage migration associated with inflammation in diabetic vascular complication. PMID:23442498

  5. Short-range, overpressure-driven methane migration in coarse-grained gas hydrate reservoirs

    DOE PAGES

    Nole, Michael; Daigle, Hugh; Cook, Ann E.; ...

    2016-08-31

    Two methane migration mechanisms have been proposed for coarse-grained gas hydrate reservoirs: short-range diffusive gas migration and long-range advective fluid transport from depth. Herein we demonstrate that short-range fluid flow due to overpressure in marine sediments is a significant additional methane transport mechanism that allows hydrate to precipitate in large quantities in thick, coarse-grained hydrate reservoirs. Two-dimensional simulations demonstrate that this migration mechanism, short-range advective transport, can supply significant amounts of dissolved gas and is unencumbered by limitations of the other two end-member mechanisms. Here, short-range advective migration can increase the amount of methane delivered to sands as compared tomore » the slow process of diffusion, yet it is not necessarily limited by effective porosity reduction as is typical of updip advection from a deep source.« less

  6. Short-range, overpressure-driven methane migration in coarse-grained gas hydrate reservoirs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nole, Michael; Daigle, Hugh; Cook, Ann E.

    Two methane migration mechanisms have been proposed for coarse-grained gas hydrate reservoirs: short-range diffusive gas migration and long-range advective fluid transport from depth. Herein we demonstrate that short-range fluid flow due to overpressure in marine sediments is a significant additional methane transport mechanism that allows hydrate to precipitate in large quantities in thick, coarse-grained hydrate reservoirs. Two-dimensional simulations demonstrate that this migration mechanism, short-range advective transport, can supply significant amounts of dissolved gas and is unencumbered by limitations of the other two end-member mechanisms. Here, short-range advective migration can increase the amount of methane delivered to sands as compared tomore » the slow process of diffusion, yet it is not necessarily limited by effective porosity reduction as is typical of updip advection from a deep source.« less

  7. Fluid flow and assessment of the leakage potential in the Snohvit reservoir and overburden in the Barents Sea

    NASA Astrophysics Data System (ADS)

    Tasianas, A.

    2012-12-01

    Department of Geology, University of Tromsø, Dramsveien 201, 9037 Tromsø, Norway Abstract ____________________________________________________________________________ The Snøhvit reservoir and overburden have been an important location for testing Carbon Capture and Storage (CCS) techniques. Fluid flow in the region is caused mainly by repeated glacial cycles and differential geographic uplift, which caused tilting and spilling of various structural traps in the area. Geological modeling, undertaken as part of the ECO2 project activities, has allowed to model the local stratigraphy and any potential fluid flow pathways in order to determine how effective CCS would be in the area. 3D seismic data related to cube ST0306 from the Hammerfest Sedimentary Basin (HFB), covering the Snohvit and Albatross fields, were used to better understand the pathways and mechanisms related to fluid flow in the area and thus propose also potential leakage scenarios. The inclusion of geological features such as gas chimneys, faults, wells, pockmarks at the seabed and vertical fluid flow structures underlying the pockmarks in the models has also allowed to accurately simulate fluid flow through realistic geological models. Leaking of CO2 from the Tubåen Formation (Fm) can partially migrate upwards to the Hekkingen Fm or less deep formations via the faults. If leaking reaches the tertiary faults, CO2 can migrate through the Top kvitting Fm and maybe continue via pipe structures, faults or the clinoforms of the Torsk Fm and accumulate under the Upper Regional Unconformity (URU). The presence of pockmarks at the seabed could indicate further leakage between the URU and the seabed via vertical fluid flow structures underlying the pockmarks. Depending on the leakage mode, models of different types of domain size and grid resolution were created and populated with properties such as porosity (SPhi), vertical permeability (kv), horizontal permeability (Kh), anisotropy ratio (AnIso), Total Oganic Carbon, [Cl],[CaCO3], [CH4] and various alkalinities. A temperature vs depth profile (Trock) and a lithology model were also associated with it. Modelling results indicate that the most likely sites for leakage, when the crust is subject to erosion-related compressive stresses, would be the faults. The possible presence of any gas hydrates above the BSR could act as a seal for the free gas accumulating below the BSR. This reason as well as the fact that we don't expect any major stress changes in the region in the next few Million years signifies that the faults should remain sealing and thus prevent any CO2 leakage. Preliminary simulation results indicate highest saturation values of CO2 near the base of the overburden with no signs of any CO2 reaching the seabed, thus reducing to a minimum the threat of any contamination to the seawater and marine wildlife. Both Composition 2 and 3 gas hydrates are stable, providing a supplementary sealing effect that prevents any potential leaking fluid reaching the seabed. The study area is however lying outside the Composition 1 pure methane gas hydrate stability field. Any fluid with such composition leaking from the reservoir will thus not form gas hydrates. Keywords : geological modeling, CO2, fluid flow, leakage mechanisms, gas hydrate

  8. Nonlinear Fluid Migration Patterns in Fractured Reservoirs due to Stress-Pressure Coupling induced Changes in Reservoir Permeabilities

    NASA Astrophysics Data System (ADS)

    Annewandter, R.; Geiger, S.; Main, I. G.

    2011-12-01

    Sustainable storage of carbon dioxide (CO2) requires a thorough understanding of injection induced pressure build-up and its effects on the storage formation's integrity, since it determines the cap rock's sealing properties as well as the total storable amount of carbon dioxide. Fractures are abundant in the subsurface and difficult to detect due to their subseismic characteristic. If present in the cap during injection, they can be primary pathways for CO2 leakage. The North Sea is considered as Europe's most important carbon dioxide storage area. However, almost all of the potential storage formations have been exposed to post-glacial lithospheric flexure, possibly causing the generation of new fracture networks in the overburden whilst rebounding. Drawing upon, fast carbon dioxide uprise can be facilitated due to opening of fractures caused by changes in the stress field over time. The overall effective permeability, and hence possible leakage rates, of a fractured storage formation is highly sensitive to the fracture aperture which itself depends on the far field and in situ stress field. For this reason, our in-house general purpose reservoir simulator Complex System Modeling Platform (CSMP++) has been expanded, which is particularly designed to simulate multiphase flow on fractured porous media. It combines finite element (FE) and finite volume (FV) methods on mixed-dimensional hybrid-element meshes. The unstructured FE-FV based scheme allows us to model complex geological structures, such as fractures, at great detail. The simulator uses a compositional model for NaCl-H2O-CO2-systems for compressible fluids for computing thermophysical properties as a function of formation pressure and temperature. A fixed stress-split sequential procedure is being used to calculate coupled fluid flow and geomechanics. Numerical proof of concept studies will be presented showing the impact of fracture opening and closure on fluid migration patterns due to coupled stress-pressure induced changes in effective permeabilities.

  9. Enhanced migration of tissue inhibitor of metalloproteinase overexpressing hepatoma cells is attributed to gelatinases: Relevance to intracellular signaling pathways

    PubMed Central

    Roeb, Elke; Bosserhoff, Anja-Katrin; Hamacher, Sabine; Jansen, Bettina; Dahmen, Judith; Wagner, Sandra; Matern, Siegfried

    2005-01-01

    AIM: To study the effect of gelatinases (especially MMP-9) on migration of tissue inhibitor of metalloproteinase (TIMP-1) overexpressing hepatoma cells. METHODS: Wild type HepG2 cells, cells stably transfected with TIMP-1 and TIMP-1 antagonist (MMP-9-H401A, a catalytically inactive matrix metalloproteinase (MMP) which still binds and neutralizes TIMP-1) were incubated in Boyden chambers either with or without Galardin (a synthetic inhibitor of MMP-1, -2, -3, -8, -9) or a specific inhibitor of gelatinases. RESULTS: Compared to wild type HepG2 cells, the cells overexpressing TIMP-1 showed 115% migration (P<0.05) and the cells overexpressing MMP-9-H401A showed 62% migration (P<0.01). Galardin reduced cell migration dose dependently in all cases. The gelatinase inhibitor reduced migration in TIMP-1 overexpressing cells predominantly. Furthermore, we examined intracellular signal transduction pathways of TIMP-1-dependent HepG2 cells. TIMP-1 deactivates cell signaling pathways of MMP-2 and MMP-9 involving p38 mitogen-activated protein kinase. Specific blockade of the ERK pathway suppresses gelatinase expression either in the presence or absence of TIMP-1. CONCLUSION: Overexpressing functional TIMP-1- enhanced migration of HepG2-TIMP-1 cells depends on enhanced MMP-activity, especially MMP-9. PMID:15754388

  10. NADPH oxidase-mediated redox signal contributes to lipoteichoic acid-induced MMP-9 upregulation in brain astrocytes

    PubMed Central

    2012-01-01

    Background Lipoteichoic acid (LTA) is a component of gram-positive bacterial cell walls and may be elevated in the cerebrospinal fluid of patients suffering from meningitis. Among matrix metalloproteinases (MMPs), MMP-9 has been observed in patients with brain inflammatory diseases and may contribute to the pathology of brain diseases. Moreover, several studies have suggested that increased oxidative stress is implicated in the pathogenesis of brain inflammation and injury. However, the molecular mechanisms underlying LTA-induced redox signal and MMP-9 expression in brain astrocytes remain unclear. Objective Herein we explored whether LTA-induced MMP-9 expression was mediated through redox signals in rat brain astrocytes (RBA-1 cells). Methods Upregulation of MMP-9 by LTA was evaluated by zymographic and RT-PCR analyses. Next, the MMP-9 regulatory pathways were investigated by pretreatment with pharmacological inhibitors or transfection with small interfering RNAs (siRNAs), Western blotting, and chromatin immunoprecipitation (ChIP)-PCR and promoter activity reporter assays. Moreover, we determined the cell functional changes by migration assay. Results These results showed that LTA induced MMP-9 expression via a PKC(α)-dependent pathway. We further demonstrated that PKCα stimulated p47phox/NADPH oxidase 2 (Nox2)-dependent reactive oxygen species (ROS) generation and then activated the ATF2/AP-1 signals. The activated-ATF2 bound to the AP-1-binding site of MMP-9 promoter, and thereby turned on MMP-9 gene transcription. Additionally, the co-activator p300 also contributed to these responses. Functionally, LTA-induced MMP-9 expression enhanced astrocytic migration. Conclusion These results demonstrated that in RBA-1 cells, activation of ATF2/AP-1 by the PKC(α)-mediated Nox(2)/ROS signals is essential for upregulation of MMP-9 and cell migration enhanced by LTA. PMID:22643046

  11. Development and Application of a Paleomagnetic/Geochemical Method for Constraining the Timing of Burial Diagenetic and Fluid

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Elmore, Richard D.; Engel, Michael H.

    2005-03-10

    Studies of diagenesis caused by fluid migration or other events are commonly hindered by a lack of temporal control. Our results to date demonstrate that a paleomagnetic/geochemical approach can be used to date fluid migration as well as burial diagenetic events. Our principal working hypothesis is that burial diagenetic processes (e.g., maturation of organic-rich sediments and clay diagenesis) and the migration of fluids can trigger the authigenesis of magnetic mineral phases. The ages of these events can be constrained by comparing chemical remanent magnetizations (CRMs) to independently established Apparent Polar Wander Paths. While geochemical (e.g. stable isotope and organic analyses)more » and petrographic studies provide important clues for establishing these relationships, the ultimate test of this hypothesis requires the application of independent dating methods to verify the paleomagnetic ages. Towards this end, we have used K-Ar dating of illitization as an alternative method for constraining the ages of magnetic mineral phases in our field areas.« less

  12. New hydrologic model of fluid migration in deep porous media

    NASA Astrophysics Data System (ADS)

    Dmitrievsky, A.; Balanyuk, I.

    2009-04-01

    The authors present a new hydrological model of mantle processes that effect on formation of oil-and-gas bearing basins, fault tectonics and thermal convection. Any fluid migration is initially induced by lateral stresses in the crust and lithosphere which result from global geodynamic processes related to the mantle convection. The global processes are further transformed into regional movements in weakness zones. Model of porous media in deep fractured zones and idea of self-oscillation processes in mantle layers and fractured zones of the crust at different depths was used as the basis for developed concept. The content of these notions resides in the fact that there are conditions of dynamic balance in mantle layers originating as a result of combination and alternate actions of compaction and dilatance mechanisms. These mechanisms can be manifested in different combinations and under different conditions as well as can be complemented by other processes influencing on regime of fluid migration. They can act under condition of passive margin, ocean rift and ocean subduction zones as well as in consolidated platform and sheet. Self-oscillation regime, sub vertical direction of fluid flows, anomalously high layer pressure, and high level of anomalies of various geophysical fields are common for them. A certain class of fluid dynamic models describing consolidation of sedimentary basins, free oscillation processes slow and quick (at the final stage) fluid dynamic processes of the evolution of a sedimentary basin in subduction zones is considered for the first time. The last model of quick fluid dynamic processes reflects the process of formation of hydrocarbon deposits in the zones of collision of lithosphere plates. The results of numerical simulation and diagrams reflecting consecutive stages of the gas-fluid dynamic front propagation are assessed of the Pri-Caspian depression as the example. Calculations with this model will simultaneously be carried out for the sedimentary basins of Timan-Pechora region, Barents Sea, Volga-Ural area, etc. Hydrologic model of deep porous media and the idea of self-oscillation processes in fractured layers of the crust at different depths were used as the basis for developed concept. The content of these notions resides in the fact that there are conditions of dynamic balance in fractured layers originating as a result of combination and alternate actions of compaction and dilatance mechanisms. These mechanisms can be manifested in different combinations and under different conditions as well as can be complemented by other processes influencing on regime of fluid migration. They can act under condition of passive margin, rift and subduction zones as well as in consolidated platform and sheet. Self-oscillation regime, sub vertical direction of fluid flows, anomalously high layer pressure, and high level of anomalies of various geophysical fields are common for them. Specific manifestations of these mechanisms can vary in dependence on geological settings and geodynamic situations. In particular, periods of self-oscillations and depths of fractured layers can be various. Orientation of layers can be not only horizontal, but vertical as well, that is, self-oscillations can occur not only in deep porous media, but in faults and impaired fractured zones as well. Predominating vertical fluid migration can be accompanied by horizontal migration along crust waveguide. A set of fluid dynamic models is considered. Mathematical modeling of geodynamic and fluid dynamic processes in these zones seems very promising. Combined consideration of geodynamic and fluid dynamic aspects in a model of lithosphere plates collision enables to understand the influence of P-T conditions and shear deformations on the mechanism of hydrocarbon generation and to look after their migration and to explain these processes, but also to predict some features essential for the search and exploration of hydrocarbon fields in these regions and their classification. In terms of compaction models, multiphase filtration in a piezo-conduction mode and models of deep porous media major stages of fluid evolution under the conditions of developing passive margins and in the zones of collision of plates are described. In particular, compaction models of one of the stages of fluid mode evolution within a sedimentary basin and fluid migration from the convergence zones toward the upper layers are considered. In the final part of work, computation of fluid transfer of hydrocarbons in a pulse mode described by the equation of piezo-conductivity is presented for a mature oil-bearing sedimentary basin over individual sections for short periods of a few hundreds of years. These calculations were executed on the basis of a new mathematical method TEKON and computer programs for quantitative analysis of fluid migration and formation of hydrocarbon deposits with account taken for actual geometrical and lithological properties of the layers. On the basis of the specified numerical calculations the scales, form, and routes of fluid movement were disclosed, as well as the formation of zones of anomalously high rock pressure and non-traditional hydrocarbon deposits.

  13. Sendai-Okura earthquake swarm induced by the 2011 Tohoku-Oki earthquake in the stress shadow of NE Japan: Detailed fault structure and hypocenter migration

    NASA Astrophysics Data System (ADS)

    Yoshida, Keisuke; Hasegawa, Akira

    2018-05-01

    We investigated the distribution and migration of hypocenters of an earthquake swarm that occurred in Sendai-Okura (NE Japan) 15 days after the 2011 M9.0 Tohoku-Oki earthquake, despite the decrease in shear stress due to the static stress change. Hypocenters of 2476 events listed in the JMA catalogue were relocated based on the JMA unified catalogue data in conjunction with data obtained by waveform cross correlation. Hypocenter relocation was successful in delineating several thin planar structures, although the original hypocenters presented a cloud-like distribution. The hypocenters of this swarm event migrated along several planes from deeper to shallower levels rather than diffusing three-dimensionally. One of the nodal planes of the focal mechanisms was nearly parallel to the planar structure of the hypocenters, supporting the idea that each earthquake occurred by causing slip on parts of the same plane. The overall migration velocity of the hypocenters could be explained by the fluid diffusion model with a typical value of hydraulic diffusivity (0.15 m2/s); however, the occurrence of some burst-like activity with much higher migration velocity suggests the possibility that aseismic slip also contributed to triggering the earthquakes. We suggest that the 2011 Sendai-Okura earthquake swarm was generated as follows. (1) The 2011 Tohoku-Oki earthquake caused WNW-ESE extension in the focal region of the swarm, which accordingly reduced shear stress on the fault planes. However, the WNW-ESE extension allowed fluids to move upward from the S-wave reflectors in the mid-crust immediately beneath the focal region. (2) The fluids rising from the mid-crust intruded into several existing planes, which reduced their frictional strengths and caused the observed earthquake swarm. (3) The fluids, and accordingly, the hypocenters of the triggered earthquakes, migrated upward along the fault planes. It is possible that the fluids also triggered aseismic slip, which caused intermittent burst-like activity.

  14. Computer Simulations of the Tumor Vasculature: Applications to Interstitial Fluid Flow, Drug Delivery, and Oxygen Supply.

    PubMed

    Welter, Michael; Rieger, Heiko

    2016-01-01

    Tumor vasculature, the blood vessel network supplying a growing tumor with nutrients such as oxygen or glucose, is in many respects different from the hierarchically organized arterio-venous blood vessel network in normal tissues. Angiogenesis (the formation of new blood vessels), vessel cooption (the integration of existing blood vessels into the tumor vasculature), and vessel regression remodel the healthy vascular network into a tumor-specific vasculature. Integrative models, based on detailed experimental data and physical laws, implement, in silico, the complex interplay of molecular pathways, cell proliferation, migration, and death, tissue microenvironment, mechanical and hydrodynamic forces, and the fine structure of the host tissue vasculature. With the help of computer simulations high-precision information about blood flow patterns, interstitial fluid flow, drug distribution, oxygen and nutrient distribution can be obtained and a plethora of therapeutic protocols can be tested before clinical trials. This chapter provides an overview over the current status of computer simulations of vascular remodeling during tumor growth including interstitial fluid flow, drug delivery, and oxygen supply within the tumor. The model predictions are compared with experimental and clinical data and a number of longstanding physiological paradigms about tumor vasculature and intratumoral solute transport are critically scrutinized.

  15. Interstitial flow influences direction of tumor cell migration through competing mechanisms

    PubMed Central

    Polacheck, William J.; Charest, Joseph L.; Kamm, Roger D.

    2011-01-01

    Interstitial flow is the convective transport of fluid through tissue extracellular matrix. This creeping fluid flow has been shown to affect the morphology and migration of cells such as fibroblasts, cancer cells, endothelial cells, and mesenchymal stem cells. A microfluidic cell culture system was designed to apply stable pressure gradients and fluid flow and allow direct visualization of transient responses of cells seeded in a 3D collagen type I scaffold. We used this system to examine the effects of interstitial flow on cancer cell morphology and migration and to extend previous studies showing that interstitial flow increases the metastatic potential of MDA-MB-435S melanoma cells [Shields J, et al. (2007) Cancer Cell 11:526–538]. Using a breast carcinoma line (MDA-MB-231) we also observed cell migration along streamlines in the presence of flow; however, we further demonstrated that the strength of the flow as well as the cell density determined directional bias of migration along the streamline. In particular, we found that cells either at high seeding density or with the CCR-7 receptor inhibited migration against, rather than with the flow. We provide further evidence that CCR7-dependent autologous chemotaxis is the mechanism that leads to migration with the flow, but also demonstrate a competing CCR7-independent mechanism that causes migration against the flow. Data from experiments investigating the effects of cell concentration, interstitial flow rate, receptor activity, and focal adhesion kinase phosphorylation support our hypothesis that the competing stimulus is integrin mediated. This mechanism may play an important role in development of metastatic disease. PMID:21690404

  16. Decreased nuclear stiffness via FAK-ERK1/2 signaling is necessary for osteopontin-promoted migration of bone marrow-derived mesenchymal stem cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Lingling, E-mail: liulingling2012@163.com; Luo, Qing, E-mail: qing.luo@cqu.edu.cn; Sun, Jinghui, E-mail: sunjhemail@163.com

    Migration of bone marrow-derived mesenchymal stem cells (BMSCs) plays an important role in many physiological and pathological settings, including wound healing. During the migration of BMSCs through interstitial tissues, the movement of the nucleus must be coordinated with the cytoskeletal dynamics, which in turn affects the cell migration efficiency. Our previous study indicated that osteopontin (OPN) significantly promotes the migration of rat BMSCs. However, the nuclear behaviors and involved molecular mechanisms in OPN-mediated BMSC migration are largely unclear. In the present study, using an atomic force microscope (AFM), we found that OPN could decrease the nuclear stiffness of BMSCs andmore » reduce the expression of lamin A/C, which is the main determinant of nuclear stiffness. Increased lamin A/C expression attenuates BMSC migration by increasing nuclear stiffness. Decreased lamin A/C expression promotes BMSC migration by decreasing nuclear stiffness. Furthermore, OPN promotes BMSC migration by diminishing lamin A/C expression and decreasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This study provides strong evidence for the role of nuclear mechanics in BMSC migration as well as new insight into the molecular mechanisms of OPN-promoted BMSC migration. - Highlights: • OPN promotes BMSC migration by decreasing nuclear stiffness. • Lamin A/C knockdown decreases, while its overexpression enhances, the nuclear stiffness of BMSCs. • Lamin A/C overexpression and downregulation affect the migration of BMSCs. • OPN diminishes lamin A/C expression and decreases nuclear stiffness through the activation of the FAK-ERK1/2 signaling pathway. • OPN promotes BMSC migration via the FAK-ERK1/2 signaling pathway.« less

  17. Long non-coding RNA BCAR4 promotes chondrosarcoma cell proliferation and migration through activation of mTOR signaling pathway

    PubMed Central

    Shui, Xiaolong; Zhou, Chengwei; Lin, Wei; Yu, Yang; Feng, Yongzeng

    2017-01-01

    Background: Chondrosarcoma is one of the common malignant histologic tumors, very difficult to treat, but the concrete cause and mechanism have not yet been elucidated. The present study aimed to investigate the functional involvement of BCAR4 in chondrosarcoma and its potentially underlying mechanism. QRT-PCR and western blot were used to determine the expression of BCAR4 and mTOR signaling pathway proteins both in chondrosarcoma tissues and cells. Chondrosarcoma cell proliferation and migration were assessed by MTT assay and transwell migration assay, respectively. The expression vectors were constructed and used to modulate the expression of BCAR4 and mTOR. Chondrosarcoma xenograft mouse model was established by subcutaneous injection with chondrosarcoma cell lines. The tumor volume was monitored to evaluate the effect of BCAR4 on chondrosarcoma cell tumorigenicity. The expressions of BCAR4, p-mTOR and p-P70S6K were up-regulated in chondrosarcoma tissues and cell lines. Moreover, BCAR4 overexpression had significant promoting effect on cell proliferation and migration in chondrosarcoma cells. Furthermore, mTOR signaling pathway was epigenetically activated by BCAR4-induced hyperacetylation of histone H3. We also found that mTOR overexpression abolished the decrease of chondrosarcoma cell proliferation and migration induced by BCAR4 knockdown. In vivo experiments confirmed that BCAR4 overexpression significantly accelerated tumor growth, while the knockdown of BCAR4 significantly inhibited tumor growth. BCAR4 promoted chondrosarcoma cell proliferation and migration through activation of mTOR signaling pathway, and thus contributed to chondrosarcoma progression. Impact statement LncRNA BCAR4 promoted chondrosarcoma cell proliferation and migration through activation of mTOR signaling pathway, and thus contributed to chondrosarcoma progression. PMID:28399646

  18. Long non-coding RNA BCAR4 promotes chondrosarcoma cell proliferation and migration through activation of mTOR signaling pathway.

    PubMed

    Shui, Xiaolong; Zhou, Chengwei; Lin, Wei; Yu, Yang; Feng, Yongzeng; Kong, Jianzhong

    2017-05-01

    Chondrosarcoma is one of the common malignant histologic tumors, very difficult to treat, but the concrete cause and mechanism have not yet been elucidated. The present study aimed to investigate the functional involvement of BCAR4 in chondrosarcoma and its potentially underlying mechanism. QRT-PCR and western blot were used to determine the expression of BCAR4 and mTOR signaling pathway proteins both in chondrosarcoma tissues and cells. Chondrosarcoma cell proliferation and migration were assessed by MTT assay and transwell migration assay, respectively. The expression vectors were constructed and used to modulate the expression of BCAR4 and mTOR. Chondrosarcoma xenograft mouse model was established by subcutaneous injection with chondrosarcoma cell lines. The tumor volume was monitored to evaluate the effect of BCAR4 on chondrosarcoma cell tumorigenicity. The expressions of BCAR4, p-mTOR and p-P70S6K were up-regulated in chondrosarcoma tissues and cell lines. Moreover, BCAR4 overexpression had significant promoting effect on cell proliferation and migration in chondrosarcoma cells. Furthermore, mTOR signaling pathway was epigenetically activated by BCAR4-induced hyperacetylation of histone H3. We also found that mTOR overexpression abolished the decrease of chondrosarcoma cell proliferation and migration induced by BCAR4 knockdown. In vivo experiments confirmed that BCAR4 overexpression significantly accelerated tumor growth, while the knockdown of BCAR4 significantly inhibited tumor growth. BCAR4 promoted chondrosarcoma cell proliferation and migration through activation of mTOR signaling pathway, and thus contributed to chondrosarcoma progression. Impact statement LncRNA BCAR4 promoted chondrosarcoma cell proliferation and migration through activation of mTOR signaling pathway, and thus contributed to chondrosarcoma progression.

  19. Hypoxia Regulates mTORC1-Mediated Keratinocyte Motility and Migration via the AMPK Pathway

    PubMed Central

    Yan, Tiantian; Zhang, Junhui; Tang, Di; Zhang, Xingyue; Jiang, Xupin; Zhao, Liping; Zhang, Qiong; Zhang, Dongxia; Huang, Yuesheng

    2017-01-01

    Keratinocyte migration, the initial event and rate-limiting step in wound healing, plays a vital role in restoration of the intact skin barrier, also known as re-epithelialization. After acute tissue injury, hypoxic microenvironment gradually develops and acts as an early stimulus to initiate the healing process. Although we have previously found that hypoxia induces keratinocyte migration, the underlying mechanism remains unknown. Here, we first observed that hypoxia increased mTORC1 activity. Recombinant lentivirus vector and Rapamycin were used for silencing mTORC1 in HaCaT cells and primary mouse keratinocytes (MKs). Using cell migration assay and a Zeiss chamber equipped with imaging system, we also demonstrated that mTORC1 downregulation reversed hypoxia-induced keratinocyte motility and lateral migration. Importantly, hypoxia-activated mTORC1 was accompanied by the AMPK downregulation, and we found that the AMPK pathway activators Metformin (Met) and 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) decreased the mTORC1 activity, cell motility and lateral migration. Thus, our results suggest that hypoxia regulates mTORC1-mediated keratinocyte motility and migration via the AMPK pathway. PMID:28068384

  20. Shear induced migration of particles in a yield stress fluid: experiment

    NASA Astrophysics Data System (ADS)

    Hormozi, Sarah; Gholami, Mohammad; Rashedi, Ahmadreza; Lenoir, Nicolas; Ovarlez, Guillaume

    2017-11-01

    We have performed rheometry coupled with X-ray radiography in a narrow gap Couette cell filled with a suspension of spherical particles in a yield stress fluid. In this setup, the shear rate is discontinuous changing from a constant value in the gap to zero in the reservoir located at the top. This shear rate inhomogeneity results in the migration of particles from the gap to the reservoir, so-called Shear Induced Migration (SIM). The rheometry results give us insight into understanding the bulk rheology in the presence of shear rate and solid volume fraction inhomogeneities. In addition to that, our recent X-ray radiography technique (Gholami et al., JOR. 2017) provides detailed information about the evolution of the solid volume fraction in the domain. These measurements allow us to refine the recent continuum model frameworks (Hormozi & Frigaard, JFM 2017) for SIM of particles in a yield stress suspending fluid. We show that complex rheology of the yield stress suspending fluid and formation of the islands of unyielded regions in the reservoir strongly affects the SIM of particles. This feature is absent when we deal with a Newtonian suspending fluid. NSF (Grant No. CBET-1554044- CAREER), ACS PRF (Grant No. 55661-DNI9).

  1. Are polygonal faults the keystone for better understanding the timing of fluid migration in sedimentary basins?

    NASA Astrophysics Data System (ADS)

    Gay, Aurélien

    2017-06-01

    The initial sediment lithification starts with complex interactions involving minerals, surface water, decomposing organic matter and living organisms. This is the eogenesis domain (0 to 2 km below the seafloor) in which the sediments are subject to physical, chemical and mechanical transformations defining the early fabric of rocks. This interval is intensively prospected for its energy/mining resources (hydrocarbons, metal deposits, geothermal energy). In most basins worldwide it is composed of very fine-grained sediments and it is supposed to play the role of a seal for fluids migration. However, it is affected by polygonal faulting due to a volume loss during burial by contraction of clay sediments with a high smectite content. This process is of high interest for fractured reservoirs and/or cover integrity but it is not well constrained giving an uncertainty as this interval can either promote the migration of deeper fluids and the mineralized fluids intensifies diagenesis in the fracture planes, rendering this interval all the more impermeable. The next challenge will be to define where, when and how does this polygonal fault interval occur and this can only be done by understanding the behavior of clay grains and fluids during early burial.

  2. From Gender-Not-an-Issue to Gender Is the Issue: The Educational and Migrational Pathways of Middle-Class Women Moving from Urban Bangladesh to Britain

    ERIC Educational Resources Information Center

    Mahbub, Rifat

    2015-01-01

    This paper explores the educational and migrational pathways which a number of middle-class women from Bangladesh took as they grew up in the 1980s and 1990s. It draws on qualitative research, conducted between July and November 2011, with highly educated Bangladeshi women who migrated to Britain in the early 2000s. French Sociologist Pierre…

  3. The geothermal system of Caviahue-Copahue Volcanic Complex (Chile-Argentina): New insights from self-potential, soil CO2 degassing, temperature measurements and helium isotopes, with structural and fluid circulation implications.

    NASA Astrophysics Data System (ADS)

    Roulleau, Emilie; Bravo, Francisco; Barde-Cabusson, Stephanie; Pizarro, Marcela; Muños, Carlos; Sanchez, Juan; Tardani, Daniele; Sano, Yuji; Takahata, Naoto; de Cal, Federico; Esteban, Carlos

    2016-04-01

    Geothermal systems represent natural heat transfer engines in a confined volume of rock which are strongly influenced by the regional volcano-tectonic setting controlling the formation of shallow magmatic reservoirs, and by the local faults/fracture network, that permits the development of hydrothermal circulation cells and promote the vertical migration of fluids and heat. In the Southern Volcanic Zone of Chile-Argentina, geothermal resources occur in close spatial relationship with active volcanism along the Cordillera which is primarily controlled by the 1000 km long, NNE Liquiñe-Ofqui Fault Zone (LOFZ), an intra-arc dextral strike-slip fault system, associated with second-order intra-arc anisotropy of overall NE-SW (extensional) and NW-SE orientation (compressional). However there is still a lack of information on how fault network (NE and WNW strinking faults) and lithology control the fluid circulation. In this study, we propose new data of dense self-potential (SP), soil CO2 emanation and temperature (T) measurements within the geothermal area from Caviahue-Copahue Volcanic Complex (CCVC), coupled with helium isotopes ratios measured in fumaroles and thermal springs. We observe that inside the geothermal system the NE-striking faults, characterized by a combination of SP-CO2 and T maxima with high 3He/4He ratios (7.86Ra), promote the formation of high vertical permeability pathways for fluid circulation. Whereas, the WNW-striking faults represent low permeability pathways for hydrothermal fluids ascent associated with moderate 3He/4He ratios (5.34Ra), promoting the infiltration of meteoric water at shallow depth. These active zones are interspersed by SP-CO2- T minima, which represent self-sealed zones (e.g. impermeable altered rocks) at depth, creating a barrier inhibiting fluids rise. The NE-striking faults seem to be associated with the upflow zones of the geothermal system, where the boiling process produces a high vapor-dominated zone close to the surface. The WNW-striking faults seems to limit to the south the Copahue geothermal area.

  4. Transverse bacterial migration induced by chemotaxis in a packed column with structured physical heterogeneity.

    PubMed

    Wang, Meng; Ford, Roseanne M

    2009-08-01

    The significance of chemotaxis in directing bacterial migration toward contaminants in natural porous media was investigated under groundwater flow conditions. A laboratory-scale column, with a coarse-grained sand core surrounded by a fine-grained annulus, was used to simulate natural aquifers with strata of different hydraulic conductivities. A chemoattractant source was placed along the central axis of the column to model contaminants trapped in the heterogeneous subsurface. Chemotactic bacterial strains, Escherichia coli HCB1 and Pseudomonas putida F1, introduced into the column by a pulse injection, were found to alter their transport behaviors under the influence of the attractant chemical emanating from the central source. For E. coil HCB1, approximately 18% more of the total population relative to the control without attractant exited the column from the coarse sand layer due to the chemotactic effects of alpha-methylaspartate under an average fluid velocity of 5.1 m/d. Although P. putida F1 demonstrated no observable changes in migration pathways with the model contaminant acetate under the same flow rate, when the flow rate was reduced to 1.9 m/d, approximately 6-10% of the population relative to the control migrated from the fine sand layer toward attractant into the coarse sand layer. Microbial transport properties were further quantified by a mathematical model to examine the significance of bacterial motility and chemotaxis under different hydrodynamic conditions, which suggested important considerations for strain selection and practical operation of bioremediation schemes.

  5. Cannabinoid Receptor 2 Suppresses Leukocyte Inflammatory Migration by Modulating the JNK/c-Jun/Alox5 Pathway*

    PubMed Central

    Liu, Yi-Jie; Fan, Hong-Bo; Jin, Yi; Ren, Chun-Guang; Jia, Xiao-E; Wang, Lei; Chen, Yi; Dong, Mei; Zhu, Kang-Yong; Dong, Zhi-Wei; Ye, Bai-Xin; Zhong, Zhong; Deng, Min; Liu, Ting Xi; Ren, Ruibao

    2013-01-01

    Inflammatory migration of immune cells is involved in many human diseases. Identification of molecular pathways and modulators controlling inflammatory migration could lead to therapeutic strategies for treating human inflammation-associated diseases. The role of cannabinoid receptor type 2 (Cnr2) in regulating immune function had been widely investigated, but the mechanism is not fully understood. Through a chemical genetic screen using a zebrafish model for leukocyte migration, we found that both an agonist of the Cnr2 and inhibitor of the 5-lipoxygenase (Alox5, encoded by alox5) inhibit leukocyte migration in response to acute injury. These agents have a similar effect on migration of human myeloid cells. Consistent with these results, we found that inactivation of Cnr2 by zinc finger nuclease-mediated mutagenesis enhances leukocyte migration, while inactivation of Alox5 blocks leukocyte migration. Further investigation indicates that there is a signaling link between Cnr2 and Alox5 and that alox5 is a target of c-Jun. Cnr2 activation down-regulates alox5 expression by suppressing the JNK/c-Jun activation. These studies demonstrate that Cnr2, JNK, and Alox5 constitute a pathway regulating leukocyte migration. The cooperative effect between the Cnr2 agonist and Alox5 inhibitor also provides a potential therapeutic strategy for treating human inflammation-associated diseases. PMID:23539630

  6. A synthetic mechano-growth factor E peptide promotes rat tenocyte migration by lessening cell stiffness and increasing F-actin formation via the FAK-ERK1/2 signaling pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Bingyu; Luo, Qing, E-mail: qing.luo@cqu.edu.cn; Mao, Xinjian

    Tendon injuries are common in sports and are frequent reasons for orthopedic consultations. The management of damaged tendons is one of the most challenging problems in orthopedics. Mechano-growth factor (MGF), a recently discovered growth repair factor, plays positive roles in tissue repair through the improvement of cell proliferation and migration and the protection of cells against injury-induced apoptosis. However, it remains unclear whether MGF has the potential to accelerate tendon repair. We used a scratch wound assay in this study to demonstrate that MGF-C25E (a synthetic mechano-growth factor E peptide) promotes the migration of rat tenocytes and that this promotionmore » is accompanied by an elevation in the expression of the following signaling molecules: focal adhesion kinase (FAK) and extracellular signal regulated kinase1/2 (ERK1/2). Inhibitors of the FAK and ERK1/2 pathways inhibited the MGF-C25E-induced tenocyte migration, indicating that MGF-C25E promotes tenocyte migration through the FAK-ERK1/2 signaling pathway. The analysis of the mechanical properties showed that the Young's modulus of tenocytes was decreased through treatment of MGF-C25E, and an obvious formation of pseudopodia and F-actin was observed in MGF-C25E-treated tenocytes. The inhibition of the FAK or ERK1/2 signals restored the decrease in Young's modulus and inhibited the formation of pseudopodia and F-actin. Overall, our study demonstrated that MGF-C25E promotes rat tenocyte migration by lessening cell stiffness and increasing pseudopodia formation via the FAK-ERK1/2 signaling pathway. - Highlights: • Mechano-growth factor E peptide (MGF-C25E) promotes migration of rat tenocytes. • MGF-C25E activates the FAK-ERK1/2 pathway in rat tenocytes. • MGF-C25E induces the actin remodeling and the formation of pseudopodia, and decreases the stiffness in rat tenocytes. • MGF-C25E promotes tenocyte migration via altering stiffness and forming pseudopodia by the activation of the FAK-ERK1/2 pathway.« less

  7. Dexamethasone disrupts cytoskeleton organization and migration of T47D Human breast cancer cells by modulating the AKT/mTOR/RhoA pathway.

    PubMed

    Meng, Xian-Guo; Yue, Shou-Wei

    2014-01-01

    Glucocorticoids are commonly co-administered with chemotherapy to prevent drug-induced allergic reactions, nausea, and vomiting, and have anti-tumor functions clinically; however, the distinct effects of GC on subtypes of tumor cells, especially in breast cancer cells, are still not well understood. In this study, we aimed to clarify the effect of GC on subtypes of T47D breast cancer cells by focusing on apoptosis, cell organization and migration, and underluing molecular mechanisms. The cell scratch test was performed to observe the cell migration rate in T47D cells treated with dexamethasone (Dex). Hoechst and MTT assays were conducted to detect cell survival and rhodamine-labeled phalloidin staining to observe cytoskeleton dynamics. Related factors in the AKT/mTOR pathway were determined by Western blotting. Dex treatment could effectively inhibit T47D breast cancer cell migration with disruption of the cytoskeletal dynamic organization. Moreover, the effect of Dex on cell migration and cytoskeleton may be mediated by AKT/ mTOR/RhoA pathway. Although Dex inhibited T47D cell migration, it alone may not induce cell apoptosis in T47D cells. Dex in T47D human breast cancer cells could effectively inhibit cell migration by disrupting the cytoskeletal dynamic organization, which may be mediated by the AKT/mTOR/RhoA pathway. Our work suggests that glucocorticoid/Dex clinical use may prove helpful for the treatment of breast cancer metastasis.

  8. Syntectonic Fluid-Rock Interactions Involving Surficial Waters in the Sevier Thrust Belt, Tendoy Mountains, Southwest Montana

    NASA Astrophysics Data System (ADS)

    Johnson, A. C.; Anastasio, D. J.; Bebout, G. E.

    2002-05-01

    Calcite veins and Mississippian carbonates from the Sevier thrust front record syntectonic meteoric fluid infiltration and hydrocarbon migration. The Tendoy and Four Eyes Canyon thrust sheets were emplaced onto the western margin of the Late Cretaceous Western Interior Seaway \\{WIS\\}. Low salinity \\{Tice = -0.6° C to +3.6° C\\} and low temperature \\{110° C +/- 10\\} fluids interacted with hanging-wall carbonates at a depth of 5km. Most veins have single or multiple generations of varying apertures, composed predominately of large euhedral crystals with some finer grained layers and protolith inclusions. Orientation analysis of mutually cross-cutting, high-angle vein sets suggest development concurrent with Four Eyes Canyon thrusting but prior to Tendoy thrusting. These vein sets are generally cut by later synfolding bed-parallel shear veins. Reactivation of both the bed-parallel and bed-perpendicular vein sets \\{strike parallel and strike perpendicular\\} in the Four Eyes Canyon thrust sheet occurred subsequent to Sevier compression, creating wide, coarse crystalline veins that often transect Sevier structures. Oxygen and Carbon isotope analyses of veins allow for reconstruction of fluid-rock interactions during thrust sheet emplacement and later reactivation. All veins and variably deformed host-rocks were microsampled and analyzed for δ 18OV-SMOW and δ 13CV-PDB. Small Tendoy veins \\{1mm-1cm wide\\} have calcite δ 18O values of +8.9 to +28.8‰ and calculated fluid \\{as H2O\\} of -8.3 to +11.6‰ \\{100° C\\}, -7.3 to +12.6‰ \\{110° C\\}, and -6.3 to +13.6‰ \\{120° C\\}. Four Eyes Canyon veins \\{1cm-3m wide\\} have calcite δ 18O values of +5.9 to +17.0‰ and calculated fluid of -11.3 to -0.2‰ \\{100° C\\}, -10.3 to +0.8‰ \\{110° C\\}, and -9.3 to +1.8‰ \\{120° C\\}. While there is significant variation in δ 18O there is relatively little systematic variation seen in δ 13C. Protolith carbonate has δ 18O values of +22.2‰ +/- 3.2; and some multi-layered veins are more depleted in δ 18O in earlier-formed generations. For three sites in the Lost River Range \\{LRR\\}, Idaho, the calculated minimum fluid δ 18O is -7.5‰ \\{+150 to +250° C\\} \\{Bebout et al., 2001; GRL\\}. Although the uncertainty of the regional temperature is large, when assuming a temperature of 110° C +/- 10 the Tendoy has a minimum calculated δ 18O H2O value of -8.3 to -6.3‰ and the Four Eyes Canyon has a minimum calculated δ 18O H2O value of -11.3 to -9.3‰ . These fluid O-isotope compositions are similar to the minimum H2O δ 18O calculated for the LRR sites - all pointing to infiltration of the thrust sheets by meteoric waters, possibly relatively nearshore meteoric waters with isotopic compositions strongly influenced by the nearby WIS. Surficial fluids possibly infiltrated into the thrust sheets by topographic recharge and migrated updip towards the foreland, mixing to varying degrees with more deeply roused fluids. Smaller veins and longer travel times and distances favored more extensive fluid-rock interaction and thus more rock-controlled fluid compositions. Microfractures in veins healed by hydrocarbons indicate that hydrocarbons migrated with freshwater fluids. Calcite veins record a dynamic history of fluid pathways and fluid flow as permeability evolved during thrust emplacement.

  9. Enhancement of human mesenchymal stem cell infiltration into the electrospun poly(lactic-co-glycolic acid) scaffold by fluid shear stress.

    PubMed

    Kim, Min Sung; Lee, Mi Hee; Kwon, Byeong-Ju; Koo, Min-Ah; Seon, Gyeung Mi; Park, Jong-Chul

    The infiltration of the cells into the scaffolds is important phenomenon to give them good biocompatibility and even biodegradability. Fluid shear stress is one of the candidates for the infiltration of cells into scaffolds. Here we investigated the directional migration of human mesenchymal stem cells and infiltration into PLGA scaffold by fluid shear stress. The human mesenchymal stem cells showed directional migrations following the direction of the flow (8, 16 dyne/cm(2)). In the scaffold models, the fluid shear stress (8 dyne/cm(2)) enhanced the infiltration of cells but did not influence on the infiltration of Poly(lactic-co-glycolic acid) particles. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Fast intraslab fluid-flow events linked to pulses of high pore fluid pressure at the subducted plate interface

    NASA Astrophysics Data System (ADS)

    Taetz, Stephan; John, Timm; Bröcker, Michael; Spandler, Carl; Stracke, Andreas

    2018-01-01

    A better understanding of the subduction zone fluid cycle and its chemical-mechanical feedback requires in-depth knowledge about how fluids flow within and out of descending slabs. Relicts of fluid-flow systems in exhumed rocks of fossil subduction zones allow for identification of the general relationships between dehydration reactions, fluid pathway formation, the dimensions and timescales of distinct fluid flow events; all of which are required for quantitative models for fluid-induced subduction zone processes. Two types of garnet-quartz-phengite veins can be distinguished in an eclogite-facies mélange block from the Pouébo Eclogite Mélange, New Caledonia. These veins record synmetamorphic internal fluid release by mineral breakdown reactions (type I veins), and infiltration of an external fluid (type II veins) with the associated formation of a reaction selvage. The dehydration and fluid migration documented by the type I veins likely occurred on a timescale of 105-106 years, based on average subduction rates and metamorphic conditions required for mineral dehydration and fluid flow. The timeframe of fluid-rock interaction between the external fluid and the wall-rock of the type II veins is quantified using a continuous bulk-rock Li-diffusion profile perpendicular to a vein and its metasomatic selvage. Differences in Li concentration between the internal and external fluid reservoirs resulted in a distinct diffusion profile (decreasing Li concentration and increasing δ7 Li) as the reaction front propagated into the host rock. Li-chronometric constraints indicate that the timescales of fluid-rock interaction associated with type II vein formation are on the order of 1 to 4 months (0.150-0.08+0.14 years). The short-lived, pulse-like character of this process is consistent with the notion that fluid flow caused by oceanic crust dehydration at the blueschist-to-eclogite transition contributes to or even dominates episodic pore fluid pressure increases at the plate interface, which in turn, may trigger slip events reported from many subduction zones.

  11. Geochemical Evidence for Possible Natural Migration of Marcellus Formation Brine to Shallow Aquifers in Pennsylvania

    NASA Astrophysics Data System (ADS)

    Warner, N. R.; Darrah, T. H.; Jackson, R. B.; Osborn, S.; Down, A.; Vengosh, A.

    2012-12-01

    The acceleration in production of natural gas from shale formations through horizontal drilling and hydraulic fracturing has altered the landscape of domestic energy production in the USA. Yet shale gas exploration has generated an increased awareness of risks to drinking water quality amid concerns for the possible migration of stray gas or hydraulic fracturing fluid and/or flowback brine to shallow drinking water aquifers. The degree to which shallow drinking water is at risk from hydraulic fracturing could depend upon the hydraulic connectivity between the shale gas formations and the surface. In this study, we analyzed the geochemistry of over 400 water samples located across six counties of northeastern Pennsylvania in the three principle aquifers, two Upper Devonian Age bedrock aquifers (Catskill and Lock Haven) and one Quaternary Age (Alluvium) that overlie the Marcellus Formation. Based on a detailed analysis of major (Br, Cl, Na, Mg, Ba, and Sr) and trace (Li) element geochemistry, coupled with utilization of a specific spectrum of isotopic tracers (87Sr/86Sr, 228Ra/ 226Ra, 2H/H, 18O/16O), we identify a salinized (Cl> 20 mg/L) shallow groundwater type which suggests conservative mixing relationships between fresh shallow groundwater and an underlying brine. Identification of the brine source is complicated as many of the brines in the northern Appalachian Basin likely share a common origin as the expelled remnants of the formation of the Silurian Salina evaporate deposits. To determine the ultimate source of the diluted brine we compared the observed geochemistry to over 80 brines produced from northern Appalachian Basin formations. The shallow salinized groundwater most closely resembles diluted produced water from the Middle Devonian Marcellus Formation. The 18O/16O and 2H/H of the salinized groundwater indicate that the brine is likely diluted with post-glacial (<10,000 ybp) meteoric water. Combined, these data indicate that hydraulic connections allowed cross formational migration of brine from deeper formations (1-2 kilometers below ground surface) and subsequent dilution. The occurrence of the saline water does not appear to be correlated with the location of shale-gas wells. Also, salinized groundwater with similar major element chemistry was reported prior to the most recent shale-gas development in the region. The source of the salinized water is likely not the recent drilling and hydraulic fracturing; instead brine migrated into the shallow aquifers and was recently diluted through natural pathways and processes. However, the presence of natural hydraulic connections to deeper formations suggests specific structural and hydrodynamic regimes in northeastern Pennsylvania where shallow drinking water resources are at greater risk of contamination, particularly with fugitive gases, during drilling and hydraulic fracturing of shale gas. The severity of the risk could depend upon the presence of pathways that allow the migration of fluids into the shallow aquifers on human time scales.

  12. Inflammatory and Repair Pathways Induced in Human Bronchoalveolar Lavage Cells with Ozone Inhalation

    PubMed Central

    Wong, Hofer; Tenney, Rachel; Chen, Chun; Stiner, Rachel; Balmes, John R.; Paquet, Agnès C.; Arjomandi, Mehrdad

    2015-01-01

    Background Inhalation of ambient levels of ozone causes airway inflammation and epithelial injury. Methods To examine the responses of airway cells to ozone-induced oxidative injury, 19 subjects (7 with asthma) were exposed to clean air (0ppb), medium (100ppb), and high (200ppb) ambient levels of ozone for 4h on three separate occasions in a climate-controlled chamber followed by bronchoscopy with bronchoalveolar lavage (BAL) 24h later. BAL cell mRNA expression was examined using Affymetrix GeneChip Microarray. The role of a differentially expressed gene (DEG) in epithelial injury was evaluated in an in vitro model of injury [16HBE14o- cell line scratch assay]. Results Ozone exposure caused a dose-dependent up-regulation of several biologic pathways involved in inflammation and repair including chemokine and cytokine secretion, activity, and receptor binding; metalloproteinase and endopeptidase activity; adhesion, locomotion, and migration; and cell growth and tumorigenesis regulation. Asthmatic subjects had 1.7- to 3.8-fold higher expression of many DEGs suggestive of increased proinflammatory and matrix degradation and remodeling signals. The most highly up-regulated gene was osteopontin, the protein level of which in BAL fluid increased in a dose-dependent manner after ozone exposure. Asthmatic subjects had a disproportionate increase in non-polymerized osteopontin with increasing exposure to ozone. Treatment with polymeric, but not monomeric, osteopontin enhanced the migration of epithelial cells and wound closure in an α9β1 integrin-dependent manner. Conclusions Expression profiling of BAL cells after ozone exposure reveals potential regulatory genes and pathways activated by oxidative stress. One DEG, osteopontin, promotes epithelial wound healing in an in vitro model of injury. PMID:26035830

  13. Microgravity electrophoresis: A study of the factors that affect free-fluid separation

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Electrophoresis experiments have been performed in the microgravity environment of the Space Shuttle. Test particles (fixed human and rabbit erythrocytes) migrated as expected in a static column and test macromolecules (human serum albumin, ovalbumin, hemoglobin A, and Pneumococcus polysaccharide 6B) migrated as expected in a continuous flow apparatus. The concentrations studied exceeded those that can be used in free-fluid separation and purification processes at unit gravity.

  14. Gas production and migration in landfills and geological materials.

    PubMed

    Nastev, M; Therrien, R; Lefebvre, R; Gélinas, P

    2001-11-01

    Landfill gas, originating from the anaerobic biodegradation of the organic content of waste, consists mainly of methane and carbon dioxide, with traces of volatile organic compounds. Pressure, concentration and temperature gradients that develop within the landfill result in gas emissions to the atmosphere and in lateral migration through the surrounding soils. Environmental and safety issues associated with the landfill gas require control of off-site gas migration. The numerical model TOUGH2-LGM (Transport of Unsaturated Groundwater and Heat-Landfill Gas Migration) has been developed to simulate landfill gas production and migration processes within and beyond landfill boundaries. The model is derived from the general non-isothermal multiphase flow simulator TOUGH2, to which a new equation of state module is added. It simulates the migration of five components in partially saturated media: four fluid components (water, atmospheric air, methane and carbon dioxide) and one energy component (heat). The four fluid components are present in both the gas and liquid phases. The model incorporates gas-liquid partitioning of all fluid components by means of dissolution and volatilization. In addition to advection in the gas and liquid phase, multi-component diffusion is simulated in the gas phase. The landfill gas production rate is proportional to the organic substrate and is modeled as an exponentially decreasing function of time. The model is applied to the Montreal's CESM landfill site, which is located in a former limestone rock quarry. Existing data were used to characterize hydraulic properties of the waste and the limestone. Gas recovery data at the site were used to define the gas production model. Simulations in one and two dimensions are presented to investigate gas production and migration in the landfill, and in the surrounding limestone. The effects of a gas recovery well and landfill cover on gas migration are also discussed.

  15. Linkages between life history type and migration pathways in freshwater and marine environments for Chinook salmon, Oncorhynchus tshawytscha

    NASA Astrophysics Data System (ADS)

    Sharma, Rishi; Quinn, Thomas P.

    2012-05-01

    Chinook salmon, Oncorhynchus tshawytscha, are commonly categorized as ocean-type (migrating to the ocean in their first year of life) or stream-type (migrating after a full year in freshwater). These two forms have been hypothesized to display different ocean migration pathways; the former are hypothesized to migrate primarily on the continental shelf whereas the latter are hypothesized to migrate off the shelf to the open ocean. These differences in migration patterns have important implications for management, as fishing mortality rates are strongly influenced by ocean migration. Ocean-type Chinook salmon predominate in coastal rivers in the southern part of the species' range, whereas stream-type predominate in the interior and northerly rivers. This latitudinal gradient has confounded previous efforts to test the hypothesis regarding ocean migration pathways. To address this problem, we used a pair-wise design based on coded wire tagging data to compare the marine distributions of stream- and ocean-type Chinook salmon from a suite of rivers producing both forms. Both forms of Chinook salmon from the lower Columbia River, Oregon coast, lower Fraser River, and northern British Columbia rivers followed similar migration paths, contradicting the hypothesis. In contrast, recoveries of tagged Chinook salmon from the upper Columbia River, Snake River, and the upper Fraser River revealed migration patterns consistent with the hypothesis. These findings have important implications for our understanding of these life history types, and also for the conservation and management of declining, threatened, or endangered stream-type Chinook salmon populations in the US and Canada.

  16. Low-level shear stress promotes migration of liver cancer stem cells via the FAK-ERK1/2 signalling pathway.

    PubMed

    Sun, Jinghui; Luo, Qing; Liu, Lingling; Song, Guanbin

    2018-07-28

    Cancer stem cells (CSCs) are a small subpopulation of tumour cells that have been proposed to be responsible for cancer initiation, chemotherapy resistance and cancer recurrence. Shear stress activated cellular signalling is involved in cellular migration, proliferation and differentiation. However, little is known about the effects of shear stress on the migration of liver cancer stem cells (LCSCs). Here, we studied the effects of shear stress that are generated from a parallel plated flow chamber system, on LCSC migration and the activation of focal adhesion kinase (FAK) and extracellular signal regulated kinase1/2 (ERK1/2), using transwell assay and western blot, respectively. We found that 2 dyne/cm 2 shear stress loading for 6 h promotes LCSC migration and activation of the FAK and ERK1/2 signalling pathways, whereas treatment with the FAK phosphorylation inhibitor PF573228 or the ERK1/2 phosphorylation inhibitor PD98059 suppressed the shear stress-promoted migration, indicating the involvement of FAK and ERK1/2 activation in shear stress-induced LCSC migration. Additionally, atomic force microscopy (AFM) analysis showed that shear stress lowers LCSC stiffness via the FAK and ERK1/2 pathways, suggesting that the mechanism by which shear stress promotes LCSC migration might partially be responsible for the decrease in cell stiffness. Further experiments focused on the role of the actin cytoskeleton, demonstrating that the F-actin filaments in LCSCs are less well-defined after shear stress treatment, providing an explanation for the reduction in cell stiffness and the promotion of cell migration. Overall, our study demonstrates that shear stress promotes LCSC migration through the activation of the FAK-ERK1/2 signalling pathways, which further results in a reduction of organized actin and softer cell bodies. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Boron desorption and fractionation in Subduction Zone Fore Arcs: Implications for the sources and transport of deep fluids

    NASA Astrophysics Data System (ADS)

    Saffer, Demian M.; Kopf, Achim J.

    2016-12-01

    At many subduction zones, pore water geochemical anomalies at seafloor seeps and in shallow boreholes indicate fluid flow and chemical transport from depths of several kilometers. Identifying the source regions for these fluids is essential toward quantifying flow pathways and volatile fluxes through fore arcs, and in understanding their connection to the loci of excess pore pressure at depth. Here we develop a model to track the coupled effects of boron desorption, smectite dehydration, and progressive consolidation within sediment at the top of the subducting slab, where such deep fluid signals likely originate. Our analysis demonstrates that the relative timing of heating and consolidation is a dominant control on pore water composition. For cold slabs, pore water freshening is maximized because dehydration releases bound water into low porosity sediment, whereas boron concentrations and isotopic signatures are modest because desorption is strongly sensitive to temperature and is only partially complete. For warmer slabs, freshening is smaller, because dehydration occurs earlier and into larger porosities, but the boron signatures are larger. The former scenario is typical of nonaccretionary margins where insulating sediment on the subducting plate is commonly thin. This result provides a quantitative explanation for the global observation that signatures of deeply sourced fluids are generally strongest at nonaccretionary margins. Application of our multitracer approach to the Costa Rica, N. Japan, N. Barbados, and Mediterranean Ridge subduction zones illustrates that desorption and dehydration are viable explanations for observed geochemical signals, and suggest updip fluid migration from these source regions over tens of km.

  18. Geochemical assessment of hydrocarbon migration phenomena: Case studies from the south-western margin of the Dead Sea Basin

    NASA Astrophysics Data System (ADS)

    Sokol, Ella; Kozmenko, Olga; Smirnov, Sergey; Sokol, Ivan; Novikova, Sofya; Tomilenko, Anatoliy; Kokh, Svetlana; Ryazanova, Tatyana; Reutsky, Vadim; Bul'bak, Taras; Vapnik, Yevgeny; Deyak, Michail

    2014-10-01

    Calcite veins with fluid and solid bitumen inclusions have been discovered in the south-western shoulder of the Dead Sea rift within the Masada-Zohar block, where hydrocarbons exist in small commercial gas fields and non-commercial fields of heavy and light oils. The gas-liquid inclusions in calcite are dominated either by methane or CO2, and aqueous inclusions sometimes bear minor dissolved hydrocarbons. The enclosed flake-like solid bitumen matter is a residue of degraded oil, which may be interpreted as “dead carbon”. About 2/3 of this matter is soot-like amorphous carbon and 1/3 consists of n-C8sbnd C18 carboxylic acids and traces of n-alkanes, light dicarboxylic acids, and higher molecular weight (>C20) branched and/or cyclic carboxylic acids. Both bitumen and the host calcites show genetic relationship with mature Maastrichtian chalky source rocks (MCSRs) evident in isotopic compositions (δ13C, δ34S, and δ18O) and in REE + Y patterns. The bitumen precursor may have been heavy sulfur-rich oil which was generated during the burial compaction of the MCSR strata within the subsided blocks of the Dead Sea graben. The δ18O and δ13C values and REE + Y signatures in calcites indicate mixing of deep buried fluids equilibrated with post-mature sediments and meteoric waters. The temperatures of fluid generation according to Mg-Li-geothermometer data range from 55 °С to 90 °С corresponding to the 2.5-4.0 km depths, and largely overlap with the oil window range (60-90 °С) in the Dead Sea rift (Hunt, 1996; Gvirtzman and Stanislavsky, 2000; Buryakovsky et al., 2005). The bitumen-rich vein calcites originated in the course of Late Cenozoic rifting and related deformation, when tectonic stress triggers damaged small hydrocarbon reservoirs in the area, produced pathways, and caused hydrocarbon-bearing fluids to rise to the subsurface; the fluids filled open fractures and crystallized to calcite with entrapped bitumen. The reported results are in good agreement with the existing views of maturation, migration, and accumulation of hydrocarbons, as well as basin fluid transport processes in the Dead Sea area.

  19. Seismic characterization of fluid migration and Pockmarks in the Estremadura Spur, West Iberian Margin, Portugal

    NASA Astrophysics Data System (ADS)

    Duarte, Débora; Magalhães, Vitor Hugo; Terrinha, Pedro; Ribeiro, Carlos; Madureira, Pedro; Menezes Pinheiro, Luís; Benazzouz, Omar; Kim, Jung-Hyun; Duarte, Henrique

    2017-04-01

    Recently a field with more than 70 pockmarks was discovered in the NW region of the Estremadura Spur outer shelf (West Iberian margin), a trapezoidal promontory elongated in an east-west direction, between Cabo Carvoeiro and Cabo da Roca, extending until the Tore seamount. Pockmarks are the seabed culminations of fluid migration through the sedimentary column and their characteristic seabed morphologies correspond to cone-shaped circular or elliptical depressions. These features and the associated fluid escape process are the main objectives of this work. Here we characterize these structures to understand their structural and stratigraphic control based on: 1) Seismic processing and interpretation of the high resolution 2D single-channel sparker seismic dataset, 2) Bathymetric and Backscatter interpretation and 3) ROV direct observation of the seafloor. The analysis of the seismic profiles allowed the identification of six seismic units, disturbed by the migration and accumulation of fluids. The Estremadura Spur outer shelf has been affected by several episodes of fluid migration and fluid escape during the Pliocene-Quaternary that are expressed by a vast number of seabed and buried pockmarks. At present, the pockmarks are mainly inactive, as the seabed pockmarks are covered by recent sediments. The stacking of various pockmarks suggests a cyclical fluid flow activity that can possibly be the result of the eustatic sea level variations and the subsequent changes of the hydrostatic pressure. The origin of the seep fluids is still under debate but considering the low-sedimentation rate of the area and the low productivity a deep source for the fluids is most probable, possibly related with the Jurassic hydrocarbon system. It was concluded that the migration of fluids to the seabed occurred over the Pliocene-Quaternary in several episodes, as indicated by the buried pockmarks at different depths. Acknowledgements: This work was carried out in the framework of the PES project - Pockmarks and fluid seepage in the Estremadura Spur: implications for regional geology, biology, and petroleum systems (PTDC/GEOFIQ/5162/2014) financed by the Portuguese Foundation for Science and Technology (FCT). The seismic dataset was acquired within the PACEMAKER project funded by the European Research Council (ERC) under the European Union's Seventh Framework Program (FP7/2007-2013) ERC agreement (226600). The Instituto Portugues do Mar e da Atmosfera acknowledges support by Landmark Graphics (SeisWorks) via the Landmark University Grant Program. We thank the Estrutura de Missão para a Extensão da Plataforma Continental (EMEPC) for allowing me to have access and use the data collected in the Estremadura Spur during the EMEPC/PEPC/LUSO/2015 cruise and the ROV Luso team. We also thank Prof. Dr. Luis Matias (FCUL & IDL) for the help with SPW and processing steps.

  20. Taspine derivative 12k suppressed A549 cell migration through the Wnt/β-catenin and EphrinB2 signaling pathway.

    PubMed

    Dai, Bingling; Ma, Yujiao; Yang, Tianfeng; Wang, Wenjie; Zhang, Yanmin

    2017-03-01

    12k, a taspine derivative, has been demonstrated to have the potent anti-tumor activity in lung cancer and colorectal cancer. The study aims to further explore the underlying mechanisms of 12k on A549 cell migration in vitro. Our data demonstrated that 12k negatively regulated Wnt signaling pathway by suppressing the phosphorylation of LRP5/6, and inhibiting the expression and nuclear translocation of β-catenin. 12k was shown to downregulate MMP3 and MMP7 expression which regulated by β-catenin interacts with TCF/LEF in the nucleus, and effectively impaired the related migration protein expression of MMP2 and MMP9 in A549 cells. In addition, 12k repressed the EphrinB2 and its PDZ protein, impairing the VEGFR2 and VEGFR3 expression in A549 cells, as well as inhibited the downstream of VEGFR2 included PI3K/AKT/mTOR and ERK/MAPK signaling pathways. Taken together, our findings revealed that 12k suppressed migration of A549 cells through the Wnt/β-catenin signaling pathway and EphrinB2 related signaling pathway. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. PHP14 regulates hepatic stellate cells migration in liver fibrosis via mediating TGF-β1 signaling to PI3Kγ/AKT/Rac1 pathway.

    PubMed

    Xu, Anjian; Li, Yanmeng; Zhao, Wenshan; Hou, Fei; Li, Xiaojin; Sun, Lan; Chen, Wei; Yang, Aiting; Wu, Shanna; Zhang, Bei; Yao, Jingyi; Wang, Huan; Huang, Jian

    2018-02-01

    Hepatic fibrosis is characterized by the activation of hepatic stellate cells (HSCs). Migration of the activated HSCs to the site of injury is one of the key characteristics during the wound healing process. We have previously demonstrated that 14 kDa phosphohistidine phosphatase (PHP14) is involved in migration and lamellipodia formation of HSCs. However, the role of PHP14 in liver fibrosis remains unknown. In this study, we first assessed PHP14 expression and distribution in liver fibrotic tissues using western blot, immunohistochemistry, and double immunofluorescence staining. Next, we investigated the role of PHP14 in liver fibrosis and, more specifically, the migration of HSCs by Transwell assay and 3D collagen matrices assay. Finally, we explored the possible molecular mechanisms of the effects of PHP14 on these processes. Our results show that the PHP14 expression is up-regulated in fibrotic liver and mainly in HSCs. Importantly, TGF-β1 can induce PHP14 expression in HSCs accompanied with the activation of HSCs. Consistent with the previous study, PHP14 promotes HSCs migration, especially, promotes 3D floating collagen matrices contraction but inhibits stressed-released matrices contraction. Mechanistically, the PI3Kγ/AKT/Rac1 pathway is involved in migration regulated by PHP14. Moreover, PHP14 specifically mediates the TGF-β1 signaling to PI3Kγ/AKT pathway and regulates HSC migration, and thus participates in liver fibrosis. Our study identified the role of PHP14 in liver fibrosis, particularly HSC migration, and suggested a novel mediator of transducting TGF-β1 signaling to PI3Kγ/AKT/Rac1 pathway. PHP14 is up-regulated in fibrotic liver and activated hepatic stellate cells. The expression of PHP14 is induced by TGF-β1. The migration of hepatic stellate cells is regulated by PHP14. PHP14 is a mediator of TGF-β1 signaling to PI3Kγ/AKT/Rac1 pathway in hepatic stellate cells.

  2. Episodic fluid expulsion and fluid pathways during high-pressure dehydration of serpentinite

    NASA Astrophysics Data System (ADS)

    Padrón-Navarta, J.; Garrido, C. J.; López Sánchez-Vizcaíno, V.; Gómez-Pugnaire, M.; Tommasi, A.; Marchesi, C.

    2011-12-01

    Our understanding of subduction zone processes is tightly connected to our knowledge of the cycling of volatiles in the Earth, namely the loci of devolatilization reactions and the fluid migration mechanism. The exact nature of fluid pathways at high-pressure conditions is poorly known and still highly speculative. The study of metamorphic terrains that record main dehydration reaction are, thus, an invaluable tool to decipher the mechanism for fluid expulsion. Among other dehydration reactions in subduction zones, the antigorite (Atg) breakdown is rather discontinuous, releases the largest amount of fluids (ca. 9 wt. %) and is considered to have important seismological implications. The antigorite dehydration front in the Cerro del Almirez (Betic Cordillera, Spain) offers, thus, an unique opportunity to investigate the dynamics of fluid expulsion through the study of micro- and macrotextures recorded in the prograde assemblage (chlorite harzburgite). Chl-harzburgites show two textures interspersed in decameter-sized domains: granoblastic and spinifex-like. Both were formed under similar P-T conditions (~1.6-1.9 GPa and 680-710°C)). We ascribe the change in texture to shifts of the growth rate due to temporal and spatial fluctuations of the affinity of the Atg-breakdown reaction. These fluctuations are driven by cyclic variations of the excess fluid pressure which are ultimately controlled by the hydrodynamics of deserpentinization fluid expulsion. Crystallization at a low affinity of the reaction, correspondig to the granoblastic texture, may be attained if fluids are slowly drained out from the dehydration front. During the advancement of the dehydration front, overpressured domains are left behind preserving highly metastable Atg-serpentinite domains. Brittle failure results in a sudden drop of the fluid pressure, and a displacement of Atg equilibrium towards the prograde products that crystallizes at a high affinity of the reaction (spinifex-like texture). Evidences of brittle failure are found along grain-size reduction zones (GSRZ), a few mm to meters wide, which form roughly planar conjugate structures and crosscut the metamorphic texture. GSRZ are characterized by (1) sharp, irregular shapes and abrupt terminations contacts with undeformed metaperidotite, (2) an important reduction of the olivine grain size (60-250 μm), and (3) decrease in the opx modal amount. Analysis of olivine crystal-preferred orientations in GSRZ shows similar patterns, but a higher dispersion than in neighboring metaperidotite. These structures are interpreted as due to hydrofracturing allowing for the formation of high permeability channelways for overpressured fluids. This textural bimodality (granofels and spinifex-like) and the record of brittle failure witness a unique example of feedback between cyclic metamorphic fluid expulsion, reaction rates, and deformation in the Atg-dehydrating system.

  3. Silibinin inhibits migration and invasion of the rhabdoid tumor G401 cell line via inactivation of the PI3K/Akt signaling pathway.

    PubMed

    Li, Yumei; Zhang, Chunmei; Cai, Danfeng; Chen, Congde; Mu, Dongmei

    2017-12-01

    Rhabdoid tumors, which tend to occur prior to the age of 2 years, are one of the most aggressive malignancies and have a poor prognosis due to the frequency of metastasis. Silibinin, a natural extract, has been approved as a potential tumor suppressor in various studies, however, whether or not it also exerts its antitumor capacity in rhabdoid tumors, particularly with regards to tumor migration and invasion, is unclear. The rhabdoid tumor G401 cell line was used in the present in vitro study. An MTT assay was used to assess the cytotoxicity of silibinin on G401 cells, cell migration was studied using a wound healing assay and a Transwell migration assay, and cell invasion was determined using a Transwell invasion assay. The underlying mechanism in silibinin inhibited cell migration and invasion was investigated by western blot analysis and further confirmed using a specific inhibitor. Experimental results demonstrated that high doses of silibinin suppressed cell viability, and that low doses of silibinin inhibited cell migration and invasion without affecting cell proliferation. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway was involved in the silibinin-induced inhibition of metastasis. Silibinin inactivated the PI3K/Akt pathway, and inhibited cell migration and invasion, an effect that was further enhanced when LY294002, a classic PI3K inhibitor, was used concurrently. In general, silibinin inhibits migration and invasion of the rhabdoid tumor G401 cell line via inactivation of the PI3K/Akt signaling pathway and may be a potential chemotherapeutic drug to combat rhabdoid tumors in the future.

  4. Requirement of zebrafish pcdh10a and pcdh10b in melanocyte precursor migration.

    PubMed

    Williams, Jason S; Hsu, Jessica Y; Rossi, Christy Cortez; Artinger, Kristin Bruk

    2018-03-29

    Melanocytes derive from neural crest cells, which are a highly migratory population of cells that play an important role in pigmentation of the skin and epidermal appendages. In most vertebrates, melanocyte precursor cells migrate solely along the dorsolateral pathway to populate the skin. However, zebrafish melanocyte precursors also migrate along the ventromedial pathway, in route to the yolk, where they interact with other neural crest derivative populations. Here, we demonstrate the requirement for zebrafish paralogs pcdh10a and pcdh10b in zebrafish melanocyte precursor migration. pcdh10a and pcdh10b are expressed in a subset of melanocyte precursor and somatic cells respectively, and knockdown and TALEN mediated gene disruption of pcdh10a results in aberrant migration of melanocyte precursors resulting in fully melanized melanocytes that differentiate precociously in the ventromedial pathway. Live cell imaging analysis demonstrates that loss of pchd10a results in a reduction of directed cell migration of melanocyte precursors, caused by both increased adhesion and a loss of cell-cell contact with other migratory neural crest cells. Also, we determined that the paralog pcdh10b is upregulated and can compensate for the genetic loss of pcdh10a. Disruption of pcdh10b alone by CRISPR mutagenesis results in somite defects, while the loss of both paralogs results in enhanced migratory melanocyte precursor phenotype and embryonic lethality. These results reveal a novel role for pcdh10a and pcdh10b in zebrafish melanocyte precursor migration and suggest that pcdh10 paralogs potentially interact for proper transient migration along the ventromedial pathway. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Evolution of migrating protoplanets heated by pebble accretion

    NASA Astrophysics Data System (ADS)

    Chrenko, Ondrej; Broz, Miroslav; Lambrechts, Michiel

    2017-10-01

    We study the interactions in a protoplanetary system consisting of a gas disk, a pebble disk and embedded low-mass protoplanets. The hydrodynamic simulations are performed using a new code based on 2D FARGO (Masset 2000) which we call FARGO_THORIN (http://sirrah.troja.mff.cuni.cz/~chrenko/). The code treats the hydrodynamics of gas and pebbles within a two-fluid approximation, accounts for the heating and cooling processes in the gaseous component (including heating due to pebble accretion) and propagates the planets in 3D using a high-order integration scheme (IAS15; Rein & Spiegel 2015). Our aim is to investigate how pebble accretion alters the orbital evolution of protoplanets undergoing Type-I migration.First, we demonstrate that pebble accretion can heat the protoplanets so that their luminosity induces the heating torque (Benítez-Llambay et al. 2015) and the hot-trail effect (Chrenko et al. 2017; Eklund & Masset 2017). The heating torque is always positive and alters the migration rates and directions profoundly, thus changing the position of planet traps and deserts. The hot-trail effect, on the other hand, pumps the eccentricity of initially circular orbits up to e ~ h. After becoming eccentric, the protoplanets exhibit reduced probability of resonant locking during the migration and moreover, their close encounters become more frequent and provide more opportunities for scattering or merger events. The mergers can be massive enough to become giant planet cores. We discuss the importance of the excited eccentricities and violent orbital evolution for the extrasolar planet population synthesis. Finally, we present an extended model with flux-mean opacities caused by a coupled disk of coagulating dust grains with a realistic size distribution. The aim of this model is to constrain possible pathways of migrating planets towards the inner rim of the protoplanetary disk.

  6. Peridote-water interaction generating migration pathways of H2-rich fluids in subduction context: Common processes in the ophiolites of Oman, New-Caledonia, Philippines and Turkey

    NASA Astrophysics Data System (ADS)

    Deville, E. P.; Prinzhofer, A.; Pillot, D.; Vacquand, C.; Sissmann, O.

