Sample records for actively migrating headcuts

  1. Effect of soil texture, tailwater height, and pore-water pressure on the morphodynamics of migrating headcuts in upland concentrated flows

    USDA-ARS?s Scientific Manuscript database

    Rill and gully erosion in upland and agricultural areas can result in significant soil degradation worldwide, and headcuts are the primary mechanism by which this landscape dissection occurs. Experiments were conducted to further examine the morphodynamic behavior of actively migrating headcuts in u...

  2. Headcut Erosion in Wyoming's Sweetwater Subbasin.

    PubMed

    Cox, Samuel E; Booth, D Terrance; Likins, John C

    2016-02-01

    Increasing human population and intensive land use combined with a warming climate and chronically diminished snowpacks are putting more strain on water resources in the western United States. Properly functioning riparian systems slow runoff and store water, thus regulating extreme flows; however, riparian areas across the west are in a degraded condition with a majority of riparian systems not in proper functioning condition, and with widespread catastrophic erosion of water-storing peat and organic soils. Headcuts are the leading edge of catastrophic channel erosion. We used aerial imagery (1.4-3.3-cm pixel) to locate 163 headcuts in riparian areas in the Sweetwater subbasin of central Wyoming. We found 1-m-the generally available standard resolution for land management-and 30-cm pixel imagery to be inadequate for headcut identification. We also used Structure-from-Motion models built from ground-acquired imagery to model 18 headcuts from which we measured soil loss of 425-720 m3. Normalized by channel length, this represents a loss of 1.1-1.8 m3 m(-1) channel. Monitoring headcuts, either from ground or aerial imagery, provides an objective indicator of sustainable riparian land management and identifies priority disturbance-mitigation areas. Image-based headcut monitoring must use data on the order of 3.3 cm ground sample distance, or greater resolution, to effectively capture the information needed for accurate assessments of riparian conditions.

  3. Evaluation of a gully headcut retreat model using multitemporal aerial photographs and digital elevation models

    NASA Astrophysics Data System (ADS)

    Campo-Bescós, M. A.; Flores-Cervantes, J. H.; Bras, R. L.; Casalí, J.; Giráldez, J. V.

    2013-12-01

    large fraction of soil erosion in temperate climate systems proceeds from gully headcut growth processes. Nevertheless, headcut retreat is not well understood. Few erosion models include gully headcut growth processes, and none of the existing headcut retreat models have been tested against long-term retreat rate estimates. In this work the headcut retreat resulting from plunge pool erosion in the Channel Hillslope Integrated Landscape Development (CHILD) model is calibrated and compared to long-term evolution measurements of six gullies at the Bardenas Reales, northeast Spain. The headcut retreat module of CHILD was calibrated by adjusting the shape factor parameter to fit the observed retreat and volumetric soil loss of one gully during a 36 year period, using reported and collected field data to parameterize the rest of the model. To test the calibrated model, estimates by CHILD were compared to observations of headcut retreat from five other neighboring gullies. The differences in volumetric soil loss rates between the simulations and observations were less than 0.05 m3 yr-1, on average, with standard deviations smaller than 0.35 m3 yr-1. These results are the first evaluation of the headcut retreat module implemented in CHILD with a field data set. These results also show the usefulness of the model as a tool for simulating long-term volumetric gully evolution due to plunge pool erosion.

  4. Episodic bedrock erosion by gully-head migration, Colorado High Plains, USA

    USGS Publications Warehouse

    Rengers, Francis K.; Tucker, G.E.; Mahan, Shannon

    2016-01-01

    This study explores the frequency of bedrock exposure in a soil-mantled low-relief (i.e. non-mountainous) landscape. In the High Plains of eastern Colorado, gully headcuts are among the few erosional features that will incise through the soil mantle to expose bedrock. We measured the last time of bedrock exposure using optically stimulated luminescence dating of alluvial sediment overlying bedrock in gully headcuts. Our dating suggests that headcuts in adjacent gullies expose bedrock asynchronously, and therefore, the headcuts are unlikely to have been triggered by a base-level drop in the trunk stream. This finding supports the hypothesis that headcuts can develop locally in gullies as a result of focused scour in locations where hydraulic stress during a flash flood is sufficiently high, and/or ground cover is sufficiently weak, to generate a scour hole that undermines vegetation. Alluvium dating also reveals that gullies have been a persistent part of this landscape since the early Holocene. 

  5. Migration and Extension of Solar Active Longitudinal Zones

    NASA Astrophysics Data System (ADS)

    Gyenge, N.; Baranyi, T.; Ludmány, A.

    2014-02-01

    Solar active longitudes show a characteristic migration pattern in the Carrington coordinate system if they can be identified at all. By following this migration, the longitudinal activity distribution around the center of the band can be determined. The half-width of the distribution is found to be varying in Cycles 21 - 23, and in some time intervals it was as narrow as 20 - 30 degrees. It was more extended around a maximum but it was also narrow when the activity jumped to the opposite longitude. Flux emergence exhibited a quasi-periodic variation within the active zone with a period of about 1.3 years. The path of the active-longitude migration does not support the view that it might be associated with the 11-year solar cycle. These results were obtained for a limited time interval of a few solar cycles and, bearing in mind uncertainties of the migration-path definition, are only indicative. For the major fraction of the dataset no systematic active longitudes were found. Sporadic migration of active longitudes was identified only for Cycles 21 - 22 in the northern hemisphere and Cycle 23 in the southern hemisphere.

  6. Controls on the breach geometry and flood hydrograph during overtopping of non-cohesive earthen dams

    USGS Publications Warehouse

    Walder, Joseph S.; Iverson, Richard M.; Godt, Jonathan W.; Logan, Matthew; Solovitz, Stephen A.

    2015-01-01

    Overtopping failure of non-cohesive earthen dams was investigated in 13 large-scale experiments with dams built of compacted, damp, fine-grained sand. Breaching was initiated by cutting a notch across the dam crest and allowing water escaping from a finite upstream reservoir to form its own channel. The channel developed a stepped profile, and upstream migration of the steps, which coalesced into a headcut, led to the establishment of hydraulic control (critical flow) at the channel head, or breach crest, an arcuate erosional feature that functions hydraulically as a weir. Novel photogrammetric methods, along with underwater videography, revealed that the retreating headcut maintained a slope near the angle of friction of the sand, while the cross section at the breach crest maintained a geometrically similar shape through time. That cross-sectional shape was nearly unaffected by slope failures, contrary to the assumption in many models of dam breaching. Flood hydrographs were quite reproducible--for sets of dams ranging in height from 0.55 m to 0.98 m--when the time datum was chosen as the time that the migrating headcut intersected the breach crest. Peak discharge increased almost linearly as a function of initial dam height. Early-time variability between flood hydrographs for nominally identical dams is probably a reflection of subtle experiment-to-experiment differences in groundwater hydrology and the interaction between surface water and groundwater.

  7. A critical discussion on the applicability of Compound Topographic Index (CTI) for predicting ephemeral gully erosion

    NASA Astrophysics Data System (ADS)

    Casalí, Javier; Chahor, Youssef; Giménez, Rafael; Campo-Bescós, Miguel

    2016-04-01

    The so-called Compound Topographic Index (CTI) can be calculated for each grid cell in a DEM and be used to identify potential locations for ephemeral gullies (e. g.) based on land topography (CTI = A.S.PLANC, where A is upstream drainage area, S is local slope and PLANC is planform curvature, a measure of the landscape convergence) (Parker et al., 2007). It can be shown that CTI represents stream power per unit bed area and it considers the major parameters controlling the pattern and intensity of concentrated surface runoff in the field (Parker et al., 2007). However, other key variables controlling e.g. erosion (e. g. e.) such as soil characteristics, land-use and management, are not had into consideration. The critical CTI value (CTIc) "represents the intensity of concentrated overland flow necessary to initiate erosion and channelised flow under a given set of circumstances" (Parker et al., 2007). AnnAGNPS (Annualized Agriculture Non-Point Source) pollution model is an important management tool developed by (USDA) and uses CTI to locate potential ephemeral gullies. Then, and depending on rainfall characteristics of the period simulated by AnnAGNPS, potential e. g. can become "actual", and be simulated by the model accordingly. This paper presents preliminary results and a number of considerations after evaluating the CTI tool in Navarre. CTIc values found are similar to those cited by other authors, and the e. g. networks that on average occur in the area have been located reasonably well. After our experience we believe that it is necessary to distinguish between the CTIc corresponding to the location of headcuts whose migrations originate the e. g. (CTIc1); and the CTIc necessary to represent the location of the gully networks in the watershed (CTIc2), where gully headcuts are located in the upstream end of the gullies. Most scientists only consider one CTIc value, although, from our point of view, the two situations are different. CTIc1 would represent the

  8. Geomorphic processes affecting meadow ecosystems [chapter 3

    Treesearch

    Jerry R. Miller; Dru Germanoski; Mark L. Lord

    2011-01-01

    Three geomorphic processes are of primary concern with respect to the current and future state of wet meadow ecosystems: channel incision, avulsion (the abrupt movement of the channel to a new location on the valley floor), and gully formation. Gully formation often is accompanied by upvalley headcut migration and a phenomenon referred to as "groundwater sapping...

  9. Light Activated Cell Migration in Synthetic Extracellular Matrices

    PubMed Central

    Guo, Qiongyu; Wang, Xiaobo; Tibbitt, Mark W.; Anseth, Kristi S.; Montell, Denise J.; Elisseeff, Jennifer H.

    2012-01-01

    Synthetic extracellular matrices provide a framework in which cells can be exposed to defined physical and biological cues. However no method exists to manipulate single cells within these matrices. It is desirable to develop such methods in order to understand fundamental principles of cell migration and define conditions that support or inhibit cell movement within these matrices. Here, we present a strategy for manipulating individual mammalian stem cells in defined synthetic hydrogels through selective optical activation of Rac, which is an intracellular signaling protein that plays a key role in cell migration. Photoactivated cell migration in synthetic hydrogels depended on mechanical and biological cues in the biomaterial. Real-time hydrogel photodegradation was employed to create geometrically defined channels and spaces in which cells could be photoactivated to migrate. Cell migration speed was significantly higher in the photo-etched channels and cells could easily change direction of movement compared to the bulk hydrogels. PMID:22889487

  10. Fibroblast Activation Protein (FAP) Is Essential for the Migration of Bone Marrow Mesenchymal Stem Cells through RhoA Activation

    PubMed Central

    Chung, Kuei-Min; Hsu, Shu-Ching; Chu, Yue-Ru; Lin, Mei-Yao; Jiaang, Weir-Tong; Chen, Ruey-Hwa; Chen, Xin

    2014-01-01

    Background The ability of human bone marrow mesenchymal stem cells (BM-MSCs) to migrate and localize specifically to injured tissues is central in developing therapeutic strategies for tissue repair and regeneration. Fibroblast activation protein (FAP) is a cell surface serine protease expressed at sites of tissue remodeling during embryonic development. It is also expressed in BM-MSCs, but not in normal tissues or cells. The function of FAP in BM-MSCs is not known. Principal Findings We found that depletion of FAP proteins significantly inhibited the migration of BM-MSCs in a transwell chemotaxis assay. Such impaired migration ability of BM-MSCs could be rescued by re-expressing FAP in these cells. We then demonstrated that depletion of FAP activated intracellular RhoA GTPase. Consistently, inhibition of RhoA activity using a RhoA inhibitor rescued its migration ability. Inhibition of FAP activity with an FAP-specific inhibitor did not affect the activation of RhoA or the migration of BM-MSCs. Furthermore, the inflammatory cytokines interleukin-1beta (IL-1β) and transforming growth factor-beta (TGF-β) upregulated FAP expression, which coincided with better BM-MSC migration. Conclusions Our results indicate FAP plays an important role in the migration of BM-MSCs through modulation of RhoA GTPase activity. The peptidase activity of FAP is not essential for such migration. Cytokines IL-1β and TGF-β upregulate the expression level of FAP and thus enhance BM-MSC migration. PMID:24551161

  11. Fibroblast activation protein (FAP) is essential for the migration of bone marrow mesenchymal stem cells through RhoA activation.

    PubMed

    Chung, Kuei-Min; Hsu, Shu-Ching; Chu, Yue-Ru; Lin, Mei-Yao; Jiaang, Weir-Tong; Chen, Ruey-Hwa; Chen, Xin

    2014-01-01

    The ability of human bone marrow mesenchymal stem cells (BM-MSCs) to migrate and localize specifically to injured tissues is central in developing therapeutic strategies for tissue repair and regeneration. Fibroblast activation protein (FAP) is a cell surface serine protease expressed at sites of tissue remodeling during embryonic development. It is also expressed in BM-MSCs, but not in normal tissues or cells. The function of FAP in BM-MSCs is not known. We found that depletion of FAP proteins significantly inhibited the migration of BM-MSCs in a transwell chemotaxis assay. Such impaired migration ability of BM-MSCs could be rescued by re-expressing FAP in these cells. We then demonstrated that depletion of FAP activated intracellular RhoA GTPase. Consistently, inhibition of RhoA activity using a RhoA inhibitor rescued its migration ability. Inhibition of FAP activity with an FAP-specific inhibitor did not affect the activation of RhoA or the migration of BM-MSCs. Furthermore, the inflammatory cytokines interleukin-1beta (IL-1β) and transforming growth factor-beta (TGF-β) upregulated FAP expression, which coincided with better BM-MSC migration. Our results indicate FAP plays an important role in the migration of BM-MSCs through modulation of RhoA GTPase activity. The peptidase activity of FAP is not essential for such migration. Cytokines IL-1β and TGF-β upregulate the expression level of FAP and thus enhance BM-MSC migration.

  12. Bursts of activity in collective cell migration

    PubMed Central

    Chepizhko, Oleksandr; Giampietro, Costanza; Mastrapasqua, Eleonora; Nourazar, Mehdi; Ascagni, Miriam; Sugni, Michela; Fascio, Umberto; Leggio, Livio; Malinverno, Chiara; Scita, Giorgio; Santucci, Stéphane; Alava, Mikko J.; Zapperi, Stefano; La Porta, Caterina A. M.

    2016-01-01

    Dense monolayers of living cells display intriguing relaxation dynamics, reminiscent of soft and glassy materials close to the jamming transition, and migrate collectively when space is available, as in wound healing or in cancer invasion. Here we show that collective cell migration occurs in bursts that are similar to those recorded in the propagation of cracks, fluid fronts in porous media, and ferromagnetic domain walls. In analogy with these systems, the distribution of activity bursts displays scaling laws that are universal in different cell types and for cells moving on different substrates. The main features of the invasion dynamics are quantitatively captured by a model of interacting active particles moving in a disordered landscape. Our results illustrate that collective motion of living cells is analogous to the corresponding dynamics in driven, but inanimate, systems. PMID:27681632

  13. The annealing helicase and branch migration activities of Drosophila HARP.

    PubMed

    Kassavetis, George A; Kadonaga, James T

    2014-01-01

    HARP (SMARCAL1, MARCAL1) is an annealing helicase that functions in the repair and restart of damaged DNA replication forks through its DNA branch migration and replication fork regression activities. HARP is conserved among metazoans. HARP from invertebrates differs by the absence of one of the two HARP-specific domain repeats found in vertebrates. The annealing helicase and branch migration activity of invertebrate HARP has not been documented. We found that HARP from Drosophila melanogaster retains the annealing helicase activity of human HARP, the ability to disrupt D-loops and to branch migrate Holliday junctions, but fails to regress model DNA replication fork structures. A comparison of human and Drosophila HARP on additional substrates revealed that both HARPs are competent in branch migrating a bidirectional replication bubble composed of either DNA:DNA or RNA:DNA hybrid. Human, but not Drosophila, HARP is also capable of regressing a replication fork structure containing a highly stable poly rG:dC hybrid. Persistent RNA:DNA hybrids in vivo can lead to replication fork arrest and genome instability. The ability of HARP to strand transfer hybrids may signify a hybrid removal function for this enzyme, in vivo.

  14. 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.

  15. Activating the nuclear piston mechanism of 3D migration in tumor cells

    PubMed Central

    2017-01-01

    Primary human fibroblasts have the remarkable ability to use their nucleus like a piston, switching from low- to high-pressure protrusions in response to the surrounding three-dimensional (3D) matrix. Although migrating tumor cells can also change how they migrate in response to the 3D matrix, it is not clear if they can switch between high- and low-pressure protrusions like primary fibroblasts. We report that unlike primary fibroblasts, the nuclear piston is not active in fibrosarcoma cells. Protease inhibition rescued the nuclear piston mechanism in polarized HT1080 and SW684 cells and generated compartmentalized pressure. Achieving compartmentalized pressure required the nucleoskeleton–cytoskeleton linker protein nesprin 3, actomyosin contractility, and integrin-mediated adhesion, consistent with lobopodia-based fibroblast migration. In addition, this activation of the nuclear piston mechanism slowed the 3D movement of HT1080 cells. Together, these data indicate that inhibiting protease activity during polarized tumor cell 3D migration is sufficient to restore the nuclear piston migration mechanism with compartmentalized pressure characteristic of nonmalignant cells. PMID:27998990

  16. Why sub-Saharan African health workers migrate to European countries that do not actively recruit: a qualitative study post-migration.

    PubMed

    Poppe, Annelien; Jirovsky, Elena; Blacklock, Claire; Laxmikanth, Pallavi; Moosa, Shabir; De Maeseneer, Jan; Kutalek, Ruth; Peersman, Wim

    2014-01-01

    Many studies have investigated the migration intentions of sub-Saharan African medical students and health professionals within the context of a legacy of active international recruitment by receiving countries. However, many health workers migrate outside of this recruitment paradigm. This paper aims to explore the reasons for migration of health workers from sub-Saharan Africa to Belgium and Austria; European countries without a history of active recruitment in sub-Saharan Africa. Data were collected using semistructured interviews. Twenty-seven health workers were interviewed about their migration experiences. Included participants were born in sub-Saharan Africa, had trained as health workers in sub-Saharan Africa, and were currently living in Belgium or Austria, though not necessarily currently working as a health professional. Both Austria and Belgium were shown not to be target countries for the health workers, who instead moved there by circumstance, rather than choice. Three principal reasons for migration were reported: 1) educational purposes; 2) political instability or insecurity in their country of origin; and 3) family reunification. In addition, two respondents mentioned medical reasons and, although less explicit, economic factors were also involved in several of the respondents' decision to migrate. These results highlight the importance of the broader economic, social, and political context within which migration decisions are made. Training opportunities proved to be an important factor for migration. A further development and upgrade of primary care might help to counter the common desire to specialize and improve domestic training opportunities.

  17. Agricultural activity shapes the communication and migration patterns in Senegal.

    PubMed

    Martin-Gutierrez, S; Borondo, J; Morales, A J; Losada, J C; Tarquis, A M; Benito, R M

    2016-06-01

    The communication and migration patterns of a country are shaped by its socioeconomic processes. The economy of Senegal is predominantly rural, as agriculture employs over 70% of the labor force. In this paper, we use mobile phone records to explore the impact of agricultural activity on the communication and mobility patterns of the inhabitants of Senegal. We find two peaks of phone calls activity emerging during the growing season. Moreover, during the harvest period, we detect an increase in the migration flows throughout the country. However, religious holidays also shape the mobility patterns of the Senegalese people. Hence, in the light of our results, agricultural activity and religious holidays are the primary drivers of mobility inside the country.

  18. Agricultural activity shapes the communication and migration patterns in Senegal

    NASA Astrophysics Data System (ADS)

    Martin-Gutierrez, S.; Borondo, J.; Morales, A. J.; Losada, J. C.; Tarquis, A. M.; Benito, R. M.

    2016-06-01

    The communication and migration patterns of a country are shaped by its socioeconomic processes. The economy of Senegal is predominantly rural, as agriculture employs over 70% of the labor force. In this paper, we use mobile phone records to explore the impact of agricultural activity on the communication and mobility patterns of the inhabitants of Senegal. We find two peaks of phone calls activity emerging during the growing season. Moreover, during the harvest period, we detect an increase in the migration flows throughout the country. However, religious holidays also shape the mobility patterns of the Senegalese people. Hence, in the light of our results, agricultural activity and religious holidays are the primary drivers of mobility inside the country.

  19. PDK1-mediated activation of MRCKα regulates directional cell migration and lamellipodia retraction

    PubMed Central

    Gagliardi, Paolo Armando; di Blasio, Laura; Puliafito, Alberto; Seano, Giorgio; Sessa, Roberto; Chianale, Federica; Leung, Thomas; Bussolino, Federico

    2014-01-01

    Directional cell migration is of paramount importance in both physiological and pathological processes, such as development, wound healing, immune response, and cancer invasion. Here, we report that 3-phosphoinositide-dependent kinase 1 (PDK1) regulates epithelial directional migration and invasion by binding and activating myotonic dystrophy kinase–related CDC42-binding kinase α (MRCKα). We show that the effect of PDK1 on cell migration does not involve its kinase activity but instead relies on its ability to bind membrane phosphatidylinositol (3,4,5)-trisphosphate. Upon epidermal growth factor (EGF) stimulation, PDK1 and MRCKα colocalize at the cell membrane in lamellipodia. We demonstrate that PDK1 positively modulates MRCKα activity and drives its localization within lamellipodia. Likewise, the retraction phase of lamellipodia is controlled by PDK1 through an MRCKα-dependent mechanism. In summary, we discovered a functional pathway involving PDK1-mediated activation of MRCKα, which links EGF signaling to myosin contraction and directional migration. PMID:25092657

  20. Type I interferon dependence of plasmacytoid dendritic cell activation and migration

    PubMed Central

    Asselin-Paturel, Carine; Brizard, Géraldine; Chemin, Karine; Boonstra, Andre; O'Garra, Anne; Vicari, Alain; Trinchieri, Giorgio

    2005-01-01

    Differential expression of Toll-like receptor (TLR) by conventional dendritic cells (cDCs) and plasmacytoid DC (pDCs) has been suggested to influence the type of immune response induced by microbial pathogens. In this study we show that, in vivo, cDCs and pDCs are equally activated by TLR4, -7, and -9 ligands. Type I interferon (IFN) was important for pDC activation in vivo in response to all three TLR ligands, whereas cDCs required type I IFN signaling only for TLR9- and partially for TLR7-mediated activation. Although TLR ligands induced in situ migration of spleen cDC into the T cell area, spleen pDCs formed clusters in the marginal zone and in the outer T cell area 6 h after injection of TLR9 and TLR7 ligands, respectively. In vivo treatment with TLR9 ligands decreased pDC ability to migrate ex vivo in response to IFN-induced CXCR3 ligands and increased their response to CCR7 ligands. Unlike cDCs, the migration pattern of pDCs required type I IFN for induction of CXCR3 ligands and responsiveness to CCR7 ligands. These data demonstrate that mouse pDCs differ from cDCs in the in vivo response to TLR ligands, in terms of pattern and type I IFN requirement for activation and migration. PMID:15795237

  1. Profilin1 activity in cerebellar granule neurons is required for radial migration in vivo

    PubMed Central

    Kullmann, Jan A; Wickertsheim, Ines; Minnerup, Lara; Costell, Mercedes; Friauf, Eckhard; Rust, Marco B

    2015-01-01

    Neuron migration defects are an important aspect of human neuropathies. The underlying molecular mechanisms of such migration defects are largely unknown. Actin dynamics has been recognized as an important determinant of neuronal migration, and we recently found that the actin-binding protein profilin1 is relevant for radial migration of cerebellar granule neurons (CGN). As the exploited brain-specific mutants lacked profilin1 in both neurons and glial cells, it remained unknown whether profilin1 activity in CGN is relevant for CGN migration in vivo. To test this, we capitalized on a transgenic mouse line that expresses a tamoxifen-inducible Cre variant in CGN, but no other cerebellar cell type. In these profilin1 mutants, the cell density was elevated in the molecular layer, and ectopic CGN occurred. Moreover, 5-bromo-2′-deoxyuridine tracing experiments revealed impaired CGN radial migration. Hence, our data demonstrate the cell autonomous role of profilin1 activity in CGN for radial migration. PMID:25495756

  2. Novel Role for p21-activated Kinase 2 in Thrombin-induced Monocyte Migration*

    PubMed Central

    Gadepalli, Ravisekhar; Kotla, Sivareddy; Heckle, Mark R.; Verma, Shailendra K.; Singh, Nikhlesh K.; Rao, Gadiparthi N.

    2013-01-01

    To understand the role of thrombin in inflammation, we tested its effects on migration of THP-1 cells, a human monocytic cell line. Thrombin induced THP-1 cell migration in a dose-dependent manner. Thrombin induced tyrosine phosphorylation of Pyk2, Gab1, and p115 RhoGEF, leading to Rac1- and RhoA-dependent Pak2 activation. Downstream to Pyk2, Gab1 formed a complex with p115 RhoGEF involving their pleckstrin homology domains. Furthermore, inhibition or depletion of Pyk2, Gab1, p115 RhoGEF, Rac1, RhoA, or Pak2 levels substantially attenuated thrombin-induced THP-1 cell F-actin cytoskeletal remodeling and migration. Inhibition or depletion of PAR1 also blocked thrombin-induced activation of Pyk2, Gab1, p115 RhoGEF, Rac1, RhoA, and Pak2, resulting in diminished THP-1 cell F-actin cytoskeletal remodeling and migration. Similarly, depletion of Gα12 negated thrombin-induced Pyk2, Gab1, p115 RhoGEF, Rac1, RhoA, and Pak2 activation, leading to attenuation of THP-1 cell F-actin cytoskeletal remodeling and migration. These novel observations reveal that thrombin induces monocyte/macrophage migration via PAR1-Gα12-dependent Pyk2-mediated Gab1 and p115 RhoGEF interactions, leading to Rac1- and RhoA-targeted Pak2 activation. Thus, these findings provide mechanistic evidence for the role of thrombin and its receptor PAR1 in inflammation. PMID:24025335

  3. 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.

  4. Association between migration and physical activity of school-age children left behind in rural Mexico.

    PubMed

    Palos-Lucio, Gabriela; Flores, Mario; Rivera-Pasquel, Marta; Salgado-de-Snyder, V Nelly; Monterrubio, Eric; Henao, Santiago; Macias, Nayeli

    2015-01-01

    The purpose of this study was to explore in rural communities of Mexico, the association between physical activity (PA) in school-age children and exposure to migration. We measured PA through a questionnaire validated in school-age children and used in Mexican National Surveys. Migration status was measured as the number of years a family member had been in the US, and the amount of remittances that family member had sent to their household in Mexico. We used multivariable linear regression to measure the association between physical activity and migration. School-age children who had a migrant family member spent less time on PA per day, especially recreation activities, compared to school-age children without the migrating influence. Also, children who belonged to a family that received remittances and their migrant relative lived ≥ 5 years in US were less likely to engage in PA. Exposure to migration may predict reduction in PA in school-age children left behind in Mexican rural communities from the State of Morelos. These findings call for PA-tailored interventions that consider household migration characteristics.

  5. Improvement of Human Keratinocyte Migration by a Redox Active Bioelectric Dressing

    PubMed Central

    Banerjee, Jaideep; Das Ghatak, Piya; Roy, Sashwati; Khanna, Savita; Sequin, Emily K.; Bellman, Karen; Dickinson, Bryan C.; Suri, Prerna; Subramaniam, Vish V.; Chang, Christopher J.; Sen, Chandan K.

    2014-01-01

    Exogenous application of an electric field can direct cell migration and improve wound healing; however clinical application of the therapy remains elusive due to lack of a suitable device and hence, limitations in understanding the molecular mechanisms. Here we report on a novel FDA approved redox-active Ag/Zn bioelectric dressing (BED) which generates electric fields. To develop a mechanistic understanding of how the BED may potentially influence wound re-epithelialization, we direct emphasis on understanding the influence of BED on human keratinocyte cell migration. Mapping of the electrical field generated by BED led to the observation that BED increases keratinocyte migration by three mechanisms: (i) generating hydrogen peroxide, known to be a potent driver of redox signaling, (ii) phosphorylation of redox-sensitive IGF1R directly implicated in cell migration, and (iii) reduction of protein thiols and increase in integrinαv expression, both of which are known to be drivers of cell migration. BED also increased keratinocyte mitochondrial membrane potential consistent with its ability to fuel an energy demanding migration process. Electric fields generated by a Ag/Zn BED can cross-talk with keratinocytes via redox-dependent processes improving keratinocyte migration, a critical event in wound re-epithelialization. PMID:24595050

  6. [Curcumine inhibits migration and invasion of hepatic stellate cells by reducing MMP-2 expression and activity].

    PubMed

    Huang, Jian-xian; Zhu, Bao-he; He, De; Huang, Lin; Hu, Ke; Huang, Bo

    2009-11-01

    To investigate the molecular mechanism of the inhibitory effect of curcumine on the migration and invasion of hepatic stellate cells (HSC). Rat hepatic stellate cells were cultured and activated with ConA. Matrix metalloproteinase-2 (MMP-2) expression and activity was determined by Western blot and gelatin zymography. Migration and invasion of HSC was assessed by wound healing assay and modified Boyden chamber assay. Curcumine reduced the level and activity of MMP-2 expression in activated HSC in a dose-dependent manner. When treated with 25, 50 or 100 micromol/L curcumine, the expression of MMP-2 was reduced by 21.8%+/-5.1%, 65.5%+/-9.2% or 87.9%+/-11.5% (P < 0.05), and the activity of MMP-2 was also significantly reduced by curcumine. Migration and invasion of activated HSC was also inhibited by curcumine in a dose-dependent way. When treated with 25, 50 or 100 micromol/L curcumine, the migration of activated HSC was reduced by 27.5%+/-5.8%, 54.4%+/-7.6% or 67.1%+/-9.3% (P < 0.05), and the invasion of activated HSC was also significantly reduced by curcumine. Curcumine inhibits migration and invasion of activated HSC by reducing MMP-2 expression and activity.

  7. Validating proposed migration equation and parameters' values as a tool to reproduce and predict 137Cs vertical migration activity in Spanish soils.

    PubMed

    Olondo, C; Legarda, F; Herranz, M; Idoeta, R

    2017-04-01

    This paper shows the procedure performed to validate the migration equation and the migration parameters' values presented in a previous paper (Legarda et al., 2011) regarding the migration of 137 Cs in Spanish mainland soils. In this paper, this model validation has been carried out checking experimentally obtained activity concentration values against those predicted by the model. This experimental data come from the measured vertical activity profiles of 8 new sampling points which are located in northern Spain. Before testing predicted values of the model, the uncertainty of those values has been assessed with the appropriate uncertainty analysis. Once establishing the uncertainty of the model, both activity concentration values, experimental versus model predicted ones, have been compared. Model validation has been performed analyzing its accuracy, studying it as a whole and also at different depth intervals. As a result, this model has been validated as a tool to predict 137 Cs behaviour in a Mediterranean environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Periodic sediment shift in migrating ripples influences benthic microbial activity

    NASA Astrophysics Data System (ADS)

    Zlatanović, Sanja; Fabian, Jenny; Mendoza-Lera, Clara; Woodward, K. Benjamin; Premke, Katrin; Mutz, Michael

    2017-06-01

    Migrating bedforms have high levels of particulate organic matter and high rates of pore water exchange, causing them to be proposed as hot spots of carbon turnover in rivers. Yet, the shifting of sediments and associated mechanical disturbance within migrating bedforms, such as ripples, may stress and abrade microbial communities, reducing their activity. In a microcosm experiment, we replicated the mechanical disturbances caused by the periodic sediment shift within ripples under oligotrophic conditions. We assessed the effects on fungal and bacterial biomass ratio (F:B), microbial community respiration (CR), and bacterial production (BCP) and compared with stable undisturbed sediments. Interactions between periodic mechanical disturbance and sediment-associated particulate organic matter (POM) were tested by enriching sediments collected from migrating ripples with different qualities of POM (fish feces, leaf litter fragments and no addition treatments). F:B and BCP were affected by an interaction between mechanical disturbance and POM quality. Fish feces enriched sediments showed increased F:B and BCP compared to sediments with lower POM quality and responded with a decrease of F:B and BCP to sediment disturbance. In the other POM treatments F:B and BCP were not affected by disturbance. Microbial respiration was however reduced by mechanical disturbance to similar low activity levels regardless of POM qualities added, whereas fish feces enriched sediment showed short temporary boost of CR. With the worldwide proliferation of migrating sand ripples due to massive catchment erosion, suppressed mineralization of POM will increasingly affect stream metabolism, downstream transport of POM and carbon cycling from reach to catchment scale.

  9. 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

  10. 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

  11. Tiam1 interaction with the PAR complex promotes talin-mediated Rac1 activation during polarized cell migration

    PubMed Central

    Wang, Shujie; Watanabe, Takashi; Matsuzawa, Kenji; Katsumi, Akira; Kakeno, Mai; Matsui, Toshinori; Ye, Feng; Sato, Kazuhide; Murase, Kiyoko; Sugiyama, Ikuko; Kimura, Kazushi; Mizoguchi, Akira; Ginsberg, Mark H.; Collard, John G.

    2012-01-01

    Migrating cells acquire front-rear polarity with a leading edge and a trailing tail for directional movement. The Rac exchange factor Tiam1 participates in polarized cell migration with the PAR complex of PAR3, PAR6, and atypical protein kinase C. However, it remains largely unknown how Tiam1 is regulated and contributes to the establishment of polarity in migrating cells. We show here that Tiam1 interacts directly with talin, which binds and activates integrins to mediate their signaling. Tiam1 accumulated at adhesions in a manner dependent on talin and the PAR complex. The interactions of talin with Tiam1 and the PAR complex were required for adhesion-induced Rac1 activation, cell spreading, and migration toward integrin substrates. Furthermore, Tiam1 acted with talin to regulate adhesion turnover. Thus, we propose that Tiam1, with the PAR complex, binds to integrins through talin and, together with the PAR complex, thereby regulates Rac1 activity and adhesion turnover for polarized migration. PMID:23071154

  12. Activated Rac1 requires gp130 for Stat3 activation, cell proliferation and migration

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

    Arulanandam, Rozanne; Geletu, Mulu; Feracci, Helene

    2010-03-10

    Rac1 (Rac) is a member of the Rho family of small GTPases which controls cell migration by regulating the organization of actin filaments. Previous results suggested that mutationally activated forms of the Rho GTPases can activate the Signal Transducer and Activator of Transcription-3 (Stat3), but the exact mechanism is a matter of controversy. We recently demonstrated that Stat3 activity of cultured cells increases dramatically following E-cadherin engagement. To better understand this pathway, we now compared Stat3 activity levels in mouse HC11 cells before and after expression of the mutationally activated Rac1 (Rac{sup V12}), at different cell densities. The results revealedmore » for the first time a dramatic increase in protein levels and activity of both the endogenous Rac and Rac{sup V12} with cell density, which was due to inhibition of proteasomal degradation. In addition, Rac{sup V12}-expressing cells had higher Stat3, tyrosine-705 phosphorylation and activity levels at all densities, indicating that Rac{sup V12} is able to activate Stat3. Further examination of the mechanism of Stat3 activation showed that Rac{sup V12} expression caused a surge in mRNA of Interleukin-6 (IL6) family cytokines, known potent Stat3 activators. Knockdown of gp130, the common subunit of this family reduced Stat3 activity, indicating that these cytokines may be responsible for the Stat3 activation by Rac{sup V12}. The upregulation of IL6 family cytokines was required for cell migration and proliferation induced by Rac{sup V12}, as shown by gp130 knockdown experiments, thus demonstrating that the gp130/Stat3 axis represents an essential effector of activated Rac for the regulation of key cellular functions.« less

  13. HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via geranylgeranylation and RhoA activation

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

    Al-Haidari, Amr A.; Syk, Ingvar; Thorlacius, Henrik, E-mail: henrik.thorlacius@med.lu.se

    2014-03-28

    Highlights: • Simvastatin blocked CCL17-induced and CCR4-dependent RhoA activation in HT29 cells. • CCL17/CCR4-mediated migration of colon cancer cells was antagonised by simvastatin. • Cell migration recovered by adding Mevalonate and geranylgeranyl pyrophosphate. • Targeting HMG-CoA reductase might be useful to inhibit colon cancer metastasis. - Abstract: Background: Simvastatin is widely used to lower cholesterol levels in patients with cardiovascular diseases, although accumulating evidence suggests that statins, such as simvastatin, also exert numerous anti-tumoral effects. Aim: The aim of this study was to examine the effect of simvastatin on colon cancer cell migration. Methods: Migration assays were performed to evaluatemore » CCL17-induced colon cancer cell (HT-29) chemotaxis. In vitro tumor growth and apoptosis were assessed using a proliferation assay and annexin V assay, respectively. Active RhoA protein levels in CCL17-stimulated colon cancer cells were quantified using a G-LISA assay. Results: We found that simvastatin dose-dependently decreased CCL17-induced colon cancer cell migration. Simvastatin had no effect on colon cancer cell proliferation or apoptosis. Inhibition of beta chemokine receptor 4, CCR4, reduced CCL17-evoked activation of RhoA in colon cancer cells. Moreover, administration of mevalonate reversed the inhibitory effect of simvastatin on CCL17-induced colon cancer cell migration. Interestingly, co-incubation with geranylgeranyl pyrophosphate (GGPP) antagonized the inhibitory impact of simvastatin on colon cancer cell migration triggered by CCL17. Moreover, we observed that simvastatin decreased CCL17-induced activation of RhoA in colon cancer cells. Administration of mevalonate and GGPP reversed the inhibitory effect of simvastatin on CCL17-provoked RhoA activation in colon cancer cells. Conclusions: Taken together, our findings show for the first time that HMG-CoA reductase regulates CCL17-induced colon cancer cell

  14. An essential role for platelet-activating factor in activating mast cell migration following ultraviolet irradiation

    PubMed Central

    Chacón-Salinas, Rommel; Chen, Limo; Chávez-Blanco, Alma D.; Limón-Flores, Alberto Y.; Ma, Ying; Ullrich, Stephen E.

    2014-01-01

    The UVB (290–320 nm) radiation in sunlight is responsible for inducing skin cancer. Exposure to UV radiation is also immunosuppressive, and the systemic immune suppression induced by UV is a well-recognized risk factor for cancer induction. As UVB radiation is absorbed within the upper layers of the skin, indirect mechanisms must play a role in activating systemic immune suppression. One prominent example is mast cell migration, which from the skin to the draining LN is an essential step in the cascade of events leading to immune suppression. What triggers mast cell migration is not entirely clear. Here, we tested the hypothesis that PAF, a lipid mediator of inflammation produced by the skin in response to UV exposure, is involved. Mast cell-deficient mice (KitW-sh/W-sh) are resistant to the suppressive effect of UV radiation, and reconstituting mast cell-deficient mice with normal bone marrow-derived mast cells restores susceptibility to immunosuppression. However, when mast cells from PAFR−/− mice were used, the reconstituted mice were not susceptible to the suppressive effects of UV. Furthermore, PAFR−/− mice showed impaired UV-induced mast cell migration when compared with WT mice. Finally, injecting PAF into WT mice mimicked the effect of UV irradiation and induced mast cell migration but not in PAFR−/− mice. Our findings indicate that PAFR binding induces mast cells to migrate from the skin to the LNs, where they mediate immune suppression. PMID:24009177

  15. Tropomyosin-related kinase C (TrkC) enhances podocyte migration by ERK-mediated WAVE2 activation.

    PubMed

    Gromnitza, Sascha; Lepa, Carolin; Weide, Thomas; Schwab, Albrecht; Pavenstädt, Hermann; George, Britta

    2018-03-01

    Podocyte malfunction is central to glomerular diseases and is marked by defective podocyte intercellular junctions and actin cytoskeletal dynamics. Podocytes share many morphologic features with neurons, so that similar sets of proteins appear to regulate cell process formation. One such protein is the tropomyosin-related kinase C (TrkC). TrkC deficiency in mice leads to proteinuria as a surrogate of defective kidney filter function. Activation of endogenous TrkC by its ligand neurotrophin-3 resulted in increased podocyte migration-a surrogate of podocyte actin dynamics in vivo. Employing a mutagenesis approach, we found that the Src homologous and collagen-like (Shc) binding site Tyr 516 within the TrkC cytoplasmic domain was necessary for TrkC-induced migration of podocytes. TrkC activation led to a mobility shift of Wiskott-Aldrich syndrome family verprolin-homologous protein (WAVE)-2 which is known to orchestrate Arp2/3 activation and actin polymerization. Chemical inactivation of Erk or mutagenesis of 2 of 4 known Erk target sites within WAVE2, Thr 346 and Ser 351 , abolished the TrkC-induced WAVE2 mobility shift. Knockdown of WAVE2 by shRNA abolished TrkC-induced podocyte migration. In summary, TrkC signals to the podocyte actin cytoskeleton to induce migration by phosphorylating WAVE2 Erk dependently. This signaling mechanism may be important for TrkC-mediated cytoskeletal dynamics in podocyte disease.-Gromnitza, S., Lepa, C., Weide, T., Schwab, A., Pavenstädt, H., George, B. Tropomyosin-related kinase C (TrkC) enhances podocyte migration by ERK-mediated WAVE2 activation.

  16. Differential Expression and Enzymatic Activity of DPPIV/CD26 Affects Migration Ability of Cervical Carcinoma Cells

    PubMed Central

    Beckenkamp, Aline; Willig, Júlia Biz; Santana, Danielle Bertodo; Nascimento, Jéssica; Paccez, Juliano Domiraci; Zerbini, Luiz Fernando; Bruno, Alessandra Nejar; Pilger, Diogo André; Wink, Márcia Rosângela; Buffon, Andréia

    2015-01-01

    Dipeptidyl peptidase IV (DPPIV/CD26) is a transmembrane glycoprotein that inactivates or degrades some bioactive peptides and chemokines. For this reason, it regulates cell proliferation, migration and adhesion, showing its role in cancer processes. This enzyme is found mainly anchored onto the cell membrane, although it also has a soluble form, an enzymatically active isoform. In the present study, we investigated DPPIV/CD26 activity and expression in cervical cancer cell lines (SiHa, HeLa and C33A) and non-tumorigenic HaCaT cells. The effect of the DPPIV/CD26 inhibitor (sitagliptin phosphate) on cell migration and adhesion was also evaluated. Cervical cancer cells and keratinocytes exhibited DPPIV/CD26 enzymatic activity both membrane-bound and in soluble form. DPPIV/CD26 expression was observed in HaCaT, SiHa and C33A, while in HeLa cells it was almost undetectable. We observed higher migratory capacity of HeLa, when compared to SiHa. But in the presence of sitagliptin SiHa showed an increase in migration, indicating that, at least in part, cell migration is regulated by DPPIV/CD26 activity. Furthermore, in the presence of sitagliptin phosphate, SiHa and HeLa cells exhibited a significant reduction in adhesion. However this mechanism seems to be mediated independent of DPPIV/CD26. This study demonstrates, for the first time, the activity and expression of DPPIV/CD26 in cervical cancer cells and the effect of sitagliptin phosphate on cell migration and adhesion. PMID:26222679

  17. Differential Expression and Enzymatic Activity of DPPIV/CD26 Affects Migration Ability of Cervical Carcinoma Cells.

    PubMed

    Beckenkamp, Aline; Willig, Júlia Biz; Santana, Danielle Bertodo; Nascimento, Jéssica; Paccez, Juliano Domiraci; Zerbini, Luiz Fernando; Bruno, Alessandra Nejar; Pilger, Diogo André; Wink, Márcia Rosângela; Buffon, Andréia

    2015-01-01

    Dipeptidyl peptidase IV (DPPIV/CD26) is a transmembrane glycoprotein that inactivates or degrades some bioactive peptides and chemokines. For this reason, it regulates cell proliferation, migration and adhesion, showing its role in cancer processes. This enzyme is found mainly anchored onto the cell membrane, although it also has a soluble form, an enzymatically active isoform. In the present study, we investigated DPPIV/CD26 activity and expression in cervical cancer cell lines (SiHa, HeLa and C33A) and non-tumorigenic HaCaT cells. The effect of the DPPIV/CD26 inhibitor (sitagliptin phosphate) on cell migration and adhesion was also evaluated. Cervical cancer cells and keratinocytes exhibited DPPIV/CD26 enzymatic activity both membrane-bound and in soluble form. DPPIV/CD26 expression was observed in HaCaT, SiHa and C33A, while in HeLa cells it was almost undetectable. We observed higher migratory capacity of HeLa, when compared to SiHa. But in the presence of sitagliptin SiHa showed an increase in migration, indicating that, at least in part, cell migration is regulated by DPPIV/CD26 activity. Furthermore, in the presence of sitagliptin phosphate, SiHa and HeLa cells exhibited a significant reduction in adhesion. However this mechanism seems to be mediated independent of DPPIV/CD26. This study demonstrates, for the first time, the activity and expression of DPPIV/CD26 in cervical cancer cells and the effect of sitagliptin phosphate on cell migration and adhesion.

  18. Lysophospholipids stimulate prostate cancer cell migration via TRPV2 channel activation.

    PubMed

    Monet, Michaël; Gkika, Dimitra; Lehen'kyi, V'yacheslav; Pourtier, Albin; Vanden Abeele, Fabien; Bidaux, Gabriel; Juvin, Véronique; Rassendren, François; Humez, Sandrine; Prevarsakaya, Natalia

    2009-03-01

    The physiological role, the mechanisms of activation, as well as the endogenous regulators for the non-selective cationic channel TRPV2 are not known so far. In the present work we report that endogenous lysophospholipids such as lysophosphatidylcholine (LPC) and lysophosphatidylinositol (LPI) induce a calcium influx via TRPV2 channel. This activation is dependent on the length of the side-chain and the nature of the lysophospholipid head-group. TRPV2-mediated calcium uptake stimulated by LPC and LPI occurred via Gq/Go-protein and phosphatidylinositol-3,4 kinase (PI3,4K) signalling. We have shown that the mechanism of TRPV2 activation induced by LPC and LPI is due to the TRPV2 channel translocation to the plasma membrane. The activation of TRPV2 channel by LPC and LPI leads to an increase in the cell migration of the prostate cancer cell line PC3. We have demonstrated that TRPV2 is directly involved in both steady-state and lysophospholipid-stimulated cancer cell migration. Thus, for the first time, we have identified one of the natural regulators of TRPV2 channel, one of the mechanisms of TRPV2 activation and regulation, as well as its pathophysiological role in cancer.

  19. The role of aquaporin-5 in cancer cell migration: A potential active participant.

    PubMed

    Jensen, Helene H; Login, Frédéric H; Koffman, Jennifer S; Kwon, Tae-Hwan; Nejsum, Lene N

    2016-10-01

    Emerging data identifies the water channel aquaporin-5 as a major player in multiple cancers. Over-expression of aquaporin-5 has been associated with increased metastasis and poor prognosis, suggesting that aquaporin-5 may enhance cancer cell migration. This review aims to highlight the current knowledge and hypothesis regarding downstream signaling partners of aquaporin-5 in relation to cancer cell migration. The molecular mechanisms that link aquaporin-5 to cell migration are not completely understood. Aquaporin-5 may promote cell movement by increasing water uptake into the front of the cell allowing local swelling. Aquaporin-5 may also activate extracellular-regulated kinases, increasing proliferation and potentially stimulating the migration machinery. Thus, further studies are warranted to identify the underlying mechanisms and signaling pathways. This will reveal whether aquaporin-5 and downstream effectors could be targets for developing new cancer therapeutics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Spatial Distribution of Protein Kinase A Activity during Cell Migration Is Mediated by A-kinase Anchoring Protein AKAP Lbc*

    PubMed Central

    Paulucci-Holthauzen, Adriana A.; Vergara, Leoncio A.; Bellot, Larry J.; Canton, David; Scott, John D.; O'Connor, Kathleen L.

    2009-01-01

    Protein kinase A (PKA) has been suggested to be spatially regulated in migrating cells due to its ability to control signaling events that are critical for polarized actin cytoskeletal dynamics. Here, using the fluorescence resonance energy transfer-based A-kinase activity reporter (AKAR1), we find that PKA activity gradients form with the strongest activity at the leading edge and are restricted to the basal surface in migrating cells. The existence of these gradients was confirmed using immunocytochemistry using phospho-PKA substrate antibodies. This observation holds true for carcinoma cells migrating randomly on laminin-1 or stimulated to migrate on collagen I with lysophosphatidic acid. Phosphodiesterase inhibition allows the formation of PKA activity gradients; however, these gradients are no longer polarized. PKA activity gradients are not detected when a non-phosphorylatable mutant of AKAR1 is used, if PKA activity is inhibited with H-89 or protein kinase inhibitor, or when PKA anchoring is perturbed. We further find that a specific A-kinase anchoring protein, AKAP-Lbc, is a major contributor to the formation of these gradients. In summary, our data show that PKA activity gradients are generated at the leading edge of migrating cells and provide additional insight into the mechanisms of PKA regulation of cell motility. PMID:19106088

  1. Role of human pulmonary fibroblast-derived MCP-1 in cell activation and migration in experimental silicosis

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

    Liu, Xueting; Fang, Shencun; Liu, Haijun

    Background: Silicosis is a systemic disease caused by inhaling silicon dioxide (SiO{sub 2}). Phagocytosis of SiO{sub 2} in the lung initiates an inflammatory cascade that results in fibroblast proliferation and migration and subsequent fibrosis. Clinical evidence indicates that the activation of alveolar macrophages by SiO{sub 2} produces rapid and sustained inflammation that is characterized by the generation of monocyte chemotactic protein 1 (MCP-1), which induces fibrosis. Pulmonary fibroblast-derived MCP-1 may play a critical role in fibroblast proliferation and migration. Methods and results: Experiments using primary cultured adult human pulmonary fibroblasts (HPF-a) demonstrated the following results: 1) SiO{sub 2} treatment resultedmore » in the rapid and sustained induction of MCP-1 as well as the elevation of the CC chemokine receptor type 2 (CCR2) protein levels; 2) pretreatment of HPF-a with RS-102895, a specific CCR2 inhibitor, abolished the SiO{sub 2}-induced increase in cell activation and migration in both 2D and 3D culture systems; and 3) RNA interference targeting CCR2 prevented the SiO{sub 2}-induced increase in cell migration. Conclusion: These data demonstrated that the up-regulation of pulmonary fibroblast-derived MCP-1 is involved in pulmonary fibroblast migration induced by SiO{sub 2}. CCR2 was also up-regulated in response to SiO{sub 2}, and this up-regulation facilitated the effect of MCP-1 on fibroblasts. Our study deciphered the link between fibroblast-derived MCP-1 and SiO{sub 2}-induced cell migration. This finding provides novel insight into the potential of MCP-1 in the development of novel therapeutic strategies for silicosis. - Highlights: • Role of pulmonary fibroblast-derived MCP-1 in experimental silicosis was studied. • SiO{sub 2} induced MCP-1 release from cultured human pulmonary fibroblast (HPF-a). • SiO{sub 2} directly activated HPF-a via the MCP-1/CCR2 pathway. • SiO{sub 2} increased HPF-a migration in both 2D

  2. Neural crest specification and migration independently require NSD3-related lysine methyltransferase activity

    PubMed Central

    Jacques-Fricke, Bridget T.; Gammill, Laura S.

    2014-01-01

    Neural crest precursors express genes that cause them to become migratory, multipotent cells, distinguishing them from adjacent stationary neural progenitors in the neurepithelium. Histone methylation spatiotemporally regulates neural crest gene expression; however, the protein methyltransferases active in neural crest precursors are unknown. Moreover, the regulation of methylation during the dynamic process of neural crest migration is unclear. Here we show that the lysine methyltransferase NSD3 is abundantly and specifically expressed in premigratory and migratory neural crest cells. NSD3 expression commences before up-regulation of neural crest genes, and NSD3 is necessary for expression of the neural plate border gene Msx1, as well as the key neural crest transcription factors Sox10, Snail2, Sox9, and FoxD3, but not gene expression generally. Nevertheless, only Sox10 histone H3 lysine 36 dimethylation requires NSD3, revealing unexpected complexity in NSD3-dependent neural crest gene regulation. In addition, by temporally limiting expression of a dominant negative to migratory stages, we identify a novel, direct requirement for NSD3-related methyltransferase activity in neural crest migration. These results identify NSD3 as the first protein methyltransferase essential for neural crest gene expression during specification and show that NSD3-related methyltransferase activity independently regulates migration. PMID:25318671

  3. AMPK activity regulates trafficking of mitochondria to the leading edge during cell migration and matrix invasion

    PubMed Central

    Cunniff, Brian; McKenzie, Andrew J.; Heintz, Nicholas H.; Howe, Alan K.

    2016-01-01

    Cell migration is a complex behavior involving many energy-expensive biochemical events that iteratively alter cell shape and location. Mitochondria, the principal producers of cellular ATP, are dynamic organelles that fuse, divide, and relocate to respond to cellular metabolic demands. Using ovarian cancer cells as a model, we show that mitochondria actively infiltrate leading edge lamellipodia, thereby increasing local mitochondrial mass and relative ATP concentration and supporting a localized reversal of the Warburg shift toward aerobic glycolysis. This correlates with increased pseudopodial activity of the AMP-activated protein kinase (AMPK), a critically important cellular energy sensor and metabolic regulator. Furthermore, localized pharmacological activation of AMPK increases leading edge mitochondrial flux, ATP content, and cytoskeletal dynamics, whereas optogenetic inhibition of AMPK halts mitochondrial trafficking during both migration and the invasion of three-dimensional extracellular matrix. These observations indicate that AMPK couples local energy demands to subcellular targeting of mitochondria during cell migration and invasion. PMID:27385336

  4. CD73 promotes proliferation and migration of human cervical cancer cells independent of its enzyme activity.

    PubMed

    Gao, Zhao-Wei; Wang, Hui-Ping; Lin, Fang; Wang, Xi; Long, Min; Zhang, Hui-Zhong; Dong, Ke

    2017-02-15

    CD73 has both enzymatic and non-enzymatic functions in cells. As a nucleotidase, CD73 plays its enzymatic function by catalyzing the hydrolysis of AMP into adenosine and phosphate. In addition to this, accumulating data have shown that CD73 is a key regulatory molecule involved in cancer growth and metastasis, but this non-enzymatic function of CD73 in cervical cancer cells has not been well studied. CD73 was overexpressed by pcDNA-NT5E expression vector transfection in Hela and SiHa cells. Cell's proliferation and migration were evaluated by MTT and scratch healing assay. The CD73 specific antagonist -APCP was used to inhibit CD73 enzymatic activity. And the effect of APCP on CD73 activity was determined by high performance liquid chromatography (HPLC). Expression level was assessed by qRT-PCR and western blotting. In the present study, we used Hela and SiHa cell lines to evaluate the effects of CD73 on cervical cancer cells proliferation and migration, and further explore the potential regulating mechanisms. Our data showed that CD73 overexpression significantly promoted cervical cancer cells proliferation and migration, and this promotive effect was not reverted by blocking CD73 enzymatic activity, both in Hela and SiHa cells. On the other hand, our data also showed that high concentration of adenosine inhibited Hela and SiHa cells proliferation and migration. These results demonstrated that the promotive effect of CD73 on cervical cancer cells proliferation and migration in vitro was independent from its enzymatic activity (i.e. production of adenosine). Furthermore, the expressions of EGFR, VEGF and Akt were significantly increased in CD73 overexpression Hela and SiHa cells. Our data suggested that CD73 might promote proliferation and migration via potentiating EGFR/Akt and VEGF/Akt pathway, which was independent of CD73 enzyme activity. These data provide a novel insight into the regulating function of CD73 in cancer cells and suggest that CD73 may be

  5. A Low-Level Carbon Dioxide Laser Promotes Fibroblast Proliferation and Migration through Activation of Akt, ERK, and JNK

    PubMed Central

    Shingyochi, Yoshiaki; Kanazawa, Shigeyuki; Tajima, Satoshi; Tanaka, Rica; Mizuno, Hiroshi; Tobita, Morikuni

    2017-01-01

    Background Low-level laser therapy (LLLT) with various types of lasers promotes fibroblast proliferation and migration during the process of wound healing. Although LLLT with a carbon dioxide (CO2) laser was also reported to promote wound healing, the underlying mechanisms at the cellular level have not been previously described. Herein, we investigated the effect of LLLT with a CO2 laser on fibroblast proliferation and migration. Materials and Methods Cultured human dermal fibroblasts were prepared. MTS and cell migration assays were performed with fibroblasts after LLLT with a CO2 laser at various doses (0.1, 0.5, 1.0, 2.0, or 5.0 J/cm2) to observe the effects of LLLT with a CO2 laser on the proliferation and migration of fibroblasts. The non-irradiated group served as the control. Moreover, western blot analysis was performed using fibroblasts after LLLT with a CO2 laser to analyze changes in the activities of Akt, extracellular signal-regulated kinase (ERK), and Jun N-terminal kinase (JNK), which are signaling molecules associated with cell proliferation and migration. Finally, the MTS assay, a cell migration assay, and western blot analysis were performed using fibroblasts treated with inhibitors of Akt, ERK, or JNK before LLLT with a CO2 laser. Results In MTS and cell migration assays, fibroblast proliferation and migration were promoted after LLLT with a CO2 laser at 1.0 J/cm2. Western blot analysis revealed that Akt, ERK, and JNK activities were promoted in fibroblasts after LLLT with a CO2 laser at 1.0 J/cm2. Moreover, inhibition of Akt, ERK, or JNK significantly blocked fibroblast proliferation and migration. Conclusions These findings suggested that LLLT with a CO2 laser would accelerate wound healing by promoting the proliferation and migration of fibroblasts. Activation of Akt, ERK, and JNK was essential for CO2 laser-induced proliferation and migration of fibroblasts. PMID:28045948

  6. Effects of surface active agents on DNAPL migration and distribution in saturated porous media.

    PubMed

    Cheng, Zhou; Gao, Bin; Xu, Hongxia; Sun, Yuanyuan; Shi, Xiaoqing; Wu, Jichun

    2016-11-15

    Dissolved surface active agents such as surfactant and natural organic matter can affect the distribution and fate of dense nonaqueous liquids (DNAPLs) in soil and groundwater systems. This work investigated how two common groundwater surface active agents, humic acid (HA) and Tween 80, affected tetrachloroethylene (PCE) migration and source zone architecture in saturated porous media under environmentally relevant conditions. Batch experiments were first conducted to measure the contact angles and interfacial tensions (IFT) between PCE and quartz surface in water containing different amount of surface active agents. Results showed that the contact angle increased and IFT decreased with concentration of surface active agent increasing, and Tween 80 was much more effective than HA. Five 2-D flow cell experiments were then conducted. Correspondingly, Tween 80 showed strong effects on the migration and distribution of PCE in the porous media due to its ability to change the medium wettability from water-wet into intermediate/NAPL-wet. The downward migration velocities of the PCE in three Tween 80 cells were slower than those in the other two cells. In addition, the final saturation of the PCE in the cells containing surface active agents was higher than that in the water-only cell. Results from this work indicate that the presence of surface active agents in groundwater may strongly affect the fate and distribution of DNAPL through altering porous medium wettability. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Morus alba and active compound oxyresveratrol exert anti-inflammatory activity via inhibition of leukocyte migration involving MEK/ERK signaling.