    2010-12-01

    The occurrence of H2 flows which were punctually known notably in the ophiolites of Oman, Zambales (Philippines) and Antalya (Turkey) appears to be a widespread phenomenon in these major peridotite massifs associated with ancient or active subduction processes. Similar H2-rich gas flows have been discovered also in the peridotite of New-Caledonia. H2 concentrations are locally high (commonly 60 to90% in Oman). H2 is frequently degassing in hyperalkaline springs but the highest flows were found directly expelled from fractures in the peridotites. Obviously, within the fracture systems, gas and associated hyperalkaline water separate at shallow depth close to the top of the upper aquifer level. Locally high flows of gas migrate vertically in the fractures, whereas water with degassing H2 tends to migrate laterally in the fracture network toward the creeks where most of the hyperalkaline springs are found. The genesis of natural H2 is interpreted as the result of the interaction, at depth, between ultrabasic mantle rocks in the upper plate and water expelled by the subducted sediments by oxidation of metals (Fe2+, Mn2+) and reduction of water during serpentinisation. CH4 is commonly associated to the H2-rich fluids and it is interpreted as the result of the reduction of available CO2 at depth. N2 is also commonly associated to the H2-rich fluids in the ophiolites, whereas N2 flows (within H2) were found in the subducted sediments (below the sole décollement of the peridotite) where it can be observed (Oman and New-Caledonia). Within the peridotites, the hyperalkaline water is rich in ions OH- and Ca2+ and characterized by high pH (between 11 and 12). Most alkaline springs are found in the vicinity of major faults and/or lithological discontinuities like the basal décollement of the ophiolites and the peridotite-gabbro contact (Moho). This hyperalkaline water migration induces a chain of diagenetic reactions starting at depth within the fracture systems by the precipitation of Mg-carbonates (dolomite, magnesite) and continuing up to the surface where it leads mostly to the precipitation of Ca-carbonates (calcite, aragonite), and brucite. This chain of diagenetic reactions is associated with the capture and sequestration of the atmospheric CO2 during the precipitation of the carbonates.

  7. Attenuation of Chemical Reactivity of Shale Matrixes following Scale Precipitation

    NASA Astrophysics Data System (ADS)

    Li, Q.; Jew, A. D.; Kohli, A. H.; Alalli, G.; Kiss, A. M.; Kovscek, A. R.; Zoback, M. D.; Brown, G. E.; Maher, K.; Bargar, J.

    2017-12-01

    Introduction of fracture fluids into shales initiates a myriad of fluid-rock reactions that can strongly influence migration of fluid and hydrocarbon through shale/fracture interfaces. Due to the extremely low permeability of shale matrixes, studies on chemical reactivity of shales have mostly focused on shale surfaces. Shale-fluid interactions inside within shale matrixes have not been examined, yet the matrix is the primary conduit through which hydrocarbons and potential contaminants are transmitted. To characterize changes in matrix mineralogy, porosity, diffusivity, and permeability during hydraulic stimulation, we reacted Marcellus (high clay and low carbonate) and Eagle Ford (low clay and high carbonate) shale cores with fracture fluids for 3 weeks at elevated pressure and temperature (80 oC, and 77 bars). In the carbonate-poor Marcellus system, fluid pH increased from 2 to 4, and secondary Fe(OH)3 precipitates were observed in the fluid. Sulfur X-ray fluorescence maps show that fluids had saturated and reacted with the entire 1-cm-diameter core. In the carbonate-rich Eagle Ford system, pH increased from 2 to 6 due to calcite dissolution. When additional Ba2+ and SO42- were present (log10(Q/K)=1.3), extensive barite precipitation was observed in the matrix of the Eagle Ford core (and on the surface). Barite precipitation was also observed on the surface of the Marcellus core, although to a lesser extent. In the Marcellus system, the presence of barite scale attenuated diffusivity in the matrix, as demonstrated by sharply reduced Fe leaching and much less sulfide oxidation. Systematic studies in homogeneous solution show that barite scale precipitation rates are highly sensitive to pH, salinity, and the presence of organic compounds. These findings imply that chemical reactions are not confined to shale/fluid interfaces but can penetrate into shale matrices, and that barite scale formation can clog diffusion pathways for both fluid and hydrocarbon.

  8. Imaging pathways in fractured rock using three-dimensional electrical resistivity tomography

    USGS Publications Warehouse

    Robinson, Judith; Slater, Lee; Johnson, Timothy B.; Shapiro, Allen M.; Tiedeman, Claire; Ntlargiannis, Dimitrios; Johnson, Carole D.; Day-Lewis, Frederick D.; Lacombe, Pierre; Imbrigiotta, Thomas; Lane, John W.

    2016-01-01

    Major challenges exist in delineating bedrock fracture zones because these cause abrupt changes in geological and hydrogeological properties over small distances. Borehole observations cannot sufficiently capture heterogeneity in these systems. Geophysical techniques offer the potential to image properties and processes in between boreholes. We used three-dimensional cross borehole electrical resistivity tomography (ERT) in a 9 m (diameter) × 15 m well field to capture high-resolution flow and transport processes in a fractured mudstone contaminated by chlorinated solvents, primarily trichloroethylene. Conductive (sodium bromide) and resistive (deionized water) injections were monitored in seven boreholes. Electrode arrays with isolation packers and fluid sampling ports were designed to enable acquisition of ERT measurements during pulsed tracer injections. Fracture zone locations and hydraulic pathways inferred from hydraulic head drawdown data were compared with electrical conductivity distributions from ERT measurements. Static ERT imaging has limited resolution to decipher individual fractures; however, these images showed alternating conductive and resistive zones, consistent with alternating laminated and massive mudstone units at the site. Tracer evolution and migration was clearly revealed in time-lapse ERT images and supported by in situ borehole vertical apparent conductivity profiles collected during the pulsed tracer test. While water samples provided important local information at the extraction borehole, ERT delineated tracer migration over spatial scales capturing the primary hydrogeological heterogeneity controlling flow and transport. The fate of these tracer injections at this scale could not have been quantified using borehole logging and/or borehole sampling methods alone.

  9. [IL-23 promotes invasion of esophageal squamous cell carcinoma cells by activating DLL4/Notch1 signaling pathway].

    PubMed

    Li, Wei; Zhou, Yuepeng; Su, Yuting; Ouyang, Yibo; Xie, Xiaodong; Wu, Yingying; Mao, Chaoming; Chen, Deyu

    2015-06-01

    To investigate the role of interlukin-23 (IL-23) in the invasion of human esophageal squamous cell carcinoma (ESCC) cells and the related mechanism. IL-23 expression in tumor and adjacent tissues from 10 ESCC patients were detected by immunohistochemistry. Real-time fluorescent PCR was used to examine the expressions of Notch1 and Foxn4 mRNAs in different concentration IL-23-treated TE-1 cells. After Notch pathway was blocked with γ-secretase inhibitor DAPT, expressions of Notch intracellular domain (NICD), Delta-like 4 (DLL4), hairy enhancer of split 1 (Hes1), matrix metalloproteinase 9 (MMP-9) in IL-23-treated TE-1 cells were measured by Western blotting. And the migration of IL-23-treated TE-1 cells was studied by TranswellTM migration assay. Compared with adjacent tissues, IL-23 was highly expressed in ESCC tissues. IL-23 treatment up-regulated significantly the expressions of NICD, DLL4, Hes1 and MMP-9 in TE-1 cells. The blockade of Notch1 pathway inhibited the expressions induced by IL-23. Migration assay revealed that IL-23 treatment significantly enhanced the migration of TE-1 cells. IL-23 could promote migration of human ESCC cells by activating DLL4/Notch1 signaling pathway.

  10. Abnormal organic-matter maturation in the Yinggehai Basin, South China Sea: Implications for hydrocarbon expulsion and fluid migration from overpressured systems

    USGS Publications Warehouse

    Hao, F.; Li, S.; Dong, W.; Hu, Z.; Huang, B.

    1998-01-01

    Three superimposed pressure systems are present in the Yinggehai Basin, South China Sea. A number of commercial, thermogenic gas accumulations have been found in an area in which shale diapirs occur. Because the reservoir intervals are shallow and very young, they must have filled with gas rapidly. The thick (up to 17 km) Tertiary and Quaternary sedimentary succession is dominated by shales, and is not disrupted by major faulting in the study area, a factor which seems to have had an important effect on both hydrocarbon generation and fluid migration. Organic-matter maturation in the deepest, most overpressured compartment has been significantly retarded as a result of the combined effects of excess pressure, the presence of large volumes of water, and the retention of generated hydrocarbons. This retardation is indicated by both kerogen-related parameters (vitrinite reflectance and Rock-Eval T(max)); and also by parameters based on the analysis of soluble organic matter (such as the C15+ hydrocarbon content, and the concentration of isoprenoid hydrocarbons relative to adjacent normal alkanes). In contrast to this, organic-matter maturation in shallow, normally-pressured strata in the diapiric area has been enhanced by hydrothermal fluid flow, which is clearly not topography-driven in origin. As a result, the hydrocarbon generation 'window' in the basin is considerably wider than could be expected from traditional geochemical modelling. These two unusual and contrasting anomalies in organic-matter maturation, together with other lines of evidence, suggest that there was a closed fluid system in the overpressured compartment until shale diapirs developed. The diapirs developed as a result of the intense overpressuring, and their growth was triggered by regional extensional stresses. They served as conduits through which fluids (both water and hydrocarbons) retained in the closed system could rapidly migrate. Fluid migration led to the modification of the thermal regime and the enhancement of organic maturation, as well as the accumulation of commercial volumes of gas in a relatively short time interval.Three superimposed pressure systems are present in the Yinggehai Basin, South China Sea. To date, a number of commercial, thermogenic gas accumulations have been found in an area in which shale diapirs occur. In fact, two unusual and contrasting anomalies in organic-matter maturation have been documented. These two anomalies, together with other lines of evidence, suggest that there was a closed fluid system in the overpressured compartment until shale diapirs developed. The diapirs developed as a result of intense overpowering, and their growth was triggered by regional extensional stresses. They served as conduits through which fluids retained in the closed system could rapidly migrate. Fluid migration led to the modification of the thermal regime and the enhancement of organic maturation, as well as the accumulation of commercial volumes of gas in a relatively short time interval.

  11. Effects of Faults on Petroleum Fluid Dynamics, Borderland Basins of Southern California

    NASA Astrophysics Data System (ADS)

    Jung, B.; Garven, G.; Boles, J. R.

    2012-12-01

    Multiphase flow modeling provides a useful quantitative tool for understanding crustal processes such as petroleum migration in geological systems, and also for characterizing subsurface environmental issues such as carbon sequestration in sedimentary basins. However, accurate modeling of multi-fluid behavior is often difficult because of the various coupled and nonlinear physics affecting multiphase fluid saturation and migration, including effects of capillarity and relative permeability, anisotropy and heterogeneity of the medium, and the effects of pore pressure, composition, and temperature on fluid properties. Regional fault structures also play a strong role in controlling fluid pathlines and mobility, so considering hydrogeologic effects of these structures is critical for testing exploration concepts, and for predicting the fate of injected fluids. To address these issues on spatially large and long temporal scales, we have developed a 2-D multiphase fluid flow model, coupled to heat flow, using a hybrid finite element and finite volume method. We have had good success in applying the multiphase flow model to fundamental issues of long-distance petroleum migration and accumulation in the Los Angeles basin, which is intensely faulted and disturbed by transpressional tectonic stresses, and host to the world's richest oil accumulation. To constrain the model, known subsurface geology and fault structures were rendered using geophysical logs from industry exploration boreholes and published seismic profiles. Plausible multiphase model parameters were estimated, either from known fault permeability measurements in similar strata in the Santa Barbara basin, and from known formation properties obtained from numerous oil fields in the Los Angeles basin. Our simulations show that a combination of continuous hydrocarbon generation and primary migration from upper Miocene source rocks in the central LA basin synclinal region, coupled with a subsiding basin fluid dynamics, favored the massive accumulation and alignment of hydrocarbon pools along the Newport-Inglewood fault zone (NIFZ). According to our multiphase flow calculations, the maximum formation water velocities within fault zones likely ranged between 1 ~ 2 m/yr during the middle Miocene to Pliocene (13 to 2.6 Ma). The estimated time for long-distance (~ 25 km) petroleum migration from source beds in the central basin to oil fields along the NIFZ is approximately 150,000 ~ 250,000 years, depending on the effective permeability assigned to the faults and adjacent interbedded sandstone and siltstone "petroleum aquifers". With an average long-distance flow rate (~ 0.6 m/yr) and fault permeability of 100 millidarcys (10-13 m2), the total petroleum oil of Inglewood oil field of 450 million barrels (~ 1.6 × 105 m3) would have accumulated rather quickly, likely over 25,000 years or less. The results also suggest that besides the thermal and structural history of the basin, the fault permeability, capillary pressure, and the configuration of aquifer and aquitard layers played an important role in controlling petroleum migration rates, patterns of flow, and the overall fluid mechanics of petroleum accumulation.

  12. Palaeomagnetic dating of widespread remagnetization on the southeastern border of the French Massif Central and implications for fluid and Mississippi Valley-type mineralization

    USGS Publications Warehouse

    Henry, B.; Rouvier, H.; Goff, M.L.; Leach, D.; Macquar, J.-C.; Thibieroz, J.; Lewchuk, Michael T.

    2001-01-01

    Palaeomagnetic dating techniques have been applied to determine the age of fluid migration that produced the Mississippi Valley-type (MVT) Pb-Zn-Ba-F deposits in the Ce??vennes region of southern France. 15 sampling sites in two gently deformed areas around the Largentie??re and Croix-de-Pallie??res mines on the Ce??vennes border were selected for palaeomagnetic study. They yielded a very well-defined direction of remagnetization corresponding to an Early-Middle Eocene age. This remagnetization cannot be related to the formation of magnetic as a result of the transformation of smectite to illite because the latter has been well dated as a Mesozoic event. The magnetic overprint in this area is related to a chemical phenomenon during fluid migration. The age of remagnetization corresponds to a major uplift in the Pyre??ne??es mountains, located to the south of the Ce??vennes. This implies that fluid migration occurred from the south to the north as a result of hydraulic head established in the Pyre??ne??es orogenic belt during orogenesis and suggests that the MVT deposits in the Ce??vennes region formed from a gravity-driven fluid system as described by Garven & Freeze (1984a,b).

  13. Silymarin suppresses the PGE2 -induced cell migration through inhibition of EP2 activation; G protein-dependent PKA-CREB and G protein-independent Src-STAT3 signal pathways.

    PubMed

    Woo, Seon Min; Min, Kyoung-Jin; Chae, In Gyeong; Chun, Kyung-Soo; Kwon, Taeg Kyu

    2015-03-01

    Silymarin has been known as a chemopreventive agent, and possesses multiple anti-cancer activities including induction of apoptosis, inhibition of proliferation and growth, and blockade of migration and invasion. However, whether silymarin could inhibit prostaglandin (PG) E2 -induced renal cell carcinoma (RCC) migration and what are the underlying mechanisms are not well elucidated. Here, we found that silymarin markedly inhibited PGE2 -stimulated migration. PGE2 induced G protein-dependent CREB phosphorylation via protein kinase A (PKA) signaling, and PKA inhibitor (H89) inhibited PGE2 -mediated migration. Silymarin reduced PGE2 -induced CREB phosphorylation and CRE-promoter activity. PGE2 also activated G protien-independent signaling pathways (Src and STAT3) and silymarin reduced PGE2 -induced phosphorylation of Src and STAT3. Inhibitor of Src (Saracatinib) markedly reduced PGE2 -mediated migration. We found that EP2, a PGE2 receptor, is involved in PGE2 -mediated cell migration. Down regulation of EP2 by EP2 siRNA and EP2 antagonist (AH6809) reduced PGE2 -inudced migration. In contrast, EP2 agonist (Butaprost) increased cell migration and silymarin effectively reduced butaprost-mediated cell migration. Moreover, PGE2 increased EP2 expression through activation of positive feedback mechanism, and PGE2 -induced EP2 expression, as well as basal EP2 levels, were reduced in silymarin-treated cells. Taken together, our study demonstrates that silymarin inhibited PGE2 -induced cell migration through inhibition of EP2 signaling pathways (G protein dependent PKA-CREB and G protein-independent Src-STAT3). © 2013 Wiley Periodicals, Inc.

  14. In-situ Mechanical Manipulation of Wellbore Cements as a Solution to Leaky Wells

    NASA Astrophysics Data System (ADS)

    Kupresan, D.; Radonjic, M.; Heathman, J.

    2013-12-01

    Wellbore cement provides casing support, zonal isolation, and casing protection from corrosive fluids, which are essential for wellbore integrity. Cements can undergo one or more forms of failure such as debonding at cement/formation and cement/casing interface, fracturing and defects within cement matrix. Failures and defects within cement will ultimately lead to fluids migration, resulting in inter-zonal fluid migration and premature well abandonment. There are over 27,000 abandoned oil and gas wells only in The Gulf of Mexico (some of them dating from the late 1940s) with no gas leakage monitoring. Cement degradation linked with carbon sequestration can potentially lead to contamination of fresh water aquifers with CO2. Gas leaks can particularly be observed in deviated wells used for hydraulic fracking (60% leakage rate as they age) as high pressure fracturing increases the potential for migration pathways. Experimental method utilized in this study enables formation of impermeable seals at interfaces present in a wellbore by mechanically manipulating wellbore cement. Preliminary measurements obtained in bench scale experiments demonstrate that an impermeable cement/formation and cement/casing interface can be obtained. In post-modified cement, nitrogen gas flow-through experiments showed complete zonal isolation and no permeability in samples with pre-engineered microannulus. Material characterization experiments of modified cement revealed altered microstructural properties of cement as well as changes in mineralogical composition. Calcium-silicate-hydrate (CSH), the dominant mineral in hydrated cement which provides low permeability of cement, was modified as a result of cement pore water displacement, resulting in more dense structures. Calcium hydroxide (CH), which is associated with low resistance of cement to acidic fluids and therefore detrimental in most wellbore cements, was almost completely displaced and/or integrated in CSH as a result of mechanical manipulation (shear stress). The main advantage of this methodology is that mechanical manipulation of cement can induce healing of existing fractures, channels and microannulus seal in a wellbore without introducing new materials (e.g. cement squeeze jobs). Furthermore, this methodology is less sensitive to the influence of downhole conditions such as pressure, temperature and formation fluids, since it uses cement pore water as a medium to alter cement sheath. Based on lab experiments observation, it is possible to perceive that once tested at the industrial scale and if successful, the implementation of this method in the field can potentially mitigate leaky wells in CO2 sequestration projects, wellbores completed for hydraulic-fracturing and other conventional oil and gas producing wells. Key words: Wellbore cement integrity; Leaky wells; Cement microstructures; Casing expansion effect on cement mineralogy alterations.

  15. Pathways of fluid transport and reabsorption across the peritoneal membrane.

    PubMed

    Asghar, R B; Davies, S J

    2008-05-01

    The three-pore model of peritoneal fluid transport predicts that once the osmotic gradient has dissipated, fluid reabsorption will be due to a combination of small-pore reabsorption driven by the intravascular oncotic pressure, and an underlying disappearance of fluid from the cavity by lymphatic drainage. Our study measured fluid transport by these pathways in the presence and absence of an osmotic gradient. Paired hypertonic and standard glucose-dwell studies were performed using radio-iodinated serum albumin as an intraperitoneal volume marker and changes in intraperitoneal sodium mass to determine small-pore versus transcellular fluid transport. Disappearance of iodinated albumin was considered to indicate lymphatic drainage. Variability in transcellular ultrafiltration was largely explained by the rate of small-solute transport across the membrane. In the absence of an osmotic gradient, fluid reabsorption occurred via the small-pore pathway, the rate being proportional to the small-solute transport characteristics of the membrane. In most cases, fluid removal from the peritoneal cavity by this pathway was faster than by lymphatic drainage. Our study shows that the three-pore model describes the pathways of peritoneal fluid transport well. In the presence of high solute transport, poor transcellular ultrafiltration was due to loss of the osmotic gradient and an enhanced small-pore reabsorption rate after this gradient dissipated.

  16. Eotaxin-1 promotes prostate cancer cell invasion via activation of the CCR3-ERK pathway and upregulation of MMP-3 expression.

    PubMed

    Zhu, Feng; Liu, Pei; Li, Jun; Zhang, Yan

    2014-05-01

    Chemokines have been reported to play crucial roles in tumor progression. Eotaxin-1 (CCL11), a member of the CC chemokine family, is elevated in many types of human cancer. Here, to reveal the molecular mechanisms of eotaxin-1 in prostate cancer cell invasion, the expression of eotaxin-1 receptors [CC chemokine receptor (CCR)2, CCR3 and CCR5] were silenced by small interfering RNA (siRNA). The ERK pathway was inhibited by the specific MEK inhibitor U0126. The role of eotaxin-1 and the CCR3-ERK pathway in prostate cancer cell invasion was assessed by invasion and migration assays. MMP-3 expression was detected by real-time PCR and ELISA assay. The results demonstrated that eotaxin-1 promoted the invasion and migration of DU-145 cells, and increased ERK1/2 activation and MMP-3 expression. Knockdown of CCR3 inhibited the invasion and migration of prostate cancer cells, and attenuated the eotaxin-1-induced ERK1/2 activation and MMP-3 expression. Furthermore, inactivation of the ERK pathway suppressed the eotaxin‑1-promoted invasion and migration, and decreased MMP-3 expression in the prostate cancer cells. Together, the present study suggests that eotaxin-1 increases MMP-3 expression via the CCR3-ERK pathway, thereby promoting prostate cancer cell invasion and migration. Thus, therapies that block eotaxin-1 and CCR3 may be effective interventions for prostate cancer.

  17. Evidence for CO2-rich fluids in rocks from the type charnockite area near Pallavaram, Tamil Nadu

    NASA Technical Reports Server (NTRS)

    Hansen, E.; Hunt, W.; Jacob, S. C.; Morden, K.; Reddi, R.; Tacy, P.

    1988-01-01

    Fluid inclusion and mineral chemistry data was presented for samples from the type charnockite area near Pallavaram (Tamil Nadu, India). The results indicate the presence of a dense CO2 fluid phase, but the data cannot distinguish between influx of this fluid from elsewhere or localized migration of CO2-rich fluids associated with dehydration melting.

  18. 40 CFR 146.6 - Area of review.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... lateral distance in which the pressures in the injection zone may cause the migration of the injection and... injection zone may cause the migration of the injection and/or formation fluid into an underground source of...

  19. 40 CFR 146.6 - Area of review.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... lateral distance in which the pressures in the injection zone may cause the migration of the injection and... injection zone may cause the migration of the injection and/or formation fluid into an underground source of...

  20. 40 CFR 146.6 - Area of review.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... lateral distance in which the pressures in the injection zone may cause the migration of the injection and... injection zone may cause the migration of the injection and/or formation fluid into an underground source of...

  1. Into the subduction plate interface: insights from exhumed terranes (Invited)

    NASA Astrophysics Data System (ADS)

    Agard, P.; Angiboust, S.; Plunder, A.

    2013-12-01

    In order to place constraints on the still elusive lithological and physical nature of the subduction plate interface, we herein present critical petrological (and modelling) data from intermediate depths along the subduction interface. Their implications, ranging from long-term underplating and exhumation to short-lived seismic events, are confronted with the recent wealth of geophysical/chemical data from the literature. Emphasis is placed on findings from two major localities showing deeply subducted ophiolitic remnants (Zermatt-Saas, Monviso), which crop out in the classic, well-preserved fossil subduction setting of the Western Alps. Both ophiolite remnants in fact represent large, relatively continuous fragments of oceanic lithosphere (i.e., several km-thick tectonic slices across tens of km) exhumed from ~80 km depths and thereby provide important constraints on interplate coupling mechanisms. We show that pervasive hydrothermal processes and seafloor alteration promoting fluid incorporation in both mafic and associated ultramafic rocks was essential, together with the presence of km-thick serpentinite soles, to decrease the density of the tectonic slices and prevent them from an irreversible sinking into the mantle. The Monviso case sudy (particularly the Lago Superiore Unit) provides further insights on both seismicity and fluid flow along the subduction plate interface at ~80 km depths: (1) Eclogite breccias, reported here for the first time, mark the locus of an ancient fault zone associated with intraslab, intermediate-depth earthquakes at ~80 km depth. They correspond to m-sized blocks made of 1-10 cm large fragments of eclogite mylonite later embedded in serpentinite in a ~100m thick eclogite facies shear zone. We suggest that seismic brecciation (possibly at magnitudes Mw ~4) occurred in the middle part of the oceanic crust, accompanied by the input of externally-derived fluids. (2) Prominent fluid-rock interactions, as attested by ubiquitous metasomatic rinds, affected the fragments of mylonitic basaltic eclogites and calcschists dragged and dismembered within serpentinite during eclogite-facies deformation. Detailed petrological and geochemical investigations point to a massive, pulse-like, fluid-mediated element transfer essentially originating from serpentinite. Antigorite breakdown, occurring ca. 15 km deeper than the maximum depth reached by these eclogites, is regarded as the likely source of this highly focused fluid/rock interaction and element transfer. Such a pulse-like, subduction-parallel fluid migration pathway within the downgoing oceanic lithosphere may have been promoted by transient slip behaviour along the LSZ under eclogite-facies conditions. Bi-phase numerical models allowing for fluid migration (driven by concentrations in the rocks, non-lithostatic pressure gradients and deformation), mantle wedge hydration and mechanical weakening of the plate interface indicate that the detachment of such large-scale oceanic tectonic slices is promoted by fluid circulation along the subduction interface (as well as by subducting a strong and originally discontinuous mafic crust).

  2. Schwann Cell Migration Induced by Earthworm Extract via Activation of PAs and MMP2/9 Mediated through ERK1/2 and p38

    PubMed Central

    Chang, Yung-Ming; Shih, Ying-Ting; Chen, Yueh-Sheng; Liu, Chien-Liang; Fang, Wen-Kuei; Tsai, Chang-Hai; Tsai, Fuu-Jen; Kuo, Wei-Wen; Lai, Tung-Yuan; Huang, Chih-Yang

    2011-01-01

    The earthworm, which has stasis removal and wound-healing functions, is a widely used Chinese herbal medicine in China. Schwann cell migration is critical for the regeneration of injured nerves. Schwann cells provide an essentially supportive activity for neuron regeneration. However, the molecular migration mechanisms induced by earthworms in Schwann cells remain unclear. Here, we investigate the roles of MAPK (ERK1/2, JNK and p38) pathways for earthworm-induced matrix-degrading proteolytic enzyme (PAs and MMP2/9) production in Schwann cells. Moreover, earthworm induced phosphorylation of ERK1/2 and p38, but not JNK, activate the downstream signaling expression of PAs and MMPs in a time-dependent manner. Earthworm-stimulated ERK1/2 and p38 phosphorylation was attenuated by pretreatment with U0126 and SB203580, resulting in migration and uPA-related signal pathway inhibition. The results were confirmed using small interfering ERK1/2 and p38 RNA. These results demonstrated that earthworms can stimulate Schwann cell migration and up-regulate PAs and MMP2/9 expression mediated through the MAPK pathways, ERK1/2 and p38. Taken together, our data suggests the MAPKs (ERK1/2, p38)-, PAs (uPA, tPA)-, MMP (MMP2, MMP9) signaling pathway of Schwann cells regulated by earthworms might play a major role in Schwann cell migration and nerve regeneration. PMID:19808845

  3. The impact of fluid advection on gas hydrate stability: Investigations at sites of methane seepage offshore Costa Rica

    NASA Astrophysics Data System (ADS)

    Crutchley, G. J.; Klaeschen, D.; Planert, L.; Bialas, J.; Berndt, C.; Papenberg, C.; Hensen, C.; Hornbach, M. J.; Krastel, S.; Brueckmann, W.

    2014-09-01

    Fluid flow through marine sediments drives a wide range of processes, from gas hydrate formation and dissociation, to seafloor methane seepage including the development of chemosynthetic ecosystems, and ocean acidification. Here, we present new seismic data that reveal the 3D nature of focused fluid flow beneath two mound structures on the seafloor offshore Costa Rica. These mounds have formed as a result of ongoing seepage of methane-rich fluids. We show the spatial impact of advective heat flow on gas hydrate stability due to the channelled ascent of warm fluids towards the seafloor. The base of gas hydrate stability (BGHS) imaged in the seismic data constrains peak heat flow values to ∼60 mW m and ∼70 mW m beneath two separate seep sites known as Mound 11 and Mound 12, respectively. The initiation of pronounced fluid flow towards these structures was likely controlled by fault networks that acted as efficient pathways for warm fluids ascending from depth. Through the gas hydrate stability zone, fluid flow has been focused through vertical conduits that we suggest developed as migrating fluids generated their own secondary permeability by fracturing strata as they forced their way upwards towards the seafloor. We show that Mound 11 and Mound 12 (about 1 km apart on the seafloor) are sustained by independent fluid flow systems through the hydrate system, and that fluid flow rates across the BGHS are probably similar beneath both mounds. 2D seismic data suggest that these two flow systems might merge at approximately 1 km depth, i.e. much deeper than the BGHS. This study provides a new level of detail and understanding of how channelled, anomalously-high fluid flow towards the seafloor influences gas hydrate stability. Thus, gas hydrate systems have good potential for quantifying the upward flow of subduction system fluids to seafloor seep sites, since the fluids have to interact with and leave their mark on the hydrate system before reaching the seafloor.

  4. Constraints on a shallow offshore gas environment determined by a multidisciplinary geophysical approach: The Malin Sea, NW Ireland

    NASA Astrophysics Data System (ADS)

    Garcia, Xavier; Monteys, Xavier; Evans, Rob L.; Szpak, Michal

    2014-04-01

    During the Irish National Seabed Survey (INSS) in 2003, a gas related pockmark field was discovered and extensively mapped in the Malin Shelf region (NW Ireland). In summer 2006, additional complementary data involving core sample analysis, multibeam and single-beam backscatter classification, and a marine controlled-source electromagnetic survey were obtained in specific locations.This multidisciplinary approach allowed us to map the upper 20 m of the seabed in an unprecedented way and to correlate the main geophysical parameters with the geological properties of the seabed. The EM data provide us with information about sediment conductivity, which can be used as a proxy for porosity and also to identify the presence of fluid and fluid migration pathways. We conclude that, as a whole, the central part of the Malin basin is characterized by higher conductivities, which we interpret as a lithological change. Within the basin several areas are characterized by conductive anomalies associated with fluid flow processes and potentially the presence of microbial activity, as suggested by previous work. Pockmark structures show a characteristic electrical signature, with high-conductivity anomalies on the edges and less conductive, homogeneous interiors with several high-conductivity anomalies, potentially associated with gas-driven microbial activity.

  5. bFGF Regulates PI3-Kinase-Rac1-JNK Pathway and Promotes Fibroblast Migration in Wound Healing

    PubMed Central

    Kanazawa, Shigeyuki; Fujiwara, Toshihiro; Matsuzaki, Shinsuke; Shingaki, Kenta; Taniguchi, Manabu; Miyata, Shingo; Tohyama, Masaya; Sakai, Yasuo; Yano, Kenji; Hosokawa, Ko; Kubo, Tateki

    2010-01-01

    Fibroblast proliferation and migration play important roles in wound healing. bFGF is known to promote both fibroblast proliferation and migration during the process of wound healing. However, the signal transduction of bFGF-induced fibroblast migration is still unclear, because bFGF can affect both proliferation and migration. Herein, we investigated the effect of bFGF on fibroblast migration regardless of its effect on fibroblast proliferation. We noticed involvement of the small GTPases of the Rho family, PI3-kinase, and JNK. bFGF activated RhoA, Rac1, PI3-kinase, and JNK in cultured fibroblasts. Inhibition of RhoA did not block bFGF-induced fibroblast migration, whereas inhibition of Rac1, PI3-kinase, or JNK blocked the fibroblast migration significantly. PI3-kinase-inhibited cells down-regulated the activities of Rac1 and JNK, and Rac1-inhibited cells down-regulated JNK activity, suggesting that PI3-kinase is upstream of Rac1 and that JNK is downstream of Rac1. Thus, we concluded that PI3-kinase, Rac1, and JNK were essential for bFGF-induced fibroblast migration, which is a novel pathway of bFGF-induced cell migration. PMID:20808927

  6. Hydrothermal dolomitization of the Bekhme formation (Upper Cretaceous), Zagros Basin, Kurdistan Region of Iraq: Record of oil migration and degradation

    NASA Astrophysics Data System (ADS)

    Mansurbeg, Howri; Morad, Daniel; Othman, Rushdy; Morad, Sadoon; Ceriani, Andrea; Al-Aasm, Ihsan; Kolo, Kamal; Spirov, Pavel; Proust, Jean Noel; Preat, Alain; Koyi, Hemin

    2016-07-01

    The common presence of oil seepages in dolostones is widespread in Cretaceous carbonate successions of the Kurdistan Region of Iraq. This integrated field, petrographic, chemical, stable C, O and Sr isotopes, and fluid inclusion study aims to link dolomitization to the origin and geochemical evolution of fluids and oil migration in the Upper Cretaceous Bekhme carbonates. Flux of hot basinal (hydrothermal) brines, which is suggested to have occurred during the Zagros Orogeny, resulted in dolomitization and cementation of vugs and fractures by coarse-crystalline saddle dolomite, equant calcite and anhydrite. The saddle dolomite and host dolostones have similar stable isotopic composition and formed prior to oil migration from hot (81-115 °C) basinal NaCl-MgCl2-H2O brines with salinities of 18-22 wt.% NaCl eq. The equant calcite cement, which surrounds and hence postdates saddle dolomite, has precipitated during oil migration from cooler (60-110 °C) NaCl-CaCl2-H2O brines (14-18 wt.% NaCl eq). The yellowish fluorescence color of oil inclusions in the equant calcite indicates that the oil had API gravity of 15-25° composition, which is lighter than present-day oil in the reservoirs (API of 10-17°). This difference in oil composition is attributed to oil degradation by the flux of meteoric water, which is evidenced by the low δ13C values (- 8.5‰ to - 3.9‰ VPDB) as well as by nil salinity and low temperature in fluid inclusions of late columnar calcite cement. This study demonstrates that linking fluid flux history and related diagenesis to the tectonic evolution of the basin provides important clues to the timing of oil migration, degradation and reservoir evolution.

  7. Understanding CO2 Plume Behavior and Basin-Scale Pressure Changes during Sequestration Projects through the use of Reservoir Fluid Modeling

    USGS Publications Warehouse

    Leetaru, H.E.; Frailey, S.M.; Damico, J.; Mehnert, E.; Birkholzer, J.; Zhou, Q.; Jordan, P.D.

    2009-01-01

    Large scale geologic sequestration tests are in the planning stages around the world. The liability and safety issues of the migration of CO2 away from the primary injection site and/or reservoir are of significant concerns for these sequestration tests. Reservoir models for simulating single or multi-phase fluid flow are used to understand the migration of CO2 in the subsurface. These models can also help evaluate concerns related to brine migration and basin-scale pressure increases that occur due to the injection of additional fluid volumes into the subsurface. The current paper presents different modeling examples addressing these issues, ranging from simple geometric models to more complex reservoir fluid models with single-site and basin-scale applications. Simple geometric models assuming a homogeneous geologic reservoir and piston-like displacement have been used for understanding pressure changes and fluid migration around each CO2 storage site. These geometric models are useful only as broad approximations because they do not account for the variation in porosity, permeability, asymmetry of the reservoir, and dip of the beds. In addition, these simple models are not capable of predicting the interference between different injection sites within the same reservoir. A more realistic model of CO2 plume behavior can be produced using reservoir fluid models. Reservoir simulation of natural gas storage reservoirs in the Illinois Basin Cambrian-age Mt. Simon Sandstone suggest that reservoir heterogeneity will be an important factor for evaluating storage capacity. The Mt. Simon Sandstone is a thick sandstone that underlies many significant coal fired power plants (emitting at least 1 million tonnes per year) in the midwestern United States including the states of Illinois, Indiana, Kentucky, Michigan, and Ohio. The initial commercial sequestration sites are expected to inject 1 to 2 million tonnes of CO2 per year. Depending on the geologic structure and permeability anisotropy, the CO2 injected into the Mt. Simon are expected to migrate less than 3 km. After 30 years of continuous injection followed by 100 years of shut-in, the plume from a 1 million tonnes a year injection rate is expected to migrate 1.6 km for a 0 degree dip reservoir and over 3 km for a 5 degree dip reservoir. The region where reservoir pressure increases in response to CO2 injection is typically much larger than the CO2 plume. It can thus be anticipated that there will be basin wide interactions between different CO2 injection sources if multiple, large volume sites are developed. This interaction will result in asymmetric plume migration that may be contrary to reservoir dip. A basin- scale simulation model is being developed to predict CO2 plume migration, brine displacement, and pressure buildup for a possible future sequestration scenario featuring multiple CO2 storage sites within the Illinois Basin Mt. Simon Sandstone. Interactions between different sites will be evaluated with respect to impacts on pressure and CO2 plume migration patterns. ?? 2009 Elsevier Ltd. All rights reserved.

  8. Rac3 Regulates Cell Invasion, Migration and EMT in Lung Adenocarcinoma through p38 MAPK Pathway

    PubMed Central

    Zhang, Chenlei; Liu, Tieqin; Wang, Gebang; Wang, Huan; Che, Xiaofang; Gao, Xinghua; Liu, Hongxu

    2017-01-01

    Background: The role of Rac3 in cell proliferation in lung adenocarcinoma has been tackled in our previous study. However, the role of Rac3 in cell invasion and migration of lung adenocarcinoma is still not clear. Methods: The expression of Rac3 in lung adenocarcinoma specimens and paired noncancerous normal tissues were evaluated by immunohistochemistry. Lentivirus-mediated RNA interference (RNAi) was employed to silence Rac3 in lung adenocarcinoma cell lines A549 and H1299. A p38 MAPK inhibitor (LY2228820) was employed to inhibit activity of p38 MAPK pathway. Cell invasion and migration in vitro were examined by invasion and migration assays, respectively. PathScan® intracellular signaling array kit and western blot were employed in mechanism investigation. Results: Rac3 expression was frequently higher in lung adenocarcinoma than paired noncancerous normal tissues. Rac3 expression was an independent risk factor for lymphonode metastasis, and was associated with worse survival outcome. Silencing of Rac3 inhibited cell invasion and cell migration in lung adenocarcinoma cell lines. Knockdown of Rac3 decreased activity of p38 MAPK pathway. LY2228820, which was an important p38 MAPK inhibitor, inhibited Rac3-induced cell invasion and migration of lung adenocarcinoma. E-cadherin expression was increased and vimentin expression was decreased after silencing of Rac3 or following the treatment of LY2228820. Conclusions: Our findings suggest that Rac3 regulates cell invasion, migration and EMT via p38 MAPK pathway. Rac3 may be a potential biomarker of invasion and metastasis for lung adenocarcinoma, and knockdown of Rac3 may potentially serve as a promising therapeutic target for lung adenocarcinoma. PMID:28900489

  9. Migrations and swimming capabilities of endangered pallid sturgeon (Scaphirhynchus albus) to guide passage designs in the fragmented Yellowstone River

    USGS Publications Warehouse

    Braaten, P. J.; Elliott, Caroline M.; Rhoten, Jason C.; Fuller, D. B.; McElroy, Brandon J.

    2015-01-01

    Fragmentation of the Yellowstone River is hypothesized to preclude recruitment of endangered Scaphirhynchus albus (pallid sturgeon) by impeding upstream spawning migrations and access to upstream spawning areas, thereby limiting the length of free-flowing river required for survival of early life stages. Building on this hypothesis, the reach of the Yellowstone River affected by Intake Diversion Dam (IDD) is targeted for modification. Structures including a rock ramp and by-pass channel have been proposed as restoration alternatives to facilitate passage. Limited information on migrations and swimming capabilities of pallid sturgeon is available to guide engineering design specifications for the proposed structures. Migration behavior, pathways (channel routes used during migrations), and swimming capabilities of free-ranging wild adult pallid sturgeon were examined using radiotelemetry, and complemented with hydraulic data obtained along the migration pathways. Migrations of 12–26% of the telemetered pallid sturgeon population persisted to IDD, but upstream passage over the dam was not detected. Observed migration pathways occurred primarily through main channel habitats; however, migrations through side channels up to 3.9 km in length were documented. The majority of pallid sturgeon used depths of 2.2–3.4 m and mean water velocities of 0.89–1.83 m/s while migrating. Results provide inferences on depths, velocities, and habitat heterogeneity of reaches successfully negotiated by pallid sturgeon that may be used to guide designs for structures facilitating passage at IDD. Passage will provide connectivity to potential upstream spawning areas on the Yellowstone River, thereby increasing the likelihood of recruitment for this endangered species.

  10. Fast fluid-flow events within a subduction-related vein system in oceanic eclogite: implications for pore fluid pressure at the plate interface

    NASA Astrophysics Data System (ADS)

    Taetz, Stephan; John, Timm; Bröcker, Michael; Spandler, Carl; Stracke, Andreas

    2017-04-01

    A better understanding of the subduction zone fluid cycle and its mechanical feedback requires in-depth knowledge of how fluids flow within and out of the descending slabs. In order to develop reliable quantitative models of fluid flow, the general relationship between dehydration reactions, fluid pathway formation, and the dimensions and timescales of distinct fluid flow events have to be explored. The high-pressure/low-temperature metamorphic rocks of the Pouébo Eclogite Mélange in New Caledonia provide an excellent opportunity to study the fluid flux in a subduction zone setting. Fluid dynamics are recorded by high-pressure veins that cross-cut eclogite facies mélange blocks from this occurrence. Two types of garnet-quartz-phengite veins can be distinguished. These veins record both synmetamorphic internal fluid release by mineral breakdown reactions (type I veins) as well as infiltration of an external fluid (type II veins) and the associated formation of a reaction halo. The overall dehydration, fluid accumulation and fluid migration documented by the type I veins occurred on a timescale of 10^5-106 years that is mainly given by the geometry and convergence rate of the subduction system. In order to quantify the timeframe of fluid-rock interaction between the external fluid and the wall-rock, we have applied Li-isotope chronology. A continuous profile was sampled perpendicular to a type II vein including material from the vein, the reaction selvage and the immediate host rock. Additional drill cores were taken from parts of the outcrop that most likely remained completely unaffected by fluid infiltration-induced alteration. Different Li concentrations in the internal and external fluid reservoirs produced a distinct diffusion profile of decreasing Li concentration and increasing δ7Li as the reaction front propagated into the host-rock. Li-chronometric constraints indicate that fluid-rock interaction related to the formation of the type II veins and had been completed within ca. 3 years. The short-lived, pulse-like character of this process is in accordance with the notion that fluid flow related to oceanic crust dehydration at the blueschist-to-eclogite transition contributes to or even dominates episodic pore fluid pressure increases at the plate interface which may trigger slip events reported from many subduction zones.

  11. Effects of long-term fluid injection on induced seismicity parameters and maximum magnitude in northwestern part of The Geysers geothermal field

    NASA Astrophysics Data System (ADS)

    Kwiatek, Grzegorz; Martínez-Garzón, Patricia; Dresen, Georg; Bohnhoff, Marco; Sone, Hiroki; Hartline, Craig

    2015-10-01

    The long-term temporal and spatial changes in statistical, source, and stress characteristics of one cluster of induced seismicity recorded at The Geysers geothermal field (U.S.) are analyzed in relation to the field operations, fluid migration, and constraints on the maximum likely magnitude. Two injection wells, Prati-9 and Prati-29, located in the northwestern part of the field and their associated seismicity composed of 1776 events recorded throughout a 7 year period were analyzed. The seismicity catalog was relocated, and the source characteristics including focal mechanisms and static source parameters were refined using first-motion polarity, spectral fitting, and mesh spectral ratio analysis techniques. The source characteristics together with statistical parameters (b value) and cluster dynamics were used to investigate and understand the details of fluid migration scheme in the vicinity of injection wells. The observed temporal, spatial, and source characteristics were clearly attributed to fluid injection and fluid migration toward greater depths, involving increasing pore pressure in the reservoir. The seasonal changes of injection rates were found to directly impact the shape and spatial extent of the seismic cloud. A tendency of larger seismic events to occur closer to injection wells and a correlation between the spatial extent of the seismic cloud and source sizes of the largest events was observed suggesting geometrical constraints on the maximum likely magnitude and its correlation to the average injection rate and volume of fluids present in the reservoir.

  12. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Harnish, Ryan A.; Johnson, Gary E.; McMichael, Geoffrey A.

    Off-channel areas (side channels, tidal flats, sand bars, and shallow-water bays) may serve as important migration corridors through estuarine environments for salmon and steelhead smolts. Relatively large percentages (21-33%) of acoustic-tagged yearling and subyearling Chinook salmon and steelhead smolts were detected migrating through off-channel areas of the Columbia River estuary in 2008. The probability of survival for off-channel migrants (0.78-0.94) was similar to or greater than the survival probability of main channel migrants (0.67-0.93). Median travel times were similar for all species or run types and migration pathways we examined, ranging from 1-2 d. The route used by smolts tomore » migrate through the estuary may affect their vulnerability to predation. Acoustic-tagged steelhead that migrated nearest to avian predator nesting colonies experienced higher predation rates (24%) than those that migrated farthest from the colonies (10%). The use of multiple migration pathways may be advantageous to out-migrating smolts because it helps to buffer against high rates of mortality, which may occur in localized areas, and helps to minimize inter- and intraspecific competition.« less

  13. Seismicity-based estimation of the driving fluid pressure in the case of swarm activity in Western Bohemia

    NASA Astrophysics Data System (ADS)

    Hainzl, S.; Fischer, T.; Dahm, T.

    2012-10-01

    Two recent major swarms in Western Bohemia occurred in the years 2000 and 2008 within almost the same portion of a fault close to Novy Kostel. Previous analysis of the year 2000 earthquake swarm revealed that fluid intrusion seemed to initiate the activity whereas stress redistribution by the individual swarm earthquakes played a major role in the further swarm evolution. Here we analyse the new swarm, which occurred in the year 2008, with regard to its correlation to the previous swarm as well its spatiotemporal migration patterns. We find that (i) the main part of the year 2008 activity ruptured fault patches adjacent to the main activity of the swarm 2000, but that also (ii) a significant overlap exists where earthquakes occurred in patches in which stress had been already released by precursory events; (iii) the activity shows a clear migration which can be described by a 1-D (in up-dip direction) diffusion process; (iv) the migration pattern can be equally well explained by a hydrofracture growth, which additionally explains the faster migration in up-dip compared to the down-dip direction as well as the maximum up-dip extension of the activity. We use these observations to estimate the underlying fluid pressure change in two different ways: First, we calculate the stress changes induced by precursory events at the location of each swarm earthquake assuming that observed stress deficits had to be compensated by pore pressure increases; and secondly, we estimate the fluid overpressure by fitting a hydrofracture model to the asymmetric seismicity patterns. Both independent methods indicate that the fluid pressure increase was initially up to 30 MPa.

  14. Structural analysis characterization of permeability pathways across reservoir-seal interface - South-Eastern Utah; Results from integrated sedimentological, structural, and geochemical studies.

    NASA Astrophysics Data System (ADS)

    Petrie, E. S.; Evans, J. P.; Richey, D.; Flores, S.; Barton, C.; Mozley, P.

    2015-12-01

    Sedimentary rocks in the San Rafael Swell, Utah, were deformed by Laramide compression and subsequent Neogene extension. We evaluate the effect of fault damage zone morphology as a function of structural position, and changes in mechanical stratigraphy on the distribution of secondary minerals across the reservoir-seal pair of the Navajo Sandstone and overlying Carmel Formation. We decipher paleo-fluid migration and examine the effect faults and fractures have on reservoir permeability and efficacy of top seal for a range of geo-engineering applications. Map-scale faults have an increased probability of allowing upward migration of fluids along the fault plane and within the damage zone, potentially bypassing the top seal. Field mapping, mesoscopic structural analyses, petrography, and geochemical observations demonstrate that fault zone thickness increases at structural intersections, fault relay zones, fault-related folds, and fault tips. Higher densities of faults with meters of slip and dense fracture populations are present in relay zones relative to single, discrete faults. Curvature analysis of the San Rafael monocline and fracture density data show that fracture density is highest where curvature is highest in the syncline hinge and near faults. Fractures cross the reservoir-seal interface where fracture density is highest and structural diagensis includes mineralization events and bleaching and calcite and gypsum mineralization. The link between fracture distributions and structural setting implys that transmissive fractures have predictable orientations and density distributions. At the m- to cm- scale, deformation-band faults and joints in the Navajo Sandstone penetrate the reservoir-seal interface and transition into open-mode fractures in the caprock seal. Scanline analysis and petrography of veins provide evidence for subsurface mineralization and fracture reactivation, suggesting that the fractures act as loci for fluid flow through time. Heterolithic caprock seals with variable fracture distributions and morphology highlight the strong link between the variation in material properties and the response to changing stress conditions. The variable connectivity of fractures and the changes in fracture density plays a critical role in subsurface fluid flow.

  15. Neutrophil-derived 5′-Adenosine Monophosphate Promotes Endothelial Barrier Function via CD73-mediated Conversion to Adenosine and Endothelial A2B Receptor Activation

    PubMed Central

    Lennon, Paul F.; Taylor, Cormac T.; Stahl, Gregory L.; Colgan, Sean P.

    1998-01-01

    During episodes of inflammation, polymorphonuclear leukocyte (PMN) transendothelial migration has the potential to disturb vascular barrier function and give rise to intravascular fluid extravasation and edema. However, little is known regarding innate mechanisms that dampen fluid loss during PMN-endothelial interactions. Using an in vitro endothelial paracellular permeability model, we observed a PMN-mediated decrease in endothelial paracellular permeability. A similar decrease was elicited by cell-free supernatants from activated PMN (FMLP 10−6 M), suggesting the presence of a PMN-derived soluble mediator(s). Biophysical and biochemical analysis of PMN supernatants revealed a role for PMN-derived 5′-adenosine monophosphate (AMP) and its metabolite, adenosine, in modulation of endothelial paracellular permeability. Supernatants from activated PMN contained micromolar concentrations of bioactive 5′-AMP and adenosine. Furthermore, exposure of endothelial monolayers to authentic 5′-AMP and adenosine increased endothelial barrier function more than twofold in both human umbilical vein endothelial cells and human microvascular endothelial cells. 5′-AMP bioactivity required endothelial CD73-mediated conversion of 5′-AMP to adenosine via its 5′-ectonucleotidase activity. Decreased endothelial paracellular permeability occurred through adenosine A2B receptor activation and was accompanied by a parallel increase in intracellular cAMP. We conclude that activated PMN release soluble mediators, such as 5′-AMP and adenosine, that promote endothelial barrier function. During inflammation, this pathway may limit potentially deleterious increases in endothelial paracellular permeability and could serve as a basic mechanism of endothelial resealing during PMN transendothelial migration. PMID:9782120

  16. Evidence for Late-Paleozoic brine migration in Cambrian carbonate rocks of the central and southern Appalachians: Implications for Mississippi Valley-type sulfide mineralization

    USGS Publications Warehouse

    Hearn, P.P.; Sutter, J.F.; Belkin, H.E.

    1987-01-01

    Many Lower Paleozoic limestones and dolostones in the Valley and Ridge province of the central and southern Appalachians contain 10 to 25 weight percent authigenic potassium feldspar. This was considered to be a product of early diagenesis, however, 40Ar 39Ar analyses of overgrowths on detrital K-feldspar in Cambrian carbonate rocks from Pennsylvania, Maryland, Virginia, and Tennessee yield Late Carboniferous-Early Permian ages (278-322 Ma). Simple mass balance calculations suggest that the feldspar could not have formed isochemically, but required the flux of multiple pore volumes of fluid through the rocks, reflecting regional fluid migration events during the Late-Paleozoic Alleghanian orogeny. Microthermometric measurements of fluid inclusions in overgrowths on detrital K-feldspar and quartz grains from unmineralized rocks throughout the study area indicate homogenization temperatures from 100?? to 200??C and freezing point depressions of -14?? to -18.5??C (18-21 wt.% NaCl equiv). The apparent similarity of these fluids to fluid inclusions in ore and gangue minerals of nearby Mississippi Valley-type (MVT) deposits suggests that the regional occurrences of authigenic K-feldspar and MVT mineralization may be genetically related. This hypothesis is supported by the discovery of authigenic K-feldspar intergrown with sphalerite in several mines of the Mascot-Jefferson City District, E. Tennessee. Regional potassic alteration in unmineralized carbonate rocks and localized occurrences of MVT mineralization are both explainable by a gravity-driven flow model, in which deep brines migrate towards the basin margin under a hydraulic gradient established during the Alleghanian orogeny. The authigenic K-feldspar may reflect the loss of K during disequilibrium cooling of the ascending brines. MVT deposits are probably localized manifestations of the same migrating fluids, occurring where the necessary physical and chemical traps are present. ?? 1987.

  17. Evidence that activation of ASIC1a by acidosis increases osteoclast migration and adhesion by modulating integrin/Pyk2/Src signaling pathway.

    PubMed

    Li, X; Ye, J-X; Xu, M-H; Zhao, M-D; Yuan, F-L

    2017-07-01

    Activated acid-sensing ion channel 1a (ASIC1a) is involved in acid-induced osteoclastogenesis by regulating activation of the transcription factor NFATc1. These results indicated that ASIC1a activation by extracellular acid may cause osteoclast migration and adhesion through Ca 2+ -dependent integrin/Pyk2/Src signaling pathway. Osteoclast adhesion and migration are responsible for osteoporotic bone loss. Acidic conditions promote osteoclastogenesis. ASIC1a in osteoclasts is associated with acid-induced osteoclastogenesis through modulating transcription factor NFATc1 activation. However, the influence and the detailed mechanism of ASIC1a in regulating osteoclast adhesion and migration, in response to extracellular acid, are not well characterized. In this study, knockdown of ASIC1a was achieved in bone marrow macrophage cells using small interfering RNA (siRNA). The adhesion and migration abilities of osteoclast precursors and osteoclasts were determined by adhesion and migration assays, in vitro. Bone resorption was performed to measure osteoclast function. Cytoskeletal changes were assessed by F-actin ring formation. αvβ3 integrin expression in osteoclasts was measured by flow cytometry. Western blotting and co-immunoprecipitation were performed to measure alterations in integrin/Pyk2/Src signaling pathway. Our results showed that blockade of ASIC1a using ASIC1a-siRNA inhibited acid-induced osteoclast precursor migration and adhesion, as well as osteoclast adhesion and bone resorption; we also demonstrated that inhibition of ASIC1a decreased the cell surface αvβ3 integrin and β3 protein expression. Moreover, blocking of ASIC1a inhibited acidosis-induced actin ring formation and reduced Pyk2 and Src phosphorylation in osteoclasts and also inhibited the acid-induced association of the αvβ3 integrin/Src/Pyk2. Together, these results highlight a key functional role of ASIC1a/αvβ3 integrin/Pyk2/Src signaling pathway in migration and adhesion of osteoclasts.

  18. The Lusi eruption site: insights from surface and subsurface investigations

    NASA Astrophysics Data System (ADS)

    Mazzini, A.

    2017-12-01

    The Indonesian Lusi eruption has been spewing boiling water, gas, and sediments since the 29th of May 2006. Initially, numerous aligned eruptions sites appeared along the Watukosek fault system (WFS) that was reactivated after the Yogyakarta earthquake occurring the 27th of May in the Java Island. Within weeks several villages were submerged by boiling mud. The most prominent eruption site was named Lusi. To date Lusi is still active and an area of 7 km2is covered by mud. Since its birth Lusi erupted with a pulsating behaviour. In the framework of the ERC grant "Lusi Lab" we conducted several years of monitoring and regional investigations coupling surface sampling and subsurface imaging in the region around Lusi. Ambient noise tomography studies, obtained with a local network of 31 stations, revealed for the first time subsurface images of the Lusi region and the adjacent Arjuno-Welirang (AW) volcanic complex. Results show that below the AW volcanic complex are present 5km deep magma chambers that are connected, through a defined corridor, with the roots of the Lusi eruption site. The Lusi subsurface shows the presence of a defined vertical hydrothermal plume that extends to at least 5km. Chemical analyses of the seeping fluids sampled from 1) the Lusi plume (using a specifically designed drone), 2) the region around Lusi, and 3) the fumaroles and the hydro thermal springs of AW, revealed striking similarities. More specifically a mantellic signature of the Lusi fluids confirms the scenario that Lusi represents a magmatic-driven hydrothermal system hosted in sedimentary basin. Seismic profiles interpretation, surface mapping, and fluid sampling show that the WFS, connecting AW and extending towards the NE of Java, acted as a preferential pathway for the igneous intrusion and fluids migration towards the subsurface. Petrography and dating of the clasts erupted at Lusi record high temperatures and indicate that the roots of the active conduit extend to at least 5km at depth, matching the observations and images obtained with geophysical investigations. Converging results support a scenario where igneous intrusions and hydrothermal fluid migrating from the AW complex moved towards the NE of Java. The triggered metamorphic reaction resulted in high overpressures that initiated the Lusi eruption site.

  19. Splay fault branching from the Hikurangi subduction shear zone: Implications for slow slip and fluid flow

    NASA Astrophysics Data System (ADS)

    Plaza-Faverola, A.; Henrys, S.; Pecher, I.; Wallace, L.; Klaeschen, D.

    2016-12-01

    Prestack depth migration data across the Hikurangi margin, East Coast of the North Island, New Zealand, are used to derive subducting slab geometry, upper crustal structure, and seismic velocities resolved to ˜14 km depth. We investigate the potential relationship between the crustal architecture, fluid migration, and short-term geodetically determined slow slip events. The subduction interface is a shallow dipping thrust at <7 km depth near the trench and steps down to 14 km depth along an ˜18 km long ramp, beneath Porangahau Ridge. This apparent step in the décollement is associated with splay fault branching and coincides with a zone of maximum slip (90 mm) inferred on the subduction interface during slow slip events in June and July 2011. A low-velocity zone beneath the plate interface, updip of the plate interface ramp, is interpreted as fluid-rich overpressured sediments capped with a low permeability condensed layer of chalk and interbedded mudstones. Fluid-rich sediments have been imbricated by splay faults in a region that coincides with the step down in the décollement from the top of subducting sediments to the oceanic crust and contribute to spatial variation in frictional properties of the plate interface that may promote slow slip behavior in the region. Further, transient fluid migration along splay faults at Porangahau Ridge may signify stress changes during slow slip.

  20. A possible mechanism for earthquakes found in the mantle wedge of the Nazca subduction zone

    NASA Astrophysics Data System (ADS)

    Warren, L. M.; Chang, Y.; Prieto, G. A.

    2017-12-01

    Beneath Colombia, the Cauca cluster of intermediate-depth earthquakes extends for 200 km along the trench (3.5°N-5.5°N, 77.0°W-75.3°W) and, with 58 earthquakes per year with local magnitude ML >= 2.5, has a higher rate of seismicity than the subduction zone immediately to the north or south. By precisely locating 433 cluster earthquakes from 1/2010-3/2014 with data from the Colombian National Seismic Network, we found that the earthquakes are located both in a continuous Nazca plate subducting at an angle of 33°-43° and in the overlying mantle wedge. The mantle wedge earthquakes (12% of the earthquakes) form two isolated 40-km-tall columns extending perpendicular to the subducting slab. Using waveform inversion, we computed focal mechanisms for 69 of the larger earthquakes. The focal mechanisms are variable, but the intraslab earthquakes are generally consistent with an in-slab extensional stress axis oriented 25° counterclockwise from the down-dip direction. We suggest that the observed mantle wedge earthquakes are the result of hydrofracture in a relatively cool mantle wedge. This segment of the Nazca Plate is currently subducting at a normal angle, but Wagner et al. (2017) suggested that a flat slab slowly developed in the region between 9-5.9 Ma and persisted until 4 Ma. During flat slab subduction, the overlying mantle wedge typically cools because it is cut off from mantle corner flow. After hydrous minerals in the slab dehydrate, the dehydrated fluid is expelled from the slab and migrates through the mantle wedge. If a cool mantle wedge remains today, fluid dehydrated from the slab may generate earthquakes by hydrofracture, with the mantle wedge earthquakes representing fluid migration pathways. Dahm's (2000) model of water-filled fracture propagation in the mantle wedge shows hydrofractures propagating normal to the subducting slab and extending tens of km into the mantle wedge, as we observe.

  1. High-resolution seismic characterization of the gas and gas hydrate system at Green Canyon 955, Gulf of Mexico, USA

    USGS Publications Warehouse

    Haines, Seth S.; Hart, Patrick E.; Collett, Timothy S.; Shedd, William; Frye, Matthew; Weimer, Paul; Boswell, Ray

    2017-01-01

    The Pliocene and Pleistocene sediments at lease block Green Canyon 955 (GC955) in the Gulf of Mexico include sand-rich strata with high saturations of gas hydrate; these gas hydrate accumulations and the associated geology have been characterized over the past decade using conventional industry three-dimensional (3D) seismic data and dedicated logging-while-drilling (LWD) borehole data. To improve structural and stratigraphic characterization and to address questions of gas flow and reservoir properties, in 2013 the U.S. Geological Survey acquired high-resolution two-dimensional (2D) seismic data at GC955. Combined analysis of all available data improves our understanding of the geological evolution of the study area, which includes basin-scale migration of the Mississippi River sediment influx as well as local-scale shifting of sedimentary channels at GC955 in response to salt-driven uplift, structural deformation associated with the salt uplift, and upward gas migration from deeper sediments that charges the main gas hydrate reservoir and shallower strata. The 2D data confirm that the sand-rich reservoir is composed principally of sediments deposited in a proximal levee setting and that episodes of channel scour, interspersed with levee deposition, have resulted in an assemblage of many individual proximal levee deposit “pods” each with horizontal extent up to several hundred meters. Joint analysis of the 2D and 3D data reveals new detail of a complex fault network that controls the fluid-flow system; large east-west trending normal faults allow fluid flow through the reservoir-sealing fine-grained unit, and smaller north-south oriented faults provide focused fluid-flow pathways (chimneys) through the shallower sediments. This system has enabled the flow of gas from the main reservoir to the seafloor throughout the recent history at GC955, and its intricacies help explain the distributed occurrences of gas hydrate in the intervening strata.

  2. 32 CFR 179.6 - Procedures.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Pathway Factor (MPF), which indicates environmental migration pathways, and contributes a level of H, M, or L based on Evident, Potential or Confined pathways, respectively. (See appendix A, table 21.) (3...

  3. 32 CFR 179.6 - Procedures.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Pathway Factor (MPF), which indicates environmental migration pathways, and contributes a level of H, M, or L based on Evident, Potential or Confined pathways, respectively. (See appendix A, table 21.) (3...

  4. Appendix for the Final Technical Report - DE FE0009284

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Duguid, Andrew

    2017-05-29

    Carbon capture utilization storage (CCUS) is a potential technology to store anthropogenic emissions for CO 2. Utilization often refers to CO 2-enhanced oil recovery (CO 2-EOR). An important factor in the success of CO 2 storage in saline formations or CO 2-EOR reservoirs is ensuring that the storage occurs safely and is long-term. Assessment of well integrity has become more important for CCS and CO 2-EOR as it has become apparent that wells represent the most likely migration pathway for CO 2 to leave a CCS storage unit or a CO 2-EOR reservoir. Although wells represent a migration pathway theymore » are also the best vehicle for employing technology monitoring CO 2 injection and storage. This contradiction of being a potential migration path and key monitoring technology leads to a need to understand how monitoring wells may be similar or different in comparison to other types of wells with respect to migration risk. The maturation and completion US Department of Energy sponsored research projects presents an opportunity to assess the integrity of monitoring wells that have been exposed to injected CO 2. This paper discusses an integrity assessment of two monitoring wells in an operating CO 2-EOR flood in Mississippi, USA. The CFU31F-2 and CFU31F-3 monitoring wells were constructed to test monitoring technologies in and above a commercial CO 2-EOR project. The materials selected and the design of the well were optimized for monitoring. Carbonation in CFU31-F2 was seen as high as 7900 ft, above what was considered top of cement based on the logs. Time-lapse comparison of cement bond amplitude data and acoustic impedance maps show a deterioration of signal that implies a deterioration of cement bond or cement along much of the cemented annulus in the long-string section. Analysis of sidewall cores using XRD and LA-ICP-MS validated the log interpretation by confirming the degradation of cement (carbonation) along the casing-cement interface. The ultrasonic image maps also clearly identify the control lines and monitoring technology attached to the outside of the of the long-string casing on each well studied. The control lines appear as microdebonded or fluid filled vertical features implying that they could act as leakage pathways. The sidewall core through the control line at 10380 ft confirms that CO 2 is migrating along the control line with heavily carbonated cement at the control line interface. LA-ICP-MS and XRD on formation interface of the sidewall cores collected in both wells indicates that CO 2 is also moving of the cement-formation interface. LA-ICP-MS and XRD indicate that the amount carbonation in the center of the cores was less than the carbonation at the interfaces. Indicating that CO 2 is reaching the center of the cores by diffusing in from the interfaces and not migrating up from the reservoir though the porous matrix of the cement. This agrees with Duguid et al. [5] and Carey et al. [1] who have found that the interfaces in the well are more conductive than the porous network of the cement. Both the materials used to construct the well and the decision to attach monitoring technology to the outside of the well may have contributed to the migration of CO 2 along the interfaces. Careful consideration should be given to material selection to ensure that it does not degrade when in contact with the fluids in the reservoir and overlying strata. The addition of the control line on the outside of the casing complicated the cement placement and likely caused no cement to bond to the casing adjacent to the control line leading out of the reservoir. Further study of other wells with external lines should be conducted to see of the results of the construction of CFU31-F2 and -F3 is normal or an exception.« less

  5. Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhu, Zhong Xin; Sun, Cong Cong; Wenzhou People's Hospital, Wenzhou, Zhejiang

    Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Westernmore » blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.« less

  6. Exendin-4 ameliorates oxidized-LDL-induced inhibition of macrophage migration in vitro via the NF-κB pathway

    PubMed Central

    Ma, Ge-fei; Chen, Song; Yin, Lei; Gao, Xiang-dong; Yao, Wen-bing

    2014-01-01

    Aim: To investigate the effects of the glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4 on oxidized low-density lipoprotein (ox-LDL)-induced inhibition of macrophage migration and the mechanisms underlying the effects of exendin-4. Methods: Primary peritoneal macrophages were extracted from the peritoneal cavity of mice treated with 3% thioglycollate (2 mL, ip). Migration of the macrophages was examined using a cell migration assay. Macrophage migration-related factors including leptin-like ox-LDL receptor (LOX-1), cyclooxygenase 2 (COX-2), tumor necrosis factor (TNF)-α, interleukin-1 (IL-1)β, matrix metalloproteinase-2 (MMP-2), intercellular adhesion molecule (ICAM)-1 and macrophage migration inhibitory factor (MIF) were measured using semi-quantitative RT-PCR. Expression of MIF and ICAM-1 proteins was examined with ELISA. Gelatin zymography was used to evaluate the activity of MMP-9. Activation of the NF-κB pathway was determined by confocal laser scanning microscopy. Results: Treatment of the macrophages with ox-LDL (50 μg/mL) markedly suppressed the macrophage migration. Furthermore, ox-LDL treatment substantially increased the expression of the macrophage migration-related factors, the activity of MMP-9 and the translocation of the NF-κB p65 subunit. These effects of ox-LDL were significantly ameliorated by pretreatment with the specific NF-κB inhibitor ammonium pyrrolidine dithiocarbamate (100 μmol/L). These effects of ox-LDL were also significantly ameliorated by pretreatment with exendin-4 (25 and 50 nmol/L). Conclusion: Exendin-4 ameliorates the inhibition of ox-LDL on macrophage migration in vitro, via suppressing ox-LDL-induced expression of ICAM-1 and MIF, which is probably mediated by the NF-κB pathway. PMID:24335838

  7. Exendin-4 ameliorates oxidized-LDL-induced inhibition of macrophage migration in vitro via the NF-κB pathway.

    PubMed

    Ma, Ge-fei; Chen, Song; Yin, Lei; Gao, Xiang-dong; Yao, Wen-bing

    2014-02-01

    To investigate the effects of the glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4 on oxidized low-density lipoprotein (ox-LDL)-induced inhibition of macrophage migration and the mechanisms underlying the effects of exendin-4. Primary peritoneal macrophages were extracted from the peritoneal cavity of mice treated with 3% thioglycollate (2 mL, ip). Migration of the macrophages was examined using a cell migration assay. Macrophage migration-related factors including leptin-like ox-LDL receptor (LOX-1), cyclooxygenase 2 (COX-2), tumor necrosis factor (TNF)-α, interleukin-1 (IL-1)β, matrix metalloproteinase-2 (MMP-2), intercellular adhesion molecule (ICAM)-1 and macrophage migration inhibitory factor (MIF) were measured using semi-quantitative RT-PCR. Expression of MIF and ICAM-1 proteins was examined with ELISA. Gelatin zymography was used to evaluate the activity of MMP-9. Activation of the NF-κB pathway was determined by confocal laser scanning microscopy. Treatment of the macrophages with ox-LDL (50 μg/mL) markedly suppressed the macrophage migration. Furthermore, ox-LDL treatment substantially increased the expression of the macrophage migration-related factors, the activity of MMP-9 and the translocation of the NF-κB p65 subunit. These effects of ox-LDL were significantly ameliorated by pretreatment with the specific NF-κB inhibitor ammonium pyrrolidine dithiocarbamate (100 μmol/L). These effects of ox-LDL were also significantly ameliorated by pretreatment with exendin-4 (25 and 50 nmol/L). Exendin-4 ameliorates the inhibition of ox-LDL on macrophage migration in vitro, via suppressing ox-LDL-induced expression of ICAM-1 and MIF, which is probably mediated by the NF-κB pathway.

  8. Coupled charge migration and fluid mixing in reactive fronts

    NASA Astrophysics Data System (ADS)

    Ghosh, Uddipta; Bandopadhyay, Aditya; Jougnot, Damien; Le Borgne, Tanguy; Meheust, Yves

    2017-04-01

    Quantifying fluid mixing in subsurface environments and its consequence on biogeochemical reactions is of paramount importance owing to its role in processes such as contaminant migration, aquifer remediation, CO2 sequestration or clogging processes, to name a few (Dentz et al. 2011). The presence of strong velocity gradients in porous media is expected to lead to enhanced diffusive mixing and augmented reaction rates (Le Borgne et al. 2014). Accurate in situ imaging of subsurface reactive solute transport and mixing remains to date a challenging proposition: the opacity of the medium prevents optical imaging and field methods based on tracer tests do not provide spatial information. Recently developed geophysical methods based on the temporal monitoring of electrical conductivity and polarization have shown promises for mapping and monitoring biogeochemical reactions in the subsurface although it remains challenging to decipher the multiple sources of electrical signals (e.g. Knight et al. 2010). In this work, we explore the coupling between fluid mixing, reaction and charge migration in porous media to evaluate the potential of mapping reaction rates from electrical measurements. To this end, we develop a new theoretical framework based on a lamellar mixing model (Le Borgne et al. 2013) to quantify changes in electrical mobility induced by chemical reactions across mixing fronts. Electrical conductivity and induced polarization are strongly dependent on the concentration of ionic species, which in turn depend on the local reaction rates. Hence, our results suggest that variation in real and complex electrical conductivity may be quantitatively related to the mixing and reaction dynamics. Thus, the presented theory provides a novel upscaling framework for quantifying the coupling between mixing, reaction and charge migration in heterogeneous porous media flows. References: Dentz. et al., Mixing, spreading and reaction in heterogeneous media: A brief review J. Contam. Hydrol. 120-121, 1 (2011). Le Borgne et al. Impact of Fluid Deformation on Mixing-Induced Chemical Reactions in heterogeneous Flows, Geophys. Res. Lett. 41, 7898 (2014). Knight, et al., Geophysics at the interface: Response of geophysical properties to solid-fluid, fluid-fluid, and solid-solid interfaces. Rev. Geophys. 48, (2010). Le Borgne et al. (2013) Stretching, coalescence and mixing in porous media, Phys. Rev. Lett., 110, 204501

  9. Action-derived molecular dynamics simulations for the migration and coalescence of vacancies in graphene and carbon nanotubes.

    PubMed

    Lee, Alex Taekyung; Ryu, Byungki; Lee, In-Ho; Chang, K J

    2014-03-19

    We report the results of action-derived molecular dynamics simulations for the migration and coalescence processes of monovacancies in graphene and carbon nanotubes with different chiralities. In carbon nanotubes, the migration pathways and barriers of a monovacancy depend on the tube chirality, while there is no preferential pathway in graphene due to the lattice symmetry and the absence of the curvature effect. The probable pathway changes from the axial to circumferential direction as the chirality varies from armchair to zigzag. The chirality dependence is attributed to the preferential orientation of the reconstructed bond formed around each vacancy site. It is energetically more favourable for two monovacancies to coalesce into a divacancy via alternative movements rather than simultaneous movements. The energy barriers for coalescence are generally determined by the migration barrier for the monovacancy, although there are some variations due to interactions between two diffusing vacancies. In graphene and armchair nanotubes, two monovacancies prefer to migrate along different zigzag atomic chains rather than a single atomic chain connecting these vacancies. On the other hand, in zigzag tubes, the energy barrier for coalescence increases significantly unless monovacancies lie on the same circumference.

  10. Nicotine promotes cervical carcinoma cell line HeLa migration and invasion by activating PI3k/Akt/NF-κB pathway in vitro.

    PubMed

    Wang, Chengze; Gu, Weiting; Zhang, Yunpeng; Ji, Yawen; Wen, Yong; Xu, Xin

    2017-07-05

    Cigarette smoking is one of highly risk factors of cervical cancer. Recently nicotine has been reported to increase proliferation and invasion in some smoking related cancers, like non-small cell lung cancer and esophageal squamous cell cancer. However, the effects and mechanisms of nicotine stimulation on cervical cancer cells are not clear. Here, we investigated the effects and mechanisms of nicotine stimulation on HeLa cells in vitro. In our study, we found that nicotine could accelerate HeLa cells migration and invasion, activate PI3K/Akt and NF-κB pathways and increase the expression of Vimentin in vitro. Moreover, we demonstrated that the specific PI3K inhibitor LY294002 could reverse nicotine-induced cell migration and invasion, NF-κB activation and up-regulation of Vimentin. Inhibition of NF-κB by Pyrrolidine dithiocarbamate (PDTC) also antagonized nicotine-induced cell migration, invasion and up-regulation of Vimentin. Simply put, these findings suggest that nicotine promotes cervical carcinoma cell line HeLa migration and invasion by activating PI3k/Akt/NF-κB pathway in vitro. Copyright © 2017 Elsevier GmbH. All rights reserved.

  11. International Climate Migration: Evidence for the Climate Inhibitor Mechanism and the Agricultural Pathway

    PubMed Central

    Nawrotzki, Raphael J.; Bakhtsiyarava, Maryia

    2016-01-01

    Research often assumes that, in rural areas of developing countries, adverse climatic conditions increase (climate driver mechanism) rather than reduce (climate inhibitor mechanism) migration, and that the impact of climate on migration is moderated by changes in agricultural productivity (agricultural pathway). Using representative census data in combination with high-resolution climate data derived from the novel Terra Populus system, we explore the climate-migration relationship in rural Burkina Faso and Senegal. We construct four threshold-based climate measures to investigate the effect of heat waves, cold snaps, droughts and excessive precipitation on the likelihood of household-level international outmigration. Results from multi-level logit models show that excessive precipitation increases international migration from Senegal while heat waves decrease international mobility in Burkina Faso, providing evidence for the climate inhibitor mechanism. Consistent with the agricultural pathway, interaction models and results from a geographically weighted regression (GWR) reveal a conditional effect of droughts on international outmigration from Senegal, which becomes stronger in areas with high levels of groundnut production. Moreover, climate change effects show a clear seasonal pattern, with the strongest effects appearing when heat waves overlap with the growing season and when excessive precipitation occurs prior to the growing season. PMID:28943813

  12. International Climate Migration: Evidence for the Climate Inhibitor Mechanism and the Agricultural Pathway.

    PubMed

    Nawrotzki, Raphael J; Bakhtsiyarava, Maryia

    2017-05-01

    Research often assumes that, in rural areas of developing countries, adverse climatic conditions increase (climate driver mechanism) rather than reduce (climate inhibitor mechanism) migration, and that the impact of climate on migration is moderated by changes in agricultural productivity (agricultural pathway). Using representative census data in combination with high-resolution climate data derived from the novel Terra Populus system, we explore the climate-migration relationship in rural Burkina Faso and Senegal. We construct four threshold-based climate measures to investigate the effect of heat waves, cold snaps, droughts and excessive precipitation on the likelihood of household-level international outmigration. Results from multi-level logit models show that excessive precipitation increases international migration from Senegal while heat waves decrease international mobility in Burkina Faso, providing evidence for the climate inhibitor mechanism. Consistent with the agricultural pathway, interaction models and results from a geographically weighted regression (GWR) reveal a conditional effect of droughts on international outmigration from Senegal, which becomes stronger in areas with high levels of groundnut production. Moreover, climate change effects show a clear seasonal pattern, with the strongest effects appearing when heat waves overlap with the growing season and when excessive precipitation occurs prior to the growing season.

  13. Lateral migration of a viscoelastic drop in a Newtonian fluid in a shear flow near a wall

    PubMed Central

    Mukherjee, Swarnajay; Sarkar, Kausik

    2014-01-01

    Wall induced lateral migration of a viscoelastic (FENE-MCR) drop in a Newtonian fluid is investigated. Just like a Newtonian drop, a viscoelastic drop reaches a quasi-steady state where the lateral velocity only depends on the instantaneous distance from the wall. The drop migration velocity and the deformation scale inversely with the square and the cube of the distance from the wall, respectively. The migration velocity varies non-monotonically with increasing viscoelasticity (increasing Deborah number); initially increasing and then decreasing. An analytical explanation has been given of the effects by computing the migration velocity as arising from an image stresslet field due to the drop. The semi-analytical expression matches well with the simulated migration velocity away from the wall. It contains a viscoelastic stresslet component apart from those arising from interfacial tension and viscosity ratio. The migration dynamics is a result of the competition between the viscous (interfacial tension and viscosity ratio) and the viscoelastic effects. The viscoelastic stresslet contribution towards the migration velocity steadily increases. But the interfacial stresslet—arising purely from the drop shape—first increases and then decreases with rising Deborah number causing the migration velocity to be non-monotonic. The geometric effect of the interfacial stresslet is caused by a corresponding nonmonotonic variation of the drop inclination. High viscosity ratio is briefly considered to show that the drop viscoelasticity could stabilize a drop against breakup, and the increase in migration velocity due to viscoelasticity is larger compared to the viscosity-matched case. PMID:25378894

  14. Multiple myeloma-related deregulation of bone marrow-derived CD34(+) hematopoietic stem and progenitor cells.

    PubMed

    Bruns, Ingmar; Cadeddu, Ron-Patrick; Brueckmann, Ines; Fröbel, Julia; Geyh, Stefanie; Büst, Sebastian; Fischer, Johannes C; Roels, Frederik; Wilk, Christian Matthias; Schildberg, Frank A; Hünerlitürkoglu, Ali-Nuri; Zilkens, Christoph; Jäger, Marcus; Steidl, Ulrich; Zohren, Fabian; Fenk, Roland; Kobbe, Guido; Brors, Benedict; Czibere, Akos; Schroeder, Thomas; Trumpp, Andreas; Haas, Rainer

    2012-09-27

    Multiple myeloma (MM) is a clonal plasma cell disorder frequently accompanied by hematopoietic impairment. We show that hematopoietic stem and progenitor cells (HSPCs), in particular megakaryocyte-erythrocyte progenitors, are diminished in the BM of MM patients. Genomic profiling of HSPC subsets revealed deregulations of signaling cascades, most notably TGFβ signaling, and pathways involved in cytoskeletal organization, migration, adhesion, and cell-cycle regulation in the patients. Functionally, proliferation, colony formation, and long-term self-renewal were impaired as a consequence of activated TGFβ signaling. In accordance, TGFβ levels in the BM extracellular fluid were elevated and mesenchymal stromal cells (MSCs) had a reduced capacity to support long-term hematopoiesis of HSPCs that completely recovered on blockade of TGFβ signaling. Furthermore, we found defective actin assembly and down-regulation of the adhesion receptor CD44 in MM HSPCs functionally reflected by impaired migration and adhesion. Still, transplantation into myeloma-free NOG mice revealed even enhanced engraftment and normal differentiation capacities of MM HSPCs, which underlines that functional impairment of HSPCs depends on MM-related microenvironmental cues and is reversible. Taken together, these data implicate that hematopoietic suppression in MM emerges from the HSPCs as a result of MM-related microenvironmental alterations.

  15. FABP4 Induces Vascular Smooth Muscle Cell Proliferation and Migration through a MAPK-Dependent Pathway

    PubMed Central

    Girona, Josefa; Rosales, Roser; Plana, Núria; Saavedra, Paula; Masana, Lluís; Vallvé, Joan-Carles

    2013-01-01

    Purpose The migration and proliferation of vascular smooth muscle cells play crucial roles in the development of atherosclerotic lesions. This study examined the effects of fatty acid binding protein 4 (FABP4), an adipokine that is associated with cardiovascular risk, endothelial dysfunction and proinflammatory effects, on the migration and proliferation of human coronary artery smooth muscle cells (HCASMCs). Methods and Results A DNA 5-bromo-2′-deoxy-uridine (BrdU) incorporation assay indicated that FABP4 significantly induced the dose-dependent proliferation of HCASMCs with a maximum stimulatory effect at 120 ng/ml (13% vs. unstimulated cells, p<0.05). An anti-FABP4 antibody (40 ng/ml) significantly inhibited the induced cell proliferation, demonstrating the specificity of the FABP4 proliferative effect. FABP4 significantly induced HCASMC migration in a dose-dependent manner with an initial effect at 60 ng/ml (12% vs. unstimulated cells, p<0.05). Time-course studies demonstrated that FABP4 significantly increased cell migration compared with unstimulated cells from 4 h (23%vs. 17%, p<0.05) to 12 h (74%vs. 59%, p<0.05). Pretreatment with LY-294002 (5 µM) and PD98059 (10 µM) blocked the FABP4-induced proliferation and migration of HCASMCs, suggesting the activation of a kinase pathway. On a molecular level, we observed an up-regulation of the MAPK pathway without activation of Akt. We found that FABP4 induced the active forms of the nuclear transcription factors c-jun and c-myc, which are regulated by MAPK cascades, and increased the expression of the downstream genes cyclin D1 and MMP2, CCL2, and fibulin 4 and 5, which are involved in cell cycle regulation and cell migration. Conclusions These findings indicate a direct effect of FABP4 on the migration and proliferation of HCASMCs, suggesting a role for this adipokine in vascular remodelling. Taken together, these results demonstrate that the FABP4-induced DNA synthesis and cell migration are mediated primarily through a MAPK-dependent pathway that activates the transcription factors c-jun and c-myc in HCASMCs. PMID:24312381

  16. FABP4 induces vascular smooth muscle cell proliferation and migration through a MAPK-dependent pathway.

    PubMed

    Girona, Josefa; Rosales, Roser; Plana, Núria; Saavedra, Paula; Masana, Lluís; Vallvé, Joan-Carles

    2013-01-01

    The migration and proliferation of vascular smooth muscle cells play crucial roles in the development of atherosclerotic lesions. This study examined the effects of fatty acid binding protein 4 (FABP4), an adipokine that is associated with cardiovascular risk, endothelial dysfunction and proinflammatory effects, on the migration and proliferation of human coronary artery smooth muscle cells (HCASMCs). A DNA 5-bromo-2'-deoxy-uridine (BrdU) incorporation assay indicated that FABP4 significantly induced the dose-dependent proliferation of HCASMCs with a maximum stimulatory effect at 120 ng/ml (13% vs. unstimulated cells, p<0.05). An anti-FABP4 antibody (40 ng/ml) significantly inhibited the induced cell proliferation, demonstrating the specificity of the FABP4 proliferative effect. FABP4 significantly induced HCASMC migration in a dose-dependent manner with an initial effect at 60 ng/ml (12% vs. unstimulated cells, p<0.05). Time-course studies demonstrated that FABP4 significantly increased cell migration compared with unstimulated cells from 4 h (23%vs. 17%, p<0.05) to 12 h (74%vs. 59%, p<0.05). Pretreatment with LY-294002 (5 µM) and PD98059 (10 µM) blocked the FABP4-induced proliferation and migration of HCASMCs, suggesting the activation of a kinase pathway. On a molecular level, we observed an up-regulation of the MAPK pathway without activation of Akt. We found that FABP4 induced the active forms of the nuclear transcription factors c-jun and c-myc, which are regulated by MAPK cascades, and increased the expression of the downstream genes cyclin D1 and MMP2, CCL2, and fibulin 4 and 5, which are involved in cell cycle regulation and cell migration. These findings indicate a direct effect of FABP4 on the migration and proliferation of HCASMCs, suggesting a role for this adipokine in vascular remodelling. Taken together, these results demonstrate that the FABP4-induced DNA synthesis and cell migration are mediated primarily through a MAPK-dependent pathway that activates the transcription factors c-jun and c-myc in HCASMCs.

  17. Planar cell polarity in moving cells: think globally, act locally

    PubMed Central

    Davey, Crystal F.

    2017-01-01

    ABSTRACT The planar cell polarity (PCP) pathway is best known for its role in polarizing epithelial cells within the plane of a tissue but it also plays a role in a range of cell migration events during development. The mechanism by which the PCP pathway polarizes stationary epithelial cells is well characterized, but how PCP signaling functions to regulate more dynamic cell behaviors during directed cell migration is much less understood. Here, we review recent discoveries regarding the localization of PCP proteins in migrating cells and their impact on the cell biology of collective and individual cell migratory behaviors. PMID:28096212

  18. Unsteady Thermocapillary Migration of Isolated Drops in Creeping Flow

    NASA Technical Reports Server (NTRS)

    Dill, Loren H.; Balasubramaniam, R.

    1992-01-01

    The problem of an isolated immiscible drop that slowly migrates due to unsteady thermocapillary stresses is considered. All physical properties except for interfacial tension are assumed constant for the two Newtonian fluids. Explicit expressions are found for the migration rate and stream functions in the Laplace domain. The resulting microgravity theory is useful, e.g., in predicting the distance a drop will migrate due to an impulsive interfacial temperature gradient as well as the time required to attain steady flow conditions from an initially resting state.

  19. Depressurization-induced fines migration in hydrate-bearing clayey sands: X-ray CT imaging and quantification

    NASA Astrophysics Data System (ADS)

    Han, G.; Kwon, T. H.; Lee, J. Y.

    2016-12-01

    As gas and water flows induced by depressurization of hydrate-bearing sediments exert seepage forces on fines in sediments, such as clay particles, depressurization is reported to accompany the transport of fine particles through sediment pores, i.e., fines migration. Because such fines migration can cause pore clogging, the fines migration is considered as one of the critical phenomena contributing to the transport of fluids among various pore-scale processes associated with depressurization. However, quantification of fines migration during depressurization still remains poorly understood. This study thus investigated fines migration caused by depressurization using X-ray computerized tomography(X-ray CT) imaging. A host sediment was prepared by mixing fine sand with kaolinite clay minerals to achieve 10% mass fraction of fines (less than 75 um). Then, methane hydrate was synthesized in the host clayey sand, and thereafter water was injected to saturate the hydrate-bearing sediment sample. Step-wise depressurization was applied while the produced gas was collected through an outlet fluid port. X-ray CT imaging was conducted on the sediment sample over the courses of the experiment to monitor the sample preparation, hydrate formation, depressurization, and fines migration. Based on the calibration tests, the amount and locations of methane hydrate formed in the sample was estimated, and the gas migration path was also identified. Finally, the spatial distribution of fines after completion of depressurization was first assessed using the obtained X-ray images and then compared with the post-mortem mine-back results.Notably, we found that the middle part of the sample was clogged possibly by fines or by re-formed hydrate, leading to a big pressure difference between the inlet and outlet fluid port of the sample by 3 MPa. Owing to this clogging and the lost in pressure communication, hydrate dissociation first occurred at the bottom half and the hydrate dissociation in the top half part followed later. Our study demonstrates that X-ray CT imaging can be a useful tool to visualize and quantify the fines migration during hydrate depressurization, and our results present an experimental evidence that depressurization can cause pore clogging in sediments containing more than 10% fines fraction.

  20. Functional Coordination of WAVE and WASP in C. elegans Neuroblast Migration.

    PubMed

    Zhu, Zhiwen; Chai, Yongping; Jiang, Yuxiang; Li, Wenjing; Hu, Huifang; Li, Wei; Wu, Jia-Wei; Wang, Zhi-Xin; Huang, Shanjin; Ou, Guangshuo

    2016-10-24

    Directional cell migration is critical for metazoan development. We define two molecular pathways that activate the Arp2/3 complex during neuroblast migration in Caenorhabditis elegans. The transmembrane protein MIG-13/Lrp12 is linked to the Arp2/3 nucleation-promoting factors WAVE or WASP through direct interactions with ABL-1 or SEM-5/Grb2, respectively. WAVE mutations partially impaired F-actin organization and decelerated cell migration, and WASP mutations did not inhibit cell migration but enhanced migration defects in WAVE-deficient cells. Purified SEM-5 and MIG-2 synergistically stimulated the F-actin branching activity of WASP-Arp2/3 in vitro. In GFP knockin animals, WAVE and WASP were largely organized into separate clusters at the leading edge, and the amount of WASP was less than WAVE but could be elevated by WAVE mutations. Our results indicate that the MIG-13-WAVE pathway provides the major force for directional cell motility, whereas MIG-13-WASP partially compensates for its loss, underscoring their coordinated activities in facilitating robust cell migration. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Regulation of macrophage migration by products of the complement system.

    PubMed Central

    Bianco, C; Götze, O; Cohn, Z A

    1979-01-01

    Agents formerly shown to induce rapid macrophage spreading were examined for their ability to modify the migration of macrophages in the capillary tube assay. Products of the activation of the contact phase of blood coagulation as well as the purified component Bb, the large cleavage fragment of factor B of the alternative complement pathway produced a dose-dependent inhibition of migration. In addition, inflammatory macrophages elicited with either a lipopolysaccharide endotoxin or thioglycollate medium exhibited rapid spreading and inhibited migration, whereas resident cells did not. A close correlation existed, therefore, between enhanced spreading and inhibited migration under both in vitro induced and in vivo situations. Cleavage products of component C5 of the classical complement pathway enhanced macrophage migration and did not alter spreading. In mixtures of C5 cleavage products and Bb, the predominant peptide determined the outcome of the reaction. Factor B, a normal secretory product of macrophages, may represent a common substrate for several of the proteases that induce spreading, inhibit migration, and lead to the generation of the enzymatically active fragment Bb. PMID:284412

  2. Aquifer susceptibility to perchlorate contamination in a highly urbanized environment

    USGS Publications Warehouse

    Woolfenden, Linda R.; Trefly, Michael G.

    2007-01-01

    Perchlorate contamination from anthropogenic sources has been released into the Rialto-Colton, California, USA, groundwater flow system since the 1940s during its production, distribution, storage, and use. Preliminary analysis of lithological, geophysical, and water-chemistry data provided new understanding of the pathways of perchlorate migration that aid in assessing the susceptibility of drinking-water supplies to contamination within the Rialto-Colton basin. Vertical migration of perchlorate into the main water-producing aquifers is restricted by an areally extensive old soil surface; however, perchlorate data indicate contamination below this soil surface. Possible pathways for the downward migration of the contaminated water include wellbore flow and discontinuities in the old soil surface. Horizontal migration of perchlorate is influenced by lithology and faults within the basin. The basin fill is a heterogeneous mixture of boulders, gravel, sand, silt, and clay, and internal faults may restrict perchlorate migration in some areas.

  3. An Assessment of Risk of Migration of Hydrocarbons or Fracturing Fluids to Fresh Water Aquifers: Wattenberg Field, CO

    NASA Astrophysics Data System (ADS)

    Eustes, A. W.; Fleckenstein, W. W.; Stone, C.; Howell, P.

    2015-12-01

    The United States National Science Foundation, engaging 29 researchers at nine institutions, has funded a Sustainability Research Network (SRN) focused on natural gas development. The mission of this Sustainability Research Network is to provide a logical, science-based framework for evaluating the environmental, economic, and social trade-offs between development of natural gas resources and protection of water and air resources and to convey the results of these evaluations to the public in a way that improves the development of policies and regulations governing natural gas and oil development. Currently, there are a wide range of estimates of the probability of shallow aquifer contamination. There are a series of independent events that must occur to allow hydrocarbon migration and estimates were made of these probabilities. An analysis of data from drilling in the Wattenberg field, CO was made to quantify the probability of contamination. It has been determined that there are five events that must each independently happen to allow the migration of fracturing fluids, and there are three events that must occur independently for the migration of hydrocarbons. The lower number of independent events, which must arise for hydrocarbon migration to occur, explains the infrequent, but well publicized natural gas migrations in poorly constructed wellbores, and the lack of such publicized events of hydraulic fracturing fluid contamination, which was confirmed by our analysis. The significance of these results is to help quantify the risks associated with natural gas development, as related to the contamination of surface aquifers. These results will help shape the discussion of the risks of natural gas development and will assist in identifying areas of improved well construction and hydraulic fracturing practices to minimize risk.

  4. The cleaved FAS ligand activates the Na(+)/H(+) exchanger NHE1 through Akt/ROCK1 to stimulate cell motility.

    PubMed

    Monet, Michael; Poët, Mallorie; Tauzin, Sébastien; Fouqué, Amélie; Cophignon, Auréa; Lagadic-Gossmann, Dominique; Vacher, Pierre; Legembre, Patrick; Counillon, Laurent

    2016-06-15

    Transmembrane CD95L (Fas ligand) can be cleaved to release a promigratory soluble ligand, cl-CD95L, which can contribute to chronic inflammation and cancer cell dissemination. The motility signaling pathway elicited by cl-CD95L remains poorly defined. Here, we show that in the presence of cl-CD95L, CD95 activates the Akt and RhoA signaling pathways, which together orchestrate an allosteric activation of the Na(+)/H(+) exchanger NHE1. Pharmacologic inhibition of Akt or ROCK1 independently blocks the cl-CD95L-induced migration. Confirming these pharmacologic data, disruption of the Akt and ROCK1 phosphorylation sites on NHE1 decreases cell migration in cells exposed to cl-CD95L. Together, these findings demonstrate that NHE1 is a novel molecular actor in the CD95 signaling pathway that drives the cl-CD95L-induced cell migration through both the Akt and RhoA signaling pathways.

  5. The cleaved FAS ligand activates the Na+/H+ exchanger NHE1 through Akt/ROCK1 to stimulate cell motility

    PubMed Central

    Monet, Michael; Poët, Mallorie; Tauzin, Sébastien; Fouqué, Amélie; Cophignon, Auréa; Lagadic-Gossmann, Dominique; Vacher, Pierre; Legembre, Patrick; Counillon, Laurent

    2016-01-01

    Transmembrane CD95L (Fas ligand) can be cleaved to release a promigratory soluble ligand, cl-CD95L, which can contribute to chronic inflammation and cancer cell dissemination. The motility signaling pathway elicited by cl-CD95L remains poorly defined. Here, we show that in the presence of cl-CD95L, CD95 activates the Akt and RhoA signaling pathways, which together orchestrate an allosteric activation of the Na+/H+ exchanger NHE1. Pharmacologic inhibition of Akt or ROCK1 independently blocks the cl-CD95L-induced migration. Confirming these pharmacologic data, disruption of the Akt and ROCK1 phosphorylation sites on NHE1 decreases cell migration in cells exposed to cl-CD95L. Together, these findings demonstrate that NHE1 is a novel molecular actor in the CD95 signaling pathway that drives the cl-CD95L-induced cell migration through both the Akt and RhoA signaling pathways. PMID:27302366

  6. Imaging Pathways in Fractured Rock Using Three-Dimensional Electrical Resistivity Tomography.

    PubMed

    Robinson, Judith; Slater, Lee; Johnson, Timothy; Shapiro, Allen; Tiedeman, Claire; Ntarlagiannis, Dimitrios; Johnson, Carole; Day-Lewis, Frederick; Lacombe, Pierre; Imbrigiotta, Thomas; Lane, John

    2016-03-01

    Major challenges exist in delineating bedrock fracture zones because these cause abrupt changes in geological and hydrogeological properties over small distances. Borehole observations cannot sufficiently capture heterogeneity in these systems. Geophysical techniques offer the potential to image properties and processes in between boreholes. We used three-dimensional cross borehole electrical resistivity tomography (ERT) in a 9 m (diameter) × 15 m well field to capture high-resolution flow and transport processes in a fractured mudstone contaminated by chlorinated solvents, primarily trichloroethylene. Conductive (sodium bromide) and resistive (deionized water) injections were monitored in seven boreholes. Electrode arrays with isolation packers and fluid sampling ports were designed to enable acquisition of ERT measurements during pulsed tracer injections. Fracture zone locations and hydraulic pathways inferred from hydraulic head drawdown data were compared with electrical conductivity distributions from ERT measurements. Static ERT imaging has limited resolution to decipher individual fractures; however, these images showed alternating conductive and resistive zones, consistent with alternating laminated and massive mudstone units at the site. Tracer evolution and migration was clearly revealed in time-lapse ERT images and supported by in situ borehole vertical apparent conductivity profiles collected during the pulsed tracer test. While water samples provided important local information at the extraction borehole, ERT delineated tracer migration over spatial scales capturing the primary hydrogeological heterogeneity controlling flow and transport. The fate of these tracer injections at this scale could not have been quantified using borehole logging and/or borehole sampling methods alone. © 2015, National Ground Water Association.

  7. Encapsulated proppants

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Aines, Roger D.; Bourcier, William L.; Duoss, Eric B.

    2018-01-30

    A capsule for carrying a proppant for emplaced in a formation containing formation fluid by a hydraulic fracture operation using a fracturing fluid. The capsule includes a capsule body. The capsule body includes a proppant. There is a surface layer on the capsule body that is permeable to the formation fluid or the fracturing fluid or is permeable to both the formation fluid and the fracturing fluid. The proppant material is dry cement that interacts with the formation fluid or the fracturing fluid or both the formation fluid and the fracturing fluid that migrate through the surface layer and ismore » taken up by the dry cement causing the dry cement to harden.« less

  8. Encapsulated proppants

    DOEpatents

    Aines, Roger D.; Bourcier, William L.; Duoss, Eric B.; Roberts, Jeffery James; Spadaccini, Christopher M.; Stolaroff, Joshuah K.

    2018-01-09

    A capsule for carrying a proppant for emplaced in a formation containing formation fluid by a hydraulic fracture operation using a fracturing fluid. The capsule includes a capsule body. The capsule body includes a proppant. There is a surface layer on the capsule body that is permeable to the formation fluid or the fracturing fluid or is permeable to both the formation fluid and the fracturing fluid. The proppant material is dry cement that interacts with the formation fluid or the fracturing fluid or both the formation fluid and the fracturing fluid that migrate through the surface layer and is taken up by the dry cement causing the dry cement to harden.

  9. Experimental analysis on viscoelasticity-induced migration of RBCs using digital holographic microscopy

    NASA Astrophysics Data System (ADS)

    Go, Taesik; Byeon, Hyeokjun; Lee, Sang Joon

    2016-11-01

    Migration of particles in viscoelastic fluids has recently received large attention, because the generated elastic forces in viscoelastic fluids give rise to a simple focusing pattern over a wide range of flow rates. In this study, the vertical focusing and alignment of rigid spherical particles, normal and hardened RBCs in a viscoelastic fluid were experimentally investigated by employing a digital in-line holographic microscopy (DIHM). By the elastic forces, the three different particles are pushed away from the walls and concentrated in the midplane of the rectangular microchannel. Furthermore, most of both RBCs maintain face-on orientation in the microchannel. The effects of deformability of RBC on the viscoelasticity-induced migration and orientation in the channel were also examined. In contrary to non-deformable particles, normal RBCs are dispersed as flow rate increases. In the region near side wall of the microchannel, normal RBCs have edge-on orientation with a large angle of inclination, compared to hardened RBCs. These findings have a strong potential in the design of microfluidic devices for deformability-based separation of cells in viscoelastic fluid flows and label-free diagnoses of certain hematological diseases. This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIP) (No. 2008-0061991).

  10. Vertical migration of motile phytoplankton chains through turbulence

    NASA Astrophysics Data System (ADS)

    Climent, Eric; Lovecchio, Salvatore; Durham, William; Stocker, Roman

    2017-11-01

    Daily, phytoplankton needs to migrate vertically from and towards the ocean surface to find nutrients such as dissolved oxygen. To travel through the water column they need to fight against gravity (by swimming) and fluid turbulence which can make their journey longer. It is often observed that cells migrate across the water column as chains. The first benefit to form chains is that micro-organisms sum up their thrust while reducing their drag. Therefore, upwards swimming is faster for chains in a quiescent fluid with steady vertical orientation. However, as chain length increases their tendency to periodically tumble in turbulent structures increases which reduces orientation stability and limits their capacity to swim upwards. The purpose of our study is to elaborate on this apparent contradiction. We carried out direct numerical simulations and physical analysis of the coupled system of homogeneous isotropic turbulence and chain trajectories through Lagrangian tracking. Formation of chains is indeed favorable for vertical migration through the upper layer of the ocean.

  11. JC Virus Mediates Invasion and Migration in Colorectal Metastasis

    PubMed Central

    Link, Alexander; Shin, Sung Kwan; Nagasaka, Takeshi; Balaguer, Francesc; Koi, Minoru; Jung, Barbara; Boland, C. Richard; Goel, Ajay

    2009-01-01

    Introduction JC Virus (JCV), a human polyomavirus, is frequently present in colorectal cancers (CRCs). JCV large T-Ag (T-Ag) expressed in approximately half of all CRC's, however, its functional role in CRC is poorly understood. We hypothesized that JCV T-Ag may mediate metastasis in CRC cells through increased migration and invasion. Material and Methods CRC cell lines (HCT116 and SW837) were stably transfected with JCV early transcript sequences cloned into pCR3 or empty vectors. Migration and invasion assays were performed using Boyden chambers. Global gene expression analysis was performed to identify genetic targets and pathways altered by T-Ag expression. Microarray results were validated by qRT-PCR, protein expression analyses and immunohistochemistry. Matching primary CRCs and liver metastases from 33 patients were analyzed for T-Ag expression by immunohistochemistry. Results T-Ag expressing cell lines showed 2 to 3-fold increase in migration and invasion compared to controls. JCV T-Ag expression resulted in differential expression of several genetic targets, including genes that mediate cell migration and invasion. Pathway analysis suggested a significant involvement of these genes with AKT and MAPK signaling. Treatment with selective PI3K/AKT and MAPK pathway inhibitors resulted in reduced migration and invasion. In support of our in-vitro results, immunohistochemical staining of the advanced stage tumors revealed frequent JCV T-Ag expression in metastatic primary tumors (92%) as well as in their matching liver metastasis (73%). Conclusion These data suggest that JCV T-Ag expression in CRC associates with a metastatic phenotype, which may partly be mediated through the AKT/MAPK signaling pathway. Frequent expression of JCV T-Ag in CRC liver metastasis provides further clues supporting a mechanistic role for JCV as a possible mediator of cellular motility and invasion in CRC. PMID:19997600

  12. Use of navigation channels by Lake Sturgeon: Does channelization increase vulnerability of fish to ship strikes?

    PubMed

    Hondorp, Darryl W; Bennion, David H; Roseman, Edward F; Holbrook, Christopher M; Boase, James C; Chiotti, Justin A; Thomas, Michael V; Wills, Todd C; Drouin, Richard G; Kessel, Steven T; Krueger, Charles C

    2017-01-01

    Channelization for navigation and flood control has altered the hydrology and bathymetry of many large rivers with unknown consequences for fish species that undergo riverine migrations. In this study, we investigated whether altered flow distributions and bathymetry associated with channelization attracted migrating Lake Sturgeon (Acipenser fulvescens) into commercial navigation channels, potentially increasing their exposure to ship strikes. To address this question, we quantified and compared Lake Sturgeon selection for navigation channels vs. alternative pathways in two multi-channel rivers differentially affected by channelization, but free of barriers to sturgeon movement. Acoustic telemetry was used to quantify Lake Sturgeon movements. Under the assumption that Lake Sturgeon navigate by following primary flow paths, acoustic-tagged Lake Sturgeon in the more-channelized lower Detroit River were expected to choose navigation channels over alternative pathways and to exhibit greater selection for navigation channels than conspecifics in the less-channelized lower St. Clair River. Consistent with these predictions, acoustic-tagged Lake Sturgeon in the more-channelized lower Detroit River selected the higher-flow and deeper navigation channels over alternative migration pathways, whereas in the less-channelized lower St. Clair River, individuals primarily used pathways alternative to navigation channels. Lake Sturgeon selection for navigation channels as migratory pathways also was significantly higher in the more-channelized lower Detroit River than in the less-channelized lower St. Clair River. We speculated that use of navigation channels over alternative pathways would increase the spatial overlap of commercial vessels and migrating Lake Sturgeon, potentially enhancing their vulnerability to ship strikes. Results of our study thus demonstrated an association between channelization and the path use of migrating Lake Sturgeon that could prove important for predicting sturgeon-vessel interactions in navigable rivers as well as for understanding how fish interact with their habitat in landscapes altered by human activity.

  13. Feedback Activation of Basic Fibroblast Growth Factor Signaling via the Wnt/β-Catenin Pathway in Skin Fibroblasts

    PubMed Central

    Wang, Xu; Zhu, Yuting; Sun, Congcong; Wang, Tao; Shen, Yingjie; Cai, Wanhui; Sun, Jia; Chi, Lisha; Wang, Haijun; Song, Na; Niu, Chao; Shen, Jiayi; Cong, Weitao; Zhu, Zhongxin; Xuan, Yuanhu; Li, Xiaokun; Jin, Litai

    2017-01-01

    Skin wound healing is a complex process requiring the coordinated behavior of many cell types, especially in the proliferation and migration of fibroblasts. Basic fibroblast growth factor (bFGF) is a member of the FGF family that promotes fibroblast migration, but the underlying molecular mechanism remains elusive. The present RNA sequencing study showed that the expression levels of several canonical Wnt pathway genes, including Wnt2b, Wnt3, Wnt11, T-cell factor 7 (TCF7), and Frizzled 8 (FZD8) were modified by bFGF stimulation in fibroblasts. Enzyme-linked immunosorbent assay (ELISA) analysis also showed that Wnt pathway was activated under bFGF treatment. Furthermore, treatment of fibroblasts with lithium chloride or IWR-1, an inducer and inhibitor of the Wnt signaling pathway, respectively, promoted and inhibited cell migration. Also, levels of cytosolic glycogen synthase kinase 3 beta phosphorylated at serine9 (pGSK3β Ser9) and nuclear β-catenin were increased upon exposure to bFGF. Molecular and biochemical assays indicated that phosphoinositide 3-kinase (PI3K) signaling activated the GSK3β/β-catenin/Wnt signaling pathway via activation of c-Jun N-terminal kinase (JNK), suggesting that PI3K and JNK act at the upstream of β-catenin. In contrast, knock-down of β-catenin delayed fibroblast cell migration even under bFGF stimulation. RNA sequencing analysis of β-catenin knock-down fibroblasts demonstrated that β-catenin positively regulated the transcription of bFGF and FGF21. Moreover, FGF21 treatment activated AKT and JNK, and accelerated fibroblast migration to a similar extent as bFGF does. In addition, ELISA analysis demonstrated that both of bFGF and FGF21 were auto secretion factor and be regulated by Wnt pathway stimulators. Taken together, our analyses define a feedback regulatory loop between bFGF (FGF21) and Wnt signaling acting through β-catenin in skin fibroblasts. PMID:28217097

  14. Use of navigation channels by Lake Sturgeon: Does channelization increase vulnerability of fish to ship strikes?

    PubMed Central

    Bennion, David H.; Roseman, Edward F.; Holbrook, Christopher M.; Boase, James C.; Chiotti, Justin A.; Thomas, Michael V.; Wills, Todd C.; Drouin, Richard G.; Kessel, Steven T.; Krueger, Charles C.

    2017-01-01

    Channelization for navigation and flood control has altered the hydrology and bathymetry of many large rivers with unknown consequences for fish species that undergo riverine migrations. In this study, we investigated whether altered flow distributions and bathymetry associated with channelization attracted migrating Lake Sturgeon (Acipenser fulvescens) into commercial navigation channels, potentially increasing their exposure to ship strikes. To address this question, we quantified and compared Lake Sturgeon selection for navigation channels vs. alternative pathways in two multi-channel rivers differentially affected by channelization, but free of barriers to sturgeon movement. Acoustic telemetry was used to quantify Lake Sturgeon movements. Under the assumption that Lake Sturgeon navigate by following primary flow paths, acoustic-tagged Lake Sturgeon in the more-channelized lower Detroit River were expected to choose navigation channels over alternative pathways and to exhibit greater selection for navigation channels than conspecifics in the less-channelized lower St. Clair River. Consistent with these predictions, acoustic-tagged Lake Sturgeon in the more-channelized lower Detroit River selected the higher-flow and deeper navigation channels over alternative migration pathways, whereas in the less-channelized lower St. Clair River, individuals primarily used pathways alternative to navigation channels. Lake Sturgeon selection for navigation channels as migratory pathways also was significantly higher in the more-channelized lower Detroit River than in the less-channelized lower St. Clair River. We speculated that use of navigation channels over alternative pathways would increase the spatial overlap of commercial vessels and migrating Lake Sturgeon, potentially enhancing their vulnerability to ship strikes. Results of our study thus demonstrated an association between channelization and the path use of migrating Lake Sturgeon that could prove important for predicting sturgeon-vessel interactions in navigable rivers as well as for understanding how fish interact with their habitat in landscapes altered by human activity. PMID:28678798

  15. Focusing and alignment of erythrocytes in a viscoelastic medium

    NASA Astrophysics Data System (ADS)

    Go, Taesik; Byeon, Hyeokjun; Lee, Sang Joon

    2017-01-01

    Viscoelastic fluid flow-induced cross-streamline migration has recently received considerable attention because this process provides simple focusing and alignment over a wide range of flow rates. The lateral migration of particles depends on the channel geometry and physicochemical properties of particles. In this study, digital in-line holographic microscopy (DIHM) is employed to investigate the lateral migration of human erythrocytes induced by viscoelastic fluid flow in a rectangular microchannel. DIHM provides 3D spatial distributions of particles and information on particle orientation in the microchannel. The elastic forces generated in the pressure-driven flows of a viscoelastic fluid push suspended particles away from the walls and enforce erythrocytes to have a fixed orientation. Blood cell deformability influences the lateral focusing and fixed orientation in the microchannel. Different from rigid spheres and hardened erythrocytes, deformable normal erythrocytes disperse from the channel center plane, as the flow rate increases. Furthermore, normal erythrocytes have a higher angle of inclination than hardened erythrocytes in the region near the side-walls of the channel. These results may guide the label-free diagnosis of hematological diseases caused by abnormal erythrocyte deformability.

  16. Interleukin‑6 induces an epithelial‑mesenchymal transition phenotype in human adamantinomatous craniopharyngioma cells and promotes tumor cell migration.

    PubMed

    Zhou, Jie; Zhang, Chao; Pan, Jun; Chen, Ligang; Qi, Song-Tao

    2017-06-01

    Total resection of adamantinomatous craniopharyngioma (ACP) is complex and often leads to postoperative recurrence. This is due to the tendency of the tumor to invade the surrounding brain tissue and the generation of a local inflammatory state between the tumor cells and parenchyma. While there is evidence to suggest that interleukin‑6 (IL‑6) induces craniopharyngioma (CP)‑associated inflammation, particularly in ACP, the role of IL‑6 in the progression of ACP remains unclear. The results of the present study demonstrated that CP inflammation was associated with pathological classification, extent of surgery, degree of calcification and postoperative hypothalamic status scale. Cytokine antibody arrays were conducted to measure the expression of IL‑6 and other inflammatory factors in tumor tissues in response to various levels of inflammatory exposure. IL‑6, IL‑6 receptor (IL‑6R) and glycoprotein 130 expression was detected by immunohistochemistry. In addition, an ELISA was performed to quantify the levels of soluble IL‑6R (sIL‑6R) in the cystic fluid and supernatants of ACP cells and tumor‑associated fibroblasts. These measurements demonstrated that ACP cells produce IL‑6 and its associated proteins. In addition, the results revealed that while the viability of ACP cells was not affected, the migration of ACP cells was promoted by IL‑6 treatment in a concentration‑dependent manner. Conversely, treatment with an IL‑6‑blocking monoclonal antibody significantly decreased the migration of ACP cells. In addition, IL‑6 treatment increased the expression of vimentin and decreased the expression of E‑cadherin in a dose‑dependent manner. The findings of the present study demonstrate that IL‑6 may promote migration in vitro via the classic‑ and trans‑signaling pathways by inducing epithelial‑mesenchymal transition in ACP cell cultures.

  17. Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human adamantinomatous craniopharyngioma cells and promotes tumor cell migration

    PubMed Central

    Zhou, Jie; Zhang, Chao; Pan, Jun; Chen, Ligang; Qi, Song-Tao

    2017-01-01

    Total resection of adamantinomatous craniopharyngioma (ACP) is complex and often leads to postoperative recurrence. This is due to the tendency of the tumor to invade the surrounding brain tissue and the generation of a local inflammatory state between the tumor cells and parenchyma. While there is evidence to suggest that interleukin-6 (IL-6) induces craniopharyngioma (CP)-associated inflammation, particularly in ACP, the role of IL-6 in the progression of ACP remains unclear. The results of the present study demonstrated that CP inflammation was associated with pathological classification, extent of surgery, degree of calcification and postoperative hypothalamic status scale. Cytokine antibody arrays were conducted to measure the expression of IL-6 and other inflammatory factors in tumor tissues in response to various levels of inflammatory exposure. IL-6, IL-6 receptor (IL-6R) and glycoprotein 130 expression was detected by immunohistochemistry. In addition, an ELISA was performed to quantify the levels of soluble IL-6R (sIL-6R) in the cystic fluid and supernatants of ACP cells and tumor-associated fibroblasts. These measurements demonstrated that ACP cells produce IL-6 and its associated proteins. In addition, the results revealed that while the viability of ACP cells was not affected, the migration of ACP cells was promoted by IL-6 treatment in a concentration-dependent manner. Conversely, treatment with an IL-6-blocking monoclonal antibody significantly decreased the migration of ACP cells. In addition, IL-6 treatment increased the expression of vimentin and decreased the expression of E-cadherin in a dose-dependent manner. The findings of the present study demonstrate that IL-6 may promote migration in vitro via the classic- and trans-signaling pathways by inducing epithelial-mesenchymal transition in ACP cell cultures. PMID:28487953

  18. Endothelial differentiation of bone marrow mesenchyme stem cells applicable to hypoxia and increased migration through Akt and NFκB signals.

    PubMed

    Liu, Cheng; Tsai, An-Ly; Li, Ping-Chia; Huang, Chia-Wei; Wu, Chia-Ching

    2017-02-07

    Bone marrow mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) are used to repair hypoxic or ischemic tissue. However, the underlining mechanism of resistance in the hypoxic microenvironment and the efficacy of migration to the injured tissue are still unknown. The current study aims to understand the hypoxia resistance and migration ability of MSCs during differentiation toward endothelial lineages by biochemical and mechanical stimuli. MSCs were harvested from the bone marrow of 6-8-week-old Sprague-Dawley rats. The endothelial growth medium (EGM) was added to MSCs for 3 days to initiate endothelial differentiation. Laminar shear stress was used as the fluid mechanical stimulation. Application of EGM facilitated the early endothelial lineage cells (eELCs) to express EPC markers. When treating the hypoxic mimetic desferrioxamine, both MSCs and eELCs showed resistance to hypoxia as compared with the occurrence of apoptosis in rat fibroblasts. The eELCs under hypoxia increased the wound closure and C-X-C chemokine receptor type 4 (CXCR4) gene expression. Although the shear stress promoted eELC maturation and aligned cells parallel to the flow direction, their migration ability was not superior to that of eELCs either under normoxia or hypoxia. The eELCs showed higher protein expressions of CXCR4, phosphorylated Akt (pAkt), and endogenous NFκB and IκBα than MSCs under both normoxia and hypoxia conditions. The potential migratory signals were discovered by inhibiting either Akt or NFκB using specific inhibitors and revealed decreases of wound closure and transmigration ability in eELCs. The Akt and NFκB pathways are important to regulate the early endothelial differentiation and its migratory ability under a hypoxic microenvironment.

  19. HGF potentiates extracellular matrix-driven migration of human myoblasts: involvement of matrix metalloproteinases and MAPK/ERK pathway.

    PubMed

    González, Mariela Natacha; de Mello, Wallace; Butler-Browne, Gillian S; Silva-Barbosa, Suse Dayse; Mouly, Vincent; Savino, Wilson; Riederer, Ingo

    2017-10-10

    The hepatocyte growth factor (HGF) is required for the activation of muscle progenitor cells called satellite cells (SC), plays a role in the migration of proliferating SC (myoblasts), and is present as a soluble factor during muscle regeneration, along with extracellular matrix (ECM) molecules. In this study, we aimed at determining whether HGF is able to interact with ECM proteins, particularly laminin 111 and fibronectin, and to modulate human myoblast migration. We evaluated the expression of the HGF-receptor c-Met, laminin, and fibronectin receptors by immunoblotting, flow cytometry, or immunofluorescence and used Transwell assays to analyze myoblast migration on laminin 111 and fibronectin in the absence or presence of HGF. Zymography was used to check whether HGF could modulate the production of matrix metalloproteinases by human myoblasts, and the activation of MAPK/ERK pathways was evaluated by immunoblotting. We demonstrated that human myoblasts express c-Met, together with laminin and fibronectin receptors. We observed that human laminin 111 and fibronectin have a chemotactic effect on myoblast migration, and this was synergistically increased when low doses of HGF were added. We detected an increase in MMP-2 activity in myoblasts treated with HGF. Conversely, MMP-2 inhibition decreased the HGF-associated stimulation of cell migration triggered by laminin or fibronectin. HGF treatment also induced in human myoblasts activation of MAPK/ERK pathways, whose specific inhibition decreased the HGF-associated stimulus of cell migration triggered by laminin 111 or fibronectin. We demonstrate that HGF induces ERK phosphorylation and MMP production, thus stimulating human myoblast migration on ECM molecules. Conceptually, these data state that the mechanisms involved in the migration of human myoblasts comprise both soluble and insoluble moieties. This should be taken into account to optimize the design of therapeutic cell transplantation strategies by improving the migration of donor cells within the host tissue, a main issue regarding this approach.

  20. Controls on the Migration of Fluids in Subduction Zones

    NASA Astrophysics Data System (ADS)

    Wilson, C. R.; Spiegelman, M. W.; Van Keken, P. E.; Kelemen, P. B.; Hacker, B. R.

    2013-12-01

    Arc volcanism associated with subduction is generally considered to be caused by the transport in the slab of hydrated minerals to sub-arc depths. In a qualitative sense it appears clear that progressive dehydration reactions in the down-going slab release fluids to the hot overlying mantle wedge, causing flux melting and the migration of melts to the volcanic front. However, the quantitative details of fluid release, migration, melt generation and transport in the wedge remain poorly understood. In particular, there are two fundamental observations that defy quantitative modeling. The first is the location of the volcanic front with respect to intermediate depth earthquakes (e.g. 100+/-40 km; England et al., 2004, Syracuse and Abers, 2006) which is remarkably robust yet insensitive to subduction parameters. This is particularly surprising given new estimates on the variability of fluid release in global subduction zones (e.g. van Keken et al. 2011) which show great sensitivity of fluid release to slab thermal conditions. Reconciling these results implies some robust mechanism for focusing fluids and/or melts toward the wedge corner. The second observation is the global existence of thermally hot erupted basalts and andesites that, if derived from flux melting of the mantle requires sub-arc mantle temperatures of 1300 degrees C over shallow pressures of 1-2 GPa which are not that different from mid-ocean ridge conditions. These observations impose significant challenges for geodynamic models of subduction zones, and in particular for those that do not include the explicit transport of fluids and melts. We present a range of high-resolution models that include a more complete description of coupled fluid and solid mechanics (allowing the fluid to interact with solid rheological variations) together with rheologically consistent solution for temperature and solid flow. Focusing on end-members of a global suite of arc geometries and thermal histories we discuss how successful these interactions are at focusing both fluids and hot solids to sub-arc regions worldwide. We will also evaluate the efficacy of current wet melting parameterizations in these models. When driven by buoyancy alone, fluid migrates through the mantle wedge along a near vertical trajectory. Only interactions with the solid flow at very low values of permeability or high values of fluid viscosity can cause deviations from this path. However, in a viscous, permeable medium, additional pressure gradients are generated by volumetric deformation due to variations in fluid flux. These pressure gradients can significantly modify the fluid flow paths. At shallow depths, compaction channels form along the rheological contrast with the overriding plate while in the mantle wedge itself porosity waves concentrate the fluid. When considering multiple, distributed sources of fluid, interaction between layers in the slab itself can also cause significant focusing. As well as permeability, rheological controls and numerical regularizations place upper and lower bounds on the length-scales over which such interactions occur further modifying the degree of focusing seen. The wide range of behaviors described here is modeled using TerraFERMA (the Transparent Finite Element Rapid Model Assembler), which harnesses the advanced computational libraries FEniCS, PETSc and SPuD to provide the required numerical flexibility.

  1. Apigenin inhibits cell proliferation, migration, and invasion by targeting Akt in the A549 human lung cancer cell line.

    PubMed

    Zhou, Zhongping; Tang, Miaomiao; Liu, Yi; Zhang, Zhuyi; Lu, Rongzhu; Lu, Jian

    2017-04-01

    Apigenin (APG), a widely distributed flavonoid in vegetables and fruits, with low toxicity, and a nonmutagenic characteristic, has been reported to have many targets. Evidence indicates that APG can inhibit the proliferation, migration, invasion, and metastasis of some tumor cells, but the mechanism, specifically in lung cancer, is unclear. The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway regulates a diverse set of cellular functions relevant to the growth and progression of lung cancer, including proliferation, survival, migration, and invasion. Our results showed that APG exerted anti-proliferation, anti-migration, and anti-invasion effects in A549 human lung cancer cells by targeting the PI3K/Akt signaling pathway. 3-(4, 5-dimethylthiszol-2-yl)-2, 5-diphenytetrazolium bromide assay and colony formation assay showed that APG suppressed cell proliferation in a dose-dependent and time-dependent manner. Cell motility and invasiveness were assayed using a wound healing and Transwell assay, suggesting that APG inhibited the migration and invasion of A549 cells. Western blot analyses were carried out to examine the Akt signaling pathways. The results confirmed that APG decreased Akt expression and its activation. Then, cells were transfected with Akt-active and Akt-DN plasmids separately. The migration and invasion of A549 cells were significantly changed, constitutively activating Akt or knocking down Akt, indicating that APG can suppress the migration and invasion of lung cancer cells by modulating the PI3K/Akt signaling pathway. Furthermore, the results indicated that APG not only suppressed phosphorylation of Akt, thereby preventing its activation, but also inhibited its downstream gene expression of matrix metalloproteinases-9, glycogen synthase kinase-3β, and HEF1. Together, APG is a new inhibitor of Akt in lung cancer and a potential natural compound for cancer chemoprevention.

  2. Protocatechuic Acid from Alpinia oxyphylla Induces Schwann Cell Migration via ERK1/2, JNK and p38 Activation.

    PubMed

    Ju, Da-Tong; Kuo, Wei-Wen; Ho, Tsung-Jung; Paul, Catherine Reena; Kuo, Chia-Hua; Viswanadha, Vijaya Padma; Lin, Chien-Chung; Chen, Yueh-Sheng; Chang, Yung-Ming; Huang, Chih-Yang

    2015-01-01

    Alpinia oxyphylla MIQ (Alpinate Oxyphyllae Fructus, AOF) is an important traditional Chinese medicinal herb whose fruits is widely used to prepare tonics and is used as an aphrodisiac, anti salivary, anti diuretic and nerve-protective agent. Protocatechuic acid (PCA), a simple phenolic compound was isolated from the kernels of AOF. This study investigated the role of PCA in promoting neural regeneration and the underlying molecular mechanisms. Nerve regeneration is a complex physiological response that takes place after injury. Schwann cells play a crucial role in the endogenous repair of peripheral nerves due to their ability to proliferate and migrate. The role of PCA in Schwann cell migration was determined by assessing the induced migration potential of RSC96 Schwann cells. PCA induced changes in the expression of proteins of three MAPK pathways, as determined using Western blot analysis. In order to determine the roles of MAPK (ERK1/2, JNK, and p38) pathways in PCA-induced matrix-degrading proteolytic enzyme (PAs and MMP2/9) production, the expression of several MAPK-associated proteins was analyzed after siRNA-mediated inhibition assays. Treatment with PCA-induced ERK1/2, JNK, and p38 phosphorylation that activated the downstream expression of PAs and MMPs. PCA-stimulated ERK1/2, JNK and p38 phosphorylation was attenuated by individual pretreatment with siRNAs or MAPK inhibitors (U0126, SP600125, and SB203580), resulting in the inhibition of migration and the uPA-related signal pathway. Taken together, our data suggest that PCA extract regulate the MAPK (ERK1/2, JNK, and p38)/PA (uPA, tPA)/MMP (MMP2, MMP9) mediated regeneration and migration signaling pathways in Schwann cells. Therefore, PCA plays a major role in Schwann cell migration and the regeneration of damaged peripheral nerve.

  3. Neuregulin Facilitates Nerve Regeneration by Speeding Schwann Cell Migration via ErbB2/3-Dependent FAK Pathway

    PubMed Central

    Chang, Hung-Ming; Shyu, Ming-Kwang; Tseng, Guo-Fang; Liu, Chiung-Hui; Chang, Hung-Shuo; Lan, Chyn-Tair; Hsu, Wen-Ming; Liao, Wen-Chieh

    2013-01-01

    Background Adequate migration of Schwann cells (Sc) is crucial for axon-guidance in the regenerative process after peripheral nerve injury (PNI). Considering neuregulin-erbB-FAK signaling is an essential pathway participating in the regulation of Sc migration during development, the present study is aimed to examine whether neuregulin would exert its beneficial effects on adult following PNI and further determine the potential changes of downstream pathway engaged in neuro-regeneration by both in vitro and in vivo approaches. Methodology and Principal Findings Cultured RSC96 cells treated with neuregulin were processed for erbB2/3 immunofluorescence and FAK immunoblotings. The potential effects of neuregulin on Sc were assessed by cell adherence, spreading, and migration assays. In order to evaluate the functional significance of neuregulin on neuro-regeneration, the in vivo model of PNI was performed by chronic end-to-side neurorrhaphy (ESN). In vitro studies indicated that after neuregulin incubation, erbB2/3 were not only expressed in cell membranes, but also distributed throughout the cytoplasm and nucleus of RSC96 cells. Activation of erbB2/3 was positively correlated with FAK phosphorylation. Neuregulin also increases Sc adherence, spreading, and migration by 127.2±5.0%, 336.8±3.0%, and 80.0±5.7%, respectively. As for in vivo study, neuregulin significantly accelerates the speed of Sc migration and increases Sc expression in the distal stump of injured nerves. Retrograde labeling and compound muscle action potential recordings (CMAP) also showed that neuregulin successfully facilitates nerve regeneration by eliciting noticeably larger CMAP and promoting quick re-innervation of target muscles. Conclusions As neuregulin successfully improves axo-glial interaction by speeding Sc migration via the erbB2/3-FAK pathway, therapeutic use of neuregulin may thus serve as a promising strategy to facilitate the progress of nerve regeneration after PNI. PMID:23301073

  4. Geospatial Analysis of Oil and Gas Wells in California

    NASA Astrophysics Data System (ADS)

    Riqueros, N. S.; Kang, M.; Jackson, R. B.

    2015-12-01

    California currently ranks third in oil production by U.S. state and more than 200,000 wells have been drilled in the state. Oil and gas wells provide a potential pathway for subsurface migration, leading to groundwater contamination and emissions of methane and other fluids to the atmosphere. Here we compile available public databases on oil and gas wells from the California Department of Conservation's Division of Oil, Gas, and Geothermal Resources, the U.S. Geological Survey, and other state and federal sources. We perform geospatial analysis at the county and field levels to characterize depths, producing formations, spud/completion/abandonment dates, land cover, population, and land ownership of active, idle, buried, abandoned, and plugged wells in California. The compiled database is designed to serve as a quantitative platform for developing field-based groundwater and air emission monitoring plans.

  5. High Glucose-Induced Reactive Oxygen Species Stimulates Human Mesenchymal Stem Cell Migration Through Snail and EZH2-Dependent E-Cadherin Repression.

    PubMed

    Oh, Ji Young; Choi, Gee Euhn; Lee, Hyun Jik; Jung, Young Hyun; Ko, So Hee; Chae, Chang Woo; Kim, Jun Sung; Kim, Seo Yihl; Lim, Jae Ryong; Lee, Chang-Kyu; Han, Ho Jae

    2018-01-01

    Glucose plays an important role in stem cell fate determination and behaviors. However, it is still not known how glucose contributes to the precise molecular mechanisms responsible for stem cell migration. Thus, we investigate the effect of glucose on the regulation of the human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) migration, and analyze the mechanism accompanied by this effect. Western blot analysis, wound healing migration assays, immunoprecipitation, and chromatin immunoprecipitation assay were performed to investigate the effect of high glucose on hUCB-MSC migration. Additionally, hUCB-MSC transplantation was performed in the mouse excisional wound splinting model. High concentration glucose (25 mM) elicits hUCB-MSC migration compared to normal glucose and high glucose-pretreated hUCB-MSC transplantation into the wound sites in mice also accelerates skin wound repair. We therefore elucidated the detailed mechanisms how high glucose induces hUCB-MSC migration. We showed that high glucose regulates E-cadherin repression through increased Snail and EZH2 expressions. And, we found high glucose-induced reactive oxygen species (ROS) promotes two signaling; JNK which regulates γ-secretase leading to the cleavage of Notch proteins and PI3K/Akt signaling which enhances GSK-3β phosphorylation. High glucose-mediated JNK/Notch pathway regulates the expression of EZH2, and PI3K/Akt/GSK-3β pathway stimulates Snail stabilization, respectively. High glucose enhances the formation of EZH2/Snail/HDAC1 complex in the nucleus, which in turn causes E-cadherin repression. This study reveals that high glucose-induced ROS stimulates the migration of hUCB-MSC through E-cadherin repression via Snail and EZH2 signaling pathways. © 2018 The Author(s). Published by S. Karger AG, Basel.

  6. Differential role of PTEN in transforming growth factor β (TGF-β) effects on proliferation and migration in prostate cancer cells.

    PubMed

    Kimbrough-Allah, Mawiyah N; Millena, Ana C; Khan, Shafiq A

    2018-04-01

    Transforming growth factor-β (TGF-β) acts as a tumor suppressor in normal epithelial cells but as a tumor promoter in advanced prostate cancer cells. PI3-kinase pathway mediates TGF-β effects on prostate cancer cell migration and invasion. PTEN inhibits PI3-kinase pathway and is frequently mutated in prostate cancers. We investigated possible role(s) of PTEN in TGF-β effects on proliferation and migration in prostate cancer cells. Expression of PTEN mRNA and proteins were determined using RT-PCR and Western blotting in RWPE1 and DU145 cells. We also studied the role of PTEN in TGF-β effects on cell proliferation and migration in DU145 cells after transient silencing of endogenous PTEN. Conversely, we determined the role of PTEN in cell proliferation and migration after over-expression of PTEN in PC3 cells which lack endogenous PTEN. TGF-β1 and TGF-β3 had no effect on PTEN mRNA levels but both isoforms increased PTEN protein levels in DU145 and RWPE1 cells indicating that PTEN may mediate TGF-β effects on cell proliferation. Knockdown of PTEN in DU145 cells resulted in significant increase in cell proliferation which was not affected by TGF-β isoforms. PTEN overexpression in PC3 cells inhibited cell proliferation. Knockdown of endogenous PTEN enhanced cell migration in DU145 cells, whereas PTEN overexpression reduced migration in PC3 cells and reduced phosphorylation of AKT in response to TGF-β. We conclude that PTEN plays a role in inhibitory effects of TGF-β on cell proliferation whereas its absence may enhance TGF-β effects on activation of PI3-kinase pathway and cell migration. © 2018 Wiley Periodicals, Inc.

  7. Ginkgolide K promotes astrocyte proliferation and migration after oxygen-glucose deprivation via inducing protective autophagy through the AMPK/mTOR/ULK1 signaling pathway.

    PubMed

    Zhang, Ying; Miao, Ju-Mei

    2018-05-19

    Ischemic stroke is the leading cause of death around the world. Ginkgolide K (GK) has been used to treat ischemic stroke due to its neuroprotective potential. However, the molecular mechanism underlying the neuroprotective effect of GK in ischemic stroke is still almost blank. In this study, astrocytes were divided into four groups: control group, oxygen-glucose deprivation (OGD) group, OGD + GK group and OGD + GK + Compound C (CC) group. The viability and proliferation of astrocytes were examined by Cell Counting Kit-8 assay and 5-ethynyl-20-deoxyuridine (EdU) assay, respectively. Transwell migration and wound scratch assays were conducted to evaluate astrocyte migration. The protein expression in astrocytes were determined by western blot assay. We found that GK pretreatment promoted astrocyte proliferation and migration after OGD as shown by the increase in the viability of astrocytes, glial fibrillary acidic protein level, the number of EdU positive cells and migrated cells, and the migration distance. GK pretreatment induced autophagy after OGD, as indicated by upregulation of autophagy-related protein 7, Beclin-1 protein and increase of microtubule-associated protein 1 light chain 3 (LC3)-II/LC3-I, and downregulation of p62 protein. Moreover, GK pretreatment activated the AMP activated protein kinase (AMPK)/mammalian target of rapamycin (m-TOR)/ULK1 pathway in astrocytes following OGD. Notably, CC treatment blocked the promotory effect of GK on astrocyte proliferation and migration after OGD. Collectively, GK promoted astrocyte proliferation and migration after OGD via inducing protective autophagy through the AMPK/mTOR/ULK1 signaling pathway. Our findings suggested that GK might be a potential agent for cerebral ischemia/reperfusion injury. Copyright © 2018. Published by Elsevier B.V.

  8. Low-Dose Radiation Promotes Dendritic Cell Migration and IL-12 Production via the ATM/NF-KappaB Pathway.

    PubMed

    Yu, Nan; Wang, Sinian; Song, Xiujun; Gao, Ling; Li, Wei; Yu, Huijie; Zhou, Chuanchuan; Wang, Zhenxia; Li, Fengsheng; Jiang, Qisheng

    2018-04-01

    For dendritic cells (DCs) to initiate an immune response, their ability to migrate and to produce interleukin-12 (IL-12) is crucial. It has been previously shown that low-dose radiation (LDR) promoted IL-12 production by DCs, resulting in increased DC activity that contributed to LDR hormesis in the immune system. However, the molecular mechanism of LDR-induced IL-12 production, as well as the effect of LDR on DC migration capacity require further elucidation. Using the JAWSII immortalized mouse dendritic cell line, we showed that in vitro X-ray irradiation (0.2 Gy) of DCs significantly increased DC migration and IL-12 production, and upregulated CCR7. The neutralizing antibody against CCR7 has been shown to abolish LDR-enhanced DC migration, demonstrating that CCR7 mediates LDR-promoting DC migration. We identified nuclear factor kappaB (NF-κB) as the central signaling pathway that mediated LDR-enhanced expression of IL-12 and CCR7 based on findings that 0.2 Gy X-ray irradiation activated NF-κB, showing increased nuclear p65 translocation and NF-κB DNA-binding activity, while an NF-κB inhibitor blocked LDR-enhanced expression of IL-12 and CCR7, as well as DC migration. Finally, we demonstrated that 0.2 Gy X-ray irradiation promoted ATM phosphorylation and reactive oxygen species generation; however, only the ATM inhibitor abolished the LDR-induced NF-κB-mediated expression of IL-12 and CCR7. Altogether, our data show that exposure to LDR resulted in a hormetic effect on DCs regarding CCR7-mediated migration and IL-12 production by activating the ATM/NF-κB pathway.

  9. 17β-Estradiol Reverses Leptin-Inducing Ovarian Cancer Cell Migration by the PI3K/Akt Signaling Pathway.

    PubMed

    Hoffmann, Marta; Fiedor, Elżbieta; Ptak, Anna

    2016-11-01

    Accumulating evidence suggests that leptin is expressed at higher levels in obese women and stimulates cell migration in epithelial cancers. However, the biology of ovarian cancer is different from others, mainly due to the production of estrogens because of the involvement of ovarian tissue, which is the main source of estrogens; as a result, the levels are at least 100- to 1000-fold higher than normal circulating levels. Thus, ovarian cancer tissues are exposed to 17β-estradiol, which promotes ovarian cancer cell migration and may modulate the effect of other hormones. Therefore, this study investigated the effects of 17β-estradiol (1 nmol/L) with leptin (1-40 ng/mL) at physiological levels, on the migration of OVCAR-3 and SKOV-3 ovarian cancer cells, and the expression levels and activity of metalloproteinases (MMPs) 2 and 9. Here, we found that leptin stimulated ovarian cancer cell line migration, which is mediated via the expression and activity of MMP-9 in the OVCAR-3 but not in the SKOV-3 cells. After the administration of 17β-estradiol and leptin, we observed antagonistic effects of 17β-estradiol on leptin-induced OVCAR-3 cell migration and MMP-9 expression and activity. Moreover, the antagonistic effect of 17β-estradiol on leptin-induced cancer cell migration was reversed by pretreatment of the cells with the phosphatidylinositol 3-kinase (PI3K) pathway inhibitor. Taken together, our results, for the first time, show that in ovarian cancer cells ObR + /ER + , 17β-estradiol has an antagonistic effect on leptin-induced cell migration as well as MMP-9 expression and activity, which is mediated by the PI3K pathway. © The Author(s) 2016.

  10. Beyond Compartmentalization: A Relational Approach towards Agency and Vulnerability of Young Migrants

    ERIC Educational Resources Information Center

    Huijsmans, Roy

    2012-01-01

    Based on fieldwork material from Lao People's Democratic Republic, this paper introduces an analytical framework that transcends compartmentalized approaches towards migration involving young people. The notions of fluid and institutionalized forms of migration illuminate key differences and commonalities in the relational fabric underpinning…

  11. Extracorporeal shock wave stimulates expression of the angiogenic genes via mechanosensory complex in endothelial cells: mimetic effect of fluid shear stress in endothelial cells.

    PubMed

    Ha, Chang Hoon; Kim, Sunghyen; Chung, Jihwa; An, Shung Hyen; Kwon, Kihwan

    2013-10-09

    Extracorporeal shock wave has been used in the noninvasive treatment of various diseases including musculoskeletal disorders. In particular, shock wave with low energy level showed anti-inflammatory effect and increased angiogenesis in ischemic tissues. However, the detailed cellular pathway in endothelial signaling is not fully understood. We investigate the role of shock wave with low energy level in angiogenic gene expression and underlying molecular mechanism by comparing the laminar and oscillatory fluid shear stresses in endothelial cells. We show that shock wave with low energy level (0.012-0.045 mJ/mm(2)) stimulated phosphorylation of Akt, eNOS and Erk 1/2 in a time-dependent manner which is similar to the effect of laminar fluid shear stress. The transfection of endothelial cells with siRNA encoding VEGFR2, VE-cadherin and PECAM-1 inhibited shock wave-induced phosphorylation of Akt, eNOS and Erk 1/2 and angiogenic gene expressions, including Akt, eNOS, KLF2/4, and Nur77. Moreover, mechanical stimulation through extracorporeal shock wave induced endothelial cell migration and tube formation. Our results demonstrate that shock wave-induced Akt/eNOS phosphorylation and angiogenic gene expression were mediated through the mechanosensory complex formation involving VEGFR-2, VE-cadherin and PECAM-1 which was similar to the effect of laminar shear stress. © 2013.

  12. Method and apparatus for separation of heavy and tritiated water

    DOEpatents

    Lee, Myung W.

    2001-01-01

    The present invention is a bi-thermal membrane process for separating and recovering hydrogen isotopes from a fluid containing hydrogen isotopes, such as water and hydrogen gas. The process in accordance with the present invention provides counter-current cold and hot streams of the fluid separated with a thermally insulating and chemically transparent proton exchange membrane (PEM). The two streams exchange hydrogen isotopes through the membrane: the heavier isotopes migrate into the cold stream, while the lighter isotopes migrate into the hot stream. The heavy and light isotopes are continuously withdrawn from the cold and hot streams respectively.

  13. FGF coordinates air sac development by activation of the EGF ligand Vein through the transcription factor PntP2.

    PubMed

    Cruz, Josefa; Bota-Rabassedas, Neus; Franch-Marro, Xavier

    2015-12-03

    How several signaling pathways are coordinated to generate complex organs through regulation of tissue growth and patterning is a fundamental question in developmental biology. The larval trachea of Drosophila is composed of differentiated functional cells and groups of imaginal tracheoblasts that build the adult trachea during metamorphosis. Air sac primordium cells (ASP) are tracheal imaginal cells that form the dorsal air sacs that supply oxygen to the flight muscles of the Drosophila adult. The ASP emerges from the tracheal branch that connects to the wing disc by the activation of both Bnl-FGF/Btl and EGFR signaling pathways. Together, these pathways promote cell migration and proliferation. In this study we demonstrate that Vein (vn) is the EGF ligand responsible for the activation of the EGFR pathway in the ASP. We also find that the Bnl-FGF/Btl pathway regulates the expression of vn through the transcription factor PointedP2 (PntP2). Furthermore, we show that the FGF target gene escargot (esg) attenuates EGFR signaling at the tip cells of the developing ASP, reducing their mitotic rate to allow proper migration. Altogether, our results reveal a link between Bnl-FGF/Btl and EGFR signaling and provide novel insight into how the crosstalk of these pathways regulates migration and growth.

  14. FGF coordinates air sac development by activation of the EGF ligand Vein through the transcription factor PntP2

    PubMed Central

    Cruz, Josefa; Bota-Rabassedas, Neus; Franch-Marro, Xavier

    2015-01-01

    How several signaling pathways are coordinated to generate complex organs through regulation of tissue growth and patterning is a fundamental question in developmental biology. The larval trachea of Drosophila is composed of differentiated functional cells and groups of imaginal tracheoblasts that build the adult trachea during metamorphosis. Air sac primordium cells (ASP) are tracheal imaginal cells that form the dorsal air sacs that supply oxygen to the flight muscles of the Drosophila adult. The ASP emerges from the tracheal branch that connects to the wing disc by the activation of both Bnl-FGF/Btl and EGFR signaling pathways. Together, these pathways promote cell migration and proliferation. In this study we demonstrate that Vein (vn) is the EGF ligand responsible for the activation of the EGFR pathway in the ASP. We also find that the Bnl-FGF/Btl pathway regulates the expression of vn through the transcription factor PointedP2 (PntP2). Furthermore, we show that the FGF target gene escargot (esg) attenuates EGFR signaling at the tip cells of the developing ASP, reducing their mitotic rate to allow proper migration. Altogether, our results reveal a link between Bnl-FGF/Btl and EGFR signaling and provide novel insight into how the crosstalk of these pathways regulates migration and growth. PMID:26632449

  15. High-resolution seismic survey for the characterization of planned PIER-ICDP fluid-monitoring sites in the Eger Rift zone

    NASA Astrophysics Data System (ADS)

    Simon, H.; Buske, S.

    2017-12-01

    The Eger Rift zone (Czech Republic) is a intra-continental non-volcanic region and is characterized by outstanding geodynamic activities, which result in earthquake swarms and significant CO2 emanations. Because fluid-induced stress can trigger earthquake swarms, both natural phenomena are probably related to each other. The epicentres of the earthquake swarms cluster at the northern edge of the Cheb Basin. Although the location of the cluster coincides with the major Mariánské-Lázně Fault Zone (MLFZ) the strike of the focal plane indicates another fault zone, the N-S trending Počátky-Plesná Zone (PPZ). Isotopic analysis of the CO2-rich fluids revealed a significant portion of upper mantle derived components, hence a magmatic fluid source in the upper mantle was postulated. Because of these phenomena, the Eger Rift area is a unique site for interdisciplinary drilling programs to study the fluid-earthquake interaction. The ICDP project PIER (Probing of Intra-continental magmatic activity: drilling the Eger Rift) will set up an observatory, consisting of five monitoring boreholes. In preparation for the drilling, the goal of the seismic survey is the characterization of the projected fluid-monitoring drill site at the CO2 degassing mofette field near Hartoušov. This will be achieved by a 6 km long profile with dense source and receiver spacing. The W-E trending profile will cross the proposed drill site and the surface traces of MLFZ and PPZ. The outcome of the seismic survey will be a high-resolution structural image of potential reflectors related to these fault zones. This will be achieved by the application of advanced pre-stack depth migration methods and a detailed P-wave velocity distribution of the area obtained from first arrival tomography. During interpretation of the seismic data, a geoelectrical resistivity model, acquired along the same profile line, will provide important constraints, especially with respect to fluid pathways.

  16. How the gas hydrate system gives insight into subduction wedge dewatering processes in a zone of highly-oblique convergence on the southern Hikurangi margin of New Zealand

    NASA Astrophysics Data System (ADS)

    Crutchley, Gareth; Klaeschen, Dirk; Pecher, Ingo; Henrys, Stuart

    2017-04-01

    The southern end of New Zealand's Hikurangi subduction margin is characterised by highly-oblique convergence as it makes a southward transition into a right-lateral transform plate boundary at the Alpine Fault. Long-offset seismic data that cross part of the offshore portion of this transition zone give new insight into the nature of the plate boundary. We have carried out 2D pre-stack depth migrations, with an iterative reflection tomography to update the velocity field, on two seismic lines in this area to investigate fluid flow processes that have implications for the mechanical stability of the subduction interface. The results show distinct and focused fluid expulsion pathways from the subduction interface to the shallow sub-surface. For example, on one of the seismic lines there is a clear disruption of the gas hydrate system at its intersection with a splay fault - a clear indication of focused fluid release from the subduction interface. The seismic velocities derived from tomography also highlight a broad, pronounced low velocity zone beneath the deforming wedge that we interpret as a thick zone of gas-charged fluids that may have important implications for the long-term frictional stability of the plate boundary in this area. The focused flow upward toward the seafloor has the potential to result in the formation of concentrated gas hydrate deposits. Our on-going work on these data will include amplitude versus offset analysis in an attempt to better characterise the nature of the subduction interface, the fluids in that region, and also the shallower gas hydrate system.

  17. Usp7 promotes medulloblastoma cell survival and metastasis by activating Shh pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhan, Meixiao; Zhuhai Precision Medicine Center, Zhuhai People's Hospital, Jinan University, Zhuhai; Sun, Xiaohan

    The ubiquitin-specific protease Usp7 plays roles in multiple cellular processes through deubiquitinating and stabilizing numerous substrates, including P53, Pten and Gli. Aberrant Usp7 activity has been implicated in many disorders and tumorigenesis, making it as a potential target for therapeutic intervention. Although it is clear that Usp7 is involved in many types of cancer, its role in regulating medulloblastoma (MB) is still unknown. In this study, we show that knockdown of Usp7 inhibits the proliferation and migration of MB cells, while Usp7 overexpression exerts an opposite effect. Furthermore, we establish Usp7 knockout MB cell line using the CRISPR/Cas9 system andmore » further confirm that Usp7 knockout also blocks MB cell proliferation and metastasis. In addition, we reveal that knockdown of Usp7 compromises Shh pathway activity and decrease Gli protein levels, while P53 level and P53 target gene expression have no obvious changes. Finally, we find that Usp7 inhibitors apparently inhibit MB cell viability and migration. Taken together, our findings suggest that Usp7 is important for MB cell proliferation and metastasis by activating Shh pathway, and is a putative therapeutic target for MBs. - Highlights: • Loss of usp7 blocks the proliferation and metastasis of MB cells. • Usp7 regulates MB cell growth and migration through stimulating Shh pathway. • Usp7 inhibitors hamper MB cell proliferation and migration. • Usp7 inhibitors could attenuate Shh pathway activity.« less

  18. Involvement of PI3K and ROCK signaling pathways in migration of bone marrow-derived mesenchymal stem cells through human brain microvascular endothelial cell monolayers.

    PubMed

    Lin, Mei-Na; Shang, De-Shu; Sun, Wei; Li, Bo; Xu, Xin; Fang, Wen-Gang; Zhao, Wei-Dong; Cao, Liu; Chen, Yu-Hua

    2013-06-04

    Bone marrow-derived mesenchymal stem cells (MSC) represent an important and easily available source of stem cells for potential therapeutic use in neurological diseases. The entry of circulating cells into the central nervous system by intravenous administration requires, firstly, the passage of the cells across the blood-brain barrier (BBB). However, little is known of the details of MSC transmigration across the BBB. In the present study, we employed an in vitro BBB model constructed using a human brain microvascular endothelial cell monolayer to study the mechanism underlying MSC transendothelial migration. Transmigration assays, transendothelial electrical resistance (TEER) and horseradish peroxidase (HRP) flux assays showed that MSC could transmigrate through human brain microvascular endothelial cell monolayers by a paracellular pathway. Cell fractionation and immunofluorescence assays confirmed the disruption of tight junctions. Inhibition assays showed that a Rho-kinase (ROCK) inhibitor (Y27632) effectively promoted MSC transendothelial migration; conversely, a PI3K inhibitor (LY294002) blocked MSC transendothelial migration. Interestingly, adenovirus-mediated interference with ROCK in MSC significantly increased MSC transendothelial migration, and overexpression of a PI3K dominant negative mutant in MSC cells could block transendothelial migration. Our findings provide clear evidence that the PI3K and ROCK pathways are involved in MSC migration through human brain microvascular endothelial cell monolayers. The information yielded by this study may be helpful in constructing gene-modified mesenchymal stem cells that are able to penetrate the BBB effectively for cell therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Neuronal migration is regulated by endogenous RNAi and chromatin-binding factor ZFP-1/AF10 in Caenorhabditis elegans.

    PubMed

    Kennedy, Lisa M; Grishok, Alla

    2014-05-01

    Endogenous short RNAs and the conserved plant homeodomain (PHD) zinc-finger protein ZFP-1/AF10 regulate overlapping sets of genes in Caenorhabditis elegans, which suggests that they control common biological pathways. We have shown recently that the RNAi factor RDE-4 and ZFP-1 negatively modulate transcription of the insulin/PI3 signaling-dependent kinase PDK-1 to promote C. elegans fitness. Moreover, we have demonstrated that the insulin/IGF-1-PI3K-signaling pathway regulates the activity of the DAF-16/FOXO transcription factor in the hypodermis to nonautonomously promote the anterior migrations of the hermaphrodite-specific neurons (HSNs) during embryogenesis of C. elegans. In this study, we implicate the PHD-containing isoform of ZFP-1 and endogenous RNAi in the regulation of HSN migration. ZFP-1 affects HSN migration in part through its negative effect on pdk-1 transcription and modulation of downstream DAF-16 activity. We also identify a novel role for ZFP-1 and RNAi pathway components, including RDE-4, in the regulation of HSN migration in parallel with DAF-16. Therefore, the coordinated activities of DAF-16, ZFP-1, and endogenous RNAi contribute to gene regulation during development to ensure proper neuronal positioning.