    PubMed

    Chen, Yi-Ching; Tien, Yin-Jing; Chen, Chun-Houh; Beltran, Francesca N; Amor, Evangeline C; Wang, Ran-Juh; Wu, Den-Jen; Mettling, Clément; Lin, Yea-Lih; Yang, Wen-Chin

    2013-02-23

    Morus alba has long been used in traditional Chinese medicine to treat inflammatory diseases; however, the scientific basis for such usage and the mechanism of action are not well understood. This study investigated the action of M. alba on leukocyte migration, one key step in inflammation. Gas chromatography-mass spectrometry (GC-MS) and cluster analyses of supercritical CO2 extracts of three Morus species were performed for chemotaxonomy-aided plant authentication. Phytochemistry and CXCR4-mediated chemotaxis assays were used to characterize the chemical and biological properties of M. alba and its active compound, oxyresveratrol. fluorescence-activated cell sorting (FACS) and Western blot analyses were conducted to determine the mode of action of oxyresveratrol. Chemotaxonomy was used to help authenticate M. alba. Chemotaxis-based isolation identified oxyresveratrol as an active component in M. alba. Phytochemical and chemotaxis assays showed that the crude extract, ethyl acetate fraction and oxyresveratrol from M. alba suppressed cell migration of Jurkat T cells in response to SDF-1. Mechanistic study indicated that oxyresveratrol diminished CXCR4-mediated T-cell migration via inhibition of the MEK/ERK signaling cascade. A combination of GC-MS and cluster analysis techniques are applicable for authentication of the Morus species. Anti-inflammatory benefits of M. alba and its active compound, oxyresveratrol, may involve the inhibition of CXCR-4-mediated chemotaxis and MEK/ERK pathway in T and other immune cells.

  8. High targeted migration of human mesenchymal stem cells grown in hypoxia is associated with enhanced activation of RhoA

    PubMed Central

    2013-01-01

    Introduction A feature which makes stem cells promising candidates for cell therapy is their ability to migrate effectively into damaged or diseased tissues. Recent reports demonstrated the increased motility of human mesenchymal stem cells (hMSC) grown under hypoxic conditions compared to normoxic cells. However, the directional migration of hMSC cultured in hypoxia has not been investigated. In this study we examined the in vitro transmembrane migration of hMSC permanently cultured in hypoxia in response to various cytokines. We also studied the involvement of RhoA, a molecule believed to play an essential role in the migration of MSC via reorganization of the cytoskeleton. Methods We compared the directional migration of human hMSCs grown permanently under normal (21%, normoxic) and low O2 (5%, hypoxic) conditions until passage 4 using an in vitro transmembrane migration assay. A series of 17 cytokines was used to induce chemotaxis. We also compared the level of GTP-bound RhoA in the cell extracts of calpeptin-activated hypoxic and normoxic hMSC. Results We found that hMSC cultured in hypoxia demonstrate markedly higher targeted migration activity compared to normoxic cells, particularly towards wound healing cytokines, including those found in ischemic and myocardial infarction. We also demonstrated for the first time that hMSC are dramatically more sensitive to activation of RhoA. Conclusions The results of this study indicate that high directional migration of hMSCs permanently grown in hypoxia is associated with the enhanced activation of RhoA. The enhanced migratory capacity of hypoxic hMSC would further suggest their potential advantages for clinical applications. PMID:23295150

  9. 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.

  10. Modulation of Female Genital Tract-Derived Dendritic Cell Migration and Activation in Response to Inflammatory Cytokines and Toll-Like Receptor Agonists.

    PubMed

    Shey, Muki S; Maharaj, Niren; Archary, Derseree; Ngcapu, Sinaye; Garrett, Nigel; Abdool Karim, Salim; Passmore, Jo-Ann S

    2016-01-01

    HIV transmission across the genital mucosa is a major mode of new HIV infections in women. The probability of infection may be influenced by several factors including recruitment and activation of HIV target cells, such as dendritic cells (DCs) and cytokine production, associated with genital inflammation. We evaluated the role of inflammatory cytokines and TLR signaling in migration and activation of genital tract DCs in the human cervical explant model. Hysterectomy tissues from 10 HIV-negative and 7 HIV-positive donor women were separated into ecto- and endocervical explants, and incubated with inflammatory cytokines (TNF-α, IL-1β, IL-8, MIP-1β) or agonists for TLR4 (LPS), TLR2/1 (PAM3) and TLR7/8 (R848). Migration (frequency) and activation (HLA-DR expression) of myeloid and plasmacytoid DCs and Langerhans cells were measured by flow cytometry. We observed that cytokines, LPS and PAM3 induced activation of migrating myeloid and plasmacytoid DCs. LPS induced a 3.6 fold lower levels of migration of plasmacytoid DCs from HIV-infected women compared with HIV-uninfected women (median activation indices of 2.932 vs 0.833). There was however a 4.5 fold increase in migration of Langerhans cells in HIV-infected compared with HIV-uninfected women in response to cytokines (median activation indices of 3.539 vs 0.77). Only TLR agonists induced migration and activation of DCs from endocervical explants. Hormonal contraception use was associated with an increase in activation of DC subsets in the endo and ectocervical explants. We conclude that inflammatory signals in the female genital tract induced DC migration and activation, with possible important implications for HIV susceptibility of cervical tissues.

  11. p53/PUMA expression in human pulmonary fibroblasts mediates cell activation and migration in silicosis.

    PubMed

    Wang, Wei; Liu, Haijun; Dai, Xiaoniu; Fang, Shencun; Wang, Xingang; Zhang, Yingming; Yao, Honghong; Zhang, Xilong; Chao, Jie

    2015-11-18

    Phagocytosis of SiO2 into the lung causes an inflammatory cascade that results in fibroblast proliferation and migration, followed by fibrosis. Clinical evidence has indicated that the activation of alveolar macrophages by SiO2 produces rapid and sustained inflammation characterized by the generation of monocyte chemotactic protein 1, which, in turn, induces fibrosis. However, the details of events downstream of monocyte chemotactic protein 1 activity in pulmonary fibroblasts remain unclear. Here, to elucidate the role of p53 in fibrosis induced by silica, both the upstream molecular mechanisms and the functional effects on cell proliferation and migration were investigated. Experiments using primary cultured adult human pulmonary fibroblasts led to the following results: 1) SiO2 treatment resulted in a rapid and sustained increase in p53 and PUMA protein levels; 2) the MAPK and PI3K pathways were involved in the SiO2-induced alteration of p53 and PUMA expression; and 3) RNA interference targeting p53 and PUMA prevented the SiO2-induced increases in fibroblast activation and migration. Our study elucidated a link between SiO2-induced p53/PUMA expression in fibroblasts and cell migration, thereby providing novel insight into the potential use of p53/PUMA in the development of novel therapeutic strategies for silicosis treatment.

  12. Leader cells regulate collective cell migration via Rac activation in the downstream signaling of integrin β1 and PI3K.

    PubMed

    Yamaguchi, Naoya; Mizutani, Takeomi; Kawabata, Kazushige; Haga, Hisashi

    2015-01-07

    Collective cell migration plays a crucial role in several biological processes, such as embryonic development, wound healing, and cancer metastasis. Here, we focused on collectively migrating Madin-Darby Canine Kidney (MDCK) epithelial cells that follow a leader cell on a collagen gel to clarify the mechanism of collective cell migration. First, we removed a leader cell from the migrating collective with a micromanipulator. This then caused disruption of the cohesive migration of cells that followed in movement, called "follower" cells, which showed the importance of leader cells. Next, we observed localization of active Rac, integrin β1, and PI3K. These molecules were clearly localized in the leading edge of leader cells, but not in follower cells. Live cell imaging using active Rac and active PI3K indicators was performed to elucidate the relationship between Rac, integrin β1, and PI3K. Finally, we demonstrated that the inhibition of these molecules resulted in the disruption of collective migration. Our findings not only demonstrated the significance of a leader cell in collective cell migration, but also showed that Rac, integrin β1, and PI3K are upregulated in leader cells and drive collective cell migration.

  13. [Glyburide prevents pulmonary artery smooth muscle cell proliferation and migration via inhibiting NLRP3 activation].

    PubMed

    Liu, Y F; Wang, W; Liu, T; Zhang, W; Liu, J; Wang, J

    2017-06-12

    Objective: To investigate whether glyburide prevents platelet-derived growth factor (PDGF) induced pulmonary artery smooth muscle cells(PASMCs) proliferation and migration via inhibiting nucleotide binding domain leucine-rich repeat-containing receptors protein 3(NLRP3) inflammasome activation. Methods: PASMCs were divided into 4 groups: control group, glyburide group, PDGF group and PDGF+ glyburide group. Cell proliferation and migration were assessed by MTT and Transwell respectively. The NLRP3 inflammasome activation was assessed by Western blot. Results: Compared with the control group, the protein expressions of NLRP3, caspase-1 and IL-1β in PASMCs were increased to (1.38±0.09, t =3.998, P <0.001), (1.32±0.1, t =3.268, P <0.01)and(1.43±0.19) ( t =2.096, P <0.05) folds in the PDGF group. Glyburide had no effect on NLRP3, caspase-1 and IL-1β expression as compared with the control group, while the NLRP3, caspase-1 and IL-1β were decreased by(20.49±7.6)% ( t =2.862, P <0.01), (32.94±3.44)% ( t =4.154, P <0.001) and (24.67±5.29)% ( t =2.335, P <0.05) in the PDGF+ glyburide group, respectively, as compared with the PDGF group. Compared with the control group, the PASMCs proliferation and migration in the PDGF group were significantly increased to (1.74±0.23, t =4.717, P <0.001) and (3.12±0.8, t =5.249, P <0.001) folds, respectively. Compared with the control group, glyburide had no effect on PASMCs proliferation and migration. In PDGF+ glyburide group, cell proliferation was reduced by (50.5±4.27)% ( t =4.462, P <0.001) and cell migration count was lower than in the PDGF group (42.77±2.84)% ( t =3.716, P <0.001). Conclusion: Glyburide could ameliorate PDGF-induced PASMCs proliferation and migration by inhibiting NLRP3 inflammasome activation.

  14. AMP-activated protein kinase activation mediates CCL3-induced cell migration and matrix metalloproteinase-2 expression in human chondrosarcoma

    PubMed Central

    2013-01-01

    Chemokine (C-C motif) ligand 3 (CCL3), also known as macrophage inflammatory protein-1α, is a cytokine involved in inflammation and activation of polymorphonuclear leukocytes. CCL3 has been detected in infiltrating cells and tumor cells. Chondrosarcoma is a highly malignant tumor that causes distant metastasis. However, the effect of CCL3 on human chondrosarcoma metastasis is still unknown. Here, we found that CCL3 increased cellular migration and expression of matrix metalloproteinase (MMP)-2 in human chondrosarcoma cells. Pre-treatment of cells with the MMP-2 inhibitor or transfection with MMP-2 specific siRNA abolished CCL3-induced cell migration. CCL3 has been reported to exert its effects through activation of its specific receptor, CC chemokine receptor 5 (CCR5). The CCR5 and AMP-activated protein kinase (AMPK) inhibitor or siRNA also attenuated CCL3-upregulated cell motility and MMP-2 expression. CCL3-induced expression of MMP-2 and migration were also inhibited by specific inhibitors, and inactive mutants of AMPK, p38 mitogen activated protein kinase (p38 or p38-MAPK), and nuclear factor κB (NF-κB) cascades. On the other hand, CCL3 treatment demonstrably activated AMPK, p38, and NF-κB signaling pathways. Furthermore, the expression levels of CCL3, CCR5, and MMP-2 were correlated in human chondrosarcoma specimens. Taken together, our results indicate that CCL3 enhances the migratory ability of human chondrosarcoma cells by increasing MMP-2 expression via the CCR5, AMPK, p38, and NF-κB pathways. PMID:24047437

  15. Study on flavonoid migration from active low-density polyethylene film into aqueous food simulants.

    PubMed

    Zhang, Shuangling; Zhao, Haiyan

    2014-08-15

    The migration of flavonoids from low-density polyethylene (LDPE) film (0.4%, w/w) to aqueous food simulants over 16 weeks at 0, 15, and 30 °C was investigated. The migration amount of total flavonoids was calculated based on the rutin contents determined by high-performance liquid chromatography (HPLC). Diffusion and partition coefficients, along with the activation energy (Ea) were calculated based on Fick's second law. The results showed that the migration of flavonoids was influenced by temperature, time and the simulants. The Ea values for flavonoid diffusion were 49.2, 55.9, and 25.8 kJ mol(-1) in distilled water, 4% acetic acid and 30% ethanol, respectively. This study indicated that the flavonoids in LDPE film easily migrated into food simulants; and this behaviour was related to the low Ea values of flavonoid diffusion, especially in ethanol at 0-30 °C, when the antioxidants were released from the film. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. TWEAK promotes migration and invasion in MEFs through a mechanism dependent on ERKs activation and Fibulin 3 down-regulation.

    PubMed

    Sequera, Celia; Vázquez-Carballo, Ana; Arechederra, María; Fernández-Veledo, Sonia; Porras, Almudena

    2018-02-01

    TWEAK regulates multiple physio-pathological processes in fibroblasts such as fibrosis. It also induces migration and invasion in tumors and it can activate p38 MAPK in various cell types. Moreover, p38α MAPK promotes migration and invasion in several cancer cells types and in mouse embryonic fibroblasts (MEFs). However, it remains unknown if TWEAK could promote migration in fibroblasts and whether p38α MAPK might play a role. Our results reveal that TWEAK activates ERKs, Akt, and p38α/β MAPKs and reduces secreted Fibulin 3 in MEFs. TWEAK also increases migration and invasion in wt and p38α deficient MEFs, which indicates that p38α MAPK is not required to mediate these effects. In contrast, ERKs inhibition significantly decreases TWEAK-induced migration and Fibulin 3 knock-down mimics TWEAK effect. These results indicate that both ERKs activation and Fibulin 3 down-regulation would contribute to mediate TWEAK pro-migratory effect. In fact, the additional regulation of ERKs and/or p38β as a consequence of Fibulin 3 decrease might be also involved in the pro-migratory effect of TWEAK in MEFs. In conclusion, our studies uncover novel mechanisms by which TWEAK would favor tissue repair by promoting fibroblasts migration. © 2017 Wiley Periodicals, Inc.

  17. CAPN 7 promotes the migration and invasion of human endometrial stromal cell by regulating matrix metalloproteinase 2 activity.

    PubMed

    Liu, Hongyu; Jiang, Yue; Jin, Xiaoyan; Zhu, Lihua; Shen, Xiaoyue; Zhang, Qun; Wang, Bin; Wang, Junxia; Hu, Yali; Yan, Guijun; Sun, Haixiang

    2013-07-15

    Matrix metalloproteinase 2 (MMP-2) has been reported to be an important regulator of cell migration and invasion through degradation of the extracellular matrix (ECM) in many diseases, such as cancer and endometriosis. Here, we found calcium-activated neutral protease 7 (CAPN 7) expression was markedly upregulated in the eutopic endometrium and endometrial stromal cells of women diagnosed with endometriosis. Our studies were carried out to detect the effects of CAPN 7 on human endometrial stromal cell (hESC) migration and invasion. Western blotting and quantitative real-time PCR were used to detect the expression of CAPN 7 in endometriosis patients and normal fertile women. Scratch-wound-healing and invasion chamber assay were used to investigate the role of CAPN 7 in hESC migration and invasion. Western blotting, quantitative real-time PCR and zymography were carried out to detect the effect of CAPN 7 on the expressions and activity of MMP-2. CAPN 7 was markedly up-regulated in endometriosis, thereby promoting the migration and invasion of hESC. CAPN 7 overexpression led to increased expression of MMP-2 and tissue inhibitor of metalloproteinases 2 (TIMP-2); CAPN 7 knockdown reversed these changes. CAPN 7 increased MMP-2 activity by increasing the ratio of MMP-2 to TIMP-2. We also found that OA-Hy (an MMP-2 inhibitor) decreased the effects of CAPN 7 overexpression on hESC migration and invasion by approximately 50% and 55%, respectively. Additionally, a coimmunoprecipitation assay demonstrated that CAPN 7 interacted with activator protein 2α (AP-2α): an important transcription factor of MMP-2. CAPN 7 promotes hESC migration and invasion by increasing the activity of MMP-2 via an increased ratio of MMP-2 to TIMP-2.

  18. CAPN 7 promotes the migration and invasion of human endometrial stromal cell by regulating matrix metalloproteinase 2 activity

    PubMed Central

    2013-01-01

    Background Matrix metalloproteinase 2 (MMP-2) has been reported to be an important regulator of cell migration and invasion through degradation of the extracellular matrix (ECM) in many diseases, such as cancer and endometriosis. Here, we found calcium-activated neutral protease 7 (CAPN 7) expression was markedly upregulated in the eutopic endometrium and endometrial stromal cells of women diagnosed with endometriosis. Our studies were carried out to detect the effects of CAPN 7 on human endometrial stromal cell (hESC) migration and invasion. Methods Western blotting and quantitative real-time PCR were used to detect the expression of CAPN 7 in endometriosis patients and normal fertile women. Scratch-wound-healing and invasion chamber assay were used to investigate the role of CAPN 7 in hESC migration and invasion. Western blotting, quantitative real-time PCR and zymography were carried out to detect the effect of CAPN 7 on the expressions and activity of MMP-2. Results CAPN 7 was markedly up-regulated in endometriosis, thereby promoting the migration and invasion of hESC. CAPN 7 overexpression led to increased expression of MMP-2 and tissue inhibitor of metalloproteinases 2 (TIMP-2); CAPN 7 knockdown reversed these changes. CAPN 7 increased MMP-2 activity by increasing the ratio of MMP-2 to TIMP-2. We also found that OA-Hy (an MMP-2 inhibitor) decreased the effects of CAPN 7 overexpression on hESC migration and invasion by approximately 50% and 55%, respectively. Additionally, a coimmunoprecipitation assay demonstrated that CAPN 7 interacted with activator protein 2α (AP-2α): an important transcription factor of MMP-2. Conclusions CAPN 7 promotes hESC migration and invasion by increasing the activity of MMP-2 via an increased ratio of MMP-2 to TIMP-2. PMID:23855590

  19. Monitoring channel head erosion processes in response to an artificially induced abrupt base level change using time-lapse photography

    NASA Astrophysics Data System (ADS)

    Nichols, M. H.; Nearing, M.; Hernandez, M.; Polyakov, V. O.

    2016-07-01

    Gullies that terminate at a vertical-wall are ubiquitous throughout arid and semiarid regions. Multi-year assessments of gully evolution and headcut advance are typically accomplished using traditional ground surveys and aerial photographs, with much recent research focused on integrating data collected at very high spatial resolutions using new techniques such as aerial surveys with blimps or kites and ground surveys with LiDar scanners. However, knowledge of specific processes that drive headcut advance is limited due to inadequate observation and documentation of flash floods and subsequent erosion that can occur at temporal resolutions not captured through repeat surveys. This paper presents a method for using very-high temporal resolution ground-based time-lapse photography to capture short-duration flash floods and gully head evolution in response. In 2004, a base level controlling concrete weir was removed from the outlet of a 1.29 ha semiarid headwater drainage on the Walnut Gulch Experimental Watershed in southeastern Arizona, USA. During the ten year period from 2004 to 2014 the headcut migrated upchannel a total of 14.5 m reducing the contributing area at the headwall by 9.5%. Beginning in July 2012, time-lapse photography was employed to observe event scale channel evolution dynamics. The most frequent erosion processes observed during three seasons of time-lapse photography were plunge pool erosion and mass wasting through sidewall or channel headwall slumping that occurred during summer months. Geomorphic change during the ten year period was dominated by a single piping event in August 2014 that advanced the channel head 7.4 m (51% of the overall advance) and removed 11.3 m3 of sediment. High temporal resolution time-lapse photography was critical for identifying subsurface erosion processes, in the absence of time-lapse images piping would not have been identified as an erosion mechanism responsible for advancing the gully headwall at this site.

  20. Morus alba and active compound oxyresveratrol exert anti-inflammatory activity via inhibition of leukocyte migration involving MEK/ERK signaling

    PubMed Central

    2013-01-01

    Background Morus alba has long been used in traditional Chinese medicine to treat inflammatory diseases; however, the scientific basis for such usage and the mechanism of action are not well understood. This study investigated the action of M. alba on leukocyte migration, one key step in inflammation. Methods Gas chromatography-mass spectrometry (GC-MS) and cluster analyses of supercritical CO2 extracts of three Morus species were performed for chemotaxonomy-aided plant authentication. Phytochemistry and CXCR4-mediated chemotaxis assays were used to characterize the chemical and biological properties of M. alba and its active compound, oxyresveratrol. fluorescence-activated cell sorting (FACS) and Western blot analyses were conducted to determine the mode of action of oxyresveratrol. Results Chemotaxonomy was used to help authenticate M. alba. Chemotaxis-based isolation identified oxyresveratrol as an active component in M. alba. Phytochemical and chemotaxis assays showed that the crude extract, ethyl acetate fraction and oxyresveratrol from M. alba suppressed cell migration of Jurkat T cells in response to SDF-1. Mechanistic study indicated that oxyresveratrol diminished CXCR4-mediated T-cell migration via inhibition of the MEK/ERK signaling cascade. Conclusions A combination of GC-MS and cluster analysis techniques are applicable for authentication of the Morus species. Anti-inflammatory benefits of M. alba and its active compound, oxyresveratrol, may involve the inhibition of CXCR-4-mediated chemotaxis and MEK/ERK pathway in T and other immune cells. PMID:23433072

  1. Activation of cell-surface proteases promotes necroptosis, inflammation and cell migration.

    PubMed

    Cai, Zhenyu; Zhang, Anling; Choksi, Swati; Li, Weihua; Li, Tao; Zhang, Xue-Min; Liu, Zheng-Gang

    2016-08-01

    Necroptosis is a programmed, caspase-independent cell death that is morphologically similar to necrosis. TNF-induced necroptosis is mediated by receptor-interacting protein kinases, RIP1 and RIP3, and the mixed lineage kinase domain-like (MLKL). After being phosphorylated by RIP3, MLKL is translocated to the plasma membrane and mediates necroptosis. However, the execution of necroptosis and its role in inflammation and other cellular responses remain largely elusive. In this study, we report that MLKL-mediated activation of cell-surface proteases of the a disintegrin and metalloprotease (ADAM) family promotes necroptosis, inflammation and cell migration. ADAMs are specifically activated at the early stage of necroptosis when MLKL is phosphorylated and translocated to the cell plasma membrane. Activation of ADAMs induces ectodomain shedding of diverse cell-surface proteins including adhesion molecules, receptors, growth factors and cytokines. Importantly, the shedding of cell-surface proteins disrupts cell adhesion and accelerates necroptosis, while the soluble fragments of the cleaved proteins trigger the inflammatory responses. We also demonstrate that the shedding of E-cadherin ectodomain from necroptotic cells promotes cell migration. Thus, our study provides a novel mechanism of necroptosis-induced inflammation and new insights into the physiological and pathological functions of this unique form of cell death.

  2. Activation of cell-surface proteases promotes necroptosis, inflammation and cell migration

    PubMed Central

    Cai, Zhenyu; Zhang, Anling; Choksi, Swati; Li, Weihua; Li, Tao; Zhang, Xue-Min; Liu, Zheng-Gang

    2016-01-01

    Necroptosis is a programmed, caspase-independent cell death that is morphologically similar to necrosis. TNF-induced necroptosis is mediated by receptor-interacting protein kinases, RIP1 and RIP3, and the mixed lineage kinase domain-like (MLKL). After being phosphorylated by RIP3, MLKL is translocated to the plasma membrane and mediates necroptosis. However, the execution of necroptosis and its role in inflammation and other cellular responses remain largely elusive. In this study, we report that MLKL-mediated activation of cell-surface proteases of the a disintegrin and metalloprotease (ADAM) family promotes necroptosis, inflammation and cell migration. ADAMs are specifically activated at the early stage of necroptosis when MLKL is phosphorylated and translocated to the cell plasma membrane. Activation of ADAMs induces ectodomain shedding of diverse cell-surface proteins including adhesion molecules, receptors, growth factors and cytokines. Importantly, the shedding of cell-surface proteins disrupts cell adhesion and accelerates necroptosis, while the soluble fragments of the cleaved proteins trigger the inflammatory responses. We also demonstrate that the shedding of E-cadherin ectodomain from necroptotic cells promotes cell migration. Thus, our study provides a novel mechanism of necroptosis-induced inflammation and new insights into the physiological and pathological functions of this unique form of cell death. PMID:27444869

  3. Leader cells regulate collective cell migration via Rac activation in the downstream signaling of integrin β1 and PI3K

    PubMed Central

    Yamaguchi, Naoya; Mizutani, Takeomi; Kawabata, Kazushige; Haga, Hisashi

    2015-01-01

    Collective cell migration plays a crucial role in several biological processes, such as embryonic development, wound healing, and cancer metastasis. Here, we focused on collectively migrating Madin-Darby Canine Kidney (MDCK) epithelial cells that follow a leader cell on a collagen gel to clarify the mechanism of collective cell migration. First, we removed a leader cell from the migrating collective with a micromanipulator. This then caused disruption of the cohesive migration of cells that followed in movement, called “follower” cells, which showed the importance of leader cells. Next, we observed localization of active Rac, integrin β1, and PI3K. These molecules were clearly localized in the leading edge of leader cells, but not in follower cells. Live cell imaging using active Rac and active PI3K indicators was performed to elucidate the relationship between Rac, integrin β1, and PI3K. Finally, we demonstrated that the inhibition of these molecules resulted in the disruption of collective migration. Our findings not only demonstrated the significance of a leader cell in collective cell migration, but also showed that Rac, integrin β1, and PI3K are upregulated in leader cells and drive collective cell migration. PMID:25563751

  4. 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

  5. Spatial control of active CDC-42 during collective migration of hypodermal cells in Caenorhabditis elegans.

    PubMed

    Ouellette, Marie-Hélène; Martin, Emmanuel; Lacoste-Caron, Germain; Hamiche, Karim; Jenna, Sarah

    2016-08-01

    Collective epithelial cell migration requires the maintenance of cell-cell junctions while enabling the generation of actin-rich protrusions at the leading edge of migrating cells. Ventral enclosure of Caenorhabditis elegans embryos depends on the collective migration of anterior-positioned leading hypodermal cells towards the ventral midline where they form new junctions with their contralateral neighbours. In this study, we characterized the zygotic function of RGA-7/SPV-1, a CDC-42/Cdc42 and RHO-1/RhoA-specific Rho GTPase-activating protein, which controls the formation of actin-rich protrusions at the leading edge of leading hypodermal cells and the formation of new junctions between contralateral cells. We show that RGA-7 controls these processes in an antagonistic manner with the CDC-42's effector WSP-1/N-WASP and the CDC-42-binding proteins TOCA-1/2/TOCA1. RGA-7 is recruited to spatially distinct locations at junctions between adjacent leading cells, where it promotes the accumulation of clusters of activated CDC-42. It also inhibits the spreading of these clusters towards the leading edge of the junctions and regulates their accumulation and distribution at new junctions formed between contralateral leading cells. Our study suggests that RGA-7 controls collective migration and junction formation between epithelial cells by spatially restricting active CDC-42 within cell-cell junctions. © The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

  6. Scutellarin suppresses migration and invasion of human hepatocellular carcinoma by inhibiting the STAT3/Girdin/Akt activity.

    PubMed

    Ke, Yang; Bao, Tianhao; Wu, Xuesong; Tang, Haoran; Wang, Yan; Ge, Jiayun; Fu, Bimang; Meng, Xu; Chen, Li; Zhang, Cheng; Tan, Yuqi; Chen, Haotian; Guo, Zhitang; Ni, Fan; Lei, Xuefen; Shi, Zhitian; Wei, Dong; Wang, Lin

    2017-01-29

    Scutellarin is an active flavone from Erigeron breviscapine (vant) Hand Mass. This study aimed to investigate the potential role of scutellarin in migration and invasion of human hepatocellular carcinoma (HCC) cells and its possible mechanism. In comparison with the vehicle-treated controls, treatment with scutellarin (50 mg/kg/day) for 35 days significantly mitigated the lung and intrahepatic metastasis of HCC tumors in vivo. Scutellarin treatment significantly reduced HepG2 cell viability in a dose-dependent manner, and inhibited migration and invasion of HCC cells in vitro. Scutellarin treatment significantly reduced STAT3 and Girders of actin filaments (Girdin) expression, STAT3 and Akt phosphorylation in HCC cells. Introduction of STAT3 overexpression restored the scutellarin-downregulated Girdin expression, Akt activation, migration and invasion of HCC cells. Furthermore, induction of Girdin overexpression completely abrogated the inhibition of scutellarin on the Akt phosphorylation, migration and invasion of HCC cells. Scutellarin can inhibit HCC cell metastasis in vivo, and migration and invasion in vitro by down-regulating the STAT3/Girdin/Akt signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Tanshinone IIA inhibits cervix carcinoma stem cells migration and invasion via inhibiting YAP transcriptional activity.

    PubMed

    Qin, Jinghao; Shi, Hongbing; Xu, Yanjie; Zhao, Fang; Wang, Qing

    2018-06-14

    This study aims to explore the effects and related mechanisms of Tanshinone IIA in cervix carcinoma (CC) stemness-like cells migration, invasion, stemness and chemotherapeutical sensitivity. Here, we found that Tanshinone IIA suppressed CC stemness-like cells migration and invasion in a concentration- and time-dependent manner. And consistent results were obtained in CC cells stemness characterized as the decrease of CC stemness markers expression and cells spheroid formation ability. Mechanistically, we found that Tanshinone IIA suppressed RNA binding protein HuR translocation from nuclear to cytoplasm, and thus reduced YAP mRNAs stability and transcriptional activity. Importantly, overexpression YAP-5SA rescued the inhibition of Tanshinone IIA on CC cells stemness. Furthermore, Tanshinone IIA enhanced adriamycin sensitivity in CC stemness-like cells, this effect was attenuated by YAP-5SA overexpression too. Therefore, Tanshinone IIA could suppress CC stemness-like cells migration and invasion by inhibiting YAP transcriptional activity. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  8. Conservation physiology of animal migration

    PubMed Central

    Lennox, Robert J.; Chapman, Jacqueline M.; Souliere, Christopher M.; Tudorache, Christian; Wikelski, Martin; Metcalfe, Julian D.; Cooke, Steven J.

    2016-01-01

    Migration is a widespread phenomenon among many taxa. This complex behaviour enables animals to exploit many temporally productive and spatially discrete habitats to accrue various fitness benefits (e.g. growth, reproduction, predator avoidance). Human activities and global environmental change represent potential threats to migrating animals (from individuals to species), and research is underway to understand mechanisms that control migration and how migration responds to modern challenges. Focusing on behavioural and physiological aspects of migration can help to provide better understanding, management and conservation of migratory populations. Here, we highlight different physiological, behavioural and biomechanical aspects of animal migration that will help us to understand how migratory animals interact with current and future anthropogenic threats. We are in the early stages of a changing planet, and our understanding of how physiology is linked to the persistence of migratory animals is still developing; therefore, we regard the following questions as being central to the conservation physiology of animal migrations. Will climate change influence the energetic costs of migration? Will shifting temperatures change the annual clocks of migrating animals? Will anthropogenic influences have an effect on orientation during migration? Will increased anthropogenic alteration of migration stopover sites/migration corridors affect the stress physiology of migrating animals? Can physiological knowledge be used to identify strategies for facilitating the movement of animals? Our synthesis reveals that given the inherent challenges of migration, additional stressors derived from altered environments (e.g. climate change, physical habitat alteration, light pollution) or interaction with human infrastructure (e.g. wind or hydrokinetic turbines, dams) or activities (e.g. fisheries) could lead to long-term changes to migratory phenotypes. However, uncertainty remains

  9. Conservation physiology of animal migration.

    PubMed

    Lennox, Robert J; Chapman, Jacqueline M; Souliere, Christopher M; Tudorache, Christian; Wikelski, Martin; Metcalfe, Julian D; Cooke, Steven J

    2016-01-01

    Migration is a widespread phenomenon among many taxa. This complex behaviour enables animals to exploit many temporally productive and spatially discrete habitats to accrue various fitness benefits (e.g. growth, reproduction, predator avoidance). Human activities and global environmental change represent potential threats to migrating animals (from individuals to species), and research is underway to understand mechanisms that control migration and how migration responds to modern challenges. Focusing on behavioural and physiological aspects of migration can help to provide better understanding, management and conservation of migratory populations. Here, we highlight different physiological, behavioural and biomechanical aspects of animal migration that will help us to understand how migratory animals interact with current and future anthropogenic threats. We are in the early stages of a changing planet, and our understanding of how physiology is linked to the persistence of migratory animals is still developing; therefore, we regard the following questions as being central to the conservation physiology of animal migrations. Will climate change influence the energetic costs of migration? Will shifting temperatures change the annual clocks of migrating animals? Will anthropogenic influences have an effect on orientation during migration? Will increased anthropogenic alteration of migration stopover sites/migration corridors affect the stress physiology of migrating animals? Can physiological knowledge be used to identify strategies for facilitating the movement of animals? Our synthesis reveals that given the inherent challenges of migration, additional stressors derived from altered environments (e.g. climate change, physical habitat alteration, light pollution) or interaction with human infrastructure (e.g. wind or hydrokinetic turbines, dams) or activities (e.g. fisheries) could lead to long-term changes to migratory phenotypes. However, uncertainty remains

  10. Enhanced Upconversion Luminescence in Yb3+/Tm3+-Codoped Fluoride Active Core/Active Shell/Inert Shell Nanoparticles through Directed Energy Migration

    PubMed Central

    Qiu, Hailong; Yang, Chunhui; Shao, Wei; Damasco, Jossana; Wang, Xianliang; Ågren, Hans; Prasad, Paras N.; Chen, Guanying

    2014-01-01

    The luminescence efficiency of lanthanide-doped upconversion nanoparticles is of particular importance for their embodiment in biophotonic and photonic applications. Here, we show that the upconversion luminescence of typically used NaYF4:Yb3+30%/Tm3+0.5% nanoparticles can be enhanced by ~240 times through a hierarchical active core/active shell/inert shell (NaYF4:Yb3+30%/Tm3+0.5%)/NaYbF4/NaYF4 design, which involves the use of directed energy migration in the second active shell layer. The resulting active core/active shell/inert shell nanoparticles are determined to be about 11 times brighter than that of well-investigated (NaYF4:Yb3+30%/Tm3+0.5%)/NaYF4 active core/inert shell nanoparticles when excited at ~980 nm. The strategy for enhanced upconversion in Yb3+/Tm3+-codoped NaYF4 nanoparticles through directed energy migration might have implications for other types of lanthanide-doped upconversion nanoparticles. PMID:28348285

  11. Enhanced Upconversion Luminescence in Yb3+/Tm3+-Codoped Fluoride Active Core/Active Shell/Inert Shell Nanoparticles through Directed Energy Migration.

    PubMed

    Qiu, Hailong; Yang, Chunhui; Shao, Wei; Damasco, Jossana; Wang, Xianliang; Ågren, Hans; Prasad, Paras N; Chen, Guanying

    2014-01-03

    The luminescence efficiency of lanthanide-doped upconversion nanoparticles is of particular importance for their embodiment in biophotonic and photonic applications. Here, we show that the upconversion luminescence of typically used NaYF₄:Yb 3+ 30%/Tm 3+ 0.5% nanoparticles can be enhanced by ~240 times through a hierarchical active core/active shell/inert shell (NaYF₄:Yb 3+ 30%/Tm 3+ 0.5%)/NaYbF₄/NaYF₄ design, which involves the use of directed energy migration in the second active shell layer. The resulting active core/active shell/inert shell nanoparticles are determined to be about 11 times brighter than that of well-investigated (NaYF₄:Yb 3+ 30%/Tm 3+ 0.5%)/NaYF₄ active core/inert shell nanoparticles when excited at ~980 nm. The strategy for enhanced upconversion in Yb 3+ /Tm 3+ -codoped NaYF₄ nanoparticles through directed energy migration might have implications for other types of lanthanide-doped upconversion nanoparticles.

  12. The anticancer phytochemical rocaglamide inhibits Rho GTPase activity and cancer cell migration

    PubMed Central

    Becker, Michael S.; Müller, Paul M.; Bajorat, Jörg; Schroeder, Anne; Giaisi, Marco; Amin, Ehsan; Ahmadian, Mohammad R.; Rocks, Oliver; Köhler, Rebecca; Krammer, Peter H.; Li-Weber, Min

    2016-01-01

    Chemotherapy is one of the pillars of anti-cancer therapy. Although chemotherapeutics cause regression of the primary tumor, many chemotherapeutics are often shown to induce or accelerate metastasis formation. Moreover, metastatic tumors are largely resistant against chemotherapy. As more than 90% of cancer patients die due to metastases and not due to primary tumor formation, novel drugs are needed to overcome these shortcomings. In this study, we identified the anticancer phytochemical Rocaglamide (Roc-A) to be an inhibitor of cancer cell migration, a crucial event in metastasis formation. We show that Roc-A inhibits cellular migration and invasion independently of its anti-proliferative and cytotoxic effects in different types of human cancer cells. Mechanistically, Roc-A treatment induces F-actin-based morphological changes in membrane protrusions. Further investigation of the molecular mechanisms revealed that Roc-A inhibits the activities of the small GTPases RhoA, Rac1 and Cdc42, the master regulators of cellular migration. Taken together, our results provide evidence that Roc-A may be a lead candidate for a new class of anticancer drugs that inhibit metastasis formation. PMID:27340868

  13. Deformation and Oil Migration Along the Active Newport-Inglewood Fault Zone, Southern California, USA

    NASA Astrophysics Data System (ADS)

    Sample, J. C.

    2006-12-01

    Deformation bands occur in an outcrop of a petroleum-bearing, sandstone-rich unit of the Monterey Formation along the active Newport-Inglewood fault zone (NIFZ), near Corona del Mar, California. The deformation bands likely developed in a damage zone associated with a strand of the NIFZ. The bands appear to have formed in poorly lithified sandstone. They are relatively oil-free whereas the matrix sandstone contains oil in pore space. The deformation bands acted as baffles to flow, but continuing deformation likely breached permeability barriers over time. Thus the bands did not completely isolate compartments from oil migration, but similar structures in the subsurface would likely slow the rate of production in reservoirs. The network of bands at Corona del Mar forms a mesh with band intersection lines lying parallel to the trend of the NIFZ (northwest). This geometry formed as continuing deformation in the NIFZ rotated early bands into unfavorable orientations for continuing deformation, and new bands formed at high angles to the first set. Permeability in this setting is likely to have been anisotropic, higher parallel to strike of the NIFZ and lower vertically and perpendicular to the strike of the fault zone. One unique type of deformation band found here formed by dilation and early oil migration along fractures, and consequent carbonate cementation along fracture margins. These are thin, planar zones of oil 1 - 2 mm thick sandwiched between parallel, carbonate-cemented, positively weathering ribs. These bands appear to represent early oil migration by hydrofracture. Based on crosscutting relationships between structures and cements, there are three distinct phases of oil migration: early migration along discrete hydrofractures; dominant pore migration associated with periodic breaching of deformation bands; and late migration along open fractures, some several centimeters in width. This sequence may be representative of migration histories along the NIFZ in

  14. Activation of a C. elegans Antennapedia homologue in migrating cells controls their direction of migration.

    PubMed

    Salser, S J; Kenyon, C

    1992-01-16

    Anterior-posterior patterning in insects, vertebrates and nematodes involves members of conserved Antennapedia-class homeobox gene clusters (HOM-C) that are thought to give specific body regions their identities. The effects of these genes on region-specific body structures have been described extensively, particularly in Drosophila, but little is known about how HOM-C genes affect the behaviours of cells that migrate into their domains of function. In Caenorhabditis elegans, the Antennapedia-like HOM-C gene mab-5 not only specifies postembryonic fates of cells in a posterior body region, but also influences the migration of mesodermal and neural cells that move through this region. Here we show that as one neuroblast migrates into this posterior region, it switches on mab-5 gene expression; mab-5 then acts as a developmental switch to control the migratory behaviour of the neuroblast descendants. HOM-C genes can therefore not only direct region-specific patterns of cell division and differentiation, but can also act within migrating cells to programme region-specific migratory behaviour.

  15. MAGE-A1 promotes melanoma proliferation and migration through C-JUN activation

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

    Wang, Dong; The 309th Hospital of China People's Liberation Army, Beijing 100091; Wang, Junyun

    2016-05-13

    MAGE-A1 belongs to the chromosome X-clustered genes of cancer-testis antigen family and is normally expressed in the human germ line but is also overexpressed in various tumors. Previous studies of MAGE-A1 in melanoma mainly focused on methylation changes or its role in immunotherapy, however, its biological functions in melanoma have remained unknown. In order to determine the role of MAGE-A1 in melanoma growth and metastasis, we manipulated melanoma cell lines with overexpression and knockdown of MAGE-A1. Integration of cell proliferation assays, transwell migration and invasion assays, and RNA-Seq analysis revealed that up-regulation of MAGE-A1 dramatically promoted proliferation, migration, and invasionmore » of human melanoma cell lines in vitro, while down-regulation of MAGE-A1 inhibited those characteristics associated with tumor cells. Furthermore, transcriptome sequencing revealed that MAGE-A1 exerts its tumor promoting activity by activating p-C-JUN directly or through ERK-MAPK signaling pathways. Based on our findings, we propose that MAGE-A1 may be a potential therapeutic target for melanoma patients. - Highlights: • MAGE-A1 promotes proliferation and clone formation in melanoma cell lines. • MAGE-A1 enhances tumor cell migration and invasion in melanoma cell lines. • Network including C-JUN, IL8, and ARHGAP29 play critical role in malignant melanoma. • Oncogenic MAGE-A1 increases p-C-JUN levels, possibly via ERK-MAPK signaling pathway.« less

  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. Contribution of reactive oxygen species to migration/invasion of human glioblastoma cells U87 via ERK-dependent COX-2/PGE(2) activation.

    PubMed

    Chiu, Wen-Ta; Shen, Shing-Chuan; Chow, Jyh-Ming; Lin, Cheng-Wei; Shia, Ling-Tin; Chen, Yen-Chou

    2010-01-01

    In the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulation, an increase in the migration/invasion of U87 glioblastoma cells was detected by a wound healing assay, transwell analysis, and spheroid formation assay by inducing matrix metalloproteinase-9 (MMP-9) enzyme activity via a gelatin zymographic analysis. A dose- and time-dependent increase in cyclooxygenase-2 (COX-2) gene expression with elevated prostaglandin E(2) (PGE(2)) production was identified in TPA- but not in 4alpha-TPA (a respective inactive compound)-treated U87 cells TPA-induced migration/invasion was significantly blocked by adding the COX-2-specific inhibitor, NS398, through a reduction in PGE(2) production. Data from the pharmacological studies using specific chemical inhibitors showed that activation of protein kinase C (PKC) and extracellular signal-regulated kinases (ERKs) was involved in TPA-induced migration/invasion, COX-2 protein expression, and MMP-9 activation. Stimulation of intracellular peroxide production by TPA was detected by a DCHF-DA assay, and the addition of superoxide dismutase (SOD) or tempol significantly inhibited TPA-induced migration/invasion and COX-2 protein expression accompanied by a decrease in peroxide production. An increase in NADPH oxidase activity by TPA was examined, and TPA-induced migration/invasion was blocked by adding DPI, an NADPH oxidase inhibitor. Additionally, the natural flavonoids quercetin (QE), baicalein (BE), and myricetin (ME) effectively blocked TPA-induced migration/invasion while simultaneously inhibiting COX-2/PGE(2) production, MMP-9 enzyme activity, and peroxide production in U87 cells. The contribution of ROS production to the migration/invasion of U87 glioblastoma cells via ERK-activated COX-2/PGE(2) and MMP-9 induction was first investigated here, and agents such as QE, BE, and ME with the ability to block these events possess the potential to be developed for use against migration/invasion by glioblastomas.

  18. Night-time neuronal activation of Cluster N in a day- and night-migrating songbird.

    PubMed

    Zapka, Manuela; Heyers, Dominik; Liedvogel, Miriam; Jarvis, Erich D; Mouritsen, Henrik

    2010-08-01

    Magnetic compass orientation in a night-migratory songbird requires that Cluster N, a cluster of forebrain regions, is functional. Cluster N, which receives input from the eyes via the thalamofugal pathway, shows high neuronal activity in night-migrants performing magnetic compass-guided behaviour at night, whereas no activation is observed during the day, and covering up the birds' eyes strongly reduces neuronal activation. These findings suggest that Cluster N processes light-dependent magnetic compass information in night-migrating songbirds. The aim of this study was to test if Cluster N is active during daytime migration. We used behavioural molecular mapping based on ZENK activation to investigate if Cluster N is active in the meadow pipit (Anthus pratensis), a day- and night-migratory species. We found that Cluster N of meadow pipits shows high neuronal activity under dim-light at night, but not under full room-light conditions during the day. These data suggest that, in day- and night-migratory meadow pipits, the light-dependent magnetic compass, which requires an active Cluster N, may only be used during night-time, whereas another magnetosensory mechanism and/or other reference system(s), like the sun or polarized light, may be used as primary orientation cues during the day.

  19. The sGC activator inhibits the proliferation and migration, promotes the apoptosis of human pulmonary arterial smooth muscle cells via the up regulation of plasminogen activator inhibitor-2

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

    Zhang, Shuai; Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, 8 Gongti South Rd, Beijing; Zou, Lihui

    Background: Different types of pulmonary hypertension (PH) share the same process of pulmonary vascular remodeling, the molecular mechanism of which is not entirely clarified by far. The abnormal biological behaviors of pulmonary arterial smooth muscle cells (PASMCs) play an important role in this process. Objectives: We investigated the regulation of plasminogen activator inhibitor-2 (PAI-2) by the sGC activator, and explored the effect of PAI-2 on PASMCs proliferation, apoptosis and migration. Methods: After the transfection with PAI-2 overexpression vector and specific siRNAs or treatment with BAY 41-2272 (an activator of sGC), the mRNA and protein levels of PAI-2 in cultured humanmore » PASMCs were detected, and the proliferation, apoptosis and migration of PASMCs were investigated. Results: BAY 41-2272 up regulated the endogenous PAI-2 in PASMCs, on the mRNA and protein level. In PAI-2 overexpression group, the proliferation and migration of PASMCs were inhibited significantly, and the apoptosis of PASMCs was increased. In contrast, PAI-2 knockdown with siRNA increased PASMCs proliferation and migration, inhibited the apoptosis. Conclusions: PAI-2 overexpression inhibits the proliferation and migration and promotes the apoptosis of human PASMCs. Therefore, sGC activator might alleviate or reverse vascular remodeling in PH through the up-regulation of PAI-2. - Highlights: • sGC activator BAY41-2272 up regulated PAI-2 in PASMCs, on the mRNA and protein level. • PAI-2 overexpression inhibits the proliferation and migration of human PASMCs. • PAI-2 overexpression promotes the apoptosis of human PASMCs. • sGC activator might alleviate the vascular remodeling in pulmonary hypertension.« less

  20. Glioma-mediated microglial activation promotes glioma proliferation and migration: roles of Na+/H+ exchanger isoform 1

    PubMed Central

    Zhu, Wen; Carney, Karen E.; Pigott, Victoria M.; Falgoust, Lindsay M.; Clark, Paul A.; Kuo, John S.; Sun, Dandan

    2016-01-01

    Microglia play important roles in extracellular matrix remodeling, tumor invasion, angiogenesis, and suppression of adaptive immunity in glioma. Na+/H+ exchanger isoform 1 (NHE1) regulates microglial activation and migration. However, little is known about the roles of NHE1 in intratumoral microglial activation and microglia–glioma interactions. Our study revealed up-regulation of NHE1 protein expression in both glioma cells and tumor-associated Iba1+ microglia in glioma xenografts and glioblastoma multiforme microarrays. Moreover, we observed positive correlation of NHE1 expression with Iba1 intensity in microglia/macrophages. Glioma cells, via conditioned medium or non-contact glioma-microglia co-cultures, concurrently upregulated microglial expression of NHE1 protein and other microglial activation markers (iNOS, arginase-1, TGF-β, IL-6, IL-10 and the matrix metalloproteinases MT1-MMP and MMP9). Interestingly, glioma-stimulated microglia reciprocally enhanced glioma proliferation and migration. Most importantly, inhibition of microglial NHE1 activity via small interfering RNA (siRNA) knockdown or the potent NHE1-specific inhibitor HOE642 significantly attenuated microglial activation and abolished microglia-stimulated glioma migration and proliferation. Taken together, our findings provide the first evidence that NHE1 function plays an important role in glioma–microglia interactions, enhancing glioma proliferation and invasion by stimulating microglial release of soluble factors. NHE1 upregulation is a novel marker of the glioma-associated microglial activation phenotype. Inhibition of NHE1 represents a novel glioma therapeutic strategy by targeting tumor-induced microglial activation. PMID:27287871

  1. Anti-inflammatory cytokine interleukin-19 inhibits smooth muscle cell migration and activation of cytoskeletal regulators of VSMC motility

    PubMed Central

    Gabunia, Khatuna; Jain, Surbhi; England, Ross N.

    2011-01-01

    Vascular smooth muscle cell (VSMC) migration is an important cellular event in multiple vascular diseases, including atherosclerosis, restenosis, and transplant vasculopathy. Little is known regarding the effects of anti-inflammatory interleukins on VSMC migration. This study tested the hypothesis that an anti-inflammatory Th2 interleukin, interleukin-19 (IL-19), could decrease VSMC motility. IL-19 significantly decreased platelet-derived growth factor (PDGF)-stimulated VSMC chemotaxis in Boyden chambers and migration in scratch wound assays. IL-19 significantly decreased VSMC spreading in response to PDGF. To determine the molecular mechanism(s) for these cellular effects, we examined the effect of IL-19 on activation of proteins that regulate VSMC cytoskeletal dynamics and locomotion. IL-19 decreased PDGF-driven activation of several cytoskeletal regulatory proteins that play an important role in smooth muscle cell motility, including heat shock protein-27 (HSP27), myosin light chain (MLC), and cofilin. IL-19 decreased PDGF activation of the Rac1 and RhoA GTPases, important integrators of migratory signals. IL-19 was unable to inhibit VSMC migration nor was able to inhibit activation of cytoskeletal regulatory proteins in VSMC transduced with a constitutively active Rac1 mutant (RacV14), suggesting that IL-19 inhibits events proximal to Rac1 activation. Together, these data are the first to indicate that IL-19 can have important inhibitory effects on VSMC motility and activation of cytoskeletal regulatory proteins. This has important implications for the use of anti-inflammatory cytokines in the treatment of vascular occlusive disease. PMID:21209363

  2. COX2 expression and Erk1/Erk2 activity mediate Cot-induced cell migration.

    PubMed

    Rodríguez, Cristina; López, Pilar; Pozo, Maite; Duce, Antonio Martín; López-Pelaéz, Marta; Fernández, Margarita; Alemany, Susana

    2008-09-01

    The MAPKKK8 Cot/tpl-2, identified as an oncogene (Cot-T), participates in the intracellular signaling activated by members of the TLR and TNFalpha receptor superfamilies. Here we demonstrate that Cot promotes cell migration by regulating different steps involved in this process, such as cell adhesion and metalloproteinase activity. Indeed, Cot also regulates the cytoskeleton and Cot-T overexpression provokes the polarization of microtubules and the loss of stress fibers. Moreover, and in accordance with the increased Rac-GTP levels observed, Cot-T overexpressing cells develop more lamellipodia than control cells. Conversely, depletion of endogenous Cot increases the formation of stress fibers which is correlated with the high levels of Rho-GTP observed in these cells. In addition, the increase in COX2 expression and the activation of Erk1/2 regulated by Cot are essential for the induction of cell migration. Together, these data provide evidence of a new role for both proto-oncogenic and oncogenic Cot.

  3. Dynamical optical imaging monocytes/macrophages migration and activation in contact hypersensitivity (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Zhang, Zhihong

    2017-02-01

    Inflammatory monocytes/macrophages (Mon/Mφ) play an important role in cutaneous allergic inflammation. However, their migration and activation in dermatitis and how they accelerate the inflammatory reaction are largely unknown. Optical molecular imaging is the most promising tool for investigating the function and motility of immune cells in vivo. We have developed a multi-scale optical imaging approach to evaluate the spatio-temporal dynamic behavior and properties of immune cells from the whole field of organs to the cellular level at the inflammatory site in delayed type hypersensitivity reaction. Here, we developed some multi-color labeling mouse models based on the endogenous labeling with fluorescent proteins and the exogenous labeling with fluorescent dyes. We investigated the cell movement, cell interaction and function of immunocytes (e.g. Mon/Mφ, DC, T cells and neutrophils) in the skin allergy inflammation (e.g., contact hypersensitivity) by using intravital microscopy. The long-term imaging data showed that after inflammatory Mon/Mφ transendothelial migration in dermis, they migrating in interstitial space of dermis. Depletion of blood monocyte with clodronate liposome extremely reduced the inflammatory reaction. Our finding provided further insight into inflammatory Mon/Mφ mediating the inflammatory cascade through functional migration in allergic contact dermatitis.

  4. Migration of antimony from PET bottles into beverages: determination of the activation energy of diffusion and migration modelling compared with literature data.

    PubMed

    Welle, F; Franz, R

    2011-01-01

    Plastics bottles made from polyethylene terephthalate (PET) are increasingly used for soft drinks, mineral water, juices and beer. In this study a literature review is presented concerning antimony levels found both in PET materials as well as in foods and food simulants. On the other hand, 67 PET samples from the European bottle market were investigated for their residual antimony concentrations. A mean value of 224 ± 32 mg kg(-1) was found, the median was 220 mg kg(-1). Diffusion coefficients for antimony in PET bottle materials were experimentally determined at different temperature between 105 and 150°C. From these data, the activation energy of diffusion for antimony species from the PET bottle wall into beverages and food simulants was calculated. The obtained value of 189 kJ mol(-1) was found to be in good agreement with published data on PET microwave trays (184 kJ mol(-1)). Based on these results, the migration of antimony into beverages was predicted by mathematical migration modelling for different surface/volume ratios and antimony bottle wall concentrations. The results were compared with literature data as well as international legal limits and guidelines values for drinking water and the migration limit set from food packaging legislation. It was concluded that antimony levels in beverages due to migration from PET bottles manufactured according to the state of the art can never reach or exceed the European-specific migration limit of 40 microg kg(-1). Maximum migration levels caused by room-temperature storage even after 3 years will never be essentially higher than 2.5 microg kg(-1) and in any case will be below the European limit of 5 microg kg(-1) for drinking water. The results of this study confirm that the exposure of the consumer by antimony migration from PET bottles into beverages and even into edible oils reaches approximately 1% of the current tolerable daily intake (TDI) established by World Health Organisation (WHO). Having

  5. P311 Accelerates Skin Wound Reepithelialization by Promoting Epidermal Stem Cell Migration Through RhoA and Rac1 Activation.

    PubMed

    Yao, Zhihui; Li, Haisheng; He, Weifeng; Yang, Sisi; Zhang, Xiaorong; Zhan, Rixing; Xu, Rui; Tan, Jianglin; Zhou, Junyi; Wu, Jun; Luo, Gaoxing

    2017-03-15

    P311 is a newly discovered functional gene, and it has been proved to play a key role in blood pressure homeostasis, glioblastoma invasion, renal fibrosis, hypertrophic scar formation, and others. In this study, for the first time, we found that P311 could enhance reepithelialization during wound healing via promoting epidermal stem cell (EpSC) migration through Rho GTPases. P311 expression was highly increased in neo-epidermal cells during human and mouse skin wound healing, and P311was co-localized with 5-bromo-2'-deoxyuridine positive label-retaining cells in a mouse superficial second-degree burn wound model. Furthermore, transfection of human EpSCs with adenovirus encoding P311 significantly accelerated the cell migration in vitro. Moreover, highly expressed P311 could enhance the activities of the Rho GTPases (RhoA, Rac1, and Cdc42) in cultured human EpSCs. P311-knockout mouse EpSCs showed dramatically decreased cell migration and activities of Rho GTPases (RhoA, Rac1, and Cdc42). Besides, both the RhoA-specific inhibitor and the Rac1 inhibitor, not the Cdc42 inhibitor, could significantly suppress P311-induced human EpSC migration. In vivo, the reepithelialization was markedly impaired during wound healing after P311 was knocked out. Together, our results suggested that P311 could accelerate skin wound reepithelialization by promoting the migration of EpSCs through RhoA and Rac1 activation. P311 could serve as a novel target for regulation of EpSC migration during cutaneous wound healing.