  20. Neuronal Migration Is Regulated by Endogenous RNAi and Chromatin-Binding Factor ZFP-1/AF10 in Caenorhabditis elegans

    PubMed Central

    Kennedy, Lisa M.; Grishok, Alla

    2014-01-01

    Endogenous short RNAs and the conserved plant homeodomain (PHD) zinc-finger protein ZFP-1/AF10 regulate overlapping sets of genes in Caenorhabditis elegans, which suggests that they control common biological pathways. We have shown recently that the RNAi factor RDE-4 and ZFP-1 negatively modulate transcription of the insulin/PI3 signaling-dependent kinase PDK-1 to promote C. elegans fitness. Moreover, we have demonstrated that the insulin/IGF-1-PI3K-signaling pathway regulates the activity of the DAF-16/FOXO transcription factor in the hypodermis to nonautonomously promote the anterior migrations of the hermaphrodite-specific neurons (HSNs) during embryogenesis of C. elegans. In this study, we implicate the PHD-containing isoform of ZFP-1 and endogenous RNAi in the regulation of HSN migration. ZFP-1 affects HSN migration in part through its negative effect on pdk-1 transcription and modulation of downstream DAF-16 activity. We also identify a novel role for ZFP-1 and RNAi pathway components, including RDE-4, in the regulation of HSN migration in parallel with DAF-16. Therefore, the coordinated activities of DAF-16, ZFP-1, and endogenous RNAi contribute to gene regulation during development to ensure proper neuronal positioning. PMID:24558261

  1. CXCL1 inhibits airway smooth muscle cell migration through the decoy receptor Duffy antigen receptor for chemokines.

    PubMed

    Al-Alwan, Laila A; Chang, Ying; Rousseau, Simon; Martin, James G; Eidelman, David H; Hamid, Qutayba

    2014-08-01

    Airway smooth muscle cell (ASMC) migration is an important mechanism postulated to play a role in airway remodeling in asthma. CXCL1 chemokine has been linked to tissue growth and metastasis. In this study, we present a detailed examination of the inhibitory effect of CXCL1 on human primary ASMC migration and the role of the decoy receptor, Duffy AgR for chemokines (DARC), in this inhibition. Western blots and pathway inhibitors showed that this phenomenon was mediated by activation of the ERK-1/2 MAPK pathway, but not p38 MAPK or PI3K, suggesting a biased selection in the signaling mechanism. Despite being known as a nonsignaling receptor, small interference RNA knockdown of DARC showed that ERK-1/2 MAPK activation was significantly dependent on DARC functionality, which, in turn, was dependent on the presence of heat shock protein 90 subunit α. Interestingly, DARC- or heat shock protein 90 subunit α-deficient ASMCs responded to CXCL1 stimulation by enhancing p38 MAPK activation and ASMC migration through the CXCR2 receptor. In conclusion, we demonstrated DARC's ability to facilitate CXCL1 inhibition of ASMC migration through modulation of the ERK-1/2 MAPK-signaling pathway. Copyright © 2014 by The American Association of Immunologists, Inc.

  2. Extracellular acidification synergizes with PDGF to stimulate migration of mouse embryo fibroblasts through activation of p38MAPK with a PTX-sensitive manner

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    An, Caiyan; Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi; Clinical Medicine Research Center of the Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia

    The elucidation of the functional mechanisms of extracellular acidification stimulating intracellular signaling pathway is of great importance for developing new targets of treatment for solid tumors, and inflammatory disorders characterized by extracellular acidification. In the present study, we focus on the regulation of extracellular acidification on intracellular signaling pathways in mouse embryo fibroblasts (MEFs). We found extracellular acidification was at least partly involved in stimulating p38MAPK pathway through PTX-sensitive behavior to enhance cell migration in the presence or absence of platelet-derived growth factor (PDGF). Statistical analysis showed that the actions of extracellular acidic pH and PDGF on inducing enhancement ofmore » cell migration were not an additive effect. However, we also found extracellular acidic pH did inhibit the viability and proliferation of MEFs, suggesting that extracellular acidification stimulates cell migration probably through proton-sensing mechanisms within MEFs. Using OGR1-, GPR4-, and TDAG8-gene knock out technology, and real-time qPCR, we found known proton-sensing G protein-coupled receptors (GPCRs), transient receptor potential vanilloid subtype 1 (TRPV1), and acid-sensing ion channels (ASICs) were unlikely to be involved in the regulation of acidification on cell migration. In conclusion, our present study validates that extracellular acidification stimulates chemotactic migration of MEFs through activation of p38MAPK with a PTX-sensitive mechanism either by itself, or synergistically with PDGF, which was not regulated by the known proton-sensing GPCRs, TRPV1, or ASICs. Our results suggested that others proton-sensing GPCRs or ion channels might exist in MEFs, which mediates cell migration induced by extracellular acidification in the presence or absence of PDGF. - Highlights: • Acidic pH and PDGF synergize to stimulate MEFs migration via Gi/p38MAPK pathway. • Extracellular acidification inhibits the viability and proliferation of MEFs. • MEFs sense acidic pH was not regulated by known proton-sensing GPCRs, TRPV1 or ASICs.« less

  3. Microalga propels along vorticity direction in a shear flow

    NASA Astrophysics Data System (ADS)

    Chengala, Anwar; Hondzo, Miki; Sheng, Jian

    2013-05-01

    Using high-speed digital holographic microscopy and microfluidics, we discover that, when encountering fluid flow shear above a threshold, unicellular green alga Dunaliella primolecta migrates unambiguously in the cross-stream direction that is normal to the plane of shear and coincides with the local fluid flow vorticity. The flow shear drives motile microalgae to collectively migrate in a thin two-dimensional horizontal plane and consequently alters the spatial distribution of microalgal cells within a given suspension. This shear-induced algal migration differs substantially from periodic rotational motion of passive ellipsoids, known as Jeffery orbits, as well as gyrotaxis by bottom-heavy swimming microalgae in a shear flow due to the subtle interplay between torques generated by gravity and viscous shear. Our findings could facilitate mechanistic solutions for modeling planktonic thin layers and sustainable cultivation of microalgae for human nutrition and bioenergy feedstock.

  4. Mib1 contributes to persistent directional cell migration by regulating the Ctnnd1-Rac1 pathway.

    PubMed

    Mizoguchi, Takamasa; Ikeda, Shoko; Watanabe, Saori; Sugawara, Michiko; Itoh, Motoyuki

    2017-10-31

    Persistent directional cell migration is involved in animal development and diseases. The small GTPase Rac1 is involved in F-actin and focal adhesion dynamics. Local Rac1 activity is required for persistent directional migration, whereas global, hyperactivated Rac1 enhances random cell migration. Therefore, precise control of Rac1 activity is important for proper directional cell migration. However, the molecular mechanism underlying the regulation of Rac1 activity in persistent directional cell migration is not fully understood. Here, we show that the ubiquitin ligase mind bomb 1 (Mib1) is involved in persistent directional cell migration. We found that knockdown of MIB1 led to an increase in random cell migration in HeLa cells in a wound-closure assay. Furthermore, we explored novel Mib1 substrates for cell migration and found that Mib1 ubiquitinates Ctnnd1. Mib1-mediated ubiquitination of Ctnnd1 K547 attenuated Rac1 activation in cultured cells. In addition, we found that posterior lateral line primordium cells in the zebrafish mib1 ta52b mutant showed increased random migration and loss of directional F-actin-based protrusion formation. Knockdown of Ctnnd1 partially rescued posterior lateral line primordium cell migration defects in the mib1 ta52b mutant. Taken together, our data suggest that Mib1 plays an important role in cell migration and that persistent directional cell migration is regulated, at least in part, by the Mib1-Ctnnd1-Rac1 pathway. Published under the PNAS license.

  5. Aurora kinase A revives dormant laryngeal squamous cell carcinoma cells via FAK/PI3K/Akt pathway activation

    PubMed Central

    Yang, Li-yun; He, Chang-yu; Chen, Xue-hua; Su, Li-ping; Liu, Bing-ya; Zhang, Hao

    2016-01-01

    Revival of dormant tumor cells may be an important tumor metastasis mechanism. We hypothesized that aurora kinase A (AURKA), a cell cycle control kinase, promotes the transition of laryngeal squamous cell carcinoma (LSCC) cells from G0 phase to active division. We therefore investigated whether AURKA could revive dormant tumor cells to promote metastasis. Western blotting revealed that AURKA expression was persistently low in dormant laryngeal cancer Hep2 (D-Hep2) cells and high in non-dormant (T-Hep2) cells. Decreasing AURKA expression in T-Hep2 cells induced dormancy and reduced FAK/PI3K/Akt pathway activity. Increasing AURKA expression in D-Hep2 cells increased FAK/PI3K/Akt pathway activity and enhanced cellular proliferation, migration, invasion and metastasis. In addition, FAK/PI3K/Akt pathway inhibition caused dormancy-like behavior and reduced cellular mobility, migration and invasion. We conclude that AURKA may revive dormant tumor cells via FAK/PI3K/Akt pathway activation, thereby promoting migration and invasion in laryngeal cancer. AURKA/FAK/PI3K/Akt inhibitors may thus represent potential targets for clinical LSCC treatment. PMID:27356739

  6. Selective placement disposal of drilling fluids in west Texas

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McFarland, M.L.

    1988-01-01

    Burial of spent drilling fluids used in petroleum and natural gas exploration was evaluated as an alternative disposal technique for reducing surface soil contamination in western Texas. Simulated reserve pits were constructed to provide burial depths of 30, 90, and 150 cm below the surface, with orderly replacement of stockpiled subsoil and topsoil. Movement of soluble salts and heavy metals from drilling fluids into the overlying soil was monitored over a 20-month period. The effects of depth of drilling fluid burial on establishment, yields, and chemical composition of transplanted fourwing saltbush (Atriplex canescens (Pursh) Nutt.) and buffalograss (Buchloe dactyloides (Nutt.)more » Engelm.) were determined for two growing seasons. Sodium, Ca{sup +2}, and Cl{sup {minus}} were the dominant mobile ions, while migration of Mg{sup +2}, K{sup +}, and SO{sub 4}{sup {minus}2} was observed to a lesser degree. Exchangeable sodium percentages in the 15-cm zone immediately above drilling fluid ranged from 1.9 to 19.0 after 20 months. Total concentrations of Ba, Cr, Cu, Ni, and Zn were greater in drilling fluids than in native soil, but there was no evidence of migration of these metals into overlying soil.« less

  7. A Theoretical Study of Remobilizing Surfactant Retarded Fluid Particle Interfaces

    NASA Technical Reports Server (NTRS)

    Wang, Yanping; Papageorgiou, Dimitri; Maldarelli, Charles

    1996-01-01

    Microgravity processes must rely on mechanisms other than bouyancy to move bubbles or droplets from one region to another in a continuous liquid phase. One suggested method is thermocapillary migration in which a temperature gradient is applied to the continuous phase. When a fluid particle contacts this gradient, one pole of the particle becomes warmer than the opposing pole. The interfacial tension between the drop or bubble phase and the continuous phase usually decreases with temperature. Thus the cooler pole is of higher interfacial tension than the warmer pole, and the interface is tugged in the direction of the cooler end. This thermocapillary or thermally induced Marangoni surface stress causes a fluid streaming in the continuous phase from which develops a viscous shear traction and pressure gradient which together propel the particle in the direction of the warmer fluid. In this paper, we provide a theoretical basis for remobilizing surfactant retarded fluid particle interfaces in an effort to make viable the use of thermocapillary migrations for the management of bubbles and drops in microgravity,

  8. Comprehensive Analysis of Migration Pathways (CAMP): Contaminant Migration Pathways at Confined Dredged Material Disposal Facilities

    DTIC Science & Technology

    1990-09-01

    fluctuating flow rates make such approximations relatively inexact. Accuracy of mass loading estimates can be improved by increasing the number of...Engler, Patin, and Theriot 1988; Patin and Baylot 1989). 26. Effluent flow from an upland CDF is highest when large quantities of water are being...dispersion in conjunction with lower flows during placement of mechanical dredged material. Interactions between sediment and water that occur during

  9. Apatinib inhibits cellular invasion and migration by fusion kinase KIF5B-RET via suppressing RET/Src signaling pathway

    PubMed Central

    Xie, Weiwei; Zheng, Rongliang; Gan, Yu; Chang, Jianhua

    2016-01-01

    The Rearranged during transfection (RET) fusion gene is a newly identified oncogenic mutation in non-small cell lung cancer (NSCLC). The aim of this study is to explore the biological functions of the gene in tumorigenesis and metastasis in RET gene fusion-driven preclinical models. We also investigate the anti-tumor activity of Apatinib, a potent inhibitor of VEGFR-2, PDGFR-β, c-Src and RET, in RET-rearranged lung adenocarcinoma, together with the mechanisms underlying. Our results suggested that KIF5B-RET fusion gene promoted cell invasion and migration, which were probably mediated through Src signaling pathway. Apatinib exerted its anti-cancer effect not only via cytotoxicity, but also via inhibition of migration and invasion by suppressing RET/Src signaling pathway, supporting a potential role for Apatinib in the treatment of KIF5B-RET driven tumors. PMID:27494860

  10. Apatinib inhibits cellular invasion and migration by fusion kinase KIF5B-RET via suppressing RET/Src signaling pathway.

    PubMed

    Lin, Chen; Wang, Shanshan; Xie, Weiwei; Zheng, Rongliang; Gan, Yu; Chang, Jianhua

    2016-09-13

    The Rearranged during transfection (RET) fusion gene is a newly identified oncogenic mutation in non-small cell lung cancer (NSCLC). The aim of this study is to explore the biological functions of the gene in tumorigenesis and metastasis in RET gene fusion-driven preclinical models. We also investigate the anti-tumor activity of Apatinib, a potent inhibitor of VEGFR-2, PDGFR-β, c-Src and RET, in RET-rearranged lung adenocarcinoma, together with the mechanisms underlying. Our results suggested that KIF5B-RET fusion gene promoted cell invasion and migration, which were probably mediated through Src signaling pathway. Apatinib exerted its anti-cancer effect not only via cytotoxicity, but also via inhibition of migration and invasion by suppressing RET/Src signaling pathway, supporting a potential role for Apatinib in the treatment of KIF5B-RET driven tumors.

  11. Rho-associated coiled-coil kinase (ROCK) protein controls microtubule dynamics in a novel signaling pathway that regulates cell migration.

    PubMed

    Schofield, Alice V; Steel, Rohan; Bernard, Ora

    2012-12-21

    The two members of the Rho-associated coiled-coil kinase (ROCK1 and 2) family are established regulators of actin dynamics that are involved in the regulation of the cell cycle as well as cell motility and invasion. Here, we discovered a novel signaling pathway whereby ROCK regulates microtubule (MT) acetylation via phosphorylation of the tubulin polymerization promoting protein 1 (TPPP1/p25). We show that ROCK phosphorylation of TPPP1 inhibits the interaction between TPPP1 and histone deacetylase 6 (HDAC6), which in turn results in increased HDAC6 activity followed by a decrease in MT acetylation. As a consequence, we show that TPPP1 phosphorylation by ROCK increases cell migration and invasion via modulation of cellular acetyl MT levels. We establish here that the ROCK-TPPP1-HDAC6 signaling pathway is important for the regulation of cell migration and invasion.

  12. HGF and c-Met Interaction Promotes Migration in Human Chondrosarcoma Cells

    PubMed Central

    Tsou, Hsi-Kai; Chen, Hsien-Te; Hung, Ya-Huey; Chang, Chia-Hao; Li, Te-Mao; Fong, Yi-Chin; Tang, Chih-Hsin

    2013-01-01

    Chondrosarcoma is a type of highly malignant tumor with a potent capacity for local invasion and causing distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. Hepatocyte growth factor (HGF) has been demonstrated to stimulate cancer proliferation, migration, and metastasis. However, the effect of HGF on migration activity of human chondrosarcoma cells is not well known. Here, we found that human chondrosarcoma tissues demonstrated significant expression of HGF, which was higher than that in normal cartilage. We also found that HGF increased the migration and expression of matrix metalloproteinase (MMP)-2 in human chondrosarcoma cells. c-Met inhibitor and siRNA reduced HGF-increased cell migration and MMP-2 expression. HGF treatment resulted in activation of the phosphatidylinositol 3′-kinase (PI3K)/Akt/PKCδ/NF-κB pathway, and HGF-induced expression of MMP-2 and cell migration was inhibited by specific inhibitors or siRNA-knockdown of PI3K, Akt, PKCδ, and NF-κB cascades. Taken together, our results indicated that HGF enhances migration of chondrosarcoma cells by increasing MMP-2 expression through the c-Met receptor/PI3K/Akt/PKCδ/NF-κB signal transduction pathway. PMID:23320110

  13. Evidence for chemokine synergy during neutrophil migration in ARDS.

    PubMed

    Williams, Andrew E; José, Ricardo J; Mercer, Paul F; Brealey, David; Parekh, Dhruv; Thickett, David R; O'Kane, Cecelia; McAuley, Danny F; Chambers, Rachel C

    2017-01-01

    Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterised by pulmonary oedema, respiratory failure and severe inflammation. ARDS is further characterised by the recruitment of neutrophils into the lung interstitium and alveolar space. The factors that regulate neutrophil infiltration into the inflamed lung and our understanding of the pathomechanisms in ARDS remain incomplete. This study aimed at determining the role of the chemokine (C-C motif) ligand (CCL)2 and CCL7 in ARDS. CCL2 and CCL7 protein levels were measured in bronchoalveolar lavage (BAL) fluid obtained from lipopolysaccharide(LPS)-challenged human volunteers and two separate cohorts of patients with ARDS. Neutrophil chemotaxis to ARDS BAL fluid was evaluated and the contribution of each was assessed and compared with chemokine (C-X-C motif) ligand 8 (CXCL8). Chemokine receptor expression on neutrophils from blood or BAL fluid of patients with ARDS was analysed by flow cytometry. CCL2 and CCL7 were significantly elevated in BAL fluid recovered from LPS-challenged volunteers and patients with ARDS. BAL fluid from patients with ARDS was highly chemotactic for human neutrophils and neutralising either CCL2 or CCL7 attenuated the neutrophil chemotactic response. Moreover, CCL2 and CCL7 synergised with CXCL8 to promote neutrophil migration. Furthermore, neutrophils isolated from the blood or BAL fluid differentially regulated the cell surface expression of chemokine (C-X-C motif) receptor 1 and C-C chemokine receptor type 2 during ARDS. This study highlights important inflammatory chemokines involved in regulating neutrophil migration, which may have potential value as therapeutic targets for the treatment of ARDS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  14. Evidence for chemokine synergy during neutrophil migration in ARDS

    PubMed Central

    Williams, Andrew E; José, Ricardo J; Mercer, Paul F; Brealey, David; Parekh, Dhruv; Thickett, David R; O'Kane, Cecelia; McAuley, Danny F; Chambers, Rachel C

    2017-01-01

    Background Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterised by pulmonary oedema, respiratory failure and severe inflammation. ARDS is further characterised by the recruitment of neutrophils into the lung interstitium and alveolar space. Objectives The factors that regulate neutrophil infiltration into the inflamed lung and our understanding of the pathomechanisms in ARDS remain incomplete. This study aimed at determining the role of the chemokine (C-C motif) ligand (CCL)2 and CCL7 in ARDS. Methods CCL2 and CCL7 protein levels were measured in bronchoalveolar lavage (BAL) fluid obtained from lipopolysaccharide(LPS)-challenged human volunteers and two separate cohorts of patients with ARDS. Neutrophil chemotaxis to ARDS BAL fluid was evaluated and the contribution of each was assessed and compared with chemokine (C-X-C motif) ligand 8 (CXCL8). Chemokine receptor expression on neutrophils from blood or BAL fluid of patients with ARDS was analysed by flow cytometry. Results CCL2 and CCL7 were significantly elevated in BAL fluid recovered from LPS-challenged volunteers and patients with ARDS. BAL fluid from patients with ARDS was highly chemotactic for human neutrophils and neutralising either CCL2 or CCL7 attenuated the neutrophil chemotactic response. Moreover, CCL2 and CCL7 synergised with CXCL8 to promote neutrophil migration. Furthermore, neutrophils isolated from the blood or BAL fluid differentially regulated the cell surface expression of chemokine (C-X-C motif) receptor 1 and C-C chemokine receptor type 2 during ARDS. Conclusion This study highlights important inflammatory chemokines involved in regulating neutrophil migration, which may have potential value as therapeutic targets for the treatment of ARDS. PMID:27496101

  15. Rare Esophageal Migration of AXIOS Stent Used for Walled-off Pancreatic Necrosis Drainage

    PubMed Central

    Renno, Anas; Hammad, Tariq; Nawras, Ali

    2017-01-01

    The AXIOS stent (Boston Scientific, Marlborough, MA) is a novel lumen-apposing self-expandable metallic stent designed for enteric drainage of nonadherent lumens. Efficacy and safety of using the AXIOS stent for pancreatic fluid drainage have been consistently shown in several studies. Although it is less common with this novel stent, stent migration still may happen. We present a case of AXIOS stent migration into the esophagus. PMID:28584846

  16. Integrative models of vascular remodeling during tumor growth

    PubMed Central

    Rieger, Heiko; Welter, Michael

    2015-01-01

    Malignant solid tumors recruit the blood vessel network of the host tissue for nutrient supply, continuous growth, and gain of metastatic potential. Angiogenesis (the formation of new blood vessels), vessel cooption (the integration of existing blood vessels into the tumor vasculature), and vessel regression remodel the healthy vascular network into a tumor-specific vasculature that is in many respects different from the hierarchically organized arterio-venous blood vessel network of the host tissues. Integrative models based on detailed experimental data and physical laws implement in silico the complex interplay of molecular pathways, cell proliferation, migration, and death, tissue microenvironment, mechanical and hydrodynamic forces, and the fine structure of the host tissue vasculature. With the help of computer simulations high-precision information about blood flow patterns, interstitial fluid flow, drug distribution, oxygen and nutrient distribution can be obtained and a plethora of therapeutic protocols can be tested before clinical trials. In this review, we give an overview over the current status of integrative models describing tumor growth, vascular remodeling, blood and interstitial fluid flow, drug delivery, and concomitant transformations of the microenvironment. © 2015 The Authors. WIREs Systems Biology and Medicine published by Wiley Periodicals, Inc. PMID:25808551

  17. Polarised Clathrin-Mediated Endocytosis of EGFR During Chemotactic Invasion

    PubMed Central

    Mutch, Laura Jane; Howden, Jake Davey; Jenner, Emma Poppy Louise; Poulter, Natalie Sarah; Rappoport, Joshua Zachary

    2014-01-01

    Directed cell migration is critical for numerous physiological processes including development and wound healing. However chemotaxis is also exploited during cancer progression. Recent reports have suggested links between vesicle trafficking pathways and directed cell migration. Very little is known about the potential roles of endocytosis pathways during metastasis. Therefore we performed a series of studies employing a previously characterised model for chemotactic invasion of cancer cells to assess specific hypotheses potentially linking endocytosis to directed cell migration. Our results demonstrate that clathrin-mediated endocytosis is indispensable for epidermal growth factor (EGF) directed chemotactic invasion of MDA-MB-231 cells. Conversely, caveolar endocytosis is not required in this mode of migration. We further found that chemoattractant receptor (EGFR) trafficking occurs by clathrin-mediated endocytosis and is polarised towards the front of migrating cells. However, we found no role for clathrin-mediated endocytosis in focal adhesion disassembly in this migration model. Thus, this study has characterised the role of endocytosis during chemotactic invasion and has identified functions mechanistically linking clathrin-mediated endocytosis to directed cell motility. PMID:24921075

  18. Linking the tectonic evolution with fluid history in magma-poor rifted margins: tracking mantle- and continental crust-related fluids

    NASA Astrophysics Data System (ADS)

    Pinto, V. H. G.; Manatschal, G.; Karpoff, A. M.

    2014-12-01

    The thinning of the crust and the exhumation of subcontinental mantle is accompanied by a series of extensional detachment faults. Exhumation of mantle and crustal rocks is intimately related to percolation of fluids along detachment faults leading to changes in mineralogy and chemistry of the mantle, crustal and sedimentary rocks. Field observation, analytical methods, refraction/reflection and well-core data, allowed us to investigate the role of fluids in the Iberian margin and former Alpine Tethys distal margins and the Pyrenees rifted system. In the continental crust, fluid-rock interaction leads to saussuritization that produces Si and Ca enriched fluids found in forms of veins along the fault zone. In the zone of exhumed mantle, large amounts of water are absorbed in the first 5-6 km of serpentinized mantle, which has the counter-effect of depleting the mantle of elements (e.g., Si, Ca, Mg, Fe, Mn, Ni and Cr) forming mantle-related fluids. Using Cr-Ni-V and Fe-Mn as tracers, we show that in the distal margin, mantle-related fluids used detachment faults as pathways and interacted with the overlying crust, the sedimentary basin and the seawater, while further inward parts of the margin, continental crust-related fluids enriched in Si and Ca impregnated the fault zone and may have affected the sedimentary basin. The overall observations and results enable us to show when, where and how these interactions occurred during the formation of the rifted margin. In a first stage, continental crust-related fluids dominated the rifted systems. During the second stage, mantle-related fluids affected the overlying syn-tectonic sediments through direct migration along detachment faults at the future distal margin. In a third stage, these fluids reached the seafloor, "polluted" the seawater and were absorbed by post-tectonic sediments. We conclude that a significant amount of serpentinization occurred underneath the thinned continental crust, that the mantle-related fluids might have modified the chemical composition of the sediments and seawater. We propose that the chemical signature of serpentinization that occurs during the mantle exhumation is recorded in the sediments and may serve as a proxy to date serpentinization and mantle exhumation in present day magma-poor rifted margins.

  19. Genetics Home Reference: 3MC syndrome

    MedlinePlus

    ... pathway is thought to help direct the movement (migration) of cells during early development before birth to ... appears to be particularly important in directing the migration of neural crest cells, which give rise to ...

  20. Endothelial cell-derived GABA signaling modulates neuronal migration and postnatal behavior

    PubMed Central

    Li, Suyan; Kumar T, Peeyush; Joshee, Sampada; Kirschstein, Timo; Subburaju, Sivan; Khalili, Jahan S; Kloepper, Jonas; Du, Chuang; Elkhal, Abdallah; Szabó, Gábor; Jain, Rakesh K; Köhling, Rüdiger; Vasudevan, Anju

    2018-01-01

    The cerebral cortex is essential for integration and processing of information that is required for most behaviors. The exquisitely precise laminar organization of the cerebral cortex arises during embryonic development when neurons migrate successively from ventricular zones to coalesce into specific cortical layers. While radial glia act as guide rails for projection neuron migration, pre-formed vascular networks provide support and guidance cues for GABAergic interneuron migration. This study provides novel conceptual and mechanistic insights into this paradigm of vascular-neuronal interactions, revealing new mechanisms of GABA and its receptor-mediated signaling via embryonic forebrain endothelial cells. With the use of two new endothelial cell specific conditional mouse models of the GABA pathway (Gabrb3ΔTie2-Cre and VgatΔTie2-Cre), we show that partial or complete loss of GABA release from endothelial cells during embryogenesis results in vascular defects and impairs long-distance migration and positioning of cortical interneurons. The downstream effects of perturbed endothelial cell-derived GABA signaling are critical, leading to lasting changes to cortical circuits and persistent behavioral deficits. Furthermore, we illustrate new mechanisms of activation of GABA signaling in forebrain endothelial cells that promotes their migration, angiogenesis and acquisition of blood-brain barrier properties. Our findings uncover and elucidate a novel endothelial GABA signaling pathway in the CNS that is distinct from the classical neuronal GABA signaling pathway and shed new light on the etiology and pathophysiology of neuropsychiatric diseases, such as autism spectrum disorders, epilepsy, anxiety, depression and schizophrenia. PMID:29086765

  1. Src promotes cutaneous wound healing by regulating MMP-2 through the ERK pathway.

    PubMed

    Wu, Xue; Yang, Longlong; Zheng, Zhao; Li, Zhenzhen; Shi, Jihong; Li, Yan; Han, Shichao; Gao, Jianxin; Tang, Chaowu; Su, Linlin; Hu, Dahai

    2016-03-01

    Wound healing is a highly orchestrated, multistep process, and delayed wound healing is a significant symptomatic clinical problem. Keratinocyte migration and re-epithelialization play the most important roles in wound healing, as they determine the rate of wound healing. In our previous study, we found that Src, one of the oldest proto‑oncogenes encoding a membrane-associated, non-receptor protein tyrosine kinase, promotes keratinocyte migration. We therefore hypothesized that Src promotes wound healing through enhanced keratinocyte migration. In order to test this hypothesis, vectors for overexpressing Src and small interfering RNAs (siRNAs) for silencing of Src were used in the present study. We found that the overexpression of Src accelerated keratinocyte migration in vitro and promoted wound healing in vivo without exerting a marked effect on cell proliferation. The extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways play important roles in Src-accelerated keratinocyte migration. Further experiments demonstrated that Src induced the protein expression of matrix metalloproteinase-2 (MMP-2) and decreased the protein expression of E-cadherin. We suggest that ERK signaling is involved in the Src-mediated regulation of MMP-2 expression. The present study provided evidence that Src promotes keratinocyte migration and cutaneous wound healing, in which the regulation of MMP-2 through the ERK pathway plays an important role, and thus we also demonstrated a potential therapeutic role for Src in cutaneous wound healing.

  2. Calcium Hydroxide-induced Proliferation, Migration, Osteogenic Differentiation, and Mineralization via the Mitogen-activated Protein Kinase Pathway in Human Dental Pulp Stem Cells.

    PubMed

    Chen, Luoping; Zheng, Lisha; Jiang, Jingyi; Gui, Jinpeng; Zhang, Lingyu; Huang, Yan; Chen, Xiaofang; Ji, Jing; Fan, Yubo

    2016-09-01

    Calcium hydroxide has been extensively used as the gold standard for direct pulp capping in clinical dentistry. It induces proliferation, migration, and mineralization in dental pulp stem cells (DPSCs), but the underlying mechanisms are still unclear. The aim of this study was to investigate the role of the mitogen-activated protein (MAP) kinase pathway in calcium hydroxide-induced proliferation, migration, osteogenic differentiation, and mineralization in human DPSCs. Human DPSCs between passages 3 and 6 were used. DPSCs were preincubated with inhibitors of MAP kinases and cultured with calcium hydroxide. The phosphorylated MAP kinases were detected by Western blot analysis. Cell viability was analyzed via the methylthiazol tetrazolium assay. Cell migration was estimated using the wound healing assay. Alkaline phosphatase (ALP) expression was analyzed using the ALP staining assay. Mineralization was studied by alizarin red staining analysis. Calcium hydroxide significantly promoted the phosphorylation of the c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase. The inhibition of JNK and p38 signaling abolished calcium hydroxide-induced proliferation of DPSCs. The inhibition of JNK, p38, and extracellular signal-regulated kinase signaling suppressed the migration, ALP expression, and mineralization of DPSCs. Our study showed that the MAP kinase pathway was involved in calcium hydroxide-induced proliferation, migration, osteogenic differentiation, and mineralization in human DPSCs. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  3. Notch signaling mediates granulocyte-macrophage colony-stimulating factor priming-induced transendothelial migration of human eosinophils.

    PubMed

    Liu, L Y; Wang, H; Xenakis, J J; Spencer, L A

    2015-07-01

    Priming with cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances eosinophil migration and exacerbates the excessive accumulation of eosinophils within the bronchial mucosa of asthmatics. However, mechanisms that drive GM-CSF priming are incompletely understood. Notch signaling is an evolutionarily conserved pathway that regulates cellular processes, including migration, by integrating exogenous and cell-intrinsic cues. This study investigates the hypothesis that the priming-induced enhanced migration of human eosinophils requires the Notch signaling pathway. Using pan Notch inhibitors and newly developed human antibodies that specifically neutralize Notch receptor 1 activation, we investigated a role for Notch signaling in GM-CSF-primed transmigration of human blood eosinophils in vitro and in the airway accumulation of mouse eosinophils in vivo. Notch receptor 1 was constitutively active in freshly isolated human blood eosinophils, and inhibition of Notch signaling or specific blockade of Notch receptor 1 activation during GM-CSF priming impaired priming-enhanced eosinophil transendothelial migration in vitro. Inclusion of Notch signaling inhibitors during priming was associated with diminished ERK phosphorylation, and ERK-MAPK activation was required for GM-CSF priming-induced transmigration. In vivo in mice, eosinophil accumulation within allergic airways was impaired following systemic treatment with Notch inhibitor, or adoptive transfer of eosinophils treated ex vivo with Notch inhibitor. These data identify Notch signaling as an intrinsic pathway central to GM-CSF priming-induced eosinophil tissue migration. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. WIF1 re-expression in glioblastoma inhibits migration through attenuation of non-canonical WNT signaling by downregulating the lncRNA MALAT1.

    PubMed

    Vassallo, I; Zinn, P; Lai, M; Rajakannu, P; Hamou, M-F; Hegi, M E

    2016-01-07

    Glioblastoma is the most aggressive primary brain tumor in adults and due to the invasive nature cannot be completely removed. The WNT inhibitory factor 1 (WIF1), a secreted inhibitor of WNTs, is systematically downregulated in glioblastoma and acts as strong tumor suppressor. The aim of this study was the dissection of WIF1-associated tumor-suppressing effects mediated by canonical and non-canonical WNT signaling. We found that WIF1 besides inhibiting the canonical WNT pathway selectively downregulates the WNT/calcium pathway associated with significant reduction of p38-MAPK (p38-mitogen-activated protein kinase) phosphorylation. Knockdown of WNT5A, the only WNT ligand overexpressed in glioblastoma, phenocopied this inhibitory effect. WIF1 expression inhibited cell migration in vitro and in an orthotopic brain tumor model, in accordance with the known regulatory function of the WNT/Ca(2+) pathway on migration and invasion. In search of a mediator for this function differential gene expression profiles of WIF1-expressing cells were performed. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA and key positive regulator of invasion, emerged as the top downregulated gene. Indeed, knockdown of MALAT1 reduced migration in glioblastoma cells, without effect on proliferation. Hence, loss of WIF1 enhances the migratory potential of glioblastoma through WNT5A that activates the WNT/Ca(2+) pathway and MALAT1. These data suggest the involvement of canonical and non-canonical WNT pathways in glioblastoma promoting key features associated with this deadly disease, proliferation on one hand and invasion on the other. Successful targeting will require a dual strategy affecting both canonical and non-canonical WNT pathways.

  5. Irisin suppresses the migration, proliferation, and invasion of lung cancer cells via inhibition of epithelial-to-mesenchymal transition

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shao, Lei; Jinan Central Hospital Affiliated to Shandong University, Jinan, 250012; Li, Huanjie

    Irisin is involved in promoting metabolism, immune regulation, and affects chronic inflammation in many systemic diseases, including gastric cancer. However, the role of irisin in lung cancer is not well characterized. To determine whether irisin has a protective effect against lung cancer, we cultured A549 and NCI-H446 lung cancer cells and treated them with irisin. We detected the proliferation by MTT assay, and assessed the migration and invasion of the cells by scratch wound healing assay and Tran-swell assay. The expression levels of epithelial-to-mesenchymal transition (EMT) markers and the related signaling pathways were detected by western blot analysis. Meanwhile, anmore » inhibitor of PI3K was used to investigate the effect of irsin. Finally, the expression of Snail was detected. We demonstrated that irisin inhibits the proliferation, migration, and invasion of lung cancer cells, and has a novel role in mediating the PI3K/AKT pathway in the cells. Irisin can reverse the activity of EMT and inhibit the expression of Snail via mediating the PI3K/AKT pathway, which is a key regulator of Snail. These results revealed that irisin inhibited EMT and reduced the invasion of lung cancer cells via the PI3K/AKT/Snail pathway. - Highlights: • Irisin inhibits the proliferation of lung cancer cells. • Irisin inhibits the migration and invasion of lung cancer cells. • Irisin affects the expression of EMT markers via inhibiting the PI3K/AKT pathway in lung cancer cells. • Irisin induces Snail downregulation via PI3K/AKT pathway activation.« less

  6. Fluid-faulting evolution in high definition: Connecting fault structure and frequency-magnitude variations during the 2014 Long Valley Caldera, California earthquake swarm

    USGS Publications Warehouse

    Shelly, David R.; Ellsworth, William L.; Hill, David P.

    2016-01-01

    An extended earthquake swarm occurred beneath southeastern Long Valley Caldera between May and November 2014, culminating in three magnitude 3.5 earthquakes and 1145 cataloged events on 26 September alone. The swarm produced the most prolific seismicity in the caldera since a major unrest episode in 1997-1998. To gain insight into the physics controlling swarm evolution, we used large-scale cross-correlation between waveforms of cataloged earthquakes and continuous data, producing precise locations for 8494 events, more than 2.5 times the routine catalog. We also estimated magnitudes for 18,634 events (~5.5 times the routine catalog), using a principal component fit to measure waveform amplitudes relative to cataloged events. This expanded and relocated catalog reveals multiple episodes of pronounced hypocenter expansion and migration on a collection of neighboring faults. Given the rapid migration and alignment of hypocenters on narrow faults, we infer that activity was initiated and sustained by an evolving fluid pressure transient with a low-viscosity fluid, likely composed primarily of water and CO2 exsolved from underlying magma. Although both updip and downdip migration were observed within the swarm, downdip activity ceased shortly after activation, while updip activity persisted for weeks at moderate levels. Strongly migrating, single-fault episodes within the larger swarm exhibited a higher proportion of larger earthquakes (lower Gutenberg-Richter b value), which may have been facilitated by fluid pressure confined in two dimensions within the fault zone. In contrast, the later swarm activity occurred on an increasingly diffuse collection of smaller faults, with a much higher b value.

  7. Clathrin light chains are required for the gyrating-clathrin recycling pathway and thereby promote cell migration.

    PubMed

    Majeed, Sophia R; Vasudevan, Lavanya; Chen, Chih-Ying; Luo, Yi; Torres, Jorge A; Evans, Timothy M; Sharkey, Andrew; Foraker, Amy B; Wong, Nicole M L; Esk, Christopher; Freeman, Theresa A; Moffett, Ashley; Keen, James H; Brodsky, Frances M

    2014-05-23

    The clathrin light chain (CLC) subunits participate in several membrane traffic pathways involving both clathrin and actin, through binding the actin-organizing huntingtin-interacting proteins (Hip). However, CLCs are dispensable for clathrin-mediated endocytosis of many cargoes. Here we observe that CLC depletion affects cell migration through Hip binding and reduces surface expression of β1-integrin by interference with recycling following normal endocytosis of inactive β1-integrin. CLC depletion and expression of a modified CLC also inhibit the appearance of gyrating (G)-clathrin structures, known mediators of rapid recycling of transferrin receptor from endosomes. Expression of the modified CLC reduces β1-integrin and transferrin receptor recycling, as well as cell migration, implicating G-clathrin in these processes. Supporting a physiological role for CLC in migration, the CLCb isoform of CLC is upregulated in migratory human trophoblast cells during uterine invasion. Together, these studies establish CLCs as mediating clathrin-actin interactions needed for recycling by G-clathrin during migration.

  8. Determining the Area of Review for Industrial Waste Disposal Wells.

    DTIC Science & Technology

    1981-12-01

    pressure increases sufficiently to force formation fluids and/or injected wastes up abandoned well bores to contaminate underground sources of drinking...Drilling Mud Circulating System . . 72 9. Increase in Gel Strength of Various Mud Types With Time . . . . . . . . . . . . . . . . . . 96 10. Gel... increased fluid pressure in a disposal zone which results from a waste injection operation may force injected and/or formation fluid to migrate up an

  9. Planar polarity pathway and Nance-Horan syndrome-like 1b have essential cell-autonomous functions in neuronal migration.

    PubMed

    Walsh, Gregory S; Grant, Paul K; Morgan, John A; Moens, Cecilia B

    2011-07-01

    Components of the planar cell polarity (PCP) pathway are required for the caudal tangential migration of facial branchiomotor (FBM) neurons, but how PCP signaling regulates this migration is not understood. In a forward genetic screen, we identified a new gene, nhsl1b, required for FBM neuron migration. nhsl1b encodes a WAVE-homology domain-containing protein related to human Nance-Horan syndrome (NHS) protein and Drosophila GUK-holder (Gukh), which have been shown to interact with components of the WAVE regulatory complex that controls cytoskeletal dynamics and with the polarity protein Scribble, respectively. Nhsl1b localizes to FBM neuron membrane protrusions and interacts physically and genetically with Scrib to control FBM neuron migration. Using chimeric analysis, we show that FBM neurons have two modes of migration: one involving interactions between the neurons and their planar-polarized environment, and an alternative, collective mode involving interactions between the neurons themselves. We demonstrate that the first mode of migration requires the cell-autonomous functions of Nhsl1b and the PCP components Scrib and Vangl2 in addition to the non-autonomous functions of Scrib and Vangl2, which serve to polarize the epithelial cells in the environment of the migrating neurons. These results define a role for Nhsl1b as a neuronal effector of PCP signaling and indicate that proper FBM neuron migration is directly controlled by PCP signaling between the epithelium and the migrating neurons.

  10. Planar polarity pathway and Nance-Horan syndrome-like 1b have essential cell-autonomous functions in neuronal migration

    PubMed Central

    Walsh, Gregory S.; Grant, Paul K.; Morgan, John A.; Moens, Cecilia B.

    2011-01-01

    Components of the planar cell polarity (PCP) pathway are required for the caudal tangential migration of facial branchiomotor (FBM) neurons, but how PCP signaling regulates this migration is not understood. In a forward genetic screen, we identified a new gene, nhsl1b, required for FBM neuron migration. nhsl1b encodes a WAVE-homology domain-containing protein related to human Nance-Horan syndrome (NHS) protein and Drosophila GUK-holder (Gukh), which have been shown to interact with components of the WAVE regulatory complex that controls cytoskeletal dynamics and with the polarity protein Scribble, respectively. Nhsl1b localizes to FBM neuron membrane protrusions and interacts physically and genetically with Scrib to control FBM neuron migration. Using chimeric analysis, we show that FBM neurons have two modes of migration: one involving interactions between the neurons and their planar-polarized environment, and an alternative, collective mode involving interactions between the neurons themselves. We demonstrate that the first mode of migration requires the cell-autonomous functions of Nhsl1b and the PCP components Scrib and Vangl2 in addition to the non-autonomous functions of Scrib and Vangl2, which serve to polarize the epithelial cells in the environment of the migrating neurons. These results define a role for Nhsl1b as a neuronal effector of PCP signaling and indicate that proper FBM neuron migration is directly controlled by PCP signaling between the epithelium and the migrating neurons. PMID:21693519

  11. Forming Hot Jupiters: Observational Constraints on Gas Giant Formation and migration

    NASA Astrophysics Data System (ADS)

    Becker, Juliette; Vanderburg, Andrew; Adams, Fred C.; Khain, Tali; Bryan, Marta

    2018-04-01

    Since the first extrasolar planets were detected, the existence of hot Jupiters has challenged prevailing theories of planet formation. The three commonly considered pathways for hot Jupiter formation are in situ formation, runaway accretion in the outer disk followed by disk migration, and tidal migration (occurring after the disk has dissipated). None of these explains the entire observed sample of hot Jupiters, suggesting that different selections of systems form via different pathways. The way forward is to use observational data to constrain the migration pathways of particular classes of systems, and subsequently assemble these results into a coherent picture of hot Jupiter formation. We present constraints on the migratory pathway for one particular type of system: hot Jupiters orbiting cool stars (T< 6200 K). Using the full observational sample, we find that the orbits of most wide planetary companions to hot Jupiters around these cool stars must be well aligned with the orbits of the hot Jupiters and the spins of the host stars. The population of systems containing both a hot Jupiter and an exterior companion around a cool star thus generally exist in roughly coplanar configurations, consistent with the idea that disk-driven migratory mechanisms have assembled most of this class of systems. We then discuss the overall applicability of this result to a wider range of systems and the broader implications on planet formation.

  12. An early colonisation pathway into northwest Australia 70-60,000 years ago

    NASA Astrophysics Data System (ADS)

    Norman, Kasih; Inglis, Josha; Clarkson, Chris; Faith, J. Tyler; Shulmeister, James; Harris, Daniel

    2018-01-01

    Colonisation of Sahul 70-60 thousand years ago (kya) represents the first great maritime migration undertaken by anatomically modern humans in one of the final phases of the Out of Africa dispersal. Visual connectivity network analyses, agent-based simulations and ocean current modelling reveal that modern humans could follow numerous northern and southern migration pathways into Sahul. Our results support a southern route out of Africa through South Asia with entry into ISEA through the Banda Arc, culminating in an early colonisation of Sahul on the northwest shelf. Our results show multiple colonisation events through other entry points were also probable, and raise interesting possibilities for complex regional migration and population histories.

  13. Methane seepage along the Hikurangi Margin offshore New Zealand: 6 years of multidisciplinary studies

    NASA Astrophysics Data System (ADS)

    Greinert, J.; Bialas, J.; Klaucke, I.; Crutchley, G.; Dale, A.; Linke, P.; Sommer, S.; Bowden, D.; Rowden, A.; de Haas, H.; de Stigter, H.; Faure, K.

    2012-12-01

    Detailed studies in 2006, 2007 and 2011 along the east coast of New Zealand's North Island highlighted the close link of sub-bottom fluid pathways and seafloor expressions of methane seepage such as clam fields, carbonate build-ups, tubeworms, bacterial mats and methane release (Marine Geology 272). Prior to our studies, only accidental observations of hydroacoustic anomalies, recoveries of calyptogena shells and methane-derived carbonate chimneys indicated active seepage. Wide areas of the sub-seafloor show BSR structures, gas migration pathways, gas chimneys and blanking zones, which are closely linked to actual seep sites. Sidescan surveys showed four prominent seep areas at Omakere Ridge in 1120m water depth, three of them perfectly matching the shapes and locations of faults seen in high resolution 3D-seismic surveys. The fourth seep, Bear's Paw, on its western side represents an old seep which developed into a cold water coral habitat. At the actively seeping eastern part, gas hydrates could be retrieved and bubble release was observed hydroacoustically and confirmed by high dissolved methane values (380nM). No strong microbial oxidation effects could be found in δ13C values plotting along a mixing curve between pure seep (-70 ‰PDB) and atmospheric methane (-47 ‰PDB). Lander deployments show a tide-influenced gas discharge with sometimes eruptive bubble release with possible plume development transporting methane-charged water higher up into the water column. Rock Garden, with just above 600m water depth at its top outside the gas hydrate stability zone, hosts two main seep areas. ROV observations at Faure Site document eruptive releases of free gas from decimeter-wide craters at the seafloor. Flux estimates show peak releases of 420ml/min with bubbles up to 9mm in diameter. Concentrations of dissolved methane reach up to 3500nM close to the bottom, but higher concentrations are limited to below 400m of water depth; here, methane is transported towards the sea surface or even into the mixed layer. Faure site is just at the limit of the gas hydrate phase boundary, where relatively high-permeable sediment layers act as preferred pathway for fluids from below a shallow BSR. Seismic studies at the seep site LM-3 show gas chimneys as main fluid migration pathways in the sub-seafloor. Opouawe Bank has the densest occurrence of seeps. In water depths between 800 and 1200m, seeps of different ages and appearances exist in close proximity. North and South Tower resemble old structures with massive aragonitic carbonate blocks paving the seafloor, tube worms, bacterial mats, clams and beds of ampharetid polychaetes. These patchy polychaetes habitats have a very high total oxygen uptake of up to 83.7 mmol m^-2 day^-1) feeding from organic carbon generated via aerobic methane oxidation. Hydroacoustic flares at the 1200m deep Towers rise more than 600m into the water column above, which the dissolved gas concentrations quickly drop to background. In contrast, the isolated Takahe seep only 2 miles away shows no carbonates at the seafloor surface despite a well developed acoustic gas chimney and surface-near gas hydrates. This seep represents a much younger seep which highlights the great spatial and temporal variability in seep occurrences and activity, which can also be found in fossil seeps on land.

  14. Development of a microfluidics model for studying migration of sperm in the female reproductive tract

    NASA Astrophysics Data System (ADS)

    Tung, Chih-Kuan; Ardón, Florencia; Wu, Mingming; Suárez, Susan

    2013-03-01

    Infertility is a significant issue, both for humans and dairy cattle. In order for fertilization to happen, sperm must migrate through the female reproductive tract to reach the egg in the oviduct (fallopian tube). There is strong evidence that sperm interact with the female tract via both chemical and physical mechanisms. In this work, we focus on how the physical environment of the female tract influences the migration of bull sperm, which also serve as models for human sperm. In order for bull and human sperm to pass from the vagina into the uterus, they must swim through the cervical canal, which is lined by microchannels. Then, sperm must swim through the uterotubal junction, which also contains microchannels, in order to reach the oviduct. In both passageways, sperm must swim against a fluid flow, which would be less in the microchannels than in the central passageways. We have developed a microfluidic model for studying the sperm migration effects of the geometry of the cervix and uterotubal junction and the fluid flow within. Supported by NIH grant 1R01HD070038.

  15. The SH3BGR/STAT3 Pathway Regulates Cell Migration and Angiogenesis Induced by a Gammaherpesvirus MicroRNA

    PubMed Central

    Ding, Xiangya; Shen, Chenyou; Hu, Minmin; Zhu, Ying; Qin, Di; Lu, Hongmei; Krueger, Brian J.; Renne, Rolf; Gao, Shou-Jiang; Lu, Chun

    2016-01-01

    Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) is a gammaherpesvirus etiologically associated with KS, a highly disseminated angiogenic tumor of hyperproliferative spindle endothelial cells. KSHV encodes 25 mature microRNAs but their roles in KSHV-induced tumor dissemination and angiogenesis remain unknown. Here, we investigated KSHV-encoded miR-K12-6-3p (miR-K6-3p) promotion of endothelial cell migration and angiogenesis, which are the underlying mechanisms of tumor dissemination and angiogenesis. We found that ectopic expression of miR-K6-3p promoted endothelial cell migration and angiogenesis. Mass spectrometry, bioinformatics and luciferase reporter analyses revealed that miR-K6-3p directly targeted sequence in the 3’ untranslated region (UTR) of SH3 domain binding glutamate-rich protein (SH3BGR). Overexpression of SH3BGR reversed miR-K6-3p induction of cell migration and angiogenesis. Mechanistically, miR-K6-3p downregulated SH3BGR, hence relieved STAT3 from SH3BGR direct binding and inhibition, which was required for miR-K6-3p maximum activation of STAT3 and induction of cell migration and angiogenesis. Finally, deletion of miR-K6 from the KSHV genome abrogated its effect on the SH3BGR/STAT3 pathway, and KSHV-induced migration and angiogenesis. Our results illustrated that, by inhibiting SH3BGR, miR-K6-3p enhances cell migration and angiogenesis by activating the STAT3 pathway, and thus contributes to the dissemination and angiogenesis of KSHV-induced malignancies. PMID:27128969

  16. Red wine consumption improves in vitro migration of endothelial progenitor cells in young, healthy individuals.

    PubMed

    Hamed, Saher; Alshiek, Jonia; Aharon, Anat; Brenner, Benjamin; Roguin, Ariel

    2010-07-01

    Endothelial progenitor cells (EPCs) contribute to the maintenance of vascular endothelial function. The moderate consumption of red wine provides cardiovascular protection. We investigated the underlying molecular mechanism of EPC migration in young, healthy individuals who drank red wine. Fourteen healthy volunteers consumed 250 mL red wine daily for 21 consecutive days. Vascular endothelial function, plasma stromal cell-derived factor 1alpha (SDF1alpha) concentrations, and the number, migration, and nitric oxide production of EPCs were determined before and after the daily consumption of red wine. EPCs were glucose stressed to study the effect of red wine on EPC migration, proliferation, and senescence and to study the expressions of CXC chemokine receptor 4 (CXCR4) and members of the Pi3K/Akt/eNOS (phosphatidylinositol 3-kinase/protein kinase B/endothelial nitric oxide synthase) signaling pathway by Western blotting. Daily red wine consumption for 21 consecutive days significantly enhanced vascular endothelial function. Although plasma SDF1alpha concentrations were unchanged, EPC count and migration were significantly increased after this 21-d consumption period. Red wine increased the migration, proliferation, CXCR4 expression, and activity of the Pi3K/Akt/eNOS signaling pathway and decreased the extent of apoptosis in glucose-stressed EPCs. The results of the present study indicate that red wine exerts its effect through the up-regulation of CXCR4 expression and activation of the SDF1alpha/CXCR4/Pi3K/Akt/eNOS signaling pathway, which results in increased EPC migration and proliferation and decreased extent of apoptosis. Our findings suggest that these effects could be linked to the mechanism of cardiovascular protection that is associated with the regular consumption of red wine.

  17. Inhibition of cell migration by focal adhesion kinase: Time-dependent difference in integrin-induced signaling between endothelial and hepatoblastoma cells.

    PubMed

    Yu, Hongchi; Gao, Min; Ma, Yunlong; Wang, Lijuan; Shen, Yang; Liu, Xiaoheng

    2018-05-01

    angiogenesis plays an important role in the development and progression of tumors, and it involves a series of signaling pathways contributing to the migration of endothelial cells for vascularization and to the invasion of cancer cells for secondary tumor formation. Among these pathways, the focal adhesion kinase (FAK) signaling cascade has been implicated in a variety of human cancers in connection with cell adhesion and migration events leading to tumor angiogenesis, metastasis and invasion. Therefore, the inhibition of FAK in endothelial and/or cancer cells is a potential target for anti‑angiogenic therapy. In the present study, a small‑molecule FAK inhibitor, 1,2,4,5-benzenetetramine tetrahydrochloride (Y15), was used to study the effects of FAK inhibition on the adhesion and migration behaviors of vascular endothelial cells (VECs) and human hepatoblastoma cells. Furthermore, the time-dependent differences in proteins associated with the integrin-mediated FAK/Rho GTPases signaling pathway within 2 h were examined. The results indicated that the inhibition of FAK significantly decreased the migration ability of VECs and human hepatoblastoma cells in a dose-dependent manner. Inhibition of FAK promoted cell detachment by decreasing the expression of focal adhesion components, and blocked cell motility by reducing the level of Rho GTPases. However, the expression of crucial proteins involved in integrin-induced signaling in two cell lines exhibited a time-dependent difference with increased duration of FAK inhibitor treatment, suggesting different mechanisms of FAK-mediated cell migration behavior. These results suggest that the mechanism underlying FAK-mediated adhesion and migration behavior differs among various cells, which is expected to provide evidence for future FAK therapy targeted against tumor angiogenesis.

  18. Combination of Cyclopamine and Tamoxifen Promotes Survival and Migration of MCF-7 Breast Cancer Cells – Interaction of Hedgehog-Gli and Estrogen Receptor Signaling Pathways

    PubMed Central

    Uzarevic, Zvonimir; Ozretic, Petar; Musani, Vesna; Rafaj, Maja; Cindric, Mario; Levanat, Sonja

    2014-01-01

    Hedgehog-Gli (Hh-Gli) signaling pathway is one of the new molecular targets found upregulated in breast tumors. Estrogen receptor alpha (ERα) signaling has a key role in the development of hormone-dependent breast cancer. We aimed to investigate the effects of inhibiting both pathways simultaneously on breast cancer cell survival and the potential interactions between these two signaling pathways. ER-positive MCF-7 cells show decreased viability after treatment with cyclopamine, a Hh-Gli pathway inhibitor, as well as after tamoxifen (an ERα inhibitor) treatment. Simultaneous treatment with cyclopamine and tamoxifen on the other hand, causes short-term survival of cells, and increased migration. We found upregulated Hh-Gli signaling under these conditions and protein profiling revealed increased expression of proteins involved in cell proliferation and migration. Therefore, even though Hh-Gli signaling seems to be a good potential target for breast cancer therapy, caution must be advised, especially when combining therapies. In addition, we also show a potential direct interaction between the Shh protein and ERα in MCF-7 cells. Our data suggest that the Shh protein is able to activate ERα independently of the canonical Hh-Gli signaling pathway. Therefore, this may present an additional boost for ER-positive cells that express Shh, even in the absence of estrogen. PMID:25503972

  19. Revealing fate of CO2 leakage pathways in the Little Grand Wash Fault, Green River, Utah

    NASA Astrophysics Data System (ADS)

    Han, K.; Han, W. S.; Watson, Z. T.; Guyant, E.; Park, E.

    2015-12-01

    To assure long-term security of geologic carbon sequestration site, evaluation of natural CO2 leakage should be preceded before actual construction of the CO2 facility by comparing natural and artificial reservoir systems. The Little Grand Wash fault is located at the northwestern margin of the Paradox Basin and roles on a bypass of deep subsurface CO2 and brine water onto the surface, e.g., cold water geyser, CO2 spring, and surface travertine deposits. CO2 degassed out from brine at the Little Grand Wash fault zone may react with formation water and minerals while migrating through the fault conduit. Leakage observed by soil CO2 flux on the fault trace shows this ongoing transition of CO2, from supersaturated condition in deep subsurface to shallow surface equilibria. The present study aims to investigate the reactions induced by changes in hydrological and mineralogical factors inside of the fault zone. The methodology to develop site-specific geochemical model of the Little Grand Wash Fault combines calculated mechanical movements of each fluid end-member, along with chemical reactions among fluid, free CO2 gas and rock formations. Reactive transport modeling was conducted to simulate these property changes inside of the fault zone, using chemistry dataset based on 86 effluent samples of CO2 geysers, springs and in situ formation water from Entrada, Carmel, and Navajo Sandstone. Meanwhile, one- and two-dimensional models were separately developed to delineate features mentioned above. The results from the 3000-year simulation showed an appearance of self-sealing processes near the surface of the fault conduit. By tracking physicochemical changes at the depth of 15 m on the 2-dimensional model, significant changes induced by fluid mixing were indicated. Calculated rates of precipitation for calcite, illite, and pyrite showed increase in 2.6 x 10-4, 2.25 x 10-5, and 3.0 x 10-6 in mineral volume fraction at the depth of 15m, respectively. Concurrently, permeability and porosity were decreased 4.0 x 10-18 m2 and 3.0 x 10-4 due to precipitation of minerals. At the middle of the fault conduit (400 m), however, indicates consistent dissolution of minerals in formation which enhances vertical fluid migration.

  20. Brief Report: Robo1 Regulates the Migration of Human Subventricular Zone Neural Progenitor Cells During Development.

    PubMed

    Guerrero-Cazares, Hugo; Lavell, Emily; Chen, Linda; Schiapparelli, Paula; Lara-Velazquez, Montserrat; Capilla-Gonzalez, Vivian; Clements, Anna Christina; Drummond, Gabrielle; Noiman, Liron; Thaler, Katrina; Burke, Anne; Quiñones-Hinojosa, Alfredo

    2017-07-01

    Human neural progenitor cell (NPC) migration within the subventricular zone (SVZ) of the lateral ganglionic eminence is an active process throughout early brain development. The migration of human NPCs from the SVZ to the olfactory bulb during fetal stages resembles what occurs in adult rodents. As the human brain develops during infancy, this migratory stream is drastically reduced in cell number and becomes barely evident in adults. The mechanisms regulating human NPC migration are unknown. The Slit-Robo signaling pathway has been defined as a chemorepulsive cue involved in axon guidance and neuroblast migration in rodents. Slit and Robo proteins expressed in the rodent brain help guide neuroblast migration from the SVZ through the rostral migratory stream to the olfactory bulb. Here, we present the first study on the role that Slit and Robo proteins play in human-derived fetal neural progenitor cell migration (hfNPC). We describe that Robo1 and Robo2 isoforms are expressed in the human fetal SVZ. Furthermore, we demonstrate that Slit2 is able to induce a chemorepellent effect on the migration of hfNPCs derived from the human fetal SVZ. In addition, when Robo1 expression is inhibited, hfNPCs are unable to migrate to the olfactory bulb of mice when injected in the anterior SVZ. Our findings indicate that the migration of human NPCs from the SVZ is partially regulated by the Slit-Robo axis. This pathway could be regulated to direct the migration of NPCs in human endogenous neural cell therapy. Stem Cells 2017;35:1860-1865. © 2017 AlphaMed Press.

  1. Subglacial geomorphology reveals connections between glacial dynamics and deeper hydrocarbon reservoir leakages at the Polar north Atlantic continental margin

    NASA Astrophysics Data System (ADS)

    Andreassen, Karin; Deryabin, Alexey; Rafaelsen, Bjarne; Richarsen, Morten

    2014-05-01

    Three-dimensional (3D) seismic data from the Barents Sea continental shelf and margin reveal spatial links between subsurface distributions of inferred glacitectonic geomorphic landforms and seismic indications of fluid flow from deeper hydrocarbon reservoirs. Particularly 3D seismic techniques allow detailed mapping and visualization of buried glacial geomorphology and geophysical indications of fluid flow and gas accumulations. Several subsurface glacitectonic landforms show pronounced depressions up to 200 m deep and several km wide. These appear in many locations just upstream from hills of similar sizes and volumes, and are inferred to be hill-hole pairs. The hills are interpreted as thrusted and compressed slabs of sediments and bedrock which have been removed from their original location by moving glaciers during the last glacial, leaving the holes as depressions. The mapped depressions seem often to appear in sediments of different lithology and age. The appearance of mega-scale glacial lineations indicates that fast-flowing ice streams, draining the former Barents Sea and Fennoscandian ice sheets were the main agents of these glacitectonic landforms. Mapped fluid flow migration pathways from deeper reservoirs and shallow gas accumulations show evidence of active fluid migration systems over longer time periods, and their spatial relationship with the glacitectonic landforms is documented for several areas of the Barents Sea continental shelf. A conceptual model is proposed for the depressions, where brittle glacitectonic deformation takes place along a weak layer at the base of gas-hydrate cemented sediments. Fluid flow from deeper hydrocarbon reservoirs is inferred to be associated with cycles of glaciations and unloading due to glacial erosion and ice retreat, causing gas to expand, which in turn potentially breaks the traps, reactivates faults and creates new faults. Gas hydrate stability modeling indicates that the south-western Barents Sea is today outside the stability area for methane gas hydrates of structure I, but hydrates of this type would have been stable when grounded ice covered the area. Structure II hydrates, with a few percent of heavier hydrocarbons are likely stable within the area today. Acknowledgements. This research is part of the Centre of Excellence for Gas Hydrate, Environment and Climate (CAGE) funded by the Research Council of Norway (RCN) grant 223259. It is also a contribution to the project "Glaciations in the Barents Sea area (GlaciBar)" RCN grant 20067 and to the Research Centre for Arctic Petroleum Exploration (ARCEx) RCN grant 228107.

  2. Migration of magnetotactic bacteria in porous media.

    PubMed

    Rismani Yazi, Saeed; Nosrati, Reza; Stevens, Corey A; Vogel, David; Escobedo, Carlos

    2018-01-01

    Magnetotactic bacteria (MTB) migrate in complex porous sediments where fluid flow is ubiquitous. Here, we demonstrate that magnetotaxis enables MTB to migrate effectively through porous micromodels. Directed MTB can circumvent curved obstacles by traveling along the boundaries and pass flat obstacles by repeatedly switching between forward and backward runs. Magnetotaxis enables directed motion of MTB through heterogeneous porous media, overcoming tortuous flow fields with local velocities as high as 250  μ m s -1 . Our findings bring new insights into the migration behaviour of MTB in their natural habitats and their potential in vivo applications as microbiorobots.

  3. Rubus idaeus Inhibits Migration and Invasion of Human Nasopharyngeal Carcinoma Cells by Suppression of MMP-2 through Modulation of the ERK1/2 Pathway.

    PubMed

    Hsin, Chung-Han; Huang, Cheng-Chen; Chen, Pei-Ni; Hsieh, Yih-Shou; Yang, Shun-Fa; Ho, Yu-Ting; Lin, Chiao-Wen

    2017-01-01

    Nasopharyngeal carcinoma (NPC) is characterized by a high incidence of metastasis in the neck lymph nodes, resulting in a poor prognosis and posing challenges for treatment. In this study, we investigated the in vitro antimetastatic properties of Rubus idaeus extract (RIE) on human nasopharyngeal carcinoma cells. HONE-1, NPC-39 and NPC-BM cells were subjected to RIE treatment, and effects on the migration and invasion of tumor cells were analyzed. The results showed that RIE suppressed the migration and invasion of NPC cells. Gelatin zymography assay, Western blotting and real-time PCR showed that matrix metalloproteinases-2 (MMP-2) enzyme activity, protein expression and mRNA levels were down-regulated by RIE treatment. To identify the signaling pathway, mitogen-activated protein kinase proteins were examined, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of RIE. In summary, our data showed that RIE inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by down-regulating the ERK1/2 signaling pathway, suggesting that Rubus idaeus may serve as chemotherapeutic and chemopreventive agent for NPC.

  4. TRIM25 blockade by RNA interference inhibited migration and invasion of gastric cancer cells through TGF-β signaling.

    PubMed

    Zhu, Zhenya; Wang, Yong; Zhang, Chunhui; Yu, Shiyong; Zhu, Qi; Hou, Kun; Yan, Bo

    2016-01-12

    Tripartite Motif Containing 25 (TRIM25), a member of TRIM proteins, has been found abnormally expressed in cancers of female reproductive system. Here, TRIM25 was conspicuously expressed in human gastric cancer (GC) tissues in which its higher expression generally correlated with the poor prognosis of patients. Small interfering RNA (siRNA)-mediated knockdown of TRIM25 expression in MGC-803 and AGS cells had no effects on cell proliferation, whereas reduced cell migration and invasion. Gene set enrichment analysis on The Cancer Genome Atlas stomach adenocarcinoma (STAD) dataset revealed that several signaling pathways, including the migration, E-cadherin and transforming growth factor-β (TGF-β) pathways, were enriched in TRIM25 higher expression patients. Moreover, ectopic expression of TRIM25 in a GC cell line with lower expression of TRIM25 significantly promoted the migration and invasion. Further experiments with TGF-β inhibitor suggested that TRIM25 may exert its function through TGF-β pathway. In summary, our results indicate that TRIM25 acts as an oncogene in GC and thus presents a novel target for the detection and treatment of GC.

  5. TRIM25 blockade by RNA interference inhibited migration and invasion of gastric cancer cells through TGF-β signaling

    PubMed Central

    Zhu, Zhenya; Wang, Yong; Zhang, Chunhui; Yu, Shiyong; Zhu, Qi; Hou, Kun; Yan, Bo

    2016-01-01

    Tripartite Motif Containing 25 (TRIM25), a member of TRIM proteins, has been found abnormally expressed in cancers of female reproductive system. Here, TRIM25 was conspicuously expressed in human gastric cancer (GC) tissues in which its higher expression generally correlated with the poor prognosis of patients. Small interfering RNA (siRNA)-mediated knockdown of TRIM25 expression in MGC-803 and AGS cells had no effects on cell proliferation, whereas reduced cell migration and invasion. Gene set enrichment analysis on The Cancer Genome Atlas stomach adenocarcinoma (STAD) dataset revealed that several signaling pathways, including the migration, E-cadherin and transforming growth factor-β (TGF-β) pathways, were enriched in TRIM25 higher expression patients. Moreover, ectopic expression of TRIM25 in a GC cell line with lower expression of TRIM25 significantly promoted the migration and invasion. Further experiments with TGF-β inhibitor suggested that TRIM25 may exert its function through TGF-β pathway. In summary, our results indicate that TRIM25 acts as an oncogene in GC and thus presents a novel target for the detection and treatment of GC. PMID:26754079

  6. Rab14 and Its Exchange Factor FAM116 Link Endocytic Recycling and Adherens Junction Stability in Migrating Cells

    PubMed Central

    Linford, Andrea; Yoshimura, Shin-ichiro; Bastos, Ricardo Nunes; Langemeyer, Lars; Gerondopoulos, Andreas; Rigden, Daniel J.; Barr, Francis A.

    2012-01-01

    Summary Rab GTPases define the vesicle trafficking pathways underpinning cell polarization and migration. Here, we find that Rab4, Rab11, and Rab14 and the candidate Rab GDP-GTP exchange factors (GEFs) FAM116A and AVL9 are required for cell migration. Rab14 and its GEF FAM116A localize to and act on an intermediate compartment of the transferrin-recycling pathway prior to Rab11 and after Rab5 and Rab4. This Rab14 intermediate recycling compartment has specific functions in migrating cells discrete from early and recycling endosomes. Rab14-depleted cells show increased N-cadherin levels at junctional complexes and cannot resolve cell-cell junctions. This is due to decreased shedding of cell-surface N-cadherin by the ADAM family protease ADAM10/Kuzbanian. In FAM116A- and Rab14-depleted cells, ADAM10 accumulates in a transferrin-positive endocytic compartment, and the cell-surface level of ADAM10 is correspondingly reduced. FAM116 and Rab14 therefore define an endocytic recycling pathway needed for ADAM protease trafficking and regulation of cell-cell junctions. PMID:22595670

  7. Numerical modeling of fluid migration in subduction zones

    NASA Astrophysics Data System (ADS)

    Walter, M. J.; Quinteros, J.; Sobolev, S. V.

    2015-12-01

    It is well known that fluids play a crucial role in subduction evolution. For example, mechanical weakening along tectonic interfaces, due to high fluid pressure, may enable oceanic subduction. Hence, the fluid content seems to be a critical parameter for subduction initiation. Studies have also shown a correlation between the location of slab dehydration and intermediate seismic activity. Furthermore, expelled fluids from the subduction slab affect the melting temperature, consequently, contributing to partial melting in the wedge above the down-going plate and extensive volcanism. In summary, fluids have a great impact on tectonic processes and therefore should be incorporated into geodynamic numerical models. Here we use existing approaches to couple and solve fluid flow equations in the SLIM-3D thermo-mechanical code. SLIM-3D is a three-dimensional thermo-mechanical code capable of simulating lithospheric deformation with elasto-visco-plastic rheology. It has been successfully applied to model geodynamic processes at different tectonic settings, including subduction zones. However, although SLIM-3D already includes many features, fluid migration has not been incorporated into the model yet. To this end, we coupled solid and fluid flow assuming that fluids flow through a porous and deformable solid. Thereby, we introduce a two-phase flow into the model, in which the Stokes flow is coupled with the Darcy law for fluid flow. Ultimately, the evolution of porosity is governed by a compaction pressure and the advection of the porous solid. We show the details of our implementation of the fluid flow into the existing thermo-mechanical finite element code and present first results of benchmarks and experiments. We are especially interested in the coupling of subduction processes and the evolution of the magmatic arc. Thereby, we focus on the key factors controlling magma emplacement and its influence on subduction processes.

  8. Identifying Conventionally Sub-Seismic Faults in Polygonal Fault Systems

    NASA Astrophysics Data System (ADS)

    Fry, C.; Dix, J.

    2017-12-01

    Polygonal Fault Systems (PFS) are prevalent in hydrocarbon basins globally and represent potential fluid pathways. However the characterization of these pathways is subject to the limitations of conventional 3D seismic imaging; only capable of resolving features on a decametre scale horizontally and metres scale vertically. While outcrop and core examples can identify smaller features, they are limited by the extent of the exposures. The disparity between these scales can allow for smaller faults to be lost in a resolution gap which could mean potential pathways are left unseen. Here the focus is upon PFS from within the London Clay, a common bedrock that is tunnelled into and bears construction foundations for much of London. It is a continuation of the Ieper Clay where PFS were first identified and is found to approach the seafloor within the Outer Thames Estuary. This allows for the direct analysis of PFS surface expressions, via the use of high resolution 1m bathymetric imaging in combination with high resolution seismic imaging. Through use of these datasets surface expressions of over 1500 faults within the London Clay have been identified, with the smallest fault measuring 12m and the largest at 612m in length. The displacements over these faults established from both bathymetric and seismic imaging ranges from 30cm to a couple of metres, scales that would typically be sub-seismic for conventional basin seismic imaging. The orientations and dimensions of the faults within this network have been directly compared to 3D seismic data of the Ieper Clay from the offshore Dutch sector where it exists approximately 1km below the seafloor. These have typical PFS attributes with lengths of hundreds of metres to kilometres and throws of tens of metres, a magnitude larger than those identified in the Outer Thames Estuary. The similar orientations and polygonal patterns within both locations indicates that the smaller faults exist within typical PFS structure but are sub-seismic in conventional imaging techniques. These unseen faults could create additional unseen pathways that impact construction in London via water ingress and influence fluid migration within hydrocarbon basins.

  9. Submarine slope failures due to pipe structure formation.

    PubMed

    Elger, Judith; Berndt, Christian; Rüpke, Lars; Krastel, Sebastian; Gross, Felix; Geissler, Wolfram H

    2018-02-19

    There is a strong spatial correlation between submarine slope failures and the occurrence of gas hydrates. This has been attributed to the dynamic nature of gas hydrate systems and the potential reduction of slope stability due to bottom water warming or sea level drop. However, 30 years of research into this process found no solid supporting evidence. Here we present new reflection seismic data from the Arctic Ocean and numerical modelling results supporting a different link between hydrates and slope stability. Hydrates reduce sediment permeability and cause build-up of overpressure at the base of the gas hydrate stability zone. Resulting hydro-fracturing forms pipe structures as pathways for overpressured fluids to migrate upward. Where these pipe structures reach shallow permeable beds, this overpressure transfers laterally and destabilises the slope. This process reconciles the spatial correlation of submarine landslides and gas hydrate, and it is independent of environmental change and water depth.

  10. Zebrafish Pronephros Development.

    PubMed

    Naylor, Richard W; Qubisi, Sarah S; Davidson, Alan J

    The pronephros is the first kidney type to form in vertebrate embryos. The first step of pronephrogenesis in the zebrafish is the formation of the intermediate mesoderm during gastrulation, which occurs in response to secreted morphogens such as BMPs and Nodals. Patterning of the intermediate mesoderm into proximal and distal cell fates is induced by retinoic acid signaling with downstream transcription factors including wt1a, pax2a, pax8, hnf1b, sim1a, mecom, and irx3b. In the anterior intermediate mesoderm, progenitors of the glomerular blood filter migrate and fuse at the midline and recruit a blood supply. More posteriorly localized tubule progenitors undergo epithelialization and fuse with the cloaca. The Notch signaling pathway regulates the formation of multi-ciliated cells in the tubules and these cells help propel the filtrate to the cloaca. The lumenal sheer stress caused by flow down the tubule activates anterior collective migration of the proximal tubules and induces stretching and proliferation of the more distal segments. Ultimately these processes create a simple two-nephron kidney that is capable of reabsorbing and secreting solutes and expelling excess water-processes that are critical to the homeostasis of the body fluids. The zebrafish pronephric kidney provides a simple, yet powerful, model system to better understand the conserved molecular and cellular progresses that drive nephron formation, structure, and function.