  6. Brk activates rac1 and promotes cell migration and invasion by phosphorylating paxillin.

    PubMed

    Chen, Hsin-Yi; Shen, Che-Hung; Tsai, Yuh-Tyng; Lin, Feng-Chi; Huang, Yuan-Ping; Chen, Ruey-Hwa

    2004-12-01

    Brk (for breast tumor kinase) is a nonreceptor tyrosine kinase containing SH3, SH2, and tyrosine kinase catalytic domains. Brk was originally identified from a human metastatic breast tumor, and its overexpression is frequently observed in breast cancer and several other cancer types. However, the molecular mechanism by which this kinase participates in tumorigenesis remains poorly characterized. In the present study, we not only identified paxillin as the binding partner and substrate of Brk but also discovered a novel signaling pathway by which Brk mediates epidermal growth factor (EGF)-induced paxillin phosphorylation. We show that EGF stimulation activates the catalytic activity of Brk, which in turn phosphorylates paxillin at Y31 and Y118. These phosphorylation events promote the activation of small GTPase Rac1 via the function of CrkII. Through this pathway, Brk is capable of promoting cell motility and invasion and functions as a mediator of EGF-induced migration and invasion. In accordance with these functional roles, Brk translocates to membrane ruffles, where it colocalizes with paxillin during cell migration. Together, our findings identify novel signaling and biological roles of Brk and indicate the first potential link between Brk and metastatic malignancy.

  7. Novel Anti-inflammatory Activity of Epoxyazadiradione against Macrophage Migration Inhibitory Factor

    PubMed Central

    Alam, Athar; Haldar, Saikat; Thulasiram, Hirekodathakallu V.; Kumar, Rahul; Goyal, Manish; Iqbal, Mohd Shameel; Pal, Chinmay; Dey, Sumanta; Bindu, Samik; Sarkar, Souvik; Pal, Uttam; Maiti, Nakul C.; Bandyopadhyay, Uday

    2012-01-01

    Macrophage migration inhibitory factor (MIF) is responsible for proinflammatory reactions in various infectious and non-infectious diseases. We have investigated the mechanism of anti-inflammatory activity of epoxyazadiradione, a limonoid purified from neem (Azadirachta indica) fruits, against MIF. Epoxyazadiradione inhibited the tautomerase activity of MIF of both human (huMIF) and malaria parasites (Plasmodium falciparum (PfMIF) and Plasmodium yoelii (PyMIF)) non-competitively in a reversible fashion (Ki, 2.11–5.23 μm). Epoxyazadiradione also significantly inhibited MIF (huMIF, PyMIF, and PfMIF)-mediated proinflammatory activities in RAW 264.7 cells. It prevented MIF-induced macrophage chemotactic migration, NF-κB translocation to the nucleus, up-regulation of inducible nitric-oxide synthase, and nitric oxide production in RAW 264.7 cells. Epoxyazadiradione not only exhibited anti-inflammatory activity in vitro but also in vivo. We tested the anti-inflammatory activity of epoxyazadiradione in vivo after co-administering LPS and MIF in mice to mimic the disease state of sepsis or bacterial infection. Epoxyazadiradione prevented the release of proinflammatory cytokines such as IL-1α, IL-1β, IL-6, and TNF-α when LPS and PyMIF were co-administered to BALB/c mice. The molecular basis of interaction of epoxyazadiradione with MIFs was explored with the help of computational chemistry tools and a biological knowledgebase. Docking simulation indicated that the binding was highly specific and allosteric in nature. The well known MIF inhibitor (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) inhibited huMIF but not MIF of parasitic origin. In contrast, epoxyazadiradione inhibited both huMIF and plasmodial MIF, thus bearing an immense therapeutic potential against proinflammatory reactions induced by MIF of both malaria parasites and human. PMID:22645149

  8. A case study of methane gas migration through sealed mine GOB into active mine workings

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

    Garcia, F.; McCall, F.E.; Trevits, M.A.

    1995-12-31

    The U.S. Bureau of Mines investigated the influence of atmospheric pressure changes on methane gas migration through mine seals at a mine site located in the Pittsburgh Coalbed. The mine gained access to a coal reserve through part of an abandoned mine and constructed nine seals to isolate the extensive old workings from the active mine area. Underground problems were experienced when atmospheric pressure fell, causing methane gas to migrate around the seals and into the active workings. During mining operations, methane gas levels exceeded legal limits and coal production was halted until the ventilation system could be improved. Whenmore » mining resumed with increased air flow, methane gas concentrations occasionally exceeded the legal limits and production had to be halted until the methane level fell within the mandated limit. To assist the ventilation system, a pressure relief borehole located in the abandoned workings near the mine seals was proposed. Preliminary estimates by a gob gas simulator (computer model) suggested that a 0.76 m (2.5 ft) diameter pressure relief borehole with an exhaust fan would be necessary to remove enough methane from the abandoned area so that the ventilation system could dilute the gas in the active workings. However, by monitoring methane gas emissions and seal pressure, during periods of low atmospheric pressure, the amount of methane gas that migrated into the active mine workings was calculated. Researchers then determined that a relief borehole, 20.3 cm (8-in) with an exhaust fan could remove at least twice the maximum measured volume of migrating methane gas. Because gas concentrations in the abandoned workings could potentially reach explosive limits, it was proposed that the mine eliminate the exhaust fan. Installation of the recommended borehole and enlarging two other ventilation boreholes located In the abandoned area reduced methane gas leakage through the seals by at least 63%.« less

  9. Low dose of kaempferol suppresses the migration and invasion of triple-negative breast cancer cells by downregulating the activities of RhoA and Rac1.

    PubMed

    Li, Shoushan; Yan, Ting; Deng, Rong; Jiang, Xuesong; Xiong, Huaping; Wang, Yuan; Yu, Qiao; Wang, Xiaohua; Chen, Cheng; Zhu, Yichao

    2017-01-01

    Triple-negative breast cancer (TNBC) is an especially aggressive and hard-to-treat disease. Although the anticancer role of kaempferol has been reported in breast cancer, the effect of kaempferol on TNBC remains unclear. This experiment investigated the migration-suppressive role of a low dose of kaempferol in TNBC cells. Wound-healing assays and cell invasion assays were used to confirm the migration and invasion of cells treated with kaempferol or transfected indicated constructs. We evaluated the activations of RhoA, Rac1 and Cdc42 in TNBC cells with a Rho activation assay. A panel of inhibitors of estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 (ER/PR/HER2) treated non-TNBC (SK-BR-3 and MCF-7) cells and blocked the ER/PR/HER2 activity. Wound-healing assays and Rho activation assays were employed to measure the effect of kaempferol and ER/PR/HER2 inhibitors on Rho activation and cell migration rates. A low dose of kaempferol (20 μmol/L) had a potent inhibitory effect on the migration and invasion of TNBC cells, but not on the migration of non-TNBC (SK-BR-3 and MCF-7) cells. The low dose of kaempferol downregulated the activations of RhoA and Rac1 in TNBC cells. Moreover, the low dose of kaempferol also inhibited the migration and RhoA activations of HER2-silence SK-BR-3 and ER/PR-silence MCF-7 cells. Overexpressed HER2 rescued the cell migration and RhoA and Rac1 activations of kaempferol-treated MDA-MB-231 cells. The low dose of kaempferol inhibits the migration and invasion of TNBC cells via blocking RhoA and Rac1 signaling pathway.

  10. 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.

  11. WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar-bipolar transition as well as the initiation of glia-guided migration.

    PubMed

    Xie, Min-Jue; Yagi, Hideshi; Kuroda, Kazuki; Wang, Chen-Chi; Komada, Munekazu; Zhao, Hong; Sakakibara, Akira; Miyata, Takaki; Nagata, Koh-Ichi; Oka, Yuichiro; Iguchi, Tokuichi; Sato, Makoto

    2013-06-01

    Glia-guided migration (glia-guided locomotion) during radial migration is a characteristic yet unique mode of migration. In this process, the directionality of migration is predetermined by glial processes and not by growth cones. Prior to the initiation of glia-guided migration, migrating neurons transform from multipolar to bipolar, but the molecular mechanisms underlying this multipolar-bipolar transition and the commencement of glia-guided migration are not fully understood. Here, we demonstrate that the multipolar-bipolar transition is not solely a cell autonomous event; instead, the interaction of growth cones with glial processes plays an essential role. Time-lapse imaging with lattice assays reveals the importance of vigorously active growth cones in searching for appropriate glial scaffolds, completing the transition, and initiating glia-guided migration. These growth cone activities are regulated by Abl kinase and Cdk5 via WAVE2-Abi2 through the phosphorylation of tyrosine 150 and serine 137 of WAVE2. Neurons that do not display such growth cone activities are mispositioned in a more superficial location in the neocortex, suggesting the significance of growth cones for the final location of the neurons. This process occurs in spite of the "inside-out" principle in which later-born neurons are situated more superficially.

  12. Intra-household conflicts in migration decisionmaking: return and pendulum migration in Morocco.

    PubMed

    De Haas, Hein; Fokkema, Tineke

    2010-01-01

    By analyzing the migration behavior and transnational residential strategies of first-generation, aging migrants from a particular Moroccan sending region, this study contributes to a conceptual critique of migration theories that identify the household as the most relevant decisionmaking unit. It highlights the role of intra-household power inequalities and conflicts in migration decisionmaking as well as the effects of migration decisions for intra-household power relations. Many labor migrants who left Morocco to work in Europe in the 1960s and 1970s did not realize their wish to return but instead ended up reunifying their families at the destination. An increasing proportion adopts a pendulum migration strategy to reconcile their own wish to retain strong ties with Morocco with the reluctance of children and spouses to return. Migrants who unilaterally decided not to reunify their families usually return after their active working life. However, this unilateral decision also blocks legal entry into Europe for their children, which has generated considerable intergenerational tensions.

  13. Control of cortical neuronal migration by glutamate and GABA

    PubMed Central

    Luhmann, Heiko J.; Fukuda, A.; Kilb, W.

    2015-01-01

    Neuronal migration in the cortex is controlled by the paracrine action of the classical neurotransmitters glutamate and GABA. Glutamate controls radial migration of pyramidal neurons by acting primarily on NMDA receptors and regulates tangential migration of inhibitory interneurons by activating non-NMDA and NMDA receptors. GABA, acting on ionotropic GABAA-rho and GABAA receptors, has a dichotomic action on radially migrating neurons by acting as a GO signal in lower layers and as a STOP signal in upper cortical plate (CP), respectively. Metabotropic GABAB receptors promote radial migration into the CP and tangential migration of interneurons. Besides GABA, the endogenous GABAergic agonist taurine is a relevant agonist controlling radial migration. To a smaller extent glycine receptor activation can also influence radial and tangential migration. Activation of glutamate and GABA receptors causes increases in intracellular Ca2+ transients, which promote neuronal migration by acting on the cytoskeleton. Pharmacological or genetic manipulation of glutamate or GABA receptors during early corticogenesis induce heterotopic cell clusters in upper layers and loss of cortical lamination, i.e., neuronal migration disorders which can be associated with neurological or neuropsychiatric diseases. The pivotal role of NMDA and ionotropic GABA receptors in cortical neuronal migration is of major clinical relevance, since a number of drugs acting on these receptors (e.g., anti-epileptics, anesthetics, alcohol) may disturb the normal migration pattern when present during early corticogenesis. PMID:25688185

  14. Somatostatin, acting at receptor subtype 1, inhibits Rho activity, the assembly of actin stress fibers, and cell migration.

    PubMed

    Buchan, Alison M J; Lin, Chin-Yu; Choi, Jimmy; Barber, Diane L

    2002-08-09

    Somatostatin regulates multiple biological functions by acting through a family of five G protein-coupled receptors, somatostatin receptors (SSTRs) 1-5. Although all five receptor subtypes inhibit adenylate cyclase activity and decrease intracellular cAMP levels, specific receptor subtypes also couple to additional signaling pathways. In CCL39 fibroblasts expressing either human SSTR1 or SSTR2, we demonstrate that activation of SSTR1 (but not SSTR2) attenuated both thrombin- and integrin-stimulated Rho-GTP complex formation. The reduction in Rho-GTP formation in the presence of somatostatin was associated with decreased translocation of Rho and LIM kinase to the plasma membrane and fewer focal contacts. Activation of Rho resulted in the formation of intracellular actin stress fibers and cell migration. In CCL39-R1 cells, somatostatin treatment prevented actin stress fiber assembly and attenuated thrombin-stimulated cell migration through Transwell membranes to basal levels. To show that native SSTR1 shares the ability to inhibit Rho activation, we demonstrated that somatostatin treatment of human umbilical vein endothelial cells attenuated thrombin-stimulated Rho-GTP accumulation. These data show for the first time that a G protein-coupled receptor, SSTR1, inhibits the activation of Rho, the assembly of focal adhesions and actin stress fibers, and cell migration.

  15. Constrained Adherable Area of Nanotopographic Surfaces Promotes Cell Migration through the Regulation of Focal Adhesion via Focal Adhesion Kinase/Rac1 Activation.

    PubMed

    Lim, Jiwon; Choi, Andrew; Kim, Hyung Woo; Yoon, Hyungjun; Park, Sang Min; Tsai, Chia-Hung Dylan; Kaneko, Makoto; Kim, Dong Sung

    2018-05-02

    Cell migration is crucial in physiological and pathological processes such as embryonic development and wound healing; such migration is strongly guided by the surrounding nanostructured extracellular matrix. Previous studies have extensively studied the cell migration on anisotropic nanotopographic surfaces; however, only a few studies have reported cell migration on isotropic nanotopographic surfaces. We herein, for the first time, propose a novel concept of adherable area on cell migration using isotropic nanopore surfaces with sufficient nanopore depth by adopting a high aspect ratio. As the pore size of the nanopore surface was controlled to 200, 300, and 400 nm in a fixed center-to-center distance of 480 nm, it produced 86, 68, and 36% of adherable area, respectively, on the fabricated surface. A meticulous investigation of the cell migration in response to changes in the constrained adherable area of the nanotopographic surface showed 1.4-, 1.5-, and 1.6-fold increase in migration speeds and a 1.4-, 2-, and 2.5-fold decrease in the number of focal adhesions as the adherable area was decreased to 86, 68, and 36%, respectively. Furthermore, a strong activation of FAK/Rac1 signaling was observed to be involved in the promoted cell migration. These results suggest that the reduced adherable area promotes cell migration through decreasing the FA formation, which in turn upregulates FAK/Rac1 activation. The findings in this study can be utilized to control the cell migration behaviors, which is a powerful tool in the research fields involving cell migration such as promoting wound healing and tissue repair.

  16. Fisetin inhibits epidermal growth factor-induced migration of ARPE-19 cells by suppression of AKT activation and Sp1-dependent MMP-9 expression.

    PubMed

    Lin, Hung-Yu; Chen, Yong-Syuan; Wang, Kai; Chien, Hsiang-Wen; Hsieh, Yi-Hsien; Yang, Shun-Fa

    2017-01-01

    Proliferative vitreoretinopathy (PVR) can result in abnormal migration of RPE cells. Fisetin is a naturally occurring compound that has been reported to have antitumor effects, but its effects on epidermal growth factor (EGF)-induced cell migration and the underlying mechanisms remain unclear. Effects of fisetin on EGF-induced cell viability and migration were examined with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and in vitro migration assays. Reverse transcription-PCR (RT-PCR) and immunoblotting were performed to evaluate matrix metallopeptidase-9 (MMP-9) expression and activation of specificity protein-1 (Sp1) and protein kinase B (AKT) in ARPE-19 cells treated with EGF and with or without fisetin. Luciferase and chromatin immunoprecipitation (ChIP) assays were performed to examine Sp1 transcription activity and MMP-9 binding activity. Fisetin did not affect ARPE-19 cell viability and significantly inhibited the EGF-induced migration capacity of ARPE-19 cells. Furthermore, fisetin exerted an antimigratory effect and suppressed MMP-9 mRNA and protein expression. Treatment with EGF induced phosphorylation of AKT and expression of MMP-9 and Sp1. Fisetin combined with LY294002 (an inhibitor of AKT) prevented the EGF-induced migration involved in downregulation of Sp1 and MMP-9 expression. Luciferase and ChIP assays suggested that fisetin remarkably decreased the EGF-induced transcription activity of MMP-9 and Sp1 and inhibited EGF-mediated Sp1 from directly binding to the MMP-9 promoter in ARPE-19 cells. Fisetin inhibited EGF-induced cell migration via modulation of AKT/Sp1-dependent MMP-9 transcriptional activity. Therefore, fisetin may be a potential agent in the treatment of migratory PVR diseases.

  17. Polyamine-dependent migration of retinal pigment epithelial cells.

    PubMed

    Johnson, Dianna A; Fields, Carolyn; Fallon, Amy; Fitzgerald, Malinda E C; Viar, Mary Jane; Johnson, Leonard R

    2002-04-01

    Migration of retinal pigment epithelial (RPE) cells can be triggered by disruption of the RPE monolayer or injury to the neural retina. Migrating cells may re-establish a confluent monolayer, or they may invade the neural retina and disrupt visual function. The purpose of this study was to examine the role of endogenous polyamines in mechanisms of RPE migration. Endogenous polyamine levels were determined in an immortalized RPE cell line, D407, using HPLC. Activities of the two rate-limiting enzymes for polyamine synthesis, ornithine decarboxylase (ODC), and S-adenosylmethionine decarboxylase (SAMdc), were measured by liberation of ((14)CO(2))(.) Migration was assessed in confluent cultures by determining the number of cells migrating into a mechanically denuded area. All measurements were obtained both in control cultures and in cultures treated with synthesis inhibitors that deplete endogenous polyamines. Subcellular localization of endogenous polyamines was determined using a polyamine antibody. The polyamines, spermidine and spermine, as well as their precursor, putrescine, were normal constituents of RPE cells. The two rate-limiting synthetic enzymes were also present, and their activities were stimulated dramatically by addition of serum to the culture medium. Cell migration was similarly stimulated by serum exposure. When endogenous polyamines were depleted, migration was blocked. When polyamines were replenished through uptake, migration was restored. Polyamine immunoreactivity was limited to membrane patches in quiescent cells. In actively migrating and dividing cells, immunoreactivity was enhanced throughout the cytoplasm. Polyamines are essential for RPE migration. Pharmacologic manipulation of the polyamine pathway could provide a therapeutic strategy for regulating anomalous migration.

  18. S100A8 and S100A9 Promotes Invasion and Migration through p38 Mitogen-Activated Protein Kinase-Dependent NF-κB Activation in Gastric Cancer Cells

    PubMed Central

    Kwon, Chae Hwa; Moon, Hyun Jung; Park, Hye Ji; Choi, Jin Hwa; Park, Do Youn

    2013-01-01

    S100A8 and S100A9 (S100A8/A9) are low-molecular weight members of the S100 family of calcium-binding proteins. Recent studies have reported S100A8/A9 promote tumorigenesis. We have previously reported that S100A8/A9 is mostly expressed in stromal cells and inflammatory cells between gastric tumor cells. However, the role of environmental S100A8/A9 in gastric cancer has not been defined. We observed in the present study the effect of S100A8/A9 on migration and invasion of gastric cancer cells. S100A8/A9 treatment increased migration and invasionat lower concentrations that did not affect cell proliferation and cell viability. S100A8/A9 caused activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB). The phosphorylation of p38 MAPK was not affected by the NF-κB inhibitor Bay whereas activation of NF-κB was blocked by p38 MAPK inhibitor SB203580, indicating that S100A8/A9-induced NF-κB activation is mediated by phosphorylation of p38 MAPK. S100A8/A9-induced cell migration and invasion was inhibited by SB203580 and Bay, suggesting that activation of p38 MAPK and NF-κB is involved in the S100A8/A9 induced cell migration and invasion. S100A8/A9 caused an increase in matrix metalloproteinase 2 (MMP2) and MMP12 expression, which were inhibited by SB203580 and Bay. S100A8/A9-induced cell migration and invasion was inhibited by MMP2 siRNA and MMP12 siRNA, indicating that MMP2 and MMP12 is related to the S100A8/A9 induced cell migration and invasion. Taken together, these results suggest that S100A8/A9 promotes cell migration and invasion through p38 MAPK-dependent NF-κB activation leading to an increase of MMP2 and MMP12 in gastric cancer. PMID:23456298

  19. 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

  20. Vulnerable transportation and utility assets near actively migrating streams in Indiana

    USGS Publications Warehouse

    Sperl, Benjamin J.

    2017-11-02

    An investigation was completed by the U.S. Geological Survey in cooperation with the Indiana Office of Community and Rural Affairs that found 1,132 transportation and utility assets in Indiana are vulnerable to fluvial erosion hazards due to close proximity to actively migrating streams. Locations of transportation assets (bridges, roadways, and railroad lines) and selected utility assets (high-capacity overhead power-transmission lines, underground pipelines, water treatment facilities, and in-channel dams) were determined using aerial imagery hosted by the Google Earth platform. Identified assets were aggregated by stream reach, county, and class. Accompanying the report is a polyline shapefile of the stream reaches documented by Robinson. The shapefile, derived from line work in the National Hydrography Dataset and attributed with channel migration rates, is released with complete Federal Geographic Data Committee metadata. The data presented in this report are intended to help stakeholders and others identify high-risk areas where transportation and utility assets may be threatened by fluvial erosion hazards thus warranting consideration for mitigation strategies.

  1. Active Shaping of Chemokine Gradients by Atypical Chemokine Receptors: A 4D Live-Cell Imaging Migration Assay.

    PubMed

    Werth, Kathrin; Förster, Reinhold

    2016-01-01

    Diffusion of chemokines away from their site of production results in the passive formation of chemokine gradients. We have recently shown that chemokine gradients can also be formed in an active manner, namely by atypical chemokine receptors (ACKRs) that scavenge chemokines locally. Here, we describe an advanced method that allows the visualization of leukocyte migration in a three-dimensional environment along a chemokine gradient that is actively established by cells expressing an ACKR. Initially developed to visualize the migration of dendritic cells along gradients of CCL19 or CCL21 that were actively shaped by an ACKR4-expressing cell line, we expect that this chamber system can be exploited to study many other combinations of atypical and conventional chemokine receptor-expressing cells. © 2016 Elsevier Inc. All rights reserved.

  2. Displacement correlations between a single mesenchymal-like cell and its nucleus effectively link subcellular activities and motility in cell migration analysis

    NASA Astrophysics Data System (ADS)

    Lan, Tian; Cheng, Kai; Ren, Tina; Arce, Stephen Hugo; Tseng, Yiider

    2016-09-01

    Cell migration is an essential process in organism development and physiological maintenance. Although current methods permit accurate comparisons of the effects of molecular manipulations and drug applications on cell motility, effects of alterations in subcellular activities on motility cannot be fully elucidated from those methods. Here, we develop a strategy termed cell-nuclear (CN) correlation to parameterize represented dynamic subcellular activities and to quantify their contributions in mesenchymal-like migration. Based on the biophysical meaning of the CN correlation, we propose a cell migration potential index (CMPI) to measure cell motility. When the effectiveness of CMPI was evaluated with respect to one of the most popular cell migration analysis methods, Persistent Random Walk, we found that the cell motility estimates among six cell lines used in this study were highly consistent between these two approaches. Further evaluations indicated that CMPI can be determined using a shorter time period and smaller cell sample size, and it possesses excellent reliability and applicability, even in the presence of a wide range of noise, as might be generated from individual imaging acquisition systems. The novel approach outlined here introduces a robust strategy through an analysis of subcellular locomotion activities for single cell migration assessment.

  3. [Migration and urbanization in the Sahel. Consequences of the Sahelian migrations].

    PubMed

    Traore, S

    1997-10-01

    The consequences of Sahelian migration are multiple and diverse. In rural areas there may be a loss of income in the short run and a reduced possibility of development in the long run. Apart from its implications for urban growth, Sahelian migration may have four series of consequences in the places of origin. In detaching peasants from their lands, migration may contribute to loss of appreciation and reverence for the lands. Attachment to the lands of the ancestors loses its meaning as soon as questions of survival or economic rationality are raised. Migration contributes to the restructuring of the societies of origin. Increasing monetarization of market relations and introduction of new needs create new norms that favor stronger integration into the world economy. Migration may cause a decline in production because of the loss of the most active population, and it changes the age and sex distribution of households and usually increases their dependency burden. The effects on fertility and mortality are less clear. The effects of migration on the zones of arrival in the Sahel depend on the type of area. Conflicts between natives and in-migrants are common in rural-rural migration. Degradation of land may result from the increased demands placed upon it. Migrants to cities in Africa, and especially in the Sahel, appear to conserve their cultural values and to transplant and reinterpret their village rules of solidarity.

  4. Fisetin inhibits epidermal growth factor–induced migration of ARPE-19 cells by suppression of AKT activation and Sp1-dependent MMP-9 expression

    PubMed Central

    Lin, Hung-Yu; Chen, Yong-Syuan; Wang, Kai; Chien, Hsiang-Wen

    2017-01-01

    Purpose Proliferative vitreoretinopathy (PVR) can result in abnormal migration of RPE cells. Fisetin is a naturally occurring compound that has been reported to have antitumor effects, but its effects on epidermal growth factor (EGF)–induced cell migration and the underlying mechanisms remain unclear. Methods Effects of fisetin on EGF-induced cell viability and migration were examined with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and in vitro migration assays. Reverse transcription–PCR (RT–PCR) and immunoblotting were performed to evaluate matrix metallopeptidase-9 (MMP-9) expression and activation of specificity protein-1 (Sp1) and protein kinase B (AKT) in ARPE-19 cells treated with EGF and with or without fisetin. Luciferase and chromatin immunoprecipitation (ChIP) assays were performed to examine Sp1 transcription activity and MMP-9 binding activity. Results Fisetin did not affect ARPE-19 cell viability and significantly inhibited the EGF-induced migration capacity of ARPE-19 cells. Furthermore, fisetin exerted an antimigratory effect and suppressed MMP-9 mRNA and protein expression. Treatment with EGF induced phosphorylation of AKT and expression of MMP-9 and Sp1. Fisetin combined with LY294002 (an inhibitor of AKT) prevented the EGF-induced migration involved in downregulation of Sp1 and MMP-9 expression. Luciferase and ChIP assays suggested that fisetin remarkably decreased the EGF-induced transcription activity of MMP-9 and Sp1 and inhibited EGF-mediated Sp1 from directly binding to the MMP-9 promoter in ARPE-19 cells. Conclusions Fisetin inhibited EGF-induced cell migration via modulation of AKT/Sp1–dependent MMP-9 transcriptional activity. Therefore, fisetin may be a potential agent in the treatment of migratory PVR diseases. PMID:29296070

  5. AMF/PGI transactivates the MMP-3 gene through the activation of Src-RhoA-phosphatidylinositol 3-kinase signaling to induce hepatoma cell migration.

    PubMed

    Shih, Wen-Ling; Liao, Ming-Huei; Yu, Feng-Ling; Lin, Ping-Yuan; Hsu, Hsue-Yin; Chiu, Shu-Jun

    2008-11-08

    We have previously shown that AMF/PGI induces hepatoma cell migration through the induction of MMP-3. This work investigates how AMF/PGI activates the MMP-3 gene. We demonstrated that AMF/PGI transactivates the MMP-3 gene promoter through AP-1. The transactivation and induction of cell migration effect of AMF/PGI directly correlates with its enzymatic activity. Various analyses showed that AMF/PGI stimulated the Src-RhoA-PI3-kinase signaling pathway, and these three signaling molecules could form a complex. Our results demonstrate a new mechanism of AMF/PGI-induced cell migration and a link between Src-RhoA-PI3-kinase, AP-1, MMP-3 and hepatoma cell migration.

  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. Stereotactic core needle breast biopsy marker migration: An analysis of factors contributing to immediate marker migration.

    PubMed

    Jain, Ashali; Khalid, Maria; Qureshi, Muhammad M; Georgian-Smith, Dianne; Kaplan, Jonah A; Buch, Karen; Grinstaff, Mark W; Hirsch, Ariel E; Hines, Neely L; Anderson, Stephan W; Gallagher, Katherine M; Bates, David D B; Bloch, B Nicolas

    2017-11-01

    To evaluate breast biopsy marker migration in stereotactic core needle biopsy procedures and identify contributing factors. This retrospective study analyzed 268 stereotactic biopsy markers placed in 263 consecutive patients undergoing stereotactic biopsies using 9G vacuum-assisted devices from August 2010-July 2013. Mammograms were reviewed and factors contributing to marker migration were evaluated. Basic descriptive statistics were calculated and comparisons were performed based on radiographically-confirmed marker migration. Of the 268 placed stereotactic biopsy markers, 35 (13.1%) migrated ≥1 cm from their biopsy cavity. Range: 1-6 cm; mean (± SD): 2.35 ± 1.22 cm. Of the 35 migrated biopsy markers, 9 (25.7%) migrated ≥3.5 cm. Patient age, biopsy pathology, number of cores, and left versus right breast were not associated with migration status (P> 0.10). Global fatty breast density (P= 0.025) and biopsy in the inner region of breast (P = 0.031) were associated with marker migration. Superior biopsy approach (P= 0.025), locally heterogeneous breast density, and t-shaped biopsy markers (P= 0.035) were significant for no marker migration. Multiple factors were found to influence marker migration. An overall migration rate of 13% supports endeavors of research groups actively developing new biopsy marker designs for improved resistance to migration. • Breast biopsy marker migration is documented in 13% of 268 procedures. • Marker migration is affected by physical, biological, and pathological factors. • Breast density, marker shape, needle approach etc. affect migration. • Study demonstrates marker migration prevalence; marker design improvements are needed.

  8. 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

  9. Activation of Adenosine A2A Receptors Inhibits Neutrophil Transuroepithelial Migration

    PubMed Central

    Säve, Susanne; Mohlin, Camilla; Vumma, Ravi; Persson, Katarina

    2011-01-01

    Adenosine has been identified as a significant inhibitor of inflammation by acting on adenosine A2A receptors. In this study, we examined the role of adenosine and A2A receptors in the transmigration of human neutrophils across an in vitro model of the transitional bladder urothelium. Human uroepithelial cells (UROtsa) were grown on transwell inserts; uropathogenic Escherichia coli (UPEC) and neutrophils were added to the transwell system; and the number of migrating neutrophils was evaluated. Reverse transcription-PCR (RT-PCR), immunohistochemistry, and flow cytometry were used to investigate the expression of adenosine receptors, the epithelial adhesion molecule ICAM-1, and the neutrophil integrin CD11b. Levels of proinflammatory interleukin-8 (IL-8) and phosphorylated IκBα were measured by enzyme-linked immunosorbent assays (ELISA) and Luminex assays, respectively. The neutrophils expressed all four adenosine receptor subtypes (A1, A2A, A2B, and A3 receptors), but A3 receptors were not expressed by UROtsa cells. UPEC stimulated neutrophil transuroepithelial migration, which was significantly decreased in response to the specific A2A receptor agonist CGS 21680. The inhibitory effect of CGS 21680 on neutrophil migration was reversed by the A2A receptor antagonist SCH 58261. The production of chemotactic IL-8 and the expression of the adhesion molecule ICAM-1 or CD11b were not significantly affected by CGS 21680. However, a significant decrease in the level of phosporylated IκBα was revealed in response to CGS 21680. In conclusion, UPEC infection in vitro evoked neutrophil migration through a multilayered human uroepithelium. The UPEC-evoked neutrophil transmigration decreased in response to A2A receptor activation, possibly through inhibition of NF-κB signaling pathways. PMID:21646447

  10. Vascular endothelial growth factor receptor-1 mediates migration of human colorectal carcinoma cells by activation of Src family kinases

    PubMed Central

    Lesslie, D P; Summy, J M; Parikh, N U; Fan, F; Trevino, J G; Sawyer, T K; Metcalf, C A; Shakespeare, W C; Hicklin, D J; Ellis, L M; Gallick, G E

    2006-01-01

    Vascular endothelial growth factor (VEGF) is the predominant pro-angiogenic cytokine in human malignancy, and its expression correlates with disease recurrence and poor outcomes in patients with colorectal cancer. Recently, expression of vascular endothelial growth factor receptors (VEGFRs) has been observed on tumours of epithelial origin, including those arising in the colon, but the molecular mechanisms governing potential VEGF-driven biologic functioning in these tumours are not well characterised. In this report, we investigated the role of Src family kinases (SFKs) in VEGF-mediated signalling in human colorectal carcinoma (CRC) cell lines. Vascular endothelial growth factor specifically activated SFKs in HT29 and KM12L4 CRC cell lines. Further, VEGF stimulation resulted in enhanced cellular migration, which was effectively blocked by pharmacologic inhibition of VEGFR-1 or Src kinase. Correspondingly, migration studies using siRNA clones with reduced Src expression confirmed the requirement for Src in VEGF-induced migration in these cells. Furthermore, VEGF treatment enhanced VEGFR-1/SFK complex formation and increased tyrosine phosphorylation of focal adhesion kinase, p130 cas and paxillin. Finally, we demonstrate that VEGF-induced migration is not due, at least in part, to VEGF acting as a mitogen. These results suggest that VEGFR-1 promotes migration of tumour cells through a Src-dependent pathway linked to activation of focal adhesion components that regulate this process. PMID:16685275

  11. Evolution of cutoffs across meander necks in Powder River, Montana, USA

    USGS Publications Warehouse

    Gay, G.R.; Gay, H.H.; Gay, W.H.; Martinson, H.A.; Meade, R.H.; Moody, J.A.

    1998-01-01

    Over a period of several decades, gullies have been observed in various stages of forming, growing and completing the cutoff of meander necks in Powder River. During one episode of overbank flow, water flowing over the down-stream bank of the neck forms a headctu. The headcut migrates up-valley, forming a gully in its wake, until it has traversed the entire neck, cutting off the meander. The river then follows the course of the gully, which is subsequently enlarged as the river develops its new channel. The complete process usually requires several episodes of high water: in only one of the five cases described herein was a meander cutoff initiated and completed during a single large flood.

  12. The Sal-like 4 - integrin α6β1 network promotes cell migration for metastasis via activation of focal adhesion dynamics in basal-like breast cancer cells.

    PubMed

    Itou, Junji; Tanaka, Sunao; Li, Wenzhao; Iida, Atsuo; Sehara-Fujisawa, Atsuko; Sato, Fumiaki; Toi, Masakazu

    2017-01-01

    During metastasis, cancer cell migration is enhanced. However, the mechanisms underlying this process remain elusive. Here, we addressed this issue by functionally analyzing the transcription factor Sal-like 4 (SALL4) in basal-like breast cancer cells. Loss-of-function studies of SALL4 showed that this transcription factor is required for the spindle-shaped morphology and the enhanced migration of cancer cells. SALL4 also up-regulated integrin gene expression. The impaired cell migration observed in SALL4 knockdown cells was restored by overexpression of integrin α6 and β1. In addition, we clarified that integrin α6 and β1 formed a heterodimer. At the molecular level, loss of the SALL4 - integrin α6β1 network lost focal adhesion dynamics, which impairs cell migration. Over-activation of Rho is known to inhibit focal adhesion dynamics. We observed that SALL4 knockdown cells exhibited over-activation of Rho. Aberrant Rho activation was suppressed by integrin α6β1 expression, and pharmacological inhibition of Rho activity restored cell migration in SALL4 knockdown cells. These results indicated that the SALL4 - integrin α6β1 network promotes cell migration via modulation of Rho activity. Moreover, our zebrafish metastasis assays demonstrated that this gene network enhances cell migration in vivo. Our findings identify a potential new therapeutic target for the prevention of metastasis, and provide an improved understanding of cancer cell migration. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Concerted action of neuroepithelial basal shrinkage and active epithelial migration ensures efficient optic cup morphogenesis

    PubMed Central

    Sidhaye, Jaydeep; Norden, Caren

    2017-01-01

    Organ formation is a multi-scale event that involves changes at the intracellular, cellular and tissue level. Organogenesis often starts with the formation of characteristically shaped organ precursors. However, the cellular mechanisms driving organ precursor formation are often not clear. Here, using zebrafish, we investigate the epithelial rearrangements responsible for the development of the hemispherical retinal neuroepithelium (RNE), a part of the optic cup. We show that in addition to basal shrinkage of RNE cells, active migration of connected epithelial cells into the RNE is a crucial player in its formation. This cellular movement is driven by progressive cell-matrix contacts and actively translocates prospective RNE cells to their correct location before they adopt neuroepithelial fate. Failure of this migration during neuroepithelium formation leads to ectopic determination of RNE cells and consequently impairs optic cup formation. Overall, this study illustrates how spatiotemporal coordination between morphogenic movements and fate determination critically influences organogenesis. DOI: http://dx.doi.org/10.7554/eLife.22689.001 PMID:28372636

  14. Earthquake cluster activity beneath the Tanzawa Mountains region, Japan: Migration of hypocenters and low stress drop

    NASA Astrophysics Data System (ADS)

    Yamada, T.; Yukutake, Y.

    2013-12-01

    An earthquake cluster activity was observed beneath the Tanzawa Mountains region, Japan with a depth of 20 km in the end of January, 2012. Japan Meteorological Agency (JMA) determined hypocenters of 76 earthquakes with M > 2 in the area within 50 hours. Five of them had magnitudes greater than 4 and the largest one was 5.4. Four out of the five earthquakes had the reverse-type focal mechanisms with the P axis in the NW-SE direction. First we relocated hypocenters of the activity following the method of Yukutake et al. (2012). We estimated relative arrival times of P and S waves by calculating the coefficients of the cross correlation and relocated hypocenters with the double-difference relocation method (Waldhauser and Ellsworth, 2000). We found that the cluster activity showed a migration from the first earthquake of the activity. The parabolic migration speed was consistent with the migration speed of the deep tremor sources (Ide et al., 2010) for which the fluid activity would play an important role. We then analyzed stress drops of 17 earthquakes with M > 3.5 that occurred from January, 2000 to June, 2012 in the area of the cluster activity. We calculated empirical Green's functions from waveforms of earthquakes with magnitudes of 3.0 to 3.2 and estimated stress drops of the earthquakes assuming that the source spectra can be expressed as the omega-squared model. We found that earthquakes of the cluster activity had smaller stress drops by an order of magnitude than the values of earthquakes that occurred in the same area before the cluster activity. These results suggest that the fluid played an important role for the earthquake cluster activity. That is, the fluid increased the pore pressure, decreased the effective normal stress and triggered the cluster activity. The difference of the rupture speed and the change of the rigidity might also be candidates that account for our results. They, however, can hardly explain the results quantitatively. Fig

  15. Multiscale Cues Drive Collective Cell Migration

    NASA Astrophysics Data System (ADS)

    Nam, Ki-Hwan; Kim, Peter; Wood, David K.; Kwon, Sunghoon; Provenzano, Paolo P.; Kim, Deok-Ho

    2016-07-01

    To investigate complex biophysical relationships driving directed cell migration, we developed a biomimetic platform that allows perturbation of microscale geometric constraints with concomitant nanoscale contact guidance architectures. This permits us to elucidate the influence, and parse out the relative contribution, of multiscale features, and define how these physical inputs are jointly processed with oncogenic signaling. We demonstrate that collective cell migration is profoundly enhanced by the addition of contract guidance cues when not otherwise constrained. However, while nanoscale cues promoted migration in all cases, microscale directed migration cues are dominant as the geometric constraint narrows, a behavior that is well explained by stochastic diffusion anisotropy modeling. Further, oncogene activation (i.e. mutant PIK3CA) resulted in profoundly increased migration where extracellular multiscale directed migration cues and intrinsic signaling synergistically conspire to greatly outperform normal cells or any extracellular guidance cues in isolation.

  16. Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1

    PubMed Central

    Beaulieu, Lea M.; Church, Frank C.

    2014-01-01

    Activated protein C (APC) is a serine protease that regulates thrombin (IIa) production through inactivation of blood coagulation factors Va and VIIIa. APC also has non-hemostatic functions related to inflammation, proliferation, and apoptosis through various mechanisms. Using two breast cancer cell lines, MDA-MB-231 and MDA-MB-435, we investigated the role of APC in cell chemotaxis and invasion. Treatment of cells with increasing APC concentrations (1–50 μg/ml) increased invasion and chemotaxis in a concentration-dependent manner. Only the active form of APC increased invasion and chemotaxis of the MDA-MB-231 cells when compared to 3 inactive APC derivatives. Using a modified “checkerboard” analysis, APC was shown to only affect migration when plated with the cells; therefore, APC is not a chemoattractant. Blocking antibodies to endothelial protein C receptor (EPCR) and protease-activated receptor-1 (PAR-1) attenuated the effects of APC on chemotaxis in the MDA-MB-231 cells. Finally, treatment of the MDA-MB-231 cells with the proliferation inhibitor, Na butyrate, showed that APC did not increase migration by increasing cell number. Therefore, APC increases invasion and chemotaxis of cells by binding to the cell surface and activating specific signaling pathways through EPCR and PAR-1. PMID:17254565

  17. Effects of rosuvastatin on the production and activation of matrix metalloproteinase-2 and migration of cultured rat vascular smooth muscle cells induced by homocysteine.

    PubMed

    Shi, Ya-fei; Chi, Ju-fang; Tang, Wei-liang; Xu, Fu-kang; Liu, Long-bin; Ji, Zheng; Lv, Hai-tao; Guo, Hang-yuan

    2013-08-01

    To test the influence of homocysteine on the production and activation of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of matrix metalloproteinase-2 (TIMP-2) and on cell migration of cultured rat vascular smooth muscle cells (VSMCs). Also, to explore whether rosuvastatin can alter the abnormal secretion and activation of MMP-2 and TIMP-2 and migration of VSMCs induced by homocysteine. Rat VSMCs were incubated with different concentrations of homocysteine (50-5000 μmol/L). Western blotting and gelatin zymography were used to investigate the expressions and activities of MMP-2 and TIMP-2 in VSMCs in culture medium when induced with homocysteine for 24, 48, and 72 h. Transwell chambers were employed to test the migratory ability of VSMCs when incubated with homocysteine for 48 h. Different concentrations of rosuvastatin (10(-9)-10(-5) mol/L) were added when VSMCs were induced with 1000 μmol/L homocysteine. The expressions and activities of MMP-2 and TIMP-2 were examined after incubating for 24, 48, and 72 h, and the migration of VSMCs was also examined after incubating for 48 h. Homocysteine (50-1000 μmol/L) increased the production and activation of MMP-2 and expression of TIMP-2 in a dose-dependent manner. However, when incubated with 5000 μmol/L homocysteine, the expression of MMP-2 was up-regulated, but its activity was down-regulated. Increased homocysteine-induced production and activation of MMP-2 were reduced by rosuvastatin in a dose-dependent manner whereas secretion of TIMP-2 was not significantly altered by rosuvastatin. Homocysteine (50-5000 μmol/L) stimulated the migration of VSMCs in a dose-dependent manner, but this effect was eliminated by rosuvastatin. Homocysteine (50-1000 μmol/L) significantly increased the production and activation of MMP-2, the expression of TIMP-2, and the migration of VSMCs in a dose-dependent manner. Additional extracellular rosuvastatin can decrease the excessive expression and activation of MMP-2 and

  18. 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.

  19. Moderate plasma activated media suppresses proliferation and migration of MDCK epithelial cells

    NASA Astrophysics Data System (ADS)

    Mohades, Soheila; Laroussi, Mounir; Maruthamuthu, Venkat

    2017-05-01

    Low-temperature plasma has been shown to have diverse biomedical uses, including its applications in cancer and wound healing. One recent approach in treating mammalian cells with plasma is through the use of plasma activated media (PAM), which is produced by exposing cell culture media to plasma. While the adverse effects of PAM treatment on cancerous epithelial cell lines have been recently studied, much less is known about the interaction of PAM with normal epithelial cells. In this paper, non-cancerous canine kidney MDCK (Madin-Darby Canine Kidney) epithelial cells were treated by PAM and time-lapse microscopy was used to directly monitor their proliferation and random migration upon treatment. While longer durations of PAM treatment led to cell death, we found that moderate levels of PAM treatment inhibited proliferation in these epithelial cells. We also found that PAM treatment reduced random cell migration within epithelial islands. Immunofluorescence staining showed that while there were no major changes in the actin/adhesion apparatus, there was a significant change in the nuclear localization of proliferation marker Ki-67, consistent with our time-lapse results.

  20. Soluble tissue factor has unique angiogenic activities that selectively promote migration and differentiation but not proliferation of endothelial cells

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

    He Yingbo; Chang Guodong; Zhan Shunli

    2008-06-06

    The level of circulating tissue factor (TF) is up-regulated in human angiogenesis-related malignancies. However, whether circulating TF has angiogenic activities has not been determined. Soluble TF (sTF) is the main domain of circulating TF. Here, using cell migration, wound healing, and tubule formation assays, human recombinant sTF was found to significantly promote the migration and differentiation of endothelial cells. The stress fiber formation and rearrangement induced by sTF observed through immunofluorescence microscope may be responsible for the stimulatory migration effect of sTF. Nevertheless, sTF had no effects on endothelial cell proliferation. Interestingly, sTF can be internalized by endothelial cells, whichmore » implies a novel mechanism for sTF in angiogenesis. These results suggest that sTF has unique angiogenic activities and may serve as a potential therapeutic target to treat diseases associated with angiogenesis such as cancer and rheumatoid arthritis.« less

  1. 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.

  2. A source migration of low frequency earthquakes during the 2000 activity of Miyake-jima volcano, Japan

    NASA Astrophysics Data System (ADS)

    Kobayashi, T.; Ohminato, T.; Fujita, E.; Ida, Y.

    2002-12-01

    The volcanic activity of Miyake-jima started at 18:30 (JST) on June 26, 2000 with large ground deformation and earthquake swarms. The seismic activity started at the southern part of the island. The hypocenter distribution migrated northwestward and slipped away out of the island by early in the morning, June 27. Low frequency (LF) earthquakes with dominant frequencies of 0.2 and 0.4 Hz were first observed in the afternoon of June 27. The LF activity lasted till the first summit eruption on July 8. Earthquake Research Institute of Tokyo University and National Research Institute for Earth Science and Disaster Prevention deployed 3 CMG-3T and 4 STS-2 broadband seismometers in the island. More than 300 LF earthquakes are detected during the period from June 27 to July 8. Most of the LF events whose dominant frequency is 0.2Hz occurred before July 1, while LF events with dominant frequency of 0.4Hz mainly occurred after July 2. We determine hypocenters of these LF events by using the following technique. For each LF event, we assume a source location on a grid point in a homogeneous half-space. A reference station is chosen among all the stations. The cross correlation coefficients are computed between the waveform of the reference station and those of other stations. Then, the coefficients for all the stations are summed. In the same manner, summations of the coefficients are computed grid by grid. A grid point that gives the maximum value of the sum of the coefficients is regarded as the best estimate of the source location of the LF event under consideration. The result shows that hypocenters of LF events are spread over the southern to western part of the island and they migrate from south to the west day by day. Hypocenter migrations associated with volcanic activity have been often reported but usually for short period events. This is one of remarkable cases in which a migration of earthquakes with dominant frequencies as low as 0.2 and 0.4Hz are clearly

  3. Antioxidant activity of Coriandrum sativum and protection against DNA damage and cancer cell migration.

    PubMed

    Tang, Esther L H; Rajarajeswaran, Jayakumar; Fung, Shin Yee; Kanthimathi, M S

    2013-12-09

    Coriandrum sativum is a popular culinary and medicinal herb of the Apiaceae family. Health promoting properties of this herb have been reported in pharmacognostical, phytochemical and pharmacological studies. However, studies on C. sativum have always focused on the aerial parts of the herb and scientific investigation on the root is limited. The aim of this research was to investigate the antioxidant and anticancer activities of C. sativum root, leaf and stem, including its effect on cancer cell migration, and its protection against DNA damage, with special focus on the roots. Powdered roots, leaves and stems of C. sativum were extracted through sequential extraction using hexane, dichloromethane, ethyl acetate, methanol and water. Total phenolic content, FRAP and DPPH radical scavenging activities were measured. Anti-proliferative activitiy on the breast cancer cell line, MCF-7, was assayed using the MTT assay. Activities of the antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase, and of the caspases-3, -8 and -9 were assayed on treatment with the extract. Cell cycle progression was analysed using flow cytometry. The scratch motility assay was used to assess inhibition of MCF-7 cell migration. DNA damage in 3 T3-L1 fibroblasts was evaluated by the comet assay. The components in the extract were identified by HPLC and GC-MS. The ethyl acetate extract of C. sativum roots showed the highest antiproliferative activity on MCF-7 cells (IC50 = 200.0 ± 2.6 μg/mL) and had the highest phenolic content, FRAP and DPPH scavenging activities among the extracts. C. sativum root inhibited DNA damage and prevented MCF-7 cell migration induced by H2O2, suggesting its potential in cancer prevention and inhibition of metastasis. The extract exhibited anticancer activity in MCF-7 cells by affecting antioxidant enzymes possibly leading to H2O2 accumulation, cell cycle arrest at the G2/M phase and apoptotic cell death by the death receptor and

  4. Antioxidant activity of Coriandrum sativum and protection against DNA damage and cancer cell migration

    PubMed Central

    2013-01-01

    Background Coriandrum sativum is a popular culinary and medicinal herb of the Apiaceae family. Health promoting properties of this herb have been reported in pharmacognostical, phytochemical and pharmacological studies. However, studies on C. sativum have always focused on the aerial parts of the herb and scientific investigation on the root is limited. The aim of this research was to investigate the antioxidant and anticancer activities of C. sativum root, leaf and stem, including its effect on cancer cell migration, and its protection against DNA damage, with special focus on the roots. Methods Powdered roots, leaves and stems of C. sativum were extracted through sequential extraction using hexane, dichloromethane, ethyl acetate, methanol and water. Total phenolic content, FRAP and DPPH radical scavenging activities were measured. Anti-proliferative activitiy on the breast cancer cell line, MCF-7, was assayed using the MTT assay. Activities of the antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase, and of the caspases-3, -8 and -9 were assayed on treatment with the extract. Cell cycle progression was analysed using flow cytometry. The scratch motility assay was used to assess inhibition of MCF-7 cell migration. DNA damage in 3 T3-L1 fibroblasts was evaluated by the comet assay. The components in the extract were identified by HPLC and GC-MS. Results The ethyl acetate extract of C. sativum roots showed the highest antiproliferative activity on MCF-7 cells (IC50 = 200.0 ± 2.6 μg/mL) and had the highest phenolic content, FRAP and DPPH scavenging activities among the extracts. C. sativum root inhibited DNA damage and prevented MCF-7 cell migration induced by H2O2, suggesting its potential in cancer prevention and inhibition of metastasis. The extract exhibited anticancer activity in MCF-7 cells by affecting antioxidant enzymes possibly leading to H2O2 accumulation, cell cycle arrest at the G2/M phase and apoptotic cell death by

  5. Smad4 inhibits cell migration via suppression of JNK activity in human pancreatic carcinoma PANC-1 cells.

    PubMed

    Zhang, Xueying; Cao, Junxia; Pei, Yujun; Zhang, Jiyan; Wang, Qingyang

    2016-05-01

    Smad4 is a common Smad and is a key downstream regulator of the transforming growth factor-β signaling pathway, in which Smad4 often acts as a potent tumor suppressor and functions in a highly context-dependent manner, particularly in pancreatic cancer. However, little is known regarding whether Smad4 regulates other signaling pathways involved in pancreatic cancer. The present study demonstrated that Smad4 downregulates c-Jun N-terminal kinase (JNK) activity using a Smad4 loss-of-function or gain-of-function analysis. Additionally, stable overexpression of Smad4 clearly affected the migration of human pancreatic epithelioid carcinoma PANC-1 cells, but did not affect cell growth. In addition, the present study revealed that upregulation of mitogen-activated protein kinase phosphatase-1 is required for the reduction of JNK activity by Smad4, leading to a decrease in vascular endothelial growth factor expression and inhibiting cell migration. Overall, the present findings indicate that Smad4 may suppress JNK activation and inhibit the tumor characteristics of pancreatic cancer cells.

  6. 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.

  7. A note on the modelling of circular smallholder migration.

    PubMed

    Bigsten, A

    1988-01-01

    "It is argued that circular migration [in Africa] should be seen as an optimization problem, where the household allocates its labour resources across activities, including work which requires migration, so as to maximize the joint family utility function. The migration problem is illustrated in a simple diagram, which makes it possible to analyse economic aspects of migration." excerpt

  8. Optimal migration energetics of humpback whales and the implications of disturbance.

    PubMed

    Braithwaite, Janelle E; Meeuwig, Jessica J; Hipsey, Matthew R

    2015-01-01

    Whales migrate long distances and reproduce on a finite store of energy. Budgeting the use of this limited energy reserve is an important factor to ensure survival over the period of migration and to maximize reproductive investment. For some whales, migration routes are closely associated with coastal areas, exposing animals to high levels of human activity. It is currently unclear how various forms of human activity may disturb whales during migration, how this might impact their energy balance and how this could translate into long-term demographic changes. Here, we develop a theoretical bioenergetic model for migrating humpback whales to investigate the optimal migration strategy that minimizes energy use. The average migration velocity was an important driver of the total energy used by a whale, and an optimal velocity of 1.1 m s(-1) was determined. This optimal velocity is comparable to documented observed migration speeds, suggesting that whales migrate at a speed that conserves energy. Furthermore, the amount of resting time during migration was influenced by both transport costs and feeding rates. We simulated hypothetical disturbances to the optimal migration strategy in two ways, by altering average velocity to represent changes in behavioural activity and by increasing total travelled distance to represent displacement along the migration route. In both cases, disturbance increased overall energy use, with implications for the growth potential of calves.

  9. Optimal migration energetics of humpback whales and the implications of disturbance

    PubMed Central

    Braithwaite, Janelle E.; Meeuwig, Jessica J.; Hipsey, Matthew R.

    2015-01-01

    Whales migrate long distances and reproduce on a finite store of energy. Budgeting the use of this limited energy reserve is an important factor to ensure survival over the period of migration and to maximize reproductive investment. For some whales, migration routes are closely associated with coastal areas, exposing animals to high levels of human activity. It is currently unclear how various forms of human activity may disturb whales during migration, how this might impact their energy balance and how this could translate into long-term demographic changes. Here, we develop a theoretical bioenergetic model for migrating humpback whales to investigate the optimal migration strategy that minimizes energy use. The average migration velocity was an important driver of the total energy used by a whale, and an optimal velocity of 1.1 m s−1 was determined. This optimal velocity is comparable to documented observed migration speeds, suggesting that whales migrate at a speed that conserves energy. Furthermore, the amount of resting time during migration was influenced by both transport costs and feeding rates. We simulated hypothetical disturbances to the optimal migration strategy in two ways, by altering average velocity to represent changes in behavioural activity and by increasing total travelled distance to represent displacement along the migration route. In both cases, disturbance increased overall energy use, with implications for the growth potential of calves. PMID:27293686

  10. Detoxification enzyme activities (CYP1A1 and GST) in the skin of humpback whales as a function of organochlorine burdens and migration status.

    PubMed

    Bengtson Nash, S; Dawson, A; Burkhard, M; Waugh, C; Huston, W

    2014-10-01

    The activities of glutathione-s-transferase (GST) and cytochrome P-450 1A1 (CYP1A1) enzymes were measured in freshly extracted epidermis of live-biopsied, migrating, southern hemisphere humpback whales (Megaptera novaeangliae). The two quantified enzyme activities did not correlate strongly with each other. Similarly, neither correlated strongly with any of the organochlorine compound groups previously measured in the superficial blubber of the sample biopsy core, likely reflecting the anticipated low levels of typical aryl-hydrocarbon receptor ligands. GST activity did not differ significantly between genders or between northward (early migration) or southward (late migration) migrating cohorts. Indeed, the inter-individual variability in GST measurements was relatively low. This observation raises the possibility that measured activities were basal activities and that GST function was inherently impacted by the fasting state of the sampled animals, as seen in other species. These results do not support the implementation of CYP1A1 or GST as effective biomarkers of organochlorine contaminant burdens in southern hemisphere populations of humpback whales as advocated for other cetacean species. Further investigation of GST activity in feeding versus fasting cohorts may, however, provide some insight into the fasting metabolism of these behaviourally adapted populations. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Annexin-1 Mediates Microglial Activation and Migration via the CK2 Pathway during Oxygen–Glucose Deprivation/Reperfusion

    PubMed Central

    Liu, Shuangxi; Gao, Yan; Yu, Xiaoli; Zhao, Baoming; Liu, Lu; Zhao, Yin; Luo, Zhenzhao; Shi, Jing

    2016-01-01

    Annexin-1 (ANXA1) has shown neuroprotective effects and microglia play significant roles during central nervous system injury, yet the underlying mechanisms remain unclear. This study sought to determine whether ANXA1 regulates microglial response to oxygen–glucose deprivation/reperfusion (OGD/R) treatment and to clarify the downstream molecular mechanism. In rat hippocampal slices, OGD/R treatment enhanced the ANXA1 expression in neuron, the formyl peptide receptor (FPRs) expression in microglia, and the microglial activation in the CA1 region (cornu ammonis 1). These effects were reversed by the FPRs antagonist Boc1. The cell membrane currents amplitude of BV-2 microglia (the microglial like cell-line) was increased when treated with Ac2-26, the N-terminal peptide of ANXA1. Ac2-26 treatment enhanced BV-2 microglial migration whereas Boc1 treatment inhibited the migration. In BV-2 microglia, both the expression of the CK2 target phosphorylated α-E-catenin and the binding of casein kinase II (CK2) with α-E-catenin were elevated by Ac2-26, these effects were counteracted by the CK2 inhibitor TBB and small interfering (si) RNA directed against transcripts of CK2 and FPRs. Moreover, both TBB and siRNA-mediated inhibition of CK2 blocked Ac2-26-mediated BV-2 microglia migration. Our findings indicate that ANXA1 promotes microglial activation and migration during OGD/R via FPRs, and CK2 target α-E-catenin phosphorylation is involved in this process. PMID:27782092

  12. Gβ1 is required for neutrophil migration in zebrafish.

    PubMed

    Ke, Wenfan; Ye, Ding; Mersch, Kacey; Xu, Hui; Chen, Songhai; Lin, Fang

    2017-08-01

    Signaling mediated by G protein-coupled receptors (GPCRs) is essential for the migration of cells toward chemoattractants. The recruitment of neutrophils to injured tissues in zebrafish larvae is a useful model for studying neutrophil migration and trafficking in vivo. Indeed, the study of this process led to the discovery that PI3Kγ is required for the polarity and motility of neutrophils, features that are necessary for the directed migration of these cells to wounds. However, the mechanism by which PI3Kγ is activated remains to be determined. Here we show that signaling by specifically the heterotrimeric G protein subunit Gβ1 is critical for neutrophil migration in response to wounding. In embryos treated with small-molecule inhibitors of Gβγ signaling, neutrophils failed to migrate to wound sites. Although both the Gβ1 and Gβ4 isoforms are expressed in migrating neutrophils, only deficiency for the former (morpholino-based knockdown) interfered with the directed migration of neutrophils towards wounds. The Gβ1 deficiency also impaired the ability of cells to change cell shape and reduced their general motility, defects that are similar to those in neutrophils deficient for PI3Kγ. Transplantation assays showed that the requirement for Gβ1 in neutrophil migration is cell autonomous. Finally, live imaging revealed that Gβ1 is required for polarized activation of PI3K, and for the actin dynamics that enable neutrophil migration. Collectively, our data indicate that Gβ1 signaling controls proper neutrophil migration by activating PI3K and modulating actin dynamics. Moreover, they illustrate a role for a specific Gβ isoform in chemotaxis in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Photonic modulation of EGFR: 280nm low level light arrests cancer cell activation and migration

    NASA Astrophysics Data System (ADS)

    Botelho, Cláudia M.; Marques, Rogério; Viruthachalam, Thiagarajan; Gonçalves, Odete; Vorum, Henrik; Gomes, Andreia C.; Neves-Petersen, Maria Teresa

    2017-02-01

    Overexpression of the Epidermal Growth Factor Receptor (EGFR) by cancer cells is associated with a poor prognosis for the patient. For several decades, therapies targeting EGFR have been designed, including the use of monoclonal antibodies and small molecule tyrosine kinase inhibitors. The use of these molecules had good clinical results, although its efficiency (and specificity) is still far from being optimal. In this paper, we present a new approach for a possible new cancer therapy targeting EGFR and using low intensity 280nm light. The influence of 280nm UVB illumination on cancer cells stimulated with 2nM of EGF was followed by time-lapse confocal microscopy. The 280nm illumination of the cancer cells blocks EGFR activation, inhibiting EGFR internalization and cell migration thus inhibiting the transition to the metastatic phenotype. Exposure time is a very important factor. The higher the illumination time the more significant differences were observed: 280nm light delayed or completely halted EGFR activation in the cell membrane, mainly at the cell junction level, and delayed or halted EGFR endocytic internalization, filopodia formation and cell migration.

  14. Active and passive migration in boring isopods Limnoria spp. (Crustacea, Peracarida) from kelp holdfasts

    NASA Astrophysics Data System (ADS)

    Miranda, Leonardo; Thiel, Martin

    2008-10-01

    Many boring isopods inhabit positively buoyant substrata (wood and algae), which float after detachment, permitting passive migration of inhabitants. Based on observations from previous studies, it was hypothesized that juvenile, subadult and male isopods migrate actively, and will rapidly abandon substrata after detachment. In contrast, reproductive females and small offspring were predicted to remain in floating substrata and thus have a high probability to disperse passively via rafting. In order to test this hypothesis, a colonization and an emigration experiment were conducted with giant kelp ( Macrocystis integrifolia), the holdfasts of which are inhabited by boring isopods from the genus Limnoria. A survey of benthic substrata in the kelp forest confirmed that limnoriids inhabited the holdfasts and did not occur in holdfast-free samples. Results of the colonization experiment showed that all life history stages of the boring isopods immigrated into young, largely uncolonized holdfasts, and after 16 weeks all holdfasts were densely colonized. In the emigration experiment, all life history stages of the isopods rapidly abandoned the detached holdfasts — already 5 min after detachment only few individuals remained in the floating holdfasts. After this initial rapid emigration of isopods, little changes in isopod abundance occurred during the following 24 h, and at the end of the experiment some individuals of all life history stages still remained in the holdfasts. These results indicate that all life history stages of Limnoria participate in both active migration and passive dispersal. It is discussed that storm-related dynamics within kelp forests may contribute to intense mixing of local populations of these burrow-dwelling isopods, and that most immigrants to young holdfasts probably are individuals emigrating from old holdfasts detached during storm events. The fact that some individuals of all life history stages and both sexes remain in floating

  15. Arc/Arg3.1 governs inflammatory dendritic cell migration from the skin and thereby controls T cell activation.

    PubMed

    Ufer, Friederike; Vargas, Pablo; Engler, Jan Broder; Tintelnot, Joseph; Schattling, Benjamin; Winkler, Hana; Bauer, Simone; Kursawe, Nina; Willing, Anne; Keminer, Oliver; Ohana, Ora; Salinas-Riester, Gabriela; Pless, Ole; Kuhl, Dietmar; Friese, Manuel A

    2016-09-23

    Skin-migratory dendritic cells (migDCs) are pivotal antigen-presenting cells that continuously transport antigens to draining lymph nodes and regulate immune responses. However, identification of migDCs is complicated by the lack of distinguishing markers, and it remains unclear which molecules determine their migratory capacity during inflammation. We show that, in the skin, the neuronal plasticity molecule activity-regulated cytoskeleton-associated protein/activity-regulated gene 3.1 (Arc/Arg3.1) was strictly confined to migDCs. Mechanistically, Arc/Arg3.1 was required for accelerated DC migration during inflammation because it regulated actin dynamics through nonmuscle myosin II. Accordingly, Arc/Arg3.1-dependent DC migration was critical for mounting T cell responses in experimental autoimmune encephalomyelitis and allergic contact dermatitis. Thus, Arc/Arg3.1 was restricted to migDCs in the skin and drove fast DC migration by exclusively coordinating cytoskeletal changes in response to inflammatory challenges. These findings commend Arc/Arg3.1 as a universal switch in migDCs that may be exploited to selectively modify immune responses. Copyright © 2016, American Association for the Advancement of Science.

  16. Mammalian EAK-7 activates alternative mTOR signaling to regulate cell proliferation and migration.

    PubMed

    Nguyen, Joe Truong; Ray, Connor; Fox, Alexandra Lucienne; Mendonça, Daniela Baccelli; Kim, Jin Koo; Krebsbach, Paul H

    2018-05-01

    Nematode EAK-7 (enhancer-of- akt -1-7) regulates dauer formation and controls life span; however, the function of the human ortholog mammalian EAK-7 (mEAK-7) is unknown. We report that mEAK-7 activates an alternative mechanistic/mammalian target of rapamycin (mTOR) signaling pathway in human cells, in which mEAK-7 interacts with mTOR at the lysosome to facilitate S6K2 activation and 4E-BP1 repression. Despite interacting with mTOR and mammalian lethal with SEC13 protein 8 (mLST8), mEAK-7 does not interact with other mTOR complex 1 (mTORC1) or mTOR complex 2 (mTORC2) components; however, it is essential for mTOR signaling at the lysosome. This phenomenon is distinguished by S6 and 4E-BP1 activity in response to nutrient stimulation. Conventional S6K1 phosphorylation is uncoupled from S6 phosphorylation in response to mEAK-7 knockdown. mEAK-7 recruits mTOR to the lysosome, a crucial compartment for mTOR activation. Loss of mEAK-7 results in a marked decrease in lysosomal localization of mTOR, whereas overexpression of mEAK-7 results in enhanced lysosomal localization of mTOR. Deletion of the carboxyl terminus of mEAK-7 significantly decreases mTOR interaction. mEAK-7 knockdown decreases cell proliferation and migration, whereas overexpression of mEAK-7 enhances these cellular effects. Constitutively activated S6K rescues mTOR signaling in mEAK-7-knocked down cells. Thus, mEAK-7 activates an alternative mTOR signaling pathway through S6K2 and 4E-BP1 to regulate cell proliferation and migration.

  17. Role of exchange protein directly activated by cAMP (EPAC1) in breast cancer cell migration and apoptosis.

    PubMed

    Kumar, Naveen; Gupta, Sonal; Dabral, Surbhi; Singh, Shailja; Sehrawat, Seema

    2017-06-01

    Despite the current progress in cancer research and therapy, breast cancer remains the leading cause of mortality among half a million women worldwide. Migration and invasion of cancer cells are associated with prevalent tumor metastasis as well as high mortality. Extensive studies have powerfully established the role of prototypic second messenger cAMP and its two ubiquitously expressed intracellular cAMP receptors namely the classic protein kinaseA/cAMP-dependent protein kinase (PKA) and the more recently discovered exchange protein directly activated by cAMP/cAMP-regulated guanine nucleotide exchange factor (EPAC/cAMP-GEF) in cell migration, cell cycle regulation, and cell death. Herein, we performed the analysis of the Cancer Genome Atlas (TCGA) dataset to evaluate the essential role of cAMP molecular network in breast cancer. We report that EPAC1, PKA, and AKAP9 along with other molecular partners are amplified in breast cancer patients, indicating the importance of this signaling network. To evaluate the functional role of few of these proteins, we used pharmacological modulators and analyzed their effect on cell migration and cell death in breast cancer cells. Hence, we report that inhibition of EPAC1 activity using pharmacological modulators leads to inhibition of cell migration and induces cell death. Additionally, we also observed that the inhibition of EPAC1 resulted in disruption of its association with the microtubule cytoskeleton and delocalization of AKAP9 from the centrosome as analyzed by in vitro imaging. Finally, this study suggests for the first time the mechanistic insights of mode of action of a primary cAMP-dependent sensor, Exchange protein activated by cAMP 1 (EPAC1), via its interaction with A-kinase anchoring protein 9 (AKAP9). This study provides a new cell signaling cAMP-EPAC1-AKAP9 direction to the development of additional biotherapeutics for breast cancer.

  18. Phytoplankton can actively diversify their migration strategy in response to turbulent cues

    NASA Astrophysics Data System (ADS)

    Sengupta, Anupam; Carrara, Francesco; Stocker, Roman

    2017-03-01

    Marine phytoplankton inhabit a dynamic environment where turbulence, together with nutrient and light availability, shapes species fitness, succession and selection. Many species of phytoplankton are motile and undertake diel vertical migrations to gain access to nutrient-rich deeper layers at night and well-lit surface waters during the day. Disruption of this migratory strategy by turbulence is considered to be an important cause of the succession between motile and non-motile species when conditions turn turbulent. However, this classical view neglects the possibility that motile species may actively respond to turbulent cues to avoid layers of strong turbulence. Here we report that phytoplankton, including raphidophytes and dinoflagellates, can actively diversify their migratory strategy in response to hydrodynamic cues characteristic of overturning by Kolmogorov-scale eddies. Upon experiencing repeated overturning with timescales and statistics representative of ocean turbulence, an upward-swimming population rapidly (5-60 min) splits into two subpopulations, one swimming upward and one swimming downward. Quantitative morphological analysis of the harmful-algal-bloom-forming raphidophyte Heterosigma akashiwo together with a model of cell mechanics revealed that this behaviour was accompanied by a modulation of the cells’ fore-aft asymmetry. The minute magnitude of the required modulation, sufficient to invert the preferential swimming direction of the cells, highlights the advanced level of control that phytoplankton can exert on their migratory behaviour. Together with observations of enhanced cellular stress after overturning and the typically deleterious effects of strong turbulence on motile phytoplankton, these results point to an active adaptation of H. akashiwo to increase the chance of evading turbulent layers by diversifying the direction of migration within the population, in a manner suggestive of evolutionary bet-hedging. This migratory

  19. Phytoplankton can actively diversify their migration strategy in response to turbulent cues.

    PubMed

    Sengupta, Anupam; Carrara, Francesco; Stocker, Roman

    2017-03-23

    Marine phytoplankton inhabit a dynamic environment where turbulence, together with nutrient and light availability, shapes species fitness, succession and selection. Many species of phytoplankton are motile and undertake diel vertical migrations to gain access to nutrient-rich deeper layers at night and well-lit surface waters during the day. Disruption of this migratory strategy by turbulence is considered to be an important cause of the succession between motile and non-motile species when conditions turn turbulent. However, this classical view neglects the possibility that motile species may actively respond to turbulent cues to avoid layers of strong turbulence. Here we report that phytoplankton, including raphidophytes and dinoflagellates, can actively diversify their migratory strategy in response to hydrodynamic cues characteristic of overturning by Kolmogorov-scale eddies. Upon experiencing repeated overturning with timescales and statistics representative of ocean turbulence, an upward-swimming population rapidly (5-60 min) splits into two subpopulations, one swimming upward and one swimming downward. Quantitative morphological analysis of the harmful-algal-bloom-forming raphidophyte Heterosigma akashiwo together with a model of cell mechanics revealed that this behaviour was accompanied by a modulation of the cells' fore-aft asymmetry. The minute magnitude of the required modulation, sufficient to invert the preferential swimming direction of the cells, highlights the advanced level of control that phytoplankton can exert on their migratory behaviour. Together with observations of enhanced cellular stress after overturning and the typically deleterious effects of strong turbulence on motile phytoplankton, these results point to an active adaptation of H. akashiwo to increase the chance of evading turbulent layers by diversifying the direction of migration within the population, in a manner suggestive of evolutionary bet-hedging. This migratory behaviour

  20. 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.

  1. Tyrosine Phosphorylation of the Guanine Nucleotide Exchange Factor GIV Promotes Activation of PI3K During Cell Migration

    PubMed Central

    Lin, Changsheng; Ear, Jason; Pavlova, Yelena; Mittal, Yash; Kufareva, Irina; Ghassemian, Majid; Abagyan, Ruben; Garcia-Marcos, Mikel; Ghosh, Pradipta

    2014-01-01

    GIV (Gα-interacting vesicle-associated protein; also known as Girdin), enhances Akt activation downstream of multiple growth factor– and G-protein–coupled receptors to trigger cell migration and cancer invasion. Here we demonstrate that GIV is a tyrosine phosphoprotein that directly binds to and activates phosphoinositide 3-kinase (PI3K). Upon ligand stimulation of various receptors, GIV was phosphorylated at Tyr1764 and Tyr1798 by both receptor and non-receptor tyrosine kinases. These phosphorylation events enabled direct binding of GIV to the N- and C-terminal SH2 domains of p85α, a regulatory subunit of PI3K, stabilized receptor association with PI3K, and enhanced PI3K activity at the plasma membrane to trigger cell migration. Tyrosine phosphorylation of GIV and its association with p85α increased during metastatic progression of a breast carcinoma. These results suggest a mechanism by which multiple receptors activate PI3K through tyrosine phosphorylation of GIV, thereby making the GIVPI3K interaction a potential therapeutic target within the PI3K-Akt pathway. PMID:21954290

  2. Investigations of the potential effects of underwater noise from petroleum-industry activities on migrating gray-whale behavior. Phase 2: January 1984 migration

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

    Malme, C.I.; Miles, P.R.; Clark, C.W.

    1984-08-01

    The study supplements work performed during 1983 in the Monterey, California region in determining the degree of behavioral response of migrating gray whales to acoustic stimuli associated with oil and gas exploration and development activities. A computer-implemented trackline program analyzed the theodolite data for any possible changes in distance from shore, speed, linearity of track, orientation toward the sound source, and course heading of the whale group. A history of marine seismic exploration off California was compiled that showed no long-term relationship with growth rates in the gray whale population.

  3. Involvement of nitric oxide synthase in matrix metalloproteinase-9- and/or urokinase plasminogen activator receptor-mediated glioma cell migration

    PubMed Central

    2013-01-01

    Background Src tyrosine kinase activates inducible nitric oxide synthase (iNOS) and, in turn, nitric oxide production as a means to transduce cell migration. Src tyrosine kinase plays a key proximal role to control α9β1 signaling. Our recent studies have clearly demonstrated the role of α9β1 integrin in matrix metalloproteinase-9 (MMP-9) and/or urokinase plasminogen activator receptor (uPAR)-mediated glioma cell migration. In the present study, we evaluated the involvement of α9β1 integrin-iNOS pathway in MMP-9- and/or uPAR-mediated glioma cell migration. Methods MMP-9 and uPAR shRNAs and overexpressing plasmids were used to downregulate and upregulate these molecules, respectively in U251 glioma cells and 5310 glioma xenograft cells. The effect of treatments on migration and invasion potential of these glioma cells were assessed by spheroid migration, wound healing, and Matrigel invasion assays. In order to attain the other objectives we also performed immunocytochemical, immunohistochemical, RT-PCR, Western blot and fluorescence-activated cell sorting (FACS) analysis. Results Immunohistochemical analysis revealed the prominent association of iNOS with glioblastoma multiforme (GBM). Immunofluorescence analysis showed prominent expression of iNOS in glioma cells. MMP-9 and/or uPAR knockdown by respective shRNAs reduced iNOS expression in these glioma cells. RT-PCR analysis revealed elevated iNOS mRNA expression in either MMP-9 or uPAR overexpressed glioma cells. The migration potential of MMP-9- and/or uPAR-overexpressed U251 glioma cells was significantly inhibited after treatment with L-NAME, an inhibitor of iNOS. Similarly, a significant inhibition of the invasion potential of the control or MMP-9/uPAR-overexpressed glioma cells was noticed after L-NAME treatment. A prominent reduction of iNOS expression was observed in the tumor regions of nude mice brains, which were injected with 5310 glioma cells, after MMP-9 and/or uPAR knockdown. Protein expressions

  4. Evidence for tension-based regulation of Drosophila MAL and SRF during invasive cell migration.

    PubMed

    Somogyi, Kálmán; Rørth, Pernille

    2004-07-01

    Cells migrating through a tissue exert force via their cytoskeleton and are themselves subject to tension, but the effects of physical forces on cell behavior in vivo are poorly understood. Border cell migration during Drosophila oogenesis is a useful model for invasive cell movement. We report that this migration requires the activity of the transcriptional factor serum response factor (SRF) and its cofactor MAL-D and present evidence that nuclear accumulation of MAL-D is induced by cell stretching. Border cells that cannot migrate lack nuclear MAL-D but can accumulate it if they are pulled by other migrating cells. Like mammalian MAL, MAL-D also responds to activated Diaphanous, which affects actin dynamics. MAL-D/SRF activity is required to build a robust actin cytoskeleton in the migrating cells; mutant cells break apart when initiating migration. Thus, tension-induced MAL-D activity may provide a feedback mechanism for enhancing cytoskeletal strength during invasive migration.

  5. [Migration mobility and movement of the population].

    PubMed

    Zaslavska, T; Ribakovski, L

    1983-01-01

    "The functions of migration are reviewed from the viewpoint of the demographic situation in the USSR (by regions, sex, age, education, profession, labour and social activity, nationality, rural-urban, etc.). Some effects of migration on fertility are shown. The authors investigate the role of the economic functions of migration for the process of professional mobility. The territorial mobility of the population is analysed on a wider scale as a part of the social mobility in the socialist society. In connection with this, some problems of the migration policy as an element of the demographic policy of the USSR are outlined." (summary in ENG, RUS) excerpt

  6. Critical behavior of subcellular density organization during neutrophil activation and migration.

    PubMed

    Baker-Groberg, Sandra M; Phillips, Kevin G; Healy, Laura D; Itakura, Asako; Porter, Juliana E; Newton, Paul K; Nan, Xiaolin; McCarty, Owen J T

    2015-12-01

    Physical theories of active matter continue to provide a quantitative understanding of dynamic cellular phenomena, including cell locomotion. Although various investigations of the rheology of cells have identified important viscoelastic and traction force parameters for use in these theoretical approaches, a key variable has remained elusive both in theoretical and experimental approaches: the spatiotemporal behavior of the subcellular density. The evolution of the subcellular density has been qualitatively observed for decades as it provides the source of image contrast in label-free imaging modalities (e.g., differential interference contrast, phase contrast) used to investigate cellular specimens. While these modalities directly visualize cell structure, they do not provide quantitative access to the structures being visualized. We present an established quantitative imaging approach, non-interferometric quantitative phase microscopy, to elucidate the subcellular density dynamics in neutrophils undergoing chemokinesis following uniform bacterial peptide stimulation. Through this approach, we identify a power law dependence of the neutrophil mean density on time with a critical point, suggesting a critical density is required for motility on 2D substrates. Next we elucidate a continuum law relating mean cell density, area, and total mass that is conserved during neutrophil polarization and migration. Together, our approach and quantitative findings will enable investigators to define the physics coupling cytoskeletal dynamics with subcellular density dynamics during cell migration.

  7. Critical behavior of subcellular density organization during neutrophil activation and migration

    PubMed Central

    Baker-Groberg, Sandra M.; Phillips, Kevin G.; Healy, Laura D.; Itakura, Asako; Porter, Juliana E.; Newton, Paul K.; Nan, Xiaolin; McCarty, Owen J.T.

    2015-01-01

    Physical theories of active matter continue to provide a quantitative understanding of dynamic cellular phenomena, including cell locomotion. Although various investigations of the rheology of cells have identified important viscoelastic and traction force parameters for use in these theoretical approaches, a key variable has remained elusive both in theoretical and experimental approaches: the spatiotemporal behavior of the subcellular density. The evolution of the subcellular density has been qualitatively observed for decades as it provides the source of image contrast in label-free imaging modalities (e.g., differential interference contrast, phase contrast) used to investigate cellular specimens. While these modalities directly visualize cell structure, they do not provide quantitative access to the structures being visualized. We present an established quantitative imaging approach, non-interferometric quantitative phase microscopy, to elucidate the subcellular density dynamics in neutrophils undergoing chemokinesis following uniform bacterial peptide stimulation. Through this approach, we identify a power law dependence of the neutrophil mean density on time with a critical point, suggesting a critical density is required for motility on 2D substrates. Next we elucidate a continuum law relating mean cell density, area, and total mass that is conserved during neutrophil polarization and migration. Together, our approach and quantitative findings will enable investigators to define the physics coupling cytoskeletal dynamics with subcellular density dynamics during cell migration. PMID:26640599

  8. Synthetic seismic monitoring using reverse-time migration and Kirchhoff migration for CO2 sequestration in Korea

    NASA Astrophysics Data System (ADS)

    Kim, W.; Kim, Y.; Min, D.; Oh, J.; Huh, C.; Kang, S.

    2012-12-01

    During last two decades, CO2 sequestration in the subsurface has been extensively studied and progressed as a direct tool to reduce CO2 emission. Commercial projects such as Sleipner, In Salah and Weyburn that inject more than one million tons of CO2 per year are operated actively as well as test projects such as Ketzin to study the behavior of CO2 and the monitoring techniques. Korea also began the CCS (CO2 capture and storage) project. One of the prospects for CO2 sequestration in Korea is the southwestern continental margin of Ulleung basin. To monitor the behavior of CO2 underground for the evaluation of stability and safety, several geophysical monitoring techniques should be applied. Among various geophysical monitoring techniques, seismic survey is considered as the most effective tool. To verify CO2 migration in the subsurface more effectively, seismic numerical simulation is an essential process. Furthermore, the efficiency of the seismic migration techniques should be investigated for various cases because numerical seismic simulation and migration test help us accurately interpret CO2 migration. In this study, we apply the reverse-time migration and Kirchhoff migration to synthetic seismic monitoring data generated for the simplified model based on the geological structures of Ulleung basin in Korea. Synthetic seismic monitoring data are generated for various cases of CO2 migration in the subsurface. From the seismic migration images, we can investigate CO2 diffusion patterns indirectly. From seismic monitoring simulation, it is noted that while the reverse-time migration generates clear subsurface images when subsurface structures are steeply dipping, Kirchhoff migration has an advantage in imaging horizontal-layered structures such as depositional sediments appearing in the continental shelf. The reverse-time migration and Kirchhoff migration present reliable subsurface images for the potential site characterized by stratigraphical traps. In case of

  9. ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1.

    PubMed

    Pasten, Consuelo; Cerda, Joaquín; Jausoro, Ignacio; Court, Felipe A; Cáceres, Alfredo; Marzolo, Maria-Paz

    2015-11-01

    ApoER2 and its ligand Reelin participate in neuronal migration during development. Upon receptor binding, Reelin induces the proteolytic processing of ApoER2 as well as the activation of signaling pathway, including small Rho GTPases. Besides its presence in the central nervous system (CNS), Reelin is also secreted by Schwann cells (SCs), the glial cells of the peripheral nervous system (PNS). Reelin deficient mice (reeler) show decreased axonal regeneration in the PNS; however neither the presence of ApoER2 nor the role of the Reelin signaling pathway in the PNS have been evaluated. Interestingly SC migration occurs during PNS development and during injury-induced regeneration and involves activation of small Rho GTPases. Thus, Reelin-ApoER2 might regulate SC migration during axon regeneration in the PNS. Here we demonstrate the presence of ApoER2 in PNS. After sciatic nerve injury Reelin was induced and its receptor ApoER2 was proteolytically processed. In vitro, SCs express both Reelin and ApoER2 and Reelin induces SC migration. To elucidate the molecular mechanism underlying Reelin-dependent SC migration, we examined the involvement of Rac1, a conspicuous small GTPase family member. FRET experiments revealed that Reelin activates Rac1 at the leading edge of SCs. In addition, Tiam1, a major Rac1-specific GEF was required for Reelin-induced SC migration. Moreover, Reelin-induced SC migration was decreased after suppression of the polarity protein PAR3, consistent with its association to Tiam1. Even more interesting, we demonstrated that PAR3 binds preferentially to the full-length cytoplasmic tail of ApoER2 corresponding to the splice-variant containing the exon 19 that encodes a proline-rich insert and that ApoER2 was required for SC migration. Our study reveals a novel function for Reelin/ApoER2 in PNS, inducing cell migration of SCs, a process relevant for PNS development and regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Soluble guanylyl cyclase-activated cyclic GMP-dependent protein kinase inhibits arterial smooth muscle cell migration independent of VASP-serine 239 phosphorylation.

    PubMed

    Holt, Andrew W; Martin, Danielle N; Shaver, Patti R; Adderley, Shaquria P; Stone, Joshua D; Joshi, Chintamani N; Francisco, Jake T; Lust, Robert M; Weidner, Douglas A; Shewchuk, Brian M; Tulis, David A

    2016-09-01

    Coronary artery disease (CAD) accounts for over half of all cardiovascular disease-related deaths. Uncontrolled arterial smooth muscle (ASM) cell migration is a major component of CAD pathogenesis and efforts aimed at attenuating its progression are clinically essential. Cyclic nucleotide signaling has long been studied for its growth-mitigating properties in the setting of CAD and other vascular disorders. Heme-containing soluble guanylyl cyclase (sGC) synthesizes cyclic guanosine monophosphate (cGMP) and maintains vascular homeostasis predominantly through cGMP-dependent protein kinase (PKG) signaling. Considering that reactive oxygen species (ROS) can interfere with appropriate sGC signaling by oxidizing the cyclase heme moiety and so are associated with several CVD pathologies, the current study was designed to test the hypothesis that heme-independent sGC activation by BAY 60-2770 (BAY60) maintains cGMP levels despite heme oxidation and inhibits ASM cell migration through phosphorylation of the PKG target and actin-binding vasodilator-stimulated phosphoprotein (VASP). First, using the heme oxidant ODQ, cGMP content was potentiated in the presence of BAY60. Using a rat model of arterial growth, BAY60 significantly reduced neointima formation and luminal narrowing compared to vehicle (VEH)-treated controls. In rat ASM cells BAY60 significantly attenuated cell migration, reduced G:F actin, and increased PKG activity and VASP Ser239 phosphorylation (pVASP·S239) compared to VEH controls. Site-directed mutagenesis was then used to generate overexpressing full-length wild type VASP (FL-VASP/WT), VASP Ser239 phosphorylation-mimetic (FL-VASP/239D) and VASP Ser239 phosphorylation-resistant (FL-VASP/239A) ASM cell mutants. Surprisingly, FL-VASP/239D negated the inhibitory effects of FL-VASP/WT and FL-VASP/239A cells on migration. Furthermore, when FL-VASP mutants were treated with BAY60, only the FL-VASP/239D group showed reduced migration compared to its VEH controls

  11. 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

  12. Cell Migration

    PubMed Central

    Trepat, Xavier; Chen, Zaozao; Jacobson, Ken

    2015-01-01

    Cell migration is fundamental to establishing and maintaining the proper organization of multicellular organisms. Morphogenesis can be viewed as a consequence, in part, of cell locomotion, from large-scale migrations of epithelial sheets during gastrulation, to the movement of individual cells during development of the nervous system. In an adult organism, cell migration is essential for proper immune response, wound repair, and tissue homeostasis, while aberrant cell migration is found in various pathologies. Indeed, as our knowledge of migration increases, we can look forward to, for example, abating the spread of highly malignant cancer cells, retarding the invasion of white cells in the inflammatory process, or enhancing the healing of wounds. This article is organized in two main sections. The first section is devoted to the single-cell migrating in isolation such as occurs when leukocytes migrate during the immune response or when fibroblasts squeeze through connective tissue. The second section is devoted to cells collectively migrating as part of multicellular clusters or sheets. This second type of migration is prevalent in development, wound healing, and in some forms of cancer metastasis. PMID:23720251

  13. Aspirin Inhibits Platelet-Derived Sphingosine-1-Phosphate Induced Endothelial Cell Migration.

    PubMed

    Polzin, Amin; Knoop, Betül; Böhm, Andreas; Dannenberg, Lisa; Zurek, Mark; Zeus, Tobias; Kelm, Malte; Levkau, Bodo; Rauch, Bernhard H

    2018-01-01

    Aspirin plays a crucial role in the prevention of cardiovascular diseases. We previously described that aspirin has effects beyond inhibition of platelet aggregation, as it inhibited thrombin-mediated release of sphingosine-1-phosphate (S1P) from human platelets. S1P is a bioactive lipid with important functions on inflammation and apoptosis. In endothelial cells (EC), S1P is a key regulator of cell migration. In this study, we aimed to analyze the effects of aspirin on platelet-induced EC migration. Human umbilical EC migration was measured by Boyden chamber assay. EC migration was induced by platelet supernatants of thrombin receptor-activating peptide-1 (AP1) stimulated platelets. To investigate the S1P receptor subtype that promotes EC migration, specific inhibitors of S1P receptor subtypes were applied. S1P induced EC migration in a concentration-dependent manner. EC migration induced by AP1-stimulated platelet supernatants was reduced by aspirin. S1P1 receptor inhibition almost completely abolished EC migration induced by activated platelets. The inhibition of S1P2 or S1P3 receptor had no effect. Aspirin inhibits EC migration induced by activated platelets that is in part due to S1P and mediated by the endothelial S1P1 receptor. The clinical significance of this novel mechanism of aspirin action has to be investigated in future studies. © 2017 S. Karger AG, Basel.

  14. Aroma profile design of wine spirits: Multi-objective optimization using response surface methodology.

    PubMed

    Matias-Guiu, Pau; Rodríguez-Bencomo, Juan José; Pérez-Correa, José R; López, Francisco

    2018-04-15

    Developing new distillation strategies can help the spirits industry to improve quality, safety and process efficiency. Batch stills equipped with a packed column and an internal partial condenser are an innovative experimental system, allowing a fast and flexible management of the rectification. In this study, the impact of four factors (heart-cut volume, head-cut volume, pH and cooling flow rate of the internal partial condenser during the head-cut fraction) on 18 major volatile compounds of Muscat spirits was optimized using response surface methodology and desirability function approaches. Results have shown that high rectification at the beginning of the heart-cut enhances the overall positive aroma compounds of the product, reducing off-flavor compounds. In contrast, optimum levels of heart-cut volume, head-cut volume and pH factors varied depending on the process goal. Finally, three optimal operational conditions (head off-flavors reduction, flowery terpenic enhancement and fruity ester enhancement) were evaluated by chemical and sensory analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Ena/VASP proteins regulate activated T-cell trafficking by promoting diapedesis during transendothelial migration

    PubMed Central

    Estin, Miriam L.; Thompson, Scott B.; Traxinger, Brianna; Fisher, Marlie H.; Friedman, Rachel S.; Jacobelli, Jordan

    2017-01-01

    Vasodilator-stimulated phosphoprotein (VASP) and Ena-VASP–like (EVL) are cytoskeletal effector proteins implicated in regulating cell morphology, adhesion, and migration in various cell types. However, the role of these proteins in T-cell motility, adhesion, and in vivo trafficking remains poorly understood. This study identifies a specific role for EVL and VASP in T-cell diapedesis and trafficking. We demonstrate that EVL and VASP are selectively required for activated T-cell trafficking but are not required for normal T-cell development or for naïve T-cell trafficking to lymph nodes and spleen. Using a model of multiple sclerosis, we show an impairment in trafficking of EVL/VASP-deficient activated T cells to the inflamed central nervous system of mice with experimental autoimmune encephalomyelitis. Additionally, we found a defect in trafficking of EVL/VASP double-knockout (dKO) T cells to the inflamed skin and secondary lymphoid organs. Deletion of EVL and VASP resulted in the impairment in α4 integrin (CD49d) expression and function. Unexpectedly, EVL/VASP dKO T cells did not exhibit alterations in shear-resistant adhesion to, or in crawling on, primary endothelial cells under physiologic shear forces. Instead, deletion of EVL and VASP impaired T-cell diapedesis. Furthermore, T-cell diapedesis became equivalent between control and EVL/VASP dKO T cells upon α4 integrin blockade. Overall, EVL and VASP selectively mediate activated T-cell trafficking by promoting the diapedesis step of transendothelial migration in a α4 integrin-dependent manner. PMID:28320969

  16. Cdk1 Activates Pre-mitotic Nuclear Envelope Dynein Recruitment and Apical Nuclear Migration in Neural Stem Cells.

    PubMed

    Baffet, Alexandre D; Hu, Daniel J; Vallee, Richard B

    2015-06-22

    Dynein recruitment to the nuclear envelope is required for pre-mitotic nucleus-centrosome interactions in nonneuronal cells and for apical nuclear migration in neural stem cells. In each case, dynein is recruited to the nuclear envelope (NE) specifically during G2 via two nuclear pore-mediated mechanisms involving RanBP2-BicD2 and Nup133-CENP-F. The mechanisms responsible for cell-cycle control of this behavior are unknown. We now find that Cdk1 serves as a direct master controller for NE dynein recruitment in neural stem cells and HeLa cells. Cdk1 phosphorylates conserved sites within RanBP2 and activates BicD2 binding and early dynein recruitment. Late recruitment is triggered by a Cdk1-induced export of CENP-F from the nucleus. Forced NE targeting of BicD2 overrides Cdk1 inhibition, fully rescuing dynein recruitment and nuclear migration in neural stem cells. These results reveal how NE dynein recruitment is cell-cycle regulated and identify the trigger mechanism for apical nuclear migration in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Estrogen-related receptor α decreases RHOA stability to induce orientated cell migration

    PubMed Central

    Sailland, Juliette; Tribollet, Violaine; Forcet, Christelle; Billon, Cyrielle; Barenton, Bruno; Carnesecchi, Julie; Bachmann, Alice; Gauthier, Karine Cécile; Yu, Shan; Giguère, Vincent; Chan, Franky L.; Vanacker, Jean-Marc

    2014-01-01

    Several physiopathological processes require orientated cellular migration. This phenomenon highly depends on members of the RHO family of GTPases. Both excessive and deficient RHO activity impair directional migration. A tight control is thus exerted on these proteins through the regulation of their activation and of their stability. Here we show that the estrogen-related receptor α (ERRα) directly activates the expression of TNFAIP1, the product of which [BTB/POZ domain-containing adapter for Cullin3-mediated RhoA degradation 2 (BACURD2)] regulates RHOA protein turnover. Inactivation of the receptor leads to enhanced RHOA stability and activation. This results in cell disorientation, increased actin network, and inability to form a lamellipodium at the migration edge. As a consequence, directional migration, but not cell motility per se, is impaired in the absence of the receptor, under pathological as well as physiological conditions. Altogether, our results show that the control exerted by ERRα on RHOA stability is required for directional migration. PMID:25288732

  18. Estrogen-related receptor α decreases RHOA stability to induce orientated cell migration.

    PubMed

    Sailland, Juliette; Tribollet, Violaine; Forcet, Christelle; Billon, Cyrielle; Barenton, Bruno; Carnesecchi, Julie; Bachmann, Alice; Gauthier, Karine Cécile; Yu, Shan; Giguère, Vincent; Chan, Franky L; Vanacker, Jean-Marc

    2014-10-21

    Several physiopathological processes require orientated cellular migration. This phenomenon highly depends on members of the RHO family of GTPases. Both excessive and deficient RHO activity impair directional migration. A tight control is thus exerted on these proteins through the regulation of their activation and of their stability. Here we show that the estrogen-related receptor α (ERRα) directly activates the expression of TNFAIP1, the product of which [BTB/POZ domain-containing adapter for Cullin3-mediated RhoA degradation 2 (BACURD2)] regulates RHOA protein turnover. Inactivation of the receptor leads to enhanced RHOA stability and activation. This results in cell disorientation, increased actin network, and inability to form a lamellipodium at the migration edge. As a consequence, directional migration, but not cell motility per se, is impaired in the absence of the receptor, under pathological as well as physiological conditions. Altogether, our results show that the control exerted by ERRα on RHOA stability is required for directional migration.

  19. Activation of matrix metalloproteinase-9 (MMP-9) by neurotensin promotes cell invasion and migration through ERK pathway in gastric cancer.

    PubMed

    Akter, Hafeza; Park, Min; Kwon, Oh-Seung; Song, Eun Joo; Park, Won-Sang; Kang, Min-Jung

    2015-08-01

    Neurotensin (NT) is distributed throughout the brain and gastrointestinal tract. Although the relationship between NT and matrix metalloproteinase-9 (MMP-9) activity in gastric cancer has not been reported, the elevation of MMP-9 and NT is reported in the breast, lung, prostate, and gastric cancer. The aim of our study is to investigate the relationship between NT and MMP-9 activity and the underlying signaling mechanism in gastric cancer cell lines. Commercial ELISA kits were used for estimation of NT and MMP-9 expression, and fluorescence resonance energy transfer (FRET) assay was used for measurement of MMP-9 activity. Cell migration and invasion were determined by wound healing and transwell assay. The expression of signaling proteins was measured by Western blotting. Our study reveals a positive correlation between increased plasma NT and MMP-9 activity in both of patient's serum and gastric cancer cell lines. A dose-dependent elevation of MMP-9 activity was observed by NT treatment in gastric cancer cells (MKN-1 and MKN-45) compared to untreated gastric cancer and normal epithelial cell (HFE-145). Moreover, NT-mediated migration and invasion were observed in gastric cancer cells unlike in normal cell. The signaling mechanism of NT in gastric cancer cells was confirmed in protein kinase C (PKC), extracellular-signal regulated kinase (ERK), and phosphatidylinositol 3-kinase (PI3K) pathway. In addition, pretreatment of gastric cancer cells with NTR1 inhibitor SR48692 was shown to significantly inhibit the NT-mediated MMP-9 activity, cell invasion, and migration. Our finding illustrated NTR1 could be a possible therapeutic target for gastric cancer.

  20. Peroxisome proliferator-activated receptor (PPAR)-gamma expression in human vascular smooth muscle cells: inhibition of growth, migration, and c-fos expression by the peroxisome proliferator-activated receptor (PPAR)-gamma activator troglitazone.

    PubMed

    Benson, S; Wu, J; Padmanabhan, S; Kurtz, T W; Pershadsingh, H A

    2000-01-01

    This study was conducted to determine whether cultured human coronary artery and aorta vascular smooth muscle (VSM) cells express the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPARgamma); whether the thiazolidinedione troglitazone, a ligand for PPARgamma, would inhibit c-fos expression by these cells; and whether troglitazone would inhibit proliferation and migration induced in these cells by mitogenic growth factors. Using immunoblotting and reverse-transcriptase polymerase chain reaction (RT-PCR) techniques, we show that both human aorta and coronary artery VSM cell lines expressed PPARgamma protein and mRNA for both PPARgamma isoforms, PPARgamma1 and PPARgamma2. Immunocytochemical staining localized the PPARgamma protein primarily within the nucleus. Troglitazone inhibited basic fibroblast growth factor and platelet-derived growth factor-BB induced DNA synthesis in a dose-dependent manner and downregulated the growth-factor-induced expression of c-fos. Troglitazone also inhibited the migration of coronary artery VSM cells along a platelet-derived growth factor-BB concentration gradient. These findings demonstrate for the first time the expression and nuclear localization of PPARgamma in human coronary artery and aorta VSM cells. The data also suggest that the downregulation of c-fos expression, growth-factor-induced proliferation, and migration by VSM may, in part, be mediated by activation of the PPARgamma receptor.

  1. Migration: a concept analysis from a nursing perspective.

    PubMed

    Freeman, Michelle; Baumann, Andrea; Blythe, Jennifer; Fisher, Anita; Akhtar-Danesh, Noori

    2012-05-01

      This article is a report of a concept analysis of nurse migration.   International migration is increasing and nurse migrants are active participants in this movement. Migration is a complex term and can be examined from a range of perspectives. Analysis of nurse migration is needed to guide policy, practice and research.   A literature search was undertaken using electronic literature indexes, specific journals and websites, internet search engines and hand searches. No timeframe was placed on the search. Most literature found was published between 2001 and 2009. A sample of 80 documents met the inclusion criteria.   Walker and Avant's approach guided the analysis.   Nurse migration can be defined by five attributes: the motivation and decisions of individuals; external barriers and facilitators; freedom of choice to migrate; freedom to migrate as a human right, and dynamic movement. Antecedents of migration include the political, social, economic, legal, historical and educational forces that comprise the push and pull framework. The consequences of migration are positive or negative depending on the viewpoint and its affect on the individual and other stakeholders such as the source country, destination country, healthcare systems and the nursing profession.   This concept analysis clarified the complexities surrounding nurse migration. A nursing-specific middle-range theory was proposed to guide the understanding and study of nurse migration. © 2011 Blackwell Publishing Ltd.

  2. Protein migration from transplanted nuclei in Amoeba proteus. I. The relation to the cell cycle and RNA migration, as studied by autoradiography

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

    Mills, K.I.; Bell, L.G.

    1982-11-01

    Autoradiography has been used to examine the migration of proteins from a radioactivity labelled amoeba nucleus following transplantation into an unlabelled homophasic amoeba. Nuclei were transferred at three times in the cell cycle coinciding with DNA synthesis (4 h post-division); a peak of RNA synthesis (25 h); and a relative lull in synthetic activity (43 h). Six amino acids were added individually to the culture medium to label the nuclear proteins. Migration of the proteins from the donor nucleui and least with proteins labelled with the basic amino acids. All amino acids exhibited the greatest extent of migration following themore » 25-h transfers, i.e., coinciding with a peak of RNA synthesis at 26-27.5 h. Actinomycin D (actD) inhibition of RNA synthesis reduced, but did not eliminate the extent of protein migration from the transplanted nucleus, thus indicating the existence of two classes of migratory proteins. Firstly, proteins, associated with RNA transport, which migrated mainly into the host cytoplasm. The second class migrated into the host nucleus from the transplanted nucleus, irrespective of RNA synthesis. The shuttling character of the latter class of proteins is consistent with a role of regulation of nuclear activity.« less

  3. Thymic stromal lymphopoietin-induced HOTAIR activation promotes endothelial cell proliferation and migration in atherosclerosis

    PubMed Central

    Peng, Yudong; Meng, Kai; Jiang, Lili; Zhong, Yucheng; Yang, Yong; Lan, Yin

    2017-01-01

    Endothelial cells’ (EC) injury is a major step for the pathological progression of atherosclerosis. Recent study demonstrated that thymic stromal lymphopoietin (TSLP) exerts a protective role in atherosclerosis. However, the effect of TSLP and the exact molecular mechanism involved in EC remains unknown. In the present study, we found that long noncoding RNA (lncRNA) HOTAIR was much lower in EC from atherosclerotic plaque. Functional assays showed that HOTAIR facilitated cell proliferation and migration, and suppressed apoptosis in EC. Moreover, we demonstrated that TSLP functions upstream of HOTAIR. We found that serum level of TSLP was decreased in atherosclerosis patients and serum TSLP level positively correlated with HOTAIR expression in EC. Further investigation demonstrated that TSLP activated HOTAIR transcription through PI3K/AKT-IRF1 pathway and then regulates the EC proliferation and migration. TSLP-HOTAIR axis also plays a protective role in low-density lipoprotein (ox-LDL)-induced EC injury. Taken together, TSLP-HOTAIR may be a potential therapy for EC dysfunction in atherosclerosis. PMID:28615347

  4. 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.

  5. UV-B Radiation Induces Macrophage Migration Inhibitory Factor–Mediated Melanogenesis through Activation of Protease-Activated Receptor-2 and Stem Cell Factor in Keratinocytes

    PubMed Central

    Enomoto, Akiko; Yoshihisa, Yoko; Yamakoshi, Takako; Ur Rehman, Mati; Norisugi, Osamu; Hara, Hiroshi; Matsunaga, Kenji; Makino, Teruhiko; Nishihira, Jun; Shimizu, Tadamichi

    2011-01-01

    UV radiation indirectly regulates melanogenesis in melanocytes through a paracrine regulatory mechanism involving keratinocytes. Protease-activated receptor (PAR)-2 activation induces melanosome transfer by increasing phagocytosis of melanosomes by keratinocytes. This study demonstrated that macrophage migration inhibitory factor (MIF) stimulated PAR-2 expression in human keratinocytes. In addition, we showed that MIF stimulated stem cell factor (SCF) release in keratinocytes; however, MIF had no effect on the release of endothelin-1 or prostaglandin E2 in keratinocytes. In addition, MIF had no direct effect on melanin and tyrosinase synthesis in cultured human melanocytes. The effect of MIF on melanogenesis was also examined using a three-dimensional reconstituted human epidermal culture model, which is a novel, commercially available, cultured human epidermis containing functional melanocytes. Migration inhibitory factor induced an increase in melanin content in the epidermis after a 9-day culture period. Moreover, melanin synthesis induced by UV-B stimulation was significantly down-regulated by anti-MIF antibody treatment. An in vivo study showed that the back skin of MIF transgenic mice had a higher melanin content than that of wild-type mice after 12 weeks of UV-B exposure. Therefore, MIF-mediated melanogenesis occurs mainly through the activation of PAR-2 and SCF expression in keratinocytes after exposure to UV-B radiation. PMID:21281800

  6. 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

  7. 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

  8. Longitudinal changes in physical activity, sedentary behavior and body mass index in adolescence: Migrations towards different weight cluster.

    PubMed

    Devís-Devís, José; Lizandra, Jorge; Valencia-Peris, Alexandra; Pérez-Gimeno, Esther; García-Massò, Xavier; Peiró-Velert, Carmen

    2017-01-01

    This study examined longitudinal changes in physical activity, sedentary behavior and body mass index in adolescents, specifically their migrations towards a different weight cluster. A cohort of 755 adolescents participated in a three-year study. A clustering Self-Organized Maps Analysis was performed to visualize changes in subjects' characteristics between the first and second assessment, and how adolescents were grouped. Also a classification tree was used to identify the behavioral characteristics of the groups that changed their weight cluster. Results indicated that boys were more active and less sedentary than girls. Boys were especially keen to technological-based activities while girls preferred social-based activities. A moderate competing effect between sedentary behaviors and physical activities was observed, especially in girls. Overweight and obesity were negatively associated with physical activity, although a small group of overweight/obese adolescents showed a positive relationship with vigorous physical activity. Cluster migrations indicated that 22.66% of adolescents changed their weight cluster to a lower category and none of them moved in the opposite direction. The behavioral characteristics of these adolescents did not support the hypothesis that the change to a lower weight cluster was a consequence of an increase in time devoted to physical activity or a decrease in time spent on sedentary behavior. Physical activity and sedentary behavior does not exert a substantial effect on overweight and obesity. Therefore, there are other ways of changing to a lower-weight status in adolescents apart from those in which physical activity and sedentary behavior are involved.

  9. Longitudinal changes in physical activity, sedentary behavior and body mass index in adolescence: Migrations towards different weight cluster

    PubMed Central

    Lizandra, Jorge; Valencia-Peris, Alexandra; Pérez-Gimeno, Esther; García-Massò, Xavier; Peiró-Velert, Carmen

    2017-01-01

    This study examined longitudinal changes in physical activity, sedentary behavior and body mass index in adolescents, specifically their migrations towards a different weight cluster. A cohort of 755 adolescents participated in a three-year study. A clustering Self-Organized Maps Analysis was performed to visualize changes in subjects’ characteristics between the first and second assessment, and how adolescents were grouped. Also a classification tree was used to identify the behavioral characteristics of the groups that changed their weight cluster. Results indicated that boys were more active and less sedentary than girls. Boys were especially keen to technological-based activities while girls preferred social-based activities. A moderate competing effect between sedentary behaviors and physical activities was observed, especially in girls. Overweight and obesity were negatively associated with physical activity, although a small group of overweight/obese adolescents showed a positive relationship with vigorous physical activity. Cluster migrations indicated that 22.66% of adolescents changed their weight cluster to a lower category and none of them moved in the opposite direction. The behavioral characteristics of these adolescents did not support the hypothesis that the change to a lower weight cluster was a consequence of an increase in time devoted to physical activity or a decrease in time spent on sedentary behavior. Physical activity and sedentary behavior does not exert a substantial effect on overweight and obesity. Therefore, there are other ways of changing to a lower-weight status in adolescents apart from those in which physical activity and sedentary behavior are involved. PMID:28636644

  10. Postnatal Migration of Cerebellar Interneurons

    PubMed Central

    Galas, Ludovic; Bénard, Magalie; Lebon, Alexis; Komuro, Yutaro; Schapman, Damien; Vaudry, Hubert; Vaudry, David; Komuro, Hitoshi

    2017-01-01

    Due to its continuing development after birth, the cerebellum represents a unique model for studying the postnatal orchestration of interneuron migration. The combination of fluorescent labeling and ex/in vivo imaging revealed a cellular highway network within cerebellar cortical layers (the external granular layer, the molecular layer, the Purkinje cell layer, and the internal granular layer). During the first two postnatal weeks, saltatory movements, transient stop phases, cell-cell interaction/contact, and degradation of the extracellular matrix mark out the route of cerebellar interneurons, notably granule cells and basket/stellate cells, to their final location. In addition, cortical-layer specific regulatory factors such as neuropeptides (pituitary adenylate cyclase-activating polypeptide (PACAP), somatostatin) or proteins (tissue-type plasminogen activator (tPA), insulin growth factor-1 (IGF-1)) have been shown to inhibit or stimulate the migratory process of interneurons. These factors show further complexity because somatostatin, PACAP, or tPA have opposite or no effect on interneuron migration depending on which layer or cell type they act upon. External factors originating from environmental conditions (light stimuli, pollutants), nutrients or drug of abuse (alcohol) also alter normal cell migration, leading to cerebellar disorders. PMID:28587295

  11. Activation of glial FGFRs is essential in glial migration, proliferation, and survival and in glia-neuron signaling during olfactory system development.

    PubMed

    Gibson, Nicholas J; Tolbert, Leslie P; Oland, Lynne A

    2012-01-01

    Development of the adult olfactory system of the moth Manduca sexta depends on reciprocal interactions between olfactory receptor neuron (ORN) axons growing in from the periphery and centrally-derived glial cells. Early-arriving ORN axons induce a subset of glial cells to proliferate and migrate to form an axon-sorting zone, in which later-arriving ORN axons will change their axonal neighbors and change their direction of outgrowth in order to travel with like axons to their target areas in the olfactory (antennal) lobe. These newly fasciculated axon bundles will terminate in protoglomeruli, the formation of which induces other glial cells to migrate to surround them. Glial cells do not migrate unless ORN axons are present, axons fail to fasciculate and target correctly without sufficient glial cells, and protoglomeruli are not maintained without a glial surround. We have shown previously that Epidermal Growth Factor receptors and the IgCAMs Neuroglian and Fasciclin II play a role in the ORN responses to glial cells. In the present work, we present evidence for the importance of glial Fibroblast Growth Factor receptors in glial migration, proliferation, and survival in this developing pathway. We also report changes in growth patterns of ORN axons and of the dendrites of olfactory (antennal lobe) neurons following blockade of glial FGFR activation that suggest that glial FGFR activation is important in reciprocal communication between neurons and glial cells.

  12. Ion migration in crystalline and amorphous HfOX

    NASA Astrophysics Data System (ADS)

    Schie, Marcel; Müller, Michael P.; Salinga, Martin; Waser, Rainer; De Souza, Roger A.

    2017-03-01

    The migration of ions in HfOx was investigated by means of large-scale, classical molecular-dynamics simulations over the temperature range 1000 ≤T /K ≤2000 . Amorphous HfOx was studied in both stoichiometric and oxygen-deficient forms (i.e., with x = 2 and x = 1.9875); oxygen-deficient cubic and monoclinic phases were also studied. The mean square displacement of oxygen ions was found to evolve linearly as a function of time for the crystalline phases, as expected, but displayed significant negative deviations from linear behavior for the amorphous phases, that is, the behavior was sub-diffusive. That oxygen-ion migration was observed for the stoichiometric amorphous phase argues strongly against applying the traditional model of vacancy-mediated migration in crystals to amorphous HfO2. In addition, cation migration, whilst not observed for the crystalline phases (as no cation defects were present), was observed for both amorphous phases. In order to obtain activation enthalpies of migration, the residence times of the migrating ions were analyzed. The analysis reveals four activation enthalpies for the two amorphous phases: 0.29 eV, 0.46 eV, and 0.66 eV (values very close to those obtained for the monoclinic structure) plus a higher enthalpy of at least 0.85 eV. In comparison, the cubic phase is characterized by a single value of 0.43 eV. Simple kinetic Monte Carlo simulations suggest that the sub-diffusive behavior arises from nanoscale confinement of the migrating ions.

  13. 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.

  14. Tangeretin, a citrus flavonoid, inhibits PGDF-BB-induced proliferation and migration of aortic smooth muscle cells by blocking AKT activation.

    PubMed

    Seo, Juhee; Lee, Hyun Sun; Ryoo, Sungwoo; Seo, Jee Hee; Min, Byung-Sun; Lee, Jeong-Hyung

    2011-12-30

    Tangeretin, a natural polymethoxylated flavone concentrated in the peel of citrus fruits, is known to have antiproliferative, antiinvasive, antimetastatic and antioxidant activities. However, the effect of tangeretin on vascular smooth muscle cells (VSMCs) is unknown. This study examined the effect of tangeretin on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of rat aortic smooth muscle cells (RASMCs) as well as its underlying mechanisms. Tangeretin significantly inhibited proliferation, DNA synthesis and migration of PDGF-BB-stimulated RASMCs without inducing cell death. Treatment with tangeretin-induced cell-cycle arrest in the G₀/G₁ phase was associated with down-regulation of cyclin D1 and cyclin E in addition to up-regulation of p27(kip1). We also showed that tangeretin inhibited PDGF-BB-induced phosphorylation of AKT, while it had no effect on the phosphorylation of phospholipase Cγ (PLCγ), PDGF receptor β-chain (PDGF-Rβ) and extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs). An in vitro kinase assay revealed that tangeretin inhibited AKT activity in a dose-dependent manner. Moreover, treatment of LY294002, a phosphoinositide 3-kinase (PI3K) inhibitor, had similar effects than that of tangeretin on the expression of p27(kip1) and cyclin D1, as well as cell migration in PDFG-BB-stimulated RASMCs. Taken together, these findings suggest that tangeretin could suppress PDGF-BB-induced proliferation and migration of RASMCs through the suppression of PI3K/AKT signaling pathway, and may be a potential candidate for preventing or treating vascular diseases, such as atherosclerosis and restenosis. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Fine Tuning Cell Migration by a Disintegrin and Metalloproteinases

    PubMed Central

    Theodorou, K.

    2017-01-01

    Cell migration is an instrumental process involved in organ development, tissue homeostasis, and various physiological processes and also in numerous pathologies. Both basic cell migration and migration towards chemotactic stimulus consist of changes in cell polarity and cytoskeletal rearrangement, cell detachment from, invasion through, and reattachment to their neighboring cells, and numerous interactions with the extracellular matrix. The different steps of immune cell, tissue cell, or cancer cell migration are tightly coordinated in time and place by growth factors, cytokines/chemokines, adhesion molecules, and receptors for these ligands. This review describes how a disintegrin and metalloproteinases interfere with several steps of cell migration, either by proteolytic cleavage of such molecules or by functions independent of proteolytic activity. PMID:28260841

  16. Aloe emodin inhibits colon cancer cell migration/angiogenesis by downregulating MMP-2/9, RhoB and VEGF via reduced DNA binding activity of NF-κB.

    PubMed

    Suboj, Priya; Babykutty, Suboj; Valiyaparambil Gopi, Deepak Roshan; Nair, Rakesh S; Srinivas, Priya; Gopala, Srinivas

    2012-04-11

    Aloe emodin (AE), a natural anthraquinone, is reported to have antiproliferative activity in various cancer cell lines. In this study we analyzed molecular mechanisms involved in the antimigratory and antiangiogenic activity of this hydroxy anthraquinone in colon cancer cell, WiDr. Our results show that a relatively non toxic concentration of AE suppressed the phorbol-12-myristyl-13-acetate (PMA) induced migration and invasion of tumor cells. On analysis for the molecules involved in the migration/invasion, we found AE downregulated mRNA expression and promoter/gelatinolytic activity of Matrix Metalloproteinase (MMP)-2/9, as well as the RhoB expression at gene and protein level. It was also a strong inhibitor of Vascular Endothelial Growth Factor (VEGF) expression, promoter activity and endothelial cell migration/invasion and in vitro angiogenesis. AE suppressed the nuclear translocation and DNA binding of NF-κB, which is an important transcription factor for controlling MMP-2/9 and VEGF gene expression. Taken together these data indicate that AE target multiple molecules responsible for cellular invasion, migration and angiogenesis. Inhibitory effect on angiogenic and metastatic regulatory processes make AE a sensible candidate as a specific blocker of tumor associated events. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Compound C Inhibits Vascular Smooth Muscle Cell Proliferation and Migration in an AMP-Activated Protein Kinase-Independent Fashion

    PubMed Central

    Peyton, Kelly J.; Yu, Yajie; Yates, Benjamin; Shebib, Ahmad R.; Liu, Xiao-ming; Wang, Hong

    2011-01-01

    6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrazolo[1,5-a] pyrimidine (compound C) is a cell-permeable pyrrazolopyrimidine derivative that acts as a potent inhibitor of AMP-activated protein kinase (AMPK). Although compound C is often used to determine the role of AMPK in various physiological processes, it also evokes AMPK-independent actions. In the present study, we investigated whether compound C influences vascular smooth muscle cell (SMC) function through the AMPK pathway. Treatment of rat aortic SMCs with compound C (0.02–10 μM) inhibited vascular SMC proliferation and migration in a concentration-dependent fashion. These actions of compound C were not mimicked or affected by silencing AMPKα expression or infecting SMCs with an adenovirus expressing a dominant-negative mutant of AMPK. In contrast, the pharmacological activator of AMPK 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside inhibited the proliferation and migration of SMCs in a manner that was strictly dependent on AMPK activity. Flow cytometry experiments revealed that compound C arrested SMCs in the G0/G1 phase of the cell cycle, and this was associated with a decrease in cyclin D1 and cyclin A protein expression and retinoblastoma protein phosphorylation and an increase in p21 protein expression. Finally, local perivascular delivery of compound C immediately after balloon injury of rat carotid arteries markedly attenuated neointima formation. These studies identify compound C as a novel AMPK-independent regulator of vascular SMC function that exerts inhibitory effects on SMC proliferation and migration and neointima formation after arterial injury. Compound C represents a potentially new therapeutic agent in treating and preventing occlusive vascular disease. PMID:21566210

  18. Compound C inhibits vascular smooth muscle cell proliferation and migration in an AMP-activated protein kinase-independent fashion.