  11. Isotopic analysis of dissolved organic carbon in produced water brines by wet chemical oxidation and cavity ring-down spectroscopy

    NASA Astrophysics Data System (ADS)

    Thomas, Randal; Conaway, Christopher; Saad, Nabil; Kharaka, Yousif

    2013-04-01

    Identification of fluid migration and escape from intentionally altered subsurface geologic systems, such as in hydraulic fracturing, enhanced oil recovery, and carbon sequestration activities, is an important issue for environmental regulators based on the traction that the "fracking" process is gathering across the United States. Given diverse injected fluid compositions and the potential for toxic or regulated compounds to be released, one of the most important steps in the process is accurately identifying evidence of injected fluid escape during and after injection processes. An important tool in identifying differences between the natural groundwater and injected fluid is the isotopic composition of dissolved constituents including inorganic components such as Sr and carbon isotopes of the dissolved organic compounds. Since biological processes in the mesothermal subsurface can rapidly alter the organic composition of a fluid, stable carbon isotopes of the dissolved organic compounds (DOC) are an effective means to identify differences in the origin of two fluids, especially when coupled with inorganic compound analyses. The burgeoning field of cavity ring-down spectroscopy (CRDS) for isotopic analysis presents an opportunity to obtain rapid, reliable and cost-effective isotopic measurements of DOC in potentially affected groundwater for the identification of leakage or the improvement of hydrogeochemical pathway models. Here we adapt the use of the novel hyphenated TOC-CRDS carbon isotope analyzer for the analysis of DOC in produced water by wet oxidation and describe the methods to evaluate performance and obtain useful information at higher salinities. Our methods are applied to a specific field example in a CO2-enhanced EOR field in Cranfield, Mississippi (USA) as a means to demonstrate the ability to distinguish natural and injected DOC using the stable isotopic composition of the dissolved organic carbon when employing the novel TOC-CRDS instrumentation set up.

  12. Noble Gases as tracers of fluid migration in the Haynesville shale and overlying strata

    NASA Astrophysics Data System (ADS)

    Byrne, D. J.; Barry, P. H.; Lawson, M.; Ballentine, C. J.

    2017-12-01

    Noble gases are ideal tracers of physical processes and fluid provenance in crustal systems. Due to their inert nature, they are unaffected by chemical alteration, redox, or biological phenomena that fractionate other geochemical tracers. Noble gas analysis has been used to quantify fluid provenance, interactions, and ages in petroleum systems [1,2], but the effects of hydrocarbon migration on noble gas signatures have not been directly observed. The Haynesville Shale (East Texas & Louisiana), is exploited commercially for unconventional shale gas, but also acts as the source-rock for overlying conventional reservoirs. We present noble gas isotope and abundance data in samples collected from 9 natural gas wells sourced from the Haynesville Shale, as well as 21 from reservoirs in the overlying Cotton Valley (n=7), Travis Peak (n=9), and James (n=5) groups. Using a stratigraphic model, we observe systematic changes in the noble gas signatures as the fluids migrate from the Haynesville source rock to the overlying conventional accumulations. Helium isotope ratios (3He/4He) are strongly radiogenic in the Haynesville and stratigraphically older conventional reservoirs, with the younger reservoirs showing evidence of a mantle helium input. Argon isotope ratios (40Ar/36Ar) are strongly correlated with high 3He/4He, suggesting a similar provenance for radiogenic 40Ar and mantle 3He. Concentrations of groundwater-derived 36Ar are consistently higher in the conventional reservoirs than in the Haynesville shale, reflecting the greater interaction with groundwater during migration. However, 20Ne/36Ar ratios are not significantly different, suggesting that solubility-dependent partitioning is not simply dependent on vertical or horizontal migration distance. Krypton and xenon abundances are higher than expected for groundwater in all samples, a phenomenon that has been observed in many other hydrocarbon accumulations [3]. The excess Xe/Kr ratio is highest in the Haynesville itself, suggesting that this excess Xe and Kr originates from within the source-rock, and is subsequently shifted towards normal Xe/Kr values by mixing with groundwater-derived noble gases during migration. [1] Barry et al., 2016, GCA 194, 291-309; [2] Darrah et al., 2014, PNAS 111, 14076-81; [3] Zhou et al., 2005, GCA 69, 5413-28

  13. Intracellular signaling pathways required for rat vascular smooth muscle cell migration. Interactions between basic fibroblast growth factor and platelet-derived growth factor.

    PubMed Central

    Bilato, C; Pauly, R R; Melillo, G; Monticone, R; Gorelick-Feldman, D; Gluzband, Y A; Sollott, S J; Ziman, B; Lakatta, E G; Crow, M T

    1995-01-01

    Intracellular signaling pathways activated by both PDGF and basic fibroblast growth factor (bFGF) have been implicated in the migration of vascular smooth muscle cells (VSMC), a key step in the pathogenesis of many vascular diseases. We demonstrate here that, while bFGF is a weak chemoattractant for VSMCs, it is required for the PDGF-directed migration of VSMCs and the activation of calcium/calmodulin-dependent protein kinase II (CamKinase II), an intracellular event that we have previously shown to be important in the regulation of VSMC migration. Neutralizing antibodies to bFGF caused a dramatic reduction in the size of the intracellular calcium transient normally seen after PDGF stimulation and inhibited both PDGF-directed VSMC migration and CamKinase II activation. Partially restoring the calcium transient with ionomycin restored migration and CamKinase II activation as did the forced expression of a mutant CamKinase II that had been "locked" in the active state by site-directed mutagenesis. These results suggest that bFGF links PDGF receptor stimulation to changes in intracellular calcium and CamKinase II activation, reinforcing the central role played by CamKinase II in regulating VSMC migration. Images PMID:7560082

  14. Migration of Carbon Adatoms on the Surface of Charged SWCNT

    NASA Astrophysics Data System (ADS)

    Han, Longtao; Krstic, Predrag; Kaganovich, Igor

    2016-10-01

    In volume plasma, the growth of SWCNT from a transition metal catalyst could be enhanced by incoming carbon flux on SWCNT surface, which is generated by the adsorption and migration of carbon adatoms on SWCNT surface. In addition, the nanotube can be charged by the irradiation of plasma particles. How this charging effect will influence the adsorption and migration behavior of carbon atom has not been revealed. Using Density Functional Theory, Nudged Elastic Band and Kinetic Monte Carlo method, we found equilibrium sites, vibrational frequency, adsorption energy, most probable pathways for migration of adatoms, and the barrier sizes along these pathways. The metallic (5,5) SWCNT can support a fast migration of the carbon adatom along a straight path with low barriers, which is further enhanced by the presence of negative charge on SWCNT. The enhancement is contributed by the higher adsorption energy and thence longer lifetime of adatom on the charged SWCNT surface. The lifetime and migration distance of adatom increase by three and two orders of magnitude, respectively, as shown by Kinetic Monte Carlo simulation. These results support the surface migration mechanism of SWCNT growth in plasma environment. This work was supported by the U.S. Department of Energy, Office of Science, Basic Energy Sciences, Material Sciences and Engineering Division.

  15. Effects of Artificial Ligaments with Different Porous Structures on the Migration of BMSCs

    PubMed Central

    Wang, Chun-Hui; Hou, Wei; Yan, Ming; Guo, Zhong-shang; Wu, Qi; Bi, Long; Han, Yi-Sheng

    2015-01-01

    Polyethylene terephthalate- (PET-) based artificial ligaments (PET-ALs) are commonly used in anterior cruciate ligament (ACL) reconstruction surgery. The effects of different porous structures on the migration of bone marrow mesenchymal stem cells (BMSCs) on artificial ligaments and the underlying mechanisms are unclear. In this study, a cell migration model was utilized to observe the migration of BMSCs on PET-ALs with different porous structures. A rabbit extra-articular graft-to-bone healing model was applied to investigate the in vivo effects of four types of PET-ALs, and a mechanical test and histological observation were performed at 4 weeks and 12 weeks. The BMSC migration area of the 5A group was significantly larger than that of the other three groups. The migration of BMSCs in the 5A group was abolished by blocking the RhoA/ROCK signaling pathway with Y27632. The in vivo study demonstrated that implantation of 5A significantly improved osseointegration. Our study explicitly demonstrates that the migration ability of BMSCs can be regulated by varying the porous structures of the artificial ligaments and suggests that this regulation is related to the RhoA/ROCK signaling pathway. Artificial ligaments prepared using a proper knitting method and line density may exhibit improved biocompatibility and clinical performance. PMID:26106429

  16. Pressure solution and microfracturing in primary oil migration, Upper Cretaceous Austin Chalk, Texas Gulf Coast

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chanchani, J.; Berg, R.R.; Lee, C.I.

    1996-09-01

    The Upper Cretaceous Austin Chalk is a well known source rock and fractured reservoir in the Gulf Coast. Production is mainly from tectonic fractures, and the mechanism by which oil migrated from the matrix into the fractures is poorly understood. Microfracturing due to oil generation offers a possible explanation for the mechanism of the primary migration of oil in the Austin Chalk. Petrographic study shows that the major components of the primary migration system are the solution seams and the associated microfractures. Pressure solution is manifest as centimeter to millimeter-scale solution seams and smaller microseams. The solution seams are compositesmore » formed by the superposition of the smaller microseams. A significant amount of organic matter was concentrated in the seams along with other insoluble residue. Swarms of horizontal microfractures, many of them filled with calcite and other residue, are associated with the seams. Vertical, tectonic fractures that constitute the reservoir porosity, intersect the solution seams. Pressure solution concentrated organic matter within the solution seams and oil was generated there. It is postulated that the accompanying increase in fluid volume raised the pore pressures and fractured the rock. The newly created microfractures were avenues for migration of fluids from the seams, perhaps by microfracture propagation.« less

  17. C-Kit Promotes Growth and Migration of Human Cardiac Progenitor Cells via the PI3K-AKT and MEK-ERK Pathways

    PubMed Central

    Al-Maqtari, Tareq; Cao, Pengxiao; Keith, Matthew C. L.; Wysoczynski, Marcin; Zhao, John; Moore IV, Joseph B.; Bolli, Roberto

    2015-01-01

    A recent phase I clinical trial (SCIPIO) has shown that autologous c-kit+ cardiac progenitor cells (CPCs) improve cardiac function and quality of life when transplanted into patients with ischemic heart disease. Although c-kit is widely used as a marker of resident CPCs, its role in the regulation of the cellular characteristics of CPCs remains unknown. We hypothesized that c-kit plays a role in the survival, growth, and migration of CPCs. To test this hypothesis, human CPCs were grown under stress conditions in the presence or absence of SCF, and the effects of SCF-mediated activation of c-kit on CPC survival/growth and migration were measured. SCF treatment led to a significant increase in cell survival and a reduction in cell death under serum depletion conditions. In addition, SCF significantly promoted CPC migration in vitro. Furthermore, the pro-survival and pro-migratory effects of SCF were augmented by c-kit overexpression and abrogated by c-kit inhibition with imatinib. Mechanistically, c-kit activation in CPCs led to activation of the PI3K and the MAPK pathways. With the use of specific inhibitors, we confirmed that the SCF/c-kit-dependent survival and chemotaxis of CPCs are dependent on both pathways. Taken together, our findings suggest that c-kit promotes the survival/growth and migration of human CPCs cultured ex vivo via the activation of PI3K and MAPK pathways. These results imply that the efficiency of CPC homing to the injury site as well as their survival after transplantation may be improved by modulating the activity of c-kit. PMID:26474484

  18. Dioscin Inhibits HSC-T6 Cell Migration via Adjusting SDC-4 Expression: Insights from iTRAQ-Based Quantitative Proteomics.

    PubMed

    Yin, Lianhong; Qi, Yan; Xu, Youwei; Xu, Lina; Han, Xu; Tao, Xufeng; Song, Shasha; Peng, Jinyong

    2017-01-01

    Hepatic stellate cells (HSCs) migration, an important bioprocess, contributes to the development of liver fibrosis. Our previous studies have found the potent activity of dioscin against liver fibrosis by inhibiting HSCs proliferation, triggering the senescence and inducing apoptosis of activated HSCs, but the molecular mechanisms associated with cell migration were not clarified. In this work, iTRAQ (isobaric tags for relative and absolution quantitation)-based quantitative proteomics study was carried out, and a total of 1566 differentially expressed proteins with fold change ≥2.0 and p < 0.05 were identified in HSC-T6 cells treated by dioscin (5.0 μg/mL). Based on Gene Ontology classification, String and KEGG pathway assays, the effects of dioscin to inhibit cell migration via regulating SDC-4 were carried out. The results of wound-healing, cell migration and western blotting assays indicated that dioscin significantly inhibit HSC-T6 cell migration through SDC-4-dependent signal pathway by affecting the expression levels of Fn, PKCα, Src, FAK, and ERK1/2. Specific SDC-4 knockdown by shRNA also blocked HSC-T6 cell migration, and dioscin slightly enhanced the inhibiting effect. Taken together, the present work showed that SDC-4 played a crucial role on HSC-T6 cell adhesion and migration of dioscin against liver fibrosis, which may be one potent therapeutic target for fibrotic diseases.

  19. MicroRNA-21 promotes bone mesenchymal stem cells migration in vitro by activating PI3K/Akt/MMPs pathway.

    PubMed

    Lv, Chen; Yang, Shengwu; Chen, Xin; Zhu, Xiongbai; Lin, Wenjun; Wang, Lu; Huang, Zhengxiang; Wang, Mingyue; Tu, Guanjun

    2017-12-01

    MicroRNA-21 (miR-21) contributes to anti-apoptosis in bone marrow mesenchymal stem cells (BMSC), but its role in the migration of BMSCs remains vague. The aim of this study was to determine the possible effect of miR-21 on regulating BMSCs directional migration and the expression of MMP-2/MMP-9 in BMSCs in vitro. BMSCs were successfully infected with miR-21-up lentivirus. Cell migration using Transwell assay indicated that upregulated expression of miR-21 could significantly promote BMSCs migration. Western blot analysis indicated that miR-21 significantly upregulated the expression of MMP-2 and MMP-9, which were related to metastasis-associated genes. GM6001, the specific MMPs inhibitor, abrogated the upregulated expression of MMP-2/MMP-9 and abolished the positive effect of miR-21 on promoting BMSCs migration. Meanwhile, miR-21 significantly enhanced Akt phosphorylation, as measured by Western blot analysis. LY294002, an inhibitor of Akt activation, abrogated the phosphorylation of Akt and abolished the positive effect of miR-21 on promoting BMSCs migration and upregulating MMP-2/MMP-9 expression. These results suggest that miR-21 contributes to BMSCs migration by upregulating MMP-2/MMP-9, potentially via the PI3K/Akt pathway. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Plume capture by a migrating ridge: Analog geodynamic experiments

    NASA Astrophysics Data System (ADS)

    Mendez, J. S.; Hall, P.

    2010-12-01

    Paleomagnetic data from the Hawaii-Emperor Seamount Chain (HESC) suggests that the Hawaiian hotspot moved rapidly (~40 mm/yr) between 81 - 47 Ma but has remained relatively stationary since that time. This implies that the iconic bend in the HESC may in fact reflect the transition from a period of rapid hotspot motion to a stationary state, rather than a change in motion of the Pacific plate. Tarduno et al. (2009) have suggested that this period of rapid hotspot motion might be the surface expression of a plume conduit returning to a largely vertical orientation after having been “captured” and tilted by a migrating mid-ocean ridge. We report on a series of analog fluid dynamic experiments designed to characterize the interaction between a migrating spreading center and a thermally buoyant mantle plume. Experiments were conducted in a clear acrylic tank (100 cm x 70 cm x 50 cm) filled with commercial grade high-fructose corn syrup. Plate-driven flow is modeled by dragging two sheets of Mylar film (driven by independent DC motors) in opposite directions over the surface of the fluid. Ridge migration is achieved by moving the point at which the mylar sheets diverge using a separate motor drive. Buoyant plume flow is modeled using corn syrup introduced into the bottom of the tank from an external, heated, pressurized reservoir. Small (~2 mm diameter), neutrally buoyant Delrin spheres are mixed into reservoir of plume material to aid in visualization. Plate velocities and ridge migration rate are controlled and plume temperature monitored using LabView software. Experiments are recorded using digital video which is then analyzed using digital image analysis software to track the position and shape of the plume conduit throughout the course of the experiment. The intersection of the plume conduit with the surface of the fluid is taken as an analog for the locus of hotspot volcanism and tracked as a function of time to obtain a hotspot migration rate. Experiments are scaled to the Earth's mantle through a combination of a Peclet number and a plume buoyancy number. A range of spreading rates, ridge migration rates, and plume excess temperatures representative of the Earth are considered.

  1. 40 CFR 300.420 - Remedial site evaluation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... existing information about a release such as information on the pathways of exposure, exposure targets, and... known contaminants; (iii) A description of pathways of migration of contaminants; (iv) An identification...

  2. 40 CFR 300.420 - Remedial site evaluation.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... existing information about a release such as information on the pathways of exposure, exposure targets, and... known contaminants; (iii) A description of pathways of migration of contaminants; (iv) An identification...

  3. 40 CFR 300.420 - Remedial site evaluation.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... existing information about a release such as information on the pathways of exposure, exposure targets, and... known contaminants; (iii) A description of pathways of migration of contaminants; (iv) An identification...

  4. Perfluorooctanoic acid stimulates ovarian cancer cell migration, invasion via ERK/NF-κB/MMP-2/-9 pathway.

    PubMed

    Li, Xiaozhao; Bao, Chunyu; Ma, Zhinan; Xu, Boqun; Liu, Xiaoqiu; Ying, Xiaoyan; Zhang, Xuesen

    2018-05-09

    As widely used in consumer products, perfluorooctanoic acid (PFOA) has become a common environmental pollutant, which has been detected in human serum and associated with cancers. Our previous study showed that PFOA is a carcinogen that promotes endometrial cancer cell migration and invasion through activation of ERK/mTOR signaling. Here, we showed that PFOA (≥100 nM) treatment also stimulated A2780 ovarian cancer cell invasion and migration, which correlated with increased matrix metalloproteinases MMP-2/-9 expression, important proteases associated with tumor invasion and migration. Notably, PFOA treatment induced activation of ERK1/2/ NF-κB signaling. Pre-treatment with U0126, an ERK1/2inhibitor;or JSH-23, a NF-kB inhibitor, can reverse the PFOA-induced cell migration and invasion. Consistent with these results, inhibiting ERK1/2 or NF-κB signaling abolished PFOA-induced up-regulation of MMP-2/-9 expression. These results indicate that PFOA can stimulate ovarian cancer cell migration, invasion and MMP-2/-9 expression by up-regulating ERK/NF-κB pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Dexamethasone Inhibits TGF-β1–Induced Cell Migration by Regulating the ERK and AKT Pathways in Human Colon Cancer Cells Via CYR61

    PubMed Central

    Han, Sanghoon; Bui, Ngoc Thuy; Ho, Manh Tin; Kim, Young Mee; Cho, Moonjae; Shin, Dong Bok

    2016-01-01

    Purpose One of the features in cancer development is the migration of cancer cells to form metastatic lesions. CYR61 protein promotes migration and the epithelial-mesenchymal transition in several cancer cell types. Evidence suggests that CYR61 and dexamethasone are relevant to colorectal cancer. However, relationships between them and colorectal cancer are still unclear. Understanding the molecular mechanism of colorectal cancer progression related with CYR61 and dexamethasone, which is widely used for combination chemotherapy, is necessary for improved therapy. Materials and Methods We used colorectal cancer cells, HCT116, co-treated with transforming growth factor β1 (TGF-β1) and dexamethasone to examine the inhibitory migration effect of dexamethasone by migratory assay. Alternatively, both migratory pathways, expression of AKT and ERK, and the target factor CYR61 was also tested by co-treatment with TGF-β1 and dexamethasone. Results We report that dexamethasone significantly inhibited TGF-β1–induced cell migration, without affecting cell proliferation. Importantly, we observed that TGF-β1 promoted the epithelial-mesenchymal transition process and that dexamethasone co-treatment abolished this effect. ERK and AKT signaling pathways were found to mediate TGF-β1–induced migration, which was inhibited by dexamethasone. In addition, TGF-β1 treatment induced CYR61 expression whereas dexamethasone reduced it. These observations were compatible with the modulation of migration observed following treatment of HCT116 cells with human recombinant CYR61 and anti-CYR61 antibody. Our results also indicated that TGF-β1 enhanced collagen I and reduced matrix metalloproteinase 1 expression, which was reversed by dexamethasone treatment. Conclusion These findings suggested that dexamethasone inhibits AKT and ERK phosphorylation, leading to decreased CYR61 expression, which in turn blocks TGF-β1–induced migration. PMID:26693911

  6. Regional fluid migration in the Illinois basin: evidence from in situ oxygen isotope analysis of authigenic K-feldspar and quartz from the Mount Simon Sandstone

    USGS Publications Warehouse

    Chen, Zhensheng; Riciputi, Lee R.; Mora, Claudia I.; Fishman, Neil S.

    2001-01-01

    Oxygen isotope compositions of widespread, authigenic K-feldspar and quartz overgrowths and cements in the Upper Cambrian Mount Simon Sandstone were measured by ion microprobe in 11 samples distributed across the Illinois basin and its periphery. Average K-feldspar δ18O values increase systematically from +14‰ ± 1‰ in the southernmost and deepest samples in Illinois to +24‰ ± 2‰ in the northernmost outcrop sample in Wisconsin. A similar trend was observed for quartz overgrowths (22‰ ± 2‰ to 28‰ ± 2‰). Constant homogenization temperatures (100–130 °C) of fluid inclusions associated with quartz overgrowths throughout the basin suggest that the geographic trend in oxygen isotope compositions is a result of diagenetic modification of a south to north migrating basinal fluid.

  7. Multiplex Particle Focusing via Hydrodynamic Force in Viscoelastic Fluids

    NASA Astrophysics Data System (ADS)

    Lee, Doo Jin; Brenner, Howard; Youn, Jae Ryoun; Song, Young Seok

    2013-11-01

    We introduce a multiplex particle focusing phenomenon that arises from the hydrodynamic interaction between the viscoelastic force and the Dean drag force in a microfluidic device. In a confined microchannel, the first normal stress difference of viscoelastic fluids results in a lateral migration of suspended particles. Such a viscoelastic force was harnessed to focus different sized particles in the middle of a microchannel, and spiral channel geometry was also considered in order to take advantage of the counteracting force, Dean drag force that induces particle migration in the outward direction. For theoretical understanding, we performed a numerical analysis of viscoelastic fluids in the spiral microfluidic channel. From these results, a concept of the `Dean-coupled Elasto-inertial Focusing band (DEF)' was proposed. This study provides in-depth physical insight into the multiplex focusing of particles that can open a new venue for microfluidic particle dynamics for a concrete high throughput platform at microscale.

  8. Fluid shear stress activates YAP1 to promote cancer cell motility

    NASA Astrophysics Data System (ADS)

    Lee, Hyun Jung; Diaz, Miguel F.; Price, Katherine M.; Ozuna, Joyce A.; Zhang, Songlin; Sevick-Muraca, Eva M.; Hagan, John P.; Wenzel, Pamela L.

    2017-01-01

    Mechanical stress is pervasive in egress routes of malignancy, yet the intrinsic effects of force on tumour cells remain poorly understood. Here, we demonstrate that frictional force characteristic of flow in the lymphatics stimulates YAP1 to drive cancer cell migration; whereas intensities of fluid wall shear stress (WSS) typical of venous or arterial flow inhibit taxis. YAP1, but not TAZ, is strictly required for WSS-enhanced cell movement, as blockade of YAP1, TEAD1-4 or the YAP1-TEAD interaction reduces cellular velocity to levels observed without flow. Silencing of TEAD phenocopies loss of YAP1, implicating transcriptional transactivation function in mediating force-enhanced cell migration. WSS dictates expression of a network of YAP1 effectors with executive roles in invasion, chemotaxis and adhesion downstream of the ROCK-LIMK-cofilin signalling axis. Altogether, these data implicate YAP1 as a fluid mechanosensor that functions to regulate genes that promote metastasis.

  9. Variations in Gas and Water Pulses at an Arctic Seep: Fluid Sources and Methane Transport

    NASA Astrophysics Data System (ADS)

    Hong, W.-L.; Torres, M. E.; Portnov, A.; Waage, M.; Haley, B.; Lepland, A.

    2018-05-01

    Methane fluxes into the oceans are largely dependent on the methane phase as it migrates upward through the sediments. Here we document decoupled methane transport by gaseous and aqueous phases in Storfjordrenna (offshore Svalbard) and propose a three-stage evolution model for active seepage in the region where gas hydrates are present in the shallow subsurface. In a preactive seepage stage, solute diffusion is the primary transport mechanism for methane in the dissolved phase. Fluids containing dissolved methane have high 87Sr/86Sr ratios due to silicate weathering in the microbial methanogenesis zone. During the active seepage stage, migration of gaseous methane results in near-seafloor gas hydrate formation and vigorous seafloor gas discharge with a thermogenic fingerprint. In the postactive seepage stage, the high concentration of dissolved lithium points to the contribution of a deeper-sourced aqueous fluid, which we postulate advects upward following cessation of gas discharge.

  10. Frontline Science: Pathological conditioning of human neutrophils recruited to the airway milieu in cystic fibrosis.

    PubMed

    Forrest, Osric A; Ingersoll, Sarah A; Preininger, Marcela K; Laval, Julie; Limoli, Dominique H; Brown, Milton R; Lee, Frances E; Bedi, Brahmchetna; Sadikot, Ruxana T; Goldberg, Joanna B; Tangpricha, Vin; Gaggar, Amit; Tirouvanziam, Rabindra

    2018-05-09

    Recruitment of neutrophils to the airways, and their pathological conditioning therein, drive tissue damage and coincide with the loss of lung function in patients with cystic fibrosis (CF). So far, these key processes have not been adequately recapitulated in models, hampering drug development. Here, we hypothesized that the migration of naïve blood neutrophils into CF airway fluid in vitro would induce similar functional adaptation to that observed in vivo, and provide a model to identify new therapies. We used multiple platforms (flow cytometry, bacteria-killing, and metabolic assays) to characterize functional properties of blood neutrophils recruited in a transepithelial migration model using airway milieu from CF subjects as an apical chemoattractant. Similarly to neutrophils recruited to CF airways in vivo, neutrophils migrated into CF airway milieu in vitro display depressed phagocytic receptor expression and bacterial killing, but enhanced granule release, immunoregulatory function (arginase-1 activation), and metabolic activities, including high Glut1 expression, glycolysis, and oxidant production. We also identify enhanced pinocytic activity as a novel feature of these cells. In vitro treatment with the leukotriene pathway inhibitor acebilustat reduces the number of transmigrating neutrophils, while the metabolic modulator metformin decreases metabolism and oxidant production, but fails to restore bacterial killing. Interestingly, we describe similar pathological conditioning of neutrophils in other inflammatory airway diseases. We successfully tested the hypothesis that recruitment of neutrophils into airway milieu from patients with CF in vitro induces similar pathological conditioning to that observed in vivo, opening new avenues for targeted therapeutic intervention. ©2018 Society for Leukocyte Biology.

  11. The regulation of inflammatory pathways and infectious disease of the cervix by seminal fluid.

    PubMed

    Adefuye, Anthonio; Katz, Arieh Anthony; Sales, Kurt Jason

    2014-01-01

    The connection between human papillomavirus (HPV) infection and the consequent sequelae which establishes cervical neoplastic transformation and invasive cervical cancer has redefined many aspects of cervical cancer research. However there is still much that we do not know. In particular, the impact of external factors, like seminal fluid in sexually active women, on pathways that regulate cervical inflammation and tumorigenesis, have yet to be fully understood. HPV infection is regarded as the initiating noninflammatory cause of the disease; however emerging evidence points to resident HPV infections as drivers of inflammatory pathways that play important roles in tumorigenesis as well as in the susceptibility to other infections such as human immunodeficiency virus (HIV) infection. Moreover there is emerging evidence to support a role for seminal fluid, in particular, the inflammatory bioactive lipids, and prostaglandins which are present in vast quantities in seminal fluid in regulating pathways that can exacerbate inflammation of the cervix, speed up tumorigenesis, and enhance susceptibility to HIV infection. This review will highlight some of our current knowledge of the role of seminal fluid as a potent driver of inflammatory and tumorigenic pathways in the cervix and will provide some evidence to propose a role for seminal plasma prostaglandins in HIV infection and AIDS-related cancer.

  12. The Regulation of Inflammatory Pathways and Infectious Disease of the Cervix by Seminal Fluid

    PubMed Central

    Katz, Arieh Anthony

    2014-01-01

    The connection between human papillomavirus (HPV) infection and the consequent sequelae which establishes cervical neoplastic transformation and invasive cervical cancer has redefined many aspects of cervical cancer research. However there is still much that we do not know. In particular, the impact of external factors, like seminal fluid in sexually active women, on pathways that regulate cervical inflammation and tumorigenesis, have yet to be fully understood. HPV infection is regarded as the initiating noninflammatory cause of the disease; however emerging evidence points to resident HPV infections as drivers of inflammatory pathways that play important roles in tumorigenesis as well as in the susceptibility to other infections such as human immunodeficiency virus (HIV) infection. Moreover there is emerging evidence to support a role for seminal fluid, in particular, the inflammatory bioactive lipids, and prostaglandins which are present in vast quantities in seminal fluid in regulating pathways that can exacerbate inflammation of the cervix, speed up tumorigenesis, and enhance susceptibility to HIV infection. This review will highlight some of our current knowledge of the role of seminal fluid as a potent driver of inflammatory and tumorigenic pathways in the cervix and will provide some evidence to propose a role for seminal plasma prostaglandins in HIV infection and AIDS-related cancer. PMID:25180120

  13. Mathematical models as tools for probing long-term safety of CO2 storage

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pruess, Karsten; Birkholzer, Jens; Zhou, Quanlin

    Subsurface reservoirs being considered for storing CO{sub 2} include saline aquifers, oil and gas reservoirs, and unmineable coal seams (Baines and Worden, 2004; IPCC, 2005). By far the greatest storage capacity is in saline aquifers (Dooley et al., 2004), and our discussion will focus primarily on CO{sub 2} storage in saline formations. Most issues for safety and security of CO{sub 2} storage arise from the fact that, at typical temperature and pressure conditions encountered in terrestrial crust, CO{sub 2} is less dense than aqueous fluids. Accordingly, CO{sub 2} will experience an upward buoyancy force in most subsurface environments, and willmore » tend to migrate upwards whenever (sub-)vertical permeable pathways are available, such as fracture zones, faults, or improperly abandoned wells (Bachu, 2008; Pruess, 2008a, b; Tsang et al., 2008). CO{sub 2} injection will increase fluid pressures in the target formation, thereby altering effective stress distributions, and potentially triggering movement along fractures and faults that could increase their permeability and reduce the effectiveness of a caprock in containing CO{sub 2} (Rutqvist et al., 2008; Chiaramonte et al., 2008). Induced seismicity as a consequence of fluid injection is also a concern (Healy et al., 1968; Raleigh et al., 1976; Majer et al., 2007). Dissolution of CO{sub 2} in the aqueous phase generates carbonic acid, which may induce chemical corrosion (dissolution) of minerals with associated increase in formation porosity and permeability, and may also mediate sequestration of CO{sub 2} as solid carbonate (Gaus et al., 2008). Chemical dissolution of caprock minerals could promote leakage of CO{sub 2} from a storage reservoir (Gherardi et al., 2007). Chemical dissolution and geomechanical effects could reinforce one another in compromising CO{sub 2} containment. Additional issues arise from the potential of CO{sub 2} to mobilize hazardous chemical species (Kharaka et al., 2006), and from migration of the large amounts of brine that would be mobilized by industrial-scale CO{sub 2} injection (Nicot et al., 2008; Birkholzer et al., 2008a, b).« less

  14. Connective tissue growth factor enhances the migration of gastric cancer through downregulation of E-cadherin via the NF-κB pathway.

    PubMed

    Mao, Zhengfa; Ma, Xiaoyan; Rong, Yefei; Cui, Lei; Wang, Xuqing; Wu, Wenchuan; Zhang, Jianxin; Jin, Dayong

    2011-01-01

    Local invasion and distant metastasis are difficult problems for surgical intervention and treatment in gastric cancer. Connective tissue growth factor (CTGF/CCN2) was considered to have an important role in this process. In this study, we demonstrated that expression of CTGF was significantly upregulated in clinical tissue samples of gastric carcinoma (GC) samples. Forced expression of CTGF in AGS GC cells promoted their migration in culture and significantly increased tumor metastasis in nude mice, whereas RNA interference-mediated knockdown of CTGF in GC cells significantly inhibited cell migration in vitro. We disclose that CTGF downregulated the expression of E-cadherin through activation of the nuclear factor-κappa B (NF-κB) pathway. The effects of CTGF in GC cells were abolished by dominant negative IκappaB. Collectively, these data reported here demonstrate CTGF could modulate the NF-κappaB pathway and perhaps be a promising therapeutic target for gastric cancer invasion and metastasis. © 2010 Japanese Cancer Association.

  15. Mesenchymal chemotaxis requires selective inactivation of Myosin II at the leading edge via a non-canonical PLCγ/PKCα pathway

    PubMed Central

    Asokan, Sreeja B.; Johnson, Heath E.; Rahman, Anisur; King, Samantha J.; Rotty, Jeremy D.; Lebedeva, Irina P.; Haugh, Jason M.; Bear, James E.

    2014-01-01

    Summary Chemotaxis, migration towards soluble chemical cues, is critical for processes such as wound healing and immune surveillance, and is exhibited by various cell types from rapidly-migrating leukocytes to slow-moving mesenchymal cells. To interrogate the mechanisms involved in mesenchymal chemotaxis, we observed cell migration in microfluidic chambers that generate stable gradients of the chemoattractant PDGF. Surprisingly, we found that pathways implicated in amoeboid chemotaxis, such as PI3K and mTOR signaling, are dispensable for chemotaxis to PDGF. Instead, we find that local inactivation of Myosin IIA, through a non-canonical Ser1/2 phosphorylation of the regulatory light chain, is essential. This site is phosphorylated by PKCα, which is activated by an intracellular gradient of diacylglycerol generated by PLCγ. Using a combination of TIRF imaging and gradients of activators/inhibitors in the microfluidic chambers, we demonstrate that this signaling pathway and subsequent inhibition of Myosin II activity at the leading edge is required for mesenchymal chemotaxis. PMID:25482883

  16. Fluid-driven normal faulting earthquake sequences in the Taiwan orogen

    NASA Astrophysics Data System (ADS)

    Wang, Ling-hua; Rau, Ruey-Juin; Lee, En-Jui

    2017-04-01

    Seismicity in the Central Range of Taiwan shows normal faulting mechanisms with T-axes directing NE, subparallel to the strike of the mountain belt. We analyze earthquake sequences occurred within 2012-2015 in the Nanshan area of northern Taiwan which indicating swarm behavior and migration characteristics. We select events larger than 2.0 from Central Weather Bureau catalog and use the double-difference relocation program hypoDD with waveform cross-correlation in the Nanshan area. We obtained a final count of 1406 (95%) relocated earthquakes. Moreover, we compute focal mechanisms using USGS program HASH by P-wave first motion and S/P ratio picking and 114 fault plane solutions with M 3.0-5.87 were determined. To test for fluid diffusion, we model seismicity using the equation of Shapiro et al. (1997) by fitting earthquake diffusing rate D during the migration period. According to the relocation result, seismicity in the Taiwan orogenic belt present mostly N25E orientation parallel to the mountain belt with the same direction of the tension axis. In addition, another seismic fracture depicted by seismicity rotated 35 degree counterclockwise to the NW direction. Nearly all focal mechanisms are normal fault type. In the Nanshan area, events show N10W distribution with a focal depth range from 5-12 km and illustrate fault plane dipping about 45-60 degree to SW. Three months before the M 5.87 mainshock which occurred in March, 2013, there were some foreshock events occurred in the shallow part of the fault plane of the mainshock. Half a year following the mainshock, earthquakes migrated to the north and south, respectively with processes matched the diffusion model at a rate of 0.2-0.6 m2/s. This migration pattern and diffusion rate offer an evidence of 'fluid-driven' process in the fault zone. We also find the upward migration of earthquakes in the mainshock source region. These phenomena are likely caused by the opening of the permeable conduit due to the M 5.87 earthquake and the rise of the high pressure fluid.

  17. Large-Scale Multiphase Flow Modeling of Hydrocarbon Migration and Fluid Sequestration in Faulted Cenozoic Sedimentary Basins, Southern California

    NASA Astrophysics Data System (ADS)

    Jung, B.; Garven, G.; Boles, J. R.

    2011-12-01

    Major fault systems play a first-order role in controlling fluid migration in the Earth's crust, and also in the genesis/preservation of hydrocarbon reservoirs in young sedimentary basins undergoing deformation, and therefore understanding the geohydrology of faults is essential for the successful exploration of energy resources. For actively deforming systems like the Santa Barbara Basin and Los Angeles Basin, we have found it useful to develop computational geohydrologic models to study the various coupled and nonlinear processes affecting multiphase fluid migration, including relative permeability, anisotropy, heterogeneity, capillarity, pore pressure, and phase saturation that affect hydrocarbon mobility within fault systems and to search the possible hydrogeologic conditions that enable the natural sequestration of prolific hydrocarbon reservoirs in these young basins. Subsurface geology, reservoir data (fluid pressure-temperature-chemistry), structural reconstructions, and seismic profiles provide important constraints for model geometry and parameter testing, and provide critical insight on how large-scale faults and aquifer networks influence the distribution and the hydrodynamics of liquid and gas-phase hydrocarbon migration. For example, pore pressure changes at a methane seepage site on the seafloor have been carefully analyzed to estimate large-scale fault permeability, which helps to constrain basin-scale natural gas migration models for the Santa Barbara Basin. We have developed our own 2-D multiphase finite element/finite IMPES numerical model, and successfully modeled hydrocarbon gas/liquid movement for intensely faulted and heterogeneous basin profiles of the Los Angeles Basin. Our simulations suggest that hydrocarbon reservoirs that are today aligned with the Newport-Inglewood Fault Zone were formed by massive hydrocarbon flows from deeply buried source beds in the central synclinal region during post-Miocene time. Fault permeability, capillarity forces between the fault and juxtaposition of aquifers/aquitards, source oil saturation, and rate of generation control the efficiency of a petroleum trap and carbon sequestration. This research is focused on natural processes in real geologic systems, but our results will also contribute to an understanding of the subsurface behavior of injected anthropogenic greenhouse gases, especially when targeted storage sites may be influenced by regional faults, which are ubiquitous in the Earth's crust.

  18. Natural analogues for CO2 storage sites - analysis of a global dataset

    NASA Astrophysics Data System (ADS)

    Miocic, Johannes; Gilfillan, Stuart; McDermott, Christopher; Haszeldine, R. Stuart

    2013-04-01

    Carbon Capture and Storage is the only industrial scale technology currently available to reduce CO2 emissions from fossil-fuelled power plants and large industrial source to the atmosphere and thus mitigate climate change. CO2 is captured at the source and transported to subsurface storage sites, such as depleted oil and gas fields or saline aquifers. In order to have an effect on emissions and to be considered safe it is crucial that the amount of CO2 leaking from storage sites to shallow aquifers or the surface remains very low (<1% over 1000 years). Some process that influence the safety of a reservoir, such as CO2-rock-brine interactions, can be studied using experiments on both laboratory and field-scale. However, long-term processes such as the development of leakage pathways can only be understood by either predictive modelling or by studying natural CO2 reservoirs as analogues for long term CO2 storage sites. Natural CO2 reservoirs have similar geological trapping mechanisms as anticipated for CO2 storage sites and often have held CO2 for a geological period of time (millions of years) without any indication for leakage. Yet, migration of CO2 from reservoirs to the surface is also common and evidenced by gas seeps such as springs and soil degassing. We have compiled and analysed a dataset comprising of more than 50 natural CO2 reservoirs from different settings all around the globe to provide an overview of the factors that are important for the retention of CO2 in the subsurface and what processes lead to leakage of CO2 from the reservoir. Initial results indicate that if the reservoir is found to be leaking, CO2 migration is along faults and not through caprock layers. This indicates that faults act as fluid pathways and play an important role when characterizing a storage site. Additionally, it appears that overpressure of the overburden and the state of CO2 in the reservoir influence the likelihood of migration and hence the safety of a reservoir.

  19. Ore-forming fluid system of bauxite in WZD area of northern Guizhou province, China

    NASA Astrophysics Data System (ADS)

    Cui, Tao

    2017-12-01

    The ore-forming fluid system of bauxite in Wuchuan-Zheng,an-Daozhen (short for WZD) Area of northern Guizhou Province was studied from the perspective of deposit formation mechanism. It was discovered that ore-forming fluids were mainly effective for transporting and leaching during the formation of bauxite. The means of transport mainly included colloidal transport, suspended transport and gravity flow transport. In the course of their leaching, fluids had a range of chemical reactions, as a result of which elements such as silicon and iron migrated downwards. In this process, properties of fluids changed as well.

  20. Effects of faults as barriers or conduits to displaced brine flow on a putative CO2 storage site in the Southern North Sea

    NASA Astrophysics Data System (ADS)

    Hannis, Sarah; Bricker, Stephanie; Williams, John

    2013-04-01

    The Bunter Sandstone Formation in the Southern North Sea is a potential reservoir being considered for carbon dioxide storage as a climate change mitigation option. A geological model of a putative storage site within this saline aquifer was built from 3D seismic and well data to investigate potential reservoir pressure changes and their effects on fault movement, brine and CO2 migration as a result of CO2 injection. The model is located directly beneath the Dogger Bank Special Area of Conservation, close to the UK-Netherlands median line. Analysis of the seismic data reveals two large fault zones, one in each of the UK and Netherlands sectors, many tens of kilometres in length, extending from reservoir level to the sea bed. Although it has been shown that similar faults compartmentalise gas fields elsewhere in the Netherlands sector, significant uncertainty remains surrounding the properties of the faults in our model area; in particular their cross- and along-fault permeability and geomechanical behaviour. Despite lying outside the anticipated CO2 plume, these faults could provide potential barriers to pore fluid migration and pressure dissipation, until, under elevated pressures, they provide vertical migration pathways for brine. In this case, the faults will act to enhance injectivity, but potential environmental impacts, should the displaced brine be expelled at the sea bed, will require consideration. Pressure gradients deduced from regional leak-off test data have been input into a simple geomechanical model to estimate the threshold pressure gradient at which faults cutting the Mesozoic succession will fail, assuming reactivation of fault segments will cause an increase in vertical permeability. Various 4D scenarios were run using a single-phase groundwater modelling code, calibrated to results from a multi-phase commercial simulator. Possible end-member ranges of fault parameters were input to investigate the pressure change with time and quantify brine flux to the seabed in potentially reactivated sections of each fault zone. Combining the modelled pressure field with the calculated fault failure criterion suggests that only the fault in the Netherlands sector reactivates, allowing brine displacement at a maximum rate of 800 - 900 m3/d. Model results indicate that the extent of brine displacement is most sensitive to the fault reactivation pressure gradient and fault zone thickness. In conclusion, CO2 injection into a saline aquifer results in a significant increase in pore-fluid pressure gradients. In this case, brine displacement along faults acting as pressure relief valves could increase injectivity in a similar manner to pressure management wells, thereby facilitating the storage operation. However, if the faults act as brine migration pathways, an understanding of seabed flux rates and environmental impacts will need to be demonstrated to regulators prior to injection. This study, close to an international border, also highlights the need to inform neighbouring countries authorities of proposed operations and, potentially, to obtain licences to increase reservoir pressure and/or displace brine across international borders.

  1. Enforced hematopoietic cell E- and L-selectin ligand (HCELL) expression primes transendothelial migration of human mesenchymal stem cells.

    PubMed

    Thankamony, Sai P; Sackstein, Robert

    2011-02-08

    According to the multistep model of cell migration, chemokine receptor engagement (step 2) triggers conversion of rolling interactions (step 1) into firm adhesion (step 3), yielding transendothelial migration. We recently reported that glycosyltransferase-programmed stereosubstitution (GPS) of CD44 on human mesenchymal stem cells (hMSCs) creates the E-selectin ligand HCELL (hematopoietic cell E-selectin/L-selectin ligand) and, despite absence of CXCR4, systemically administered HCELL(+)hMSCs display robust osteotropism visualized by intravital microscopy. Here we performed studies to define the molecular effectors of this process. We observed that engagement of hMSC HCELL with E-selectin triggers VLA-4 adhesiveness, resulting in shear-resistant adhesion to ligand VCAM-1. This VLA-4 activation is mediated via a Rac1/Rap1 GTPase signaling pathway, resulting in transendothelial migration on stimulated human umbilical vein endothelial cells without chemokine input. These findings indicate that hMSCs coordinately integrate CD44 ligation and integrin activation, circumventing chemokine-mediated signaling, yielding a step 2-bypass pathway of the canonical multistep paradigm of cell migration.

  2. Wogonin suppresses TNF-{alpha}-induced MMP-9 expression by blocking the NF-{kappa}B activation via MAPK signaling pathways in human aortic smooth muscle cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Syng-Ook; Jeong, Yun-Jeong; Yu, Mi Hee

    2006-12-08

    Matrix metalloproteinase-9 (MMP-9) plays a major role in the pathogenesis of atherosclerosis and restenosis by regulating both migration and proliferation of vascular smooth muscle cells (VSMC) after an arterial injury. In this study, we examined the inhibitory effect of three major flavonoids in Scutellariae Radix, baicalin, baicalein, and wogonin, on TNF-{alpha}-induced MMP-9 expression in human aortic smooth muscle cells (HASMC). Wogonin, but not baicalin and baicalein, significantly and selectively suppressed TNF-{alpha}-induced MMP-9 expression in HASMC. Reporter gene, electrophoretic mobility shift, and Western blotting assays showed that wogonin inhibits MMP-9 gene transcriptional activity by blocking the activation of NF-{kappa}B via MAPKmore » signaling pathways. Moreover, the Matrigel migration assay showed that wogonin reduced TNF-{alpha}-induced HASMC migration. These results suggest that wogonin effectively suppresses TNF-{alpha}-induced HASMC migration through the selective inhibition of MMP-9 expression and represents a potential agent for the prevention of vascular disorders related to the migration of VSMC.« less

  3. Methylcobalamin promotes proliferation and migration and inhibits apoptosis of C2C12 cells via the Erk1/2 signaling pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Okamoto, Michio; Tanaka, Hiroyuki, E-mail: tanahiro-osk@umin.ac.jp; Okada, Kiyoshi

    2014-01-17

    Highlights: •Methylcobalamin activated the Erk1/2 signaling pathway in C2C12 cells. •Methylcobalamin promoted the proliferation and migration in C2C12 cells. •C2C12 cell apoptosis during differentiation was inhibited by methylcobalamin. -- Abstract: Methylcobalamin (MeCbl) is a vitamin B12 analog that has some positive effects on peripheral nervous disorders. Although some previous studies revealed the effects of MeCbl on neurons, its effect on the muscle, which is the final target of motoneuron axons, remains to be elucidated. This study aimed to determine the effect of MeCbl on the muscle. We found that MeCbl promoted the proliferation and migration of C2C12 myoblasts in vitromore » and that these effects are mediated by the Erk1/2 signaling pathway without affecting the activity of the Akt signaling pathway. We also demonstrated that MeCbl inhibits C2C12 cell apoptosis during differentiation. Our results suggest that MeCbl has beneficial effects on the muscle in vitro. MeCbl administration may provide a novel therapeutic approach for muscle injury or degenerating muscle after denervation.« less

  4. Meisoindigo, but not its core chemical structure indirubin, inhibits zebrafish interstitial leukocyte chemotactic migration.

    PubMed

    Ye, Baixin; Xiong, Xiaoxing; Deng, Xu; Gu, Lijuan; Wang, Qiongyu; Zeng, Zhi; Gao, Xiang; Gao, Qingping; Wang, Yueying

    2017-12-01

    Inflammatory disease is a big threat to human health. Leukocyte chemotactic migration is required for efficient inflammatory response. Inhibition of leukocyte chemotactic migration to the inflammatory site has been shown to provide therapeutic targets for treating inflammatory diseases. Our study was designed to discover effective and safe compounds that can inhibit leukocyte chemotactic migration, thus providing possible novel therapeutic strategy for treating inflammatory diseases. In this study, we used transgenic zebrafish model (Tg:zlyz-EGFP line) to visualize the process of leukocyte chemotactic migration. Then, we used this model to screen the hit compound and evaluate its biological activity on leukocyte chemotactic migration. Furthermore, western blot analysis was performed to evaluate the effect of the hit compound on the AKT or ERK-mediated pathway, which plays an important role in leukocyte chemotactic migration. In this study, using zebrafish-based chemical screening, we identified that the hit compound meisoindigo (25 μM, 50 μM, 75 μM) can significantly inhibit zebrafish leukocyte chemotactic migration in a dose-dependent manner (p = 0.01, p = 0.0006, p < 0.0001). Also, we found that meisoindigo did not affect the process of leukocyte reverse migration (p = 0.43). Furthermore, our results unexpectedly showed that indirubin, the core structure of meisoindigo, had no significant effect on zebrafish leukocyte chemotactic migration (p = 0.6001). Additionally, our results revealed that meisoindigo exerts no effect on the Akt or Erk-mediated signalling pathway. Our results suggest that meisoindigo, but not indirubin, is effective for inhibiting leukocyte chemotactic migration, thus providing a potential therapeutic agent for treating inflammatory diseases.

  5. Downregulation of CD9 in Keratinocyte Contributes to Cell Migration via Upregulation of Matrix Metalloproteinase-9

    PubMed Central

    Jiang, Xu-pin; Zhang, Dong-xia; Teng, Miao; Zhang, Qiong; Zhang, Jia-ping; Huang, Yue-sheng

    2013-01-01

    Tetraspanin CD9 has been implicated in various cellular and physiological processes, including cell migration. In our previous study, we found that wound repair is delayed in CD9-null mice, suggesting that CD9 is critical for cutaneous wound healing. However, many cell types, including immune cells, endothelial cells, keratinocytes and fibroblasts undergo marked changes in gene expression and phenotype, leading to cell proliferation, migration and differentiation during wound repair, whether CD9 regulates kerationcytes migration directly remains unclear. In this study, we showed that the expression of CD9 was downregulated in migrating keratinocytes during wound repair in vivo and in vitro. Recombinant adenovirus vector for CD9 silencing or overexpressing was constructed and used to infect HaCaT cells. Using cell scratch wound assay and cell migration assay, we have also demonstrated that downregulation of CD9 promoted keratinocyte migration in vitro, whereas CD9 overexpression inhibited cell migration. Moreover, CD9 inversely regulated the activity and expression of MMP-9 in keratinocytes, which was involved in CD9-regulated keratinocyte migration. Importantly, CD9 silencing-activated JNK signaling was accompanied by the upregulation of MMP-9 activity and expression. Coincidentally, we found that SP600125, a JNK pathway inhibitor, decreased the activity and expression of MMP-9 of CD9-silenced HaCaT cells. Thus, our results suggest that CD9 is downregulated in migrating keratinocytes in vivo and in vitro, and a low level of CD9 promotes keratinocyte migration in vitro, in which the regulation of MMP-9 through the JNK pathway plays an important role. PMID:24147081

  6. State of stress and crustal fluid migration related to west-dipping structures in the slab-forearc system in the northern Chilean subduction zone

    NASA Astrophysics Data System (ADS)

    Salazar, P.; Kummerow, J.; Wigger, P.; Shapiro, S.; Asch, G.

    2017-03-01

    Previous studies in the forearc of the northern Chilean subduction zone have identified important tectonic features in the upper crust. As a result of these works, the West Fissure Fault System (WFFS) has recently been imaged using microseismic events. The WFFS is the westward-dipping, sharp lower boundary of the northern Chilean forearc and is geometrically opposed to subduction of the Nazca plate. The present article builds on this previous work and is novel in that it characterizes this structure's stress distribution using focal mechanisms and stress tensor analysis. The results of the stress tensor analysis show that the state of stress in the WFFS is related to its strike-slip tectonic context and likely represents a manifestation of local forces associated with the highest areas in the Andes. Two seismic clusters have also been identified; these clusters may be associated with a blind branch of the WFFS. We studied these clusters in order to determine their sources and possible connection with fluid migration across the upper plate. We observed that the two clusters differ from one another in some regards. The central cluster has characteristics consistent with an earthquake swarm with two clearly identifiable phases. Conversely, the SW cluster has a clear main shock associated with it, and it can be separated into two subclusters (A and A΄). In contrast, similarities among the two clusters suggest that the clusters may have a common origin. The b-values for both clusters are characteristic of tectonic plate boundaries. The spatial spreading, which is approximately confined to one plane, reflects progressive growth of the main fracture underlying the swarm and subcluster A. We also find that earthquakes themselves trigger aftershocks near the borders of their rupture areas. In addition, the spatio-temporal migration of hypocentres, as well as their spatial correlation with areas that are interpreted to be fluid migration zones, suggest that there is a close relationship between fluid movement and the earthquake sources associated with the swarm and subcluster A. These observations point to stick-slip behaviour of the rupture propagation, which can be explained by earthquake-induced stress transfer and fluid flow in a fluid-permeated, critically loaded fault zone.

  7. TNF-α-inducing protein of Helicobacter pylori induces epithelial-mesenchymal transition (EMT) in gastric cancer cells through activation of IL-6/STAT3 signaling pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Guodong; Tang, Na; Wang, Chao

    Tumor necrosis factor (TNF)-α-inducing protein (Tipα) is a newly identified carcinogenic factor secreted by Helicobacter pylori (H. pylori). Although it has been proved that Tipα is a strong inducer of epithelial-mesenchymal transition (EMT), a crucial process of migration, the exact molecular mechanism is unknown. Current evidence indicates that the oncogenic transcription factor signal transducers and activators of transcription 3 (STAT3) is inappropriately activated in multiple malignancies, including gastric cancer. In this study, we showed that Tipα significantly down-regulated the expression of EMT-related markers E-cadherin as well as up-regulated N-cadherin and vimentin in SGC7901 cells, with typical morphological changes of EMT. Tipα alsomore » promoted proliferation and migration of SGC7901 cells. Furthermore, Tipα activated interleukin-6 (IL-6)/STAT3 signaling pathway in SGC7901 cells. The effects of Tipα treatment observed was abolished when we block IL-6/STAT3 signaling pathway. Altogether, our data demonstrated that Tipα may accelerate tumor aggressiveness in gastric cancer by promoting EMT through activation of IL-6/STAT3 pathway. - Highlights: • Tipα induces EMT and activates IL-6/STAT3 pathway in gastric cancer cells. • IL-6/STAT3 pathway inhibition reverses Tipα-induced proliferation and migration in gastric cancer cells. • Tipα induces EMT in gastric cancer cells via IL-6/STAT3 pathway activation.« less

  8. Characterization of a membrane-based, electrochemically driven pumping system using aqueous electrolyte solutions.

    PubMed

    Norman, Mya A; Evans, Christine E; Fuoco, Anthony R; Noble, Richard D; Koval, Carl A

    2005-10-01

    Electrokinetic flow provides a mechanism for a variety of fluid pumping schemes. The design and characterization of an electrochemically driven pump that utilizes porous carbon electrodes, iodide/triiodide redox electrolytes, and Nafion membranes is described. Fluid pumping by the cell is reversible and controlled by the cell current. Chronopotentiometry experiments indicate that the total available fluid that can be pumped in a single electrolysis without gas evolution is determined solely by the initial concentration of electrolyte and the applied current. The magnitude of the fluid flow at a given current is determined by the nature of the cation in the electrolyte and by the water absorption properties of the Nafion membrane. For 1 M aqueous electrolytes, pumping rates ranging from 1 to 14 microL/min were obtained for current densities of 10-30 mA/cm2 of membrane area. Molar volume changes for the I3-/I- redox couple and for the alkali cation migration contribute little to the observed volumetric flow rates; the magnitude of the flow is dominated by the migration-induced flow of water.

  9. Peritoneal fluid transport: mechanisms, pathways, methods of assessment.

    PubMed

    Waniewski, Jacek

    2013-11-01

    Fluid removal during peritoneal dialysis is controlled by many mutually dependent factors and therefore its analysis is more complex than that of the removal of small solutes used as markers of dialysis adequacy. Many new tests have been proposed to assess quantitatively different components of fluid transport (transcapillary ultrafiltration, peritoneal absorption, free water, etc.) and to estimate the factors that influence the rate of fluid transport (osmotic conductance). These tests provide detailed information about indices and parameters that describe fluid transport, especially those concerning the problem of the permanent loss of ultrafiltration capacity (ultrafiltration failure). Different theories and respective mathematical models of mechanisms and pathways of fluid transport are presently discussed and applied, and some fluid transport issues are still debated. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

  10. Synergistic effect of atorvastatin and cyanidin-3-glucoside against angiotensin II-mediated vascular smooth muscle cell proliferation and migration through MAPK and PI3K/Akt pathways.

    PubMed

    Pantan, Rungusa; Tocharus, Jiraporn; Phatsara, Manussabhorn; Suksamrarn, Apichart; Tocharus, Chainarong

    2016-09-13

    This study aimed to investigate the mechanism of cyanidin-3-glucoside (C3G) in synergy with atorvastatin, even when it is used in low concentrations. Human aortic smooth muscle cells (HASMCs) were used to verify the synergistic mechanism of atorvastatin and C3G against angiotensin II-induced proliferation and migration. BrdU incorporation assay was used to evaluate cell proliferation. Wound healing and Boyden chamber assays were used to investigate cell migration. The cell cycle was examined using flow cytometry. The results revealed that atorvastatin and C3G exhibit a synergistic effect in ameliorating HASMC proliferation and migration by enhancing cell cycle arrest. In addition, these effects also decreased mitogen-activated protein kinase (MAPK) activity by attenuating the expression of phospho-p38, phospho-extracellular signaling-regulated kinase 1/2, and phospho-c-Jun N-terminal kinase. Furthermore, the combination of atorvastatin and C3G modulated the PI3K/Akt pathway and upregulated p21 Cip1 , which was associated with decreases in cyclin D 1 and phospho-retinoblastoma expressions. The synergistic effect of atorvastatin and C3G induced anti-proliferation and anti-migration through MAPK and PI3K/Akt pathways mediated by AT 1 R. These results suggest that the synergistic effect of atorvastatin and C3G may be an alternative therapy for atherosclerosis patients.

  11. C5a and C5aR are elevated in joints of rheumatoid and psoriatic arthritis patients, and C5aR blockade attenuates leukocyte migration to synovial fluid.

    PubMed

    Hornum, Lars; Hansen, Anker Jon; Tornehave, Ditte; Fjording, Marianne Scheel; Colmenero, Paula; Wätjen, Inger Falbe; Søe Nielsen, Niels Henrik; Bliddal, Henning; Bartels, Else Marie

    2017-01-01

    Complement activation correlates to rheumatoid arthritis disease activity, and increased amounts of the complement split product C5a is observed in synovial fluids from rheumatoid arthritis patients. Blockade of C5a or its receptor (C5aR) is efficacious in several arthritis models. The aim of this study was to investigate the role of C5a and C5aR in human rheumatoid arthritis and psoriatic arthritis-both with respect to expression and function. Synovial fluid, blood and synovial samples were obtained from rheumatoid arthritis, psoriatic arthritis and osteoarthritis patients as a less inflammatory arthritis type, and blood from healthy subjects. Cells infiltrating synovial tissue were analysed by immunohistochemistry and flow cytometry. SF and blood were analysed for biomarkers by flow cytometry or ELISA. The effect of a blocking anti-human C5aR mAb on leukocyte migration was determined using a Boyden chamber. Appropriate statistical tests were applied for comparisons. C5aR+ cells were detected in most rheumatoid arthritis, in all psoriatic arthritis, but not in non-inflammatory control synovia. C5aR+ cells were primarily neutrophils and macrophages. C5aR+ macrophages were mainly found in lymphoid aggregates in close contact with T cells. C5a levels were increased in both rheumatoid arthritis and psoriatic arthritis synovial fluid compared to osteoarthritis, and in blood from rheumatoid arthritis compared to healthy subjects. Neutrophil and monocyte migration to rheumatoid arthritis synovial fluid was significantly inhibited by anti-C5aR. The data support that the C5a-C5aR axis may be driving the infiltration of inflammatory cells into the synovial fluid and synovium in both rheumatoid and psoriatic arthritis, and suggest that C5a or C5aR may be a promising treatment target in both diseases.

  12. Thermocapillary Migration and Interactions of Bubbles and Drops

    NASA Technical Reports Server (NTRS)

    Balasubramaniam, R.; Lacy, Claud E.; Wozniak, Guenter; Subramanian, R. Shankar

    1996-01-01

    When a drop or bubble is placed in another fluid and subjected to the action of a temperature gradient, the drop will move. Such motion is a direct consequence of the variation of interfacial tension with temperature, and is termed thermocapillary migration. This paper discusses results from experiments conducted in reduced gravity on the thermocapillary motion of bubbles and drops.

  13. (Im)migrations, Relations, and Identities of African Peoples: Toward an Endarkened Transnational Feminist Praxis in Education

    ERIC Educational Resources Information Center

    Okpalaoka, Chinwe L.; Dillard, Cynthia B.

    2012-01-01

    This article focuses on the sense of what an "African" (American) identity could mean when viewed through the processes of migrations and fluid identities of contemporary African immigrant children as they interact with their African (Americans) peers in schools. The purpose of this article is to use data from a study of West African…

  14. Responding to flow: How phytoplankton adapt migration strategies to tackle turbulence

    NASA Astrophysics Data System (ADS)

    Sengupta, Anupam; Carrara, Francesco; Stocker, Roman

    2014-11-01

    Phytoplankton are among the ocean's most important organisms and it has long been recognized that turbulence is a primary determinant of their fitness. Yet, mechanisms by which phytoplankton may adapt to turbulence have remained unknown. We present experiments that demonstrate how phytoplankton are capable of rapid adaptive behavior in response to fluid flow disturbances that mimic turbulence. Our study organism was the toxic marine alga Heterosigma akashiwo, known to exhibit ``negative gravitaxis,'' i . e . , to frequently migrate upwards against gravity. To mimic the effect of Kolmogorov-scale turbulent eddies, which expose cells to repeated reorientations, we observed H. akashiwo in a ``flip chamber,'' whose orientation was periodically flipped. Tracking of single cells revealed a striking, robust behavioral adaptation, whereby within tens of minutes half of the population reversed its direction of migration to swim downwards, demonstrating an active response to fluid flow. Using confocal microscopy, we provide a physiological rationalization of this behavior in terms of the redistribution of internal organelles, and speculate on the motives for this bet-hedging-type strategy. This work suggests that the effects of fluid flow - not just passive but also active - on plankton represents a rich area of investigation with considerable implications for some of earth's most important organisms.

  15. Bioactive Fraction of Geopropolis from Melipona scutellaris Decreases Neutrophils Migration in the Inflammatory Process: Involvement of Nitric Oxide Pathway

    PubMed Central

    Franchin, Marcelo; da Cunha, Marcos Guilherme; Denny, Carina; Napimoga, Marcelo Henrique; Cunha, Thiago Mattar; Bueno-Silva, Bruno; Matias de Alencar, Severino; Ikegaki, Masaharu; Luiz Rosalen, Pedro

    2013-01-01

    The aim of this study was to evaluate the activity of the ethanolic extract of geopropolis (EEGP) from Melipona scutellaris and its fractions on the modulation of neutrophil migration in the inflammatory process, and the participation of nitric oxide (NO) pathway, as well as to check the chemical profile of the bioactive fraction. EEGP and its aqueous fraction decreased neutrophil migration in the peritoneal cavity and also the interaction of leukocytes (rolling and adhesion) with endothelial cells. The levels of chemokines CXCL1/KC and CXCL2/MIP-2 were not altered after treatment with EEGP and the aqueous fraction. It was found that the injection of NO pathway antagonists abolished the EEGP and the aqueous fraction inhibitory activity on the neutrophil migration. The expression of intercellular adhesion molecule type 1 (ICAM-1) was reduced, and nitrite levels increased after treatment with EEGP and aqueous fraction. In the carrageenan-induced paw edema model, EEGP and the aqueous fraction showed antiedema activity. No pattern of flavonoid and phenolic acid commonly found in propolis samples of Apis mellifera could be detected in the aqueous fraction samples. These data indicate that the aqueous fraction found has promising bioactive substances with anti-inflammatory activity. PMID:23737853

  16. Bioactive Fraction of Geopropolis from Melipona scutellaris Decreases Neutrophils Migration in the Inflammatory Process: Involvement of Nitric Oxide Pathway.

    PubMed

    Franchin, Marcelo; da Cunha, Marcos Guilherme; Denny, Carina; Napimoga, Marcelo Henrique; Cunha, Thiago Mattar; Bueno-Silva, Bruno; Matias de Alencar, Severino; Ikegaki, Masaharu; Luiz Rosalen, Pedro

    2013-01-01

    The aim of this study was to evaluate the activity of the ethanolic extract of geopropolis (EEGP) from Melipona scutellaris and its fractions on the modulation of neutrophil migration in the inflammatory process, and the participation of nitric oxide (NO) pathway, as well as to check the chemical profile of the bioactive fraction. EEGP and its aqueous fraction decreased neutrophil migration in the peritoneal cavity and also the interaction of leukocytes (rolling and adhesion) with endothelial cells. The levels of chemokines CXCL1/KC and CXCL2/MIP-2 were not altered after treatment with EEGP and the aqueous fraction. It was found that the injection of NO pathway antagonists abolished the EEGP and the aqueous fraction inhibitory activity on the neutrophil migration. The expression of intercellular adhesion molecule type 1 (ICAM-1) was reduced, and nitrite levels increased after treatment with EEGP and aqueous fraction. In the carrageenan-induced paw edema model, EEGP and the aqueous fraction showed antiedema activity. No pattern of flavonoid and phenolic acid commonly found in propolis samples of Apis mellifera could be detected in the aqueous fraction samples. These data indicate that the aqueous fraction found has promising bioactive substances with anti-inflammatory activity.

  17. Sphingosine 1-Phosphate (S1P) Receptors 1 and 2 Coordinately Induce Mesenchymal Cell Migration through S1P Activation of Complementary Kinase Pathways*

    PubMed Central

    Quint, Patrick; Ruan, Ming; Pederson, Larry; Kassem, Moustapha; Westendorf, Jennifer J.; Khosla, Sundeep; Oursler, Merry Jo

    2013-01-01

    Normal bone turnover requires tight coupling of bone resorption and bone formation to preserve bone quantity and structure. With aging and during several pathological conditions, this coupling breaks down, leading to either net bone loss or excess bone formation. To preserve or restore normal bone metabolism, it is crucial to determine the mechanisms by which osteoclasts and osteoblast precursors interact and contribute to coupling. We showed that osteoclasts produce the chemokine sphingosine 1-phosphate (S1P), which stimulates osteoblast migration. Thus, osteoclast-derived S1P may recruit osteoblasts to sites of bone resorption as an initial step in replacing lost bone. In this study we investigated the mechanisms by which S1P stimulates mesenchymal (skeletal) cell chemotaxis. S1P treatment of mesenchymal (skeletal) cells activated RhoA GTPase, but this small G protein did not contribute to migration. Rather, two S1P receptors, S1PR1 and S1PR2, coordinately promoted migration through activation of the JAK/STAT3 and FAK/PI3K/AKT signaling pathways, respectively. These data demonstrate that the chemokine S1P couples bone formation to bone resorption through activation of kinase signaling pathways. PMID:23300082

  18. Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway

    PubMed Central

    Li, Shang; Dang, Yuanye; Zhou, Xuelin; Huang, Bin; Huang, Xiaohui; Zhang, Zherui; Kwan, Yiu Wa; Chan, Shun Wan; Leung, George Pak Heng; Lee, Simon Ming Yuen; Hoi, Maggie Pui Man

    2015-01-01

    Formononetin is an isoflavone that has been shown to display estrogenic properties and induce angiogenesis activities. However, the interrelationship between the estrogenic properties and angiogenesis activities of formononetin are not well defined. In the present study, docking and enzymatic assay demonstrated that formononetin displayed direct binding to the ligand-binding domain (LBD) of estrogen receptor alpha (ERα) with an agonistic property. Results from Human Umbilical Vein Endothelial Cells (HUVEC) by using real-time migration xCELLigence system, immunofluorescence and western blotting provided strong evidences of formononetin induced endothelial cell migration and dramatic actin cytoskeleton spatial modification through ERα-enhanced-ROCK-II/MMP2/9 signaling pathways. In addition, results from co-immunoprecipitation suggested formononetin induced cell migration via recruiting of ERα/ROCK-II activated complex formation. More interestingly, in zebrafish embryo we observed that formononetin significantly promoted angiogenic sproutings in the subintestinal vessels (SIVs) that could be completely abolished by ROCK inhibitor. In this study, we elucidated the underlying mechanisms that formononetin produced proangiogenesis effects through an ERα-enhanced ROCK-II signaling pathways. Results from the present study also expand our knowledge about the enigmatic underlying mechanisms of phytoestrogenic compounds in the promotion of angiogenesis in relation to ERα and ROCK interaction in endothelial cells and their relationship with actin assembly and cell migration. PMID:26568398

  19. Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway.

    PubMed

    Li, Shang; Dang, Yuanye; Zhou, Xuelin; Huang, Bin; Huang, Xiaohui; Zhang, Zherui; Kwan, Yiu Wa; Chan, Shun Wan; Leung, George Pak Heng; Lee, Simon Ming Yuen; Hoi, Maggie Pui Man

    2015-11-16

    Formononetin is an isoflavone that has been shown to display estrogenic properties and induce angiogenesis activities. However, the interrelationship between the estrogenic properties and angiogenesis activities of formononetin are not well defined. In the present study, docking and enzymatic assay demonstrated that formononetin displayed direct binding to the ligand-binding domain (LBD) of estrogen receptor alpha (ERα) with an agonistic property. Results from Human Umbilical Vein Endothelial Cells (HUVEC) by using real-time migration xCELLigence system, immunofluorescence and western blotting provided strong evidences of formononetin induced endothelial cell migration and dramatic actin cytoskeleton spatial modification through ERα-enhanced-ROCK-II/MMP2/9 signaling pathways. In addition, results from co-immunoprecipitation suggested formononetin induced cell migration via recruiting of ERα/ROCK-II activated complex formation. More interestingly, in zebrafish embryo we observed that formononetin significantly promoted angiogenic sproutings in the subintestinal vessels (SIVs) that could be completely abolished by ROCK inhibitor. In this study, we elucidated the underlying mechanisms that formononetin produced proangiogenesis effects through an ERα-enhanced ROCK-II signaling pathways. Results from the present study also expand our knowledge about the enigmatic underlying mechanisms of phytoestrogenic compounds in the promotion of angiogenesis in relation to ERα and ROCK interaction in endothelial cells and their relationship with actin assembly and cell migration.

  20. Petrological insights into intermediate-depths of a subduction plate interface

    NASA Astrophysics Data System (ADS)

    Angiboust, Samuel; Agard, Philippe

    2013-04-01

    Understanding processes acting along the subduction interface is crucial to assess lithospheric scale coupling between tectonic plates, exhumation of deep-seated rocks and mechanisms causing intermediate-depth seismicity. Yet, despite a wealth of geophysical studies aimed at better characterizing the subduction interface, we still lack critical petrological data constraining such processes as intermediate-seismicity within oceanic subduction zones. This contribution reviews recent findings from two major localities showing deeply subducted ophiolitic remnants (Zermatt-Saas, Monviso), which crop out in the classic, well-preserved fossil subduction setting of the Western Alps. We herein show that both ophiolite remnants represent large, relatively continuous fragments of oceanic lithosphere (i.e., several km-thick tectonic slices across tens of km) exhumed from ~80 km depths and thereby provide important constraints on interplate coupling mechanisms. In both fragments (but even more so in the Zermatt-Saas one) pervasive hydrothermal processes and seafloor alteration, promoting fluid incorporation in both mafic and associated ultramafic rocks, was essential, together with the presence of km-thick serpentinite soles, to decrease the density of the tectonic slices and prevent them from an irreversible sinking into the mantle. The Monviso case sudy provides further insights into the subduction plate interface at ~80 km depths. The Lago Superiore Unit, in particular, is made of a 50-500 m thick eclogitized mafic crust (associated with minor calcschist lenses) overlying a 100-400 m thick metagabbroic body and a km-thick serpentinite sole, and is cut by two 10 to 100m thick eclogite-facies shear zones, respectively located at the boundary between basalts and gabbros, and between gabbros and serpentinites (the Lower Shear Zone: LSZ). The LSZ gives precious information on both seismicity and fluid flow: (1) Eclogite breccias, reported here for the first time, mark the locus of an ancient fault zone associated with intraslab, intermediate-depth earthquakes at ~80 km depth. They correspond to m-sized blocks made of 1-10 cm large fragments of eclogite mylonite later embedded in serpentinite in the eclogite facies LSZ. We suggest that seismic brecciation (possibly at magnitudes Mw ~4) occurred in the middle part of the oceanic crust, accompanied by the input of externally-derived fluids. (2) Prominent fluid-rock interactions, as attested by ubiquitous metasomatic rinds, affected the fragments of mylonitic basaltic eclogites and calcschists dragged and dismembered within serpentinite during eclogite-facies deformation. Detailed petrological and geochemical investigations point to a massive, pulse-like, fluid-mediated element transfer essentially originating from serpentinite. Antigorite breakdown, occurring ca. 15 km deeper than the maximum depth reached by these eclogites, is regarded as the likely source of this highly focused fluid/rock interaction and element transfer. Such a pulse-like, subduction-parallel fluid migration pathway within the downgoing oceanic lithosphere may have been promoted by transient slip behaviour along the LSZ under eclogite-facies conditions. These petrological data are finally tied to bi-phase numerical models in which fluid migration is driven by fluid concentrations in the rocks, non-lithostatic pressure gradients and deformation, and that allow for mantle wedge hydration and mechanical weakening of the plate interface. We suggest that the detachment of such oceanic tectonic slices is largely promoted by fluid circulation along the subduction interface, as well as by subducting a strong and originally discontinuous mafic crust.

  1. Arachidonic acid-induced Ca2+ entry and migration in a neuroendocrine cancer cell line.

    PubMed

    Goswamee, Priyodarshan; Pounardjian, Tamar; Giovannucci, David R

    2018-01-01

    Store-operated Ca 2+ entry (SOCE) has been implicated in the migration of some cancer cell lines. The canonical SOCE is defined as the Ca 2+ entry that occurs in response to near-maximal depletion of Ca 2+ within the endoplasmic reticulum. Alternatively, arachidonic acid (AA) has been shown to induce Ca 2+ entry in a store-independent manner through Orai1/Orai3 hetero-multimeric channels. However, the role of this AA-induced Ca 2+ entry pathway in cancer cell migration has not been adequately assessed. The present study investigated the involvement of AA-induced Ca 2+ entry in migration in BON cells, a model gastro-enteropancreatic neuroendocrine tumor (GEPNET) cell line using pharmacological and gene knockdown methods in combination with live cell fluorescence imaging and standard migration assays. We showed that both the store-dependent and AA-induced Ca 2+ entry modes could be selectively activated and that exogenous administration of AA resulted in Ca 2+ entry that was pharmacologically distinct from SOCE. Also, whereas homomeric Orai1-containing channels appeared to largely underlie SOCE, the AA-induced Ca 2+ entry channel required the expression of Orai3 as well as Orai1. Moreover, we showed that AA treatment enhanced the migration of BON cells and that this migration could be abrogated by selective inhibition of the AA-induced Ca 2+ entry. Taken together, these data revealed that an alternative Orai3-dependent Ca 2+ entry pathway is an important signal for GEPNET cell migration.