    PubMed

    Peyton, Kelly J; Yu, Yajie; Yates, Benjamin; Shebib, Ahmad R; Liu, Xiao-ming; Wang, Hong; Durante, William

    2011-08-01

    6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl]-3-pyridin-4-yl-pyrazolo[1,5-a] pyrimidine (compound C) is a cell-permeable pyrrazolopyrimidine derivative that acts as a potent inhibitor of AMP-activated protein kinase (AMPK). Although compound C is often used to determine the role of AMPK in various physiological processes, it also evokes AMPK-independent actions. In the present study, we investigated whether compound C influences vascular smooth muscle cell (SMC) function through the AMPK pathway. Treatment of rat aortic SMCs with compound C (0.02-10 μM) inhibited vascular SMC proliferation and migration in a concentration-dependent fashion. These actions of compound C were not mimicked or affected by silencing AMPKα expression or infecting SMCs with an adenovirus expressing a dominant-negative mutant of AMPK. In contrast, the pharmacological activator of AMPK 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside inhibited the proliferation and migration of SMCs in a manner that was strictly dependent on AMPK activity. Flow cytometry experiments revealed that compound C arrested SMCs in the G(0)/G(1) phase of the cell cycle, and this was associated with a decrease in cyclin D1 and cyclin A protein expression and retinoblastoma protein phosphorylation and an increase in p21 protein expression. Finally, local perivascular delivery of compound C immediately after balloon injury of rat carotid arteries markedly attenuated neointima formation. These studies identify compound C as a novel AMPK-independent regulator of vascular SMC function that exerts inhibitory effects on SMC proliferation and migration and neointima formation after arterial injury. Compound C represents a potentially new therapeutic agent in treating and preventing occlusive vascular disease.

  19. Pseudomonas aeruginosa ExoU augments neutrophil transepithelial migration.

    PubMed

    Pazos, Michael A; Lanter, Bernard B; Yonker, Lael M; Eaton, Alex D; Pirzai, Waheed; Gronert, Karsten; Bonventre, Joseph V; Hurley, Bryan P

    2017-08-01

    Excessive neutrophil infiltration of the lungs is a common contributor to immune-related pathology in many pulmonary disease states. In response to pathogenic infection, airway epithelial cells produce hepoxilin A3 (HXA3), initiating neutrophil transepithelial migration. Migrated neutrophils amplify this recruitment by producing a secondary gradient of leukotriene B4 (LTB4). We sought to determine whether this two-step eicosanoid chemoattractant mechanism could be exploited by the pathogen Pseudomonas aeruginosa. ExoU, a P. aeruginosa cytotoxin, exhibits phospholipase A2 (PLA2) activity in eukaryotic hosts, an enzyme critical for generation of certain eicosanoids. Using in vitro and in vivo models of neutrophil transepithelial migration, we evaluated the impact of ExoU expression on eicosanoid generation and function. We conclude that ExoU, by virtue of its PLA2 activity, augments and compensates for endogenous host neutrophil cPLA2α function, leading to enhanced transepithelial migration. This suggests that ExoU expression in P. aeruginosa can circumvent immune regulation at key signaling checkpoints in the neutrophil, resulting in exacerbated neutrophil recruitment.

  20. Electro-migration of impurities in TlBr

    NASA Astrophysics Data System (ADS)

    Kim, Ki Hyun; Kim, Eunlim; Kim, H.; Tappero, R.; Bolotnikov, A. E.; Camarda, G. S.; Hossain, A.; Cirignano, L.; James, R. B.

    2013-10-01

    We observed the electro-migration of Cu, Ag, and Au impurities that exist in positive-ion states in TlBr detectors under electric field strengths typically used for device operation. The migration occurred predominantly through bulk- and specific-channels, which are presumed to be a network of grain and sub-grain boundaries. The electro-migration velocity of Cu, Ag, and Au in TlBr is about 4-8 × 10-8 cm/s at room temperature under an electric field of 500-800 V/mm. The instability and polarization effects of TlBr detectors might well be correlated with the electro-migration of residual impurities in TlBr, which alters the internal electric field over time. The effect may also have been due to migration of the electrode material itself, which would allow for the possibility of a better choice for contact material and for depositing an effective diffusion barrier. From our findings, we suggest that applying our electro-migration technique for purifying material is a promising new way to remove electrically active metallic impurities in TlBr crystals, as well as other materials.

  1. 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.

  2. Do Social Casino Gamers Migrate to Online Gambling? An Assessment of Migration Rate and Potential Predictors.

    PubMed

    Kim, Hyoun S; Wohl, Michael J A; Salmon, Melissa M; Gupta, Rina; Derevensky, Jeffrey

    2015-12-01

    Social casino games (i.e., free-to-play online gambling games) are enjoyed by millions of players worldwide on a daily basis. Despite being free to play, social casino games share many similarities to traditional casino games. As such, concerns have been raised as to whether social casino games influences the migration to online gambling among people who have not engaged in such activity (see Griffiths in World Online Gambl 9:12-13, 2010). To date, however, no empirical research has assessed this possibility. Thus, the purpose of the present research was to assess the extent to which social casino gamers migrate to online gambling and potential predictors (time spent on social casino games, skill building, enhancement and micro-transactions) of such migration. To this end, social casino gamers who never gambled online (N = 409) completed a questionnaire battery assessing our variables of interest and were re-contacted 6-months later to see if they had engaged in online gambling during the intervening months. Approximately 26% of social casino gamers reported having migrated to online gambling. Importantly, engagement in micro-transactions was the only unique predictor of migration from social casino gaming to online gambling. The implications for the potential harms associated with social casino gaming are discussed.

  3. Functional characterization of the turkey macrophage migration inhibitory factor

    USDA-ARS?s Scientific Manuscript database

    Macrophage migration inhibitory factor (MIF) is a soluble protein that inhibits the random migration of macrophages and plays a pivotal immunoregulatory function in innate and adaptive immunity. The aim of this study was to clone the turkey MIF (TkMIF) gene, express the active protein, and characte...

  4. Lysophosphatidic Acid Promotes Cell Migration through STIM1- and Orai1-Mediated Ca2+i Mobilization and NFAT2 Activation

    PubMed Central

    Jans, Ralph; Mottram, Laura; Johnson, Darren L; Brown, Anna M; Sikkink, Stephen; Ross, Kehinde; Reynolds, Nick J

    2013-01-01

    Lysophosphatidic acid (LPA) enhances cell migration and promotes wound healing in vivo, but the intracellular signaling pathways regulating these processes remain incompletely understood. Here we investigated the involvement of agonist-induced Ca2+ entry and STIM1 and Orai1 proteins in regulating nuclear factor of activated T cell (NFAT) signaling and LPA-induced keratinocyte cell motility. As monitored by Fluo-4 imaging, stimulation with 10 μℳ LPA in 60 μℳ Ca2+o evoked Ca2+i transients owing to store release, whereas addition of LPA in physiological 1.2 mℳ Ca2+o triggered store release coupled to extracellular Ca2+ entry. Store-operated Ca2+ entry (SOCE) was blocked by the SOCE inhibitor diethylstilbestrol (DES), STIM1 silencing using RNA interference (RNAi), and expression of dominant/negative Orai1R91W. LPA induced significant NFAT activation as monitored by nuclear translocation of green fluorescent protein-tagged NFAT2 and a luciferase reporter assay, which was impaired by DES, expression of Orai1R91W, and inhibition of calcineurin using cyclosporin A (CsA). By using chemotactic migration assays, LPA-induced cell motility was significantly impaired by STIM1, CsA, and NFAT2 knockdown using RNAi. These data indicate that in conditions relevant to epidermal wound healing, LPA induces SOCE and NFAT activation through Orai1 channels and promotes cell migration through a calcineurin/NFAT2-dependent pathway. PMID:23096711

  5. UV-B radiation induces macrophage migration inhibitory factor-mediated melanogenesis through activation of protease-activated receptor-2 and stem cell factor in keratinocytes.

    PubMed

    Enomoto, Akiko; Yoshihisa, Yoko; Yamakoshi, Takako; Ur Rehman, Mati; Norisugi, Osamu; Hara, Hiroshi; Matsunaga, Kenji; Makino, Teruhiko; Nishihira, Jun; Shimizu, Tadamichi

    2011-02-01

    UV radiation indirectly regulates melanogenesis in melanocytes through a paracrine regulatory mechanism involving keratinocytes. Protease-activated receptor (PAR)-2 activation induces melanosome transfer by increasing phagocytosis of melanosomes by keratinocytes. This study demonstrated that macrophage migration inhibitory factor (MIF) stimulated PAR-2 expression in human keratinocytes. In addition, we showed that MIF stimulated stem cell factor (SCF) release in keratinocytes; however, MIF had no effect on the release of endothelin-1 or prostaglandin E2 in keratinocytes. In addition, MIF had no direct effect on melanin and tyrosinase synthesis in cultured human melanocytes. The effect of MIF on melanogenesis was also examined using a three-dimensional reconstituted human epidermal culture model, which is a novel, commercially available, cultured human epidermis containing functional melanocytes. Migration inhibitory factor induced an increase in melanin content in the epidermis after a 9-day culture period. Moreover, melanin synthesis induced by UV-B stimulation was significantly down-regulated by anti-MIF antibody treatment. An in vivo study showed that the back skin of MIF transgenic mice had a higher melanin content than that of wild-type mice after 12 weeks of UV-B exposure. Therefore, MIF-mediated melanogenesis occurs mainly through the activation of PAR-2 and SCF expression in keratinocytes after exposure to UV-B radiation. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  6. Family migration and employment: the importance of migration history and gender.

    PubMed

    Bailey, A J; Cooke, T J

    1998-01-01

    "This article uses event history data to specify a model of employment returns to initial migration, onward migration, and return migration among newly married persons in the U.S. Husbands are more likely to be full-time employed than wives, and being a parent reduces the employment odds among married women. Employment returns to repeated migration differ by gender, with more husbands full-time employed after onward migration and more wives full-time employed after return migration events. We interpret these empirical findings in the context of family migration theory, segmented labor market theory, and gender-based responsibilities." Data are from the National Longitudinal Survey of Youth from 1979 to 1991. excerpt

  7. Activation of Glial FGFRs Is Essential in Glial Migration, Proliferation, and Survival and in Glia-Neuron Signaling during Olfactory System Development

    PubMed Central

    Gibson, Nicholas J.; Tolbert, Leslie P.; Oland, Lynne A.

    2012-01-01

    Development of the adult olfactory system of the moth Manduca sexta depends on reciprocal interactions between olfactory receptor neuron (ORN) axons growing in from the periphery and centrally-derived glial cells. Early-arriving ORN axons induce a subset of glial cells to proliferate and migrate to form an axon-sorting zone, in which later-arriving ORN axons will change their axonal neighbors and change their direction of outgrowth in order to travel with like axons to their target areas in the olfactory (antennal) lobe. These newly fasciculated axon bundles will terminate in protoglomeruli, the formation of which induces other glial cells to migrate to surround them. Glial cells do not migrate unless ORN axons are present, axons fail to fasciculate and target correctly without sufficient glial cells, and protoglomeruli are not maintained without a glial surround. We have shown previously that Epidermal Growth Factor receptors and the IgCAMs Neuroglian and Fasciclin II play a role in the ORN responses to glial cells. In the present work, we present evidence for the importance of glial Fibroblast Growth Factor receptors in glial migration, proliferation, and survival in this developing pathway. We also report changes in growth patterns of ORN axons and of the dendrites of olfactory (antennal lobe) neurons following blockade of glial FGFR activation that suggest that glial FGFR activation is important in reciprocal communication between neurons and glial cells. PMID:22493675

  8. [Gender and physical activity in Mexican women with experience of migration to the USA].

    PubMed

    Ruiz-Rodríguez, Myriam; Arenas-Monreal, Luz; Bonilla-Fernández, Pastor; Valdez-Santiago, Rosario; Rueda-Neria, Celina M; Hernández-Tezoquipa, Isabel

    2014-01-01

    To analyze the influence of gender on the practice of physical activity, in women with experiences of migration to the U.S.A. Qualitative design with methods based on grounded theory. The information was obtained through in-depth interviews of 19 women living in rural localities in the central zone of Mexico. Through this analysis, a core category arose: social criticism of physical exercise. The results show that married women do not perform physical exercise because, due social norms, it is socially frowned upon and men are responsible for making the decision to permit it. Gender, female identity, women's role as subordinates to men, and social criticism are elements that contribute to understanding the lack of physical activity among these women. We suggest that healthcare programs be designed to promote physical activity among adult women in rural areas, taking gender perspective and the population's context into account.

  9. Neuronal cell migration in C. elegans: regulation of Hox gene expression and cell position.

    PubMed

    Harris, J; Honigberg, L; Robinson, N; Kenyon, C

    1996-10-01

    In C. elegans, the Hox gene mab-5, which specifies the fates of cells in the posterior body region, has been shown to direct the migrations of certain cells within its domain of function. mab-5 expression switches on in the neuroblast QL as it migrates into the posterior body region. mab-5 activity is then required for the descendants of QL to migrate to posterior rather than anterior positions. What information activates Hox gene expression during this cell migration? How are these cells subsequently guided to their final positions? We address these questions by describing four genes, egl-20, mig-14, mig-1 and lin-17, that are required to activate expression of mab-5 during migration of the QL neuroblast. We find that two of these genes, egl-20 and mig-14, also act in a mab-5-independent way to determine the final stopping points of the migrating Q descendants. The Q descendants do not migrate toward any obvious physical targets in wild-type or mutant animals. Therefore, these genes appear to be part of a system that positions the migrating Q descendants along the anteroposterior axis.

  10. Time-lapse cinematography of the capillary tube cell migration inhibition test.

    PubMed

    Bray, M A

    1980-01-01

    The kinetics of human and guinea pig cell migration inhibition have been studied using time-lapse cinematography of cells migrating from capillary tubes. Guinea pig and human cells exhibit markedly different kinetics in the absence of inhibitors. Specific antigen causes a dose-related inhibition of migration for up to 60 h using guinea pig cells and a peak of inhibition after 18 h using the human leucocyte system. The timing of measurement of maximum activity more critical for the latter test. The kinetics of lymphokine generation have been examined and the migration inhibitory activity of the plant mitogen (PHA), a Kurloff cell product and a continuous cell line supernatant have been compared with the inhibitory profiles of lymphokine preparations and specific antigen.

  11. Migration, Acculturation and Environment: Determinants of Obesity among Iranian Migrants in Australia

    PubMed Central

    Delavari, Maryam; Sønderlund, Anders Larrabee; Mellor, David; Mohebbi, Mohammadreza; Swinburn, Boyd

    2015-01-01

    While migration from low- to high-income countries is typically associated with weight gain, the obesity risks of migration from middle-income countries are less certain. In addition to changes in behaviours and cultural orientation upon migration, analyses of changes in environments are needed to explain post-migration risks for obesity. The present study examines the interaction between obesity-related environmental factors and the pattern of migrant acculturation in a sample of 152 Iranian immigrants in Victoria, Australia. Weight measurements, demographics, physical activity levels and diet habits were also surveyed. The pattern of acculturation (relative integration, assimilation, separation or marginalization) was not related to body mass index, diet, or physical activity behaviours. Three relevant aspects of participants’ perception of the Australian environment (physically active environments, social pressure to be fit, unhealthy food environments) varied considerably by demographic characteristics, but only one (physically active environments) was related to a pattern of acculturation (assimilation). Overall, this research highlighted a number of key relationships between acculturation and obesity-related environments and behaviours for our study sample. Theoretical models on migration, culture and obesity need to include environmental factors. PMID:25648171

  12. SIRT-1 regulates TGF-β-induced dermal fibroblast migration via modulation of Cyr61 expression.

    PubMed

    Kwon, Eun-Jeong; Park, Eun-Jung; Yu, Hyeran; Huh, Jung-Sik; Kim, Jinseok; Cho, Moonjae

    2018-05-01

    SIRT1 is a NAD-dependent protein deacetylase that participates in cellular regulation. The increased migration of fibroblasts is an important phenotype in fibroblast activation. The role of SIRT1 in cell migration remains controversial as to whether SIRT1 acts as an activator or suppressor of cell migration. Therefore, we have established the role of SIRT1 in the migration of human dermal fibroblasts and explored targets of SIRT1 during dermal fibroblast migration. SIRT1 and Cyr61 were expressed in human dermal fibroblasts and the stimulation with TGF-β further induced their expression. Treatment with resveratrol (RSV), a SIRT1 agonist, or overexpression of SIRT1 also promoted the expression Cyr61 in human dermal fibroblasts, whereas the inhibition of SIRT1 activity by nicotinamide or knockdown of SIRT1 decreased the level of Cyr61, as well as TGF-β or RSV-induced Cyr61 expression. Blocking of ERK signaling by PD98509 reduced the expression of Cyr61 induced by TGF-β or RSV. TGF-β, RSV, or SIRT1 overexpression enhanced β-catenin as well as Cyr61 expression. This stimulation was reduced by the Wnt inhibitor XAV939. RSV increased migration and nicotinamide attenuated RSV-induced migration of human dermal fibroblasts. Furthermore, SIRT1 overexpression promoted cell migration, whereas blocking Cyr61 attenuated SIRT1-stimulated migration of human dermal fibroblasts. SIRT1 increased cell migration by stimulating Cyr61 expression and the ERK and Wnt/β-catenin signaling. SIRT1-induced Cyr61 activity is very important for human dermal fibroblasts migration.

  13. Characterizing the International Migration Barriers with a Probabilistic Multilateral Migration Model

    PubMed Central

    Li, Xiaomeng; Xu, Hongzhong; Chen, Jiawei; Chen, Qinghua; Zhang, Jiang; Di, Zengru

    2016-01-01

    Human migration is responsible for forming modern civilization and has had an important influence on the development of various countries. There are many issues worth researching, and “the reason to move” is the most basic one. The concept of migration cost in the classical self-selection theory, which was introduced by Roy and Borjas, is useful. However, migration cost cannot address global migration because of the limitations of deterministic and bilateral choice. Following the idea of migration cost, this paper developed a new probabilistic multilateral migration model by introducing the Boltzmann factor from statistical physics. After characterizing the underlying mechanism or driving force of human mobility, we reveal some interesting facts that have provided a deeper understanding of international migration, such as the negative correlation between migration costs for emigrants and immigrants and a global classification with clear regional and economic characteristics, based on clustering of migration cost vectors. In addition, we deconstruct the migration barriers using regression analysis and find that the influencing factors are complicated but can be partly (12.5%) described by several macro indexes, such as the GDP growth of the destination country, the GNI per capita and the HDI of both the source and destination countries. PMID:27597319

  14. Characterizing the International Migration Barriers with a Probabilistic Multilateral Migration Model

    NASA Astrophysics Data System (ADS)

    Li, Xiaomeng; Xu, Hongzhong; Chen, Jiawei; Chen, Qinghua; Zhang, Jiang; di, Zengru

    2016-09-01

    Human migration is responsible for forming modern civilization and has had an important influence on the development of various countries. There are many issues worth researching, and “the reason to move” is the most basic one. The concept of migration cost in the classical self-selection theory, which was introduced by Roy and Borjas, is useful. However, migration cost cannot address global migration because of the limitations of deterministic and bilateral choice. Following the idea of migration cost, this paper developed a new probabilistic multilateral migration model by introducing the Boltzmann factor from statistical physics. After characterizing the underlying mechanism or driving force of human mobility, we reveal some interesting facts that have provided a deeper understanding of international migration, such as the negative correlation between migration costs for emigrants and immigrants and a global classification with clear regional and economic characteristics, based on clustering of migration cost vectors. In addition, we deconstruct the migration barriers using regression analysis and find that the influencing factors are complicated but can be partly (12.5%) described by several macro indexes, such as the GDP growth of the destination country, the GNI per capita and the HDI of both the source and destination countries.

  15. 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

  16. A novel derivative of decursin, CSL-32, blocks migration and production of inflammatory mediators and modulates PI3K and NF-κB activities in HT1080 cells.

    PubMed

    Lee, Seung-Hee; Lee, Jee Hyun; Kim, Eun-Ju; Kim, Won-Jung; Suk, Kyoungho; Kim, Joo-Hwan; Song, Gyu Yong; Lee, Won-Ha

    2012-07-01

    Decursin and related coumarin compounds in herbal extracts have a number of biological activities against inflammation, angiogenesis and cancer. We have analysed a derivative of decursin (CSL-32) for activity against inflammatory activation of cancer cells, such as migration, invasion and expression of pro-inflammatory mediators. The human fibrosarcoma cell line, HT1080, was treated with TNFα (tumour necrosis factor α) in the presence or absence of CSL-32. The cellular responses and modification of signalling adapters were analysed with respect to the production of pro-inflammatory mediators, as also migration, adhesion and invasion. Treatment of HT1080 cells with CSL-32 inhibited their proliferation, without affecting cell viability, and TNFα-induced expression of pro-inflammatory mediators, such as MMP-9 (matrix metalloproteinase-9) and IL-8 (interleukin-8). CSL-32 also suppressed phosphorylation and degradation of IκB (inhibitory κB), phosphorylation of p65 subunit of NF-κB (nuclear factor-κB) and nuclear translocation of NF-κB, which are required for the expression of pro-inflammatory mediators. In addition, CSL-32 inhibited invasion and migration of HT1080 cells, as also cellular adhesion to fibronectin, an ECM (extracellular matrix) protein. CSL-32 treatment resulted in a dose-dependent inhibition of PI3K (phosphoinositide 3-kinase) activity, required for the cellular migration. The analyses show that CSL-32 inhibits processes associated with inflammation, such as the production of pro-inflammatory mediators, as well as adhesion, migration and invasion in HT1080 cells.

  17. Muscarinic receptor agonists stimulate human colon cancer cell migration and invasion.

    PubMed

    Belo, Angelica; Cheng, Kunrong; Chahdi, Ahmed; Shant, Jasleen; Xie, Guofeng; Khurana, Sandeep; Raufman, Jean-Pierre

    2011-05-01

    Muscarinic receptors (CHRM) are overexpressed in colon cancer. To explore a role for muscarinic receptor signaling in colon cancer metastasis, we used human H508 and HT29 colon cancer cells that coexpress epidermal growth factor (ERBB) and CHRM3 receptors. In a wound closure model, following 8-h incubation of H508 cells with 100 μM ACh we observed a threefold increase in cell migration indistinguishable from the actions of epidermal growth factor (EGF). Atropine blocked the actions of ACh but not of EGF. In SNU-C4 colon cancer cells that express ERBB but not CHRM, EGF caused a threefold increase in migration; ACh had no effect. ACh-induced cell migration was attenuated by chemical inhibitors of ERBB1 activation, by anti-ERBB1 antibody, and by inhibitors of ERK and phosphatidylinositol 3-kinase (PI3K) signaling. Consistent with matrix metalloproteinase-7 (MMP7)-mediated release of an ERBB1 ligand, heparin binding epidermal growth factor-like growth factor (HBEGF), ACh-induced migration was inhibited by an MMP inhibitor and by anti-MMP7 and -HBEGF antibodies. ACh-induced cell migration was blocked by inhibiting RhoA and ROCK, key proteins that interact with the actin cytoskeleton. ACh-induced RhoA activation was attenuated by agents that inhibit ERBB1, ERK, and PI3K activation. Collectively, these findings indicate that ACh-induced cell migration is mediated by MMP7-mediated release of HBEGF, an ERBB ligand that activates ERBB1 and downstream ERK and PI3K signaling. In a cell invasion model, ACh-induced HT29 cell invasion was blocked by atropine. In concert with previous observations, these findings indicate that muscarinic receptor signaling plays a key role in colon cancer cell proliferation, survival, migration, and invasion.

  18. Muscarinic receptor agonists stimulate human colon cancer cell migration and invasion

    PubMed Central

    Belo, Angelica; Cheng, Kunrong; Chahdi, Ahmed; Shant, Jasleen; Xie, Guofeng; Khurana, Sandeep

    2011-01-01

    Muscarinic receptors (CHRM) are overexpressed in colon cancer. To explore a role for muscarinic receptor signaling in colon cancer metastasis, we used human H508 and HT29 colon cancer cells that coexpress epidermal growth factor (ERBB) and CHRM3 receptors. In a wound closure model, following 8-h incubation of H508 cells with 100 μM ACh we observed a threefold increase in cell migration indistinguishable from the actions of epidermal growth factor (EGF). Atropine blocked the actions of ACh but not of EGF. In SNU-C4 colon cancer cells that express ERBB but not CHRM, EGF caused a threefold increase in migration; ACh had no effect. ACh-induced cell migration was attenuated by chemical inhibitors of ERBB1 activation, by anti-ERBB1 antibody, and by inhibitors of ERK and phosphatidylinositol 3-kinase (PI3K) signaling. Consistent with matrix metalloproteinase-7 (MMP7)-mediated release of an ERBB1 ligand, heparin binding epidermal growth factor-like growth factor (HBEGF), ACh-induced migration was inhibited by an MMP inhibitor and by anti-MMP7 and -HBEGF antibodies. ACh-induced cell migration was blocked by inhibiting RhoA and ROCK, key proteins that interact with the actin cytoskeleton. ACh-induced RhoA activation was attenuated by agents that inhibit ERBB1, ERK, and PI3K activation. Collectively, these findings indicate that ACh-induced cell migration is mediated by MMP7-mediated release of HBEGF, an ERBB ligand that activates ERBB1 and downstream ERK and PI3K signaling. In a cell invasion model, ACh-induced HT29 cell invasion was blocked by atropine. In concert with previous observations, these findings indicate that muscarinic receptor signaling plays a key role in colon cancer cell proliferation, survival, migration, and invasion. PMID:21273532

  19. Migrating lumbar facet joint cysts.

    PubMed

    Palmieri, Francesco; Cassar-Pullicino, Victor N; Lalam, Radhesh K; Tins, Bernhard J; Tyrrell, Prudencia N M; McCall, Iain W

    2006-04-01

    The majority of lumbar facet joint cysts (LFJCs) are located in the spinal canal, on the medial aspect of the facet joint with characteristic diagnostic features. When they migrate away from the joint of origin, they cause diagnostic problems. In a 7-year period we examined by computed tomography (CT) and magnetic resonance (MR) imaging five unusual cases of facet joint cysts which migrated from the facet joint of origin. Three LFJCs were identified in the right S1 foramen, one in the right L5-S1 neural foramen and one in the left erector spinae and multifidus muscles between the levels of L2-L4 spinous process. Awareness that spinal lesions identified at MRI and CT could be due to migrating facet joint cyst requires a high level of suspicion. The identification of the appositional contact of the cyst and the facet joint needs to be actively sought in the presence of degenerative facet joints.

  20. 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.

  1. Japanese migration in contemporary Japan: economic segmentation and interprefectural migration.

    PubMed

    Fukurai, H

    1991-01-01

    This paper examines the economic segmentation model in explaining 1985-86 Japanese interregional migration. The analysis takes advantage of statistical graphic techniques to illustrate the following substantive issues of interregional migration: (1) to examine whether economic segmentation significantly influences Japanese regional migration and (2) to explain socioeconomic characteristics of prefectures for both in- and out-migration. Analytic techniques include a latent structural equation (LISREL) methodology and statistical residual mapping. The residual dispersion patterns, for instance, suggest the extent to which socioeconomic and geopolitical variables explain migration differences by showing unique clusters of unexplained residuals. The analysis further points out that extraneous factors such as high residential land values, significant commuting populations, and regional-specific cultures and traditions need to be incorporated in the economic segmentation model in order to assess the extent of the model's reliability in explaining the pattern of interprefectural migration.

  2. Androgen-Induced Cell Migration: Role of Androgen Receptor/Filamin A Association

    PubMed Central

    Castoria, Gabriella; D'Amato, Loredana; Ciociola, Alessandra; Giovannelli, Pia; Giraldi, Tiziana; Sepe, Leandra; Paolella, Giovanni; Barone, Maria Vittoria; Migliaccio, Antimo; Auricchio, Ferdinando

    2011-01-01

    Background Androgen receptor (AR) controls male morphogenesis, gametogenesis and prostate growth as well as development of prostate cancer. These findings support a role for AR in cell migration and invasiveness. However, the molecular mechanism involved in AR-mediated cell migration still remains elusive. Methodology/Principal Findings Mouse embryo NIH3T3 fibroblasts and highly metastatic human fibrosarcoma HT1080 cells harbor low levels of transcriptionally incompetent AR. We now report that, through extra nuclear action, AR triggers migration of both cell types upon stimulation with physiological concentrations of the androgen R1881. We analyzed the initial events leading to androgen-induced cell migration and observed that challenging NIH3T3 cells with 10 nM R1881 rapidly induces interaction of AR with filamin A (FlnA) at cytoskeleton. AR/FlnA complex recruits integrin beta 1, thus activating its dependent cascade. Silencing of AR, FlnA and integrin beta 1 shows that this ternary complex controls focal adhesion kinase (FAK), paxillin and Rac, thereby driving cell migration. FAK-null fibroblasts migrate poorly and Rac inhibition by EHT impairs motility of androgen-treated NIH3T3 cells. Interestingly, FAK and Rac activation by androgens are independent of each other. Findings in human fibrosarcoma HT1080 cells strengthen the role of Rac in androgen signaling. The Rac inhibitor significantly impairs androgen-induced migration in these cells. A mutant AR, deleted of the sequence interacting with FlnA, fails to mediate FAK activation and paxillin tyrosine phosphorylation in androgen-stimulated cells, further reinforcing the role of AR/FlnA interaction in androgen-mediated motility. Conclusions/Significance The present report, for the first time, indicates that the extra nuclear AR/FlnA/integrin beta 1 complex is the key by which androgen activates signaling leading to cell migration. Assembly of this ternary complex may control organ development and prostate cancer

  3. Microtubule release from the centrosome in migrating cells

    PubMed Central

    Abal, Miguel; Piel, Matthieu; Bouckson-Castaing, Veronique; Mogensen, Mette; Sibarita, Jean-Baptiste; Bornens, Michel

    2002-01-01

    In migrating cells, force production relies essentially on a polarized actomyosin system, whereas the spatial regulation of actomyosin contraction and substrate contact turnover involves a complex cooperation between the microtubule (MT) and the actin filament networks (Goode, B.L., D.G. Drubin, and G. Barnes. 2000. Curr. Opin. Cell Biol., 12:63–71). Targeting and capture of MT plus ends at the cell periphery has been described, but whether or not the minus ends of these MTs are anchored at the centrosome is not known. Here, we show that release of short MTs from the centrosome is frequent in migrating cells and that their transport toward the cell periphery is blocked when dynein activity is impaired. We further show that MT release, but not MT nucleation or polymerization dynamics, is abolished by overexpression of the centrosomal MT-anchoring protein ninein. In addition, a dramatic inhibition of cell migration was observed; but, contrary to cells treated by drugs inhibiting MT dynamics, polarized membrane ruffling activity was not affected in ninein overexpressing cells. We thus propose that the balance between MT minus-end capture and release from the centrosome is critical for efficient cell migration. PMID:12473683

  4. Motile membrane protrusions regulate cell-cell adhesion and migration of olfactory ensheathing glia.

    PubMed

    Windus, Louisa C E; Claxton, Christina; Allen, Chelsea L; Key, Brian; St John, James A

    2007-12-01

    Olfactory ensheathing cells (OECs) are candidates for therapeutic approaches for neural regeneration due to their ability to assist axon regrowth in central nervous system lesion models. However, little is understood about the processes and mechanisms underlying migration of these cells. We report here that novel lamellipodial protrusions, termed lamellipodial waves, are integral to OEC migration. Time-lapse imaging of migrating OECs revealed that these highly dynamic waves progress along the shaft of the cells and are crucial for mediating cell-cell adhesion. Without these waves, cell-cell adhesion does not occur and migrational rates decline. The activity of waves is modulated by both glial cell line-derived neurotrophic factor and inhibitors of the JNK and SRC kinases. Furthermore, the activity of lamellipodial waves can be modulated by Mek1, independently of leading edge activity. The ability to selectively regulate cell migration via lamellipodial waves has implications for manipulating the migratory behavior of OECs during neural repair. (c) 2007 Wiley-Liss, Inc.

  5. Excessive activation of AhR signaling disrupts neuronal migration in the hippocampal CA1 region in the developing mouse.

    PubMed

    Kimura, Eiki; Kubo, Ken-Ichiro; Endo, Toshihiro; Nakajima, Kazunori; Kakeyama, Masaki; Tohyama, Chiharu

    2017-01-01

    The aryl hydrocarbon receptor (AhR) avidly binds dioxin, a ubiquitous environmental contaminant. Disruption of downstream AhR signaling has been reported to alter neuronal development, and rodent offspring exposed to dioxin during gestation and lactation showed abnormalities in learning and memory, emotion, and social behavior. However, the mechanism behind the disrupted AhR signaling and developmental neurotoxicity induced by xenobiotic ligands remains elusive. Therefore, we studied how excessive AhR activation affects neuronal migration in the hippocampal CA1 region of the developing mouse brain. We transfected constitutively active (CA)-AhR, AhR, or control vector plasmids into neurons via in utero electroporation on gestational day 14 and analyzed neuronal positioning in the hippocampal CA1 region of offspring on postnatal day 14. CA-AhR transfection affected neuronal positioning, whereas no change was observed in AhR-transfected or control hippocampus. These results suggest that constitutively activated AhR signaling disrupts neuronal migration during hippocampal development. Further studies are needed to investigate whether such developmental disruption in the hippocampus leads to the abnormal cognition and behavior of rodent offspring upon maternal exposure to AhR xenobiotic ligands.

  6. Activation of TRPV2 and BKCa channels by the LL-37 enantiomers stimulates calcium entry and migration of cancer cells.

    PubMed

    Gambade, Audrey; Zreika, Sami; Guéguinou, Maxime; Chourpa, Igor; Fromont, Gaëlle; Bouchet, Ana Maria; Burlaud-Gaillard, Julien; Potier-Cartereau, Marie; Roger, Sébastien; Aucagne, Vincent; Chevalier, Stéphan; Vandier, Christophe; Goupille, Caroline; Weber, Günther

    2016-04-26

    Expression of the antimicrobial peptide hCAP18/LL-37 is associated to malignancy in various cancer forms, stimulating cell migration and metastasis. We report that LL-37 induces migration of three cancer cell lines by activating the TRPV2 calcium-permeable channel and recruiting it to pseudopodia through activation of the PI3K/AKT pathway. Ca2+ entry through TRPV2 cooperated with a K+ efflux through the BKCa channel. In a panel of human breast tumors, the expression of TRPV2 and LL-37 was found to be positively correlated. The D-enantiomer of LL-37 showed identical effects as the L-peptide, suggesting that no binding to a specific receptor was involved. LL-37 attached to caveolae and pseudopodia membranes and decreased membrane fluidity, suggesting that a modification of the physical properties of the lipid membrane bilayer was the underlying mechanism of its effects.

  7. Activation of TRPV2 and BKCa channels by the LL-37 enantiomers stimulates calcium entry and migration of cancer cells

    PubMed Central

    Guéguinou, Maxime; Chourpa, Igor; Fromont, Gaëlle; Bouchet, Ana Maria; Burlaud-Gaillard, Julien; Potier-Cartereau, Marie; Roger, Sébastien; Aucagne, Vincent; Chevalier, Stéphan; Vandier, Christophe

    2016-01-01

    Expression of the antimicrobial peptide hCAP18/LL-37 is associated to malignancy in various cancer forms, stimulating cell migration and metastasis. We report that LL-37 induces migration of three cancer cell lines by activating the TRPV2 calcium-permeable channel and recruiting it to pseudopodia through activation of the PI3K/AKT pathway. Ca2+ entry through TRPV2 cooperated with a K+ efflux through the BKCa channel. In a panel of human breast tumors, the expression of TRPV2 and LL-37 was found to be positively correlated. The D-enantiomer of LL-37 showed identical effects as the L-peptide, suggesting that no binding to a specific receptor was involved. LL-37 attached to caveolae and pseudopodia membranes and decreased membrane fluidity, suggesting that a modification of the physical properties of the lipid membrane bilayer was the underlying mechanism of its effects. PMID:26993604

  8. 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

  9. Latitudinal migration of sunspots based on the ESAI database

    NASA Astrophysics Data System (ADS)

    Zhang, Juan; Li, Fu-Yu; Feng, Wen

    2018-01-01

    The latitudinal migration of sunspots toward the equator, which implies there is propagation of the toroidal magnetic flux wave at the base of the solar convection zone, is one of the crucial observational bases for the solar dynamo to generate a magnetic field by shearing of the pre-existing poloidal magnetic field through differential rotation. The Extended time series of Solar Activity Indices (ESAI) elongated the Greenwich observation record of sunspots by several decades in the past. In this study, ESAI’s yearly mean latitude of sunspots in the northern and southern hemispheres during the years 1854 to 1985 is utilized to statistically test whether hemispherical latitudinal migration of sunspots in a solar cycle is linear or nonlinear. It is found that a quadratic function is statistically significantly better at describing hemispherical latitudinal migration of sunspots in a solar cycle than a linear function. In addition, the latitude migration velocity of sunspots in a solar cycle decreases as the cycle progresses, providing a particular constraint for solar dynamo models. Indeed, the butterfly wing pattern with a faster latitudinal migration rate should present stronger solar activity with a shorter cycle period, and it is located at higher latitudinal position, giving evidence to support the Babcock-Leighton dynamo mechanism.

  10. Analyzing bat migration

    USGS Publications Warehouse

    Cryan, Paul M.; Diehl, Robert H.

    2009-01-01

    T HE MIGRATORY MOVEIvl.ENTS OF BATS have proven ex­ tremely difficult to determine. Despite extensive efforts during the past century to track the movements of bats across landscapes, efficient methods of following small- to medium-size volant animals <240 gl for extended periods (>8 weeks) over long distances (>100 km) have not been developed. Important questions about bat migration remain unanswered: Which bats migrate? Where do they go? How far do they move? How high and fast do they fly? What are their habitat needs during migration? How do bats orient and navigate during migration? Addressing these apparently simple questions will be a considerable challenge to anyone interested in advancing the study of bat migration. In this chapter, we present direct and indirect methods used to study bat migration as well as techniques that have worked for studying bird migration that could feasibly be adapted to the study of bats.

  11. The Utility of the Extended Images in Ambient Seismic Wavefield Migration

    NASA Astrophysics Data System (ADS)

    Girard, A. J.; Shragge, J. C.

    2015-12-01

    Active-source 3D seismic migration and migration velocity analysis (MVA) are robust and highly used methods for imaging Earth structure. One class of migration methods uses extended images constructed by incorporating spatial and/or temporal wavefield correlation lags to the imaging conditions. These extended images allow users to directly assess whether images focus better with different parameters, which leads to MVA techniques that are based on the tenets of adjoint-state theory. Under certain conditions (e.g., geographical, cultural or financial), however, active-source methods can prove impractical. Utilizing ambient seismic energy that naturally propagates through the Earth is an alternate method currently used in the scientific community. Thus, an open question is whether extended images are similarly useful for ambient seismic migration processing and verifying subsurface velocity models, and whether one can similarly apply adjoint-state methods to perform ambient migration velocity analysis (AMVA). Herein, we conduct a number of numerical experiments that construct extended images from ambient seismic recordings. We demonstrate that, similar to active-source methods, there is a sensitivity to velocity in ambient seismic recordings in the migrated extended image domain. In synthetic ambient imaging tests with varying degrees of error introduced to the velocity model, the extended images are sensitive to velocity model errors. To determine the extent of this sensitivity, we utilize acoustic wave-equation propagation and cross-correlation-based migration methods to image weak body-wave signals present in the recordings. Importantly, we have also observed scenarios where non-zero correlation lags show signal while zero-lags show none. This may be a valuable missing piece for ambient migration techniques that have yielded largely inconclusive results, and might be an important piece of information for performing AMVA from ambient seismic recordings.

  12. Structural and Kinetic Analyses of Macrophage Migration Inhibitory Factor Active Site Interactions

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

    Crichlow, G.; Lubetsky, J; Leng, L

    Macrophage migration inhibitory factor (MIF) is a secreted protein expressed in numerous cell types that counters the antiinflammatory effects of glucocorticoids and has been implicated in sepsis, cancer, and certain autoimmune diseases. Interestingly, the structure of MIF contains a catalytic site resembling the tautomerase/isomerase sites of microbial enzymes. While bona fide physiological substrates remain unknown, model substrates have been identified. Selected compounds that bind in the tautomerase active site also inhibit biological functions of MIF. It had previously been shown that the acetaminophen metabolite, N-acetyl-p-benzoquinone imine (NAPQI), covalently binds to the active site of MIF. In this study, kinetic datamore » indicate that NAPQI inhibits MIF both covalently and noncovalently. The structure of MIF cocrystallized with NAPQI reveals that the NAPQI has undergone a chemical alteration forming an acetaminophen dimer (bi-APAP) and binds noncovalently to MIF at the mouth of the active site. We also find that the commonly used protease inhibitor, phenylmethylsulfonyl fluoride (PMSF), forms a covalent complex with MIF and inhibits the tautomerase activity. Crystallographic analysis reveals the formation of a stable, novel covalent bond for PMSF between the catalytic nitrogen of the N-terminal proline and the sulfur of PMSF with complete, well-defined electron density in all three active sites of the MIF homotrimer. Conclusions are drawn from the structures of these two MIF-inhibitor complexes regarding the design of novel compounds that may provide more potent reversible and irreversible inhibition of MIF.« less

  13. 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

  14. 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

  15. Proteolytic Enzymes Clustered in Specialized Plasma-Membrane Domains Drive Endothelial Cells’ Migration

    PubMed Central

    Salamone, Monica; Carfì Pavia, Francesco

    2016-01-01

    In vitro cultured endothelial cells forming a continuous monolayer establish stable cell-cell contacts and acquire a “resting” phenotype; on the other hand, when growing in sparse conditions these cells acquire a migratory phenotype and invade the empty area of the culture. Culturing cells in different conditions, we compared expression and clustering of proteolytic enzymes in cells having migratory versus stationary behavior. In order to observe resting and migrating cells in the same microscopic field, a continuous cell monolayer was wounded. Increased expression of proteolytic enzymes was evident in cell membranes of migrating cells especially at sprouting sites and in shed membrane vesicles. Gelatin zymography and western blotting analyses confirmed that in migrating cells, expression of membrane-bound and of vesicle-associated proteolytic enzymes are increased. The enzymes concerned include MMP-2, MMP-9, MT1-MMP, seprase, DPP4 (DiPeptidyl Peptidase 4) and uPA. Shed membrane vesicles were shown to exert degradative activity on ECM components and produce substrates facilitating cell migration. Vesicles shed by migrating cells degraded ECM components at an increased rate; as a result their effect on cell migration was amplified. Inhibiting either Matrix Metallo Proteases (MMPs) or Serine Integral Membrane Peptidases (SIMPs) caused a decrease in the stimulatory effect of vesicles, inhibiting the spontaneous migratory activity of cells; a similar result was also obtained when a monoclonal antibody acting on DPP4 was tested. We conclude that proteolytic enzymes have a synergistic stimulatory effect on cell migration and that their clustering probably facilitates the proteolytic activation cascades needed to produce maximal degradative activity on cell substrates during the angiogenic process. PMID:27152413

  16. Lactate dehydrogenase-A is indispensable for vascular smooth muscle cell proliferation and migration.

    PubMed

    Kim, Ji-Hyun; Bae, Kwi-Hyun; Byun, Jun-Kyu; Lee, Sungwoo; Kim, Jung-Guk; Lee, In Kyu; Jung, Gwon-Soo; Lee, You Mie; Park, Keun-Gyu

    2017-10-07

    The proliferation and migration of vascular smooth muscle cells (VSMCs) have been implicated in the pathogenesis of atherosclerosis. Increased aerobic glycolysis is a key feature of cellular phenotypes including cancer and immune cells. However, the role of aerobic glycolysis in the atherogenic phenotype of VSMCs remains largely unknown. Here, we investigated the role of lactate dehydrogenase-A (LDHA), which is a key enzyme for glycolysis, in the proliferation and migration of VSMCs. Activation of primary rat VSMCs with fetal bovine serum (FBS) or platelet-derived growth factor (PDGF) increased their proliferation and migration, glycolytic activity, and expression of LDHA. Wound healing and transwell migration assays demonstrated that small interfering RNA-mediated knockdown of LDHA and pharmacological inhibition of LDHA by oxamate both effectively inhibited VSMC proliferation and migration. Inhibition of LDHA activity by oxamate reduced PDGF-stimulated glucose uptake, lactate production, and ATP production. Taken together, this study shows that enhanced glycolysis in PDGF- or FBS-stimulated VSMCs plays an important role in their proliferation and migration and suggests that LDHA is a potential therapeutic target to prevent vessel lumen constriction during the course of atherosclerosis and restenosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Evidence of early systemic activation and transendothelial migration of neutrophils in neonates with severe respiratory distress syndrome.

    PubMed

    Sarafidis, K; Drossou-Agakidou, V; Kanakoudi-Tsakalidou, F; Taparkou, A; Tsakalidis, C; Tsandali, C; Kremenopoulos, G

    2001-03-01

    Several observations imply that the early inflammatory response involving activated neutrophils, tissue macrophages, and cytokines plays an important role in the pathogenesis of neonatal respiratory distress syndrome (RDS) and progression to bronchopulmonary dysplasia (BPD). The aim of this study was to test the hypothesis that changes in circulating neutrophil number and function and plasma levels of cytokines, consistent with neutrophil activation and migration to the tissues, occur during the early stages of neonatal RDS. For this purpose we measured peripheral blood levels of certain immunological parameters that promote neutrophil activation and transendothelial migration. Twenty preterm neonates with severe RDS and 20 healthy infants matched for gestational age were the subjects. The absolute neutrophil count (ANC), and plasma levels of interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and sL-selectin using an enzyme-linked immunosorbent assay (ELISA), neutrophil CD11b expression, and respiratory burst activity (RBA) using flow cytometry, were measured within 24 h after birth. The two groups were comparable regarding perinatal characteristics. None of the neonates studied had any clinical or laboratory evidence of infection by the time of blood sampling. The immunological investigation showed that the RDS neonates had significantly lower ANC (P = 0.032), higher expression of the CD11b on neutrophils (P = 0.0065), and higher G-CSF and IL-6 plasma levels (P = 0.0047 and P < 0.0001, respectively) in comparison to healthy preterm neonates. The neutrophil RBA and plasma sL-selectin levels did not differ significantly between the two groups. We conclude that in neonates with severe RDS, there is evidence of a systemic neutrophil activation early in the course of the disease, supporting the view of a contributing role of activated neutrophils in the pathogenesis of RDS. Copyright 2001 Wiley-Liss, Inc.

  18. Uridine adenosine tetraphosphate (Up{sub 4}A) is a strong inductor of smooth muscle cell migration via activation of the P2Y{sub 2} receptor and cross-communication to the PDGF receptor

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

    Wiedon, Annette; Toelle, Markus; Bastine, Joschika

    2012-01-20

    Highlights: Black-Right-Pointing-Pointer Up{sub 4}A induces VSMC migration. Black-Right-Pointing-Pointer VSMC migration towards Up{sub 4}A involves P2Y{sub 2} activation. Black-Right-Pointing-Pointer Up{sub 4}A-induced VSMC migration is OPN-dependent. Black-Right-Pointing-Pointer Activation of ERK1/2 pathway is necessary for VSMC migration towards Up{sub 4}A. Black-Right-Pointing-Pointer Up{sub 4}A-directed VSMC migration cross-communicates with the PDGFR. -- Abstract: The recently discovered dinucleotide uridine adenosine tetraphosphate (Up{sub 4}A) was found in human plasma and characterized as endothelium-derived vasoconstrictive factor (EDCF). A further study revealed a positive correlation between Up{sub 4}A and vascular smooth muscle cell (VSMC) proliferation. Due to the dominant role of migration in the formation of atherosclerotic lesions ourmore » aim was to investigate the migration stimulating potential of Up{sub 4}A. Indeed, we found a strong chemoattractant effect of Up{sub 4}A on VSMC by using a modified Boyden chamber. This migration dramatically depends on osteopontin secretion (OPN) revealed by the reduction of the migration signal down to 23% during simultaneous incubation with an OPN-blocking antibody. Due to inhibitory patterns using specific and unspecific purinoreceptor inhibitors, Up{sub 4}A mediates it's migratory signal mainly via the P2Y{sub 2}. The signaling behind the receptor was investigated with luminex technique and revealed an activation of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway. By use of the specific PDGF receptor (PDGFR) inhibitor AG1296 and siRNA technique against PDGFR-{beta} we found a strongly reduced migration signal after Up{sub 4}A stimulation in the PDGFR-{beta} knockdown cells compared to control cells. In this study, we present substantiate data that Up{sub 4}A exhibits migration stimulating potential probably involving the signaling cascade of MEK1 and ERK1/2 as well as the matrix protein

  19. Controlled levels of canonical Wnt signaling are required for neural crest migration.

    PubMed

    Maj, Ewa; Künneke, Lutz; Loresch, Elisabeth; Grund, Anita; Melchert, Juliane; Pieler, Tomas; Aspelmeier, Timo; Borchers, Annette

    2016-09-01

    Canonical Wnt signaling plays a dominant role in the development of the neural crest (NC), a highly migratory cell population that generates a vast array of cell types. Canonical Wnt signaling is required for NC induction as well as differentiation, however its role in NC migration remains largely unknown. Analyzing nuclear localization of β-catenin as readout for canonical Wnt activity, we detect nuclear β-catenin in premigratory but not migratory Xenopus NC cells suggesting that canonical Wnt activity has to decrease to basal levels to enable NC migration. To define a possible function of canonical Wnt signaling in Xenopus NC migration, canonical Wnt signaling was modulated at different time points after NC induction. This was accomplished using either chemical modulators affecting β-catenin stability or inducible glucocorticoid fusion constructs of Lef/Tcf transcription factors. In vivo analysis of NC migration by whole mount in situ hybridization demonstrates that ectopic activation of canonical Wnt signaling inhibits cranial NC migration. Further, NC transplantation experiments confirm that this effect is tissue-autonomous. In addition, live-cell imaging in combination with biophysical data analysis of explanted NC cells confirms the in vivo findings and demonstrates that modulation of canonical Wnt signaling affects the ability of NC cells to perform single cell migration. Thus, our data support the hypothesis that canonical Wnt signaling needs to be tightly controlled to enable migration of NC cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Migration of female construction labourers to Dhaka City, Bangladesh.

    PubMed

    Ahsan, R M

    1997-03-01

    The author analyzes migration patterns and processes of female construction workers in Dhaka City, Bangladesh, and considers the impact of this migration. "Interviews...reveal that the major goal of these female migrants, whose mobility and employment have traditionally been restricted, is to take responsibility in the struggle for livelihood.... Success of many migrations is linked with participation in construction work in the city. Employment in such activities is largely by women from male-headed households, indicating male support in the work, followed by females heading their own households." excerpt

  1. Drosophila hemocyte migration: an in vivo assay for directional cell migration.

    PubMed

    Moreira, Carolina G A; Regan, Jennifer C; Zaidman-Rémy, Anna; Jacinto, Antonio; Prag, Soren

    2011-01-01

    This protocol describes an in vivo assay for random and directed hemocyte migration in Drosophila. Drosophila is becoming an increasingly powerful model system for in vivo cell migration analysis, combining unique genetic tools with translucency of the embryo and pupa, which allows direct imaging and traceability of different cell types. In the assay we present here, we make use of the hemocyte response to epithelium wounding to experimentally induce a transition from random to directed migration. Time-lapse confocal microscopy of hemocyte migration in untreated conditions provides a random cell migration assay that allows identification of molecular mechanisms involved in this complex process. Upon laser-induced wounding of the thorax epithelium, a rapid chemotactic response changes hemocyte migratory behavior into a directed migration toward the wound site. This protocol provides a direct comparison of cells during both types of migration in vivo, and combined with recently developed resources such as transgenic RNAi, is ideal for forward genetic screens.

  2. Cadmium migration in aerospace nickel cadmium cells

    NASA Technical Reports Server (NTRS)

    Mcdermott, P. P.

    1976-01-01

    The effects of temperature, the nature of separator material, charge and discharge, carbonate contamination, and the mode of storage are studied with respect to the migration of active material from the negative toward the positive plate. A theoretical model is proposed which takes into account the solubility of cadmium in various concentrations of hydroxide and carbonate at different temperatures, the generation of the cadmiate ion, Cd(OH)3(-), during discharge, the migration of the cadmiate ion and particulate Cd(OH)2 due to electrophoretic effects and the movement of electrolyte in and out of the negative plate and, finally, the recrystallization of cadmiate ion in the separator as Cd(OH)2. Application of the theoretical model to observations of cadmium migration in cycled cells is also discussed.

  3. An extracellular-matrix-specific GEF-GAP interaction regulates Rho GTPase crosstalk for 3D collagen migration.

    PubMed

    Kutys, Matthew L; Yamada, Kenneth M

    2014-09-01

    Rho-family GTPases govern distinct types of cell migration on different extracellular matrix proteins in tissue culture or three-dimensional (3D) matrices. We searched for mechanisms selectively regulating 3D cell migration in different matrix environments and discovered a form of Cdc42-RhoA crosstalk governing cell migration through a specific pair of GTPase activator and inhibitor molecules. We first identified βPix, a guanine nucleotide exchange factor (GEF), as a specific regulator of migration in 3D collagen using an affinity-precipitation-based GEF screen. Knockdown of βPix specifically blocks cell migration in fibrillar collagen microenvironments, leading to hyperactive cellular protrusion accompanied by increased collagen matrix contraction. Live FRET imaging and RNAi knockdown linked this βPix knockdown phenotype to loss of polarized Cdc42 but not Rac1 activity, accompanied by enhanced, de-localized RhoA activity. Mechanistically, collagen phospho-regulates βPix, leading to its association with srGAP1, a GTPase-activating protein (GAP), needed to suppress RhoA activity. Our results reveal a matrix-specific pathway controlling migration involving a GEF-GAP interaction of βPix with srGAP1 that is critical for maintaining suppressive crosstalk between Cdc42 and RhoA during 3D collagen migration.

  4. Language competition in a population of migrating agents.

    PubMed

    Lipowska, Dorota; Lipowski, Adam

    2017-05-01

    Influencing various aspects of human activity, migration is associated also with language formation. To examine the mutual interaction of these processes, we study a Naming Game with migrating agents. The dynamics of the model leads to formation of low-mobility clusters, which turns out to break the symmetry of the model: although the Naming Game remains symmetric, low-mobility languages are favored. High-mobility languages are gradually eliminated from the system, and the dynamics of language formation considerably slows down. Our model is too simple to explain in detail language competition of migrating human communities, but it certainly shows that languages of settlers are favored over nomadic ones.

  5. Language competition in a population of migrating agents

    NASA Astrophysics Data System (ADS)

    Lipowska, Dorota; Lipowski, Adam

    2017-05-01

    Influencing various aspects of human activity, migration is associated also with language formation. To examine the mutual interaction of these processes, we study a Naming Game with migrating agents. The dynamics of the model leads to formation of low-mobility clusters, which turns out to break the symmetry of the model: although the Naming Game remains symmetric, low-mobility languages are favored. High-mobility languages are gradually eliminated from the system, and the dynamics of language formation considerably slows down. Our model is too simple to explain in detail language competition of migrating human communities, but it certainly shows that languages of settlers are favored over nomadic ones.

  6. Genomic and metabolic preparation of muscle in sockeye salmon Oncorhynchus nerka for spawning migration.

    PubMed

    Morash, Andrea J; Yu, Wilson; Le Moine, Christophe M R; Hills, Jayme A; Farrell, Anthony P; Patterson, David A; McClelland, Grant B

    2013-01-01

    Prolonged endurance exercise and fasting are two major metabolic challenges facing Pacific salmon during spawning migrations that often occur over 1,000 km. Because both prolonged exercise and fasting stimulate the oxidation of lipids, particularly in heavily recruited tissues such as muscle, we sought to investigate the regulatory mechanisms that establish and maintain the capacity for substrate oxidation at four separate locations during the final 750 km of nonfeeding migration in sockeye salmon Oncorhynchus nerka. Transcript levels of multiple genes encoding for important regulators of lipid, carbohydrate, and protein oxidation as well as the activity of several important enzymes involved in lipid and carbohydrate oxidation were examined in red and white muscle. We found in both muscle types that the messenger RNA (mRNA) expression of carnitine palmitoyltransferase I isoforms, peroxisome proliferator-activated receptors α and β, and adenosine monophosphate-activated protein kinase β1 were all significantly higher at the onset compared to later stages of nonfeeding migration. However, the activities of β-hydroxyacyl-CoA dehydrogenase and citrate synthase were higher only early in migration and only in red muscle. Later in the migration and as muscle lipid stores were greatly depleted, the mRNA levels of hexokinase I and aspartate aminotransferase increased in white muscle. Overall, at the onset of migration, high transcript and metabolic enzyme activity levels in skeletal muscle of sockeye salmon may help support the high rates of lipid oxidation needed for endurance swimming. Furthermore, we suggest that the muscle capacity to use carbohydrates and proteins may be adjusted throughout migration on an as-needed basis to fuel burst exercise through very difficult hydraulic passages in the river and perhaps during mating activities.