  2. Uridine 5′-Triphosphate Promotes In Vitro Schwannoma Cell Migration through Matrix Metalloproteinase-2 Activation

    PubMed Central

    Martiañez, Tania; Segura, Mònica; Figueiro-Silva, Joana; Grijota-Martinez, Carmen; Trullas, Ramón; Casals, Núria

    2014-01-01

    In response to peripheral nerve injury, Schwann cells adopt a migratory phenotype and modify the extracellular matrix to make it permissive for cell migration and axonal re-growth. Uridine 5′-triphosphate (UTP) and other nucleotides are released during nerve injury and activate purinergic receptors expressed on the Schwann cell surface, but little is known about the involvement of purine signalling in wound healing. We studied the effect of UTP on Schwannoma cell migration and wound closure and the intracellular signaling pathways involved. We found that UTP treatment induced Schwannoma cell migration through activation of P2Y2 receptors and through the increase of extracellular matrix metalloproteinase-2 (MMP-2) activation and expression. Knockdown P2Y2 receptor or MMP-2 expression greatly reduced wound closure and MMP-2 activation induced by UTP. MMP-2 activation evoked by injury or UTP was also mediated by phosphorylation of all 3 major mitogen-activated protein kinases (MAPKs): JNK, ERK1/2, and p38. Inhibition of these MAPK pathways decreased both MMP-2 activation and cell migration. Interestingly, MAPK phosphorylation evoked by UTP exhibited a biphasic pattern, with an early transient phosphorylation 5 min after treatment, and a late and sustained phosphorylation that appeared at 6 h and lasted up to 24 h. Inhibition of MMP-2 activity selectively blocked the late, but not the transient, phase of MAPK activation. These results suggest that MMP-2 activation and late MAPK phosphorylation are part of a positive feedback mechanism to maintain the migratory phenotype for wound healing. In conclusion, our findings show that treatment with UTP stimulates in vitro Schwannoma cell migration and wound repair through a MMP-2-dependent mechanism via P2Y2 receptors and MAPK pathway activation. PMID:24905332

  3. NOR1 promotes hepatocellular carcinoma cell proliferation and migration through modulating the Notch signaling pathway

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    You, Kun; Sun, Peisheng; Yue, Zhongyi

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Previous studies have reported that the oxidored-nitro domain containing protein 1 (NOR1) is a novel tumor suppressor in several tumors. Recent evidence suggests that NOR1 is strongly expressed in HCC cells. However, its role and mechanism in HCC are unclear. In the current study, Western blot and qPCR detected strong NOR1 mRNA and protein expression in HepG2 and Hep3B cells. After transfection with NOR1 siRNA or pcDNA3.1-myc-his-NOR1, the proliferation and migration of HepG2 and Hep3B cells were analyzed in vitro. HepG2 or Hep3B cells overexpressing NOR1 showed anmore » increased proliferation and migration, whereas siRNA-mediated silencing of NOR1 showed the opposite effect. Furthermore, NOR1 activated the Notch signaling pathway, indicated by increased levels of Notch1, NICD, Hes1, and Hey1 in protein. Importantly, the Notch inhibitor DAPT downregulated Notch activation and further enhanced siNOR1-induced reduction of cell proliferation and migration in HepG2 and Hep3B cells, whereas DAPT reversed the effect of NOR1 overexpression on cell proliferation and migration. In conclusion, these results indicate that NOR1 may be involved in the progression of HCC and thus may be a potential target for the treatment of liver cancer. - Highlights: • NOR1 expression is up-regulated in HCC cells. • NOR1 promotes the proliferation and migration of HCC cells. • NOR1 promotes the progression of HCC cells by activating Notch pathway.« less

  4. Bradykinin Promotes Cell Proliferation, Migration, Invasion, and Tumor Growth of Gastric Cancer Through ERK Signaling Pathway.

    PubMed

    Wang, Guojun; Sun, Junfeng; Liu, Guanghui; Fu, Yang; Zhang, Xiefu

    2017-12-01

    Bradykinin (BK) has been reported to be involved in the progression of diverse types of cancer. In the present study, we investigated the possible role of BK in cell proliferation, migration, invasion, and tumor growth of gastric cancer (GC). Cell proliferation was evaluated by MTT assays. Cell migration and invasion were assessed by Transwell assays. Tumor growth of nude mice was detected by establishing subcutaneous xenograft tumor model. Silencing of bradykinin B1 receptor (B1R) and the bradykinin B2 receptor (B2R) was performed by transfecting cells with si-B1R and si-B2R, respectively. The protein expression levels of phospho-ERK1/2 (p-ERK1/2), matrix metalloproteinase (MMP)-2, MMP-9, and E-Cadherin were examined by Western blot. Data revealed that BK promoted cell proliferation, migration, invasion, and the in vivo tumor growth of GC cells SGC-7901 and HGC-27. Furthermore, BK elevated the protein levels of p-ERK1/2, MMP-2, and MMP-9, but reduced E-Cadherin. In addition, by repressing B2R using si-B2R or inhibiting ERK signaling pathway using PD98059, BK-mediated promotion of cell proliferation, migration, and invasion and upregulation of p-ERK1/2, MMP-2/9, as well as downregulation of E-Cadherin were attenuated. Taken together, the present study demonstrated that BK promoted cell proliferation, migration, invasion, and tumor growth by binding to B2R via ERK signaling pathway. Our findings may provide promising options for the further treatment of GC. J. Cell. Biochem. 118: 4444-4453, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. Cell-autonomous inactivation of the Reelin pathway impairs adult neurogenesis in the hippocampus

    PubMed Central

    Teixeira, Catia M.; Kron, Michelle M.; Masachs, Nuria; Zhang, Helen; Lagace, Diane C.; Martinez, Albert; Reillo, Isabel; Duan, Xin; Bosch, Carles; Pujadas, Lluis; Brunso, Lucas; Song, Hongjun; Eisch, Amelia J.; Borrell, Victor; Howell, Brian W.; Parent, Jack M.; Soriano, Eduardo

    2012-01-01

    Adult hippocampal neurogenesis is thought to be essential for learning and memory and has been implicated in the pathogenesis of several disorders. Although recent studies have identified key factors regulating neuroprogenitor proliferation in the adult hippocampus, the mechanisms that control the migration and integration of adult-born neurons into circuits are largely unknown. Reelin is an extracellular matrix protein that is vital for neuronal development. Activation of the Reelin cascade leads to phosphorylation of disabled-1 (Dab1), an adaptor protein required for Reelin signaling. Here we used transgenic mouse and retroviral reporters along with Reelin signaling gain- and loss-of-function studies to show that the Reelin pathway regulates migration and dendritic development of adult-generated hippocampal neurons. Whereas overexpression of Reelin accelerated dendritic maturation, inactivation of the Reelin signaling pathway specifically in adult neuroprogenitor cells resulted in aberrant migration, decreased dendrite development, formation of ectopic dendrites in the hilus and the establishment of aberrant circuits. Our findings support a cell-autonomous and critical role for the Reelin pathway in regulating dendritic development and the integration of adult-generated granule cells and point to this pathway as a key regulator of adult neurogenesis. Moreover, our data reveal a novel role of the Reelin cascade in adult brain function with potential implications for the pathogenesis of several neurological and psychiatric disorders. PMID:22933789

  6. A porous flow approach to model thermal non-equilibrium applicable to melt migration

    NASA Astrophysics Data System (ADS)

    Schmeling, Harro; Marquart, Gabriele; Grebe, Michael

    2018-01-01

    We develop an approach for heat exchange between a fluid and a solid phase of a porous medium where the temperatures of the fluid and matrix are not in thermal equilibrium. The formulation considers moving of the fluid within a resting or deforming porous matrix in an Eulerian coordinate system. The approach can be applied, for example, to partially molten systems or to brine transport in porous rocks. We start from an existing theory for heat exchange where the energy conservation equations for the fluid and the solid phases are separated and coupled by a heat exchange term. This term is extended to account for the full history of heat exchange. It depends on the microscopic geometry of the fluid phase. For the case of solid containing hot, fluid-filled channels, we derive an expression based on a time-dependent Fourier approach for periodic half-waves. On the macroscopic scale, the temporal evolution of the heat exchange leads to a convolution integral along the flow path of the solid, which simplifies considerably in case of a resting matrix. The evolution of the temperature in both phases with time is derived by inserting the heat exchange term into the energy equations. We explore the effects of thermal non-equilibrium between fluid and solid by considering simple cases with sudden temperature differences between fluid and solid as initial or boundary conditions, and by varying the fluid velocity with respect to the resting porous solid. Our results agree well with an analytical solution for non-moving fluid and solid. The temperature difference between solid and fluid depends on the Peclet number based on the Darcy velocity. For Peclet numbers larger than 1, the temperature difference after one diffusion time reaches 5 per cent of \\tilde{T} or more (\\tilde{T} is a scaling temperature, e.g. the initial temperature difference). Thus, our results imply that thermal non-equilibrium can play an important role for melt migration through partially molten systems where melt focuses into melt channels near the transition to melt ascent by dykes. Our method is based on solving the convolution integration for the heat exchange over the full flow history, which is numerically expensive. We tested to replace the heat exchange term by an instantaneous, approximate term. We found considerable errors on the short timescale, but a good agreement on the long timescale if appropriate parameters for the approximate terms are used. We derived these parameters which may be implemented in fully dynamical two-phase flow formulations of melt migration in the Earth.

  7. Connexin 32 and its derived homotypic gap junctional intercellular communication inhibit the migration and invasion of transfected HeLa cells via enhancement of intercellular adhesion.

    PubMed

    Yang, Jie; Liu, Bing; Wang, Qin; Yuan, Dongdong; Hong, Xiaoting; Yang, Yan; Tao, Liang

    2011-01-01

    The effects of connexin (Cx) and its derived homotypic gap junctional intercellular communication (GJIC) between tumor cells on the invasion of metastatic cancers and the underlying mechanisms remain unclear. In this study, we investigated the influence of Cx32 and the homotypic GJIC mediated by this Cx on the migration, invasion and intercellular adhesion of transfected HeLa cells. The expression of Cx32 significantly increased cell adhesion and inhibited migration and invasion. The inhibition of GJIC by oleamide, a widely used GJIC inhibitor, reduced the enhanced adhesion and partly reversed the decreased migration and invasion that had been induced by Cx32 expression. Blockage of the p38 and extracellular signal-regulated kinase 1 and 2 mitogen-activated protein kinase (ERK1/2 MAPKs) pathways using their specific inhibitors attenuated the effects of Cx32, but not those of GJIC, on cell adhesion, migration and invasion. These results indicate that the homotypic GJIC mediated by Cx32, as well as the Cx itself, inhibit cell migration and invasion, most likely through the elevation of intercellular adhesion. The suppressive effect of Cx32 on the migration and invasion of cancer cells, but not that of its derived homotypic GJIC, partly depends on the activation of the p38 and the ERK1/2 MAPKs pathways.

  8. Increased dermal collagen bundle alignment in systemic sclerosis is associated with a cell migration signature and role of Arhgdib in directed fibroblast migration on aligned ECMs

    PubMed Central

    Lafyatis, Robert; Burkly, Linda C.

    2017-01-01

    Systemic sclerosis (SSc) is a devastating disease affecting the skin and internal organs. Dermal fibrosis manifests early and Modified Rodnan Skin Scores (MRSS) correlate with disease progression. Transcriptomics of SSc skin biopsies suggest the role of the in vivo microenvironment in maintaining the pathological myofibroblasts. Therefore, defining the structural changes in dermal collagen in SSc patients could inform our understanding of fibrosis pathogenesis. Here, we report a method for quantitative whole-slide image analysis of dermal collagen from SSc patients, and our findings of more aligned dermal collagen bundles in diffuse cutaneous SSc (dcSSc) patients. Using the bleomycin-induced mouse model of SSc, we identified a distinct high dermal collagen bundle alignment gene signature, characterized by a concerted upregulation in cell migration, adhesion, and guidance pathways, and downregulation of spindle, replication, and cytokinesis pathways. Furthermore, increased bundle alignment induced a cell migration gene signature in fibroblasts in vitro, and these cells demonstrated increased directed migration on aligned ECM fibers that is dependent on expression of Arhgdib (Rho GDP-dissociation inhibitor 2). Our results indicate that increased cell migration is a cellular response to the increased collagen bundle alignment featured in fibrotic skin. Moreover, many of the cell migration genes identified in our study are shared with human SSc skin and may be new targets for therapeutic intervention. PMID:28662216

  9. Role of high-mobility group box 1 in methamphetamine-induced activation and migration of astrocytes.

    PubMed

    Zhang, Yuan; Zhu, Tiebing; Zhang, Xiaotian; Chao, Jie; Hu, Gang; Yao, Honghong

    2015-09-04

    Mounting evidence has indicated that high-mobility group box 1 (HMGB1) is involved in cell activation and migration. Our previous study demonstrated that methamphetamine mediates activation of astrocytes via sigma-1 receptor (σ-1R). However, the elements downstream of σ-1R in this process remain poorly understood. Thus, we examined the molecular mechanisms involved in astrocyte activation and migration induced by methamphetamine. The expression of HMGB1, σ-1R, and glial fibrillary acidic protein (GFAP) was examined by western blot and immunofluorescent staining. The phosphorylation of cell signaling pathways was detected by western blot, and cell migration was examined using a wound-healing assay in rat C6 astroglia-like cells transfected with lentivirus containing red fluorescent protein (LV-RFP) as well as in primary human astrocytes. The role of HMGB1 in astrocyte activation and migration was validated using a siRNA approach. Exposure of C6 cells to methamphetamine increased the expression of HMGB1 via the activation of σ-1R, Src, ERK mitogen-activated protein kinase, and downstream NF-κB p65 pathways. Moreover, methamphetamine treatment resulted in increased cell activation and migration in C6 cells and primary human astrocytes. Knockdown of HMGB1 in astrocytes transfected with HMGB1 siRNA attenuated the increased cell activation and migration induced by methamphetamine, thereby implicating the role of HMGB1 in the activation and migration of C6 cells and primary human astrocytes. This study demonstrated that methamphetamine-mediated activation and migration of astrocytes involved HMGB1 up-regulation through an autocrine mechanism. Targeting HMGB1 could provide insights into the development of a potential therapeutic approach for alleviation of cell activation and migration of astrocytes induced by methamphetamine.

  10. Agmatine promotes the migration of murine brain endothelial cells via multiple signaling pathways.

    PubMed

    Jung, Hyun-Joo; Jeon, Yong-Heui; Bokara, Kiran Kumar; Koo, Bon-Nyeo; Lee, Won Taek; Park, Kyung Ah; Lee, Jong-Eun

    2013-01-17

    The combination of adhesion and migration of endothelial cells (ECs) is an integral process for evolution, organization, repair and vessel formation in living organisms. Agmatine, a polycationic amine existing in brain, has been investigated to exert neuroprotective effects. Up to date, there are no studies reporting that agmatine modulates murine brain endothelial (bEnd.3) cells migration. In the present study, we intend to investigate the role of agmatine in bEnd.3 cells migration and the molecular mechanism mediating this action. The effect of agmatine on the bEnd.3 cells migration was examined by migration assay, and the mechanism involved for this effect was investigated by western blot analysis and NO contents measurements. Agmatine treatment (50, 100 and 200 μM) significantly accelerated bEnd.3 cells migration in a concentration-dependent manner. Western blotting revealed that agmatine treatment significantly induced vascular endothelial growth factor (VEGF), VEGF receptor 2 (Flk-1/KDR or VEGFR2), phosphatidylinositol 3-kinase (PI3K), Akt/protein kinase B (also known as PKB, PI3K downstream effector protein), endothelial nitric oxide synthase (eNOS) nitric oxide (NO; product by eNOS) and intercellular adhesion molecule 1 (ICAM-1) expressions during bEnd.3 cells migration. The expression of ICAM-1 and migration of bEnd.3 cells, induced by agmatine, were significantly attenuated by treatment of wortmannin, a specific PI3K inhibitor. Taken together, we provide the first evidence that activation of VEGF/VEGFR2 and the consequential PI3K/Akt/eNOS/NO/ICAM-1 signaling pathways are serial events, through which the treatment of agmatine could lead to bEnd.3 cells migration. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Aines, Roger D; Spadaccini, Christopher M; Stolaroff, Joshuah K

    Method and apparatus for separating a target substance from a fluid or mixture. Capsules having a coating and stripping solvents encapsulated in the capsules are provided. The coating is permeable to the target substance. The capsules having a coating and stripping solvents encapsulated in the capsules are exposed to the fluid or mixture. The target substance migrates through the coating and is taken up by the stripping solvents. The target substance is separated from the fluid or mixture by driving off the target substance from the capsules.

  12. Drosophila TNF Modulates Tissue Tension in the Embryo to Facilitate Macrophage Invasive Migration.

    PubMed

    Ratheesh, Aparna; Biebl, Julia; Vesela, Jana; Smutny, Michael; Papusheva, Ekaterina; Krens, S F Gabriel; Kaufmann, Walter; Gyoergy, Attila; Casano, Alessandra Maria; Siekhaus, Daria E

    2018-05-07

    Migrating cells penetrate tissue barriers during development, inflammatory responses, and tumor metastasis. We study if migration in vivo in such three-dimensionally confined environments requires changes in the mechanical properties of the surrounding cells using embryonic Drosophila melanogaster hemocytes, also called macrophages, as a model. We find that macrophage invasion into the germband through transient separation of the apposing ectoderm and mesoderm requires cell deformations and reductions in apical tension in the ectoderm. Interestingly, the genetic pathway governing these mechanical shifts acts downstream of the only known tumor necrosis factor superfamily member in Drosophila, Eiger, and its receptor, Grindelwald. Eiger-Grindelwald signaling reduces levels of active Myosin in the germband ectodermal cortex through the localization of a Crumbs complex component, Patj (Pals-1-associated tight junction protein). We therefore elucidate a distinct molecular pathway that controls tissue tension and demonstrate the importance of such regulation for invasive migration in vivo. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Prickle1b mediates interpretation of migratory cues during zebrafish facial branchiomotor neuron migration

    PubMed Central

    Mapp, Oni M.; Wanner, Sarah J.; Rohrschneider, Monica R.; Prince, Victoria E.

    2011-01-01

    The facial branchiomotor neurons undergo a characteristic tangential migration in the vertebrate hindbrain. Several signaling mechanisms have been implicated in this process, including the non-canonical Wnt/planar cell polarity (PCP) pathway. However, the role of this signaling pathway in controlling the dynamics of these neurons is unclear. Here, we describe the cellular dynamics of the facial neurons as they migrate, focusing on the speed and direction of migration, extension of protrusions, cell shape and orientation. Furthermore, we show that the PET/LIM domain protein Prickle1b (Pk1b) is required for several aspects of these migratory behaviors, including cell orientation. However, we find that centrosome localization is not significantly affected by disruption of Pk1b function, suggesting that polarization of the neurons is not completely lost. Together, our data suggest that Pk1b function may be required to integrate the multiple migratory cues received by the neurons into polarization instructions for proper posterior movement. PMID:20503357

  14. Estradiol induces endothelial cell migration and proliferation through estrogen receptor-enhanced RhoA/ROCK pathway.

    PubMed

    Oviedo, Pilar J; Sobrino, Agua; Laguna-Fernandez, Andrés; Novella, Susana; Tarín, Juan J; García-Pérez, Miguel-Angel; Sanchís, Juan; Cano, Antonio; Hermenegildo, Carlos

    2011-03-30

    Migration and proliferation of endothelial cells are involved in re-endothelialization and angiogenesis, two important cardiovascular processes that are increased in response to estrogens. RhoA, a small GTPase which controls multiple cellular processes, is involved in the control of cell migration and proliferation. Our aim was to study the role of RhoA on estradiol-induced migration and proliferation and its dependence on estrogen receptors activity. Human umbilical vein endothelial cells were stimulated with estradiol, in the presence or absence of ICI 182780 (estrogen receptors antagonist) and Y-27632 (Rho kinase inhibitor). Estradiol increased Rho GEF-1 gene expression and RhoA (gene and protein expression and activity) in an estrogen receptor-dependent manner. Cell migration, stress fiber formation and cell proliferation were increased in response to estradiol and were also dependent on the estrogen receptors and RhoA activation. Estradiol decreased p27 levels, and significantly raised the expression of cyclins and CDK. These effects were counteracted by the use of either ICI 182780 or Y-27632. In conclusion, estradiol enhances the RhoA/ROCK pathway and increases cell cycle-related protein expression by acting through estrogen receptors. This results in an enhanced migration and proliferation of endothelial cells. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  15. Messinian Salinity Crisis and basin fluid flow

    NASA Astrophysics Data System (ADS)

    Bertoni, Claudia; Cartwight, Joe

    2014-05-01

    Syn- and post-depositional movement of fluids through sediments is one of the least understood aspects in the evolution of a basin. The conventional hydrostratigraphic view on marine sedimentary basins assumes that compactional and meteoric groundwater fluid circulation drives fluid movement and defines its timing. However, in the past few years, several examples of instantaneous and catastrophic release of fluids have been observed even through low-permeability sediments. A particularly complex case-study involves the presence of giant salt bodies in the depocentres of marine basins. Evaporites dramatically change the hydrostratigraphy and fluid-dynamics of the basin, and influence the P/T regimes, e.g. through changes in the geothermal gradient and in the compaction of underlying sediments. Our paper reviews the impact of the Messinian Salinity Crisis (MSC) and evaporites on fluid flow in the Mediterranean sub-basins. The analysis of geological and geophysical sub-surface data provides examples from this basin, and the comparison with analogues in other well-known evaporitic provinces. During the MSC, massive sea-level changes occurred in a relatively limited time interval, and affected the balance of fluid dynamics, e.g. with sudden release or unusual trapping of fluids. Fluid expulsion events are here analysed and classified in relation to the long and short-term effects of the MSC. Our main aim is to build a framework for the correct identification of the fluid flow-related events, and their genetic mechanisms. On basin margins, where evaporites are thin or absent, the sea-level changes associated with the MSC force a rapid basinward shift of the mixing zone of meteoric/gravity flow and saline/compactional flow, 100s-km away from its pre-MSC position. This phenomenon changes the geometry of converging flows, creates hydraulic traps for fluids, and triggers specific diagenetic reactions in pre-MSC deep marine sediments. In basin-centre settings, unloading and re-loading of water associated to the sea-level changes leads to the sudden release of focused fluids, enhancing pockmark formation, evaporite dissolution, gas-hydrate dissociation and methane venting. After the MSC, and in the long-term basin evolution, the aquitard effect of the thick evaporites also created favourable condition for the development of overpressures in the pre-MSC sediments. However, the traditional view of saline giants as impermeable barriers to fluid flow has been challenged in recent years, by the documented evidence of fluid migration pathways through thick evaporites. Ultimately, these events can lead not only to fluid, but also to sediment remobilisation. The review here presented has applications as a tool for identifying, quantifying and understanding controls and timing of fluid dynamics in marine basins hosting extensive evaporitic series.

  16. Capillary Imbibition of Hydraulic Fracturing Fluids into Partially Saturated Shale

    NASA Astrophysics Data System (ADS)

    Birdsell, D.; Rajaram, H.; Lackey, G.

    2015-12-01

    Understanding the migration of hydraulic fracturing fluids injected into unconventional reservoirs is important to assess the risk of aquifer contamination and to optimize oil and gas production. Capillary imbibition causes fracturing fluids to flow from fractures into the rock matrix where the fluids are sequestered for geologically long periods of time. Imbibition could explain the low amount of flowback water observed in the field (5-50% of the injected volume) and reduce the chance of fracturing fluid migrating out of formation towards overlying aquifers. We present calculations of spontaneous capillary imbibition in the form of an "imbibition rate parameter" (A) based on the only known exact analytical solution for spontaneous capillary imbibition. A depends on the hydraulic and capillary properties of the reservoir rock, the initial water saturation, and the viscosities of the wetting and nonwetting fluids. Imbibed volumes can be large for a high permeability shale gas reservoir (up to 95% of the injected volume) or quite small for a low permeability shale oil reservoir (as low as 3% of the injected volume). We also present a nondimensionalization of the imbibition rate parameter, which facilitates the calculation of A and clarifies the relation of A to initial saturation, porous medium properties, and fluid properties. Over the range of initial water saturations reported for the Marcellus shale (0.05-0.6), A varies by less than factors of ~1.8 and ~3.4 for gas and oil nonwetting phases respectively. However, A decreases significantly for larger initial water saturations. A is most sensitive to the intrinsic permeability of the reservoir rock and the viscosity of the fluids.

  17. Combination Treatment with Apricoxib and IL-27 Enhances Inhibition of Epithelial-Mesenchymal Transition in Human Lung Cancer Cells through a STAT1 Dominant Pathway

    PubMed Central

    Lee, Mi-Heon; Kachroo, Puja; Pagano, Paul C; Yanagawa, Jane; Wang, Gerald; Walser, Tonya C; Krysan, Kostyantyn; Sharma, Sherven; John, Maie St.; Dubinett, Steven M; Lee, Jay M

    2015-01-01

    Background The cyclooxygenase 2 (COX-2) pathway has been implicated in the molecular pathogenesis of many malignancies, including lung cancer. Apricoxib, a selective COX-2 inhibitor, has been described to inhibit epithelial-mesenchymal transition (EMT) in human malignancies. The mechanism by which apricoxib may alter the tumor microenvironment by affecting EMT through other important signaling pathways is poorly defined. IL-27 has been shown to have anti-tumor activity and our recent study showed that IL-27 inhibited EMT through a STAT1 dominant pathway. Objective The purpose of this study is to investigate the role of apricoxib combined with IL-27 in inhibiting lung carcinogenesis by modulation of EMT through STAT signaling. Methods and Results Western blot analysis revealed that IL-27 stimulation of human non-small cell lung cancer (NSCLC) cell lines results in STAT1 and STAT3 activation, decreased Snail protein and mesenchymal markers (N-cadherin and vimentin) and a concomitant increase in expression of epithelial markers (E-cadherin, β-and γ-catenins), and inhibition of cell migration. The combination of apricoxib and IL-27 resulted in augmentation of STAT1 activation. However, IL-27 mediated STAT3 activation was decreased by the addition of apricoxib. STAT1 siRNA was used to determine the involvement of STAT1 pathway in the enhanced inhibition of EMT and cell migration by the combined IL-27 and apricoxib treatment. Pretreatment of cells with STAT1 siRNA inhibited the effect of combined IL-27 and apricoxib in the activation of STAT1 and STAT3. In addition, the augmented expression of epithelial markers, decreased expression mesenchymal markers, and inhibited cell migration by the combination treatment were also inhibited by STAT1 siRNA, suggesting that the STAT1 pathway is important in the enhanced effect from the combination treatment. Conclusion Combined apricoxib and IL-27 has an enhanced effect in inhibition of epithelial-mesenchymal transition and cell migration in human lung cancer cells through a STAT1 dominant pathway. PMID:26523208

  18. Cdc42 Promotes Schwann Cell Proliferation and Migration Through Wnt/β-Catenin and p38 MAPK Signaling Pathway After Sciatic Nerve Injury.

    PubMed

    Han, Bin; Zhao, Jun-Ying; Wang, Wu-Tao; Li, Zheng-Wei; He, Ai-Ping; Song, Xiao-Yang

    2017-05-01

    Schwann cells (SCs) are unique glial cells in the peripheral nerve and may secrete multiple neurotrophic factors, adhesion molecules, extracellular matrix molecules to form the microenvironment of peripheral nerve regeneration, guiding and supporting nerve proliferation and migration. Cdc42 plays an important regulatory role in dynamic changes of the cytoskeleton. However, there is a little study referred to regulation and mechanism of Cdc42 on glial cells after peripheral nerve injury. The present study investigated the role of Cdc42 in the proliferation and migration of SCs after sciatic nerve injury. Cdc42 expression was tested, showing that the mRNA and protein expression levels of Cdc42 were significantly up-regulated after sciatic nerve injury. Then, we isolated and purified SCs from injuried sciatic nerve at day 7. The purified SCs were transfected with Cdc42 siRNA and pcDNA3.1-Cdc42, and the cell proliferation, cell cycle and migration were assessed. The results implied that Cdc42 siRNA remarkably inhibited Schwann cell proliferation and migration, and resulted in S phase arrest. While pcDNA3.1-Cdc42 showed a contrary effect. Besides, we also observed that Cdc42 siRNA down-regulated the protein expression of β-catenin, Cyclin D1, c-myc and p-p38, which were up-regulated by pcDNA3.1-Cdc42. Meanwhile, the inhibitor of Wnt/β-catenin and p38 MAPK signaling pathway IWP-2 and SB203580 significantly inhibited the effect of pcDNA3.1-Cdc42 on cell proliferation and migration. Overall, our data indicate that Cdc42 regulates Schwann cell proliferation and migration through Wnt/β-catenin and p38 MAPK signaling pathway after sciatic nerve injury, which provides further insights into the therapy of the sciatic nerve injury.

  19. Phoresis in fluids.

    PubMed

    Brenner, Howard

    2011-12-01

    This paper presents a unified theory of phoretic phenomena in single-component fluids. Simple formulas are given for the phoretic velocities of small inert force-free non-Brownian particles migrating through otherwise quiescent single-component gases and liquids and animated by a gradient in the fluid's temperature (thermophoresis), pressure (barophoresis), density (pycnophoresis), or any combination thereof. The ansatz builds upon a recent paper [Phys. Rev. E 84, 046309 (2011)] concerned with slip of the fluid's mass velocity at solid surfaces--that is, with phenomena arising from violations of the classical no-slip fluid-mechanical boundary condition. Experimental and other data are cited in support of the phoretic model developed herein.

  20. Effects of the Insulin-like Growth Factor Pathway on the Regulation of Mammary Gland Development.

    PubMed

    Ha, Woo Tae; Jeong, Ha Yeon; Lee, Seung Yoon; Song, Hyuk

    2016-09-01

    The insulin-like growth factor (IGF) pathway is a key signal transduction pathway involved in cell proliferation, migration, and apoptosis. In dairy cows, IGF family proteins and binding receptors, including their intracellular binding partners, regulate mammary gland development. IGFs and IGF receptor interactions in mammary glands influence the early stages of mammogenesis, i.e., mammary ductal genesis until puberty. The IGF pathway includes three major components, IGFs (such as IGF-I, IGF-II, and insulin), their specific receptors, and their high-affinity binding partners (IGF binding proteins [IGFBPs]; i.e., IGFBP1-6), including specific proteases for each IGFBP. Additionally, IGFs and IGFBP interactions are critical for the bioactivities of various intracellular mechanisms, including cell proliferation, migration, and apoptosis. Notably, the interactions between IGFs and IGFBPs in the IGF pathway have been difficult to characterize during specific stages of bovine mammary gland development. In this review, we aim to describe the role of the interaction between IGFs and IGFBPs in overall mammary gland development in dairy cows.

  1. Geodynamic modeling of the capture and release of a plume conduit by a migrating mid-ocean ridge

    NASA Astrophysics Data System (ADS)

    Hall, P. S.

    2011-12-01

    plates over the relatively stationary, long-lived conduits of mantle plumes. However, paleomagnetic data from the Hawaii-Emperor Seamount Chain suggests that the Hawaiian hotspot moved rapidly (~40 mm/yr) between 81 - 47 Ma [Tarduno et al., 2003]. Recently, Tarduno et al. [2009] suggested that this period of rapid motion might be the surface expression of a plume conduit returning to a largely vertical orientation after having been captured and tilted as the result of being "run over" by migrating mid-ocean ridge. I report on a series of analog geodynamic experiments designed to characterize the evolution of a plume conduit as a mid-ocean ridge migrates over. Experiments were conducted in a clear acrylic tank (100 cm x 70 cm x 50 cm) filled with commercial grade high-fructose corn syrup. Plate-driven flow is modeled by dragging two sheets of Mylar film (driven by independent DC motors) in opposite directions over the surface of the fluid. Ridge migration is achieved by moving the point at which the mylar sheets diverge using a separate motor drive. Buoyant plume flow is generated using a small electrical heater placed at the bottom of the tank. Plate velocities and ridge migration rate are controlled and plume temperature monitored using LabView software. Experiments are recorded using digital video which is then analyzed using digital image analysis software to track the position and shape of the plume conduit throughout the course of the experiment. The intersection of the plume conduit with the surface of the fluid is taken as an analog for the locus of hotspot volcanism and tracked as a function of time to obtain a hotspot migration rate. Results show that the plume conduit experiences significant tilting immediately following the passage of the migrating ridge.

  2. Development and Application of a Paleomagnetic/Geochemical Method for Constraining the Timing of Burial Diagenetic Events

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Elmore, Richard D.; Engel, Michael H.

    2006-01-05

    Studies of diagenesis caused by fluid migration or other events are commonly hindered by a lack of temporal control. Our results to date demonstrate that a paleomagnetic/geochemical approach can be used to date fluid migration as well as burial diagenetic events. Our principal working hypothesis is that burial diagenetic processes (e.g., maturation of organic-rich sediments and clay diagenesis) and the migration of fluids can trigger the authigenesis of magnetic mineral phases. The ages of these events can be constrained by comparing chemical remanent magnetizations (CRMs) to independently established Apparent Polar Wander Paths. Whilst geochemical (e.g. stable isotope and organic analyses)more » and petrographic studies provide important clues for establishing these relationships, the ultimate test of this hypothesis requires the application of independent dating methods to verify the paleomagnetic ages. Towards this end, we have used K-Ar dating of illitization as an alternative method for constraining the ages of magnetic mineral phases in our field areas. We have made significant progress toward understanding the origin and timing of chemical remagnetization related to burial diagenetic processes. For example, a recently completed field study documents a relationship between remagnetization and the maturation of organic matter (Blumstein et al., 2004). We have tested the hypothesized connection between clay diagenesis and remagnetization by conducting K-Ar dating of authigenic illites in units in Scotland and Montana with CRMs (e.g., Elliott et al., 2006a; Elliott et al., 2006b). We have also developed a fluid related model for alteration and remagnetization of Appalachian red beds that involves reduction and mobilization of iron phases by hydrocarbons and precipitation of authigenic hematite as a result of the introduction of meteoric fluid recharge (Cox et al., 2005). In addition, our recent studies of fluid-related CRMs along faults in Scotland provide information on the timing and origin of fluid flow events along the Moine and Great Glen faults (Parnell et al., 2004; Blumstein et al., 2005; Elmore et al., 2006).« less

  3. MicroRNA-300 promotes apoptosis and inhibits proliferation, migration, invasion and epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway by targeting CUL4B in pancreatic cancer cells.

    PubMed

    Zhang, Jia-Qiang; Chen, Shi; Gu, Jiang-Ning; Zhu, Yi; Zhan, Qian; Cheng, Dong-Feng; Chen, Hao; Deng, Xia-Xing; Shen, Bai-Yong; Peng, Cheng-Hong

    2018-01-01

    The study aims to verify the hypothesis that up-regulation of microRNA-300 (miR-300) targeting CUL4B promotes apoptosis and suppresses proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells by regulating the Wnt/β-catenin signaling pathway. Pancreatic cancer tissues and adjacent tissues were collected from 110 pancreatic cancer patients. Expression of miR-300, CUL4B, Wnt, β-catenin, E-cadherin, N-cadherin, Snail, GSK-3β, and CyclinD1 were detected using qRT-PCR and Western blot. CFPAC-1, Capan-1, and PANC-1 were classified into blank, negative control (NC), miR-300 mimics, miR-300 inhibitors, siRNA-CUL4B, and miR-300 inhibitors + siRNA-CUL4B groups. The proliferation, migration, invasion abilities, the cell cycle distribution, and apoptosis rates were measured in CCK-8 and Transwell assays. Pancreatic cancer tissues showed increased CUL4B expression but decreased miR-300 expression. When miR-300 was lowly expressed, CUL4B was upregulated which in-turn activated the Wnt/β-catenin pathway to protect the β-catenin expression and thus induce EMT. When miR-300 was highly expressed, CUL4B was downregulated which in-turn inhibited the Wnt/β-catenin pathway to prevent EMT. Weakened cell migration and invasion abilities and enhanced apoptosis were observed in the CUL4B group. The miR-300 inhibitors group exhibited an evident increase in growth rate accompanied the largest tumor volume. Smaller tumor volume and slower growth rate were observed in the miR-300 mimics and siRNA-CUL4B group. Our study concludes that lowly expressed miR-300 may contribute to highly expressed CUL4B activating the Wnt/β-catenin signaling pathway and further stimulating EMT, thus promoting proliferation and migration but suppressing apoptosis of pancreatic cancer cells. © 2017 Wiley Periodicals, Inc.

  4. Constraints from fluid inclusions on sulfide precipitation mechanisms and ore fluid migration in the Viburnum Trend lead district, Missouri

    USGS Publications Warehouse

    Rowan, E.L.; Leach, D.L.

    1989-01-01

    Homogenization temperatures and freezing point depressions were determined for fluid inclusions in Bonneterre Dolomite-hosted dolomite cements in mine samples, as well as drill core from up to 13 km outside of the district. A well-defined cathodoluminescent zonation distinguishes dolomite growth zones as older or younger than main-stage mineralization. Homogenization temperatures and salinities in samples from mines are not systematically different from those of samples outside of the district. The absence of a significant, recognizable decrease in temperature either vertically within the section or east-west across the district, coupled with the minor amount of silica in the district, argues against cooling as a primary cause of sulfide precipitation. In a reduced sulfur mineralization model with Pb carried as chloride complexes, dilution is also a possible sulfide precipitation mechanism. The difference in Pb solubility in the extremes of the chloride concentration range, 3.9 vs. 5.9 molal, reaches 1 ppm only for pH values below approximately 4.5. The distribution of warm inclusions beyond the Viburnum Trend district implies that fluid migration was regional in scale. Elevated temperatures observed in fluid inclusions at shallow stratigraphic depths are consistent with a gravity flow hydrologic system characterized by rapid flow rates and the capacity for advective heat transport. -from Authors

  5. Modern Processes of Hydrocarbon Migration and Re-Formation of Oil and Gas Fields (Based on the Results of Monitoring and Geochemical Studies)

    NASA Astrophysics Data System (ADS)

    Plotnikova, Irina; Salakhidinova, Gulmira; Nosova, Fidania; Pronin, Nikita; Ostroukhov, Sergey

    2015-04-01

    Special geochemical studies of oils allowed to allocate a movable migration component of oils in the industrial oil deposits. In the field the migration component of oils varies in different parts of the field. The largest percentage of the light migration component (gas condensate of the oil) was detected in the central part of the Kama-Kinel troughs system. Monitoring of the composition of water, oil and gas (condensate light oil component) in the sedimentary cover and ni crystalline basement led to the conclusion of modern migration of hydrocarbons in sedimentary cover. This proves the existence of the modern processes of formation and reformation of oil and gas fields. This presentation is dedicated to the problem of definition of geochemical criteria of selection of hydrocarbons deposit reformation zone in the sample wells of Minibaevskaya area of Romashkinskoye field. While carrying out this work we examined 11 samples of oil from the Upper Devonian Pashiysky horizon. Four oil samples were collected from wells reckoned among the "anomalous" zones that were marked out according to the results of geophysical, oil field and geological research. Geochemical studies of oils were conducted in the laboratory of geochemistry of the Kazan (Volga-region) Federal University. The wells where the signs of hydrocarbons influx from the deep zones of the crust were recorded are considered to be "anomalous". A number of scientists connect this fact to the hypothesis about periodic influx of deep hydrocarbons to the oil deposits of Romashkinskoye field. Other researchers believe that the source rocks of the adjacent valleys sedimentary cover generate gases when entering the main zone of gas formation, which then migrate up the section and passing through the previously formed deposits of oil, change and "lighten" their composition. Regardless of the point of view on the source of the hydrocarbons, the study of the process of deposits refilling with light hydrocarbons is an important fundamental task of exceptional practical importance. The reservoir water monitoring has been conducted in five wells that have penetrated the water-saturated, loosely aggregated zones of the South Tatarstan Arch's basement. The long-term testing resulted in the production of reservoir water from the basement. The sedimentary cover in these wells is blocked by the column, which prevents water cross-flowing from the sedimentary cover. The observations have shown that the levels, gas saturation, mineralisation, density, and composition of reservoir waters from the loosely aggregated zones of the basement change with time. The varying characteristics of the water include its component composition, redox potential, and amount of chlorine and some other components and trace elements. Compositional changes in gases of the loosely aggregated zones of the basement, variations in the gas saturation of reservoir waters and of their composition, the decreasing density of oil in the sedimentary cover, - all result from one cause. This cause is the movement of fluids (solutions and gases dissolved in them) through the loosely aggregated zones and faults of the Earth's crust and the sedimentary cover. The fluids mainly move vertically in an upward direction, although their migration through subhorizontal, loosely aggregated zones of the crystalline basement is also possible. Fluid migration still takes place in the Earth's crust of ancient platforms. This phenomenon indicates that some portions of the platforms - primarily, their margins - periodically resume tectonic activities. The fluid dynamic activity of the crust define the processes in the sedimentary cover. It affects the development of the sedimentary basin during the sedimentation period, and the formation of mineral deposits. The monitoring of the present-day movement of fluid systems in the loosely aggregated zones of the basement will permit the more detailed study of the present-day fluid regime in the upper portion of the Earth's crust and the sedimentary cover.

  6. Section 17: Air Pathway- Waste Characteristics and Targets

    EPA Pesticide Factsheets

    HRS Training. the air migration pathway evaluates the likelihood of release of hazardous substances into the atmosphere and how many people and sensitive environments could be exposed to hazardous substances carried in the air, including gases

  7. 10 CFR 60.134 - Design of seals for shafts and boreholes.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... boreholes shall be designed so that following permanent closure they do not become pathways that compromise... pathway for groundwater to contact the waste packages or (2) For radionuclide migration through existing pathways. [48 FR 28222, June 21, 1983, as amended at 50 FR 29648, July 22, 1985] Design Criteria for the...

  8. 10 CFR 60.134 - Design of seals for shafts and boreholes.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... boreholes shall be designed so that following permanent closure they do not become pathways that compromise... pathway for groundwater to contact the waste packages or (2) For radionuclide migration through existing pathways. [48 FR 28222, June 21, 1983, as amended at 50 FR 29648, July 22, 1985] Design Criteria for the...

  9. 10 CFR 60.134 - Design of seals for shafts and boreholes.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... boreholes shall be designed so that following permanent closure they do not become pathways that compromise... pathway for groundwater to contact the waste packages or (2) For radionuclide migration through existing pathways. [48 FR 28222, June 21, 1983, as amended at 50 FR 29648, July 22, 1985] Design Criteria for the...

  10. Uranium mineralization and unconformities: how do they correlate? - A look beyond the classic unconformity-type deposit model?

    NASA Astrophysics Data System (ADS)

    Markwitz, Vanessa; Porwal, Alok; Campbell McCuaig, T.; Kreuzer, Oliver P.

    2010-05-01

    Uranium deposits are usually classified based on the characteristics of their host rocks and geological environments (Dahlkamp, 1993; OECD/NEA Red Book and IAEA, 2000; Cuney, 2009). The traditional unconformity-related deposit types are the most economical deposits in the world, with the highest grades amongst all uranium deposit types. In order to predict undiscovered uranium deposits, there is a need to understand the spatial association of uranium mineralization with structures and unconformities. Hydrothermal uranium deposits develop by uranium enriched fluids from source rocks, transported along permeable pathways to their depositional environment. Unconformities are not only separating competent from incompetent sequences, but provide the physico-chemical gradient in the depositional environment. They acted as important fluid flow pathways for uranium to migrate not only for surface-derived oxygenated fluids, but also for high oxidized metamorphic and magmatic fluids, dominated by their geological environment in which the unconformities occur. We have carried out comprehensive empirical spatial analyses of various types of uranium deposits in Australia, and first results indicate that there is a strong spatial correlation between unconformities and uranium deposits, not only for traditional unconformity-related deposits but also for other styles. As a start we analysed uranium deposits in Queensland and in particular Proterozoic metasomatic-related deposits in the Mount Isa Inlier and Late Carboniferous to Early Permian volcanic-hosted uranium occurrences in Georgetown and Charters Towers Regions show strong spatial associations with contemporary and older unconformities. The Georgetown Inlier in northern Queensland consists of a diverse range of rocks, including Proterozoic and early Palaeozoic metamorphic rocks and granites and late Palaeozoic volcanic rocks and related granites. Uranium-molybdenum (+/- fluorine) mineralization in the Georgetown inlier varies from strata- to structure-bound and occurs above regional unconformities. The Proterozoic basins in the Mount Isa Inlier rest unconformably on Palaeoproterozoic basement accompanied by volcanic and igneous rocks, which were deformed and metamorphosed in the Mesoproterozoic. Uranium occurrences in the Western Succession of Mount Isa are either hosted in clastic metasediments or mafic volcanics that belong to the Palaeoproterozoic Eastern Creek Volcanics. Uranium and vanadium mineralization occur in metasomatised and hematite-magnetite-carbonate alteration zones, bounded by major faults and regional unconformities. The results of this study highlight the importance of unconformities in uranium minerals systems as possible fluid pathways and/or surfaces of physico-chemical contrast that could have facilitated the precipitation of uranium, not only in classical unconformity style uranium deposits but in several other styles of uranium mineralization as well. References Cuney, M., 2009. The extreme diversity of uranium deposits. Mineralium Deposita, 44, 3-9. Dahlkamp, F. J., 1993. Uranium ore deposits. Springer, Berlin, p 460. OECD / NEA Red Book & IAEA, 2000. Uranium 1999: Resources, Production and Demand. OECD Nuclear Energy Agency and International Atomic Energy Agency, Paris.

  11. Osthole exhibits anti-cancer property in rat glioma cells through inhibiting PI3K/Akt and MAPK signaling pathways.

    PubMed

    Ding, Daofang; Wei, Songpu; Song, Yi; Li, Linghui; Du, Guoqing; Zhan, Hongsheng; Cao, Yuelong

    2013-01-01

    The purpose of this study was to investigate how Osthole affects glioma cell proliferation, apoptosis, invasion and migration. Rat glioma cells were treated with different concentrations of Osthole (0 µM, 25 µM, 50 µM, and 100 µM). Cell proliferation was assessed by measuring PCNA expression and CCK8 assay at different time points. Apoptosis was evaluated by measuring the expression of pro-apoptotic protein including Bax, Bcl2, PARP, and cleaved Caspase3, and of anti-apoptotic protein Survivin. Cell migration and invasion were assessed using different methods. Signaling pathways such as PI3K/Akt and MAPK, which are involved in the development of glioma cells, were also investigated in this study. Treatment with Osthole markedly inhibits glioma cell proliferation, as assessed by western blot with the PCNA antibody. Osthole also induces cell apoptosis by upregulating the expression of pro-apoptotic proteins, and by reducing the expression of anti-apoptotic factors. Moreover, C6 cell migration and invasion were efficiently inhibited in groups treated with Osthole, compared to the control group. Additionally, inhibition of PI3K/Akt and MAPK signaling pathway was also observed in C6 cells treated with Osthole. Our findings showed an anti-cancer effect of Osthole on glioma cells, including the proliferation inhibition, apoptosis induction, and migration/invasion inhibition. Further investigation in C6 glioma cells implicated the role of Osthole in essential pathways controlling glioma cell progression. Taken together, our data suggested that Osthole may have a potential application in glioma therapy. © 2014 S. Karger AG, Basel.

  12. Polydatin induces bone marrow stromal cells migration by activation of ERK1/2.

    PubMed

    Chen, ZhenQiu; Wei, QiuShi; Hong, GuoJu; Chen, Da; Liang, Jiang; He, Wei; Chen, Mei Hui

    2016-08-01

    Bone marrow stromal cells (BMSCs) have proven to be useful for the treatment of numerous human diseases. However, the reparative ability of BMSCs is limited by their poor migration. Polydatin, widely used in traditional Chinese remedies, has proven to exert protective effects to BMSCs. However, little is known about its role in BMSCs migration. In this study, we studied the effects of polydatin on rat BMSCs migration using the scratch wound healing and transwell migration assays. Our results showed polydatin could promote BMSCs migration. Further experiments showed activation of ERK 1/2, but not JNK, was required for polydatin-induced BMSCs migration, suggesting that polydatin may promote BMSCs migration via the ERK 1/2 signaling pathways. Taken together, our results indicate that polydatin might be beneficial for stem cell replacement therapy by improving BMSCs migration. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Beyond compartmentalization: a relational approach towards agency and vulnerability of young migrants.

    PubMed

    Huijsmans, Roy

    2012-01-01

    Based on fieldwork material from Lao People's Democratic Republic, this paper introduces an analytical framework that transcends compartmentalized approaches towards migration involving young people. The notions of fluid and institutionalized forms of migration illuminate key differences and commonalities in the relational fabric underpinning empirically diverse migration scenarios. Applying this framework to the role of networks in becoming a young migrant, this chapter sheds light on young migrants' differential scope for exercising agency. This redirects concerns about young migrants away from descriptive and static factors towards their relational position in the process of migration, which shapes their agency and vulnerability. Copyright © 2012 Wiley Periodicals, Inc., A Wiley Company.

  14. Appearance and quantification of infectious hematopoietic necrosis virus in female sockeye salmon (Oncorhynchus nerka) during their spawning migration

    USGS Publications Warehouse

    Mulcahy, D.; Jenes, C.K.; Pascho, R.J.

    1984-01-01

    The incidence and amount of infectious hematopoietic necrosis (IHN) virus was determined in 10 organs and body fluids from each of 100 female sockeye salmon(Oncorhynchus nerka) before, during, and after their spawning migration into freshwater. Virus was found in high concentrations only in fish sampled during and after spawning. Infection rates increased from nil to 100 percent within 2 weeks. In spawning fish, incidences of IHN virus were high in all organs and fluids except brain and serum, and the highest concentrations were in the pyloric caeca and lower gut. Immediately before spawning, IHN virus was found most frequently in the gills, less frequently in the pyloric caeca and spleen, and rarely in other organs.

  15. Physical Laws for Mechanobiology

    NASA Technical Reports Server (NTRS)

    Freed, Alan D.

    2007-01-01

    Higher-level physical laws applicable to biological tissues are presented that will permit the modeling of metabolic activity at the cellular level, including variations in the mass of a tissue. Here the tissue is represented as a fluid/solid mixture, wherein molecular solutes transport within the fluid, and cells can migrate throughout the porous solid. Variations in mass can arise via exchanges in mass between the constituent phases within a control volume such that mass is conserved in the tissue overall. The governing balance laws for mass, momentum, energy, and entropy are a special case of those describing a chemically reacting mixture with diffusion. Thermodynamic constraints on the constitutive structure are addressed. Biophysics; Biomechanics; Brownian motion; Cell migration; Mixture theory; Thermodynamic laws; Tissue mechanics

  16. Temporal Changes in Stress Drop, Frictional Strength, and Earthquake Size Distribution in the 2011 Yamagata-Fukushima, NE Japan, Earthquake Swarm, Caused by Fluid Migration

    NASA Astrophysics Data System (ADS)

    Yoshida, Keisuke; Saito, Tatsuhiko; Urata, Yumi; Asano, Youichi; Hasegawa, Akira

    2017-12-01

    In this study, we investigated temporal variations in stress drop and b-value in the earthquake swarm that occurred at the Yamagata-Fukushima border, NE Japan, after the 2011 Tohoku-Oki earthquake. In this swarm, frictional strengths were estimated to have changed with time due to fluid diffusion. We first estimated the source spectra for 1,800 earthquakes with 2.0 ≤ MJMA < 3.0, by correcting the site-amplification and attenuation effects determined using both S waves and coda waves. We then determined corner frequency assuming the omega-square model and estimated stress drop for 1,693 earthquakes. We found that the estimated stress drops tended to have values of 1-4 MPa and that stress drops significantly changed with time. In particular, the estimated stress drops were very small at the beginning, and increased with time for 50 days. Similar temporal changes were obtained for b-value; the b-value was very high (b 2) at the beginning, and decreased with time, becoming approximately constant (b 1) after 50 days. Patterns of temporal changes in stress drop and b-value were similar to the patterns for frictional strength and earthquake occurrence rate, suggesting that the change in frictional strength due to migrating fluid not only triggered the swarm activity but also affected earthquake and seismicity characteristics. The estimated high Q-1 value, as well as the hypocenter migration, supports the presence of fluid, and its role in the generation and physical characteristics of the swarm.

  17. Analysis of Variability in Intraoperative Fluid Administration for Colorectal Surgery: An Argument for Goal-Directed Fluid Therapy.

    PubMed

    Quinn, Timothy D; Brovman, Ethan Y; Urman, Richard D

    2017-09-01

    Fluid therapy in the perioperative period varies greatly between anesthesia providers and may have a negative impact on surgical outcomes. We conducted a retrospective analysis of 705 elective colorectal cases consisting of colectomies, ileocolic resections, and low anterior resections at an academic institution from January 1, 2010 to May 29, 2015, collected by our electronic medical record before implementation of Enhanced Recovery After Surgery (ERAS ® ) pathways. The mean for total crystalloid administration was 2578 mL with a standard deviation (SD) that was approximately 50% of the mean value. A combination of both normal saline and lactated Ringer's solution was used in almost all cases without a clear rationale for fluid choice. Fluid administered to patients was disproportional to measured intraoperative fluid losses (estimated blood loss and urine output) by a factor of 10. The average rate of fluid given was 1050 mL/h with an SD of nearly the same amount (951 mL). There was a variability of over 67% in total crystalloid administered based on both ideal body weight and total body weight. We found that a wide variability in the amount and type of fluid therapy administered existed at our institution before implementation of a colorectal ERAS pathway or routine use of goal-directed fluid therapy (GDFT). ERAS pathways with GDFT protocols could lead to more rational and consistent fluid therapy leading to improved outcomes.

  18. PI3K-mediated proliferation of fibroblasts by Calendula officinalis tincture: implication in wound healing.

    PubMed

    Dinda, Manikarna; Dasgupta, Uma; Singh, Namrata; Bhattacharyya, Debasish; Karmakar, Parimal

    2015-04-01

    Calendula officinalis, a member of the Asteraceae family, is a flowering plant and has been used for its antibacterial, antifungal, antiviral, antiinflammatory, anticancer and wound healing activity. The mode of action of C. officinalis tincture on wound healing is poorly understood. Here, we investigated the role of C. officinalis tincture (CDOT) on cell viability and wound closure. C. officinalis tincture stimulated both proliferation and migration of fibroblasts in a statistically significant manner in a PI3K-dependent pathway. The increase in phosphorylation of FAK (Tyr 397) and Akt (Ser 473) was detected after treatment of CDOT. Inhibition of the PI3K pathway by wortmannin and LY294002 decreased both cell proliferation and cell migration. HPLC-ESI MS revealed the presence of flavonol glycosides as the major compounds of CDOT. Altogether, our results showed that CDOT potentiated wound healing by stimulating proliferation and migration of fibroblast in a PI3K-dependent pathway, and the identified compounds are likely to be responsible for wound healing activity. Copyright © 2015 John Wiley & Sons, Ltd.

  19. THE WELL-ALIGNED ORBIT OF WASP-84b: EVIDENCE FOR DISK MIGRATION OF A HOT JUPITER

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Anderson, D. R.; Triaud, A. H. M. J.; Turner, O. D.

    We report the sky-projected orbital obliquity (spin–orbit angle) of WASP-84 b, a 0.69M{sub Jup} planet in an 8.52 day orbit around a G9V/K0V star, to be λ = −0.3 ± 1.7°. We obtain a true obliquity of ψ = 17.3 ± 7.7° from a measurement of the inclination of the stellar spin axis with respect to the sky plane. Due to the young age and the weak tidal forcing of the system, we suggest that the orbit of WASP-84b is unlikely to have both realigned and circularized from the misaligned and/or eccentric orbit likely to have arisen from high-eccentricity migration.more » Therefore we conclude that the planet probably migrated via interaction with the protoplanetary disk. This would make it the first “hot Jupiter” (P<10 d) to have been shown to have migrated via this pathway. Further, we argue that the distribution of obliquities for planets orbiting cool stars (T{sub eff} < 6250 K) suggests that high-eccentricity migration is an important pathway for the formation of short-orbit, giant planets.« less

  20. Lead migration from toys by anodic stripping voltammetry using a bismuth film electrode.

    PubMed

    Leal, M Fernanda C; Catarino, Rita I L; Pimenta, Adriana M; Souto, M Renata S; Afonso, Christelle S; Fernandes, Ana F Q

    2016-09-02

    Metals may be released from toys via saliva during mouthing, via sweat during dermal contact, or via gastric and intestinal fluids after partial or whole ingestion. In this study, we determined the lead migration from toys bought on the Portuguese market for children below 3 years of age. The lead migration was performed according to the European Committee for Standardization EN 71-3, which proposes a 2-hour migration test that simulates human gastric conditions. The voltammetric determination of migrated lead was performed by anodic stripping voltammetry (ASV) at a bismuth film electrode (BiFE). For all the analyzed toys, the values of migrated lead did not exceed the limits imposed by the European Committee for Standardization EN 71-3 (90 mg kg -1 ) and by the EU Directive 2009/48/EC (13.5 mg kg -1 ) on the safety of toys.

  1. COMP-angiopoietin 1 increases proliferation, differentiation, and migration of stem-like cells through Tie-2-mediated activation of p38 MAPK and PI3K/Akt signal transduction pathways

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kook, Sung-Ho; Lim, Shin-Saeng; Cho, Eui-Sic

    2014-12-12

    Highlights: • COMP-Ang1 induces Tie-2 activation in BMMSCs, but not in primary osteoblasts. • Tie-2 knockdown inhibits COMP-Ang1-stimulated proliferation and osteoblastogenesis. • Tie-2 knockdown prevents COMP-Ang1-induced activation of PI3K/Akt and p38 MAPK. • COMP-Ang1 induces migration of cells via activation of PI3K/Akt and CXCR4 pathways. • COMP-Ang1 stimulates in vivo migration of PDLSCs into a calvarial defect site of rats. - Abstract: Recombinant COMP-Ang1, a chimera of angiopoietin-1 (Ang1) and a short coiled-coil domain of cartilage oligomeric matrix protein (COMP), is under consideration as a therapeutic agent capable of inducing the homing of cells with increased angiogenesis. However, the potentialsmore » of COMP-Ang1 to stimulate migration of mesenchymal stem cells (MSCs) and the associated mechanisms are not completely understood. We examined the potential of COMP-Ang1 on bone marrow (BM)-MSCs, human periodontal ligament stem cells (PDLSCs), and calvarial osteoblasts. COMP-Ang1 augmented Tie-2 induction at protein and mRNA levels and increased proliferation and expression of runt-related transcription factor 2 (Runx2), osterix, and CXCR4 in BMMSCs, but not in osteoblasts. The COMP-Ang1-mediated increases were inhibited by Tie-2 knockdown and by treating inhibitors of phosphoinositide 3-kinase (PI3K), LY294002, or p38 mitogen-activated protein kinase (MAPK), SB203580. Phosphorylation of p38 MAPK and Akt was prevented by siRNA-mediated silencing of Tie-2. COMP-Ang1 also induced in vitro migration of BMMSCs and PDLSCs. The induced migration was suppressed by Tie-2 knockdown and by CXCR4-specific peptide antagonist or LY294002, but not by SB203580. Furthermore, COMP-Ang1 stimulated the migration of PDLSCs into calvarial defect site of rats. Collectively, our results demonstrate that COMP-Ang1-stimulated proliferation, differentiation, and migration of progenitor cells may involve the Tie-2-mediated activation of p38 MAPK and PI3K/Akt pathways.« less

  2. Optimum Pathways of Fish Spawning Migrations in Rivers

    NASA Astrophysics Data System (ADS)

    McElroy, B. J.; Jacobson, R. B.; Delonay, A.

    2010-12-01

    Many fish species migrate large distances upstream in rivers to spawn. These migrations require energetic expenditures that are inversely related to fecundity of spawners. Here we present the theory necessary to quantify relative energetic requirements of upstream migration pathways and then test the hypothesis that least-cost paths are taken by the federally endangered pallid sturgeon (Scaphyrhyncus Albus), a benthic rheophile, in the lower Missouri River, USA. Total work done by a fish through a migratory path is proportional to the size of the fish, the total drag on the fish, and the distance traversed. Normalizing by the work required to remain stationary at the beginning of a path, relative work expenditure at each point of the path is found to be the cube of the ratio of the velocity along the path to the velocity at the start of the path. This is the velocity of the fish relative to the river flow. A least-cost migratory pathway can be determined from the velocity field in a reach as the path that minimizes a fish's relative work expenditure. We combine location data from pallid sturgeon implanted with telemetric tags and pressure-sensitive data storage tags with depth and velocity data collected with an acoustic Doppler profiler. During spring 2010 individual sturgeon were closely followed as they migrated up the Missouri River to spawn. These show that, within a small margin, pallid sturgeon in the lower Missouri River select least-cost paths as they swim upstream (typical velocities near 1.0 - 1.2 m/s). Within the range of collected data, it is also seen that many alternative paths not selected for migration are two orders of magnitude more energetically expensive (typical velocities near 2.0 - 2.5 m/s). In general these sturgeon migrated along the inner banks of bends avoiding high velocities in the thalweg, crossing the channel where the thalweg crosses in the opposite direction in order to proceed up the inner bank of subsequent bends. Overall, these results suggest a management strategy for increasing fecundity and reproductive success could be to manage flows to lower levels during prespawn migrations thereby decreasing expenditure necessary to reach spawning sites.

  3. Mathematical Development of the Spill Assessment Model (SAM) for Hydrazine and Similar Acting Materials in Water Bodies.

    DTIC Science & Technology

    1980-02-01

    migration of the chemical mass in the fluid volume according to two entirely different means, yet governed by the same form of the equation: molecular ...pressure or temperature gradients, gravitational or other body forces, or bulk fluid motion, is observed as molecular diffusion. In general, the...need be made at this stage as to whether the diffusion of a released mass in the fluid is molecular or turbulent in nature. The general form of the one

  4. High-resolution radon monitoring and hydrodynamics at Mount Vesuvius

    NASA Astrophysics Data System (ADS)

    Cigolini, Corrado; Salierno, Francesco; Gervino, Gianpiero; Bergese, Paolo; Marino, Ciro; Russo, Massimo; Prati, Paolo; Ariola, Vincenzo; Bonetti, Roberto; Begnini, Stefania

    A yearlong high-resolution radon survey has been carried on at Mount Vesuvius, starting in May 1998. Radon activities were acquired by exposing charcoal canisters and track-etch detectors. Sampling stations were deployed along two major summit faults and around the caldera bottom. Volcanically-related earthquakes, with MD ≥ 2.5, may be discriminated from regional seismic events since their cumulative radon anomalies are recorded from stations located along all the above structural features. On the contrary, radon anomalies correlated to regional earthquakes, with MD ≥ 4, are essentially recorded by the sampling sites located along the two summit faults (whose roots extend deeper into the Tertiary basement rocks that underlay the volcano). Radon migration to the surface is ruled by convection within a porous medium of relatively low porosity (ϕ ≈ 10-5), suggesting that fluid motion is strongly localised along fractures. It is suggested that fluid pressure build up, followed by fluid release and migration during incipient fracturing of the porous medium, precede the onset of volcanically-induced earthquakes.

  5. BMAL1 facilitates trophoblast migration and invasion via SP1-DNMT1/DAB2IP pathway in recurrent spontaneous abortion

    PubMed Central

    Li, Shang; Zhai, Junyu; Liu, Jiansheng; Hong, Yan; Zhao, Weixiu; Zhao, Aimin; Sun, Kang; Du, Yanzhi; Chen, Zi-Jiang

    2017-01-01

    The underlying mechanism about rhythms and epigenetics leading to aberrant trophoblast migration and invasion in recurrent spontaneous abortion (RSA) remains unknown. Brain and muscle ARNT-like protein 1 (BMAL1) is considered as a crucial role in fertility, and polymorphism of BMAL1 gene has been reported to be associated with risk of miscarriage. However, the functional role of BMAL1 in RSA is not fully understood. Previous study shows the descended expression of DNA 5′-cytosine-methyltransferases 1 (DNMT1) in the villous of early pregnancy loss. Thus, understanding of the regulation of DNMT1 expression may be of significance for the elucidation of the process of RSA. Using HTR-8/SVneo and JEG-3 cell lines, we certified the induction of specificity protein 1 (SP1) to DNMT1 and DAB2 interaction protein (DAB2IP), respectively, both of which further activated matrix metallo-proteinase 2/9 (MMP2/9), bringing out changes in trophoblast migration and invasion. Notably, BMAL1 functioned as a positive upstream factor of SP1 only in HTR-8/SVneo cells but not in JEG-3 cells, inducing SP1-DNMT1/DAB2IP pathway and facilitating migration and invasion of trophoblasts. In addition, progesterone might restore the down-regulation of BMAL1 and downstream pathway in a dose-dependent manner. Last but not least, the decreased abundance of BMAL1 was correlated positively with that of SP1, DNMT1, DAB2IP, MMP2 and MMP9 in human villous specimens of RSA. Our results demonstrate that the induction of BMAL1 to SP1 contributes to the expression of DNMT1 and DAB2IP, respectively, activating trophoblast migration and invasion. The deregulation of the BMAL1-mediated pathway in RSA can be rescued by progesterone. PMID:29163762

  6. A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1-MMP via the Wnt signaling pathway

    PubMed Central

    LIU, BINGSHAN; LI, GUOJUN; WANG, XIAO; LIU, YANG

    2014-01-01

    This study aimed to explore the exact mechanism of the effect of a furin inhibitor on the migration and invasion of MG-63 and Saos-2 osteosarcoma cells. MG-63 and Saos-2 osteosarcoma cells were treated with regular culture medium in the presence or absence of 480 nM α1-antitrypsin Portland (α1-PDX). Wound-healing and Transwell assays were used for the detection of the effects of α1-PDX on MG-63 and Saos-2 osteosarcoma cell migration and invasion. Western blot analysis and reverse transcription-polymerase chain reaction were performed to detect the expression levels of membrane type I matrix metalloproteinase (MT1-MMP), Wnt and β-catenin. A chromatin immunoprecipitation assay was used for detection of the levels of MT1-MMP gene transcription activity. The results showed that α1-PDX treatment significantly reduced the migration and invasion ability of the cells. Notably, the expression levels of MT1-MMP decreased evidently upon α1-PDX treatment, paralleled with reductions in the expression levels of Wnt and β-catenin. Further analysis of the transcriptional activity of MT1-MMP revealed that the α1-PDX-induced downregulation of the levels of MT1-MMP was mediated by the Wnt signaling pathway. These data suggest that α1-PDX plays a vital role in inhibiting MG-63 and Saos-2 osteosarcoma cell migration and invasion by downregulating the expression levels of MT1-MMP via the Wnt signaling pathway. PMID:24944664

  7. Overexpression of activin-A and -B in malignant mesothelioma – Attenuated Smad3 signaling responses and ERK activation promote cell migration and invasive growth

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tamminen, Jenni A.; Yin, Miao; Transplantation Laboratory, Haartman Institute, University of Helsinki

    Activin-A and activin-B, members of the TGF-β superfamily, are regulators of reproductive functions, inflammation and wound healing. These dimeric molecules regulate various cellular activities such as proliferation, migration and suvival. Malignant mesothelioma is an asbestos exposure related tumor affecting mainly pleura and it usually has a dismal prognosis. Here, we demonstrate that both activin-A and -B are abundantly expressed in mesothelioma tumor tissue as well as in cultured primary and established mesothelioma cells. Migratory and invasive mesothelioma cells were also found to have attenuated activation of the Smad2/3 pathway in response to activins. Migration and invasive growth of the cellsmore » in three-dimentional matrix was prevented by inhibition of activin activity using a soluble activin receptor 2B (sActR2B-Fc). This was associated with decreased ERK activity. Furthermore, migration and invasive growth was significantly inhibited by blocking ERK phosphorylation. Mesothelioma tumors are locally invasive and our results clearly suggest that acivins have a tumor-promoting function in mesothelioma through increasing expression and switching from canonical Smad3 pathway to non-canonical ERK pathway signaling. Blocking activin activity offers a new therapeutic approach for inhibition of mesothelioma invasive growth. - Highlights: • Activin-A and activin-B are highly expressed in mesothelioma. • Mesothelioma cell migration and invasive growth can be blocked with sActR2B. • Activin induced Smad3 activity is attenuated in invasive mesothelioma cells. • Activins induce ERK activity in mesothelioma cells.« less

  8. Neuropeptide-stimulated cell migration in prostate cancer cells is mediated by RhoA kinase signaling and inhibited by neutral endopeptidase.

    PubMed

    Zheng, R; Iwase, A; Shen, R; Goodman, O B; Sugimoto, N; Takuwa, Y; Lerner, D J; Nanus, D M

    2006-09-28

    The neuropeptides bombesin and endothelin-1 stimulate prostate cancer (PC) cell migration and invasion (J Clin Invest, 2000; 106: 1399-1407). The intracellular signaling pathways that direct this cell movement are not well delineated. The monomeric GTPase RhoA is required for migration in several cell types including neutrophils, monocytes and fibroblasts. We demonstrate that bombesin-stimulated PC cell migration occurs via the heterotrimeric G-protein-coupled receptors (G-protein) G alpha 13 subunit leading to activation of RhoA, and Rho-associated coiled-coil forming protein kinase (ROCK). Using siRNA to suppress expression of the three known G-protein alpha-subunit-associated RhoA guanine nucleotide exchange factors (GEFs), we also show that two of these RhoA GEFs, PDZ-RhoGEF and leukemia-associated RhoGEF (LARG), link bombesin receptors to RhoA in a non-redundant manner in PC cells. We next show that focal adhesion kinase, which activates PDZ-RhoGEF and LARG, is required for bombesin-stimulated RhoA activation. Neutral endopeptidase (NEP) is expressed on normal prostate epithelium whereas loss of NEP expression contributes to PC progression. We also demonstrate that NEP inhibits neuropeptide activation of RhoA. Together, these results establish a contiguous signaling pathway from the bombesin receptor to ROCK in PC cells, and they implicate NEP as a major regulator of neuropeptide-stimulated RhoA in these cells. This work also identifies members of this signaling pathway as potential targets for rational pharmacologic manipulation of neuropeptide-stimulated migration of PC cells.

  9. Alternative splicing disabled by Nova2.

    PubMed

    Park, Tae-Ju; Curran, Tom

    2010-06-24

    Disabled-1 is a key signaling molecule in the Reelin pathway that plays a critical role in neuronal migration and positioning during brain development. In this issue of Neuron, Yano et al. demonstrate that the neuron-specific RNA binding protein Nova2 contributes to neuronal migration by regulating alternative splicing of disabled-1.

  10. Installation Restoration Program Records Search for Dobbins Air Force Base, Georgia

    DTIC Science & Technology

    1982-04-01

    migation Death to irond water ____________ lift ogaeiitation 1 . Subsurface flow_____I a _____________ Direct aess W 4round water______ j Submrs(10 x actr...potential pathways, surface water migation , flooding, and ground-water * migration. Select the highest rating, and proceed to C. f 1. Surface water migration

  11. Low-intensity pulsed ultrasound promotes spinal fusion and enhances migration and proliferation of MG63s through sonic hedgehog signaling pathway.

    PubMed

    Zhou, Xiao-Yi; Xu, Xi-Ming; Wu, Sui-Yi; Zhang, Zi-Cheng; Wang, Fei; Yang, Yi-Lin; Li, Ming; Wei, Xian-Zhao

    2018-05-01

    Low-intensity pulsed ultrasound (LIPUS) has been found to accelerate the healing process of spinal fusion via a process closely related to osteoblast differentiation and migration. Sonic hedgehog (Shh) signaling plays an important role in development and homeostasis, including a critical function in bone formation. However, its role in spinal fusion during LIPUS treatment is still unknown. This study showed that LIPUS treatment after spinal fusion surgery increased bone formation. The increased bone mass under LIPUS treatment appeared to result from the increased migration and proliferation of osteoblasts, resulting from upregulation of the Shh signaling pathway. In contrast, inhibition of Shh reduced the migratory and proliferative ability of osteoblast-like MG63 cells and blocked the efficacy of LIPUS treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Primordial germ cells in the dorsal mesentery of the chicken embryo demonstrate left-right asymmetry and polarized distribution of the EMA1 epitope.

    PubMed

    Hen, Gideon; Friedman-Einat, Miriam; Sela-Donenfeld, Dalit

    2014-05-01

    Despite the importance of the chicken as a model system, our understanding of the development of chicken primordial germ cells (PGCs) is far from complete. Here we characterized the morphology of PGCs at different developmental stages, their migration pattern in the dorsal mesentery of the chicken embryo, and the distribution of the EMA1 epitope on PGCs. The spatial distribution of PGCs during their migration was characterized by immunofluorescence on whole-mounted chicken embryos and on paraffin sections, using EMA1 and chicken vasa homolog antibodies. While in the germinal crescent PGCs were rounded and only 25% of them were labeled by EMA1, often seen as a concentrated cluster on the cell surface, following extravasation and migration in the dorsal mesentery PGCs acquired an elongated morphology, and 90% exhibited EMA1 epitope, which was concentrated at the tip of the pseudopodia, at the contact sites between neighboring PGCs. Examination of PGC migration in the dorsal mesentery of Hamburger and Hamilton stage 20-22 embryos demonstrated a left-right asymmetry, as migration of cells toward the genital ridges was usually restricted to the right, rather than the left, side of the mesentery. Moreover, an examination of another group of cells that migrate through the dorsal mesentery, the enteric neural crest cells, revealed a similar preference for the right side of the mesentery, suggesting that the migratory pathway of PGCs is dictated by the mesentery itself. Our findings provide new insights into the migration pathway of PGCs in the dorsal mesentery, and suggest a link between EMA1, PGC migration and cell-cell interactions. These findings may contribute to a better understanding of the mechanism underlying migration of PGCs in avians. © 2014 Anatomical Society.

  13. A Fluid-driven Earthquake Cycle, Omori's Law, and Fluid-driven Aftershocks

    NASA Astrophysics Data System (ADS)

    Miller, S. A.

    2015-12-01

    Few models exist that predict the Omori's Law of aftershock rate decay, with rate-state friction the only physically-based model. ETAS is a probabilistic model of cascading failures, and is sometimes used to infer rate-state frictional properties. However, the (perhaps dominant) role of fluids in the earthquake process is being increasingly realised, so a fluid-based physical model for Omori's Law should be available. In this talk, I present an hypothesis for a fluid-driven earthquake cycle where dehydration and decarbonization at depth provides continuous sources of buoyant high pressure fluids that must eventually make their way back to the surface. The natural pathway for fluid escape is along plate boundaries, where in the ductile regime high pressure fluids likely play an integral role in episodic tremor and slow slip earthquakes. At shallower levels, high pressure fluids pool at the base of seismogenic zones, with the reservoir expanding in scale through the earthquake cycle. Late in the cycle, these fluids can invade and degrade the strength of the brittle crust and contribute to earthquake nucleation. The mainshock opens permeable networks that provide escape pathways for high pressure fluids and generate aftershocks along these flow paths, while creating new pathways by the aftershocks themselves. Thermally activated precipitation then seals up these pathways, returning the system to a low-permeability environment and effective seal during the subsequent tectonic stress buildup. I find that the multiplicative effect of an exponential dependence of permeability on the effective normal stress coupled with an Arrhenius-type, thermally activated exponential reduction in permeability results in Omori's Law. I simulate this scenario using a very simple model that combines non-linear diffusion and a step-wise increase in permeability when a Mohr Coulomb failure condition is met, and allow permeability to decrease as an exponential function in time. I show very strong spatial correlations of the simulated evolved permeability and fluid pressure field with aftershock hypocenters from this 1992 Landers and 1994 Northridge aftershock sequences, and reproduce the observed aftershock decay rates. Controls on the decay rates (p-value) will also be discussed.