  7. Population, migration and urbanization.

    PubMed

    1982-06-01

    Despite recent estimates that natural increase is becoming a more important component of urban growth than rural urban transfer (excess of inmigrants over outmigrants), the share of migration in the total population growth has been consistently increasing in both developed and developing countries. From a demographic perspective, the migration process involves 3 elements: an area of origin which the mover leaves and where he or she is considered an outmigrant; the destination or place of inmigration; and the period over which migration is measured. The 2 basic types of migration are internal and international. Internal migration consists of rural to urban migration, urban to urban migration, rural to rural migration, and urban to rural migration. Among these 4 types of migration various patterns or processes are followed. Migration may be direct when the migrant moves directly from the village to the city and stays there permanently. It can be circular migration, meaning that the migrant moves to the city when it is not planting season and returns to the village when he is needed on the farm. In stage migration the migrant makes a series of moves, each to a city closer to the largest or fastest growing city. Temporary migration may be 1 time or cyclical. The most dominant pattern of internal migration is rural urban. The contribution of migration to urbanization is evident. For example, the rapid urbanization and increase in urban growth from 1960-70 in the Republic of Korea can be attributed to net migration. In Asia the largest component of the population movement consists of individuals and groups moving from 1 rural location to another. Recently, because urban centers could no longer absorb the growing number of migrants from other places, there has been increased interest in the urban to rural population redistribution. This reverse migration also has come about due to slower rates of employment growth in the urban centers and improved economic opportunities

  8. Analysis of sediment production from two small semiarid basins in Wyoming

    USGS Publications Warehouse

    Rankl, J.G.

    1987-01-01

    Data were collected at two small, semiarid basins in Wyoming to determine the relation between rainfall, runoff, and sediment production. The basins were Dugout Creek tributary and Saint Marys Ditch tributary. Sufficient rainfall and runoff data were collected at Dugout Creek tributary to determine the source of sediment and the dominant sediment production processes. Because runoff from only one storm occurred in Saint Marys Ditch tributary, emphasis of the study was placed on the analysis of data collected at Dugout Creek tributary. At Dugout Creek tributary, detailed measurements were made to establish the source of sediment. To determine the quantity of material removed from headcuts during the study, two headcuts were surveyed. Aerial photographs were used to define movement of all headcuts. The total quantity of sediment removed from all headcuts between September 26, 1982, and September 26, 1983, was estimated to be 1,220 tons, or 15%-25% of the estimated total sediment load passing the streamflow-gaging station. A soil plot was used to sample upland erosion. A rainfall and runoff modeling system was used to evaluate the interaction between the physical processes which control sediment production. The greatest change in computed sediment load was caused by changing the parameter values for equations used to compute the detachment of sediment particles by rainfall and overland flow resulted in very small changes in computed sediment load. The upland areas were the primary source of sediment. A relationship was developed between the peak of storm runoff and the total sediment load for that storm runoff. The sediment concentration used to compute the total sediment load for the storm runoff was determined from sediment samples collected by two automatic pumping samplers. The coefficient of variation of the relationship is 34% with a 0.99 correlation coefficient. (Author 's abstract)

  9. Up-regulation of OLR1 expression by TBC1D3 through activation of TNFα/NF-κB pathway promotes the migration of human breast cancer cells.

    PubMed

    Wang, Bei; Zhao, Huzi; Zhao, Lei; Zhang, Yongchen; Wan, Qing; Shen, Yong; Bu, Xiaodong; Wan, Meiling; Shen, Chuanlu

    2017-11-01

    Metastatic spread of cancer cells is the most life-threatening aspect of breast cancer and involves multiple steps including cell migration. We recently found that the TBC1D3 oncogene promotes the migration of breast cancer cells, and its interaction with CaM enhances the effects of TBC1D3. However, little is known regarding the mechanism by which TBC1D3 induces the migration of cancer cells. Here, we demonstrated that TBC1D3 stimulated the expression of oxidized low density lipoprotein receptor 1 (OLR1), a stimulator of cell migration, in breast cancer cells at the transcriptional level. Depletion of OLR1 by siRNAs or down-regulation of OLR1 expression using pomalidomide, a TNFα inhibitor, significantly decreased TBC1D3-induced migration of these cells. Notably, TBC1D3 overexpression activated NF-κB, a major effector of TNFα signaling, while inhibition of TNFα signaling suppressed the effects of TBC1D3. Consistent with this, NF-κB inhibition using its specific inhibitor caffeic acid phenethyl ester decreased both TBC1D3-induced OLR1 expression and cell migration, suggesting a critical role for TNFα/NF-κB signaling in TBC1D3-induced migration of breast cancer cells. Mechanistically, TBC1D3 induced activation of this signaling pathway on multiple levels, including by increasing the release of TNFα, elevating the transcription of TNFR1, TRAF1, TRAF5 and TRAF6, and decreasing the degradation of TNFR1. In summary, these studies identify the TBC1D3 oncogene as a novel regulator of TNFα/NF-κB signaling that mediates this oncogene-induced migration of human breast cancer cells by up-regulating OLR1. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Migration without migraines

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

    Lines, L.; Burton, A.; Lu, H.X.

    Accurate velocity models are a necessity for reliable migration results. Velocity analysis generally involves the use of methods such as normal moveout analysis (NMO), seismic traveltime tomography, or iterative prestack migration. These techniques can be effective, and each has its own advantage or disadvantage. Conventional NMO methods are relatively inexpensive but basically require simplifying assumptions about geology. Tomography is a more general method but requires traveltime interpretation of prestack data. Iterative prestack depth migration is very general but is computationally expensive. In some cases, there is the opportunity to estimate vertical velocities by use of well information. The well informationmore » can be used to optimize poststack migrations, thereby eliminating some of the time and expense of iterative prestack migration. The optimized poststack migration procedure defined here computes the velocity model which minimizes the depth differences between seismic images and formation depths at the well by using a least squares inversion method. The optimization methods described in this paper will hopefully produce ``migrations without migraines.``« less

  11. Cathepsin D non-proteolytically induces proliferation and migration in human omental microvascular endothelial cells via activation of the ERK1/2 and PI3K/AKT pathways.

    PubMed

    Pranjol, Md Zahidul I; Gutowski, Nicholas J; Hannemann, Michael; Whatmore, Jacqueline L

    2018-01-01

    Epithelial ovarian cancer (EOC) frequently metastasises to the omentum, a process that requires pro-angiogenic activation of human omental microvascular endothelial cells (HOMECs) by tumour-secreted factors. We have previously shown that ovarian cancer cells secrete a range of factors that induce pro-angiogenic responses e.g. migration, in HOMECs including the lysosomal protease cathepsin D (CathD). However, the cellular mechanism by which CathD induces these cellular responses is not understood. The aim of this study was to further examine the pro-angiogenic effects of CathD in HOMECs i.e. proliferation and migration, to investigate whether these effects are dependent on CathD catalytic activity and to delineate the intracellular signalling kinases activated by CathD. We report, for the first time, that CathD significantly increases HOMEC proliferation and migration via a non-proteolytic mechanism resulting in activation of ERK1/2 and AKT. These data suggest that EOC cancer secreted CathD acts as an extracellular ligand and may play an important pro-angiogenic, and thus pro-metastatic, role by activating the omental microvasculature during EOC metastasis to the omentum. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. G protein-coupled receptor kinase 2 positively regulates epithelial cell migration

    PubMed Central

    Penela, Petronila; Ribas, Catalina; Aymerich, Ivette; Eijkelkamp, Niels; Barreiro, Olga; Heijnen, Cobi J; Kavelaars, Annemieke; Sánchez-Madrid, Francisco; Mayor, Federico

    2008-01-01

    Cell migration requires integration of signals arising from both the extracellular matrix and messengers acting through G protein-coupled receptors (GPCRs). We find that increased levels of G protein-coupled receptor kinase 2 (GRK2), a key player in GPCR regulation, potentiate migration of epithelial cells towards fibronectin, whereas such process is decreased in embryonic fibroblasts from hemizygous GRK2 mice or upon knockdown of GRK2 expression. Interestingly, the GRK2 effect on fibronectin-mediated cell migration involves the paracrine/autocrine activation of a sphingosine-1-phosphate (S1P) Gi-coupled GPCR. GRK2 positively modulates the activity of the Rac/PAK/MEK/ERK pathway in response to adhesion and S1P by a mechanism involving the phosphorylation-dependent, dynamic interaction of GRK2 with GIT1, a key scaffolding protein in cell migration processes. Furthermore, decreased GRK2 levels in hemizygous mice result in delayed wound healing rate in vivo, consistent with a physiological role of GRK2 as a regulator of coordinated integrin and GPCR-directed epithelial cell migration. PMID:18369319

  13. Disconnections kinks and competing modes in shear-coupled grain boundary migration

    NASA Astrophysics Data System (ADS)

    Combe, N.; Mompiou, F.; Legros, M.

    2016-01-01

    The response of small-grained metals to mechanical stress is investigated by a theoretical study of the elementary mechanisms occurring during the shear-coupled migration of grain boundaries (GB). Investigating a model Σ 17 (410 ) GB in a copper bicrystal, both <110 > and <100 > GB migration modes are studied focusing on both the structural and energetic characteristics. The minimum energy paths of these shear-coupled GB migrations are computed using the nudge elastic band method. For both modes, the GB migration occurs through the nucleation and motion of disconnections. However, the atomic mechanisms of both modes qualitatively differ: While the <110 > mode presents no metastable state, the <100 > mode shows multiple metastable states, some of them evidencing some kinks along the disconnection lines. Disconnection kinks nucleation and motion activation energies are evaluated. Besides, the activation energies of the <100 > mode are smaller than those of the <110 > one except for very high stresses. These results significantly improve our knowledge of the GB migration mechanisms and the conditions under which they occur.

  14. Protein Tyrosine Phosphatase-PEST and β8 Integrin Regulate Spatiotemporal Patterns of RhoGDI1 Activation in Migrating Cells

    PubMed Central

    Lee, Hye Shin; Cheerathodi, Mujeeburahiman; Chaki, Sankar P.; Reyes, Steve B.; Zheng, Yanhua; Lu, Zhimin; Paidassi, Helena; DerMardirossian, Celine; Lacy-Hulbert, Adam; Rivera, Gonzalo M.

    2015-01-01

    Directional cell motility is essential for normal development and physiology, although how motile cells spatiotemporally activate signaling events remains largely unknown. Here, we have characterized an adhesion and signaling unit comprised of protein tyrosine phosphatase (PTP)-PEST and the extracellular matrix (ECM) adhesion receptor β8 integrin that plays essential roles in directional cell motility. β8 integrin and PTP-PEST form protein complexes at the leading edge of migrating cells and balance patterns of Rac1 and Cdc42 signaling by controlling the subcellular localization and phosphorylation status of Rho GDP dissociation inhibitor 1 (RhoGDI1). Translocation of Src-phosphorylated RhoGDI1 to the cell's leading edge promotes local activation of Rac1 and Cdc42, whereas dephosphorylation of RhoGDI1 by integrin-bound PTP-PEST promotes RhoGDI1 release from the membrane and sequestration of inactive Rac1/Cdc42 in the cytoplasm. Collectively, these data reveal a finely tuned regulatory mechanism for controlling signaling events at the leading edge of directionally migrating cells. PMID:25666508

  15. 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

  16. Zooplankton diel vertical migration and contribution to deep active carbon flux in the NW Mediterranean

    NASA Astrophysics Data System (ADS)

    Isla, Alejandro; Scharek, Renate; Latasa, Mikel

    2015-03-01

    The diel vertical migration (DVM) of zooplankton contributes to the biological pump transporting material from surface to deep waters. We examined the DVM of the zooplankton community in different size fractions (53-200 μm, 200-500 μm, 500-1000 μm, 1000-2000 μm and > 2000 μm) during three cruises carried out in the open NW Mediterranean Sea. We assessed their metabolic rates from empirical published relationships and estimated the active fluxes of dissolved carbon to the mesopelagic zone driven by migrant zooplankton. Within the predominantly oligotrophic Mediterranean Sea, the NW region is one of the most productive ones, with a seasonal cycle characterized by a prominent spring bloom. The study area was visited at three different phases of the seasonal cycle: during the spring bloom, the post-bloom, and strongly stratified oligotrophic conditions. We found seasonal differences in DVM, less evident during the bloom. Changes in DVM intensity were related to the composition of the zooplanktonic assemblage, which also varied between cruises. Euphausiids appeared as the most active migrants in all seasons, and their life cycle conditioned the observed pattern. Immature stages, which are unable to perform large diel vertical movements, dominated during the bloom, in contrast to the higher relative importance of migrating adults in the other two sampling periods. The amount of dissolved carbon exported was determined by the migrant zooplankton biomass, being highest during the post-bloom (2.2 mmol C respired m- 2 d- 1, and up to 3.1 mmol C exported m- 2 d- 1 when DOC release estimations are added). The active transport by diel migrants represented a substantial contribution to total carbon export to deep waters, especially under stratified oligotrophic conditions, revealing the importance of zooplankton in the biological pump operating in the study area.

  17. Migration and risk: net migration in marginal ecosystems and hazardous areas

    NASA Astrophysics Data System (ADS)

    de Sherbinin, Alex; Levy, Marc; Adamo, Susana; MacManus, Kytt; Yetman, Greg; Mara, Valentina; Razafindrazay, Liana; Goodrich, Benjamin; Srebotnjak, Tanja; Aichele, Cody; Pistolesi, Linda

    2012-12-01

    The potential for altered ecosystems and extreme weather events in the context of climate change has raised questions concerning the role that migration plays in either increasing or reducing risks to society. Using modeled data on net migration over three decades from 1970 to 2000, we identify sensitive ecosystems and regions at high risk of climate hazards that have seen high levels of net in-migration and out-migration over the time period. This paper provides a literature review on migration related to ecosystems, briefly describes the methodology used to develop the estimates of net migration, then uses those data to describe the patterns of net migration for various ecosystems and high risk regions. The study finds that negative net migration generally occurs over large areas, reflecting its largely rural character, whereas areas of positive net migration are typically smaller, reflecting its largely urban character. The countries with largest population such as China and India tend to drive global results for all the ecosystems found in those countries. Results suggest that from 1970 to 2000, migrants in developing countries have tended to move out of marginal dryland and mountain ecosystems and out of drought-prone areas, and have moved towards coastal ecosystems and areas that are prone to floods and cyclones. For North America results are reversed for dryland and mountain ecosystems, which saw large net influxes of population in the period of record. Uncertainties and potential sources of error in these estimates are addressed.

  18. Restructuring of the labour market and the role of third world migrations in Europe.

    PubMed

    Pugliese, E

    1993-10-01

    "This paper is an analysis of the way in which the changes in the labour market and in the occupational structure in Europe affect the situation and the role of Third World migrants." Changes in European labor migration patterns since the 1960s are first analyzed. The author notes that "intra-European migrations were industrial migrations because manufacturing and building industries were the most important and growing economic activities....Present-day migrations are postindustrial migrations. Immigrants work mostly in service activities and not infrequently in the informal economy. In any case migrant workers are located in the secondary labour market. The picture is made more complex by the fact than many immigrants are alegal or illegal because of the restrictive immigration policies in European countries." excerpt

  19. Active migration is associated with specific and consistent changes to gut microbiota in Calidris shorebirds.

    PubMed

    Risely, Alice; Waite, David W; Ujvari, Beata; Hoye, Bethany J; Klaassen, Marcel

    2018-03-01

    Gut microbes are increasingly recognised for their role in regulating an animal's metabolism and immunity. However, identifying repeatable associations between host physiological processes and their gut microbiota has proved challenging, in part because microbial communities often respond stochastically to host physiological stress (e.g. fasting, forced exercise or infection). Migratory birds provide a valuable system in which to test host-microbe interactions under physiological extremes because these hosts are adapted to predictable metabolic and immunological challenges as they undergo seasonal migrations, including temporary gut atrophy during long-distance flights. These physiological challenges may either temporarily disrupt gut microbial ecosystems, or, alternatively, promote predictable host-microbe associations during migration. To determine the relationship between migration and gut microbiota, we compared gut microbiota composition between migrating and non-migrating ("resident") conspecific shorebirds sharing a flock. We performed this across two sandpiper species, Calidris ferruginea and Calidris ruficollis, in north-western Australia, and an additional C. ruficollis population 3,000 km away in southern Australia. We found that migrants consistently had higher abundances of the bacterial genus Corynebacterium (average 28% abundance) compared to conspecific residents (average <1% abundance), with this effect holding across both species and sites. However, other than this specific association, community structure and diversity was almost identical between migrants and residents, with migration status accounting for only 1% of gut community variation when excluding Corynebacterium. Our findings suggest a consistent relationship between Corynebacterium and Calidris shorebirds during migration, with further research required to identify causal mechanisms behind the association, and to elucidate functionality to the host. However, outside this specific

  20. Japanese Migration and the Americas: An Introduction to the Study of Migration.

    ERIC Educational Resources Information Center

    Mukai, Gary; Brunette, Rachel

    This curriculum module introduces students to the study of migration, including a brief overview of some categories of migration and reasons why people migrate. As a case study, the module uses the Japanese migration experience in the United States, Peru, Brazil, Canada, Mexico, Argentina, Bolivia, and Paraguay. The module introduces students to…

  1. Crucial role of vinexin for keratinocyte migration in vitro and epidermal wound healing in vivo

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

    Kioka, Noriyuki, E-mail: nkioka@kais.kyoto-u.ac.jp; Ito, Takuya; Yamashita, Hiroshi

    2010-06-10

    In the process of tissue injury and repair, epithelial cells rapidly migrate and form epithelial sheets. Vinexin is a cytoplasmic molecule of the integrin-containing cell adhesion complex localized at focal contacts in vitro. Here, we investigated the roles of vinexin in keratinocyte migration in vitro and wound healing in vivo. Vinexin knockdown using siRNA delayed migration of both HaCaT human keratinocytes and A431 epidermoid carcinoma cells in scratch assay but did not affect cell proliferation. Induction of cell migration by scratching the confluent monolayer culture of these cells activated both EGFR and ERK, and their inhibitors AG1478 and U0126 substantiallymore » suppressed scratch-induced keratinocyte migration. Vinexin knockdown in these cells inhibited the scratch-induced activation of EGFR, but not that of ERK, suggesting that vinexin promotes cell migration via activation of EGFR. We further generated vinexin (-/-) mice and isolated their keratinocytes. They similarly showed slow migration in scratch assay. Furthermore, vinexin (-/-) mice exhibited a delay in cutaneous wound healing in both the back skin and tail without affecting the proliferation of keratinocytes. Together, these results strongly suggest a crucial role of vinexin in keratinocyte migration in vitro and cutaneous wound healing in vivo.« less

  2. Leukotactin-1/CCL15 induces cell migration and differentiation of human eosinophilic leukemia EoL-1 cells through PKCdelta activation.

    PubMed

    Lee, Ji-Sook; Kim, In Sik

    2010-06-01

    Leukotactin-1 (Lkn-1)/CCL15 is a CC chemokine that binds to the CCR1 and CCR3. Lkn-1 functions as an essential factor in the migration of monocytes, lymphocytes, and neutrophils. Although eosinophils express both receptors, the role of Lkn-1 in immature eosinophils remains to be elucidated. In this present study, we investigated the contribution of the CCR1-binding chemokines to chemotactic activity and in the differentiation in the human eosinophilic leukemia cell line EoL-1. Lkn-1 induced the stronger migration of EoL-1 cells than other CCR1-binding chemokines such as RANTES/CCL5, MIP-1alpha/CCL3 and HCC-4/CCL16. Lkn-1-induced chemotaxis was inhibited by pertussis toxin, an inhibitor of G(i)/G(o) protein; U73122, an inhibitor of phospholipase C and rottlerin, an inhibitor of protein kinase C delta (PKCdelta). Lkn-1 increased PKCdelta activity, which was partially blocked by the pertussis toxin and U73122. Lkn-1 enhanced the butyric acid-induced differentiation via PKCdelta after binding to the increased CCR1 because Lkn-1 caused EoL-1 cells to change morphologically into mature eosinophil-like cells. Likewise, Lkn-1 increased the expression of both eosinophil peroxidase (EPO) and the major basic protein (MBP). PKCdelta activation due to Lkn-1 is involved in migration, as well as the butyric acid-induced differentiation. This finding contributes to an understanding of CC chemokines in eosinophil biology and to the development of novel therapies for the treatment of eosinophilic disorders. This study suggests the pivotal roles of Lkn-1 in the regulation of the movement and development of eosinophils.

  3. Shear-coupled grain-boundary migration dependence on normal strain/stress

    NASA Astrophysics Data System (ADS)

    Combe, N.; Mompiou, F.; Legros, M.

    2017-08-01

    In specific conditions, grain-boundary (GB) migration occurs in polycrystalline materials as an alternative vector of plasticity compared to the usual dislocation activity. The shear-coupled GB migration, the expected most efficient GB based mechanism, couples the GB motion to an applied shear stress. Stresses on GB in polycrystalline materials seldom have, however, a unique pure shear component. This work investigates the influence of a normal strain on the shear coupled migration of a Σ 13 (320 )[001 ] GB in a copper bicrystal using atomistic simulations. We show that the yield shear stress inducing the GB migration strongly depends on the applied normal stress. Beyond, the application of a normal stress on this GB qualitatively modifies the GB migration: while the Σ 13 (320 )[001 ] GB shear couples following the 〈110 〉 migration mode without normal stress, we report the observation of the 〈010 〉 mode under a sufficiently high tensile normal stress. Using the nudge elastic band method, we uncover the atomistic mechanism of this 〈010 〉 migration mode and energetically characterize it.

  4. Overexpression of HER2 signaling to WAVE2-Arp2/3 complex activates MMP-independent migration in breast cancer.

    PubMed

    Yokotsuka, Mayumi; Iwaya, Keiichi; Saito, Tsuyoshi; Pandiella, Atanasio; Tsuboi, Ryoji; Kohno, Norio; Matsubara, Osamu; Mukai, Kiyoshi

    2011-04-01

    The final signal for triggering the formation of lamellipodia that initiate directional migration of mammalian cells is binding of the Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein 2 (WAVE2) to the actin-related protein 2 and 3 (Arp2/3) complex. This WAVE2-Arp2/3 signal is suggested to be enhanced in some breast cancers, facilitating invasion, and/or metastasis. Here, we demonstrated one cause of the enhanced signal using four breast cancer cell lines (SKBR3, AU565, MCF7, and MDA-MB-231). The WAVE2-Arp2/3 signal was estimated semi-quantitatively by counting the number of lamellipodia expressing both WAVE2 and Arp2 using high-power confocal laser microscopy. Higher expression of the WAVE2-Arp2/3 signal was detected in SKBR3 and AU565, which have HER2 gene amplification, than in the other two cell lines that lack HER2 gene amplification. Trastuzumab suppressed both the formation of lamellipodia and migration in a Boyden chamber experiment in SKBR3 and AU565. When the HER2 gene was transfected into MCF7, the number of both lamellipodia and migrated cells was increased. This enhancement of migration did not occur in the presence of extracellular matrix, and zymographic analysis showed no clear difference between HER2 gene-transfected cells and MCF7 cells. Immunohistochemical analysis of 115 cases of breast cancer revealed that coexpression of WAVE2 and Arp2 was significantly correlated with HER2-overexpression (P < 0.0001). These data indicate that an abnormal signal resulting from HER2 gene amplification activates lamellipodia formation in breast cancer cells, which initiates their metalloproteinase-independent migration.

  5. [Internal migration changes from 1980 to 1990].

    PubMed

    Corona Vazquez, R

    1991-01-01

    From 1930 to the 1970s, internal migration in Mexico consisted mostly of permanent movement from rural areas to cities, and especially to the 3 metropolitan areas of Mexico City, Monterrey, and Guadalajara. The migrations highlighted the developmental disparities between different regions. Their main consequence was the transformation of Mexico from a predominantly rural to a predominantly urban country. The regions expelling population were primarily densely populated and relatively unproductive areas in the center and south. Migrant destinations were the more developed and urban states. By 1980-90, there were a number of changes in migratory patterns that, along with participation of a greater number of household members in marginal economic activities, represented alternative survival strategies adopted by large population sectors in the face of declining living standards, natural disasters such as the earthquakes of 1985, and increasing ecological and safety problems in the large cities. Changes in migratory behavior during the 1980s included appearance and growing importance of new destinations, and the combination of permanent and temporary migration and of internal and international migration in the same localities, households, or even individuals. Greater distances were covered by migrants in the 1980s, and the relationship between socioeconomic status and migration became more varied. Another change was the decreased importance of migration to the 3 metropolitan areas. Metropolitan Mexico City even became a net expeller of population. At the same time, many medium-sized cities such as Orizaba, Matamoros, Juarez, and Tiajuana have become attractive destinations for migrants from surrounding areas and from Mexico City. The case of Baja California illustrates the combined occurrence of different types of migrations. Baja California in past decades had a high rate in-migration, but its growth has slowed. A greater diversity of origins and destinations is

  6. Visualizing Human Migration Trhough Space and Time

    NASA Astrophysics Data System (ADS)

    Zambotti, G.; Guan, W.; Gest, J.

    2015-07-01

    Human migration has been an important activity in human societies since antiquity. Since 1890, approximately three percent of the world's population has lived outside of their country of origin. As globalization intensifies in the modern era, human migration persists even as governments seek to more stringently regulate flows. Understanding this phenomenon, its causes, processes and impacts often starts from measuring and visualizing its spatiotemporal patterns. This study builds a generic online platform for users to interactively visualize human migration through space and time. This entails quickly ingesting human migration data in plain text or tabular format; matching the records with pre-established geographic features such as administrative polygons; symbolizing the migration flow by circular arcs of varying color and weight based on the flow attributes; connecting the centroids of the origin and destination polygons; and allowing the user to select either an origin or a destination feature to display all flows in or out of that feature through time. The method was first developed using ArcGIS Server for world-wide cross-country migration, and later applied to visualizing domestic migration patterns within China between provinces, and between states in the United States, all through multiple years. The technical challenges of this study include simplifying the shapes of features to enhance user interaction, rendering performance and application scalability; enabling the temporal renderers to provide time-based rendering of features and the flow among them; and developing a responsive web design (RWD) application to provide an optimal viewing experience. The platform is available online for the public to use, and the methodology is easily adoptable to visualizing any flow, not only human migration but also the flow of goods, capital, disease, ideology, etc., between multiple origins and destinations across space and time.

  7. Effects of active and inactive phospholipase D2 on signal transduction, adhesion, migration, invasion, and metastasis in EL4 lymphoma cells.

    PubMed

    Knoepp, Stewart M; Chahal, Manpreet S; Xie, Yuhuan; Zhang, Zhihong; Brauner, Daniel J; Hallman, Mark A; Robinson, Stephanie A; Han, Shujie; Imai, Masaki; Tomlinson, Stephen; Meier, Kathryn E

    2008-09-01

    The phosphatidylcholine-using phospholipase D (PLD) isoform PLD2 is widely expressed in mammalian cells and is activated in response to a variety of promitogenic agonists. In this study, active and inactive hemagglutinin-tagged human PLD2 (HA-PLD2) constructs were stably expressed in an EL4 cell line lacking detectable endogenous PLD1 or PLD2. The overall goal of the study was to examine the roles of PLD2 in cellular signal transduction and cell phenotype. HA-PLD2 confers PLD activity that is activated by phorbol ester, ionomycin, and okadaic acid. Proliferation and Erk activation are unchanged in cells transfected with active PLD2; proliferation rate is decreased in cells expressing inactive PLD2. Basal tyrosine phosphorylation of focal adhesion kinase (FAK) is increased in cells expressing active PLD2, as is phosphorylation of Akt; inactive PLD2 has no effect. Expression of active PLD2 is associated with increased spreading and elongation of cells on tissue culture plastic, whereas inactive PLD2 inhibits cell spreading. Inactive PLD2 also inhibits cell adhesion, migration, and serum-induced invasion. Cells expressing active PLD2 form metastases in syngeneic mice, as do the parental cells; cells expressing inactive PLD2 form fewer metastases than parental cells. In summary, active PLD2 enhances FAK phosphorylation, Akt activation, and cell invasion in EL4 lymphoma cells, whereas inactive PLD2 exerts inhibitory effects on adhesion, migration, invasion, and tumor formation. Overall, expression of active PLD2 enhances processes favorable to lymphoma cell metastasis, whereas expression of inactive PLD2 inhibits metastasis.

  8. Macrophage migration inhibitory factor as an incriminating agent in vitiligo.

    PubMed

    Farag, Azza Gaber Antar; Hammam, Mostafa Ahmed; Habib, Mona SalahEldeen; Elnaidany, Nada Farag; Kamh, Mona Eaid

    2018-03-01

    Vitiligo is an autoimmune skin disorder in which the loss of melanocytes is mainly attributed to defective autoimmune mechanisms and, lately, there has been more emphasis on autoinflammatory mediators. Among these is the macrophage migration inhibitory factor, which is involved in many autoimmune skin diseases. However, little is known about the contribution of this factor to vitiligo vulgaris. To determine the hypothesized role of migration inhibitory factor in vitiligo via estimation of serum migration inhibitory factor levels and migration inhibitory factor mRNA concentrations in patients with vitiligo compared with healthy controls. We also aimed to assess whether there is a relationship between the values of serum migration inhibitory factor and/or migration inhibitory factor mRNA with disease duration, clinical type and severity in vitiligo patients. Evaluation of migration inhibitory factor serum level and migration inhibitory factor mRNA expression by ELISA and real-time PCR, respectively, were performed for 50 patients with different degrees of vitiligo severity and compared to 15 age- and gender-matched healthy volunteers as controls. There was a highly significant increase in serum migration inhibitory factor and migration inhibitory factor mRNA levels in vitiligo cases when compared to controls (p<0.001). There was a significant positive correlation between both serum migration inhibitory factor and migration inhibitory factor mRNA concentrations in vitiligo patients, and each of them with duration and severity of vitiligo. In addition, patients with generalized vitiligo have significantly elevated serum migration inhibitory factor and mRNA levels than control subjects. Small number of investigated subjects. Migration inhibitory factor may have an active role in the development of vitiligo, and it may also be a useful index of disease severity. Consequently, migration inhibitory factor may be a new treatment target for vitiligo patients.

  9. 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

  10. Activation of Toll-like receptor-9 promotes cellular migration via up-regulating MMP-2 expression in oral squamous cell carcinoma.

    PubMed

    Ruan, Min; Zhang, Zun; Li, Siyi; Yan, Min; Liu, Shengwen; Yang, Wenjun; Wang, Lizheng; Zhang, Chenping

    2014-01-01

    Activation of Toll like receptors (TLRs) signaling has been implicated in promoting malignant cell invasion and metastatic potential. Previously we demonstrated that increased TLR-9 expression predicted poor survival in oral cancer patients. The objective of this study is to further investigate the roles and potential molecular mechanisms of TLR-9 signaling in human oral cancer cell invasion. Cell migration, invasion and protein expression were detected by wound healing assay, Transwell chambers model and western blot. The secretion and activity levels of metalloproteinases-2/9 were quantified by ELISA and Gelatin zymography. EMSA and ChIP assays were employed to detect the activity of AP-1signal pathway. TLR-9 siRNA transfection was used to regulate the expression and activity of TLR-9 in oral cancer cell line HB cells. The results of both wound healing assay and in vitro Transwell assay revealed that activation of TLR-9 induced dose- and time- dependent migration and invasion of HB cells. An increased expression, secretion and activity of MMP-2 were observed upon the treatment of CpG-ODN. The TLR-9 signaling-mediated MMP-2 expression appeared to be a consequence of AP-1 activation, because that their DNA binding activity was enhanced by CpG-ODN treatment. All these influences were efficiently repressed by the knockdown of TLR-9 through siRNA or pretreatment of an AP-1 inhibitor. Activation of TLR-9 signaling could promote human oral cancer HB cells invasion with the induction of MMP-2 presentation by attenuating AP-1 binding activity, suggesting a novel anti-metastatic application for TLR-9 targeted therapy in oral cancer in the future.

  11. Reinventing US Internal Migration Studies in the Age of International Migration

    PubMed Central

    Ellis, Mark

    2014-01-01

    I argue that researchers have sidelined attention to issues raised by US internal migration as they shifted focus to the questions posed by the post-1960s rise in US immigration. In this paper, I offer some reasons about why immigration has garnered more attention and why there needs to be greater consideration of US internal migration and its significant and myriad social, economic, political, and cultural impacts. I offer three ideas for motivating more research into US internal geographic mobility that would foreground its empirical and conceptual connections to international migration. First, there should be more work on linked migration systems investigating the connections between internal and international flows. Second, the questions asked about immigrant social, cultural, and economic impacts and adaptations in host societies should also be asked about internal migrants. Third, and more generally, migration researchers should jettison the assumption that the national scale is the pre-eminent delimiter of migration types and processes. Some groups can move easily across borders; others are constrained in their moves within countries. These subnational scales and constraints will become more visible if migration research decentres the national from its theory and empirics. PMID:24839406

  12. Reinventing US Internal Migration Studies in the Age of International Migration.

    PubMed

    Ellis, Mark

    2012-03-01

    I argue that researchers have sidelined attention to issues raised by US internal migration as they shifted focus to the questions posed by the post-1960s rise in US immigration. In this paper, I offer some reasons about why immigration has garnered more attention and why there needs to be greater consideration of US internal migration and its significant and myriad social, economic, political, and cultural impacts. I offer three ideas for motivating more research into US internal geographic mobility that would foreground its empirical and conceptual connections to international migration. First, there should be more work on linked migration systems investigating the connections between internal and international flows. Second, the questions asked about immigrant social, cultural, and economic impacts and adaptations in host societies should also be asked about internal migrants. Third, and more generally, migration researchers should jettison the assumption that the national scale is the pre-eminent delimiter of migration types and processes. Some groups can move easily across borders; others are constrained in their moves within countries. These subnational scales and constraints will become more visible if migration research decentres the national from its theory and empirics.

  13. Recent (circa 1998 to 2011) channel-migration rates of selected streams in Indiana

    USGS Publications Warehouse

    Robinson, Bret A.

    2013-01-01

    An investigation was completed to document recent (circa 1998 to 2011) channel-migration rates at 970 meander bends along 38 of the largest streams in Indiana. Data collection was completed by using the Google Earth™ platform and, for each selected site, identifying two images with capture dates separated by multiple years. Within each image, the position of the meander-bend cutbank was measured relative to a fixed local landscape feature visible in both images, and an average channel-migration rate was calculated at the point of maximum cutbank displacement. From these data it was determined that 65 percent of the measured sites have recently been migrating at a rate less than 1 ft/yr, 75 percent of the sites have been migrating at a rate less than 10 ft/yr, and while some sites are migrating in excess of 20 ft/yr, these occurrences are rare. In addition, it is shown that recent channel-migration activity is not evenly distributed across Indiana. For the stream reaches studied, far northern and much of far southern Indiana are drained by streams that recently have been relatively stationary. At the same time, this study shows that most of the largest streams in west-central Indiana and many of the largest streams in east-central Indiana have shown significant channel-migration activity during the recent past. It is anticipated that these results will support several fluvial-erosion-hazard mitigation activities currently being undertaken in Indiana.

  14. Delphinidin inhibits BDNF-induced migration and invasion in SKOV3 ovarian cancer cells.

    PubMed

    Lim, Won-Chul; Kim, Hyunhee; Kim, Young-Joo; Park, Seung-Ho; Song, Ji-Hye; Lee, Ki Heon; Lee, In Ho; Lee, Yoo-Kyung; So, Kyeong A; Choi, Kyung-Chul; Ko, Hyeonseok

    2017-12-01

    Brain-derived neurotrophic factor (BDNF), the TrkB ligand, is associated with aggressive malignant behavior, including migration and invasion, in tumor cells and a poor prognosis in patients with various types of cancer. Delphinidin is a diphenylpropane-based polyphenolic ring structure-harboring compound, which exhibits a wide range of pharmacological activities, anti-tumor, anti-oxidant, anti-inflammatory, anti-angiogenic and anti-mutagenic activity. However, the possible role of delphinidin in the cancer migration and invasion is unclear. We investigated the suppressive effect of delphinidin on the cancer migration and invasion. Thus, we found that BDNF enhanced cancer migration and invasion in SKOV3 ovarian cancer cell. To exam the inhibitory role of delphinidin in SKOV3 ovarian cancer migration and invasion, we investigated the use of delphinidin as inhibitors of BDNF-induced motility and invasiveness in SKOV3 ovarian cancer cells in vitro. Here, we found that delphinidin prominently inhibited the BDNF-induced increase in cell migration and invasion of SKOV3 ovarian cancer cells. Furthermore, delphinidin remarkably inhibited BDNF-stimulated expression of MMP-2 and MMP-9. Also, delphinidin antagonized the phosphorylation of Akt and nuclear translocation of NF-κB permitted by the BDNF in SKOV3 ovarian cancer cells. Taken together, our findings provide new evidence that delphinidin suppressed the BDNF-induced ovarian cancer migration and invasion through decreasing of Akt activation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Involvement of PUMA in pericyte migration induced by methamphetamine.

    PubMed

    Zhang, Yanhong; Zhang, Yuan; Bai, Ying; Chao, Jie; Hu, Gang; Chen, Xufeng; Yao, Honghong

    2017-07-01

    Mounting evidence indicates that methamphetamine causes blood-brain barrier damage, with emphasis on endothelial cells. The role of pericytes in methamphetamine-induced BBB damage remains unknown. Our study demonstrated that methamphetamine increased the migration of pericytes from the endothelial basement membrane. However, the detailed mechanisms underlying this process remain poorly understood. Thus, we examined the molecular mechanisms involved in methamphetamine-induced pericyte migration. The results showed that exposure of C3H/10T1/2 cells and HBVPs to methamphetamine increased PUMA expression via activation of the sigma-1 receptor, MAPK and Akt/PI3K pathways. Moreover, methamphetamine treatment resulted in the increased migration of C3H/10T1/2 cells and HBVPs. Knockdown of PUMA in pericytes transduced with PUMA siRNA attenuated the methamphetamine-induced increase in cell migration through attenuation of integrin and tyrosine kinase mechanisms, implicating a role of PUMA in the migration of C3H/10T1/2 cells and HBVPs. This study has demonstrated that methamphetamine-mediated pericytes migration involves PUMA up-regulation. Thus, targeted studies of PUMA could provide insights to facilitate the development of a potential therapeutic approach for alleviation of methamphetamine-induced pericyte migration. Copyright © 2017. Published by Elsevier Inc.

  16. Plasma rich in growth factors promotes dermal fibroblast proliferation, migration and biosynthetic activity.

    PubMed

    Anitua, E; Pino, A; Orive, G

    2016-11-02

    The use of plasma rich in growth factors (PRGF) has gained importance in many medical fields due to its regenerative potential. The aim of this study is to evaluate the effects of PRGF on primary skin fibroblasts assessing cell proliferation, migration and secretion of growth factors. The age of the patients from who PRGF was prepared was also studied to determine whether it influenced the outcomes. Human dermal fibroblasts were isolated from three healthy volunteers. Using PRGF-Endoret technology, PRGF was prepared from two groups of different ages (18-35 years and 50+ years). The effects of increasing concentration of PRGF (5%, 10% and 20%) on cell proliferation and migration was evaluated. Biosynthetic behaviour of cells was also analysed measuring vascular endothelial growth factor (VEGF), transforming growth factor b1 (TGFb1) and pro-collagen type I secreted levels with or without PRGF treatment. Mean platelet enrichment reached 2.4X and 2X in 18-35 and 50+ groups respectively. A dose-dependent response was observed in proliferation assays achieving the highest levels with 20% PRGF. Migration was also promoted in cells but not in a dose-dependent manner. Cell proliferation and migration outcomes obtained with PRGF (from both groups) were significantly higher compared to non-stimulated groups (p<0.05), with no statistical significances were observed between the different age groups. Production of VEGF, TGFb and procollagen type I was significantly increased by cells treated with PRGF, however, with the exception of VEGF, no statistical significances were observed between the different age groups. Results from this study concluded that PRGF is safe and effective in stimulating skin regeneration by enhancing proliferation, migration and expression of pivotal bioactive molecules involved in wound healing and haemostasis.

  17. A non-mitotic role for Aurora kinase A as a direct activator of cell migration upon interaction with PLD, FAK and Src

    PubMed Central

    Mahankali, Madhu; Henkels, Karen M.; Speranza, Francis; Gomez-Cambronero, Julian

    2015-01-01

    ABSTRACT Timely activation of Aurora kinase A (AURA, also known as AURKA) is vital for centrosome formation and the progression of mitosis. Nonetheless, it is still unclear if and when other cellular functions are activated by AURA. We report here that Src phosphorylates and activates AURA at T288, and AURA also activates focal adhesion kinase (FAK, also known as PTK2), leading to initiation of cell movement. An additional and new way by which AURA is regulated, is by phospholipase D2 (PLD2), which causes AURA activation. In addition, AURA phosphorylates PLD, so both proteins engage in a positive reinforcement loop. AURA and PLD2 form a protein–protein complex and colocalize to cytoplasmic regions in cells. The reason why PLD activates AURA is because of the production of phosphatidic acid by the lipase, which binds directly to AURA, with the region E171–E211 projected to be a phosphatidic-acid-binding pocket. Furthermore, this direct interaction with phosphatidic acid enhances tubulin polymerization and cooperates synergistically with AURA, FAK and Src in yielding a fully effectual cellular migration. Thus, Src and FAK, and PLD and phosphatidic acid are new upstream regulators of AURA that mediate its role in the non-mitotic cellular function of cell migration. PMID:25501815

  18. Negative regulation of AMP-activated protein kinase (AMPK) activity by macrophage migration inhibitory factor (MIF) family members in non-small cell lung carcinomas.

    PubMed

    Brock, Stephanie E; Rendon, Beatriz E; Yaddanapudi, Kavitha; Mitchell, Robert A

    2012-11-02

    AMP-activated protein kinase (AMPK) is a nutrient- and metabolic stress-sensing enzyme activated by the tumor suppressor kinase, LKB1. Because macrophage migration inhibitory factor (MIF) and its functional homolog, d-dopachrome tautomerase (d-DT), have protumorigenic functions in non-small cell lung carcinomas (NSCLCs) but have AMPK-activating properties in nonmalignant cell types, we set out to investigate this apparent paradox. Our data now suggest that, in contrast to MIF and d-DTs AMPK-activating properties in nontransformed cells, MIF and d-DT act cooperatively to inhibit steady-state phosphorylation and activation of AMPK in LKB1 wild type and LKB1 mutant human NSCLC cell lines. Our data further indicate that MIF and d-DT, acting through their shared cell surface receptor, CD74, antagonize NSCLC AMPK activation by maintaining glucose uptake, ATP production, and redox balance, resulting in reduced Ca(2+)/calmodulin-dependent kinase kinase β-dependent AMPK activation. Combined, these studies indicate that MIF and d-DT cooperate to inhibit AMPK activation in an LKB1-independent manner.

  19. 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

  20. Sema4D, the ligand for Plexin B1, suppresses c-Met activation and migration and promotes melanocyte survival and growth

    PubMed Central

    Soong, Joanne; Chen, Yulin; Shustef, Elina; Scott, Glynis

    2011-01-01

    Semaphorins are secreted and membrane bound proteins involved in neural pathfinding, organogenesis, and tumor progression, through Plexin and neuropilins receptors. We recently reported that Plexin B1, the Semaphorin 4D receptor, is a tumor suppressor protein for melanoma, in part, through inhibition of the oncogenic c-Met tyrosine kinase receptor. In this report we show that Sema4D is a protective paracrine factor for normal human melanocyte survival in response to ultraviolet irradiation, that it stimulates proliferation, and regulates the activity of the c-Met receptor. c-Met receptor signaling stimulates melanocyte migration, in part through down-regulation of the cell adhesion molecule E-cadherin. Sema4D suppressed activation of c-Met in response to its ligand hepatocyte growth factor (HGF), and partially blocked the suppressive effects of HGF on E-cadherin expression in melanocytes and HGF-dependent migration. These data demonstrate a role for Plexin B1 in maintenance of melanocyte survival and proliferation in the skin, and suggest that Semaphorin 4D and Plexin B1 act cooperatively with HGF and c-Met to regulate c-Met dependent effects in human melanocytes. Because our data show that Plexin B1 is profoundly down-regulated by UVB in melanocytes, loss of Plexin B1 may accentuate HGF dependent effects on melanocytes, including melanocyte migration. PMID:22189792

  1. Sema4D, the ligand for Plexin B1, suppresses c-Met activation and migration and promotes melanocyte survival and growth.

    PubMed

    Soong, Joanne; Chen, Yulin; Shustef, Elina M; Scott, Glynis A

    2012-04-01

    Semaphorins are secreted and membrane-bound proteins involved in neural pathfinding, organogenesis, and tumor progression, through Plexin and neuropilin receptors. We recently reported that Plexin B1, the Semaphorin 4D (Sema4D) receptor, is a tumor-suppressor protein for melanoma, which functions, in part, through inhibition of the oncogenic c-Met tyrosine kinase receptor. In this report, we show that Sema4D is a protective paracrine factor for normal human melanocyte survival in response to UV irradiation, and that it stimulates proliferation and regulates the activity of the c-Met receptor. c-Met receptor signaling stimulates melanocyte migration, partly through downregulation of the cell adhesion molecule E-cadherin. Sema4D suppressed activation of c-Met in response to its ligand, hepatocyte growth factor (HGF), and partially blocked the suppressive effects of HGF on E-cadherin expression in melanocytes and HGF-dependent migration. These data demonstrate a role for Plexin B1 in maintenance of melanocyte survival and proliferation in the skin, and suggest that Sema4D and Plexin B1 act cooperatively with HGF and c-Met to regulate c-Met-dependent effects in human melanocytes. Because our data show that Plexin B1 is profoundly downregulated by UVB in melanocytes, loss of Plexin B1 may accentuate HGF-dependent effects on melanocytes, including melanocyte migration.

  2. The Exoplanet Migration Timescale from K2 Young Clusters

    NASA Astrophysics Data System (ADS)

    Rizzuto, Aaron

    commonly seen in the light curves of young, active stars (Rizzuto et al. in prep). We have identified 11 candidate planets in Praesepe, Hyades, Upper Sco, and the Pleiades using these methods, the first of which has now been published with follow-up (Mann et al. 2016abc; Gaidos et al. 2016). This sample of detected planet candidates gives a promising first indication of the timescale over which planet migration occurs, favoring dynamical multi-body processes. However, because rotational activity in young stars makes detection of exoplanet transits more difficult for the younger clusters (e.g, Upper Sco, Pleiades), to robustly prove that these frequencies are true representations of the short-period planet occurrence rate at different PMS ages will require robust determination of detection limits in these highly variable young-star lightcurves. We propose to address the question of planet migration with a uniform injection-recovery test of young cluster members, to robustly measure the detectability of planets of differing size and orbit. This will involve detrending the light curve data of instrumental and rotational systematics, injecting a synthetic transit signature from a grid of planetary and orbital parameters, reversing the detrending, and then executing our transit search pipeline (which is tuned for highly active young stars) and mapping the recovery rate as a function of planet parameters for every individual light curve. With this map of detectability as a function of planet properties for each light curve and a full program of detected exoplanet follow-up, we can then directly confirm any change in the occurrence rates of close-in (P<20 day) planets with cluster age and identify the most significant migration mechanism.

  3. Stimulation of Cortical Myosin Phosphorylation by p114RhoGEF Drives Cell Migration and Tumor Cell Invasion

    PubMed Central

    Zihni, Ceniz; Harris, Andrew R.; Bailly, Maryse; Charras, Guillaume T.; Balda, Maria S.; Matter, Karl

    2012-01-01

    Actinomyosin activity is an important driver of cell locomotion and has been shown to promote collective cell migration of epithelial sheets as well as single cell migration and tumor cell invasion. However, the molecular mechanisms underlying activation of cortical myosin to stimulate single cell movement, and the relationship between the mechanisms that drive single cell locomotion and those that mediate collective cell migration of epithelial sheets are incompletely understood. Here, we demonstrate that p114RhoGEF, an activator of RhoA that associates with non-muscle myosin IIA, regulates collective cell migration of epithelial sheets and tumor cell invasion. Depletion of p114RhoGEF resulted in specific spatial inhibition of myosin activation at cell-cell contacts in migrating epithelial sheets and the cortex of migrating single cells, but only affected double and not single phosphorylation of myosin light chain. In agreement, overall elasticity and contractility of the cells, processes that rely on persistent and more constant forces, were not affected, suggesting that p114RhoGEF mediates process-specific myosin activation. Locomotion was p114RhoGEF-dependent on Matrigel, which favors more roundish cells and amoeboid-like actinomyosin-driven movement, but not on fibronectin, which stimulates flatter cells and lamellipodia-driven, mesenchymal-like migration. Accordingly, depletion of p114RhoGEF led to reduced RhoA, but increased Rac activity. Invasion of 3D matrices was p114RhoGEF-dependent under conditions that do not require metalloproteinase activity, supporting a role of p114RhoGEF in myosin-dependent, amoeboid-like locomotion. Our data demonstrate that p114RhoGEF drives cortical myosin activation by stimulating myosin light chain double phosphorylation and, thereby, collective cell migration of epithelial sheets and amoeboid-like motility of tumor cells. PMID:23185572

  4. Xenon migration behaviour in titanium nitride

    NASA Astrophysics Data System (ADS)

    Gavarini, S.; Toulhoat, N.; Peaucelle, C.; Martin, P.; Mende, J.; Pipon, Y.; Jaffrezic, H.

    2007-05-01

    Titanium nitride is one of the inert matrixes proposed to surround the fuel in gas cooled fast reactor (GFR) systems. These reactors operate at high temperature and necessitate refractory materials presenting a high chemical stability and good mechanical properties. A total retention of the most volatile fission products, such as Xe, I or Cs, by the inert matrix is needed during the in pile process. The thermal migration of xenon in TiN was studied by implanting 800 keV Xe++ ions in sintered samples at an ion fluence of 5 × 1015 cm-2. Annealing was performed at temperatures ranging from 1673 to 1923 K for 1 and 3 h. Xenon concentration profiles were studied by Rutherford backscattering spectrometry (RBS) using 2.5 MeV α-particles. The migration behaviour of xenon corresponds to a gas migration model. It is dominated by a surface directed transport with a slight diffusion component. The mean activation energy corresponding to the diffusion component was found to be 2.2 ± 0.3 eV and corresponds to the Brownian motion of xenon bubbles. The directed Xe migration can be interpreted in term of bubble transport using Evans model. This last process is mostly responsible for xenon release from TiN.

  5. Counterintuitive migration patterns by Atlantic salmon Salmo salar smolts in a large lake.

    PubMed

    Honkanen, H M; Rodger, J R; Stephen, A; Adams, K; Freeman, J; Adams, C E

    2018-06-21

    What little is known about the seaward migration of Salmo salar smolt migration through standing waters indicates that it is both slow and results in high mortality rates, compared with riverine migration. This may be partly because smolts in lakes need to swim more actively and require more complex directional cues than they do in rivers. In this telemetry study of smolt migration through Loch Lomond, S. salar smolts made repeated movements in directions away from the outflowing river, which considerably increased migration time. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. Gender and Migration from Albania

    PubMed Central

    STECKLOV, GUY; CARLETTO, CALOGERO; AZZARRI, CARLO; DAVIS, BENJAMIN

    2010-01-01

    This article examines the dynamics and causes of the shift in the gender composition of migration, and more particularly, in women’s access to migration opportunities and decision-making. Our analysis focuses on Albania, a natural laboratory for studying international migration where out-migration was essentially nonexistent from the end of World War II to the end of the 1980s. Interest in the Albanian case is heightened because of the complex layers of inequality existing at the time when migration began: relatively low levels of inequality within the labor market and educational system—a product of the Communist era—while household relations remained heavily steeped in tradition and patriarchy. We use micro-level data from the Albania 2005 Living Standards Measurement Study, including migration histories for family members since migration began. Based on discrete-time hazard models, the analysis shows a dramatic increase in male migration and a gradual and uneven expansion of the female proportion of this international migration. Female migration, which is shown to be strongly associated with education, wealth, and social capital, appears responsive to economic incentives and constraints. Using information on the dependency of female migration to the household demographic structure as well as the sensitivity of female migration to household-level shocks, we show how household-level constraints and incentives affect male and female migration differently. Throughout this period, however, women’s migration behavior appears more directly aligned with household-level factors, and there is little evidence to suggest that increased female migration signals rising behavioral independence among Albanian women. PMID:21308565

  7. Gender and migration from Albania.

    PubMed

    Stecklov, Guy; Carletto, Calogero; Azzarri, Carlo; Davis, Benjamin

    2010-11-01

    This article examines the dynamics and causes of the shift in the gender composition of migration, and more particularly, in women's access to migration opportunities and decision-making. Our analysis focuses on Albania, a natural laboratory for studying international migration where out-migration was essentially nonexistent from the end of World War II to the end of the 1980s. Interest in the Albanian case is heightened because of the complex layers of inequality existing at the time when migration began: relatively low levels of inequality within the labor market and educational system-a product of the Communist era-while household relations remained heavily steeped in tradition and patriarchy. We use micro-level data from the Albania 2005 Living Standards Measurement Study, including migration histories for family members since migration began. Based on discrete-time hazard models, the analysis shows a dramatic increase in male migration and a gradual and uneven expansion of the female proportion of this international migration. Female migration, which is shown to be strongly associated with education, wealth, and social capital, appears responsive to economic incentives and constraints. Using information on the dependency of female migration to the household demographic structure as well as the sensitivity of female migration to household-level shocks, we show how household-level constraints and incentives affect male and female migration differently. Throughout this period, however, women's migration behavior appears more directly aligned with household-level factors, and there is little evidence to suggest that increased female migration signals rising behavioral independence among Albanian women.

  8. Migration in south Asia: an overview.

    PubMed

    Skeldon, R

    1983-01-01

    Past studies on migration patterns and flows in south Asia have been based on limited data. The present overview is based on a detailed study of census and survey data reaching back to the early 1950's. The study incorporates the thinking of several research scholars who have dealt with specialized areas of migration in individual countries, and in the region as a whole. The interrelationships between migration and development are considered in a final chapter, with special mention of future trends, associated with traditional practices and historical circumstances. Migration will be of great importance in the coming decades. The activities of "sons of soil" anti-migrant movements and anti-migrant legislation have had little, if any, effect on migration flows. As the population increases in villages and towns and jobs become scarce, migration is likely to become even more of a political issue. Less politically volatile is circulation between village and town or between villages, whereby the migrants can have access to resources in 2 or more places. This option may play a critical role in the continued survival of much of the population in the future. This has been perhaps the most important factor in explaining the relatively slow rate of urbanization in south Asia as it allowed the rural people to take advantage of the towns without causing a massive and permanent transfer of population. The numbers who practice this "bilocality" are therefore likely to increase and migrants will continue to make up more significant proportions of the urban populations than their contribution to urban growth would suggest owing to the importance of "turnover migration." However, this circulation is not a new phenomenon: India and the other countries of south Asia have been characterized by tremendous mobility of population through circulation for considerable time but both its volume, and the distances over which it occurs are likely to increase as these countries develop.

  9. R-Ras Regulates Migration through an Interaction with Filamin A in Melanoma Cells

    PubMed Central

    Gawecka, Joanna E.; Griffiths, Genevieve S.; Ek-Rylander, Barbro; Ramos, Joe W.; Matter, Michelle L.

    2010-01-01

    Background Changes in cell adhesion and migration in the tumor microenvironment are key in the initiation and progression of metastasis. R-Ras is one of several small GTPases that regulate cell adhesion and migration on the extracellular matrix, however the mechanism has not been completely elucidated. Using a yeast two-hybrid approach we sought to identify novel R-Ras binding proteins that might mediate its effects on integrins. Methods and Findings We identified Filamin A (FLNa) as a candidate interacting protein. FLNa is an actin-binding scaffold protein that also binds to integrin β1, β2 and β7 tails and is associated with diverse cell processes including cell migration. Indeed, M2 melanoma cells require FLNa for motility. We further show that R-Ras and FLNa interact in co-immunoprecipitations and pull-down assays. Deletion of FLNa repeat 3 (FLNaΔ3) abrogated this interaction. In M2 melanoma cells active R-Ras co-localized with FLNa but did not co-localize with FLNa lacking repeat 3. Thus, activated R-Ras binds repeat 3 of FLNa. The functional consequence of this interaction was that active R-Ras and FLNa coordinately increased cell migration. In contrast, co-expression of R-Ras and FLNaΔ3 had a significantly reduced effect on migration. While there was enhancement of integrin activation and fibronectin matrix assembly, cell adhesion was not altered. Finally, siRNA knockdown of endogenous R-Ras impaired FLNa-dependent fibronectin matrix assembly. Conclusions These data support a model in which R-Ras functionally associates with FLNa and thereby regulates integrin-dependent migration. Thus in melanoma cells R-Ras and FLNa may cooperatively promote metastasis by enhancing cell migration. PMID:20585650

  10. Migration and AIDS.

    PubMed

    1998-01-01

    This article presents the perspectives of UNAIDS and the International Organization for Migration (IOM) on migration and HIV/AIDS. It identifies research and action priorities and policy issues, and describes the current situation in major regions of the world. Migration is a process. Movement is enhanced by air transport, rising international trade, deregulation of trade practices, and opening of borders. Movements are restricted by laws and statutes. Denial to freely circulate and obtain asylum is associated with vulnerability to HIV infections. A UNAIDS policy paper in 1997 and IOM policy guidelines in 1988 affirm that refugees and asylum seekers should not be targeted for special measures due to HIV/AIDS. There is an urgent need to provide primary health services for migrants, voluntary counseling and testing, and more favorable conditions. Research is needed on the role of migration in the spread of HIV, the extent of migration, availability of health services, and options for HIV prevention. Research must be action-oriented and focused on vulnerability to HIV and risk taking behavior. There is substantial mobility in West and Central Africa, economic migration in South Africa, and nonvoluntary migration in Angola. Sex workers in southeast Asia contribute to the spread. The breakup of the USSR led to population shifts. Migrants in Central America and Mexico move north to the US where HIV prevalence is higher.

  11. 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.

  12. Outward Migration of Giant Planets in Orbital Resonance

    NASA Astrophysics Data System (ADS)

    D'Angelo, G.; Marzari, F.

    2013-05-01

    A pair of giant planets interacting with a gaseous disk may be subject to convergent orbital migration and become locked into a mean motion resonance. If the orbits are close enough, the tidal gaps produced by the planets in the disk may overlap. This represents a necessary condition to activate the outward migration of the pair. However, a number of other conditions must also be realized in order for this mechanism to operate. We have studied how disk properties, such as turbulence viscosity, temperature, surface density gradient, mass, and age, may affect the outcome of the outward migration process. We have also investigated the implications on this mechanism of the planets' gas accretion. If the pair resembles Jupiter and Saturn, the 3:2 orbital resonance may drive them outward until they reach stalling radii for migration, which are within ~10 AU of the star for disks representative of the early proto-solar nebula. However, planet post-formation conditions in the disk indicate that such planets become typically locked in the 1:2 orbital resonance, which does not lead to outward migration. Planet growth via gas accretion tends to alter the planets' mass-ratio and/or the disk accretion rate toward the star, reducing or inhibiting outward migration. Support from NASA Outer Planets Research Program and NASA Origins of Solar Systems Program is gratefully acknowledged.

  13. Plectin deficiency in liver cancer cells promotes cell migration and sensitivity to sorafenib treatment.

    PubMed

    Cheng, Chiung-Chi; Chao, Wei-Ting; Liao, Chen-Chun; Tseng, Yu-Hui; Lai, Yen-Chang Clark; Lai, Yih-Shyong; Hsu, Yung-Hsiang; Liu, Yi-Hsiang

    2018-01-02

    Plectin involved in activation of kinases in cell signaling pathway and plays important role in cell morphology and migration. Plectin knockdown promotes cell migration by activating focal adhesion kinase and Rac1-GTPase activity in liver cells. Sorafenib is a multi-targeting tyrosine kinase inhibitor that improves patient survival on hepatocellular carcinoma. The aim of this study is to investigate the correlation between the expression of plectin and cell migration as well as the sensitivity of hepatoma cell lines exposing to sorafenib. Hepatoma cell lines PLC/PRF/5 and HepG2 were used to examine the level of plectin expression and cell migration in comparison with Chang liver cell line. In addition, sensitivity of the 3 cell lines to sorafenib treatment was also measured. Expression of plectin was lower in PLC/PRF/5 and HepG2 hepatoma cells than that of Chang liver cells whereas HepG2 and PLC/PRF/5 cells exhibit higher rate of cell migration in trans-well migration assay. Immunohistofluorecent staining on E-cadherin revealed the highest rate of collective cell migration in HepG2 cells and the lowest was found in Chang liver cells. Likewise, HepG2 cell line was most sensitive to sorafenib treatment and Chang liver cells exhibited the least sensitivity. The drug sensitivity to sorafenib treatment showed inverse correlation with the expression of plectin. We suggest that plectin deficiency and increased E-cadherin in hepatoma cells were associated with higher rates of cell motility, collective cell migration as well as higher drug sensitivity to sorafenib treatment.

  14. Macrophage Migration Inhibitory Factor Enzymatic Activity, Lung Inflammation, and Cystic Fibrosis

    PubMed Central

    Adamali, Huzaifa; Armstrong, Michelle E.; McLaughlin, Anne Marie; Cooke, Gordon; McKone, Edward; Costello, Christine M.; Gallagher, Charles G.; Leng, Lin; Baugh, John A.; Fingerle-Rowson, Günter; Bucala, Richard J.; McLoughlin, Paul

    2012-01-01

    Rationale: Macrophage migration inhibitory factor (MIF) is a proinflammatory mediator with unique tautomerase enzymatic activity; the precise function has not been clearly defined. We previously demonstrated that individual patients with cystic fibrosis (CF) who are genetically predisposed to be high MIF producers develop accelerated end-organ injury. Objectives: To characterize the effects of the MIF-CATT polymorphism in patients with CF ex vivo. To investigate the role of MIF’s tautomerase activity in a murine model of Pseudomonas aeruginosa infection. Methods: MIF and tumor necrosis factor (TNF)-α protein levels were assessed in plasma or peripheral blood mononuclear cell (PBMC) supernatants by ELISA. A murine pulmonary model of chronic Pseudomonas infection was used in MIF wild-type mice (mif+/+) and in tautomerase-null, MIF gene knockin mice (mif P1G/P1G). Measurements and Main Results: MIF protein was measured in plasma and PBMCs from 5- and 6-CATT patients with CF; LPS-induced TNF-α production from PBMCs was also assessed. The effect of a specific inhibitor of MIF-tautomerase activity, ISO-1, was investigated in PBMCs. In the murine infection model, total weight loss, differential cell counts, bacterial load, and intraacinar airspace/tissue volume were measured. MIF and TNF-α levels were increased in 6-CATT compared with 5-CATT patients with CF. LPS-induced TNF-α production from PBMCs was attenuated in the presence of ISO-1. In a murine model of Pseudomonas infection, significantly less pulmonary inflammation and bacterial load was observed in mifP1G/P1G compared with mif+/+ mice. Conclusions: MIF-tautomerase activity may provide a novel therapeutic target in patients with chronic inflammatory diseases such as CF, particularly those patients who are genetically predisposed to produce increased levels of this cytokine. PMID:22592805

  15. Partial diel migration: A facultative migration underpinned by long-term inter-individual variation.

    PubMed

    Harrison, Philip M; Gutowsky, Lee F G; Martins, Eduardo G; Patterson, David A; Cooke, Steven J; Power, Michael

    2017-09-01

    The variations in migration that comprise partial diel migrations, putatively occur entirely as a consequence of behavioural flexibility. However, seasonal partial migrations are increasingly recognised to be mediated by a combination of reversible plasticity in response to environmental variation and individual variation due to genetic and environmental effects. Here, we test the hypothesis that while partial diel migration heterogeneity occurs primarily due to short-term within-individual flexibility in behaviour, long-term individual differences in migratory behaviour also underpin this migration variation. Specifically, we use a hierarchical behavioural reaction norm approach to partition within- and among-individual variation in depth use and diel plasticity in depth use, across short- and long-term time-scales, in a group of 47 burbot (Lota lota) tagged with depth-sensing acoustic telemetry transmitters. We found that within-individual variation at the among-dates-within-seasons and among-seasons scale, explained the dominant proportion of phenotypic variation. However, individuals also repeatedly differed in their expression of migration behaviour over the 2 year study duration. These results reveal that diel migration variation occurs primarily due to short-term within-individual flexibility in depth use and diel migration behaviour. However, repeatable individual differences also played a key role in mediating partial diel migration. These findings represent a significant advancement of our understanding of the mechanisms generating the important, yet poorly understood phenomena of partial diel migration. Moreover, given the pervasive occurrence of diel migrations across aquatic taxa, these findings indicate that individual differences have an important, yet previously unacknowledged role in structuring the temporal and vertical dynamics of aquatic ecosystems. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.

  16. Macrophage migration inhibitory factor promotes osteosarcoma growth and lung metastasis through activating the RAS/MAPK pathway.

    PubMed

    Wang, Chen; Zhou, Xing; Li, Wentao; Li, Mingyue; Tu, Tingyue; Ba, Ximing; Wu, Yinyu; Huang, Zhen; Fan, Gentao; Zhou, Guangxin; Wu, Sujia; Zhao, Jianning; Zhang, Junfeng; Chen, Jiangning

    2017-09-10

    Emerging evidence suggests that the tumour microenvironment plays a critical role in osteosarcoma (OS) development. Thus, cytokine immunotherapy could be a novel strategy for OS treatment. In this study, we explored the role of macrophage migration inhibitory factor (MIF), an important cytokine in OS progression, and investigated the anti-tumour effects of targeting MIF in OS. The results showed that MIF significantly increased in the tissue and serum samples of OS patients and was associated with tumour size, pulmonary metastasis and the survival rate of OS patients. We verified a positive correlation between MIF and p-ERK1/2 in OS patients. The in vitro results indicated that MIF could activate the RAS/MAPK pathway in a time- and dose-dependent manner, thereby promoting cell proliferation and migration. Furthermore, shRNA targeting MIF significantly inhibited tumour growth and lung metastasis in a mouse xenograft model and orthotopic model of OS. Additionally, inhibition of MIF significantly enhanced the sensitivity of OS cells to cisplatin and doxorubicin. Our findings suggest that immunotherapy targeting MIF to block the RAS/MAPK kinase cascade may represent a feasible and promising approach for OS treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. CXCL4-induced migration of activated T lymphocytes is mediated by the chemokine receptor CXCR3.

    PubMed

    Mueller, Anja; Meiser, Andrea; McDonagh, Ellen M; Fox, James M; Petit, Sarah J; Xanthou, Georgina; Williams, Timothy J; Pease, James E

    2008-04-01

    The chemokine CXCL4/platelet factor-4 is released by activated platelets in micromolar concentrations and is a chemoattractant for leukocytes via an unidentified receptor. Recently, a variant of the human chemokine receptor CXCR3 (CXCR3-B) was described, which transduced apoptotic but not chemotactic signals in microvascular endothelial cells following exposure to high concentrations of CXCL4. Here, we show that CXCL4 can induce intracellular calcium release and the migration of activated human T lymphocytes. CXCL4-induced chemotaxis of T lymphocytes was inhibited by a CXCR3 antagonist and pretreatment of cells with pertussis toxin (PTX), suggestive of CXCR3-mediated G-protein signaling via Galphai-sensitive subunits. Specific binding by T lymphocytes of the CXCR3 ligand CXCL10 was not effectively competed by CXCL4, suggesting that the two are allotopic ligands. We subsequently used expression systems to dissect the potential roles of each CXCR3 isoform in mediating CXCL4 function. Transient expression of the CXCR3-A and CXCR3-B isoforms in the murine pre-B cell L1.2 produced cells that migrated in response to CXCL4 in a manner sensitive to PTX and a CXCR3 antagonist. Binding of radiolabeled CXCL4 to L1.2 CXCR3 transfectants was of low affinity and appeared to be mediated chiefly by glycosaminoglycans (GAGs), as no specific CXCL4 binding was observed in GAG-deficient 745-Chinese hamster ovary cells stably expressing CXCR3. We suggest that following platelet activation, the CXCR3/CXCL4 axis may play a role in T lymphocyte recruitment and the subsequent amplification of inflammation observed in diseases such as atherosclerosis. In such a setting, antagonism of the CXCR3/CXCL4 axis may represent a useful, therapeutic intervention.

  18. Migration delays caused by anthropogenic barriers: modeling dams, temperature, and success on migrating salmon smolts

    USGS Publications Warehouse

    Marschall, Elizabeth A.; Mather, Martha E.; Parrish, Donna; Allison, Gary W.; McMenemy, James R.

    2011-01-01

    Disruption to migration is a growing problem for conservation and restoration of animal populations. Anthropogenic barriers along migration paths can delay or prolong migrations, which may result in a mismatch with migration-timing adaptations. To understand the interaction of dams (as barriers along a migration path), seasonally changing environmental conditions, timing of Atlantic salmon (Salmo salar) downstream migration, and ultimate migration success, we used 10 years of river temperature and discharge data as a template upon which we simulated downstream movement of salmon. Atlantic salmon is a cool-water species whose downstream migrating smolts must complete migration before river temperatures become too warm. We found that dams had a local effect on survival as well as a survival effect that was spatially and temporally removed from the encounter with the dam. While smolts are delayed by dams, temperatures downstream can reach lethal or near-lethal temperatures; as a result, the match between completion of migration and the window of appropriate migration conditions can be disrupted. The strength of this spatially and temporally removed effect is at least comparable to the local effects of dams in determining smolt migration success in the presence of dams. We also considered smolts from different tributaries, varying in distance from the river mouth, to assess the potential importance of locally adapted migration timing on the effect of barriers. Migration-initiation temperature affected modeled smolt survival differentially across tributaries, with the success of smolts from upstream tributaries being much more variable across years than that of smolts with a shorter distance to travel. As a whole, these results point to the importance of broadening our spatial and temporal view when managing migrating populations. We must consider not only how many individuals never make it across migration barriers, but also the spatially and temporally removed

  19. Chloride Channel 3 Channels in the Activation and Migration of Human Blood Eosinophils in Allergic Asthma.

    PubMed

    Gaurav, Rohit; Bewtra, Againdra K; Agrawal, Devendra K

    2015-08-01

    Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is responsible for respiratory burst in immune cells. Chloride channel 3 (CLC3) has been linked to the respiratory burst in eosinophils and neutrophils. The effect of cytokines and the involvement of CLC3 in the regulation of NADPH-dependent oxidative stress and on cytokine-mediated migration of eosinophils are not known. Human peripheral blood eosinophils were isolated from healthy individuals and from individuals with asthma by negative selection. Real-time PCR was used to detect the expression of NADPH oxidases in eosinophils. Intracellular reactive oxygen species (ROS) measurement was done with flow cytometry. Superoxide generation was measured with transforming growth factor (TGF)-β, eotaxin, and CLC3 blockers. CLC3 dependence of eosinophils in TGF-β- and eotaxin-induced migration was also examined. The messenger RNA (mRNA) transcripts of NADPH oxidase (NOX) 2, dual oxidase (DUOX) 1, and DUOX2 were detected in blood eosinophils, with very low expression of NOX1, NOX3, and NOX5 and no NOX4 mRNA. The level of NOX2 mRNA transcripts increased with disease severity in the eosinophils of subjects with asthma compared with healthy nonatopic volunteers. Change in granularity and size in eosinophils, but no change in intracellular ROS, was observed with phorbol myristate acetate (PMA). PMA, TGF-β, and eotaxin used the CLC3-dependent pathway to increase superoxide radicals. TGF-β and eotaxin induced CLC3-dependent chemotaxis of eosinophils. These findings support the requirement of CLC3 in the activation and migration of human blood eosinophils and may provide a potential novel therapeutic target to regulate eosinophil hyperactivity in allergic airway inflammation in asthma.

  20. Chloride Channel 3 Channels in the Activation and Migration of Human Blood Eosinophils in Allergic Asthma

    PubMed Central

    Gaurav, Rohit; Bewtra, Againdra K.

    2015-01-01

    Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is responsible for respiratory burst in immune cells. Chloride channel 3 (CLC3) has been linked to the respiratory burst in eosinophils and neutrophils. The effect of cytokines and the involvement of CLC3 in the regulation of NADPH-dependent oxidative stress and on cytokine-mediated migration of eosinophils are not known. Human peripheral blood eosinophils were isolated from healthy individuals and from individuals with asthma by negative selection. Real-time PCR was used to detect the expression of NADPH oxidases in eosinophils. Intracellular reactive oxygen species (ROS) measurement was done with flow cytometry. Superoxide generation was measured with transforming growth factor (TGF)-β, eotaxin, and CLC3 blockers. CLC3 dependence of eosinophils in TGF-β– and eotaxin-induced migration was also examined. The messenger RNA (mRNA) transcripts of NADPH oxidase (NOX) 2, dual oxidase (DUOX) 1, and DUOX2 were detected in blood eosinophils, with very low expression of NOX1, NOX3, and NOX5 and no NOX4 mRNA. The level of NOX2 mRNA transcripts increased with disease severity in the eosinophils of subjects with asthma compared with healthy nonatopic volunteers. Change in granularity and size in eosinophils, but no change in intracellular ROS, was observed with phorbol myristate acetate (PMA). PMA, TGF-β, and eotaxin used the CLC3-dependent pathway to increase superoxide radicals. TGF-β and eotaxin induced CLC3-dependent chemotaxis of eosinophils. These findings support the requirement of CLC3 in the activation and migration of human blood eosinophils and may provide a potential novel therapeutic target to regulate eosinophil hyperactivity in allergic airway inflammation in asthma. PMID:25514499

  1. Recovery Migration After Hurricanes Katrina and Rita: Spatial Concentration and Intensification in the Migration System.

    PubMed

    Curtis, Katherine J; Fussell, Elizabeth; DeWaard, Jack

    2015-08-01

    Changes in the human migration systems of the Gulf of Mexico coastline counties affected by Hurricanes Katrina and Rita provide an example of how climate change may affect coastal populations. Crude climate change models predict a mass migration of "climate refugees," but an emerging literature on environmental migration suggests that most migration will be short-distance and short-duration within existing migration systems, with implications for the population recovery of disaster-stricken places. In this research, we derive a series of hypotheses on recovery migration predicting how the migration system of hurricane-affected coastline counties in the Gulf of Mexico was likely to have changed between the pre-disaster and the recovery periods. We test these hypotheses using data from the Internal Revenue Service on annual county-level migration flows, comparing the recovery period migration system (2007-2009) with the pre-disaster period (1999-2004). By observing county-to-county ties and flows, we find that recovery migration was strong: the migration system of the disaster-affected coastline counties became more spatially concentrated, while flows within it intensified and became more urbanized. Our analysis demonstrates how migration systems are likely to be affected by the more intense and frequent storms anticipated by climate change scenarios, with implications for the population recovery of disaster-affected places.

  2. [Ethnic dimension to migration in the Senegal river valley].

    PubMed

    Traore, S

    1993-08-01

    Studies of the factors determining migratory patterns in the Senegal River Valley usually stress the importance of economic factors related to colonial domination. But when cultural factors and the social relations governing them are examined in a comparative study of ethnic groups, distinct population subgroups may be revealed to have differential migratory patterns. The Soninka and the Poular, two groups highly affected by migration, were chosen for an analysis of the impact of specific historical experiences on migratory behavior. A historical analysis of colonial archives and anthropological and historical monographs and the 1982-83 "Survey of Migration in the Valley of the Senegal River" provided data. The survey indicated that Soninka and Poular migratory patterns differed from each other, but that both differed from the migratory patterns of all other ethnic groups in the region. Soninka migration is international and oriented primarily toward Europe. It has recently become more intense than that of the poular. The determinants of migration in the two groups appear related more to the structure of households than to lack of educational and health facilities or even of food at the village level. Pastoral life and its associated beliefs and religious ideology appear to have been the principal determinants of precolonial movement among the Poular, while Soninka migration responded more to competition over control of manpower. Itinerant commercial activity was coupled with use of slave labor to ensure food production. But the suppression of slavery and crises of subsistence aggravated by colonial policy provoked ever more distant migration, which found a focus in the French demand for labor after World War II. Migration as an alternative does not appear to have been as significant for the Poular until more recently, when subsistence agriculture and the sale of animals were no longer sufficient to cover monetary needs. Male migration among the Soninka is a

  3. [Circular migration in Indonesia].

    PubMed

    Mantra, I B

    1979-12-01

    The author examines circular migration in Indonesia, with primary focus on the 1970s. It is found that circular, or repeated return migration, generally occurs over short distances and for short periods and is more frequent than lifetime migration. The relationships between improvements in the national transport system, access to labor force opportunities in both the formal and informal sectors of the economy, and circular migration are discussed.

  4. Role of a new Rho family member in cell migration and axon guidance in C. elegans.

    PubMed

    Zipkin, I D; Kindt, R M; Kenyon, C J

    1997-09-05

    Rho family GTPases are thought to regulate actin-dependent processes, but their functions in vivo are still poorly understood. We have investigated the function of a new, widely expressed Rho family member in C. elegans by analyzing mutations in the endogenous gene. Activated and null alleles all inhibit cell migration, demonstrating that this protein is required for cell migration in vivo. Only a small subset of the migrations inhibited by activating mutations are inhibited by null mutations, suggesting that considerable functional redundancy exists within this system. Our findings support this conclusion and show that mig-2 functions redundantly with another pathway to regulate nuclear migration. Surprisingly, activated alleles also cause misguided axon growth, suggesting that Rho family GTPases may couple guidance cues to process outgrowth.

  5. Indonesia's migration transition.

    PubMed

    Hugo, G

    1995-01-01

    This article describes population movements in Indonesia in the context of rapid and marked social and economic change. Foreign investment in Indonesia is increasing, and global mass media is available to many households. Agriculture is being commercialized, and structural shifts are occurring in the economy. Educational levels are increasing, and women's role and status are shifting. Population migration has increased over the decades, both short and long distance, permanent and temporary, legal and illegal, and migration to and between urban areas. This article focuses specifically on rural-to-urban migration and international migration. Population settlements are dense in the agriculturally rich inner areas of Java, Bali, and Madura. Although the rate of growth of the gross domestic product was 6.8% annually during 1969-94, the World Bank ranked Indonesia as a low-income economy in 1992 because of the large population size. Income per capita is US $670. Indonesia is becoming a large exporter of labor to the Middle East, particularly women. The predominance of women as overseas contract workers is changing women's role and status in the family and is controversial due to the cases of mistreatment. Malaysia's high economic growth rate of over 8% per year means an additional 1.3 million foreign workers and technicians are needed. During the 1980s urban growth increased at a very rapid rate. Urban growth tended to occur along corridors and major transportation routes around urban areas. It is posited that most of the urban growth is due to rural-to-urban migration. Data limitations prevent an exact determination of the extent of rural-to-urban migration. More women are estimated to be involved in movements to cities during the 1980s compared to the 1970s. Recruiters and middlemen have played an important role in rural-to-urban migration and international migration.

  6. The Calcium-Sensing Receptor and Integrins in Cellular Differentiation and Migration

    PubMed Central

    Tharmalingam, Sujeenthar; Hampson, David R.

    2016-01-01

    The calcium-sensing receptor (CaSR) is a widely expressed homodimeric G-protein coupled receptor structurally related to the metabotropic glutamate receptors and GPRC6A. In addition to its well characterized role in maintaining calcium homeostasis and regulating parathyroid hormone release, evidence has accumulated linking the CaSR with cellular differentiation and migration, brain development, stem cell engraftment, wound healing, and tumor growth and metastasis. Elevated expression of the CaSR in aggressive metastatic tumors has been suggested as a potential novel prognostic marker for predicting metastasis, especially to bone tissue where extracellular calcium concentrations may be sufficiently high to activate the receptor. Recent evidence supports a model whereby CaSR-mediated activation of integrins promotes cellular migration. Integrins are single transmembrane spanning heterodimeric adhesion receptors that mediate cell migration by binding to extracellular matrix proteins. The CaSR has been shown to form signaling complexes with the integrins to facilitate both the movement and differentiation of cells, such as neurons during normal brain development and tumor cells under pathological circumstances. Thus, CaSR/integrin complexes may function as a universal cell migration or homing complex. Manipulation of this complex may be of potential interest for treating metastatic cancers, and for developmental disorders pertaining to aberrant neuronal migration. PMID:27303307

  7. Bird migration through Middle Rio Grande riparian forests, 1994 to 1997

    Treesearch

    Michael D. Means; Deborah M. Finch

    1999-01-01

    Expanding human populations in the middle Rio Grande have increased demands on water, land, and other resources, potentially disrupting bird migration activities. From 1994 to 1997, a total of 26,350 birds of 157 species were banded and studied. Results include species composition, timing of migration, and habitat use. Recommendations for managers are included.

  8. Recovery Migration after Hurricanes Katrina and Rita: Spatial Concentration and Intensification in the Migration System

    PubMed Central

    Fussell, Elizabeth; DeWaard, Jack

    2015-01-01

    Changes in the human migration systems of Hurricane Katrina- and Rita-affected Gulf of Mexico coastline counties provide an example of how climate change may affect coastal populations. Crude climate change models predict a mass migration of “climate refugees,” but an emerging literature on environmental migration suggests most migration will be short-distance and short-duration within existing migration systems, with implications for the population recovery of disaster-struck places. In this research, we derive a series of hypotheses on recovery migration predicting how the migration system of hurricane-affected coastline counties in the Gulf of Mexico was likely to have changed between the pre-disaster and the recovery periods. We test these hypotheses using data from the Internal Revenue Service on annual county-level migration flows, comparing the recovery period migration system (2007–2009) to the pre-disaster period (1999–2004). By observing county-to-county ties and flows we find that recovery migration was strong, as the migration system of the disaster-affected coastline counties became more spatially concentrated while flows within it intensified and became more urbanized. Our analysis demonstrates how migration systems are likely to be affected by the more intense and frequent storms anticipated by climate change scenarios with implications for the population recovery of disaster-affected places. PMID:26084982

  9. Substrate stiffness regulates cadherin-dependent collective migration through myosin-II contractility

    PubMed Central

    Ng, Mei Rosa; Besser, Achim

    2012-01-01

    The mechanical microenvironment is known to influence single-cell migration; however, the extent to which mechanical cues affect collective migration of adherent cells is not well understood. We measured the effects of varying substrate compliance on individual cell migratory properties in an epithelial wound-healing assay. Increasing substrate stiffness increased collective cell migration speed, persistence, and directionality as well as the coordination of cell movements. Dynamic analysis revealed that wounding initiated a wave of motion coordination from the wound edge into the sheet. This was accompanied by a front-to-back gradient of myosin-II activation and establishment of cell polarity. The propagation was faster and farther reaching on stiff substrates, indicating that substrate stiffness affects the transmission of directional cues. Manipulation of myosin-II activity and cadherin–catenin complexes revealed that this transmission is mediated by coupling of contractile forces between neighboring cells. Thus, our findings suggest that the mechanical environment integrates in a feedback with cell contractility and cell–cell adhesion to regulate collective migration. PMID:23091067

  10. Migration delays caused by anthropogenic barriers: Modeling dams, temperature, and success of migrating salmon smolts

    USGS Publications Warehouse

    Marschall, E.A.; Mather, M. E.; Parrish, D.L.; Allison, G.W.; McMenemy, J.R.

    2011-01-01

    Disruption to migration is a growing problem for conservation and restoration of animal populations. Anthropogenic barriers along migration paths can delay or prolong migrations, which may result in a mismatch with migration-timing adaptations. To understand the interaction of dams (as barriers along a migration path), seasonally changing environmental conditions, timing of Atlantic salmon (Salmo salar) downstream migration, and ultimate migration success, we used 10 years of river temperature and discharge data as a template upon which we simulated downstream movement of salmon. Atlantic salmon is a cool-water species whose downstream migrating smolts must complete migration before river temperatures become too warm. We found that dams had a local effect on survival as well as a survival effect that was spatially and temporally removed from the encounter with the dam. While smolts are delayed by dams, temperatures downstream can reach lethal or near-lethal temperatures;as a result, the match between completion of migration and the window of appropriate migration conditions can be disrupted. The strength of this spatially and temporally removed effect is at least comparable to the local effects of dams in determining smolt migration success in the presence of dams. We also considered smolts from different tributaries, varying in distance from the river mouth, to assess the potential importance of locally adapted migration timing on the effect of barriers. Migration-initiation temperature affected modeled smolt survival differentially across tributaries, with the success of smolts from upstream tributaries being much more variable across years than that of smolts with a shorter distance to travel. As a whole, these results point to the importance of broadening our spatial and temporal view when managing migrating populations. We must consider not only how many individuals never make it across migration barriers, but also the spatially and temporally removed

  11. Human Th17 Migration in Three-Dimensional Collagen Involves p38 MAPK.

    PubMed

    Kadiri, Maleck; El Azreq, Mohammed-Amine; Berrazouane, Sofiane; Boisvert, Marc; Aoudjit, Fawzi

    2017-09-01

    T cell migration across extracellular matrix (ECM) is an important step of the adaptive immune response but is also involved in the development of inflammatory autoimmune diseases. Currently, the molecular mechanisms regulating the motility of effector T cells in ECM are not fully understood. Activation of p38 MAPK has been implicated in T cell activation and is critical to the development of immune and inflammatory responses. In this study, we examined the implication of p38 MAPK in regulating the migration of human Th17 cells through collagen. Using specific inhibitor and siRNA, we found that p38 is necessary for human Th17 migration in three-dimensional (3D) collagen and that 3D collagen increases p38 phosphorylation. We also provide evidence that the collagen receptor, discoidin domain receptor 1 (DDR1), which promotes Th17 migration in 3D collagen, is involved in p38 activation. Together, our findings suggest that targeting DDR1/p38 MAPK pathway could be beneficial for the treatment of Th17-mediated inflammatory diseases. J. Cell. Biochem. 118: 2819-2827, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. Confined Li ion migration in the silicon-graphene complex system: An ab initio investigation

    NASA Astrophysics Data System (ADS)

    Wang, Guoqing; Xu, Bo; Shi, Jing; Lei, Xueling; Ouyang, Chuying

    2018-04-01

    Silicon-Carbon complex systems play an important role in enhancing the performance of Si-based anode materials for Li ion batteries. In this work, the Li migration property of the Silicon-Graphene (Si-Gr) complex systems are investigated by using first-principles calculations. Especially, the effects of graphene coating on the migration of Li ions are discussed in detail. The distance between Si surface and graphene in the Si-Gr system significantly affects the lateral migration of Li ions. With the decrease of the distance from 4.715 to 3.844 Å, the energy barrier of Li ion migration also decreases from 0.115 to 0.067 eV, which are all lower than that of the case without graphene d(0.135 eV). However, smaller distance (3.586 Å) brings the high energy barrier (0.237 eV). Through AIMD calculations, it is found that the graphene coating in the Si-Gr complex system would result in the larger intercalation depths, more uniform distributions, and higher migration coefficients of Li ions. Further calculations of migration coefficients of Li ions at different temperature are used to obtained the activation energy for Li ions migration in the Si-Gr system, which is as low as 0.028 eV. This low activation energy shows that it is easy for Li ions migrating in the Si-Gr system. Our study provided the basically information to understand the migration mechanism of Li ions in Si-C system.

  13. MiR-375 inhibits the hepatocyte growth factor-elicited migration of mesenchymal stem cells by downregulating Akt signaling.

    PubMed

    He, Lihong; Wang, Xianyao; Kang, Naixin; Xu, Jianwei; Dai, Nan; Xu, Xiaojing; Zhang, Huanxiang

    2018-04-01

    The migration of mesenchymal stem cells (MSCs) is critical for their use in cell-based therapies. Accumulating evidence suggests that microRNAs are important regulators of MSC migration. Here, we report that the expression of miR-375 was downregulated in MSCs treated with hepatocyte growth factor (HGF), which strongly stimulates the migration of these cells. Overexpression of miR-375 decreased the transfilter migration and the migration velocity of MSCs triggered by HGF. In our efforts to determine the mechanism by which miR-375 affects MSC migration, we found that miR-375 significantly inhibited the activation of Akt by downregulating its phosphorylation at T308 and S473, but had no effect on the activity of mitogen-activated protein kinases. Further, we showed that 3'phosphoinositide-dependent protein kinase-1 (PDK1), an upstream kinase necessary for full activation of Akt, was negatively regulated by miR-375 at the protein level. Moreover, miR-375 suppressed the phosphorylation of focal adhesion kinase (FAK) and paxillin, two important regulators of focal adhesion (FA) assembly and turnover, and decreased the number of FAs at cell periphery. Taken together, our results demonstrate that miR-375 inhibits HGF-elicited migration of MSCs through downregulating the expression of PDK1 and suppressing the activation of Akt, as well as influencing the tyrosine phosphorylation of FAK and paxillin and FA periphery distribution.

  14. Environmental concerns and international migration.

    PubMed

    Hugo, G

    1996-01-01

    "This article focuses on international migration occurring as a result of environmental changes and processes. It briefly reviews attempts to conceptualize environment-related migration and then considers the extent to which environmental factors have been and may be significant in initiating migration. Following is an examination of migration as an independent variable in the migration-environment relationship. Finally, ethical and policy dimensions are addressed."

  15. Hedgehog Is a Positive Regulator of FGF Signalling during Embryonic Tracheal Cell Migration

    PubMed Central

    Butí, Elisenda; Mesquita, Duarte; Araújo, Sofia J.

    2014-01-01

    Cell migration is a widespread and complex process that is crucial for morphogenesis and for the underlying invasion and metastasis of human cancers. During migration, cells are steered toward target sites by guidance molecules that induce cell direction and movement through complex intracellular mechanisms. The spatio-temporal regulation of the expression of these guidance molecules is of extreme importance for both normal morphogenesis and human disease. One way to achieve this precise regulation is by combinatorial inputs of different transcription factors. Here we used Drosophila melanogaster mutants with migration defects in the ganglionic branches of the tracheal system to further clarify guidance regulation during cell migration. By studying the cellular consequences of overactivated Hh signalling, using ptc mutants, we found that Hh positively regulates Bnl/FGF levels during embryonic stages. Our results show that Hh modulates cell migration non-autonomously in the tissues surrounding the action of its activity. We further demonstrate that the Hh signalling pathway regulates bnl expression via Stripe (Sr), a zinc-finger transcription factor with homology to the Early Growth Response (EGR) family of vertebrate transcription factors. We propose that Hh modulates embryonic cell migration by participating in the spatio-temporal regulation of bnl expression in a permissive mode. By doing so, we provide a molecular link between the activation of Hh signalling and increased chemotactic responses during cell migration. PMID:24651658

  16. Hedgehog is a positive regulator of FGF signalling during embryonic tracheal cell migration.

    PubMed

    Butí, Elisenda; Mesquita, Duarte; Araújo, Sofia J

    2014-01-01

    Cell migration is a widespread and complex process that is crucial for morphogenesis and for the underlying invasion and metastasis of human cancers. During migration, cells are steered toward target sites by guidance molecules that induce cell direction and movement through complex intracellular mechanisms. The spatio-temporal regulation of the expression of these guidance molecules is of extreme importance for both normal morphogenesis and human disease. One way to achieve this precise regulation is by combinatorial inputs of different transcription factors. Here we used Drosophila melanogaster mutants with migration defects in the ganglionic branches of the tracheal system to further clarify guidance regulation during cell migration. By studying the cellular consequences of overactivated Hh signalling, using ptc mutants, we found that Hh positively regulates Bnl/FGF levels during embryonic stages. Our results show that Hh modulates cell migration non-autonomously in the tissues surrounding the action of its activity. We further demonstrate that the Hh signalling pathway regulates bnl expression via Stripe (Sr), a zinc-finger transcription factor with homology to the Early Growth Response (EGR) family of vertebrate transcription factors. We propose that Hh modulates embryonic cell migration by participating in the spatio-temporal regulation of bnl expression in a permissive mode. By doing so, we provide a molecular link between the activation of Hh signalling and increased chemotactic responses during cell migration.

  17. On marriage and migration.

    PubMed

    Stark, O

    1988-09-01

    Marriage, migration, and related phenomena such as marital stability, fertility, and investment in human capital may be better explained by studying marriage and migration jointly. This paper examines the role of migration in obtaining joint labor market and marriage market equilibrium. When broadly interpreted, marriage and migration share a number of common features. Both involve search and its resolution (pairing of mates in the former and matching of labor and firms in the latter). In both cases, success in finding a partner is sensitive to the availability of partners and to the distribution of their endowments and traits. Almost always, and along with separation and divorce, marriage mandates spatial relocation which may translate into migration. Both involve a movement that is associated with adjustment costs from 1 state into another. The decisions to enter marriage and undertake employment or the decisions to divorce and quit a job depend on exogenous parameters, some of which are determined by the marriage market and the labor market. Since both marriage and divorce take place in the context of broadly defined markets, they may and often are analyzed applying market concepts, theorems, and solutions. Yet the authors could not pinpoint 1 single, systematic attempt that checks through the interactions between marriage and migration, so this paper attempts to rectify this state of research. Essentially, this paper 1) discusses individual decision making pending possible migration prior to or following marriage, 2) examines whether it is easier for a married couple or a single person to migrate, and 3) considers whether marriage dissolution could cause migration when marriage is the only reason that has kept a spouse from moving. This integrated research agenda for both marriage and migration can delineate interesting new implications to examine.

  18. Effect of shear stress on the migration of hepatic stellate cells.

    PubMed

    Sera, Toshihiro; Sumii, Tateki; Fujita, Ryosuke; Kudo, Susumu

    2018-01-01

    When the liver is damaged, hepatic stellate cells (HSCs) can change into an activated, highly migratory state. The migration of HSCs may be affected by shear stress due not only to sinusoidal flow but also by the flow in the space of Disse because this space is filled with blood plasma. In this study, we evaluated the effects of shear stress on HSC migration in a scratch-wound assay with a parallel flow chamber. At regions upstream of the wound area, the migration was inhibited by 0.6 Pa and promoted by 2.0 Pa shear stress, compared to the static condition. The platelet-derived growth factor (PDGF)-BB receptor, PDGFR-β, was expressed in all conditions and the differences were not significant. PDGF increased HSC migration, except at 0.6 Pa shear stress, which was still inhibited. These results indicate that another molecular factor, such as PDGFR-α, may act to inhibit the migration under low shear stress. At regions downstream of the wound area, the migration was smaller under shear stress than under the static condition, although the expression of PDGFR-β was significantly higher. In particular, the migration direction was opposite to the wound area under high shear stress; therefore, migration might be influenced by the intercellular environment. Our results indicate that HSC migration was influenced by shear stress intensity and the intercellular environment.

  19. Bacterial migration along solid surfaces.

    PubMed Central

    Harkes, G; Dankert, J; Feijen, J

    1992-01-01

    An in vitro system was developed to study the migration of uropathogenic Escherichia coli strains. In this system an aqueous agar gel is placed against a solid surface, allowing the bacteria to migrate along the gel/solid surface interface. Bacterial strains as well as solid surfaces were characterized by means of water contact angle and zeta potential measurements. When glass was used as the solid surface, significantly different migration times for the strains investigated were observed. Relationships among the observed migration times of six strains, their contact angles, and their zeta potentials were found. Relatively hydrophobic strains exhibited migration times shorter than those of hydrophilic strains. For highly negatively charged strains shorter migration times were found than were found for less negatively charged strains. When the fastest-migrating strain with respect to glass was allowed to migrate along solid surfaces differing in hydrophobicity and charge, no differences in migration times were found. Our findings indicate that strategies to prevent catheter-associated bacteriuria should be based on inhibition of bacterial growth rather than on modifying the physicochemical character of the catheter surface. PMID:1622217

  20. 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

  1. Protein kinase D2 regulates migration and invasion of U87MG glioblastoma cells in vitro

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

    Bernhart, Eva; Damm, Sabine; Wintersperger, Andrea

    Glioblastoma multiforme (GBM) is the most common malignant brain tumor, which, despite combined modality treatment, reoccurs and is invariably fatal for affected patients. Recently, a member of the serine/threonine protein kinase D (PRKD) family, PRKD2, was shown to be a potent mediator of glioblastoma growth. Here we studied the role of PRKD2 in U87MG glioblastoma cell migration and invasion in response to sphingosine-1-phosphate (S1P), an activator of PRKD2 and a GBM mitogen. Time-lapse microscopy demonstrated that random cell migration was significantly diminished in response to PRKD2 silencing. The pharmacological PRKD family inhibitor CRT0066101 decreased chemotactic migration and invasion across uncoatedmore » or matrigel-coated Transwell inserts. Silencing of PRKD2 attenuated migration and invasion of U87MG cells even more effectively. In terms of downstream signaling, CRT0066101 prevented PRKD2 autophosphorylation and inhibited p44/42 MAPK and to a smaller extent p54/46 JNK and p38 MAPK activation. PRKD2 silencing impaired activation of p44/42 MAPK and p54/46 JNK, downregulated nuclear c-Jun protein levels and decreased c-Jun{sup S73} phosphorylation without affecting the NFκB pathway. Finally, qPCR array analyses revealed that silencing of PRKD2 downregulates mRNA levels of integrin alpha-2 and -4 (ITGA2 and -4), plasminogen activator urokinase (PLAU), plasminogen activator urokinase receptor (PLAUR), and matrix metallopeptidase 1 (MMP1). Findings of the present study identify PRKD2 as a potential target to interfere with glioblastoma cell migration and invasion, two major determinants contributing to recurrence of glioblastoma after multimodality treatment. Highlights: • Sphingosine-1-phosphate induces glioma cell migration and invasion. • Part of the effects is mediated by protein kinase D2 (PRKD2) activation. • Inactivation of PRKD2 attenuates glioblastoma cell migration and invasion. • Both, RNAi and pharmacological inhibition of PRKD2

  2. Soluble guanylate cyclase generation of cGMP regulates migration of MGE neurons.

    PubMed

    Mandal, Shyamali; Stanco, Amelia; Buys, Emmanuel S; Enikolopov, Grigori; Rubenstein, John L R

    2013-10-23

    Here we have provided evidence that nitric oxide-cyclic GMP (NO-cGMP) signaling regulates neurite length and migration of immature neurons derived from the medial ganglionic eminence (MGE). Dlx1/2(-/-) and Lhx6(-/-) mouse mutants, which exhibit MGE interneuron migration defects, have reduced expression of the gene encoding the α subunit of a soluble guanylate cyclase (Gucy1A3). Furthermore, Dlx1/2(-/-) mouse mutants have reduced expression of NO synthase 1 (NOS1). Gucy1A3(-/-) mice have a transient reduction in cortical interneuron number. Pharmacological inhibition of soluble guanylate cyclase and NOS activity rapidly induces neurite retraction of MGE cells in vitro and in slice culture and robustly inhibits cell migration from the MGE and caudal ganglionic eminence. We provide evidence that these cellular phenotypes are mediated by activation of the Rho signaling pathway and inhibition of myosin light chain phosphatase activity.

  3. Nurse migration: the effects on nursing education.

    PubMed

    Hancock, P K

    2008-09-01

    This paper is an opinion piece based on experience and supported where possible with literature, which addresses an issue of both national and international interest. It focuses on one aspect of the multifaceted social phenomenon of nurse migration, i.e. nurse education. Much has been written about the direct effects of nurse migration on the nurse migrant, the delivery of health care in the countries that supply the nurses, and the countries that receive them. However, there is little information regarding the direct effects of migration on nurse education within the literature. The aim of this paper is to raise awareness of the positive and negative effects of nurse migration on nurse education both in the countries that supply nurses and those which receive them. Both scholarly and 'grey' literature is used to support the discussion on the 'real' challenges faced by nurse educators and clinical nurses in those countries that supply or receive nurses. In addition, practical recommendations for nurse educators are presented. Furthermore, the nursing profession is challenged to become politically active, to become involved and to take responsibility for the decisions made about nurse education in order to protect the integrity of nurse education and patient safety. The quality of nurse education in many countries has been undermined as a result of rapid, mass migration. There is an urgent need to take practical steps to maintain the integrity of nurse education and the nurse's preparation for practice in order to protect patients' safety.

  4. Migration of the population.

    PubMed

    Krasinets, E

    1998-03-01

    Two factors influence foreign migration balance of the Russian Federation. The first factor involves the migration process between Russia and former union republics. The influx of population to the Russian Federation from other republics of the former Soviet Union is considered as one of the largest in the world. The average annual migratory growth of Russia during the years 1991-94 as a result of this migration exchange has tripled as compared with 1986-90, with a total of 2.7 million Russians who migrated into Russia. However, from 1996 up to the present time, the number of persons arriving in Russia declined dramatically. Meanwhile, the second factor that determines the country's migration balance is emigration to the far abroad. The most significant trend in determining the development of internal migration in Russia is the outflow of population from northern and eastern regions. The directions of internal and external migratory flows have a large influence on the migration balance in Russia's rural areas. The reduction of migratory flows in rural areas is the direct result of processes in the economic sphere. It confirms the reconstruction of rural-urban migratory exchange.

  5. Curcumin is a potent modulator of microglial gene expression and migration

    PubMed Central

    2011-01-01

    Background Microglial cells are important effectors of the neuronal innate immune system with a major role in chronic neurodegenerative diseases. Curcumin, a major component of tumeric, alleviates pro-inflammatory activities of these cells by inhibiting nuclear factor kappa B (NFkB) signaling. To study the immuno-modulatory effects of curcumin on a transcriptomic level, DNA-microarray analyses were performed with resting and LPS-challenged microglial cells after short-term treatment with curcumin. Methods Resting and LPS-activated BV-2 cells were stimulated with curcumin and genome-wide mRNA expression patterns were determined using DNA-microarrays. Selected qRT-PCR analyses were performed to confirm newly identified curcumin-regulated genes. The migration potential of microglial cells was determined with wound healing assays and transwell migration assays. Microglial neurotoxicity was estimated by morphological analyses and quantification of caspase 3/7 levels in 661W photoreceptors cultured in the presence of microglia-conditioned medium. Results Curcumin treatment markedly changed the microglial transcriptome with 49 differentially expressed transcripts in a combined analysis of resting and activated microglial cells. Curcumin effectively triggered anti-inflammatory signals as shown by induced expression of Interleukin 4 and Peroxisome proliferator activated receptor α. Several novel curcumin-induced genes including Netrin G1, Delta-like 1, Platelet endothelial cell adhesion molecule 1, and Plasma cell endoplasmic reticulum protein 1, have been previously associated with adhesion and cell migration. Consequently, curcumin treatment significantly inhibited basal and activation-induced migration of BV-2 microglia. Curcumin also potently blocked gene expression related to pro-inflammatory activation of resting cells including Toll-like receptor 2 and Prostaglandin-endoperoxide synthase 2. Moreover, transcription of NO synthase 2 and Signal transducer and activator

  6. SiMA: A simplified migration assay for analyzing neutrophil migration.

    PubMed

    Weckmann, Markus; Becker, Tim; Nissen, Gyde; Pech, Martin; Kopp, Matthias V

    2017-07-01

    In lung inflammation, neutrophils are the first leukocytes migrating to an inflammatory site, eliminating pathogens by multiple mechanisms. The term "migration" describes several stages of neutrophil movement to reach the site of inflammation, of which the passage of the interstitium and basal membrane of the airway are necessary to reach the site of bronchial inflammation. Currently, several methods exist (e.g., Boyden Chamber, under-agarose assay, or microfluidic systems) to assess neutrophil mobility. However, these methods do not allow for parameterization on single cell level, that is, the individual neutrophil pathway analysis is still considered challenging. This study sought to develop a simplified yet flexible method to monitor and quantify neutrophil chemotaxis by utilizing commercially available tissue culture hardware, simple video microscopic equipment and highly standardized tracking. A chemotaxis 3D µ-slide (IBIDI) was used with different chemoattractants [interleukin-8 (IL-8), fMLP, and Leukotriene B4 (LTB 4 )] to attract neutrophils in different matrices like Fibronectin (FN) or human placental matrix. Migration was recorded for 60 min using phase contrast microscopy with an EVOS ® FL Cell Imaging System. The images were normalized and texture based image segmentation was used to generate neutrophil trajectories. Based on these spatio-temporal information a comprehensive parameter set is extracted from each time series describing the neutrophils motility, including velocity and directness and neutrophil chemotaxis. To characterize the latter one, a sector analysis was employed enabling the quantification of the neutrophils response to the chemoattractant. Using this hard- and software framework we were able to identify typical migration profiles of the chemoattractants IL-8, fMLP, and LTB 4 , the effect of the matrices FN versus HEM as well as the response to different medications (Prednisolone). Additionally, a comparison of four asthmatic and

  7. Sirtuin 1 Mediates the Actions of Peroxisome Proliferator-Activated Receptor δ on the Oxidized Low-Density Lipoprotein-Triggered Migration and Proliferation of Vascular Smooth Muscle Cells.

    PubMed

    Hwang, Jung Seok; Ham, Sun Ah; Yoo, Taesik; Lee, Won Jin; Paek, Kyung Shin; Lee, Chi-Ho; Seo, Han Geuk

    2016-11-01

    Peroxisome proliferator-activated receptor δ (PPARδ) has been implicated in vascular pathophysiology. However, its functions in atherogenic changes of the vascular wall have not been fully elucidated. PPARδ activated by GW501516 (2-[2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid) significantly inhibited the migration and proliferation of vascular smooth muscle cells (VSMCs) triggered by oxidized low-density lipoprotein (oxLDL). These GW501516-mediated effects were significantly reversed by PPARδ-targeting small-interfering RNA (siRNA), indicating that PPARδ is involved in the action of GW501516. The antiproliferative effect of GW501516 was directly linked to cell cycle arrest at the G 0 /G 1 to S phase transition, which was followed by the down-regulation of cyclin-dependent kinase 4 along with increased levels of p21 and p53. In VSMCs treated with GW501516, the expression of sirtuin 1 (SIRT1) mRNA and protein was time-dependently increased. This GW501516-mediated up-regulation of SIRT1 expression was also demonstrated even in the presence of oxLDL. In addition, GW501516-dependent inhibition of oxLDL-triggered migration and proliferation of VSMCs was almost completely abolished in the presence of SIRT1-targeting siRNA. These effects of GW501516 on oxLDL-triggered phenotypic changes of VSMCs were also demonstrated via activation or inhibition of SIRT1 activity by resveratrol or sirtinol, respectively. Finally, gain or loss of SIRT1 function imitated the action of PPARδ on oxLDL-triggered migration and proliferation of VSMCs. Taken together, these observations indicate that PPARδ-dependent up-regulation of SIRT1 contributes to the antiatherogenic activities of PPARδ by suppressing the migration and proliferation of VSMCs linked to vascular diseases such as restenosis and atherosclerosis. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  8. Lipid rafts sense and direct electric field-induced migration.

    PubMed

    Lin, Bo-Jian; Tsao, Shun-Hao; Chen, Alex; Hu, Shu-Kai; Chao, Ling; Chao, Pen-Hsiu Grace

    2017-08-08

    Endogenous electric fields (EFs) are involved in developmental regulation and wound healing. Although the phenomenon is known for more than a century, it is not clear how cells perceive the external EF. Membrane proteins, responding to electrophoretic and electroosmotic forces, have long been proposed as the sensing molecules. However, specific charge modification of surface proteins did not change cell migration motility nor directionality in EFs. Moreover, symmetric alternating current (AC) EF directs cell migration in a frequency-dependent manner. Due to their charge and ability to coalesce, glycolipids are therefore the likely primary EF sensor driving polarization of membrane proteins and intracellular signaling. We demonstrate that detergent-resistant membrane nanodomains, also known as lipid rafts, are the primary response element in EF sensing. The clustering and activation of caveolin and signaling proteins further stabilize raft structure and feed-forward downstream signaling events, such as rho and PI3K activation. Theoretical modeling supports the experimental results and predicts AC frequency-dependent cell and raft migration. Our results establish a fundamental mechanism for cell electrosensing and provide a role in lipid raft mechanotransduction.

  9. SDN-1/Syndecan Acts in Parallel to the Transmembrane Molecule MIG-13 to Promote Anterior Neuroblast Migration.

    PubMed

    Sundararajan, Lakshmi; Norris, Megan L; Lundquist, Erik A

    2015-05-28

    The Q neuroblasts in Caenorhabditis elegans display left-right asymmetry in their migration, with QR and descendants on the right migrating anteriorly, and QL and descendants on the left migrating posteriorly. Initial QR and QL migration is controlled by the transmembrane receptors UNC-40/DCC, PTP-3/LAR, and the Fat-like cadherin CDH-4. After initial migration, QL responds to an EGL-20/Wnt signal that drives continued posterior migration by activating MAB-5/Hox activity in QL but not QR. QR expresses the transmembrane protein MIG-13, which is repressed by MAB-5 in QL and which drives anterior migration of QR descendants. A screen for new Q descendant AQR and PQR migration mutations identified mig-13 as well as hse-5, the gene encoding the glucuronyl C5-epimerase enzyme, which catalyzes epimerization of glucuronic acid to iduronic acid in the heparan sulfate side chains of heparan sulfate proteoglycans (HSPGs). Of five C. elegans HSPGs, we found that only SDN-1/Syndecan affected Q migrations. sdn-1 mutants showed QR descendant AQR anterior migration defects, and weaker QL descendant PQR migration defects. hse-5 affected initial Q migration, whereas sdn-1 did not. sdn-1 and hse-5 acted redundantly in AQR and PQR migration, but not initial Q migration, suggesting the involvement of other HSPGs in Q migration. Cell-specific expression studies indicated that SDN-1 can act in QR to promote anterior migration. Genetic interactions between sdn-1, mig-13, and mab-5 suggest that MIG-13 and SDN-1 act in parallel to promote anterior AQR migration and that SDN-1 also controls posterior migration. Together, our results indicate previously unappreciated complexity in the role of multiple signaling pathways and inherent left-right asymmetry in the control of Q neuroblast descendant migration. Copyright © 2015 Sundararajan et al.

  10. SDN-1/Syndecan Acts in Parallel to the Transmembrane Molecule MIG-13 to Promote Anterior Neuroblast Migration

    PubMed Central

    Sundararajan, Lakshmi; Norris, Megan L.; Lundquist, Erik A.

    2015-01-01

    The Q neuroblasts in Caenorhabditis elegans display left-right asymmetry in their migration, with QR and descendants on the right migrating anteriorly, and QL and descendants on the left migrating posteriorly. Initial QR and QL migration is controlled by the transmembrane receptors UNC-40/DCC, PTP-3/LAR, and the Fat-like cadherin CDH-4. After initial migration, QL responds to an EGL-20/Wnt signal that drives continued posterior migration by activating MAB-5/Hox activity in QL but not QR. QR expresses the transmembrane protein MIG-13, which is repressed by MAB-5 in QL and which drives anterior migration of QR descendants. A screen for new Q descendant AQR and PQR migration mutations identified mig-13 as well as hse-5, the gene encoding the glucuronyl C5-epimerase enzyme, which catalyzes epimerization of glucuronic acid to iduronic acid in the heparan sulfate side chains of heparan sulfate proteoglycans (HSPGs). Of five C. elegans HSPGs, we found that only SDN-1/Syndecan affected Q migrations. sdn-1 mutants showed QR descendant AQR anterior migration defects, and weaker QL descendant PQR migration defects. hse-5 affected initial Q migration, whereas sdn-1 did not. sdn-1 and hse-5 acted redundantly in AQR and PQR migration, but not initial Q migration, suggesting the involvement of other HSPGs in Q migration. Cell-specific expression studies indicated that SDN-1 can act in QR to promote anterior migration. Genetic interactions between sdn-1, mig-13, and mab-5 suggest that MIG-13 and SDN-1 act in parallel to promote anterior AQR migration and that SDN-1 also controls posterior migration. Together, our results indicate previously unappreciated complexity in the role of multiple signaling pathways and inherent left-right asymmetry in the control of Q neuroblast descendant migration. PMID:26022293

  11. Skin-Resident T Cells Drive Dermal Dendritic Cell Migration in Response to Tissue Self-Antigen.

    PubMed

    Ali, Niwa; Zirak, Bahar; Truong, Hong-An; Maurano, Megan M; Gratz, Iris K; Abbas, Abul K; Rosenblum, Michael D

    2018-05-01

    Migratory dendritic cell (DC) subsets deliver tissue Ags to draining lymph nodes (DLNs) to either initiate or inhibit T cell-mediated immune responses. The signals mediating DC migration in response to tissue self-antigen are largely unknown. Using a mouse model of inducible skin-specific self-antigen expression, we demonstrate that CD103 + dermal DCs (DDCs) rapidly migrate from skin to skin DLN (SDLNs) within the first 48 h after Ag expression. This window of time was characterized by the preferential activation of tissue-resident Ag-specific effector T cells (Teffs), with no concurrent activation of Ag-specific Teffs in SDLNs. Using genetic deletion and adoptive transfer approaches, we show that activation of skin-resident Teffs is required to drive CD103 + DDC migration in response to tissue self-antigen and this Batf3-dependent DC population is necessary to mount a fulminant autoimmune response in skin. Conversely, activation of Ag-specific Teffs in SDLNs played no role in DDC migration. Our studies reveal a crucial role for skin-resident T cell-derived signals, originating at the site of self-antigen expression, to drive DDC migration during the elicitation phase of an autoimmune response. Copyright © 2018 by The American Association of Immunologists, Inc.

  12. What's driving migration?

    PubMed

    Kane, H

    1995-01-01

    During the 1990s investment in prevention of international or internal migration declined, and crisis intervention increased. The budgets of the UN High Commissioner for Refugees and the UN Development Program remained about the same. The operating assumption is that war, persecution, famine, and environmental and social disintegration are inevitable. Future efforts should be directed to stabilizing populations through investment in sanitation, public health, preventive medicine, land tenure, environmental protection, and literacy. Forces pushing migration are likely to increase in the future. Forces include depletion of natural resources, income disparities, population pressure, and political disruption. The causes of migration are not constant. In the past, migration occurred during conquests, settlement, intermarriage, or religious conversion and was a collective movement. Current migration involves mass movement of individuals and the struggle to survive. There is new pressure to leave poor squatter settlements and the scarcities in land, water, and food. The slave trade between the 1500s and the 1800s linked continents, and only 2-3 million voluntarily crossed national borders. Involuntary migration began in the early 1800s when European feudal systems were in a decline, and people sought freedom. Official refugees, who satisfy the strict 1951 UN definition, increased from 15 million in 1980 to 23 million in 1990 but remained a small proportion of international migrants. Much of the mass movement occurs between developing countries. Migration to developed countries is accompanied by growing intolerance, which is misinformed. China practices a form of "population transfer" in Tibet in order to dilute Tibetan nationalism. Colonization of countries is a new less expensive form of control over territory. Eviction of minorities is another popular strategy in Iraq. Public works projects supported by foreign aid displace millions annually. War and civil conflicts

  13. PLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration

    PubMed Central

    Janjanam, Jagadeesh; Chandaka, Giri Kumar; Kotla, Sivareddy; Rao, Gadiparthi N.