  14. Extracellular nonmitogenic angiogenesis factor and method of isolation thereof from wound fluid

    DOEpatents

    Banda, Michael J.; Werb, Zena; Knighton, David R.; Hunt, Thomas K.

    1985-01-01

    A nonmitogenic angiogenesis factor is isolated from wound fluid by dialysis to include materials in the molecular size range of 2,000 to 14,000, lyophilization, and chromatography. The nonmitogenic angiogenesis factor is identified by activity by corneal implant assay and by cell migration assay. The angiogenesis factor is also characterized by inactivity by mitogenesis assay.

  15. Extracellular nonmitogenic angiogenesis factor and method of isolation thereof from wound fluid

    DOEpatents

    Banda, M.J.; Werb, Z.; Knighton, D.R.; Hunt, T.K.

    1985-03-05

    A nonmitogenic angiogenesis factor is isolated from wound fluid by dialysis to include materials in the molecular size range of 2,000 to 14,000, lyophilization, and chromatography. The nonmitogenic angiogenesis factor is identified by activity by corneal implant assay and by cell migration assay. The angiogenesis factor is also characterized by inactivity by mitogenesis assay. 3 figs.

  16. Fluid shear promotes chondrosarcoma cell invasion by activating matrix metalloproteinase 12 via IGF-2 and VEGF signaling pathways

    PubMed Central

    Wang, P; Chen, S-H; Hung, W-C; Paul, C; Zhu, F; Guan, P-P; Huso, DL; Kontrogianni-Konstantopoulos, A; Konstantopoulos, K

    2015-01-01

    Interstitial fluid flow in and around the tumor tissue is a physiologically relevant mechanical signal that regulates intracellular signaling pathways throughout the tumor. Yet, the effects of interstitial flow and associated fluid shear stress on the tumor cell function have been largely overlooked. Using in vitro bioengineering models in conjunction with molecular cell biology tools, we found that fluid shear (2 dyn/cm2) markedly upregulates matrix metalloproteinase 12 (MMP-12) expression and its activity in human chondrosarcoma cells. MMP-12 expression is induced in human chondrocytes during malignant transformation. However, the signaling pathway regulating MMP-12 expression and its potential role in human chondrosarcoma cell invasion and metastasis have yet to be delineated. We discovered that fluid shear stress induces the synthesis of insulin growth factor-2 (IGF-2) and vascular endothelial growth factor (VEGF) B and D, which in turn transactivate MMP-12 via PI3-K, p38 and JNK signaling pathways. IGF-2-, VEGF-B- or VEGF-D-stimulated chondrosarcoma cells display markedly higher migratory and invasive potentials in vitro, which are blocked by inhibiting MMP-12, PI3-K, p38 or JNK activity. Moreover, recombinant human MMP-12 or MMP-12 overexpression can potentiate chondrosarcoma cell invasion in vitro and the lung colonization in vivo. By reconstructing and delineating the signaling pathway regulating MMP-12 activation, potential therapeutic strategies that interfere with chondrosarcoma cell invasion may be identified. PMID:25435370

  17. Fluid shear promotes chondrosarcoma cell invasion by activating matrix metalloproteinase 12 via IGF-2 and VEGF signaling pathways.

    PubMed

    Wang, P; Chen, S-H; Hung, W-C; Paul, C; Zhu, F; Guan, P-P; Huso, D L; Kontrogianni-Konstantopoulos, A; Konstantopoulos, K

    2015-08-27

    Interstitial fluid flow in and around the tumor tissue is a physiologically relevant mechanical signal that regulates intracellular signaling pathways throughout the tumor. Yet, the effects of interstitial flow and associated fluid shear stress on the tumor cell function have been largely overlooked. Using in vitro bioengineering models in conjunction with molecular cell biology tools, we found that fluid shear (2 dyn/cm(2)) markedly upregulates matrix metalloproteinase 12 (MMP-12) expression and its activity in human chondrosarcoma cells. MMP-12 expression is induced in human chondrocytes during malignant transformation. However, the signaling pathway regulating MMP-12 expression and its potential role in human chondrosarcoma cell invasion and metastasis have yet to be delineated. We discovered that fluid shear stress induces the synthesis of insulin growth factor-2 (IGF-2) and vascular endothelial growth factor (VEGF) B and D, which in turn transactivate MMP-12 via PI3-K, p38 and JNK signaling pathways. IGF-2-, VEGF-B- or VEGF-D-stimulated chondrosarcoma cells display markedly higher migratory and invasive potentials in vitro, which are blocked by inhibiting MMP-12, PI3-K, p38 or JNK activity. Moreover, recombinant human MMP-12 or MMP-12 overexpression can potentiate chondrosarcoma cell invasion in vitro and the lung colonization in vivo. By reconstructing and delineating the signaling pathway regulating MMP-12 activation, potential therapeutic strategies that interfere with chondrosarcoma cell invasion may be identified.

  18. Raman spectroscopy of organic, solid and fluid inclusions in the Oldest Halite of LGOM area (SW Poland)

    NASA Astrophysics Data System (ADS)

    Toboła, Tomasz

    2018-01-01

    Raman spectroscopy was applied to determine the degree of recrystallization and the influence of the secondary solution migration on the Oldest Halite (Na1) in Lubin-Głogów Copper District (LGOM). Numerous organic matter (OM) inclusions which generally show weak structural ordering was found in halite crystals. In this context they are similar to solid bitumens or carbonaceous matter of low thermal alteration. The difference in the Raman line-shape of OM indicated various thermal alteration of salt from the Oldest Halite formation due to hot fluid flow. Solutions included in the secondary fluid inclusions often contain dissolved gases such as CH4, N2, H2S. The presence of these gases is connected with migration process from basement to the salt formation. Moissanite in fluid inclusions was accidentally trapped during inclusion formation, i.e. is not a daughter mineral. It was also found in the halite as an individual solid inclusions as well as in the anhydrite concentrations. Raman spectroscopy allowed to determine also such solid inclusions in halite as celestine, magnesite, pyrite, lepidocrocite and goethite as well as hydrocarbons.

  19. PIK3CA dependence and sensitivity to therapeutic targeting in urothelial carcinoma.

    PubMed

    Ross, R L; McPherson, H R; Kettlewell, L; Shnyder, S D; Hurst, C D; Alder, O; Knowles, M A

    2016-07-28

    Many urothelial carcinomas (UC) contain activating PIK3CA mutations. In telomerase-immortalized normal urothelial cells (TERT-NHUC), ectopic expression of mutant PIK3CA induces PI3K pathway activation, cell proliferation and cell migration. However, it is not clear whether advanced UC tumors are PIK3CA-dependent and whether PI3K pathway inhibition is a good therapeutic option in such cases. We used retrovirus-mediated delivery of shRNA to knock down mutant PIK3CA in UC cell lines and assessed effects on pathway activation, cell proliferation, migration and tumorigenicity. The effect of the class I PI3K inhibitor GDC-0941 was assessed in a panel of UC cell lines with a range of known molecular alterations in the PI3K pathway. Specific knockdown of PIK3CA inhibited proliferation, migration, anchorage-independent growth and in vivo tumor growth of cells with PIK3CA mutations. Sensitivity to GDC-0941 was dependent on hotspot PIK3CA mutation status. Cells with rare PIK3CA mutations and co-occurring TSC1 or PTEN mutations were less sensitive. Furthermore, downstream PI3K pathway alterations in TSC1 or PTEN or co-occurring AKT1 and RAS gene mutations were associated with GDC-0941 resistance. Mutant PIK3CA is a potent oncogenic driver in many UC cell lines and may represent a valuable therapeutic target in advanced bladder cancer.

  20. Synergistic Effects of SAM and Selenium Compounds on Proliferation, Migration and Adhesion of HeLa Cells.

    PubMed

    Sun, Licui; Zhang, Jianxin; Yang, Qiu; Si, Yang; Liu, Yiqun; Wang, Qin; Han, Feng; Huang, Zhenwu

    2017-08-01

    To determine the antitumor activities and molecular mechanism of selenium compounds in HeLa cells. Western blotting was used to detect ERK and AKT activation in HeLa cells induced by selenium compounds selenomethionine (SeMet), methylselenocysteine (MeSeCys) and methylseleninic acids (MeSeA). Using MTT, wound-healing and Matrigel adhesion assays, the antitumor effects of SAM and selenium compounds were evaluated in HeLa cells. MeSeA inhibited ERK and AKT signaling pathways and suppressed the proliferation (p<0.05 vs. HeLa control), migration (p<0.05 vs. HeLa control) and adhesion (p<0.01 vs. HeLa control) of HeLa cells. MeSeCys and SeMet inhibited AKT signaling pathways and the migration (p<0.05 vs. HeLa control) and adhesion (p<0.01 vs. HeLa control) of HeLa cells. The synergistic action of MeSeA with SAM led to a statistically significant inhibition of proliferation, migration and adhesion of HeLa cells. MeSeA, MeSeCys and SeMet exert different antitumor activities by inhibiting ERK and AKT signaling pathways. The combination of MeSeA and SAM exhibited better antitumor effects compared to the other treatments. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. Src kinases in chondrosarcoma chemoresistance and migration: dasatinib sensitises to doxorubicin in TP53 mutant cells

    PubMed Central

    van Oosterwijk, J G; van Ruler, M A J H; Briaire-de Bruijn, I H; Herpers, B; Gelderblom, H; van de Water, B; Bovée, J V M G

    2013-01-01

    Background: Chondrosarcomas are malignant cartilage-forming tumours of bone. Because of their resistance to conventional chemotherapy and radiotherapy, currently no treatment strategies exist for unresectable and metastatic chondrosarcoma. Previously, PI3K/AKT/GSK3β and Src kinase pathways were shown to be activated in chondrosarcoma cell lines. Our aim was to investigate the role of these kinases in chemoresistance and migration in chondrosarcoma in relation to TP53 mutation status. Methods: We used five conventional and three dedifferentiated chondrosarcoma cell lines and investigated the effect of PI3K/AKT/GSK3β pathway inhibition (enzastaurin) and Src pathway inhibition (dasatinib) in chemoresistance using WST assay and live cell imaging with AnnexinV staining. Immunohistochemistry on tissue microarrays (TMAs) containing 157 cartilaginous tumours was performed for Src family members. Migration assays were performed with the RTCA xCelligence System. Results: Src inhibition was found to overcome chemoresistance, to induce apoptosis and to inhibit migration. Cell lines with TP53 mutations responded better to combination therapy than wild-type cell lines (P=0.002). Tissue microarray immunohistochemistry confirmed active Src (pSrc) signalling, with Fyn being most abundantly expressed (76.1%). Conclusion: These results strongly indicate Src family kinases, in particular Fyn, as a potential target for the treatment of inoperable and metastatic chondrosarcomas, and to sensitise for doxorubicin especially in the presence of TP53 mutations. PMID:23922104

  2. Transient Ligand Docking Sites in Cerebratulus lacteus Mini-Hemoglobin

    PubMed Central

    Deng, Pengchi; Nienhaus, Karin; Palladino, Pasquale; Olson, John S.; Blouin, George; Moens, Luc; Dewilde, Sylvia; Geuens, Eva; Nienhaus, G. Ulrich

    2007-01-01

    The monomeric hemoglobin of the nemertean worm Cerebratulus lacteus functions as an oxygen storage protein to maintain neural activity under hypoxic conditions. It shares a large, apolar matrix tunnel with other small hemoglobins, which has been implicated as a potential ligand migration pathway. Here we explore ligand migration and binding within the distal heme pocket, to which the tunnel provides access to ligands from the outside. FTIR/TDS experiments performed at cryogenic temperatures reveal the presence of three transient ligand docking sites within the distal pocket, the primary docking site B on top of pyrrole C and secondary sites C and D. Site C is assigned to a cavity adjacent to the distal portion of the heme pocket, surrounded by the B and E helices. It has an opening to the apolar tunnel and is expected to be on the pathway for ligand entry and exit, whereas site D, circumscribed by TyrB10, GlnE7, and the CD corner, most likely is located on a side pathway of ligand migration. Flash photolysis experiments at ambient temperatures indicate that the rate-limiting step for ligand binding to CerHb is migration through the apolar channel to site C. Movement from C to B and iron-ligand bond formation involve low energy barriers and thus are very rapid processes in the wt protein. PMID:17531406

  3. Alpinia oxyphylla Miquel fruit extract activates MAPK-mediated signaling of PAs and MMP2/9 to induce Schwann cell migration and nerve regeneration.

    PubMed

    Chang, Yung-Ming; Ye, Chi-Xin; Ho, Tsung-Jung; Tsai, Te-Neng; Chiu, Ping-Ling; Tsai, Chin-Chuan; Lin, Yueh-Min; Kuo, Chia-Hua; Tsai, Fuu-Jen; Tsai, Chang-Hai; Huang, Chih-Yang

    2014-05-01

    This study investigates the molecular mechanisms by which Alpiniae oxyphyllae fructus (AOF) promotes neuron regeneration. A piece of silicone rubber was guided across a 15 mm gap in the sciatic nerve of a rat. This nerve gap was then filled with different concentrations of AOF extract (0-200 mg/ml). We investigated the role of MAPK (ERK1/2, JNK and p38) pathways for AOF-induced matrix-degrading proteolytic enzyme (PAs and MMP2/9) production in RSC96 Schwann cells. The results showed that AOF increased the expressions of uPA, tPA, MMP-9, and MAPKs in vivo. In vitro, our results show that treatment with AOF extract induces ERK1/2, JNK, and p38 phosphorylation to activate the downstream PAs and MMPs signaling expression. AOF-stimulated ERK1/2, JNK, and p38 phosphorylation attenuated by individual pretreatment with siRNAs or inhibitors (U0126, SP600125 and SB203580), resulting in migration and uPA-related signal pathway inhibition. Taken together our data suggests the MAPKs (ERK1/2, JNK and p38), PAs (uPA, tPA), MMP (MMP2, MMP9) regenerative and migration signaling pathway of Schwann cells regulated by AOF extract might play a major role in Schwann cell migration and damaged peripheral nerve regeneration.

  4. Non-thermal plasma inhibits human cervical cancer HeLa cells invasiveness by suppressing the MAPK pathway and decreasing matrix metalloproteinase-9 expression

    NASA Astrophysics Data System (ADS)

    Li, Wei; Yu, K. N.; Bao, Lingzhi; Shen, Jie; Cheng, Cheng; Han, Wei

    2016-01-01

    Non-thermal plasma (NTP) has been proposed as a novel therapeutic method for anticancer treatment. However, the mechanism underlying its biological effects remains unclear. In this study, we investigated the inhibitory effect of NTP on the invasion of HeLa cells, and explored the possible mechanism. Our results showed that NTP exposure for 20 or 40 s significantly suppressed the migration and invasion of HeLa cells on the basis of matrigel invasion assay and wound healing assay, respectively. Moreover, NTP reduced the activity and protein expression of the matrix metalloproteinase (MMP)-9 enzyme. Western blot analysis indicated that NTP exposure effectively decreased phosphorylation level of both ERK1/2 and JNK, but not p38 MAPK. Furthermore, treatment with MAPK signal pathway inhibitors or NTP all exhibited significant depression of HeLa cells migration and MMP-9 expression. The result showed that NTP synergistically suppressed migration and MMP-9 expression in the presence of ERK1/2 inhibitor and JNK inhibitor, but not p38 MAPK inhibitor. Taken together, these findings suggested that NTP exposure inhibited the migration and invasion of HeLa cells via down-regulating MMP-9 expression in ERK1/2 and JNK signaling pathways dependent manner. These findings provide hints to the potential clinical research and therapy of NTP on cervical cancer metastasis.

  5. Gallic acid modulates phenotypic behavior and gene expression in oral squamous cell carcinoma cells by interfering with leptin pathway.

    PubMed

    Santos, Eliane Macedo Sobrinho; da Rocha, Rogério Gonçalves; Santos, Hércules Otacílio; Guimarães, Talita Antunes; de Carvalho Fraga, Carlos Alberto; da Silveira, Luiz Henrique; Batista, Paulo Ricardo; de Oliveira, Paulo Sérgio Lopes; Melo, Geraldo Aclécio; Santos, Sérgio Henrique; de Paula, Alfredo Maurício Batista; Guimarães, André Luiz Sena; Farias, Lucyana Conceição

    2018-01-01

    Gallic acid is a polyphenolic compost appointed to interfere with neoplastic cells behavior. Evidence suggests an important role of leptin in carcinogenesis pathways, inducing a proliferative phenotype. We investigated the potential of gallic acid to modulate leptin-induced cell proliferation and migration of oral squamous cell carcinoma cell lines. The gallic acid effect on leptin secretion by oral squamous cell carcinoma cells, as well as the underlying molecular mechanisms, was also assessed. For this, we performed proliferation, migration, immunocytochemical and qPCR assays. The expression levels of cell migration-related genes (MMP2, MMP9, Col1A1, and E-cadherin), angiogenesis (HIF-1α, mir210), leptin signaling (LepR, p44/42 MAPK), apoptosis (casp-3), and secreted leptin levels by oral squamous cell carcinoma cells were also measured. Gallic acid decreased proliferation and migration of leptin-treated oral squamous cell carcinoma cells, and reduced mRNA expression of MMP2, MMP9, Col1A1, mir210, but did not change HIF-1α. Gallic acid decreased levels of leptin secreted by oral squamous cell carcinoma cells, accordingly with downregulation of p44/42 MAPK expression. Thus, gallic acid appears to break down neoplastic phenotype of oral squamous cell carcinoma cells by interfering with leptin pathway. Copyright © 2017 Elsevier GmbH. All rights reserved.

  6. Extremely low frequency electromagnetic fields promote mesenchymal stem cell migration by increasing intracellular Ca2+ and activating the FAK/Rho GTPases signaling pathways in vitro.

    PubMed

    Zhang, Yingchi; Yan, Jiyuan; Xu, Haoran; Yang, Yong; Li, Wenkai; Wu, Hua; Liu, Chaoxu

    2018-05-21

    The ability of mesenchymal stem cells (MSCs) to migrate to the desired tissues or lesions is crucial for stem cell-based regenerative medicine and tissue engineering. Optimal therapeutics for promoting MSC migration are expected to become an effective means for tissue regeneration. Electromagnetic fields (EMF), as a noninvasive therapy, can cause a lot of biological changes in MSCs. However, whether EMF can promote MSC migration has not yet been reported. We evaluated the effects of EMF on cell migration in human bone marrow-derived MSCs. With the use of Helmholtz coils and an EMF stimulator, 7.5, 15, 30, 50, and 70 Hz/1 mT EMF was generated. Additionally, we employed the L-type calcium channel blocker verapamil and the focal adhesion kinase (FAK) inhibitor PF-573228 to investigate the role of intracellular calcium content, cell adhesion proteins, and the Rho GTPase protein family (RhoA, Rac1, and Cdc42) in EMF-mediated MSC migration. Cell adhesion proteins (FAK, talin, and vinculin) were detected by Western blot analysis. The Rho GTPase protein family activities were assessed by G-LISA, and F-actin levels, which reflect actin cytoskeletal organization, were detected using immunofluorescence. All the 7.5, 15, 30, 50, and 70 Hz/1 mT EMF promoted MSC migration. EMF increased MSC migration in an intracellular calcium-dependent manner. Notably, EMF-enhanced migration was mediated by FAK activation, which was critical for the formation of focal contacts, as evidenced by increased talin and vinculin expression. Moreover, RhoA, Rac1, and Cdc42 were activated by FAK to increase cytoskeletal organization, thus promoting cell contraction. EMF promoted MSC migration by increasing intracellular calcium and activating the FAK/Rho GTPase signaling pathways. This study provides insights into the mechanisms of MSC migration and will enable the rational design of targeted therapies to improve MSC engraftment.

  7. "She mixes her business": HIV transmission and acquisition risks among female migrants in western Kenya.

    PubMed

    Camlin, Carol S; Kwena, Zachary A; Dworkin, Shari L; Cohen, Craig R; Bukusi, Elizabeth A

    2014-02-01

    Migration and HIV research in sub-Saharan Africa has focused on HIV risks to male migrants, yet women's levels of participation in internal migration have met or exceeded those of men in the region. Moreover, studies that have examined HIV risks to female migrants found higher risk behavior and HIV prevalence among migrant compared to non-migrant women. However, little is known about the pathways through which participation in migration leads to higher risk behavior in women. This study aimed to characterize the contexts and processes that may facilitate HIV acquisition and transmission among migrant women in the Kisumu area of Nyanza Province, Kenya. We used qualitative methods, including 6 months of participant observation in women's common migration destinations and in-depth semi-structured interviews conducted with 15 male and 40 female migrants selected from these destinations. Gendered aspects of the migration process may be linked to the high risks of HIV observed in female migrants - in the circumstances that trigger migration, livelihood strategies available to female migrants, and social features of migration destinations. Migrations were often precipitated by household shocks due to changes in marital status (as when widowhood resulted in disinheritance) and gender-based violence. Many migrants engaged in transactional sex, of varying regularity, from clandestine to overt, to supplement earnings from informal sector trading. Migrant women are at high risk of HIV transmission and acquisition: the circumstances that drove migration may have also increased HIV infection risk at origin; and social contexts in destinations facilitate having multiple sexual partners and engaging in transactional sex. We propose a model for understanding the pathways through which migration contributes to HIV risks in women in high HIV prevalence areas in Africa, highlighting potential opportunities for primary and secondary HIV prevention at origins and destinations, and at key 'moments of vulnerability' in the migration process. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Leptin promotes human endometriotic cell migration and invasion by up-regulating MMP-2 through the JAK2/STAT3 signaling pathway.

    PubMed

    Ahn, Ji-Hye; Choi, Youn Seok; Choi, Jung-Hye

    2015-10-01

    Despite evidence that leptin may play a role in the pathogenesis of endometriosis, the specific function of leptin in the migration and invasion of endometriotic cells is not well characterized. In this study, we investigated the effect of leptin on the migration, invasion and matrix metalloproteinase (MMP) expression levels of human endometriotic cells. We found that leptin stimulated the migration and invasion of endometriotic cells (11Z, 12Z and 22B) in a dose-dependent manner. Leptin receptor (ObR) siRNA significantly inhibited the migration and invasion induced by leptin in 11Z and 12Z cells. Leptin-induced migration and invasion were significantly attenuated by pretreatment with SB-3CT, a specific gelatinase (MMP-2 and MMP-9) inhibitor. In addition, leptin-induced increases in the mRNA and protein expression and enzyme activity of MMP-2 in 11Z and 12Z cells. Selectively inhibiting MMP-2 using siRNA and an inhibitor (GM6003), impaired the ability of leptin to stimulate the migration and invasion of endometriotic cells, suggesting that MMP-2 plays an essential role in leptin-induced migration and invasion. Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) inhibitor (AG490) significantly inhibited the migration, invasion and MMP-2 expression induced by leptin in endometriotic cells. Furthermore, the Extracellular signal-Regulated Kinase inhibitor PD98059 neutralized the migration and invasion promoting effects of leptin. Taken together, these results suggest that leptin may contribute to the migration and invasion abilities of endometriotic cells via the up-regulation of MMP-2 through an ObR-dependent JAK2/STAT3 signaling pathway. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. “She mixes her business”: HIV transmission and acquisition risks among female migrants in western Kenya

    PubMed Central

    Camlin, Carol S.; Kwena, Zachary A.; Dworkin, Shari L.; Cohen, Craig R.; Bukusi, Elizabeth A.

    2014-01-01

    Migration and HIV research in sub-Saharan Africa has focused on HIV risks to male migrants, yet women’s levels of participation in internal migration have met or exceeded those of men in the region. Moreover, studies that have examined HIV risks to female migrants found higher risk behavior and HIV prevalence among migrant compared to non-migrant women. However, little is known about the pathways through which participation in migration leads to higher risk behavior in women. This study aimed to characterize the contexts and processes that may facilitate HIV acquisition and transmission among migrant women in the Kisumu area of Nyanza Province, Kenya. We used qualitative methods, including 6 months of participant observation in women’s common migration destinations and in-depth semi-structured interviews conducted with 15 male and 40 female migrants selected from these destinations. Gendered aspects of the migration process may be linked to the high risks of HIV observed in female migrants— in the circumstances that trigger migration, livelihood strategies available to female migrants, and social features of migration destinations. Migrations were often precipitated by household shocks due to changes in marital status (as when widowhood resulted in disinheritance) and gender-based violence. Many migrants engaged in transactional sex, of varying regularity, from clandestine to overt, to supplement earnings from informal sector trading. Migrant women are at high risk of HIV transmission and acquisition: the circumstances that drove migration may have also increased HIV infection risk at origin; and social contexts in destinations facilitate having multiple sexual partners and engaging in transactional sex. We propose a model for understanding the pathways through which migration contributes to HIV risks in women in high HIV prevalence areas in Africa, highlighting potential opportunities for primary and secondary HIV prevention at origins and destinations, and at key ‘moments of vulnerability’ in the migration process. PMID:24565152

  10. Contributions of fluid convection and electrical migration to transport in cartilage: relevance to loading.

    PubMed

    Garcia, A M; Frank, E H; Grimshaw, P E; Grodzinsky, A J

    1996-09-15

    We have studied the contributions of diffusion, fluid flow and electrical migration to molecular transport through adult articular cartilage explants using neutral and charged solutes that were either radiolabeled (3H2O, [35S]sulfate, [3H]thymidine, [3H]raffinose, and a synthetic matrix metalloproteinase inhibitor) or fluorescently tagged (NSPA and Lissamine-dextran). In order to induce fluid flow within the cartilage matrix without mechanical deformation, electric current densities were applied across cartilage disks. These currents produced electroosmotic fluid velocities of 1-2 microns/s, magnitudes that have been reported to exist during joint loading in vivo. This fluid convection enhanced neutral solute flux relative to passive diffusion alone by a factor that increased with the size of the solute. While the enhancement factor for 3H2O was 2.3-fold, that for [3H]raffinose (594 Da) and similar sized neutral solutes was 10-fold, suggesting that the effect of fluid flow is important even for small solutes. The largest enhancement (25-fold) was seen for the neutral 10-kDa Lissamine-dextran, confirming that fluid convection is most important for large solutes. We also studied the electrophoretic contribution to solute flux, which is relevant to the presence of intratissue streaming potentials induced during loading in vivo. Using the negatively charged [35S]sulfate ion with a range of current densities, as much as a 10-fold enhancement in flux was observed. Values for the intrinsic transport properties of the solutes (e.g., diffusivity, electrical mobility, hydrodynamic hindrance factor) can be obtained from the data.

  11. Morphogenesis of the SW Balearic continental slope and adjacent abyssal plain, Western Mediterranean Sea

    NASA Astrophysics Data System (ADS)

    Camerlenghi, Angelo; Accettella, Daniela; Costa, Sergio; Lastras, Galderic; Acosta, Juan; Canals, Miquel; Wardell, Nigel

    2009-06-01

    We present the seafloor morphology and shallow seismic structure of the continental slope south-east of the Balearic promontory and of the adjacent Algero-Balearic abyssal plain from multibeam and chirp sonar data. The main purpose of this research was to identify the sediment pathways from the Balearic promontory to the Algero-Balearic deep basin from the Early Pliocene to the Present. The morphology of the southern Balearic margin is controlled by a SW-NE structural trend, whose main expressions are the Emile Baudot Escarpment transform fault, and a newly discovered WSW-ENE trend that affects the SW end of the escarpment and the abyssal plain. We relate the two structural trends to right-lateral simple shear as a consequence of the Miocene westward migration of the Gibraltar Arc. Newly discovered steep and narrow volcanic ridges were probably enabled to grow by local transtension along the transform margin. Abyssal plain knolls and seahills relate to the subsurface deformation of early stage halokinetic structures such as salt rollers, salt anticlines, and salt pillows. The limited thickness of the overburden and the limited amount of deformation in the deep basin prevent the formation of more mature halokinetic structures such as diapirs, salt walls, bulbs, and salt extrusions. The uppermost sediment cover is affected by a dense pattern of sub-vertical small throw normal faults resulting from extensional stress induced in the overburden by subsurface salt deformation structures. Shallow gas seismic character and the possible presence of an active polygonal fault system suggest upward fluid migration and fluid and sediment expulsion at the seafloor through a probable mud volcano and other piercement structures. One large debris flow deposit, named Formentera Debris Flow, has been identified on the lower slope and rise of the south Formentera margin. Based on current observations, we hypothesize that the landslide originating the Formentera Debris Flow occurred in the Holocene, perhaps in historical times.

  12. Structural characteristics of the décollement zone and underthrust sediments in the Nankai accretionary prism: Geologic architectures in the Site C0023, IODP Expedition 370

    NASA Astrophysics Data System (ADS)

    Yamamoto, Y.; Okutsu, N.; Yamada, Y.; Bowden, S.; Tonai, S.; Yang, K.; Tsang, M. Y.; Hirose, T.; Kamiya, N.

    2017-12-01

    Expedition 370 penetrated the accretionary prism, plate boundary décollement zone, and underthrust sediment and touched the basement basalt on the Philippine Sea Plate. The drilling site (C0023) is located 4 km NE from the legacy sites, Sites 808 and 1174. Compared to the legacy sites, the décollement zone is characterized by weak and intermittent negative reflectors in the seismic profile. Onboard physical properties, e.g. porosity and P-wave velocity data, indeed show the smaller gaps at the top of the décollement zone. The nature of the deformation along the décollement zone represented 40 m thick phacoidal deformation zone composed of fragmented mudstone with slickenlines on the surfaces in the Sites 808 and 1174. Compare with this, décollement zone in Site C0023 represented the weaker and non-localized deformation zone comprised of alternating zone of 1 m thick phacoidal deformation zones and a few 10 m of intact intervals in the Site C0023. Many normal faults striking parallel to the trench were identified just below the décollement zone, which is indicative of non-localized deformations along the décollement zone. Many of these faults were accompanied with calcite and sulphate mineral veins (anhydrite and barite), indicative of high-temperature fluid migration just above the ridge-spreading center. Based on the paleomagnetic restoration of structure to the geologic coordinate, attitudes of the bedding and fault planes in the Site C0023 are controlled by two factors: 1) subduction/accretion producing the trench-parallel bedding strikes and trench-perpendicular principal stress and 2) ridge spreading that produces ridge-parallel bedding and vein strikes. The former developed in the accretionary prism and the upper part of the underthrust sediment (<900 mbsf), whereas the latter occurs in the lower part (>900 mbsf). These tectonic variations might affect fluid migration pathways.

  13. Application of geoelectric and electromagnetic methods for the detection of failing zones and brine rising zones in the vicinity of a potential CO2-storage site

    NASA Astrophysics Data System (ADS)

    Herd, Rainer; Krause, Yvonne; Schafrik, Wlad

    2013-04-01

    Within the framework of the project "brine - CO2 storage in eastern Brandenburg" geophysical investigations are conducted by the German Research Center for Geoscience (GFZ), Potsdam and the Brandenburg University of Technology (BTU), Cottbus on different scales in order to investigate underground situations and evaluate methods suitable for a salinization early warning system. The research of BTU is focused on the distribution of underground structures up to a maximum depth of 200m. Of prevalent interest are the detection capabilities for near surface failing zones which might serve as favored pathways for brine migration and the status-quo of the freshwater-saltwater boundary. Geophysical investigations with the frequency domain electromagnetic (FDEM) and direct current (DC) geoelectric methods are qualified for the identification and monitoring of brine displacement as the measuring parameter is the resistivity/conductivity of the subsurface. In eastern Brandenburg the Oligocene Rupelian clay represents the barrier horizon separating the freshwater and saline aquifers. Due to postglacial processes this layer is locally reduced or totally eroded and might enhance upward brine migration during pressure increase. The areas of investigation were selected by known high fluid conductivity values (hydro chemical indication) and the potential presence of quaternary erosion channels in the Rupelian clay (geological indication). The geophysical results yield a vertical and horizontal resistivity/conductivity distribution. The interpretation is done by lithology profiles of nearby boreholes and correlation with fluid conductivities in groundwater wells. The results of FDEM and DC on coincident profiles are generally in accordance and show that both methods are suitable with DC geoelectrics supplementing a higher resolution close to the surface (max. 80m depth) and the electromagnetics adding coarser/less detailed conductivity information of the deeper underground (down to 200m depth).

  14. Volatile dynamics in crystal-rich magma bodies, perspectives from laboratory experiments and theory

    NASA Astrophysics Data System (ADS)

    Faroughi, S.; Parmigiani, A.; Huber, C.

    2013-12-01

    The amount of volatiles and the dynamics of bubbles play a significant role on the transition between different volcanic eruption behaviors. The transport of exsolved volatiles through zoned magma chambers is complex and remains poorly constrained. Here we focus on the different transport of volatiles under two end member regimes: crystal-poor systems (bubbles form a suspension) versus crystal-rich reservoirs (multiphase porous media flow). We present a combination of multiphase flow laboratory experiments (using silicon oil and water) and a theoretical argument based on Stokes flow streamfunctions to contrast the differences between the transport of exsolved volatiles in both regimes. The first set of experiments involves the buoyant migration of water droplets in silicon oil in the absence of glass beads. We measure the non-linear hydrodynamic interaction between bubbles and its effect on slowing down the average flux of water droplets as the water volume fraction increases. Our experimental results are compared to a theoretical argument in which a streamfunction formulation is used to estimate the effect of a suspension on bubble migration. We find a good agreement between the new theory and our experimental results. The second set of experiments focuses on the transport of water (non-wetting fluid) in porous media saturated with viscous silicon oils. Contrary to suspension dynamics, in multiphase porous media, an increase in the saturation of non-wetting fluid leads to a non-linear increase in its volumetric flux. The steady-state migration of non-wetting fluid is controlled by the formation of viscous fingering instability that greatly enhances transport. We propose that the regime of energy dissipation during the migration of bubbles in heterogeneous magma reservoirs can change, leading to bubble accumulation in crystal-poor regions as fingering becomes unstable and volatiles form a disperse bubble suspension.

  15. HIV Migration Between Blood and Cerebrospinal Fluid or Semen Over Time

    PubMed Central

    Chaillon, Antoine; Gianella, Sara; Wertheim, Joel O.; Richman, Douglas D.; Mehta, Sanjay R.; Smith, David M.

    2014-01-01

    Previous studies reported associations between neuropathogenesis and human immunodeficiency virus (HIV) compartmentalization in cerebrospinal fluid (CSF) and between sexual transmission and human immunodeficiency virus type 1 (HIV) compartmentalization in semen. It remains unclear, however, how compartmentalization dynamics change over time. To address this, we used statistical methods and Bayesian phylogenetic approaches to reconstruct temporal dynamics of HIV migration between blood and CSF and between blood and the male genital tract. We investigated 11 HIV-infected individuals with paired semen and blood samples and 4 individuals with paired CSF and blood samples. Aligned partial HIV env sequences were analyzed by (1) phylogenetic reconstruction, using a Bayesian Markov-chain Monte Carlo approach; (2) evaluation of viral compartmentalization, using tree-based and distance-based methods; and (3) analysis of migration events, using a discrete Bayesian asymmetric phylogeographic approach of diffusion with Markov jump counts estimation. Finally, we evaluated potential correlates of viral gene flow across anatomical compartments. We observed bidirectional replenishment of viral compartments and asynchronous peaks of viral migration from and to blood over time, suggesting that disruption of viral compartment is transient and directionally selected. These findings imply that viral subpopulations in anatomical sites are an active part of the whole viral population and that compartmental reservoirs could have implications in future eradication studies. PMID:24302756

  16. Time-lapse 3-D seismic imaging of shallow subsurface contaminant flow.

    PubMed

    McKenna, J; Sherlock, D; Evans, B

    2001-12-01

    This paper presents a physical modelling study outlining a technique whereby buoyant contaminant flow within water-saturated unconsolidated sand was remotely monitored utilizing the time-lapse 3-D (TL3-D) seismic response. The controlled temperature and pressure conditions, along with the high level of acquisition repeatability attainable using sandbox physical models, allow the TL3-D seismic response to pore fluid movement to be distinguished from all other effects. TL3-D seismic techniques are currently being developed to monitor hydrocarbon reserves within producing reservoirs in an endeavour to improve overall recovery. However, in many ways, sandbox models under atmospheric conditions more accurately simulate the shallow subsurface than petroleum reservoirs. For this reason, perhaps the greatest application for analogue sandbox modelling is to improve our understanding of shallow groundwater and environmental flow mechanisms. Two fluid flow simulations were conducted whereby air and kerosene were injected into separate water-saturated unconsolidated sand models. In both experiments, a base 3-D seismic volume was recorded and compared with six later monitor surveys recorded while the injection program was conducted. Normal incidence amplitude and P-wave velocity information were extracted from the TL3-D seismic data to provide visualization of contaminant migration. Reflection amplitudes displayed qualitative areal distribution of fluids when a suitable impedance contrast existed between pore fluids. TL3-D seismic reflection tomography can potentially monitor the change in areal distribution of fluid contaminants over time, indicating flow patterns. However, other research and this current work have not established a quantifiable relationship between either normal reflection amplitudes and attenuation and fluid saturation. Generally, different pore fluids will have unique seismic velocities due to differences in compressibility and density. The predictable relationships that exist between P-wave velocity and fluid saturation can allow a quantitative assessment of contaminant migration.

  17. Migratory bird pathways and the Gulf of Mexico: Importance of Louisiana's coast

    USGS Publications Warehouse

    Smith, Gregory J.; Barrow, Wylie

    2005-01-01

    Because of its geographic position, Louisiana plays an important role in the hemispheric-scale phenomenon known as the Nearctic-Neotropical bird migration system. Each year millions of landbirds migrate across or near to the coast of the Gulf of Mexico. Birds migrate in large, broad fronts that sometimes exceed 2 million individuals, and there is an advantage for them to take a direct north-south route (the shortest distance).During migration seasons, nearly all of the migratory landbird species of the eastern United States, as well as many western species, use the coastal plains of the western gulf.Spring migrants arrive with depleted energy reserves and depend on Louisiana's coastal habitats to provide food and cover after long gulf crossings.Fall migrants depend on Louisiana’s coastal habitats for food to store fat reserves just prior to gulf crossings in autumn.Mortality during the migratory period can be high. Recent research on the black-throated blue warbler (Dendroica caerulescens) indicates that more than 85% of the annual mortality for the species occurs during migration.Migrants en route tend to concentrate in habitats adjacent to ecological barriers; DOI land managers need to identify key coastal landscape features that are important to these birds.Because of the vastness of the North American continent, it is nearly impossible to delineate movement patterns and migration pathways by using traditional ground-based surveys.

  18. RNase L Suppresses Androgen Receptor Signaling, Cell Migration and Matrix Metalloproteinase Activity in Prostate Cancer Cells

    PubMed Central

    Dayal, Shubham; Zhou, Jun; Manivannan, Praveen; Siddiqui, Mohammad Adnan; Ahmad, Omaima Farid; Clark, Matthew; Awadia, Sahezeel; Garcia-Mata, Rafael; Shemshedini, Lirim; Malathi, Krishnamurthy

    2017-01-01

    The interferon antiviral pathways and prostate cancer genetics converge on a regulated endoribonuclease, RNase L. Positional cloning and linkage studies mapped Hereditary Prostate Cancer 1 (HPC1) to RNASEL. To date, there is no correlation of viral infections with prostate cancer, suggesting that RNase L may play additional roles in tumor suppression. Here, we demonstrate a role of RNase L as a suppressor of androgen receptor (AR) signaling, cell migration and matrix metalloproteinase activity. Using RNase L mutants, we show that its nucleolytic activity is dispensable for both AR signaling and migration. The most prevalent HPC1-associated mutations in RNase L, R462Q and E265X, enhance AR signaling and cell migration. RNase L negatively regulates cell migration and attachment on various extracellular matrices. We demonstrate that RNase L knockdown cells promote increased cell surface expression of integrin β1 which activates Focal Adhesion Kinase-Sarcoma (FAK-Src) pathway and Ras-related C3 botulinum toxin substrate 1-guanosine triphosphatase (Rac1-GTPase) activity to increase cell migration. Activity of matrix metalloproteinase (MMP)-2 and -9 is significantly increased in cells where RNase L levels are ablated. We show that mutations in RNase L found in HPC patients may promote prostate cancer by increasing expression of AR-responsive genes and cell motility and identify novel roles of RNase L as a prostate cancer susceptibility gene. PMID:28257035

  19. bFGF Promotes the Migration of Human Dermal Fibroblasts under Diabetic Conditions through Reactive Oxygen Species Production via the PI3K/Akt-Rac1- JNK Pathways

    PubMed Central

    Shi, Hongxue; Cheng, Yi; Ye, Jingjing; Cai, Pingtao; Zhang, Jinjing; Li, Rui; Yang, Ying; Wang, Zhouguang; Zhang, Hongyu; Lin, Cai; Lu, Xianghong; Jiang, Liping; Hu, Aiping; Zhu, Xinbo; Zeng, Qiqiang; Fu, Xiaobing; Li, Xiaokun; Xiao, Jian

    2015-01-01

    Fibroblasts play a pivotal role in the process of cutaneous wound repair, whereas their migratory ability under diabetic conditions is markedly reduced. In this study, we investigated the effect of basic fibroblast growth factor (bFGF) on human dermal fibroblast migration in a high-glucose environment. bFGF significantly increased dermal fibroblast migration by increasing the percentage of fibroblasts with a high polarity index and reorganizing F-actin. A significant increase in intracellular reactive oxygen species (ROS) was observed in dermal fibroblasts under diabetic conditions following bFGF treatment. The blockage of bFGF-induced ROS production by either the ROS scavenger N-acetyl-L-cysteine (NAC) or the NADPH oxidase inhibitor diphenylene iodonium chloride (DPI) almost completely neutralized the increased migration rate of dermal fibroblasts promoted by bFGF. Akt, Rac1 and JNK were rapidly activated by bFGF in dermal fibroblasts, and bFGF-induced ROS production and promoted dermal fibroblast migration were significantly attenuated when suppressed respectively. In addition, bFGF-induced increase in ROS production was indispensable for the activation of focal adhesion kinase (FAK) and paxillin. Therefore, our data suggested that bFGF promotes the migration of human dermal fibroblasts under diabetic conditions through increased ROS production via the PI3K/Akt-Rac1-JNK pathways. PMID:26078726

  20. Reelin is involved in transforming growth factor-β1-induced cell migration in esophageal carcinoma cells.

    PubMed

    Yuan, Yi; Chen, Hongyan; Ma, Gang; Cao, Xiaofeng; Liu, Zhihua

    2012-01-01

    Reelin (RELN), which is a glycoprotein secreted by Cajal-Retzius cells of the developing cerebral cortex, plays an important role in neuronal migration, but its role in cell migration and cancer metastasis is largely unclear. Here, we showed that cell motility was significantly increased in KYSE-510 cells by TGF-β1 treatment. Moreover, TGF-β1 decreased RELN mRNA expression and overexpression of Reelin at least partly reversed TGF-β1-induced cell migration in KYSE-30 cells. Furthermore, this negative regulation of Reelin expression by TGF-β1 was through Snail, one transcription factor which was induced by TGF-β1 in KYSE-510 cells. RELN promoter activity was reduced in parallel with the induction of Snail after TGF-β1 treatment and Snail suppressed both RELN promoter activity and expression through binding to E-box sequences in the RELN promoter region in ESCC cells. Knockdown of RELN induced cell migration in KYSE-510 cells, together with the increase of mesenchymal markers expression. Taken together, Reelin is an essential negative regulator in the TGF-β1-induced cell migration process, and is suppressed by TGF-β pathway at the transcriptional level through Snail regulation. Therefore, the correlation of Reelin and TGF-β pathway was critical in cancer metastasis, and Reelin could be one potential anti-metastasis target in future clinical practice.

  1. Numerical simulation of the environmental impact of hydraulic fracturing of tight/shale gas reservoirs on near-surface groundwater: Background, base cases, shallow reservoirs, short-term gas, and water transport.

    PubMed

    Reagan, Matthew T; Moridis, George J; Keen, Noel D; Johnson, Jeffrey N

    2015-04-01

    Hydrocarbon production from unconventional resources and the use of reservoir stimulation techniques, such as hydraulic fracturing, has grown explosively over the last decade. However, concerns have arisen that reservoir stimulation creates significant environmental threats through the creation of permeable pathways connecting the stimulated reservoir with shallower freshwater aquifers, thus resulting in the contamination of potable groundwater by escaping hydrocarbons or other reservoir fluids. This study investigates, by numerical simulation, gas and water transport between a shallow tight-gas reservoir and a shallower overlying freshwater aquifer following hydraulic fracturing operations, if such a connecting pathway has been created. We focus on two general failure scenarios: (1) communication between the reservoir and aquifer via a connecting fracture or fault and (2) communication via a deteriorated, preexisting nearby well. We conclude that the key factors driving short-term transport of gas include high permeability for the connecting pathway and the overall volume of the connecting feature. Production from the reservoir is likely to mitigate release through reduction of available free gas and lowering of reservoir pressure, and not producing may increase the potential for release. We also find that hydrostatic tight-gas reservoirs are unlikely to act as a continuing source of migrating gas, as gas contained within the newly formed hydraulic fracture is the primary source for potential contamination. Such incidents of gas escape are likely to be limited in duration and scope for hydrostatic reservoirs. Reliable field and laboratory data must be acquired to constrain the factors and determine the likelihood of these outcomes. Short-term leakage fractured reservoirs requires high-permeability pathways Production strategy affects the likelihood and magnitude of gas release Gas release is likely short-term, without additional driving forces.

  2. JWA gene regulates PANC-1 pancreatic cancer cell behaviors through MEK-ERK1/2 of the MAPK signaling pathway.

    PubMed

    Wu, Yuan-Yuan; Ma, Tie-Liang; Ge, Zhi-Jun; Lin, Jie; Ding, Wei-Liang; Feng, Jia-Ke; Zhou, Su-Jun; Chen, Guo-Chang; Tan, Yong-Fei; Cui, Guo-Xing

    2014-10-01

    The present study aimed to investigate the role of JWA gene in the proliferation, apoptosis, invasion and migration of PANC-1 pancreatic cancer cells and the effect on the MAPK signaling pathway. Human PANC-1 pancreatic cancer cells were cultured in vitro , and small interfering RNA (siRNA) was designed for the JWA gene. The siRNA was transfected into PANC-1 cells. Subsequently, the cell proliferation was measured by MTT assay; cell apoptosis was detected by analyzing BAX and Bcl-2 protein expression; cell migration and invasion were measured using Transwell ® chambers; and the protein expression of JWA and ERK1/2, JNK and p38 and their phosphorylated forms were measured by western blotting. By utilizing the MTT assay, the results showed that when JWA protein expression was inhibited, the proliferation of PANC-1 cells was enhanced. In addition, the expression of apoptosis-associated protein (AAP) BAX was substantially decreased, while the expression of the apoptosis inhibitor gene, Bcl-2 , was significantly enhanced. Using Transwell chambers, it was found that the number of penetrating PANC-1 cells was significantly increased after transfection with JWA siRNA, suggesting that the migration and invasion of the cells was substantially increased. By studying the association between JWA and the MAPK pathway in PANC-1 cells, it was found that the expression of p-ERK1/2 of the MAPK pathway was significantly downregulated following JWA siRNA transfection. However, the expression levels of ERK1/2, JNK, p38, p-JNK and p-p38 showed no significant differences. In conclusion, it was shown that JWA affects the proliferation, apoptosis, invasion and migration of PANC-1 pancreatic cancer cells which could be attributed to effects on the expression of ERK1/2 in the MAPK pathway.

  3. Downregulation of lncRNA H19 inhibits the migration and invasion of melanoma cells by inactivating the NF‑κB and PI3K/Akt signaling pathways.

    PubMed

    Liao, Zhichao; Zhao, Jun; Yang, Yun

    2018-05-01

    As the most aggressive type of skin cancer, melanoma seriously affects human health. Long noncoding (lncRNA) 19 has been demonstrated to be involved in the progression of a number of different types of human cancers. However, the involvement of lncRNA H19 in melanoma remains unknown. Therefore, the present study was performed to investigate the roles of H19 in the development and progression of melanoma. In the present study, 49 patients with melanoma were included. Expression of lncRNA H19 in tumor tissue, adjacent healthy tissue and various cell lines with different treatments was measured by reverse transcription‑quantitative polymerase chain reaction. The effects of H19 knockdown on melanoma cell proliferation, migration and invasion were detected by cell counting kit‑8, wound‑healing and transwell invasion assays, respectively. In addition, the effects of H19 knockdown on the expression of nuclear factor (NF)‑κB pathway‑associated proteins were investigated by western blotting. The results revealed that the expression level of H19 was significantly higher in tumor tissue than in the adjacent healthy tissue of 47 out of 49 patients. H19 knockdown significantly reduced the proliferation, migration and invasion ability of melanoma cells. H19 knockdown also inactivated the phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt) pathway, which in turn inhibited the activation of the NF‑κB signaling pathway. Thus, downregulation of lncRNA H19 may inhibit the migration and invasion of melanoma cells by inactivating the NF‑κB signaling pathway via the inactivation of the PI3K/Akt signaling pathway. The present study provided references for future studies on the pathogenesis of melanoma and the clinical treatment of this disease.

  4. Noble gases solubility models of hydrocarbon charge mechanism in the Sleipner Vest gas field

    NASA Astrophysics Data System (ADS)

    Barry, P. H.; Lawson, M.; Meurer, W. P.; Warr, O.; Mabry, J. C.; Byrne, D. J.; Ballentine, C. J.

    2016-12-01

    Noble gases are chemically inert and variably soluble in crustal fluids. They are primarily introduced into hydrocarbon reservoirs through exchange with formation waters, and can be used to assess migration pathways and mechanisms, as well as reservoir storage conditions. Of particular interest is the role groundwater plays in hydrocarbon transport, which is reflected in hydrocarbon-water volume ratios. Here, we present compositional, stable isotope and noble gas isotope and abundance data from the Sleipner Vest field, in the Norwegian North Sea. Sleipner Vest gases are generated from primary cracking of kerogen and the thermal cracking of oil. Gas was emplaced into the Sleipner Vest from the south and subsequently migrated to the east, filling and spilling into the Sleipner Ost fields. Gases principally consist of hydrocarbons (83-93%), CO2 (5.4-15.3%) and N2 (0.6-0.9%), as well as trace concentrations of noble gases. Helium isotopes (3He/4He) are predominantly radiogenic and range from 0.065 to 0.116 RA; reported relative to air (RA = 1.4 × 10-6; Clarke et al., 1976; Sano et al., 1988), showing predominantly (>98%) crustal contributions, consistent with Ne (20Ne/22Ne from 9.70 to 9.91; 21Ne/22Ne from 0.0290 to 0.0344) and Ar isotopes (40Ar/36Ar from 315 to 489). Air-derived noble gas isotopes (20Ne, 36Ar, 84Kr, 132Xe) are introduced into the hydrocarbon system by direct exchange with air-saturated water (ASW). The distribution of air-derived noble gas species are controlled by phase partitioning processes; in that they preferentially partition into the gas (i.e., methane) phase, due to their low solubilities in fluids. Therefore, the extent of exchange between hydrocarbon phases and formation waters - that have previously equilibrated with the atmosphere - can be determined by investigating air-derived noble gas species. We utilize both elemental ratios to address process (i.e., open vs. closed system) and concentrations to quantify the extent of hydrocarbon-water exchange (i.e., volumetric gas-water ratios). These data are discussed within the framework of several conceptual models: (i) total gas-stripping model, which assumes all noble gases have been stripped from the water phase, thus defining the minimum volume of water to have interacted with the hydrocarbon phase; (ii) equilibrium model, which assumes equilibration between groundwater and hydrocarbon phase at reservoir P, T and salinity; and (iii) open and closed system gas-stripping models, using concentrations and elemental ratios. By applying these models to Ne-Ar data from Sleipner, we estimate volumetric gas-water ratios (Vg/Vw) between 0.02 and 0.07, which are lower than standard geologic gas-water estimates of ∼0.24, estimated by combining gas-in-place estimates with groundwater porosity estimates. Sleipner Vest data can be best approximated by an open system model, which predicts more than an order of magnitude more groundwater interaction during migration than geologic estimates, indicating a dynamic aquifer system and/or a hydrous migration pathway. In an open system, the extent of gas loss can be estimated to be between 8 and 10 reservoir volumes, which have passed through the system and been lost (i.e., filled and spilled).

  5. Curcumin and Emodin Down-Regulate TGF-β Signaling Pathway in Human Cervical Cancer Cells

    PubMed Central

    Thacker, Pooja Chandrakant; Karunagaran, Devarajan

    2015-01-01

    Cervical cancer is the major cause of cancer related deaths in women, especially in developing countries and Human Papilloma Virus infection in conjunction with multiple deregulated signaling pathways leads to cervical carcinogenesis. TGF-β signaling in later stages of cancer is known to induce epithelial to mesenchymal transition promoting tumor growth. Phytochemicals, curcumin and emodin, are effective as chemopreventive and chemotherapeutic compounds against several cancers including cervical cancer. The main objective of this work was to study the effect of curcumin and emodin on TGF-β signaling pathway and its functional relevance to growth, migration and invasion in two cervical cancer cell lines, SiHa and HeLa. Since TGF-β and Wnt/β-catenin signaling pathways are known to cross talk having common downstream targets, we analyzed the effect of TGF-β on β-catenin (an important player in Wnt/β-catenin signaling) and also studied whether curcumin and emodin modulate them. We observed that curcumin and emodin effectively down regulate TGF-β signaling pathway by decreasing the expression of TGF-β Receptor II, P-Smad3 and Smad4, and also counterbalance the tumorigenic effects of TGF-β by inhibiting the TGF-β-induced migration and invasion. Expression of downstream effectors of TGF-β signaling pathway, cyclinD1, p21 and Pin1, was inhibited along with the down regulation of key mesenchymal markers (Snail and Slug) upon curcumin and emodin treatment. Curcumin and emodin were also found to synergistically inhibit cell population and migration in SiHa and HeLa cells. Moreover, we found that TGF-β activates Wnt/β-catenin signaling pathway in HeLa cells, and curcumin and emodin down regulate the pathway by inhibiting β-catenin. Taken together our data provide a mechanistic basis for the use of curcumin and emodin in the treatment of cervical cancer. PMID:25786122

  6. Curcumin and emodin down-regulate TGF-β signaling pathway in human cervical cancer cells.

    PubMed

    Thacker, Pooja Chandrakant; Karunagaran, Devarajan

    2015-01-01

    Cervical cancer is the major cause of cancer related deaths in women, especially in developing countries and Human Papilloma Virus infection in conjunction with multiple deregulated signaling pathways leads to cervical carcinogenesis. TGF-β signaling in later stages of cancer is known to induce epithelial to mesenchymal transition promoting tumor growth. Phytochemicals, curcumin and emodin, are effective as chemopreventive and chemotherapeutic compounds against several cancers including cervical cancer. The main objective of this work was to study the effect of curcumin and emodin on TGF-β signaling pathway and its functional relevance to growth, migration and invasion in two cervical cancer cell lines, SiHa and HeLa. Since TGF-β and Wnt/β-catenin signaling pathways are known to cross talk having common downstream targets, we analyzed the effect of TGF-β on β-catenin (an important player in Wnt/β-catenin signaling) and also studied whether curcumin and emodin modulate them. We observed that curcumin and emodin effectively down regulate TGF-β signaling pathway by decreasing the expression of TGF-β Receptor II, P-Smad3 and Smad4, and also counterbalance the tumorigenic effects of TGF-β by inhibiting the TGF-β-induced migration and invasion. Expression of downstream effectors of TGF-β signaling pathway, cyclinD1, p21 and Pin1, was inhibited along with the down regulation of key mesenchymal markers (Snail and Slug) upon curcumin and emodin treatment. Curcumin and emodin were also found to synergistically inhibit cell population and migration in SiHa and HeLa cells. Moreover, we found that TGF-β activates Wnt/β-catenin signaling pathway in HeLa cells, and curcumin and emodin down regulate the pathway by inhibiting β-catenin. Taken together our data provide a mechanistic basis for the use of curcumin and emodin in the treatment of cervical cancer.

  7. MiR-592 Promotes Gastric Cancer Proliferation, Migration, and Invasion Through the PI3K/AKT and MAPK/ERK Signaling Pathways by Targeting Spry2.

    PubMed

    He, Yu; Ge, Yugang; Jiang, Mingkun; Zhou, Jundong; Luo, Dakui; Fan, Hao; Shi, Liang; Lin, Linling; Yang, Li

    2018-06-21

    Gastric cancer (GC) is one of the most prevalent digestive malignancies. MicroRNAs (miRNAs) are involved in multiple cellular processes, including oncogenesis, and miR-592 itself participates in many malignancies; however, its role in GC remains unknown. In this study, we investigated the expression and molecular mechanisms of miR-592 in GC. Quantitative real-time PCR and immunohistochemistry were performed to determine the expression of miR-592 and its putative targets in human tissues and cell lines. Proliferation, migration, and invasion were evaluated by Cell Counting Kit-8, population doubling time, colony formation, Transwell, and wound-healing assays in transfected GC cells in vitro. A dual-luciferase reporter assay was used to determine whether miR-592 could directly bind its target. A tumorigenesis assay was used to study whether miR-592 affected GC growth in vivo. Proteins involved in signaling pathways and the epithelial-mesenchymal transition (EMT) were detected with western blot. The ectopic expression of miR-592 promoted GC proliferation, migration, and invasion in vitro and facilitated tumorigenesis in vivo. Spry2 was a direct target of miR-592 and Spry2 overexpression partially counteracted the effects of miR-592. miR-592 induced the EMT and promoted its progression in GC via the PI3K/AKT and MAPK/ERK signaling pathways by inhibiting Spry2. Overexpression of miR-592 promotes GC proliferation, migration, and invasion and induces the EMT via the PI3K/AKT and MAPK/ERK signaling pathways by inhibiting Spry2, suggesting a potential therapeutic target for GC. © 2018 The Author(s). Published by S. Karger AG, Basel.

  8. Protection against cerebral infarction by Withaferin A involves inhibition of neuronal apoptosis, activation of PI3K/Akt signaling pathway, and reduced intimal hyperplasia via inhibition of VSMC migration and matrix metalloproteinases.

    PubMed

    Zhang, Qi-Zhi; Guo, Yu-Dong; Li, Hao-Mei; Wang, Rui-Zheng; Guo, Shou-Gang; Du, Yi-Feng

    2017-03-01

    Stroke is a major public health concern with high rates of morbidity and mortality worldwide. Cerebral ischemia and infarction are commonly associated with stroke. Currently used medications, though effective, are also associated with adverse effects. Development of effective neuroprotective agents with fewer side effects would be of clinical value. We evaluated the effects of Withaferin A (WA), a steroidal lactone derived from the plant Withania somnifera, on experimentally induced cerebral infarction. The ability of WA to inhibit neuroapoptosis and modulate vascular smooth muscle cell (VSMC) migration and PI3K/Akt signaling was assessed. Separate groups of Sprague Dawley rats were subjected to cerebral occlusion and reperfused for 24h. WA treatment (25, 50 or 100mg/kg bodyweight) significantly reduced the infarct area in a carotid ligation model; WA reduced intimal hyperplasia and proliferating cell nuclear antigen (PCNA)-positive cell counts. Western blotting analysis revealed significantly suppressed PI3K/Akt signaling following cerebral ischemia/reperfusion injury. WA supplementation was found to downregulate apoptotic pathway proteins. WA suppressed PTEN and enhanced p-Akt and GSK-3β levels and elevated mTORc1, cyclinD1 and NF-κB p65 expression, suggesting activation of the PI3K/Akt pathway. In vitro studies with PDGF-stimulated A7r5 cells revealed that WA exposure severely downregulated matrix metalloproteinases (MMP)-2 and -9 and inhibited migration of A7r5 cells. Additionally, WA reduced the proliferation of A7r5 cells significantly. WA exerted neuroprotective effects by activating the PI3K/Akt pathway, modulating the expression of MMPs, and inhibiting the migration of VSMCs. Copyright © 2017. Published by Elsevier B.V.

  9. Tentacle extract from the jellyfish Cyanea capillata increases proliferation and migration of human umbilical vein endothelial cells through the ERK1/2 signaling pathway

    PubMed Central

    Wang, Qianqian; Zhang, Hui; Liu, Guoyan; He, Qian; Zhang, Liming

    2017-01-01

    Wound healing is a complex biological process, and current research finds that jellyfish have a great capacity for promoting growth and healing. However, the underlying mechanisms remain unclear. Thus, this study was conducted to investigate the molecular mechanisms and effects of a tentacle extract (TE) from the jellyfish Cyanea capillata (C. capillata) on cell proliferation and migration in human umbilical vein endothelial cells (HUVECs). First, our results showed that TE at the concentration of 1 μg/ml could promote cell proliferation over various durations, induce a transition of the cells from the G1-phase to the S/G2-phase of the cell cycle, and increase the expression of cell cycle proteins (CyclinB1 and CyclinD1). Second, we found that TE could activate the PI3K/Akt, ERK1/2 and JNK MAPK signaling pathways but not the NF-κB signaling pathway or the apoptosis signaling cascade. Finally, we demonstrated that the TE-induced expression of cell cycle proteins was decreased by ERK1/2 inhibitor PD98059 but not by PI3K inhibitor LY294002 or JNK inhibitor SP600125. Similarly, the TE-enhanced migration ability of HUVECs was also markedly attenuated by PD98059. Taken together, our findings indicate that TE-induced proliferation and migration in HUVECs mainly occurred through the ERK1/2 MAPK signaling pathway. These results are instructively important for further research on the isolation and purification of growth-promoting factors from C. capillata and are hopeful as a means to improve human wound repair in unfavorable conditions. PMID:29261770

  10. Tentacle extract from the jellyfish Cyanea capillata increases proliferation and migration of human umbilical vein endothelial cells through the ERK1/2 signaling pathway.

    PubMed

    Wang, Beilei; Liu, Dan; Wang, Chao; Wang, Qianqian; Zhang, Hui; Liu, Guoyan; He, Qian; Zhang, Liming

    2017-01-01

    Wound healing is a complex biological process, and current research finds that jellyfish have a great capacity for promoting growth and healing. However, the underlying mechanisms remain unclear. Thus, this study was conducted to investigate the molecular mechanisms and effects of a tentacle extract (TE) from the jellyfish Cyanea capillata (C. capillata) on cell proliferation and migration in human umbilical vein endothelial cells (HUVECs). First, our results showed that TE at the concentration of 1 μg/ml could promote cell proliferation over various durations, induce a transition of the cells from the G1-phase to the S/G2-phase of the cell cycle, and increase the expression of cell cycle proteins (CyclinB1 and CyclinD1). Second, we found that TE could activate the PI3K/Akt, ERK1/2 and JNK MAPK signaling pathways but not the NF-κB signaling pathway or the apoptosis signaling cascade. Finally, we demonstrated that the TE-induced expression of cell cycle proteins was decreased by ERK1/2 inhibitor PD98059 but not by PI3K inhibitor LY294002 or JNK inhibitor SP600125. Similarly, the TE-enhanced migration ability of HUVECs was also markedly attenuated by PD98059. Taken together, our findings indicate that TE-induced proliferation and migration in HUVECs mainly occurred through the ERK1/2 MAPK signaling pathway. These results are instructively important for further research on the isolation and purification of growth-promoting factors from C. capillata and are hopeful as a means to improve human wound repair in unfavorable conditions.

  11. Polymerisation of fibrin αC-domains promotes endothelial cell migration and proliferation.

    PubMed

    Yakovlev, S; Mikhailenko, I; Tsurupa, G; Belkin, A M; Medved, L

    2014-12-01

    Upon conversion of fibrinogen into fibrin, fibrinogen αC-domains containing the RGD recognition motif form ordered αC polymers. Our previous study revealed that polymerisation of these domains promotes integrin-dependent adhesion and spreading of endothelial cells, as well as integrin-mediated activation of the FAK and ERK1/2 signalling pathways. The major goal of this study was to test the impact of αC-domain polymerisation on endothelial cell migration and proliferation during wound healing, and to clarify the mechanism underlying superior activity of αC polymers toward endothelial cells. In an in vitro wound healing assay, confluent endothelial cell monolayers on tissue culture plates coated with the αC monomer or αC polymers were wounded by scratching and wound closure was monitored by time-lapse videomicroscopy. Although the plates were coated with equal amounts of αC species, as confirmed by ELISA, wound closure by the cells occurred much faster on αC polymers, indicating that αC-domain polymerisation promotes cell migration and proliferation. In agreement, endothelial cell proliferation was also more efficient on αC polymers, as revealed by cell proliferation assay. Wound closure on both types of substrates was equally inhibited by the integrin-blocking GRGDSP peptide and a specific antagonist of the ERK1/2 signalling pathway. In contrast, blocking the FAK signaling pathway by a specific antagonist decreased wound closure only on αC polymers. These results indicate that polymerisation of the αC-domains enhances integrin-dependent endothelial cell migration and proliferation mainly through the FAK signalling pathway. Furthermore, clustering of integrin-binding RGD motifs in αC polymers is the major mechanism triggering these events.

  12. RhoA/ROCK signaling regulates smooth muscle phenotypic modulation and vascular remodeling via the JNK pathway and vimentin cytoskeleton.

    PubMed

    Tang, Lian; Dai, Fan; Liu, Yan; Yu, Xiaoqiang; Huang, Chao; Wang, Yuqin; Yao, Wenjuan

    2018-05-20

    The RhoA/ROCK signaling pathway regulates cell morphology, adhesion, proliferation, and migration. In this study, we investigated the regulatory role of RhoA/ROCK signaling on PDGF-BB-mediated smooth muscle phenotypic modulation and vascular remodeling and clarified the molecular mechanisms behind these effects. PDGF-BB treatment induced the activation of RhoA, ROCK, PDGF-Rβ, and the expression of PDGF-Rβ in HA-VSMCs (human aortic vascular smooth muscle cells). PDGF-Rβ inhibition and RhoA suppression blocked PDGF-BB-induced RhoA activation and ROCK induction. In addition, PDGF-BB-mediated cell proliferation and migration were suppressed by PDGF-Rβ inhibition, RhoA suppression, and ROCK inhibition, suggesting that PDGF-BB promotes phenotypic modulation of HA-VSMCs by activating the RhoA/ROCK pathway via the PDGF receptor. Moreover, suppressing both ROCK1 and ROCK2 blocked cell cycle progression from G0/G1 to S phase by decreasing the transcription and protein expression of cyclin D1, CDK2, and CDK4 via JNK/c-Jun pathway, thus reducing cell proliferation in PDGF-BB-treated HA-VSMCs. ROCK1 deletion, rather than ROCK2 suppression, significantly inhibited PDGF-BB-induced migration by reducing the expression of vimentin and preventing the remodeling of vimentin and phospho-vimentin. Furthermore, ROCK1 deletion suppressed vimentin by inhibiting the phosphorylation of Smad2/3 and the nuclear translocation of Smad4. These findings suggested that ROCK1 and ROCK2 might play different roles in PDGF-BB-mediated cell proliferation and migration in HA-VSMCs. In addition, PDGF-BB and its receptor participated in neointima formation and vascular remodeling by promoting cell cycle protein expression via the JNK pathway and enhancing vimentin expression in a rat balloon injury model; effects that were inhibited by treatment with fasudil. Together, the results of this study reveal a novel mechanism through which RhoA/ROCK signaling regulates smooth muscle phenotypic modulation and vascular remodeling via the JNK pathway and vimentin cytoskeleton. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Population genetic analysis infers mMigration pathways of Phytophthora ramorum in US nurseries

    Treesearch

    Erica M. Goss; Meg Larsen; Gary A. Chastagner; Donald R. Givens; Niklaus J. Grünwald; Barbara Jane Howlett

    2009-01-01

    Recently introduced, exotic plant pathogens may exhibit low genetic diversity and be limited to clonal reproduction. However, rapidly mutating molecular markers such as microsatellites can reveal genetic variation within these populations and be used to model putative migration patterns. Phytophthora ramorum is the exotic pathogen, discovered in...

  14. A novel protein kinase D phosphorylation site in the tumor suppressor Rab interactor 1 is critical for coordination of cell migration.

    PubMed

    Ziegler, Susanne; Eiseler, Tim; Scholz, Rolf-Peter; Beck, Alexander; Link, Gisela; Hausser, Angelika

    2011-03-01

    The multifunctional signal adapter protein Ras and Rab interactor 1 (RIN1) is a Ras effector protein involved in the regulation of epithelial cell processes such as cell migration and endocytosis. RIN1 signals via two downstream pathways, namely the activation of Rab5 and Abl family kinases. Protein kinase D (PKD) phosphorylates RIN1 at serine 351 in vitro, thereby regulating interaction with 14-3-3 proteins. Here, we report the identification of serine 292 in RIN1 as an in vivo PKD phosphorylation site. PKD-mediated phosphorylation at this site was confirmed with a phospho-specific antibody and by mass spectrometry. We demonstrate that phosphorylation at serine 292 controls RIN1-mediated inhibition of cell migration by modulating the activation of Abl kinases. We further provide evidence that RIN1 in vivo phosphorylation at serine 351 occurs independently of PKD. Collectively, our data identify a novel PKD signaling pathway through RIN1 and Abl kinases that is involved in the regulation of actin remodeling and cell migration.

  15. The evolution of Devonian hydrocarbon gases in shallow aquifers of the northern Appalachian Basin: Insights from integrating noble gas and hydrocarbon geochemistry

    NASA Astrophysics Data System (ADS)

    Darrah, Thomas H.; Jackson, Robert B.; Vengosh, Avner; Warner, Nathaniel R.; Whyte, Colin J.; Walsh, Talor B.; Kondash, Andrew J.; Poreda, Robert J.

    2015-12-01

    The last decade has seen a dramatic increase in domestic energy production from unconventional reservoirs. This energy boom has generated marked economic benefits, but simultaneously evoked significant concerns regarding the potential for drinking-water contamination in shallow aquifers. Presently, efforts to evaluate the environmental impacts of shale gas development in the northern Appalachian Basin (NAB), located in the northeastern US, are limited by: (1) a lack of comprehensive ;pre-drill; data for groundwater composition (water and gas); (2) uncertainty in the hydrogeological factors that control the occurrence of naturally present CH4 and brines in shallow Upper Devonian (UD) aquifers; and (3) limited geochemical techniques to quantify the sources and migration of crustal fluids (specifically methane) at various time scales. To address these questions, we analyzed the noble gas, dissolved ion, and hydrocarbon gas geochemistry of 72 drinking-water wells and one natural methane seep all located ≫1 km from shale gas drill sites in the NAB. In the present study, we consciously avoided groundwater wells from areas near active or recent drilling to ensure shale gas development would not bias the results. We also intentionally targeted areas with naturally occurring CH4 to characterize the geochemical signature and geological context of gas-phase hydrocarbons in shallow aquifers of the NAB. Our data display a positive relationship between elevated [CH4], [C2H6], [Cl], and [Ba] that co-occur with high [4He]. Although four groundwater samples show mantle contributions ranging from 1.2% to 11.6%, the majority of samples have [He] ranging from solubility levels (∼45 × 10-6 cm3 STP/L) with below-detectable [CH4] and minor amounts of tritiogenic 3He in low [Cl] and [Ba] waters, up to high [4He] = 0.4 cm3 STP/L with a purely crustal helium isotopic end-member (3He/4He = ∼0.02 times the atmospheric ratio (R/Ra)) in samples with CH4 near saturation for shallow groundwater (P(CH4) = ∼1 atmosphere) and elevated [Cl] and [Ba]. These data suggest that 4He is dominated by an exogenous (i.e., migrated) crustal source for these hydrocarbon gas- and salt-rich fluids. In combination with published inorganic geochemistry (e.g., 87Sr/86Sr, Sr/Ba, Br-/Cl-), new noble gas and hydrocarbon isotopic data (e.g., 20Ne/36Ar, C2+/C1, δ13C-CH4) suggest that a hydrocarbon-rich brine likely migrated from the Marcellus Formation (via primary hydrocarbon migration) as a dual-phase fluid (gas + liquid) and was fractionated by solubility partitioning during fluid migration and emplacement into conventional UD traps (via secondary hydrocarbon migration). Based on the highly fractionated 4He/CH4 data relative to Marcellus and UD production gases, we propose an additional phase of hydrocarbon gas migration where natural gas previously emplaced in UD hydrocarbon traps actively diffuses out into and equilibrates with modern shallow groundwater (via tertiary hydrocarbon migration) following uplift, denudation, and neotectonic fracturing. These data suggest that by integrating noble gas geochemistry with hydrocarbon and dissolved ion chemistry, one can better determine the source and migration processes of natural gas in the Earth's crust, which are two critical factors for understanding the presence of hydrocarbon gases in shallow aquifers.

  16. Geologic Cross Section I–I′ Through the Appalachian Basin from the Eastern Margin of the Illinois Basin, Jefferson County, Kentucky, to the Valley and Ridge Province, Scott County, Virginia

    USGS Publications Warehouse

    Ryder, Robert T.; Trippi, Michael H.; Swezey, Christopher S.

    2015-12-08

    Cross section I‒I ’ contains much information that is useful for evaluating energy resources in the Appalachian basin. Many of the key elements of the Appalachian basin petroleum systems (such as source rocks, reservoir rocks, seals, and traps) can be inferred from lithologic units, unconformities, and geologic structures shown on the cross section. Other aspects of petroleum systems (such as the timing of petroleum generation and petroleum migration pathways) may be evaluated by burial history, thermal history, and fluid flow models on the basis of what is shown on the cross section. Cross section I‒I’ also provides a stratigraphic and structural framework for the Pennsylvanian coal-bearing section. In addition, geologists and engineers could use cross section I‒I’ as a reconnaissance tool to identify plausible geologic structures and strata for the subsurface storage of liquid waste or for the sequestration of carbon dioxide.

  17. Oceanic slab melting and mantle metasomatism.

    PubMed

    Scaillet, B; Prouteau, G

    2001-01-01

    Modern plate tectonic brings down oceanic crust along subduction zones where it either dehydrates or melts. Those hydrous fluids or melts migrate into the overlying mantle wedge trigerring its melting which produces arc magmas and thus additional continental crust. Nowadays, melting seems to be restricted to cases of young (< 50 Ma) subducted plates. Slab melts are silicic and strongly sodic (trondhjemitic). They are produced at low temperatures (< 1000 degrees C) and under water excess conditions. Their interaction with mantle peridotite produces hydrous metasomatic phases such as amphibole and phlogopite that can be more or less sodium rich. Upon interaction the slab melt becomes less silicic (dacitic to andesitic), and Mg, Ni and Cr richer. Virtually all exposed slab melts display geochemical evidence of ingestion of mantle material. Modern slab melts are thus unlike Archean Trondhjemite-Tonalite-Granodiorite rocks (TTG), which suggests that both types of magmas were generated via different petrogenetic pathways which may imply an Archean tectonic model of crust production different from that of the present-day, subduction-related, one.

  18. Endosomal-sorting complexes required for transport (ESCRT) pathway-dependent endosomal traffic regulates the localization of active Src at focal adhesions.

    PubMed

    Tu, Chun; Ortega-Cava, Cesar F; Winograd, Paul; Stanton, Marissa Jo; Reddi, Alagarsamy Lakku; Dodge, Ingrid; Arya, Ranjana; Dimri, Manjari; Clubb, Robert J; Naramura, Mayumi; Wagner, Kay-Uwe; Band, Vimla; Band, Hamid

    2010-09-14

    Active Src localization at focal adhesions (FAs) is essential for cell migration. How this pool is linked mechanistically to the large pool of Src at late endosomes (LEs)/lysosomes (LY) is not well understood. Here, we used inducible Tsg101 gene deletion, TSG101 knockdown, and dominant-negative VPS4 expression to demonstrate that the localization of activated cellular Src and viral Src at FAs requires the endosomal-sorting complexes required for transport (ESCRT) pathway. Tsg101 deletion also led to impaired Src-dependent activation of STAT3 and focal adhesion kinase and reduced cell migration. Impairment of the ESCRT pathway or Rab7 function led to the accumulation of active Src at aberrant LE/LY compartments followed by its loss. Analyses using fluorescence recovery after photo-bleaching show that dynamic mobility of Src in endosomes is ESCRT pathway-dependent. These results reveal a critical role for an ESCRT pathway-dependent LE/LY trafficking step in Src function by promoting localization of active Src to FAs.

  19. A role for NRAGE in NF-κB activation through the non-canonical BMP pathway

    PubMed Central

    2010-01-01

    Background Previous studies have linked neurotrophin receptor-interacting MAGE protein to the bone morphogenic protein signaling pathway and its effect on p38 mediated apoptosis of neural progenitor cells via the XIAP-Tak1-Tab1 complex. Its effect on NF-κB has yet to be explored. Results Herein we report that NRAGE, via the same XIAP-Tak1-Tab1 complex, is required for the phosphorylation of IKK -α/β and subsequent transcriptional activation of the p65 subunit of NF-κB. Ablation of endogenous NRAGE by siRNA inhibited NF-κB pathway activation, while ablation of Tak1 and Tab1 by morpholino inhibited overexpression of NRAGE from activating NF-κB. Finally, cytokine profiling of an NRAGE over-expressing stable line revealed the expression of macrophage migration inhibitory factor. Conclusion Modulation of NRAGE expression revealed novel roles in regulating NF-κB activity in the non-canonical bone morphogenic protein signaling pathway. The expression of macrophage migration inhibitory factor by bone morphogenic protein -4 reveals novel crosstalk between an immune cytokine and a developmental pathway. PMID:20100315

  20. Numerical modeling of fluid migration in subduction zones

    NASA Astrophysics Data System (ADS)

    Walter, Marius J.; Quinteros, Javier; Sobolev, Stephan V.

    2015-04-01

    It is well known that fluids play a crucial role in subduction evolution. For example, excess mechanical weakening along tectonic interfaces, due to excess fluid pressure, may enable oceanic subduction. Hence, the fluid content seems to be a critical parameter for subduction initiation. Studies have also shown a correlation between the location of slab dehydration and intermediate seismic activity. Furthermore, expelled fluids from the subduction slab affect the melting temperature, consequently, contributing to partial melting in the wedge above the downgoing plate, and resulting in chemical changes in earth interior and extensive volcanism. In summary, fluids have a great impact on tectonic processes and therefore should be incorporated into geodynamic numerical models. Here we use existing approaches to couple and solve fluid flow equations in the SLIM-3D thermo-mechanical code. SLIM-3D is a three-dimensional thermo-mechanical code capable of simulating lithospheric deformation with elasto-visco-plastic rheology. It incorporates an arbitrary Lagrangian Eulerian formulation, free surface, and changes in density and viscosity, due to endothermic and exothermic phase transitions. It has been successfully applied to model geodynamic processes at different tectonic settings, including subduction zones. However, although SLIM-3D already includes many features, fluid migration has not been incorporated into the model yet. To this end, we coupled solid and fluid flow assuming that fluids flow through a porous and deformable solid. Thereby, we introduce a two-phase flow into the model, in which the Stokes flow is coupled with the Darcy law for fluid flow. This system of equations becomes, however, nonlinear, because the rheology and permeability are depended on the porosity (fluid fraction of the matrix). Ultimately, the evolution of porosity is governed by the compaction pressure and the advection of the porous solid. We show the details of our implementation of the fluid flow into the existing thermo-mechanical finite element code and present first results of benchmarks (e.g. solitary wave) and experiments. We are especially interested in the coupling of subduction processes and the evolution of the magmatic arc. Thereby, we focus on the key factors controlling magma emplacement and its influence on subduction processes.

  1. Antioxidant dieckol downregulates the Rac1/ROS signaling pathway and inhibits Wiskott-Aldrich syndrome protein (WASP)-family verprolin-homologous protein 2 (WAVE2)-mediated invasive migration of B16 mouse melanoma cells.

    PubMed

    Park, Sun Joo; Kim, Yong Tae; Jeon, You Jin

    2012-04-01

    Reactive oxygen species (ROS) generation is linked to dynamic actin cytoskeleton reorganization, which is involved in tumor cell motility and metastasis. Thus, inhibition of ROS generation and actin polymerization in tumor cells may represent an effective anticancer strategy. However, the molecular basis of this signaling pathway is currently unknown. Here, we show that the Ecklonia cava-derived antioxidant dieckol downregulates the Rac1/ROS signaling pathway and inhibits Wiskott-Aldrich syndrome protein (WASP)-family verprolin-homologous protein 2 (WAVE2)-mediated invasive migration of B16 mouse melanoma cells. Steady-state intracellular ROS levels were higher in malignant B16F10 cells than in parental, nonmetastatic B16F0 cells. Elevation of ROS by H(2)O(2) treatment increased migration and invasion ability of B16F0 cells to level similar to that of B16F10 cells, suggesting that intracellular ROS signaling mediates the prometastatic properties of B16 mouse melanoma cells. ROS levels and the cell migration and invasion ability of B16 melanoma cells correlated with Rac1 activation and WAVE2 expression. Overexpression of dominant negative Rac1 and depletion of WAVE2 by siRNA suppressed H(2)O(2)-induced cell invasion of B16F0 and B16F10 cells. Similarly, dieckol attenuates the ROS-mediated Rac1 activation and WAVE2 expression, resulting in decreased migration and invasion of B16 melanoma cells. In addition, we found that dieckol decreases association between WAVE2 and NADPH oxidase subunit p47(phox). Therefore, this finding suggests that WAVE2 acts to couple intracellular Rac1/ROS signaling to the invasive migration of B16 melanoma cells, which is inhibited by dieckol.

  2. Antioxidant Dieckol Downregulates the Rac1/ROS Signaling Pathway and Inhibits Wiskott-Aldrich Syndrome Protein (WASP)-Family Verprolin-Homologous Protein 2 (WAVE2)-Mediated Invasive Migration of B16 Mouse Melanoma Cells

    PubMed Central

    Park, Sun Joo; Kim, Yong Tae; Jeon, You Jin

    2012-01-01

    Reactive oxygen species (ROS) generation is linked to dynamic actin cytoskeleton reorganization, which is involved in tumor cell motility and metastasis. Thus, inhibition of ROS generation and actin polymerization in tumor cells may represent an effective anticancer strategy. However, the molecular basis of this signaling pathway is currently unknown. Here, we show that the Ecklonia cava-derived antioxidant dieckol downregulates the Rac1/ROS signaling pathway and inhibits Wiskott-Aldrich syndrome protein (WASP)-family verprolin-homologous protein 2 (WAVE2)-mediated invasive migration of B16 mouse melanoma cells. Steady-state intracellular ROS levels were higher in malignant B16F10 cells than in parental, nonmetastatic B16F0 cells. Elevation of ROS by H2O2 treatment increased migration and invasion ability of B16F0 cells to level similar to that of B16F10 cells, suggesting that intracellular ROS signaling mediates the prometastatic properties of B16 mouse melanoma cells. ROS levels and the cell migration and invasion ability of B16 melanoma cells correlated with Rac1 activation and WAVE2 expression. Overexpression of dominant negative Rac1 and depletion of WAVE2 by siRNA suppressed H2O2-induced cell invasion of B16F0 and B16F10 cells. Similarly, dieckol attenuates the ROS-mediated Rac1 activation and WAVE2 expression, resulting in decreased migration and invasion of B16 melanoma cells. In addition, we found that dieckol decreases association between WAVE2 and NADPH oxidase subunit p47phox. Therefore, this finding suggests that WAVE2 acts to couple intracellular Rac1/ROS signaling to the invasive migration of B16 melanoma cells, which is inhibited by dieckol. PMID:22441674

  3. An intracellular signaling hierarchy determines direction of migration in opposing chemotactic gradients.

    PubMed

    Heit, Bryan; Tavener, Samantha; Raharjo, Eko; Kubes, Paul

    2002-10-14

    Neutrophils must follow both endogenous and bacterial chemoattractant signals out of the vasculature and through the interstitium to arrive at a site of infection. By necessity, in the setting of multiple chemoattractants, the neutrophils must prioritize, favoring end target chemoattractants (e.g., fMLP and C5a) emanating from the site of infection over intermediary endogenous chemoattractants (e.g., IL-8 and LTB4) encountered en route to sites of infection. In this study, we propose a hierarchical model of two signaling pathways mediating the decision-making process of the neutrophils, which allows end target molecules to dominate over intermediary chemoattractants. In an under agarose assay, neutrophils predominantly migrated toward end target chemoattractants via p38 MAPK, whereas intermediary chemoattractant-induced migration was phosphoinositide 3-kinase (PI3K)/Akt dependent. When faced with competing gradients of end target and intermediary chemoattractants, Akt activation was significantly reduced within neutrophils, and the cells migrated preferentially toward end target chemoattractants even at 1/1,000th that of intermediary chemoattractants. End target molecules did not require chemotactic properties, since the p38 MAPK activator, LPS, also inhibited Akt and prevented migration to intermediary chemoattractants. p38 MAPK inhibitors not only reversed this hierarchy, such that neutrophils migrated preferentially toward intermediary chemoattractants, but also allowed neutrophils to be drawn out of a local end target chemoattractant environment and toward intermediary chemoattractants unexpectedly in an exaggerated (two- to fivefold) fashion. This was entirely related to significantly increased magnitude and duration of Akt activation. Finally, end target chemoattractant responses were predominantly Mac-1 dependent, whereas nondominant chemoattractants used primarily LFA-1. These data provide support for a two pathway signaling model wherein the end target chemoattractants activate p38 MAPK, which inhibits intermediary chemoattractant-induced PI3K/Akt pathway, establishing an intracellular signaling hierarchy.

  4. Far infrared promotes wound healing through activation of Notch1 signaling.

    PubMed

    Hsu, Yung-Ho; Lin, Yuan-Feng; Chen, Cheng-Hsien; Chiu, Yu-Jhe; Chiu, Hui-Wen

    2017-11-01

    The Notch signaling pathway is critically involved in cell proliferation, differentiation, development, and homeostasis. Far infrared (FIR) has an effect that promotes wound healing. However, the underlying molecular mechanisms are unclear. In the present study, we employed in vivo and HaCaT (a human skin keratinocyte cell line) models to elucidate the role of Notch1 signaling in FIR-promoted wound healing. We found that FIR enhanced keratinocyte migration and proliferation. FIR induced the Notch1 signaling pathway in HaCaT cells and in a microarray dataset from the Gene Expression Omnibus database. We next determined the mRNA levels of NOTCH1 in paired normal and wound skin tissues derived from clinical patients using the microarray dataset and Ingenuity Pathway Analysis software. The result indicated that the Notch1/Twist1 axis plays important roles in wound healing and tissue repair. In addition, inhibiting Notch1 signaling decreased the FIR-enhanced proliferation and migration. In a full-thickness wound model in rats, the wounds healed more rapidly and the scar size was smaller in the FIR group than in the light group. Moreover, FIR could increase Notch1 and Delta1 in skin tissues. The activation of Notch1 signaling may be considered as a possible mechanism for the promoting effect of FIR on wound healing. FIR stimulates keratinocyte migration and proliferation. Notch1 in keratinocytes has an essential role in FIR-induced migration and proliferation. NOTCH1 promotes TWIST1-mediated gene expression to assist wound healing. FIR might promote skin wound healing in a rat model. FIR stimulates keratinocyte migration and proliferation. Notch1 in keratinocytes has an essential role in FIR-induced migration and proliferation. NOTCH1 promotes TWIST1-mediated gene expression to assist wound healing. FIR might promote skin wound healing in a rat model.

  5. Fluid flows and forces in development: functions, features and biophysical principles

    PubMed Central

    Freund, Jonathan B.; Goetz, Jacky G.; Hill, Kent L.; Vermot, Julien

    2012-01-01

    Throughout morphogenesis, cells experience intracellular tensile and contractile forces on microscopic scales. Cells also experience extracellular forces, such as static forces mediated by the extracellular matrix and forces resulting from microscopic fluid flow. Although the biological ramifications of static forces have received much attention, little is known about the roles of fluid flows and forces during embryogenesis. Here, we focus on the microfluidic forces generated by cilia-driven fluid flow and heart-driven hemodynamics, as well as on the signaling pathways involved in flow sensing. We discuss recent studies that describe the functions and the biomechanical features of these fluid flows. These insights suggest that biological flow determines many aspects of cell behavior and identity through a specific set of physical stimuli and signaling pathways. PMID:22395739

  6. Inhibitory effect of D3 dopamine receptors on neuropeptide Y‑induced migration in vascular smooth muscle cells.

    PubMed

    Xia, Xue-Wei; Zhou, Yong-Qiao; Luo, Hao; Zeng, Chunyu

    2017-10-01

    Abnormal migration of vascular smooth muscle cells (VSMCs) serves an important role in hypertension, atherosclerosis and restenosis following angioplasty, which is regulated numerous hormonal and humoral factors, including neuropeptide Y (NPY) and dopamine. Dopamine and NPY are both sympathetic neurotransmitters, and a previous study reported that NPY increased VSMC proliferation, while dopamine receptor inhibited it. Therefore, the authors wondered whether or not there is an inhibitory effect of dopamine receptor on NPY‑mediated VSMC migration. The present study demonstrated that stimulation with NPY dose‑dependence (10‑10‑10‑7M, 24 h) increased VSMC migration, the stimulatory effect of NPY was via the Y1 receptor. This is because, in the presence of the Y1 receptor antagonist, BIBP3226 (10‑7 M), the stimulatory effect of NPY on VSMC migration was blocked. Activation of the D3 receptor by PD128907 dose‑dependence (10‑11‑10‑8 M) reduced the stimulatory effect of NPY on VSMC migration. The effect of PD128907 was via the D3 receptor, because the inhibitory effect of PD128907 on NPY‑mediated migration was blocked by the D3 receptor antagonist, U99194. The authors' further study suggested that the inhibitory effect of the D3 receptor was via the PKA signaling pathway, in the presence of the PKA inhibitor, 14‑22 (10‑6 M), the inhibitory effect of PD128907 on VSMC migration was blocked. Moreover, the inhibitory effect of PD128907 was imitated by PKA activator, Sp‑cAMP [S], in the presence of Sp‑cAMP [S], the NPY‑mediated stimulatory effect on VSMC migration was abolished. The present study indicated that activation of the D3 receptor inhibits NPY Y1‑mediated migration on VSMCs, PKA is involved in the signaling pathway.

  7. Identification of sandstone core damage using scanning electron microscopy

    NASA Astrophysics Data System (ADS)

    Ismail, Abdul Razak; Jaafar, Mohd Zaidi; Sulaiman, Wan Rosli Wan; Ismail, Issham; Shiunn, Ng Yinn

    2017-12-01

    Particles and fluids invasion into the pore spaces causes serious damage to the formation, resulting reduction in petroleum production. In order to prevent permeability damage for a well effectively, the damage mechanisms should be identified. In this study, water-based drilling fluid was compared to oil-based drilling fluids based on microscopic observation. The cores were damaged by several drilling fluid systems. Scanning electron microscope (SEM) was used to observe the damage mechanism caused by the drilling fluids. Results showed that the ester based drilling fluid system caused the most serious damage followed by synthetic oil based system and KCI-polymer system. Fine solids and filtrate migration and emulsion blockage are believed to be the major mechanisms controlling the changes in flow properties for the sandstone samples.

  8. Interleukin 6 inhibits proliferation and, in cooperation with an epidermal growth factor receptor autocrine loop, increases migration of T47D breast cancer cells.

    PubMed

    Badache, A; Hynes, N E

    2001-01-01

    Interleukin (IL)-6, a multifunctional regulator of immune response, hematopoiesis, and acute phase reactions, has also been shown to regulate cancer cell proliferation. We have investigated IL-6 signaling pathways and cellular responses in the T47D breast carcinoma cell line. The IL-6-type cytokines, IL-6 and oncostatin M, simultaneously inhibited cell proliferation and increased cell migration. In T47D cells, IL-6 stimulated the activation of Janus-activated kinase 1 tyrosine kinase and signal transducers and activators of transcription (STAT) 1 and STAT3 transcription factors. Expression of dominant negative STAT3 in the cells strongly reduced IL-6-mediated growth inhibition but did not prevent IL-6-induced cell migration. IL-6 treatment led to activation of the mitogen-activated protein kinase (MAPK) and the phosphatidylinositol 3'-kinase (PI3K) pathways. Inhibition of MAPK or PI3K activity reversed IL-6- and oncostatin M-stimulated migration. Because cross-talk between cytokine receptors and members of the ErbB family of receptor tyrosine kinases has been described previously, we have examined their interaction in T47D cells. Down-regulation of ErbB receptor activity, through the use of specific pharmacological inhibitors or dominant negative receptor constructs, revealed that IL-6-induced MAPK activation was largely dependent on epidermal growth factor (EGF) receptor activity, but not on ErbB-2 activity. Using a monoclonal antibody that interferes with EGF receptor-ligand interaction, we have shown that in T47D cells, IL-6 cooperates with an EGF receptor autocrine activity loop for signaling through the MAPK and PI3K pathways and for cell migration. Both the tyrosine phosphatase SHP-2 and the multisubstrate docking molecule Gab1, which are potential links between IL-6 and the MAPK/PI3K pathways, were constitutively associated with the active EGF receptor. On IL-6 stimulation, SHP-2 and Gab1 were recruited to the gp130 subunit of the IL-6 receptor and tyrosine phosphorylated, allowing downstream signaling to the MAPK and PI3K pathways. Thus, in T47D breast carcinoma cells, IL-6 acts in synergy with EGF receptor autocrine activity to signal through the MAPK/PI3K pathways. Cooperation between IL-6 and the EGF receptor in T47D breast carcinoma cells illustrates how a combination of multiple stimuli, either exogenous or endogenous, may result in synergistic cellular responses.

  9. Dissociation of Multisubunit Protein-Ligand Complexes in the Gas Phase. Evidence for Ligand Migration

    NASA Astrophysics Data System (ADS)

    Zhang, Yixuan; Deng, Lu; Kitova, Elena N.; Klassen, John S.

    2013-10-01

    The results of collision-induced dissociation (CID) experiments performed on gaseous protonated and deprotonated ions of complexes of cholera toxin B subunit homopentamer (CTB5) with the pentasaccharide (β-D-Gal p-(1→3)-β-D-Gal pNAc-(1→4)[α-D-Neu5Ac-(2→3)]-β-D-Gal p-(1→4)-β-D-Glc p (GM1)) and corresponding glycosphingolipid (β-D-Gal p-(1→3)-β-D-Gal pNAc-(1→4)[α-D-Neu5Ac-(2→3)]-β-D-Gal p-(1→4)-β-D-Glc p-Cer (GM1-Cer)) ligands, and the homotetramer streptavidin (S4) with biotin (B) and 1,2-dipalmitoyl- sn-glycero-3-phosphoethanolamine-N-(biotinyl) (Btl), are reported. The protonated (CTB5 + 5GM1)n+ ions dissociated predominantly by the loss of a single subunit, with the concomitant migration of ligand to another subunit. The simultaneous loss of ligand and subunit was observed as a minor pathway. In contrast, the deprotonated (CTB5 + 5GM1)n- ions dissociated preferentially by the loss of deprotonated ligand; the loss of ligand-bound and ligand-free subunit were minor pathways. The presence of ceramide (Cer) promoted ligand migration and the loss of subunit. The main dissociation pathway for the protonated and deprotonated (S4 + 4B)n+/- ions, as well as for deprotonated (S4 + 4Btl)n- ions, was loss of the ligand. However, subunit loss from the (S4 + 4B)n+ ions was observed as a minor pathway. The (S4 + 4Btl)n+ ions dissociated predominantly by the loss of free and ligand-bound subunit. The charge state of the complex and the collision energy were found to have little effect on the relative contribution of the different dissociation channels. Thermally-driven ligand migration between subunits was captured in the results of molecular dynamics simulations performed on protonated (CTB5 + 5GM1)15+ ions (with a range of charge configurations) at 800 K. Notably, the migration pathway was found to be highly dependent on the charge configuration of the ion. The main conclusion of this study is that the dissociation pathways of multisubunit protein-ligand complexes in the gas phase depend, not only on the native topology of the complex, but also on structural changes that occur upon collisional activation.

  10. The MUC1 oncomucin regulates pancreatic cancer cell biological properties and chemoresistance. Implication of p42–44 MAPK, Akt, Bcl-2 and MMP13 pathways

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tréhoux, Solange; Duchêne, Bélinda; Jonckheere, Nicolas

    Highlights: • Loss of MUC1 decreases proliferation and tumor growth via β-catenin and p42–44 MAPK. • Inhibition of MUC1 decreases cell migration and invasion through MMP13. • Loss of MUC1 decreases survival and increases apoptosis via Akt and Bcl-2 pathways. • Loss of MUC1 sensitizes cells to gemcitabine and 5-Fluorouracil chemotherapeutic drugs. - Abstract: MUC1 is an oncogenic mucin overexpressed in several epithelial cancers, including pancreatic ductal adenocarcinoma, and is considered as a potent target for cancer therapy. To this aim, we undertook to study MUC1 biological effects on pancreatic cancer cells and identify pathways mediating these effects. Our inmore » vitro experiments indicate that inhibiting MUC1 expression decreases cell proliferation, cell migration and invasion, cell survival and increases cell apoptosis. Moreover, lack of MUC1 in these cells profoundly altered their sensitivity to gemcitabine and 5-Fluorouracil chemotherapeutic drugs. In vivo MUC1-KD cell xenografts in SCID mice grew slower. Altogether, we show that MUC1 oncogenic mucin alters proliferation, migration, and invasion properties of pancreatic cancer cells and that these effects are mediated by p42–44 MAPK, Akt, Bcl-2 and MMP13 pathways.« less

  11. Spring migratory pathways and migration chronology of Canada geese (Branta canadensis interior) wintering at the Santee National Wildlife Refuge, South Carolina

    USGS Publications Warehouse

    Giles, Molly M.; Jodice, Patrick G.R.; Baldwin, Robert F.; Stanton, John D.; Epstein, Marc

    2013-01-01

    We assessed the migratory pathways, migration chronology, and breeding ground affiliation of Canada Geese (Branta canadensis interior) that winter in and adjacent to the Santee National Wildlife Refuge in Summerton, South Carolina, United States. Satellite transmitters were fitted to eight Canada Geese at Santee National Wildlife Refuge during the winter of 2009–2010. Canada Geese departed Santee National Wildlife Refuge between 5 and 7 March 2010. Six Canada Geese followed a route that included stopovers in northeastern North Carolina and western New York, with three of those birds completing spring migration to breeding grounds associated with the Atlantic Population (AP). The mean distance between stopover sites along this route was 417 km, the mean total migration distance was 2838 km, and the Canada Geese arrived on AP breeding grounds on the eastern shore of Hudson Bay between 20 and 24 May 2010. Two Canada Geese followed a different route from that described above, with stopovers in northeastern Ohio, prior to arriving on the breeding grounds on 9 June 2010. Mean distance between stopover sites was 402 and 365 km for these two birds, and total migration distance was 4020 and 3650 km. These data represent the first efforts to track migratory Canada Geese from the southernmost extent of their current wintering range in the Atlantic Flyway. We did not track any Canada Geese to breeding grounds associated with the Southern James Bay Population. Caution should be used in the interpretation of this finding, however, because of the small sample size. We demonstrated that migratory Canada Geese wintering in South Carolina use at least two migratory pathways and that an affiliation with the Atlantic Population breeding ground exists.

  12. The histone demethylase KDM3A, and its downstream target MCAM, promote Ewing Sarcoma cell migration and metastasis

    PubMed Central

    Sechler, Marybeth; Parrish, Janet K.; Birks, Diane K.; Jedlicka, Paul

    2017-01-01

    Ewing Sarcoma is the second most common solid pediatric malignant neoplasm of bone and soft tissue. Driven by EWS/Ets, or rarely variant, oncogenic fusions, Ewing Sarcoma is a biologically and clinically aggressive disease with a high propensity for metastasis. However, the mechanisms underpinning Ewing Sarcoma metastasis are currently not well understood. In the present study, we identify and characterize a novel metastasis-promotional pathway in Ewing Sarcoma, involving the histone demethylase KDM3A, previously identified by our laboratory as a new cancer-promoting gene in this disease. Using global gene expression profiling, we show that KDM3A positively regulates genes and pathways implicated in cell migration and metastasis, and demonstrate, using functional assays, that KDM3A promotes migration in vitro and experimental, post-intravasation, metastasis in vivo. We further identify the Melanoma Cell Adhesion Molecule (MCAM) as a novel KDM3A target gene in Ewing Sarcoma, and an important effector of KDM3A pro-metastatic action. Specifically, we demonstrate that MCAM depletion, like KDM3A depletion, inhibits cell migration in vitro and experimental metastasis in vivo, and that MCAM partially rescues impaired migration due to KDM3A knock-down. Mechanistically, we show that KDM3A regulates MCAM expression both through a direct mechanism, involving modulation of H3K9 methylation at the MCAM promoter, and an indirect mechanism, via the Ets1 transcription factor. Lastly, we identify an association between high MCAM levels in patient tumors and poor survival, in two different Ewing Sarcoma clinical cohorts. Taken together, our studies uncover a new metastasis-promoting pathway in Ewing Sarcoma, with therapeutically targetable components. PMID:28319067

  13. Microglia Activate Migration of Glioma Cells through a Pyk2 Intracellular Pathway

    PubMed Central

    Rolón-Reyes, Kimberleve; Kucheryavykh, Yuriy V.; Cubano, Luis A.; Inyushin, Mikhail; Skatchkov, Serguei N.; Eaton, Misty J.; Harrison, Jeffrey K.; Kucheryavykh, Lilia Y.

    2015-01-01

    Glioblastoma is one of the most aggressive and fatal brain cancers due to the highly invasive nature of glioma cells. Microglia infiltrate most glioma tumors and, therefore, make up an important component of the glioma microenvironment. In the tumor environment, microglia release factors that lead to the degradation of the extracellular matrix and stimulate signaling pathways to promote glioma cell invasion. In the present study, we demonstrated that microglia can promote glioma migration through a mechanism independent of extracellular matrix degradation. Using western blot analysis, we found upregulation of proline rich tyrosine kinase 2 (Pyk2) protein phosphorylated at Tyr579/580 in glioma cells treated with microglia conditioned medium. This upregulation occurred in rodent C6 and GL261 as well as in human glioma cell lines with varying levels of invasiveness (U-87MG, A172, and HS683). siRNA knock-down of Pyk2 protein and pharmacological blockade by the Pyk2/focal-adhesion kinase (FAK) inhibitor PF-562,271 reversed the stimulatory effect of microglia on glioma migration in all cell lines. A lower concentration of PF-562,271 that selectively inhibits FAK, but not Pyk2, did not have any effect on glioma cell migration. Moreover, with the use of the CD11b-HSVTK microglia ablation mouse model we demonstrated that elimination of microglia in the implanted tumors (GL261 glioma cells were used for brain implantation) by the local in-tumor administration of Ganciclovir, significantly reduced the phosphorylation of Pyk2 at Tyr579/580 in implanted tumor cells. Taken together, these data indicate that microglial cells activate glioma cell migration/dispersal through the pro-migratory Pyk2 signaling pathway in glioma cells. PMID:26098895

  14. Ecological Trade-offs between Migration and Reproduction Are Mediated by the Nutrition-Sensitive Insulin-Signaling Pathway.

    PubMed

    Lin, Xinda; Yao, Yun; Wang, Bo; Emlen, Douglas J; Lavine, Laura Corley

    2016-01-01

    Crowding and changes in food availability are two critical environmental conditions that impact an animal's trajectory toward either migration or reproduction. Many insects facing this challenge have evolved wing polyphenisms. When conditions favor reproduction, wing polyphenic species produce adults that either have no wings or short, non-functional wings. Facultative wing growth reflects a physiological and evolutionary trade-off between migration and reproduction, triggered by environmental conditions. How environmental cues are transduced to produce these alternative forms, and their associated ecological shift from migration to reproduction, remains an important unsolved problem in evolutionary ecology. The brown planthopper, a wing polymorphic insect exhibiting strong trade-offs in investment between migration and reproduction, is one of the most serious rice pests in Asia. In this study, we investigated the function of four genes in the insulin-signaling pathway known to couple nutrition with growth, PI3 Kinase (PI3K), PDK1, Akt (Protein Kinase B), and the forkhead gene FOXO. Using a combination of RNA interference and pharmacological inhibitor treatment, we show that all four genes contribute to tissue level regulation of wing polymorphic development in this insect. As predicted, silencing of the NlPI3K, NlAkt and NlPDK1 through dsRNA and with the pharmacological inhibitor Perifosine resulted in short-winged brown planthoppers, whereas knockdown of NlFOXO resulted in long-winged planthoppers. Morphometric analyses confirm that phenotypes from our manipulations mimic what would be found in nature, i.e., major parameters such as bristle number, wing area and body weight are not significantly different from non-experimental animals. Taken together, these data implicate the insulin-signaling pathway in the transduction of environmental factors into condition-dependent patterns of wing growth in insects.

  15. Fibronectin induces macrophage migration through a SFK-FAK/CSF-1R pathway.

    PubMed

    Digiacomo, Graziana; Tusa, Ignazia; Bacci, Marina; Cipolleschi, Maria Grazia; Dello Sbarba, Persio; Rovida, Elisabetta

    2017-07-04

    Integrins, following binding to proteins of the extracellular matrix (ECM) including collagen, laminin and fibronectin (FN), are able to transduce molecular signals inside the cells and to regulate several biological functions such as migration, proliferation and differentiation. Besides activation of adaptor molecules and kinases, integrins transactivate Receptor Tyrosine Kinases (RTK). In particular, adhesion to the ECM may promote RTK activation in the absence of growth factors. The Colony-Stimulating Factor-1 Receptor (CSF-1R) is a RTK that supports the survival, proliferation, and motility of monocytes/macrophages, which are essential components of innate immunity and cancer development. Macrophage interaction with FN is recognized as an important aspect of host defense and wound repair. The aim of the present study was to investigate on a possible cross-talk between FN-elicited signals and CSF-1R in macrophages. FN induced migration in BAC1.2F5 and J774 murine macrophage cell lines and in human primary macrophages. Adhesion to FN determined phosphorylation of the Focal Adhesion Kinase (FAK) and Src Family Kinases (SFK) and activation of the SFK/FAK complex, as witnessed by paxillin phosphorylation. SFK activity was necessary for FAK activation and macrophage migration. Moreover, FN-induced migration was dependent on FAK in either murine macrophage cell lines or human primary macrophages. FN also induced FAK-dependent/ligand-independent CSF-1R phosphorylation, as well as the interaction between CSF-1R and β1. CSF-1R activity was necessary for FN-induced macrophage migration. Indeed, genetic or pharmacological inhibition of CSF-1R prevented FN-induced macrophage migration. Our results identified a new SFK-FAK/CSF-1R signaling pathway that mediates FN-induced migration of macrophages.

  16. 7-cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d] pyrimidin-4-ylamine inhibits the proliferation and migration of vascular smooth muscle cells by suppressing ERK and Akt pathways.

    PubMed

    Seo, Hyang-Hee; Kim, Sang Woo; Lee, Chang Youn; Lim, Kyu Hee; Lee, Jiyun; Lim, Soyeon; Lee, Seahyoung; Hwang, Ki-Chul

    2017-03-05

    Excessive vascular smooth muscle cell (VSMC) proliferation and migration after vascular injury significantly contributes to the development of occlusive vascular disease. Therefore, inhibiting the proliferation and migration of VSMCs is a validated therapeutic modality for occlusive vascular disease such as atherosclerosis and restenosis. In the present study, we screened chemical compounds for their anti-proliferative effects on VSMCs using multiple approaches, such as MTT assays, wound healing assays, and trans-well migration assays. Our data indicate that 7-cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d] pyrimidin-4-ylamine, a lymphocyte-specific protein tyrosine kinase (Lck) inhibitor, significantly inhibited both VSMC proliferation and migration. 7-cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine suppresses VSMC proliferation and migration via down-regulating the protein kinase B (Akt) and extracellular signal regulated kinase (ERK) pathways, and it significantly decreased the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 and, the phosphorylation of retinoblastoma protein (pRb). Additionally, 7-cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d] pyrimidin-4-ylamine suppressed the migration of VSMCs from endothelium-removed aortic rings, as well as neointima formation following rat carotid balloon injury. The present study identified 7-cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine as a potent VSMC proliferation and migration inhibitor and warrants further studies to elucidate its more detailed molecular mechanisms, such as its primary target, and to further validate its in vivo efficacy as a therapeutic agent for pathologic vascular conditions, such as restenosis and atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Doxycycline inhibits leukemic cell migration via inhibition of matrix metalloproteinases and phosphorylation of focal adhesion kinase

    PubMed Central

    WANG, CHUNHUAI; XIANG, RU; ZHANG, XIANGZHONG; CHEN, YUNXIAN

    2015-01-01

    Doxycycline, a tetracycline-based antibiotic, has been reported to attenuate melanoma cell migration through inhibiting the focal adhesion kinase (FAK) signaling pathway. However, it remains to be elucidated whether doxycycline exerts this effect on leukemia cell migration. The present study aimed to examine the role of doxycycline in leukemia cell migration. The invasion capacities of the human leukemia cell lines KG1a (acute myelogenous leukemia) and K562 (chronic myelogenous leukemia) were evaluated using Matrigel® matrix-coated Transwell® chamber assays; leukemic cell lines treated with doxycycline (1 µg/ml) or anti-β1-integrin antibodies were added to the upper chamber, while untreated cells were included as controls. Reverse transcription quantitative polymerase chain reaction was performed in order to further understand the influence of doxycycline treatment on the expression of FAK and gelatinases in the KG1a and K562 leukemic cell lines. In addition, FAK protein expression and phosphorylation were determined using western blot analysis in order to investigate the mechanism by which doxycycline inhibited leukemic cell migration. The results revealed that doxycycline treatment significantly attenuated the migration of KG1a and K562 cells, which was demonstrated to be associated with inhibition of the expression and phosphorylation of FAK. In addition, doxycycline treatment inhibited matrix metalloproteinase (MMP)-2 and MMP-9 expression. Furthermore, incubation with blocking anti-β1-integrin antibodies had an analogous inhibitory effect on leukemic cell migration to that of doxycycline. In conclusion, the results of the present study suggested that doxycycline attenuated leukemic cell migration through inhibiting the FAK signaling pathway. Therefore, doxycycline may have potential for use as a novel strategy for the treatment of leukemia. PMID:26004127

  18. Hyperglycemia and oxidized-LDL exert a deleterious effect on endothelial progenitor cell migration in type 2 diabetes mellitus.

    PubMed

    Hamed, Saher; Brenner, Benjamin; Abassi, Zaid; Aharon, Anat; Daoud, Deeb; Roguin, Ariel

    2010-09-01

    Type 2 diabetes mellitus (DM) patients with coronary artery disease (CAD) have elevated plasma oxidized-LDL (OxLDL) levels and impaired neovascularization. Hyperglycemia and hyperlipidemia impair endothelial progenitor cell (EPC) migration, and endothelial nitric oxide (NO) bioavailability and NO synthase (NOS) activity are essential for EPC migration. Stromal-derived factor-1alpha (SDF1alpha) contributes to EPC mobilization and homing by stimulating the CXC receptor-4 (CXCR4) on the EPC plasmalemma to activate the Pi3K/Akt/eNOS signaling pathway. Therefore, we investigated the effect of high glucose (HG) and OxLDL on the migration and NO bioavailability of EPCs from healthy individuals, and then correlated the findings with those of EPCs from type 2 DM patients with and without CAD. EPCs from 15 healthy and 55 patients were exposed to HG, OxLDL, or both before evaluating EPC count, migration and NO production, and expression of CXCR4 and members of Pi3K/Akt/eNOS signaling cascade. Counts, migration, CXCR4 expression, and NO production were significantly reduced in EPCs from DM and CAD patients compared with that obtained in EPCs from healthy, and were further reduced in DM patients with CAD. The expression of CXCR4 and activation of Pi3K/Akt/eNOS signaling cascade were suppressed in OxLDL- and HG-treated EPCs, and this suppression was exacerbated when EPCs were treated simultaneously with HG and OxLDL. Hyperglycemia and elevated circulating OxLDL in DM patients with CAD severely impair EPC migration. These results suggest that the underlying mechanism for this impaired EPC migration is linked to the CXCR4/Pi3K/Akt/eNOS signaling pathway. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  19. Daucosterol Inhibits the Proliferation, Migration, and Invasion of Hepatocellular Carcinoma Cells via Wnt/β-Catenin Signaling.

    PubMed

    Zeng, Junquan; Liu, Xing; Li, Xiaofei; Zheng, Yongliang; Liu, Bin; Xiao, Youzhang

    2017-06-02

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The purpose of this study was to determine the effects of daucosterol on HCC by investigating Wnt/β-catenin signaling. In this study, HepG2 and SMMC-7721 cells were treated with varying concentrations of daucosterol, and the corresponding inhibitory effects on HCC cells were examined via CCK-8 assays. Cell migration and invasion abilities were detected via transwell assays. β-Catenin and phospho (p)-β-catenin levels were analyzed via western blotting. Our results showed that daucosterol reduced the proliferation, migration, and invasion capacities of HCC cells in a concentration-dependent manner. In addition, daucosterol reduced the levels of β-catenin and p-β-catenin in HepG2 and SMMC-7721 cells. Furthermore, the Wnt signaling pathway inhibitor SB-216763 was used to treat HepG2 and SMMC-7721 cells with daucosterol. Our results showed that co-treatment with daucosterol and SB-216763 abolished the effects of daucosterol on cell inhibition ratios, cell migration, and cell invasion. These findings indicated that daucosterol inhibited cell migration and invasion in HCC cells via the Wnt/β-catenin signaling pathway. Therefore, our study highlights the use of daucosterol as a promising therapeutic strategy for HCC treatment.

  20. MicroRNA-146a promote cell migration and invasion in human colorectal cancer via carboxypeptidase M/src-FAK pathway

    PubMed Central

    Zhan, Cheng; Le-Meng, Zhang; Liu, Hongchun; Cai, Yu; Tu, Chuantao; Li, Xi; Zou, Yanting; Zhang, Shuncai

    2017-01-01

    Colorectal cancer (CRC) is one of the most common cancers worldwide, and microRNAs play important roles in CRC progression. This study aimed to investigate the roles of miR-146a-5p in human CRC and their molecular mechanisms. First, we found that miR-146a-5p was significantly upregulated in CRC tissues and promoted the migration of CRC cells. Then, we identified carboxypeptidase M (CPM) as a direct target of miR-146a-5p, and found that it inhibited the migration and invasion of CRC cells. Our results also showed that CPM expression was positively correlated with overall survival and negatively correlated with recurrence, lymph node invasion, and N stage. Furthermore, we demonstrated that both miR-146a-5p and CPM regulated Src and FAK expression, while the Src-FAK signaling pathway is widely known to be associated with the migration and invasion of multiple tumor cells. This study is the first to demonstrate the functional and mechanistic relationship of the miR-146a-5p/CPM/Src-FAK axis and its effect on the migration and invasion of CRC cells. Thus, miR-146a-5p represents potential targets for CRC diagnosis and therapy. PMID:28186967

  1. The activation of directional stem cell motility by green light-emitting diode irradiation.

    PubMed

    Ong, Wei-Kee; Chen, How-Foo; Tsai, Cheng-Ting; Fu, Yun-Ju; Wong, Yi-Shan; Yen, Da-Jen; Chang, Tzu-Hao; Huang, Hsien-Da; Lee, Oscar Kuang-Sheng; Chien, Shu; Ho, Jennifer Hui-Chun

    2013-03-01

    Light-emitting diode (LED) irradiation is potentially a photostimulator to manipulate cell behavior by opsin-triggered phototransduction and thermal energy supply in living cells. Directional stem cell motility is critical for the efficiency and specificity of stem cells in tissue repair. We explored that green LED (530 nm) irradiation directed the human orbital fat stem cells (OFSCs) to migrate away from the LED light source through activation of extracellular signal-regulated kinases (ERK)/MAP kinase/p38 signaling pathway. ERK inhibitor selectively abrogated light-driven OFSC migration. Phosphorylation of these kinases as well as green LED irradiation-induced cell migration was facilitated by increasing adenosine triphosphate (ATP) production in OFSCs after green LED exposure, and which was thermal stress-independent mechanism. OFSCs, which are multi-potent mesenchymal stem cells isolated from human orbital fat tissue, constitutionally express three opsins, i.e. retinal pigment epithelium-derived rhodopsin homolog (RRH), encephalopsin (OPN3) and short-wave-sensitive opsin 1 (OPN1SW). However, only two non-visual opsins, i.e. RRH and OPN3, served as photoreceptors response to green LED irradiation-induced OFSC migration. In conclusion, stem cells are sensitive to green LED irradiation-induced directional cell migration through activation of ERK signaling pathway via a wavelength-dependent phototransduction. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Human amniotic epithelial stem cells promote wound healing by facilitating migration and proliferation of keratinocytes via ERK, JNK and AKT signaling pathways.

    PubMed

    Zhao, Bin; Liu, Jia-Qi; Zheng, Zhao; Zhang, Jun; Wang, Shu-Yue; Han, Shi-Chao; Zhou, Qin; Guan, Hao; Li, Chao; Su, Lin-Lin; Hu, Da-Hai

    2016-07-01

    Wound healing is a highly orchestrated physiological process consisting in a complex interaction of cellular and biochemical events. Human amniotic epithelial stem cells (HAESCs) have been shown to be an attractive resource for wound healing because they are primitive stem cells. However, the exact effects of amnion-derived stem cells on the migration or proliferation of keratinocytes and their potential mechanism are not fully understood. We have found that HAESCs accelerate the migration of keratinocytes and induce a remarkable increase in the activity of phospho-ERK, phospho-JNK, and phospho-AKT, the blockade of which by their specific inhibitors significantly inhibits migration induced by HAESC-conditioned medium (CM). Furthermore, the co-culture of keratinocytes with HAESCs up-regulates the expression levels of cell proliferation proteins Cyclin D1, Cyclin D3 and Mdm2. In vivo animal experiments have shown that HAESC-CM improves wound healing, whereas blockade with ERK, JNK and AKT inhibitors significantly impairs wound healing. Taken together, these results reveal, for the first time, that HAESCs promote wound healing by facilitating the migration and proliferation of keratinocytes via ERK, JNK and AKT signaling pathways and might be a potential therapy in skin wound healing.

  3. FLUID EVOLUTION AND MINERAL REACTIONS DURING SHEAR ZONE FORMATION AT NUSFJORD, LOFOTEN, NORWAY (Invited)

    NASA Astrophysics Data System (ADS)

    Kullerud, K.

    2009-12-01

    At Nusfjord in Lofoten, Norway, three 0.3 - 3 m thick shear zones occur in a gabbro-anorthosite. During deformation, the shear zones were infiltrated by a hydrous fluid enriched in Cl. In the central parts of the shear zones, fluid-rock interaction resulted in complete break-down of the primary mafic silicates. Complete hydration of these minerals to Cl-free amphibole and biotite suggests that the hydrous fluid was present in excess during deformation in these parts of the shear zones. Along the margins of the shear zones, however, the igneous mafic silicates (Cpx, Bt, Opx) were only partly overgrown by hydrous minerals. Here, Cl-enriched minerals (Amph, Bt, Scp, Ap) can be observed. Amphibole shows compositions covering the range 0.1 - 4.0 wt % Cl within single thin sections. Mineral textures and extreme compositional variations of the Cl-bearing minerals indicate large chemical gradients of the fluid phase. Relics of primary mafic silicates and compositionally zoned reaction coronas around primary mafic silicates suggest that the free fluid was totally consumed before the alteration of the primary phases were completed. The extreme variations in the Cl-content of amphibole are inferred to monitor a gradual desiccation of the Cl-bearing grain-boundary fluid during fluid-mineral reactions accordingly: 1) The first amphibole that formed during the reactions principally extracted water from the fluid, resulting in a slight increase in the Cl content of the fluid. 2) Continued amphibole-forming reactions resulted in gradual consumption of the free fluid phase, principally by extracting water from the fluid, resulting in an increase in its Cl-content. Higher Cl-content of the fluid resulted in higher Cl-content of the equilibrium amphibole. 3) The most Cl-enriched amphibole (4 wt % Cl) formed in equilibrium with the last volumes of the grain-boundary fluid, which had evolved to a highly saline solution. Mineral reactions within a 1-2 thick zone of the host rock along the contact to the shear zones indicate a more complicated involvement of fluids during shear zone formation than described above. Apparently, fluids have been transported laterally from the outer parts of the shear zones into the gabbro-anorthosite along thin recrystallized zones of plagioclase. The fluid that infiltrated the undeformed host rock of the shear zones resulted in formation of Cl-free amphibole and garnet between the primary mafic minerals and plagioclase. A working hypothesis is that narrow fractures formed within the host rock, outside the sheared rock during shear zone formation. During shear zone formation, the central parts of the shear zones were completely hydrated by an externally derived Cl-bearing hydrous fluid. Some of the fluid migrated to the marginal parts of the shear zones and evolved to a highly saline solution. However, during desiccation of the fluid along the marginal parts of the shear zones, some of the fluid escaped along narrow fractures into the host rock of the shear zones. The Cl-free amphibole that formed from this fluid suggests that the narrow pathways of the fluid provided a path for water transport, but acted as a filter for the much larger ions of Cl.

  4. Integration of nodal and BMP signals in the heart requires FoxH1 to create left-right differences in cell migration rates that direct cardiac asymmetry.

    PubMed

    Lenhart, Kari F; Holtzman, Nathalia G; Williams, Jessica R; Burdine, Rebecca D

    2013-01-01

    Failure to properly establish the left-right (L/R) axis is a major cause of congenital heart defects in humans, but how L/R patterning of the embryo leads to asymmetric cardiac morphogenesis is still unclear. We find that asymmetric Nodal signaling on the left and Bmp signaling act in parallel to establish zebrafish cardiac laterality by modulating cell migration velocities across the L/R axis. Moreover, we demonstrate that Nodal plays the crucial role in generating asymmetry in the heart and that Bmp signaling via Bmp4 is dispensable in the presence of asymmetric Nodal signaling. In addition, we identify a previously unappreciated role for the Nodal-transcription factor FoxH1 in mediating cell responsiveness to Bmp, further linking the control of these two pathways in the heart. The interplay between these TGFβ pathways is complex, with Nodal signaling potentially acting to limit the response to Bmp pathway activation and the dosage of Bmp signals being critical to limit migration rates. These findings have implications for understanding the complex genetic interactions that lead to congenital heart disease in humans.

  5. Distortion of frontal bones results from cell apoptosis by the mechanical force from the up-migrating eye during metamorphosis in Paralichthys olivaceus.

    PubMed

    Sun, Mingyan; Wei, Fen; Li, Hui; Xu, Juan; Chen, Xinye; Gong, Xiaoling; Tian, Yongsheng; Chen, Songlin; Bao, Baolong

    2015-05-01

    Craniofacial remodeling during flatfish metamorphosis, including eye migration, is perhaps the most striking example of asymmetric postembryonic development in the vertebrate world. The asymmetry of the cranium mainly results from distortion of the frontal bones, which depends on eye migration during metamorphosis. However, it is unclear how the up-migrating eye causes distortion of the frontal bones. In this study, we first show that distortion of the frontal bones during metamorphosis in Paralichthys olivaceus is the result of cell apoptosis, rather than cell autophagy or cell proliferation. Secondly, we report that cell apoptosis in the frontal bones is induced by the mechanical force transferred from the up-migrating eye. The mechanical force from the up-migrating eye signals through FAK to downstream molecules that are integrated into the BMP-2 signal pathway. Finally, it is shown that cell apoptosis in the frontal bones is activated by the intrinsic mitochondrial pathway; the extrinsic death receptor is not involved in this process. Moreover, cell apoptosis in frontal bones is not induced directly by thyroid hormones, which are thought to mediate metamorphosis in flatfishes and directly mediate cell apoptosis during amphibian metamorphosis. These findings help identify the major signaling route used during regulation of frontal bone distortion during metamorphosis in flatfish, and indicate that the asymmetry of the cranium, or at least the distortion of frontal bones, is the result of rather than the reason underlying eye migration. Copyright © 2015. Published by Elsevier Ireland Ltd.

  6. Wash functions downstream of Rho1 GTPase in a subset of Drosophila immune cell developmental migrations

    PubMed Central

    Verboon, Jeffrey M.; Rahe, Travis K.; Rodriguez-Mesa, Evelyn; Parkhurst, Susan M.

    2015-01-01

    Drosophila immune cells, the hemocytes, undergo four stereotypical developmental migrations to populate the embryo, where they provide immune reconnoitering, as well as a number of non–immune-related functions necessary for proper embryogenesis. Here, we describe a role for Rho1 in one of these developmental migrations in which posteriorly located hemocytes migrate toward the head. This migration requires the interaction of Rho1 with its downstream effector Wash, a Wiskott–Aldrich syndrome family protein. Both Wash knockdown and a Rho1 transgene harboring a mutation that prevents Wash binding exhibit the same developmental migratory defect as Rho1 knockdown. Wash activates the Arp2/3 complex, whose activity is needed for this migration, whereas members of the WASH regulatory complex (SWIP, Strumpellin, and CCDC53) are not. Our results suggest a WASH complex–independent signaling pathway to regulate the cytoskeleton during a subset of hemocyte developmental migrations. PMID:25739458

  7. Effects of canonical NF-κB signaling pathway on the proliferation and odonto/osteogenic differentiation of human stem cells from apical papilla.

    PubMed

    Li, Junjun; Yan, Ming; Wang, Zilu; Jing, Shuanglin; Li, Yao; Liu, Genxia; Yu, Jinhua; Fan, Zhipeng

    2014-01-01

    NF-κB signaling pathway plays a complicated role in the biological functions of mesenchymal stem cells. However, the effects of NF-κB pathway on the odonto/osteogenic differentiation of stem cells from apical papilla (SCAPs) remain unclear. The present study was designed to evaluate the effects of canonical NF-κB pathway on the osteo/odontogenic capacity of SCAPs in vitro. Western blot results demonstrated that NF-κB pathway in SCAPs was successfully activated by TNF-α or blocked by BMS-345541. NF-κB pathway-activated SCAPs presented a higher proliferation activity compared with control groups, as indicated by dimethyl-thiazol-diphenyl tetrazolium bromide assay (MTT) and flow cytometry assay (FCM). Wound scratch assay revealed that NF-κB pathway-activated SCAPs presented an improved migration capacity, enhanced alkaline phosphatase (ALP) activity, and upregulated mineralization capacity of SCAPs, as compared with control groups. Meanwhile, the odonto/osteogenic markers (ALP/ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN, OPN/OPN, BSP/BSP, DSPP/DSP, and DMP-1/DMP-1) in NF-κB pathway-activated SCAPs were also significantly upregulated as compared with control groups at both protein and mRNA levels. However, NF-κB pathway-inhibited SCAPs exhibited a lower proliferation/migration capacity, and decreased odonto/osteogenic ability in comparison with control groups. Our findings suggest that classical NF-κB pathway plays a paramount role in the proliferation and committed differentiation of SCAPs.

  8. Beaufort Sea deep-water gas hydrate recovery from a seafloor mound in a region of widespread BSR occurrence

    USGS Publications Warehouse

    Hart, Patrick E.; Pohlman, John W.; Lorenson, T.D.; Edwards, Brian D.

    2011-01-01

    Gas hydrate was recovered from the Alaskan Beaufort Sea slope north of Camden Bay in August 2010 during a U.S. Coast Guard Cutter Healy expedition (USCG cruise ID HLY1002) under the direction of the U.S. Geological Survey (USGS). Interpretation of multichannel seismic (MCS) reflection data collected in 1977 by the USGS across the Beaufort Sea continental margin identified a regional bottom simulating reflection (BSR), indicating that a large segment of the Beaufort Sea slope is underlain by gas hydrate. During HLY1002, gas hydrate was sampled by serendipity with a piston core targeting a steep-sided bathymetric high originally thought to be an outcrop of older, exposed strata. The feature cored is an approximately 1100m diameter, 130 m high conical mound, referred to here as the Canning Seafloor Mound (CSM), which overlies the crest of a buried anticline in a region of sub-parallel compressional folds beneath the eastern Beaufort outer slope. An MCS profile shows a prominent BSR upslope and downslope from the mound. The absence of a BSR beneath the CSM and occurrence of gas hydrate near the summit indicates that free gas has migrated via deep-rooted thrust faults or by structural focusing up the flanks of the anticline to the seafloor. Gas hydrate recovered from near the CSM summit at a subbottom depth of about 5.7 meters in a water depth of 2538 m was of nodular and vein-filling morphology. Although the hydrate was not preserved, residual gas from the core liner contained >95% methane by volume when corrected for atmospheric contamination. The presence of trace C4+hydrocarbons (<0.1% by volume) confirms at least a minor thermogenic component. Authigenic carbonates and mollusk shells found throughout the core indicate sustained methane-rich fluid advection and possible sediment extrusion contributing to the development of the mound. Blister-like inflation of the seafloor caused by formation and accumulation of shallow hydrate lenses is also a likely factor in CSM growth. Pore water analysis shows the sulfate-methane transition to be very shallow (0-1 mbsf), also supporting an active high-flux interpretation. Pore water with chloride concentrations as low as 160 mM suggest fluid migration pathways may extend to the mound from buried non-marine sediments containing low-salinity fluids.

  9. Antitumor activity of taspine by modulating the EGFR signaling pathway of Erk1/2 and Akt in vitro and in vivo.

    PubMed

    Zhang, Yanmin; Zheng, Lei; Zhang, Jie; Dai, Bingling; Wang, Nan; Chen, Yinnan; He, Langchong

    2011-11-01

    EGFR, as a critical signaling pathway in many human tumors, has become an important target of cancer drug design. Taspine has shown meaningful angiogenesis activity in previous studies. This paper is to investigate the antitumor action of taspine by modulating the EGFR signaling pathway. The study determined the expression of key signaling molecules of EGFR (EGFR, Akt, p-Akt, Erk, and p-Erk) by Western blot and real-time PCR and analyzed their correlations with subsequent reactions. In addition, the cell proliferation, migration, and EGF production were examined by MTT, transwell system, and ELISA. The antitumor activity in vivo was carried out by xenograft in athymic mice. The results showed that taspine could inhibit A431 and Hek293/EGFR cell proliferation and A431 cell migration as well as EGF production. Compared to the negative control, EGFR, Akt, and phosphorylation of Akt were significantly inhibited by taspine treatment in A431 and HEK293/EGFR cells. Consistent with the inhibition of Akt activity, Erk1/2 and its phosphorylation were reduced. Moreover, taspine inhibited A431 xenograft tumor growth. These results suggest that EGFR activated by EGF and its downstream signaling pathways proteins could be downregulated by taspine in a dose-dependent manner. The antitumor mechanism of taspine through the EGFR pathway lies in the ability to inhibit A431 cell proliferation and migration by reducing EGF secretion. This occurs through the repression of EGFR which mediates not only MAPK (Erk1/2) but also Akt signals. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Seismic swarms and fluid flow offshore Central America

    NASA Astrophysics Data System (ADS)

    Dzierma, Yvonne; Thorwart, Martin; Hensen, Christian; Rabbel, Wolfgang; Wolf, Florian

    2010-05-01

    Offshore Nicaragua and Northern Costa Rica, the Cocos Plate subducts beneath the Caribbean Plate, carrying with it a large amount of fluids and volatiles. While some of these are set free at great depth beneath the volcanic arc, causing the extremely high water content observed in Nicaraguan mafic magmas (Carr et al., 2003; Kutterolf et al., 2007), some early dehydration reactions already release fluids from the subducting plate underneath the continental slope. Unlike in accretionary margins, where these fluids migrate up along the decollement towards the deformation front, fluid release at erosional margins seems to occur through fractures in the overriding plate (Ranero et al., 2008). Fluid seeps in this region have be observed at seafloor mounds, appearing as side-scan sonar backscatter anomalies or revealed by the presence of chemosynthetic communities (Sahling et al., 2008). In the framework of the General Research Area SFB 574 "Volatiles and Fluids in Subduction Zones", a network of 20 ocean-bottom-stations was deployed offshore Sta Elena Peninsula, Northern Costa Rica, from December 2005 to June 2006. Several distinct swarms of small earthquakes were observed at the seismic stations, which occurred clustered over a time period of several days and have very similar seismic waveforms. Since a correlation of fluid-release sites with the occurrence of sporadic seismic swarms would indicate that fluid migration and fracturing is the mechanism responsible for triggering the earthquake swarms, the events are re-analysed by double-difference localisation to enhance the resolution of the earthquake locations. The results are then considered to estimate the migration velocity and direction and compare the localisations with the known mound sites. Carr, M., Feigenson, M. D., Patino, L. C., and Walker, J. A., 2003: Volcanism and geochemistry in Central America: Progress and problems, in Eiler, J. (ed.), Inside the subduction factory, pp. 153-179, American Geophysical Union Kutterolf S., Freundt, A., Perez, W. Wehrmann, H., and Schmincke, H. U., 2007: Late Pleistocene to Holocene temporal succession and magnitudes of highly-explosive volcanic eruptions in west-central Nicaragua. J. Volc. Geothermal Res. 163, pp. 55-82 Ranero, C. R., Grevemeyer, I., Sahling, H., Barckhausen, U., Hensen, C., Wallmann, K., Weinrebe, W., Vannucchi, P., von Huene, R., and McIntosh, K., 2008: Hydrogeological system of erosional convergent margins and its influence on tectonics and interplate seismogenesis, Geochem. Geophys. Geosys., Vol 9, Nr 3 Sahling, H., Masson, D. G., Ranero, C. R., Hühnerbach, V., Weinrebe, W., Klauke, I., Bürk, D., Brückmann, W., and Suess, E., 2008: Fluid seepage at the continental margin offshore Costa Rica and southern Nicaragua, Geochem. Geophys. Geosys., Vol 9, Nr 5

  11. Protein and Molecular Characterization of a Clinically Compliant Amniotic Fluid Stem Cell-Derived Extracellular Vesicle Fraction Capable of Accelerating Muscle Regeneration Through Enhancement of Angiogenesis.

    PubMed

    Mellows, Ben; Mitchell, Robert; Antonioli, Manuela; Kretz, Oliver; Chambers, David; Zeuner, Marie-Theres; Denecke, Bernd; Musante, Luca; Ramachandra, Durrgah L; Debacq-Chainiaux, Florence; Holthofer, Harry; Joch, Barbara; Ray, Steve; Widera, Darius; David, Anna L; Huber, Tobias B; Dengjel, Joern; De Coppi, Paolo; Patel, Ketan

    2017-09-15

    The secretome of human amniotic fluid stem cells (AFSCs) has great potential as a therapeutic agent in regenerative medicine. However, it must be produced in a clinically compliant manner before it can be used in humans. In this study, we developed a means of producing a biologically active secretome from AFSCs that is free of all exogenous molecules. We demonstrate that the full secretome is capable of promoting stem cell proliferation, migration, and protection of cells against senescence. Furthermore, it has significant anti-inflammatory properties. Most importantly, we show that it promotes tissue regeneration in a model of muscle damage. We then demonstrate that the secretome contains extracellular vesicles (EVs) that harbor much, but not all, of the biological activity of the whole secretome. Proteomic characterization of the EV and free secretome fraction shows the presence of numerous molecules specific to each fraction that could be key regulators of tissue regeneration. Intriguingly, we show that the EVs only contain miRNA and not mRNA. This suggests that tissue regeneration in the host is mediated by the action of EVs modifying existing, rather than imposing new, signaling pathways. The EVs harbor significant anti-inflammatory activity as well as promote angiogenesis, the latter may be the mechanistic explanation for their ability to promote muscle regeneration after cardiotoxin injury.

  12. HER1 signaling mediates extravillous trophoblast differentiation in humans.

    PubMed

    Wright, J K; Dunk, C E; Amsalem, H; Maxwell, C; Keating, S; Lye, S J

    2010-12-01

    This study examines the role of HER1 signaling in the differentiation of proliferative extravillous trophoblast (EVT) into invasive EVT. Using the JAR choriocarcinoma cell line and placental villous explants as experimental models and immunohistochemical assessment of protein markers of EVT differentiation (downregulation of HER1 and Cx40 and upregulation of HER2 and alpha1 integrin), we show that the ability of decidual conditioned medium (DCM) to induce HER1/2 switching was abrogated in the presence of the HER1 antagonist, AG1478. Similarly, epidermal growth factor (EGF) treatment resulted in the downregulation of HER1 and an upregulation of HER2 expression, whereas co-incubation of EGF with AG1478 inhibited this response. However, EGF did not downregulate Cx40 or induce migration of EVT. In contrast, heparin-binding epidermal-like growth factor (HBEGF) stimulated dose-dependent JAR cell migration, which was inhibited by both AG1478 and AG825 (HER2 antagonist). Western blot analysis of HER1 activation demonstrated that HBEGF-mediated phosphorylation of the HER1 Tyr992 and Tyr1068 sites, while EGF activated the Tyr1045 site. Moreover, HBEGF induced a stronger and more sustained activation of both the mitogen-activated protein kinase and phosphoinositol 3 kinase (PIK3) signaling pathways. Migration assays using a panel of signaling pathway inhibitors demonstrated that the HBEGF-mediated migration was dependent on the PIK3 pathway. These results demonstrate that HBEGF-mediated HER1 signaling through PIK3 is an important component of EVT invasion.

  13. Low molecular weight hyaluronan induces migration of human choriocarcinoma JEG-3 cells mediated by RHAMM as well as by PI3K and MAPK pathways.

    PubMed

    Mascaró, Marilina; Pibuel, Matías A; Lompardía, Silvina L; Díaz, Mariangeles; Zotta, Elsa; Bianconi, Maria I; Lago, Néstor; Otero, Silvina; Jankilevich, Gustavo; Alvarez, Elida; Hajos, Silvia E

    2017-08-01

    Hyaluronan (HA) is the major glycosaminoglycan present in the extracellular matrix. It is produced by some tumours and promotes proliferation, differentiation and migration among others cellular processes. Gestational trophoblastic disease (GTD) is composed by non-tumour entities, such as hydatidiform mole (HM), which is the most common type of GTD and also malignant entities such as choriocarcinoma (CC) and placental site trophoblastic tumour (PSTT), being CC the most aggressive tumour. Although there is a growing understanding of GTD biology, the role of HA in the pathogenesis of this group of diseases remains largely unknown. The aim of this work was to study the role of HA in the pathogenesis of GTD by defining the expression pattern of HA and its receptors CD44 and RHAMM, as well as to determine if HA can modulate proliferation, differentiation and migration of CC cells. Receptors and signalling pathways involved were also analyzed. We demonstrated that HA and RHAMM are differently expressed among GTD entities and even among trophoblast subtypes. We also showed that HA is able to enhance the expression of extravillous trophoblast markers and also to induce migration of JEG-3 cells, the latter mediated by RHAMM as well as PI3K and MAPK pathways. These findings indicate a novel regulatory mechanism for CC cell biology and also contribute to the understanding of GTD pathophysiology.

  14. Modeling multiphase migration of organic chemicals in groundwater systems--a review and assessment.

    PubMed Central

    Abriola, L M

    1989-01-01

    Over the past two decades, a number of models have been developed to describe the multiphase migration of organic chemicals in the subsurface. This paper presents the state-of-the-art with regard to such modeling efforts. The mathematical foundations of these models are explored and individual models are presented and discussed. Models are divided into three groups: a) those that assume a sharp interface between the migrating fluids; b) those that incorporate capillarity; and c) those that consider interphase transport of mass. Strengths and weaknesses of each approach are considered along with supporting data for model validation. Future research directions are also highlighted. PMID:2695322

  15. SDF1 regulates leading process branching and speed of migrating interneurons

    PubMed Central

    Lysko, Daniel E.; Putt, Mary; Golden, Jeffrey A.

    2011-01-01

    Cell migration is required for normal embryonic development, yet how cells navigate complex paths while integrating multiple guidance cues remains poorly understood. During brain development, interneurons migrate from the ventral ganglionic eminence to the cerebral cortex within several migratory streams. They must exit these streams to invade the cortical plate. While SDF1-signaling is necessary for normal interneuron stream migration, how they switch from tangential stream migration to invade the cortical plate is unknown. Here we demonstrate that SDF1-signaling reduces interneuron branching frequency by reducing cAMP levels via a Gi-signaling pathway using an in vitro mouse explant system, resulting in the maintenance of stream migration. Blocking SDF1-signaling, or increasing branching frequency, results in stream exit and cortical plate invasion in mouse brain slices. These data support a novel model to understand how migrating interneurons switch from tangential migration to invade the cortical plate in which reducing SDF1-signaling increases leading process branching and slows the migration rate, permitting migrating interneurons to sense cortically directed guidance cues. PMID:21289183

  16. The effect of diagenesis and fluid migration on rare earth element distribution in pore fluids of the northern Cascadia accretionary margin

    USGS Publications Warehouse

    Kim, Ji-Hoon; Torres, Marta E.; Haley, Brian A.; Kastner, Miriam; Pohlman, John W.; Riedel, Michael; Lee, Young-Joo

    2012-01-01

    Analytical challenges in obtaining high quality measurements of rare earth elements (REEs) from small pore fluid volumes have limited the application of REEs as deep fluid geochemical tracers. Using a recently developed analytical technique, we analyzed REEs from pore fluids collected from Sites U1325 and U1329, drilled on the northern Cascadia margin during the Integrated Ocean Drilling Program (IODP) Expedition 311, to investigate the REE behavior during diagenesis and their utility as tracers of deep fluid migration. These sites were selected because they represent contrasting settings on an accretionary margin: a ponded basin at the toe of the margin, and the landward Tofino Basin near the shelf's edge. REE concentrations of pore fluid in the methanogenic zone at Sites U1325 and U1329 correlate positively with concentrations of dissolved organic carbon (DOC) and alkalinity. Fractionations across the REE series are driven by preferential complexation of the heavy REEs. Simultaneous enrichment of diagenetic indicators (DOC and alkalinity) and of REEs (in particular the heavy elements Ho to Lu), suggests that the heavy REEs are released during particulate organic carbon (POC) degradation and are subsequently chelated by DOC. REE concentrations are greater at Site U1325, a site where shorter residence times of POC in sulfate-bearing redox zones may enhance REE burial efficiency within sulfidic and methanogenic sediment zones where REE release ensues. Cross-plots of La concentrations versus Cl, Li and Sr delineate a distinct field for the deep fluids (z > 75 mbsf) at Site U1329, and indicate the presence of a fluid not observed at the other sites drilled on the Cascadia margin. Changes in REE patterns, the presence of a positive Eu anomaly, and other available geochemical data for this site suggest a complex hydrology and possible interaction with the igneous Crescent Terrane, located east of the drilled transect.

  17. Corridors of migrating neurons in the human brain and their decline during infancy.

    PubMed

    Sanai, Nader; Nguyen, Thuhien; Ihrie, Rebecca A; Mirzadeh, Zaman; Tsai, Hui-Hsin; Wong, Michael; Gupta, Nalin; Berger, Mitchel S; Huang, Eric; Garcia-Verdugo, Jose-Manuel; Rowitch, David H; Alvarez-Buylla, Arturo

    2011-09-28

    The subventricular zone of many adult non-human mammals generates large numbers of new neurons destined for the olfactory bulb. Along the walls of the lateral ventricles, immature neuronal progeny migrate in tangentially oriented chains that coalesce into a rostral migratory stream (RMS) connecting the subventricular zone to the olfactory bulb. The adult human subventricular zone, in contrast, contains a hypocellular gap layer separating the ependymal lining from a periventricular ribbon of astrocytes. Some of these subventricular zone astrocytes can function as neural stem cells in vitro, but their function in vivo remains controversial. An initial report found few subventricular zone proliferating cells and rare migrating immature neurons in the RMS of adult humans. In contrast, a subsequent study indicated robust proliferation and migration in the human subventricular zone and RMS. Here we find that the infant human subventricular zone and RMS contain an extensive corridor of migrating immature neurons before 18 months of age but, contrary to previous reports, this germinal activity subsides in older children and is nearly extinct by adulthood. Surprisingly, during this limited window of neurogenesis, not all new neurons in the human subventricular zone are destined for the olfactory bulb--we describe a major migratory pathway that targets the prefrontal cortex in humans. Together, these findings reveal robust streams of tangentially migrating immature neurons in human early postnatal subventricular zone and cortex. These pathways represent potential targets of neurological injuries affecting neonates.

  18. HPHT reservoir evolution: a case study from Jade and Judy fields, Central Graben, UK North Sea

    NASA Astrophysics Data System (ADS)

    di Primio, Rolando; Neumann, Volkmar

    2008-09-01

    3D basin modelling of a study area in Quadrant 30, UK North Sea was performed in order to elucidate the burial, thermal, pressure and hydrocarbon generation, migration and accumulation history in the Jurassic and Triassic high pressure high temperature sequences. Calibration data, including reservoir temperatures, pressures, petroleum compositional data, vitrinite reflectance profiles and published fluid inclusion data were used to constrain model predictions. The comparison of different pressure generating processes indicated that only when gas generation is taken into account as a pressure generating mechanism, both the predicted present day as well as palaeo-pressure evolution matches the available calibration data. Compositional modelling of hydrocarbon generation, migration and accumulation also reproduced present and palaeo bulk fluid properties such as the reservoir fluid gas to oil ratios. The reconstruction of the filling histories of both reservoirs indicates that both were first charged around 100 Ma ago and contained initially a two-phase system in which gas dominated volumetrically. Upon burial reservoir fluid composition evolved to higher GORs and became undersaturated as a function of increasing pore pressure up to the present day situation. Our results indicate that gas compositions must be taken into account when calculating the volumetric effect of gas generation on overpressure.

  19. More than just water channels: unexpected cellular roles of aquaporins.

    PubMed

    Verkman, A S

    2005-08-01

    Aquaporins (AQPs) are membrane proteins that transport water and, in some cases, also small solutes such as glycerol. AQPs are expressed in many fluid-transporting tissues, such as kidney tubules and glandular epithelia, as well as in non-fluid-transporting tissues, such as epidermis, adipose tissue and astroglia. Their classical role in facilitating trans-epithelial fluid transport is well understood, as in the urinary concentrating mechanism and gland fluid secretion. AQPs are also involved in swelling of tissues under stress, as in the injured cornea and the brain in stroke, tumor and infection. Recent analysis of AQP-knockout mice has revealed unexpected cellular roles of AQPs. AQPs facilitate cell migration, as manifested by reduced tumor angiogenesis in AQP1-knockout mice, by a mechanism that might involve facilitated water transport in lamellipodia of migrating cells. AQPs that transport both glycerol and water regulate glycerol content in epidermis and fat, and consequently skin hydration/biosynthesis and fat metabolism. AQPs might also be involved in neural signal transduction, cell volume regulation and organellar physiology. The many roles of AQPs could be exploited for clinical benefit; for example, treatments that modulate AQP expression/function could be used as diuretics, and in the treatment of brain swelling, glaucoma, epilepsy, obesity and cancer.

  20. Dynamics of fluid expulsion during high-pressure devolatilization of serpentinite in subduction settings: field, petrological and textural constraints from the Almirez ultramafic massif.

    NASA Astrophysics Data System (ADS)

    Garrido, C. J.; Padrón-Navarta, J. A.; López-Sánchez-Vizcaíno, V.; Gómez-Pugnaire, M. T.; Marchesi, C.; Tommasi, A.

    2012-04-01

    Our understanding of subduction zone processes is tightly connected to our knowledge of the cycling of volatiles in the Earth, namely the loci of devolatilization reactions and the fluid migration mechanism. The exact nature of fluid pathways at high-pressure conditions is poorly known and still highly speculative. Studies metamorphic terrains that record main dehydration reaction are, thus, an invaluable tool to decipher the mechanism for fluid expulsion. Among other dehydration reactions in subduction zones, the antigorite (Atg) breakdown is rather discontinuous, releases the largest amount of fluids (ca. 9 wt. %) and is considered to have important seismological implications. The antigorite dehydration front in the Cerro del Almirez (Betic Cordillera, Spain) offers, thus, an unique opportunity to investigate the dynamics of fluid expulsion through the study of micro- and macrotextures recorded in the prograde assemblage (chlorite harzburgite). Granoblastic texture are interspersed in decameter-sized domains with spinifex-like chl-harzburgite and were formed under similar P-T conditions (~1.6-1.9 GPa and 680-710°C). We ascribe these textures to shifts of the growth rate due to temporal and spatial fluctuations of the affinity of the Atg-breakdown reaction. These fluctuations are driven by cyclic variations of the excess fluid pressure which are ultimately controlled by the hydrodynamics of deserpentinization fluid expulsion. Crystallization at a low affinity of the reaction, correspondig to the granoblastic texture, may be attained if fluids are slowly drained out from the dehydration front. During the advancement of the dehydration front, overpressured domains are left behind preserving highly metastable Atg-serpentinite domains. Brittle failure results in a sudden drop of the fluid pressure, and a displacement of Atg equilibrium towards the prograde products that crystallizes at a high affinity of the reaction (spinifex-like texture). Evidences of brittle failure are found along grain-size reduction zones (GSRZ), a few mm to meters wide, which form roughly planar conjugate structures and crosscut the metamorphic texture. GSRZ are characterized by (1) sharp, irregular shapes and abrupt terminations contacts with undeformed metaperidotite, (2) an important reduction of the olivine grain size (60-250 µm), and (3) decrease in the opx modal amount. Analysis of olivine crystal-preferred orientations in GSRZ shows similar patterns, but a higher dispersion than in neighboring metaperidotite. These structures are interpreted as due to hydrofracturing allowing for the formation of high permeability channelways for overpressured fluids. This textural bimodality (granofels and Spinifex-like) and the record of brittle failure hence witnesses a unique example of the feedbacks between the cyclic dynamic of metamorphic fluid expulsion, the reaction rate and crystallisation of the Atg-dehydrating system.

Top