    2015-01-01

    Monocyte chemotactic protein 1 (MCP1) stimulates vascular smooth muscle cell (VSMC) migration in vascular wall remodeling. However, the mechanisms underlying MCP1-induced VSMC migration have not been understood. Here we identify the signaling pathway associated with MCP1-induced human aortic smooth muscle cell (HASMC) migration. MCP1, a G protein–coupled receptor agonist, activates phosphorylation of cortactin on S405 and S418 residues in a time-dependent manner, and inhibition of its phosphorylation attenuates MCP1-induced HASMC G-actin polymerization, F-actin stress fiber formation, and migration. Cortactin phosphorylation on S405/S418 is found to be critical for its interaction with WAVE2, a member of the WASP family of cytoskeletal regulatory proteins required for cell migration. In addition, the MCP1-induced cortactin phosphorylation is dependent on PLCβ3-mediated PKCδ activation, and siRNA-mediated down-regulation of either of these molecules prevents cortactin interaction with WAVE2, affecting G-actin polymerization, F-actin stress fiber formation, and HASMC migration. Upstream, MCP1 activates CCR2 and Gαq/11 in a time-dependent manner, and down-regulation of their levels attenuates MCP1-induced PLCβ3 and PKCδ activation, cortactin phosphorylation, cortactin–WAVE2 interaction, G-actin polymerization, F-actin stress fiber formation, and HASMC migration. Together these findings demonstrate that phosphorylation of cortactin on S405 and S418 residues is required for its interaction with WAVE2 in MCP1-induced cytoskeleton remodeling, facilitating HASMC migration. PMID:26490115

  14. Inhibition or ablation of transglutaminase 2 impairs astrocyte migration.

    PubMed

    Monteagudo, Alina; Ji, Changyi; Akbar, Abdullah; Keillor, Jeffrey W; Johnson, Gail V W

    2017-01-22

    Astrocytes play numerous complex roles that support and facilitate the function of neurons. Further, when there is an injury to the central nervous system (CNS) they can both facilitate or ameliorate functional recovery depending on the location and severity of the injury. When a CNS injury is relatively severe a glial scar is formed, which is primarily composed of astrocytes. The glial scar can be both beneficial, by limiting inflammation, and detrimental, by preventing neuronal projections, to functional recovery. Thus, understanding the processes and proteins that regulate astrocyte migration in response to injury is still of fundamental importance. One protein that is likely involved in astrocyte migration is transglutaminase 2 (TG2); a multifunctional protein expressed ubiquitously throughout the brain. Its functions include transamidation and GTPase activity, among others, and previous studies have implicated TG2 as a regulator of migration. Therefore, we examined the role of TG2 in primary astrocyte migration subsequent to injury. Using wild type or TG2 -/- astrocytes, we manipulated the different functions and conformation of TG2 with novel irreversible inhibitors or mutant versions of the protein. Results showed that both inhibition and ablation of TG2 in primary astrocytes significantly inhibit migration. Additionally, we show that the deficiency in migration caused by deletion of TG2 can only be rescued with the native protein and not with mutants. Finally, the addition of TGFβ rescued the migration deficiency independent of TG2. Taken together, our study shows that transamidation and GTP/GDP-binding are necessary for inhibiting astrocyte migration and it is TGFβ independent. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Migration and Environmental Hazards

    PubMed Central

    Hunter, Lori M.

    2011-01-01

    Losses due to natural hazards (e.g., earthquakes, hurricanes) and technological hazards (e.g., nuclear waste facilities, chemical spills) are both on the rise. One response to hazard-related losses is migration, with this paper offering a review of research examining the association between migration and environmental hazards. Using examples from both developed and developing regional contexts, the overview demonstrates that the association between migration and environmental hazards varies by setting, hazard types, and household characteristics. In many cases, however, results demonstrate that environmental factors play a role in shaping migration decisions, particularly among those most vulnerable. Research also suggests that risk perception acts as a mediating factor. Classic migration theory is reviewed to offer a foundation for examination of these associations. PMID:21886366

  16. Effect of solute concentration on grain boundary migration with segregation in stainless steel and model alloys

    NASA Astrophysics Data System (ADS)

    Kanda, H.; Hashimoto, N.; Takahashi, H.

    The phenomenon of grain boundary migration due to boundary diffusion via vacancies is a well-known process for recrystallization and grain growth during annealing. This phenomenon is known as diffusion-induced grain boundary migration (DIGM) and has been recognized in various binary systems. On the other hand, grain boundary migration often occurs under irradiation. Furthermore, such radiation-induced grain boundary migration (RIGM) gives rise to solute segregation. In order to investigate the RIGM mechanism and the interaction between solutes and point defects during the migration, stainless steel and Ni-Si model alloys were electron-irradiated using a HVEM. RIGM was often observed in stainless steels during irradiation. The migration rate of boundary varied, and three stages of the migration were recognized. At lower temperatures, incubation periods up to the occurrence of the boundary migration were observed prior to first stage. These behaviors were recognized particularly for lower solute containing alloys. From the relation between the migration rates at stage I and inverse temperatures, activation energies for the boundary migration were estimated. In comparison to the activation energy without irradiation, these values were very low. This suggests that the RIGM is caused by the flow of mixed-dumbbells toward the grain boundary. The interaction between solute and point defects and the effective defect concentration generating segregation will be discussed.

  17. Bm-TFF2, a toad trefoil factor, promotes cell migration, survival and wound healing

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

    Zhang, Yong; Graduate School of Chinese Academy of Sciences, Beijing 100049; Yu, Guoyu

    2010-07-30

    Research highlights: {yields} Bm-TFF2 binds to epithelial cells and induces cell migration and wound healing. {yields} Bm-TFF2 suppresses cell apoptosis. {yields} Bm-TFF2 has no effect on cell proliferation. -- Abstract: Toad skin is naked and continually confronted by various injurious factors. Constant skin renewal and repairs occur frequently. However, the mechanisms of the renewal and repair have not clearly elucidated. In our previous work, a trefoil factor (TFF), Bm-TFF2, has been purified from the Bombina maxima skin and characterized as a platelet agonist. The mRNA of TFFs in toad skin was up-regulated greatly during the metamorphosis, indicating a pivotal rolemore » of TFFs in amphibian skin. Here, we presented the effects of Bm-TFF2 on the cell migration, apoptosis and proliferation. Bm-TFF2 bound to epithelial cells and showed strong cell motility activity. At the concentrations of 1-100 nM, Bm-TFF2-induced migration of human epithelial AGS and HT-29 cells, and rat intestinal epithelial IEC-6 cell lines. The in vitro wound healing assay also verified the activity of Bm-TFF2. Bm-TFF2 could also inhibit cell apoptosis induced by ceramide and sodium butyrate. The cell migration-promoting activity was abolished by MEK1 inhibitors, U0126 and PD98059, suggesting that ERK1/2 activation is crucial for Bm-TFF2 to stimulate cell migration. Taken together, Bm-TFF2 promoted wound healing by stimulating cell migration via MAPK pathway and preventing cell apoptosis. The potent biological activity of Bm-TFF2 makes it a useful molecular tool for further studies of structure-function relationship of the related human TFFs.« less

  18. Pyk2 and Megakaryocytes Regulate Osteoblast Differentiation and Migration via Distinct and Overlapping Mechanisms

    PubMed Central

    Eleniste, Pierre P.; Patel, Vruti; Posritong, Sumana; Zero, Odette; Largura, Heather; Cheng, Ying-Hua; Himes, Evan R.; Hamilton, Matthew; Baughman, Jenna; Kacena, Melissa A.; Bruzzaniti, Angela

    2016-01-01

    Osteoblast differentiation and migration are necessary for bone formation during bone remodeling. Mice lacking the proline-rich tyrosine kinase Pyk2 (Pyk2-KO) have increased bone mass, in part due to increased osteoblast proliferation. Megakaryocytes (MKs), the platelet-producing cells, also promote osteoblast proliferation in vitro and bone-formation in vivo via a pathway that involves Pyk2. In the current study, we examined the mechanism of action of Pyk2, and the role of MKs, on osteoblast differentiation and migration. We found that Pyk2-KO osteoblasts express elevated alkaline phosphatase (ALP), type I collagen and osteocalcin mRNA levels as well as increased ALP activity and mineralization, confirming that Pyk2 negatively regulates osteoblast function. Since Pyk2 Y402 phosphorylation is important for its catalytic activity and for its protein-scaffolding functions, we expressed the phosphorylation-mutant (Pyk2Y402F) and kinase-mutant (Pyk2K457A) in Pyk2-KO osteoblasts. Both Pyk2Y402F and Pyk2K457A reduced ALP activity, whereas only kinase-inactive Pyk2K457A inhibited Pyk2-KO osteoblast migration. Consistent with a role for Pyk2 on ALP activity, co-culture of MKs with osteoblasts led to a decrease in the level of phosphorylated Pyk2 (pY402) as well as a decrease in ALP activity. Although Pyk2-KO osteoblasts exhibited increased migration compared to WT osteoblasts, Pyk2 expression was not required for the ability of MKs to stimulate osteoblast migration. Together, these data suggest that osteoblast differentiation and migration are inversely regulated by MKs via distinct Pyk2-dependent and independent signaling pathways. Novel drugs that distinguish between the kinase-dependent or protein-scaffolding functions of Pyk2 may provide therapeutic specificity for the control of bone-related diseases. PMID:26552846

  19. The Asian-American variant of human papillomavirus type 16 exhibits higher activation of MAPK and PI3K/AKT signaling pathways, transformation, migration and invasion of primary human keratinocytes.

    PubMed

    Hochmann, Jimena; Sobrinho, João S; Villa, Luisa L; Sichero, Laura

    2016-05-01

    Asian-American (AA) HPV-16 variants are associated with higher risk of cancer. Abnormal activation of intracellular signaling play a critical role in cancer development and progression. Our aim was to elucidate mechanisms underlying the higher oncogenic potential attributed to AA variant. We evaluated activation of MAPK and PI3K/AKT pathways in primary human keratinocytes (PHKs) transduced with E6/E7 of three HPV-16 variants: E-P, AA, E-350G. Phenotypes examined included migration, anchorage independent growth and invasion. AA PHKs presented the highest levels of active proteins involved in all cascades analyzed: MAPK-ERK, MAPK-p38 and PI3K-AKT. AA PHKs were more efficient in promoting anchorage independent growth, and in stimulating cell migration and invasion. MEK1 inhibition decreased migration. The mesenchymal phenotype marker vimentin was increased in AA PHKs. Our results suggest that MEK1, ERK2, AKT2 hyperactivation influence cellular behavior by means of GSK-3b inactivation and EMT induction prompting AA immortalized PHKs to more efficiently surpass carcinogenesis steps. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Development of an ultralow-light-level luminescence image analysis system for dynamic measurements of transcriptional activity in living and migrating cells.

    PubMed

    Maire, E; Lelièvre, E; Brau, D; Lyons, A; Woodward, M; Fafeur, V; Vandenbunder, B

    2000-04-10

    We have developed an approach to study in single living epithelial cells both cell migration and transcriptional activation, which was evidenced by the detection of luminescence emission from cells transfected with luciferase reporter vectors. The image acquisition chain consists of an epifluorescence inverted microscope, connected to an ultralow-light-level photon-counting camera and an image-acquisition card associated to specialized image analysis software running on a PC computer. Using a simple method based on a thin calibrated light source, the image acquisition chain has been optimized following comparisons of the performance of microscopy objectives and photon-counting cameras designed to observe luminescence. This setup allows us to measure by image analysis the luminescent light emitted by individual cells stably expressing a luciferase reporter vector. The sensitivity of the camera was adjusted to a high value, which required the use of a segmentation algorithm to eliminate the background noise. Following mathematical morphology treatments, kinetic changes of luminescent sources were analyzed and then correlated with the distance and speed of migration. Our results highlight the usefulness of our image acquisition chain and mathematical morphology software to quantify the kinetics of luminescence changes in migrating cells.

  1. Focal Adhesion Kinase Regulates Fibroblast Migration via Integrin beta-1 and Plays a Central Role in Fibrosis

    PubMed Central

    Zhao, Xue-Ke; Cheng, Yiju; Liang Cheng, Ming; Yu, Lei; Mu, Mao; Li, Hong; Liu, Yang; Zhang, Baofang; Yao, Yumei; Guo, Hui; Wang, Rong; Zhang, Quan

    2016-01-01

    Lung fibrosis is a major medical problem for the aging population worldwide. Fibroblast migration plays an important role in fibrosis. Focal Adhesion Kinase (FAK) senses the extracellular stimuli and initiates signaling cascades that promote cell migration. This study first examined the dose and time responses of FAK activation in human lung fibroblasts treated with platelet derived growth factor BB (PDGF-BB). The data indicate that FAK is directly recruited by integrin β1 and the subsequent FAK activation is required for fibroblast migration on fibronectin. In addition, the study has identified that α5β1 and α4β1 are the major integrins for FAK-mediated fibroblast migration on fibronect. In contrast, integrins αvβ3, αvβ6, and αvβ8 play a minor but distinct role in fibroblast migration on fibronectin. FAK inhibitor significantly reduces PDGF-BB stimulated fibroblast migration. Importantly, FAK inhibitor protects bleomycin-induced lung fibrosis in mice. FAK inhibitor blocks FAK activation and significantly reduces signaling cascade of fibroblast migration in bleomycin-challenged mice. Furthermore, FAK inhibitor decreases lung fibrotic score, collagen accumulation, fibronectin production, and myofibroblast differentiation in in bleomycin-challenged mice. These data demonstrate that FAK mediates fibroblast migration mainly via integrin β1. Furthermore, the findings suggest that targeting FAK signaling is an effective therapeutic strategy against fibrosis. PMID:26763945

  2. More Myths of Migration.

    ERIC Educational Resources Information Center

    Basch, Linda; Lerner, Gail

    1986-01-01

    Challenges "myths" about women and migration, including (1) the causes of migration are economic, not racism; (2) migrant women receive support from feminist groups and trade unions; (3) transnational corporations are positive forces in developing nations; (4) migration today has little impact on family life; and (5) most migrants cluster in…

  3. Efforts to improve international migration statistics: a historical perspective.

    PubMed

    Kraly, E P; Gnanasekaran, K S

    1987-01-01

    During the past decade, the international statistical community has made several efforts to develop standards for the definition, collection and publication of statistics on international migration. This article surveys the history of official initiatives to standardize international migration statistics by reviewing the recommendations of the International Statistical Institute, International Labor Organization, and the UN, and reports a recently proposed agenda for moving toward comparability among national statistical systems. Heightening awareness of the benefits of exchange and creating motivation to implement international standards requires a 3-pronged effort from the international statistical community. 1st, it is essential to continue discussion about the significance of improvement, specifically standardization, of international migration statistics. The move from theory to practice in this area requires ongoing focus by migration statisticians so that conformity to international standards itself becomes a criterion by which national statistical practices are examined and assessed. 2nd, the countries should be provided with technical documentation to support and facilitate the implementation of the recommended statistical systems. Documentation should be developed with an understanding that conformity to international standards for migration and travel statistics must be achieved within existing national statistical programs. 3rd, the call for statistical research in this area requires more efforts by the community of migration statisticians, beginning with the mobilization of bilateral and multilateral resources to undertake the preceding list of activities.

  4. Elk migration patterns and human activity influence wolf habitat use in the Greater Yellowstone Ecosystem.

    PubMed

    Nelson, Abigail A; Kauffman, Matthew J; Middleton, Arthur D; Jimenez, Michael D; McWhirter, Douglas E; Barber, Jarrett; Gerow, Kenneth

    2012-12-01

    Identifying the ecological dynamics underlying human-wildlife conflicts is important for the management and conservation of wildlife populations. In landscapes still occupied by large carnivores, many ungulate prey species migrate seasonally, yet little empirical research has explored the relationship between carnivore distribution and ungulate migration strategy. In this study, we evaluate the influence of elk (Cervus elaphus) distribution and other landscape features on wolf (Canis lupus) habitat use in an area of chronic wolf-livestock conflict in the Greater Yellowstone Ecosystem, USA. Using three years of fine-scale wolf (n = 14) and elk (n = 81) movement data, we compared the seasonal habitat use of wolves in an area dominated by migratory elk with that of wolves in an adjacent area dominated by resident elk. Most migratory elk vacate the associated winter wolf territories each summer via a 40-60 km migration, whereas resident elk remain accessible to wolves year-round. We used a generalized linear model to compare the relative probability of wolf use as a function of GIS-based habitat covariates in the migratory and resident elk areas. Although wolves in both areas used elk-rich habitat all year, elk density in summer had a weaker influence on the habitat use of wolves in the migratory elk area than the resident elk area. Wolves employed a number of alternative strategies to cope with the departure of migratory elk. Wolves in the two areas also differed in their disposition toward roads. In winter, wolves in the migratory elk area used habitat close to roads, while wolves in the resident elk area avoided roads. In summer, wolves in the migratory elk area were indifferent to roads, while wolves in resident elk areas strongly avoided roads, presumably due to the location of dens and summering elk combined with different traffic levels. Study results can help wildlife managers to anticipate the movements and establishment of wolf packs as they expand into areas

  5. Elk migration patterns and human activity influence wolf habitat use in the Greater Yellowstone Ecosystem

    USGS Publications Warehouse

    Nelson, Abigail; Kauffman, Matthew J.; Middleton, Arthur D.; Jimenez, Mike; McWhirter, Douglas; Barber, Jarrett; Gerow, Ken

    2012-01-01

    Identifying the ecological dynamics underlying human–wildlife conflicts is important for the management and conservation of wildlife populations. In landscapes still occupied by large carnivores, many ungulate prey species migrate seasonally, yet little empirical research has explored the relationship between carnivore distribution and ungulate migration strategy. In this study, we evaluate the influence of elk (Cervus elaphus) distribution and other landscape features on wolf (Canis lupus) habitat use in an area of chronic wolf–livestock conflict in the Greater Yellowstone Ecosystem, USA. Using three years of fine-scale wolf (n = 14) and elk (n = 81) movement data, we compared the seasonal habitat use of wolves in an area dominated by migratory elk with that of wolves in an adjacent area dominated by resident elk. Most migratory elk vacate the associated winter wolf territories each summer via a 40–60 km migration, whereas resident elk remain accessible to wolves year-round. We used a generalized linear model to compare the relative probability of wolf use as a function of GIS-based habitat covariates in the migratory and resident elk areas. Although wolves in both areas used elk-rich habitat all year, elk density in summer had a weaker influence on the habitat use of wolves in the migratory elk area than the resident elk area. Wolves employed a number of alternative strategies to cope with the departure of migratory elk. Wolves in the two areas also differed in their disposition toward roads. In winter, wolves in the migratory elk area used habitat close to roads, while wolves in the resident elk area avoided roads. In summer, wolves in the migratory elk area were indifferent to roads, while wolves in resident elk areas strongly avoided roads, presumably due to the location of dens and summering elk combined with different traffic levels. Study results can help wildlife managers to anticipate the movements and establishment of wolf packs as they expand into

  6. Recovery Migration to the City of New Orleans after Hurricane Katrina: A Migration Systems Approach.

    PubMed

    Fussell, Elizabeth; Curtis, Katherine J; Dewaard, Jack

    2014-03-01

    Hurricane Katrina's effect on the population of the City of New Orleans provides a model of how severe weather events, which are likely to increase in frequency and strength as the climate warms, might affect other large coastal cities. Our research focuses on changes in the migration system - defined as the system of ties between Orleans Parish and all other U.S. counties - between the pre-disaster (1999-2004) and recovery (2007-2009) periods. Using Internal Revenue Service county-to-county migration flow data, we find that in the recovery period Orleans Parish increased the number of migration ties with and received larger migration flows from nearby counties in the Gulf of Mexico coastal region, thereby spatially concentrating and intensifying the in-migration dimension of this predominantly urban system, while the out-migration dimension contracted and had smaller flows. We interpret these changes as the migration system relying on its strongest ties to nearby and less damaged counties to generate recovery in-migration.

  7. 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

  8. Morinda citrifolia Linn leaf extract possesses antioxidant activities and reduces nociceptive behavior and leukocyte migration.

    PubMed

    Serafini, Mairim Russo; Santos, Rodrigo Correia; Guimarães, Adriana Gibara; Dos Santos, João Paulo Almeida; da Conceicão Santos, Alan Diego; Alves, Izabel Almeida; Gelain, Daniel Pens; de Lima Nogueira, Paulo Cesar; Quintans-Júnior, Lucindo José; Bonjardim, Leonardo Rigoldi; de Souza Araújo, Adriano Antunes

    2011-10-01

    Herbal drugs have been used since ancient times to treat a wide range of diseases. Morinda citrifolia Linn (popularly known as "Noni") has been used in folk medicine by Polynesians for over 2,000 years. It is reported to have a broad range of therapeutic effects, including effects against headache, fever, arthritis, gingivitis, respiratory disorders, infections, tuberculosis, and diabetes. The aim of this study was to investigate the antioxidant, anti-inflammatory, antinociceptive, and antibacterial properties of the aqueous extract from M. citrifolia leaves (AEMC). Antioxidant activity was observed against lipid peroxidation, nitric oxide, and hydroxyl radicals. The antinociceptive effect of AEMC was observed in the acetic acid-induced writhing test at the higher dose. Moreover, AEMC significantly reduced the leukocyte migration in doses of 200 and 400 mg/kg and showed mild antibacterial activity. Together, the results suggest that properties of M. citrifolia leaf extract should be explored further in order to achieve newer tools for managing painful and inflammation conditions, including those related to oxidant states.

  9. IL-17B activated mesenchymal stem cells enhance proliferation and migration of gastric cancer cells.

    PubMed

    Bie, Qingli; Zhang, Bin; Sun, Caixia; Ji, Xiaoyun; Barnie, Prince Amoah; Qi, Chen; Peng, Jingjing; Zhang, Danyi; Zheng, Dong; Su, Zhaoliang; Wang, Shengjun; Xu, Huaxi

    2017-03-21

    Mesenchymal stem cells are important cells in tumor microenvironment. We have previously demonstrated that IL-17B/IL-17RB signal promoted progression of gastric cancer. In this study, we further explored the effect of IL-17B on mesenchymal stem cells in tumor microenvironment and its impact on the tumor progression. The results showed that IL-17B induced the expression of stemness-related genes Nanog, Sox2, and Oct4 in mesenchymal stem cells and enhanced its tumor-promoting effect. The supernatant from cultured mesenchymal stem cells after treating with exogenous rIL-17B promoted the proliferation and migration of MGC-803, therefor suggesting that rIL-17B might promote mesenchymal stem cells to produce soluble factors. In addition, rIL-17B also activated the NF-κΒ, STAT3, β-catenin pathway in mesenchymal stem cells. Our data revealed a new mechanism that IL-17B enhanced the progression of gastric cancer by activating mesenchymal stem cells.

  10. Gas6 induces cancer cell migration and epithelial–mesenchymal transition through upregulation of MAPK and Slug

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

    Lee, Yunhee; Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon; Lee, Mira

    2013-04-26

    Highlights: •We investigated the molecular mechanisms underlying Gas6-mediated cancer cell migration. •Gas6 treatment and subsequent Axl activation induce cell migration and EMT via upregulation of Slug. •Slug expression mediated by Gas6 is mainly through c-Jun and ATF-2 in an ERK1/2 and JNK-dependent manner. •The Gas6/Axl-Slug axis may be exploited as a target for anti-cancer metastasis therapy. -- Abstract: Binding of Gas6 to Axl (Gas6/Axl axis) alters cellular functions, including migration, invasion, proliferation, and survival. However, the molecular mechanisms underlying Gas6-mediated cell migration remain poorly understood. In this study, we found that Gas6 induced the activation of JNK and ERK1/2 signalingmore » in cancer cells expressing Axl, resulting in the phosphorylation of activator protein-1 (AP-1) transcription factors c-Jun and ATF-2, and induction of Slug. Depletion of c-Jun or ATF-2 by siRNA attenuated the Gas6-induced expression of Slug. Slug expression was required for cell migration and E-cadherin reduction/vimentin induction induced by Gas6. These results suggest that Gas6 induced cell migration via Slug upregulation in JNK- and ERK1/2-dependent mechanisms. These data provide an important insight into the molecular mechanisms mediating Gas6-induced cell migration.« less

  11. Integrative Mechanisms of Oriented Neuronal Migration in the Developing Brain

    PubMed Central

    Evsyukova, Irina; Plestant, Charlotte; Anton, E.S.

    2014-01-01

    The emergence of functional neuronal connectivity in the developing cerebral cortex depends on neuronal migration. This process enables appropriate positioning of neurons and the emergence of neuronal identity so that the correct patterns of functional synaptic connectivity between the right types and numbers of neurons can emerge. Delineating the complexities of neuronal migration is critical to our understanding of normal cerebral cortical formation and neurodevelopmental disorders resulting from neuronal migration defects. For the most part, the integrated cell biological basis of the complex behavior of oriented neuronal migration within the developing mammalian cerebral cortex remains an enigma. This review aims to analyze the integrative mechanisms that enable neurons to sense environmental guidance cues and translate them into oriented patterns of migration toward defined areas of the cerebral cortex. We discuss how signals emanating from different domains of neurons get integrated to control distinct aspects of migratory behavior and how different types of cortical neurons coordinate their migratory activities within the developing cerebral cortex to produce functionally critical laminar organization. PMID:23937349

  12. 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

  13. Migration and Adult Education

    ERIC Educational Resources Information Center

    Gois, William

    2007-01-01

    The objective of this paper is to highlight the role of adult education as a tool in addressing labour migration issues, specifically those concerning the protection of migrant workers' rights and the transformation of the impact of migration into positive holistic developmental gains. The view of labour migration as a means to forge the economic…

  14. Role of peptidylarginine deiminase 2 (PAD2) in mammary carcinoma cell migration.

    PubMed

    Horibata, Sachi; Rogers, Katherine E; Sadegh, David; Anguish, Lynne J; McElwee, John L; Shah, Pragya; Thompson, Paul R; Coonrod, Scott A

    2017-05-26

    Penetration of the mammary gland basement membrane by cancer cells is a crucial first step in tumor invasion. Using a mouse model of ductal carcinoma in situ, we previously found that inhibition of peptidylarginine deiminase 2 (PAD2, aka PADI2) activity appears to maintain basement membrane integrity in xenograft tumors. The goal of this investigation was to gain insight into the mechanisms by which PAD2 mediates this process. For our study, we modulated PAD2 activity in mammary ductal carcinoma cells by lentiviral shRNA-mediated depletion, lentiviral-mediated PAD2 overexpression, or PAD inhibition and explored the effects of these treatments on changes in cell migration and cell morphology. We also used these PAD2-modulated cells to test whether PAD2 may be required for EGF-induced cell migration. To determine how PAD2 might promote tumor cell migration in vivo, we tested the effects of PAD2 inhibition on the expression of several cell migration mediators in MCF10DCIS.com xenograft tumors. In addition, we tested the effect of PAD2 inhibition on EGF-induced ductal invasion and elongation in primary mouse mammary organoids. Lastly, using a transgenic mouse model, we investigated the effects of PAD2 overexpression on mammary gland development. Our results indicate that PAD2 depletion or inhibition suppresses cell migration and alters the morphology of MCF10DCIS.com cells. In addition, we found that PAD2 depletion suppresses the expression of the cytoskeletal regulatory proteins RhoA, Rac1, and Cdc42 and also promotes a mesenchymal to epithelial-like transition in tumor cells with an associated increase in the cell adhesion marker, E-cadherin. Our mammary gland organoid study found that inhibition of PAD2 activity suppresses EGF-induced ductal invasion. In vivo, we found that PAD2 overexpression causes hyperbranching in the developing mammary gland. Together, these results suggest that PAD2 plays a critical role in breast cancer cell migration. Our findings that EGF

  15. Rural-Urban Migration in Colombia.

    ERIC Educational Resources Information Center

    Schultz, T. Paul

    The rural-urban migration pattern in Colombia during the last 25 years has resulted in a population increase in urban areas from 30 to 52 percent of the total population. This study explores the causes of internal migration. Migration rates are estimated for various groups in the population to clarify who migrates and to where. A model of…

  16. Glutamate increases pancreatic cancer cell invasion and migration via AMPA receptor activation and Kras-MAPK signaling.

    PubMed

    Herner, Alexander; Sauliunaite, Danguole; Michalski, Christoph W; Erkan, Mert; De Oliveira, Tiago; Abiatari, Ivane; Kong, Bo; Esposito, Irene; Friess, Helmut; Kleeff, Jörg

    2011-11-15

    Glutamate has been implicated in tumorigenesis through activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPAR). However, the function of a glutamate-to-AMPAR signal in pancreatic ductal adenocarcinoma (PDAC) has remained elusive. We now show that glutamate-mediated AMPA receptor activation increases invasion and migration of pancreatic cancer cells via activation of the classical MAPK pathway. Glutamate levels were increased in pancreatic cancer accompanied by downregulation of GluR subunits 1, 2, and 4. In pancreatic cancer precursor lesions, pancreatic intraepithelial neoplasia (PanIN), GluR1 subunit levels were strikingly and step-wise increased but its expression was rare in PDAC. Pharmacological inhibition or RNAi-mediated suppression of GluR1 or GluR2 did not affect cancer cell growth but significantly decreased invasion. In a K-ras wildtype cell line, AMPA receptor activation enhanced K-ras activity and--further downstream--phosphorylation of p38 and of p44/42. Preemptive blockade of AMPA receptors in a mouse model of pancreatic cancer inhibited tumor cell settling. AMPA receptor activation thus not only activates MAPK signalling but also directly increases activity of K-ras. Glutamate might serve as a molecular switch that decreases the threshold of K-ras-induced oncogenic signalling and increases the chance of malignant transformation of pancreatic cancer precursor lesions. Copyright © 2011 UICC.

  17. Labor Migration by Russian Young People

    ERIC Educational Resources Information Center

    Man'shin, R. V.; Timoshenko, O. V.; Pis'mennaia, E. E.

    2009-01-01

    Russia's young people have become active participants in processes of migration. After the fall of the USSR, young people began to travel outside Russia in substantially greater numbers. At the present time, young Russians can be found in all kinds of regions and countries of the world. They are getting an education in foreign universities and…

  18. Low-Dose Curcumin Stimulates Proliferation, Migration and Phagocytic Activity of Olfactory Ensheathing Cells

    PubMed Central

    Tello Velasquez, Johana; Watts, Michelle E.; Todorovic, Michael; Nazareth, Lynnmaria; Pastrana, Erika; Diaz-Nido, Javier; Lim, Filip; Ekberg, Jenny A. K.; Quinn, Ronald J.; John, James A. St

    2014-01-01

    One of the promising strategies for neural repair therapies is the transplantation of olfactory ensheathing cells (OECs) which are the glial cells of the olfactory system. We evaluated the effects of curcumin on the behaviour of mouse OECs to determine if it could be of use to further enhance the therapeutic potential of OECs. Curcumin, a natural polyphenol compound found in the spice turmeric, is known for its anti-cancer properties at doses over 10 µM, and often at 50 µM, and it exerts its effects on cancer cells in part by activation of MAP kinases. In contrast, we found that low-dose curcumin (0.5 µM) applied to OECs strikingly modulated the dynamic morphology, increased the rate of migration by up to 4-fold, and promoted significant proliferation of the OECs. Most dramatically, low-dose curcumin stimulated a 10-fold increase in the phagocytic activity of OECs. All of these potently stimulated behavioural characteristics of OECs are favourable for neural repair therapies. Importantly, low-dose curcumin gave a transient activation of p38 kinases, which is in contrast to the high dose curcumin effects on cancer cells in which these MAP kinases tend to undergo prolonged activation. Low-dose curcumin mediated effects on OECs demonstrate cell-type specific stimulation of p38 and ERK kinases. These results constitute the first evidence that low-dose curcumin can modulate the behaviour of olfactory glia into a phenotype potentially more favourable for neural repair and thereby improve the therapeutic use of OECs for neural repair therapies. PMID:25360677

  19. Activation of the P2X₇ receptor induces migration of glial cells by inducing cathepsin B degradation of tissue inhibitor of metalloproteinase 1.

    PubMed

    Murphy, Niamh; Lynch, Marina A

    2012-12-01

    The P2X(7) receptor is an ion-gated channel, which is activated by high extracellular concentrations of adenosine triphosphate (ATP). Activation of P2X(7) receptors has been shown to induce neuroinflammatory changes associated with several neurological conditions. The matrix metalloproteinases (MMPs) are a family of endopeptidases that have several functions including degradation of the extracellular matrix, cell migration and modulation of bioactive molecules. The actions of MMPs are prevented by a family of protease inhibitors called tissue inhibitors of metalloproteinases (TIMPs). In this study, we show that ATP-treated glial cultures from neonatal C57BL/6 mice release and increase MMP-9 activity, which is coupled with a decrease in release of TIMP-1 and an increase in activated cathepsin B within the extracellular space. This process occurs independently of NLRP3-inflammasome formation. Treatment with a P2X(7) receptor antagonist prevents ATP-induced MMP-9 activity, inhibition of active cathepsin B release and allows for TIMP-1 to be released from the cell. We have shown that cathepsin B degrades TIMP-1, and inhibition of cathepsin B allows for release of TIMP-1 and inhibits MMP-9 activity. We also present data that indicate that ATP or cell damage induces glial cell migration, which is inhibited by P2X(7) antagonism, depletion of MMP-9 or inhibition of cathepsin B. © 2012 International Society for Neurochemistry.

  20. Human migration activities drive the fluctuation of ARGs: Case study of landfills in Nanjing, eastern China.

    PubMed

    Sun, Mingming; Ye, Mao; Schwab, Arthur P; Li, Xu; Wan, Jinzhong; Wei, Zhong; Wu, Jun; Friman, Ville-Petri; Liu, Kuan; Tian, Da; Liu, Manqiang; Li, Huixin; Hu, Feng; Jiang, Xin

    2016-09-05

    Landfills are perfect sites to study the effect of human migration on fluctuation of antibiotic resistance genes (ARGs) as they are the final destination of municipal waste. For example, large-scale human migration during the holidays is often accompanied by changes in waste dumping having potential effects on ARG abundance. Three landfills were selected to examine fluctuation in the abundance of fifteen ARGs and Intl1 genes for 14 months in Nanjing, eastern China. Mass human migration, the amount of dumped waste and temperature exerted the most significant effects on bimonthly fluctuations of ARG levels in landfill sites. As a middle-sized cosmopolitan city in China, millions of college students and workers migrate during holidays, contributing to the dramatic increases in waste production and fluctuation in ARG abundances. In line with this, mass migration explained most of the variation in waste dumping. The waste dumping also affected the bioaccessibility of mixed-compound pollutants that further positively impacted the level of ARGs. The influence of various bioaccessible compounds on ARG abundance followed the order: antibiotics>nutrients>metals>organic pollutants. Concentrations of bioaccessible compounds were more strongly correlated with ARG levels compared to total compound concentrations. Improved waste classification and management strategies could thus help to decrease the amount of bioaccessible pollutants leading to more effective control for urban ARG dissemination. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Rural-urban migration and urban employment opportunities in Nigeria.

    PubMed

    Okpara, E E

    1986-01-01

    The author suggests that most studies of rural-urban migration in the third world today are based on the European experience during the Industrial Revolution. He contends that the assumption that most migrants find wage employment in a rapidly growing modern industrial sector is not valid, particularly in Western Africa, where the pace of industrialization lags behind the rate of urbanization. Data from Nigeria are used to show that many potential migrants are aware of this situation and migrate seeking self-employment in informal sector trading activities.

  2. Recovery Migration to the City of New Orleans after Hurricane Katrina: A Migration Systems Approach

    PubMed Central

    Fussell, Elizabeth; Curtis, Katherine J.; DeWaard, Jack

    2014-01-01

    Hurricane Katrina’s effect on the population of the City of New Orleans provides a model of how severe weather events, which are likely to increase in frequency and strength as the climate warms, might affect other large coastal cities. Our research focuses on changes in the migration system – defined as the system of ties between Orleans Parish and all other U.S. counties – between the pre-disaster (1999–2004) and recovery (2007–2009) periods. Using Internal Revenue Service county-to-county migration flow data, we find that in the recovery period Orleans Parish increased the number of migration ties with and received larger migration flows from nearby counties in the Gulf of Mexico coastal region, thereby spatially concentrating and intensifying the in-migration dimension of this predominantly urban system, while the out-migration dimension contracted and had smaller flows. We interpret these changes as the migration system relying on its strongest ties to nearby and less damaged counties to generate recovery in-migration. PMID:24729651

  3. Zyxin regulates migration of renal epithelial cells through activation of hepatocyte nuclear factor-1β.

    PubMed

    Choi, Yun-Hee; McNally, Brian T; Igarashi, Peter

    2013-07-01

    Hepatocyte nuclear factor-1β (HNF-1β) is an epithelial tissue-specific transcription factor that regulates gene expression in the kidney, liver, pancreas, intestine, and other organs. Mutations of HNF-1β in humans produce renal cysts and congenital kidney anomalies. Here, we identify the LIM-domain protein zyxin as a novel binding partner of HNF-1β in renal epithelial cells. Zyxin shuttles to the nucleus where it colocalizes with HNF-1β. Immunoprecipitation of zyxin in leptomycin B-treated cells results in coprecipitation of HNF-1β. The protein interaction requires the second LIM domain of zyxin and two distinct domains of HNF-1β. Overexpression of zyxin stimulates the transcriptional activity of HNF-1β, whereas small interfering RNA silencing of zyxin inhibits HNF-1β-dependent transcription. Epidermal growth factor (EGF) induces translocation of zyxin into the nucleus and stimulates HNF-1β-dependent promoter activity. The EGF-mediated nuclear translocation of zyxin requires activation of Akt. Expression of dominant-negative mutant HNF-1β, knockdown of zyxin, or inhibition of Akt inhibits EGF-stimulated cell migration. These findings reveal a novel pathway by which extracellular signals are transmitted to the nucleus to regulate the activity of a transcription factor that is essential for renal epithelial differentiation.

  4. How Tissue Mechanical Properties Affect Enteric Neural Crest Cell Migration

    NASA Astrophysics Data System (ADS)

    Chevalier, N. R.; Gazguez, E.; Bidault, L.; Guilbert, T.; Vias, C.; Vian, E.; Watanabe, Y.; Muller, L.; Germain, S.; Bondurand, N.; Dufour, S.; Fleury, V.

    2016-02-01

    Neural crest cells (NCCs) are a population of multipotent cells that migrate extensively during vertebrate development. Alterations to neural crest ontogenesis cause several diseases, including cancers and congenital defects, such as Hirschprung disease, which results from incomplete colonization of the colon by enteric NCCs (ENCCs). We investigated the influence of the stiffness and structure of the environment on ENCC migration in vitro and during colonization of the gastrointestinal tract in chicken and mouse embryos. We showed using tensile stretching and atomic force microscopy (AFM) that the mesenchyme of the gut was initially soft but gradually stiffened during the period of ENCC colonization. Second-harmonic generation (SHG) microscopy revealed that this stiffening was associated with a gradual organization and enrichment of collagen fibers in the developing gut. Ex-vivo 2D cell migration assays showed that ENCCs migrated on substrates with very low levels of stiffness. In 3D collagen gels, the speed of the ENCC migratory front decreased with increasing gel stiffness, whereas no correlation was found between porosity and ENCC migration behavior. Metalloprotease inhibition experiments showed that ENCCs actively degraded collagen in order to progress. These results shed light on the role of the mechanical properties of tissues in ENCC migration during development.

  5. Tre1 GPCR initiates germ cell transepithelial migration by regulating Drosophila melanogaster E-cadherin

    PubMed Central

    Kunwar, Prabhat S.; Sano, Hiroko; Renault, Andrew D.; Barbosa, Vitor; Fuse, Naoyuki; Lehmann, Ruth

    2008-01-01

    Despite significant progress in identifying the guidance pathways that control cell migration, how a cell starts to move within an intact organism, acquires motility, and loses contact with its neighbors is poorly understood. We show that activation of the G protein–coupled receptor (GPCR) trapped in endoderm 1 (Tre1) directs the redistribution of the G protein Gβ as well as adherens junction proteins and Rho guanosine triphosphatase from the cell periphery to the lagging tail of germ cells at the onset of Drosophila melanogaster germ cell migration. Subsequently, Tre1 activity triggers germ cell dispersal and orients them toward the midgut for directed transepithelial migration. A transition toward invasive migration is also a prerequisite for metastasis formation, which often correlates with down-regulation of adhesion proteins. We show that uniform down-regulation of E-cadherin causes germ cell dispersal but is not sufficient for transepithelial migration in the absence of Tre1. Our findings therefore suggest a new mechanism for GPCR function that links cell polarity, modulation of cell adhesion, and invasion. PMID:18824569

  6. Collective cell migration in development

    PubMed Central

    Scarpa, Elena

    2016-01-01

    During embryonic development, tissues undergo major rearrangements that lead to germ layer positioning, patterning, and organ morphogenesis. Often these morphogenetic movements are accomplished by the coordinated and cooperative migration of the constituent cells, referred to as collective cell migration. The molecular and biomechanical mechanisms underlying collective migration of developing tissues have been investigated in a variety of models, including border cell migration, tracheal branching, blood vessel sprouting, and the migration of the lateral line primordium, neural crest cells, or head mesendoderm. Here we review recent advances in understanding collective migration in these developmental models, focusing on the interaction between cells and guidance cues presented by the microenvironment and on the role of cell–cell adhesion in mechanical and behavioral coupling of cells within the collective. PMID:26783298

  7. Migration kinetics and mechanisms of plasticizers, stabilizers at interfaces of NEPE propellant/HTPB liner/EDPM insulation.

    PubMed

    Huang, Zhi-ping; Nie, Hai-ying; Zhang, Yuan-yuan; Tan, Li-min; Yin, Hua-li; Ma, Xin-gang

    2012-08-30

    Migration appeared in the interfaces of nitrate ester plasticized polyether (NEPE) based propellant/hydroxyl-terminated polybutadiene (HTPB) based liner/ethylene propylene terpolymer (EPDM) based insulation was studied by aging at different temperatures. The migration components were extracted with solvent and determined by high performance liquid chromatography (HPLC). The migration occurred within 1mm to the interfaces, and the apparent migration activation energy (Ea) of nitroglycerin (NG), 1,2,4-butanetriol trinitrate (BTTN) and a kind of aniline stabilizer AD in propellant, liner and insulation was calculated respectively on the basis of HPLC data. The Ea values were among 15 and 50 kJ/mol, which were much less than chemical energy, and almost the same as hydrogen bond energy. The average diffusion coefficients were in the range of 10(-19)m(2)s(-1) to 10(-16)m(2)s(-1). It seemed the faster the migration rates, the smaller the apparent migration activation energy, the larger the diffusion coefficient and the less the amount of migration. It could be explained that the migration rate and energy were affected by the molecular volume of a mobile component and its diffusion property, and the amount of migration was resulted from the molecular polarity comparability of a mobile component to the based material. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Migration in far west Nepal: intergenerational linkages between internal and international migration of rural-to-urban migrants.

    PubMed

    Poertner, Ephraim; Junginger, Mathias; Müller-Böker, Ulrike

    2011-01-01

    In Nepal, international labor migration to India and overseas, as well as internal migration to the rural Nepalese lowlands, is of high socioeconomic significance. Scholarly debates about migration in Nepal have gradually shifted from an economic to a more holistic perspective, also incorporating social dimensions. However, little evidence has been generated about internal migration to urban destinations and the potential linkages between international and internal migration. This article draws on Bourdieu's “Theory of Practice” and sees migration as a social practice. Accordingly, migration practice is regarded as a strategy social agents apply to increase or transfer capitals and ultimately secure or improve their social position. Evidence for this argument is based on a qualitative case study of rural to urban migrants in Far West Nepal conducted in July and August 2009. The study at hand addresses linkages between internal and international migration practices and provides insight about a social stratum that is often neglected in migration research: the middle class and, more precisely, government employees. The authors show that social relations are crucial for channeling internal migration to a specific destination. Furthermore, they unveil how internal migration is connected to the international labor migration of former generations. Finally, the authors examine how migration strategies adopted over generations create multi-local social networks rooted in the family's place of origin.

  9. 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

  10. Mast cell migration to Th2 stimulated airway smooth muscle from asthmatics

    PubMed Central

    Sutcliffe, A; Kaur, D; Page, S; Woodman, L; Armour, C L; Baraket, M; Bradding, P; Hughes, J M; Brightling, C E

    2006-01-01

    Background Mast cell microlocalisation within the airway smooth muscle (ASM) bundle is an important determinant of the asthmatic phenotype. We hypothesised that mast cells migrate towards ASM in response to ASM derived chemokines. Methods Primary ASM cultures from subjects with and without asthma were stimulated with interleukin (IL)‐1β, IL‐4, and IL‐13 alone and in combination. Mast cell chemotaxis towards these ASM supernatants was investigated, and the chemotaxins mediating migration by using specific blocking antibodies for stem cell factor (SCF) and the chemokine receptors CCR3, CXCR1, 3 and 4 as well as the Gi inhibitor pertussis toxin and the tyrosine kinase inhibitor genistein were defined. The concentrations of CCL11, CXCL8, CXCL10, TGF‐β, and SCF in the supernatants were measured and the effect of non‐asthmatic ASM supernatants on the mast cell chemotactic activity of asthmatic ASM was examined. Results Human lung mast cells and HMC‐1 cells migrated towards Th2 stimulated ASM from asthmatics but not non‐asthmatics. Mast cell migration was mediated through the combined activation of CCR3 and CXCR1. CCL11 and CXCL8 expression by ASM increased markedly after stimulation, but was similar in those with and without asthma. ASM supernatants from non‐asthmatics inhibited mast cell migration towards the asthmatic ASM supernatant. Conclusion Th2 stimulated ASM from asthmatics is chemotactic for mast cells. Non‐asthmatic ASM releases a mediator or mediators that inhibit mast cell migration towards stimulated asthmatic ASM. Specifically targeting mast cell migration into the ASM bundle may provide a novel treatment for asthma. PMID:16601090

  11. Differential roles of WAVE1 and WAVE2 in dorsal and peripheral ruffle formation for fibroblast cell migration.

    PubMed

    Suetsugu, Shiro; Yamazaki, Daisuke; Kurisu, Shusaku; Takenawa, Tadaomi

    2003-10-01

    Cell migration is driven by actin polymerization at the leading edge of lamellipodia, where WASP family verprolin-homologous proteins (WAVEs) activate Arp2/3 complex. When fibroblasts are stimulated with PDGF, formation of peripheral ruffles precedes that of dorsal ruffles in lamellipodia. Here, we show that WAVE2 deficiency impairs peripheral ruffle formation and WAVE1 deficiency impairs dorsal ruffle formation. During directed cell migration in the absence of extracellular matrix (ECM), cells migrate with peripheral ruffles at the leading edge and WAVE2, but not WAVE1, is essential. In contrast, both WAVE1 and WAVE2 are essential for invading migration into ECM, suggesting that the leading edge in ECM has characteristics of both ruffles. WAVE1 is colocalized with ECM-degrading enzyme MMP-2 in dorsal ruffles, and WAVE1-, but not WAVE2-, dependent migration requires MMP activity. Thus, WAVE2 is essential for leading edge extension for directed migration in general and WAVE1 is essential in MMP-dependent migration in ECM.

  12. BIGH3 modulates adhesion and migration of hematopoietic stem and progenitor cells

    PubMed Central

    Klamer, Sofieke E; Kuijk, Carlijn GM; Hordijk, Peter L; van der Schoot, C Ellen; von Lindern, Marieke; van Hennik, Paula B; Voermans, Carlijn

    2013-01-01

    Cell adhesion and migration are important determinants of homing and development of hematopoietic stem and progenitor cells (HSPCs) in bone marrow (BM) niches. The extracellular matrix protein transforming growth factor-β (TGF-β) inducible gene H3 (BIGH3) is involved in adhesion and migration, although the effect of BIGH3 is highly cell type-dependent. BIGH3 is abundantly expressed by mesenchymal stromal cells, while its expression in HSPCs is relatively low unless induced by certain BM stressors. Here, we set out to determine how BIGH3 modulates HSPC adhesion and migration. We show that primary HSPCs adhere to BIGH3-coated substrates, which is, in part, integrin-dependent. Overexpression of BIGH3 in HSPCs and HL60 cells reduced the adhesion to the substrate fibronectin in adhesion assays, which was even more profound in electrical cell-substrate impedance sensing (ECIS) assays. Accordingly, the CXCL12 induced migration over fibronectin-coated surface was reduced in BIGH3-expressing HSPCs. The integrin expression profile of HSPCs was not altered upon BIGH3 expression. Although expression of BIGH3 did not alter actin polymerization in response to CXCL12, it inhibited the PMA-induced activation of the small GTPase RAC1 as well as the phosphorylation and activation of extracellular-regulated kinases (ERKs). Reduced activation of ERK and RAC1 may be responsible for the inhibition of cell adhesion and migration by BIGH3 in HSPCs. Induced BIGH3 expression upon BM stress may contribute to the regulation of BM homeostasis. PMID:24152593

  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. Stimulation of cell-surface urokinase-type plasminogen activator activity and cell migration in vascular endothelial cells by a novel hexapeptide analogue of neurotensin.

    PubMed

    Ushiro, S; Mizoguchi, K; Yoshida, S; Jimi, S; Fujiwara, T; Yoshida, M; Wei, E T; Kitabgi, P; Amagaya, S; Ono, M; Kuwano, M

    1997-12-01

    To investigate if neurotensin (NT) could induce activation of urokinase-type plasminogen activator (uPA) in vascular endothelial cells, we utilized the acetyl-NT (8-13) analogue, TJN-950, in which the C-terminal leucine is reduced to leucinol. TJN-950 inhibited the binding of 125I-NT to membranes of newborn rat brains and of COS-7 cells transfected with rat NT receptor cDNA, but at 10(4) higher doses than NT (8-13). However, TJN-950 was as effective as NT in inducing the fibrinolytic activity in bovine vascular aortic and human umbilical vein endothelial cells, and enhanced the migration of vascular endothelial cells. Moreover, administration of TJN-950 induced neovascularization in the rat cornea in vivo. TJN-950 had no effect on expression of uPA, plasminogen activator inhibitor-1 or uPA receptor mRNA. The binding of 125I-TJN-950 to cell membranes was blocked by unlabeled uPA and TJN-950, but not the amino-terminal or 12-32 fragment of uPA. TJN-950 may enhance uPA activity in vascular endothelial cells by interacting with the uPA receptor, resulting in induction of angiogenesis.

  15. 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

  16. Bauhinia variegata candida Fraction Induces Tumor Cell Death by Activation of Caspase-3, RIP, and TNF-R1 and Inhibits Cell Migration and Invasion In Vitro

    PubMed Central

    Santos, K. M.; Silva-Oliveira, R. J.; Pinto, F. E.; Oliveira, B. G.; Chagas, R. C. R.; Romão, W.; Reis, R. M. V.

    2018-01-01

    Metastasis remains the most common cause of death in cancer patients. Inhibition of metalloproteinases (MMPs) is an interesting approach to cancer therapy because of their role in the degradation of extracellular matrix (ECM), cell-cell, and cell-ECM interactions, modulating key events in cell migration and invasion. Herein, we show the cytotoxic and antimetastatic effects of the third fraction (FR3) from Bauhinia variegata candida (Bvc) stem on human cervical tumor cells (HeLa) and human peripheral blood mononuclear cells (PBMCs). FR3 inhibited MMP-2 and MMP-9 activity, indicated by zymogram. This fraction was cytotoxic to HeLa cells and noncytotoxic to PBMCs and decreased HeLa cell migration and invasion. FR3 is believed to stimulate extrinsic apoptosis together with necroptosis, assessed by western blotting. FR3 inhibited MMP-2 activity in the HeLa supernatant, differently from the control. The atomic mass spectrometry (ESI-MS) characterization suggested the presence of glucopyranosides, D-pinitol, fatty acids, and phenolic acid. These findings provide insight suggesting that FR3 contains components with potential tumor-selective cytotoxic action in addition to the action on the migration of tumor cells, which may be due to inhibition of MMPs. PMID:29770331

  17. The physiological basis of the migration continuum in brown trout (Salmo trutta).

    PubMed

    Boel, Mikkel; Aarestrup, Kim; Baktoft, Henrik; Larsen, Torben; Søndergaard Madsen, Steffen; Malte, Hans; Skov, Christian; Svendsen, Jon C; Koed, Anders

    2014-01-01

    Partial migration is common in many animal taxa; however, the physiological variation underpinning migration strategies remains poorly understood. Among salmonid fishes, brown trout (Salmo trutta) is one of the species that exhibits the most complex variation in sympatric migration strategies, expressed as a migration continuum, ranging from residency to anadromy. In looking at brown trout, our objective with this study was to test the hypothesis that variation in migration strategies is underpinned by physiological variation. Prior to migration, physiological samples were taken from fish in the stream and then released at the capture site. Using telemetry, we subsequently classified fish as resident, short-distance migrants (potamodromous), or long-distance migrants (potentially anadromous). Our results revealed that fish belonging to the resident strategy differed from those exhibiting any of the two migratory strategies. Gill Na,K-ATPase activity, condition factor, and indicators of nutritional status suggested that trout from the two migratory strategies were smoltified and energetically depleted before leaving the stream, compared to those in the resident strategy. The trout belonging to the two migratory strategies were generally similar; however, lower triacylglycerides levels in the short-distance migrants indicated that they were more lipid depleted prior to migration compared with the long-distance migrants. In the context of migration cost, we suggest that additional lipid depletion makes migrants more inclined to terminate migration at the first given feeding opportunity, whereas individuals that are less lipid depleted will migrate farther. Collectively, our data suggest that the energetic state of individual fish provides a possible mechanism underpinning the migration continuum in brown trout.

  18. Movement, migration, and smolting of Atlantic salmon (Salmo salar)

    USGS Publications Warehouse

    McCormick, S.D.; Hansen, Lonnie P.; Quinn, T.P.; Saunders, R.L.

    1998-01-01

    A variety of movements characterize the behavioral plasticity of Atlantic salmon (Salmo salar) in fresh water, including movements of fry from redds, establishment of feeding territories, spawning movements of sexually mature male parr, movement to and from winter habitat, and smolt migration in spring. Smolting is an adaptive specialization for downstream migration, seawater entry, and marine residence. While still in fresh water, smolts become silvery and streamlined, lose their positive rheotaxis and territoriality, and begin schooling. Physiological changes include increased salinity tolerance, olfactory sensitivity, metabolic rate, scope for growth, and altered hemoglobin and visual pigments. Through their impact on the neuroendocrine system, photoperiod and temperature regulate physiological changes, whereas temperature and water flow may initiate migration. Smolt survival is affected by a limited period of readiness (a physiological 'smolt window') and the timing of seawater entry with environmental conditions such as temperature, food, and predators (an ecological 'smolt window'). Smolt development is adversely affected by acidity, pollutants, and improper rearing conditions, and is often more sensitive than other life stages. Unfortunately, the migration corridor of smolts (mainstems of rivers and estuaries) are the most heavily impacted by pollution, dams, and other anthropogenic activities that may be directly lethal or increase mortality by delaying or inhibiting smolt migration.

  19. Essential oil of Pinus koraiensis inhibits cell proliferation and migration via inhibition of p21-activated kinase 1 pathway in HCT116 colorectal cancer cells.

    PubMed

    Cho, Sun-Mi; Lee, Eun-Ok; Kim, Sung-Hoon; Lee, Hyo-Jeong

    2014-07-30

    The essential oil of Pinus koraiensis (EOPK) is biologically active compound obtained from the leaves of P. koraiensis. The goal of this study was to investigate the anti-cancer mechanism of EOPK in HCT116 colorectal cancer cells. HCT116 cell proliferation was assessed by conducting crystal violet and BrdU assays. To assess the effects of EOPK on cell migration, we performed a wound-healing assay. Further, the contribution of PAK1 to EOPK-induced AKT and extracellular signal-regulated kinase (ERK) suppression was assessed by siRNA-mediated PAK1 knockdown. Changes to the expression and phosphorylation of PAK1 and its effectors were determined by western blotting, and changes to the actin cytoskeleton were determined by performing an immunofluorescence assay. EOPK significantly decreased HCT116 cell proliferation and migration, and induced G1 arrest without affecting normal cells. Additionally, EOPK suppressed the expression of PAK1, and decreased ERK and AKT phosphorylation in HCT116 cells. Finally, EOPK suppressed β-catenin, cyclin D1, and CDK4/6 expression. Our studies indicate that EOPK significantly reduced proliferation and migration of colorectal cancer cells. Furthermore, EOPK suppressed PAK1 expression in a dose-dependent manner, and this suppression of PAK1 led to inhibition of ERK, AKT, and β-catenin activities. Our findings suggest that EOPK exerts its anticancer activity via the inhibition of PAK1 expression, suggesting it may be a potent chemotherapeutic agent for colorectal cancer.

  20. 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.

  1. International migration and sustainable human development in eastern and southern Africa.

    PubMed

    Oucho, J O

    1995-01-01

    International migration in eastern and southern Africa (ESA) is rarely addressed in population and development policies or regional organizations, and regional organizations must in the articulation of sustainable shared development identify the role of international migration. Poor quality data on international migration hampers analysis. Sustainable, shared, and human development within the region are subregional issues. Permanent migration is characterized among ESA countries as increasing demographic ethnic pluralism that may result in redrawing of territorial boundaries and further population movement. Portuguese and Arab settlement and integration in eastern areas resulted in coexistence, while European immigration to South Africa resulted in racial segregation. Modern colonial settlement and the aftermath of political conflict resulted in independent countries after the 1960s and outmigration of nonAfrican groups. Much of the labor migration in ESA is unskilled workers moving to South African mining regions. Labor migration to Zimbabwe and Zambia declined after the 1960s. The formation of the Common Market for ESA and the potential merger with the Preferential Trade Area and South African Development Community is a key approach to integration of migration into regional cooperation and shared development. Refugee movements create the most problems. Prior to 1992 ESA countries accounted for 83.4% of refugees, particularly in Mozambique, Ethiopia, and Somalia. Some countries blame poor economic performance on the deluge of refugees. Illegal migration is currently detected because of the required work permits, but the adoption of the Common Market would obscure this phenomenon. Human development is affected most by migrations related to drought, labor migration to strong economic areas, and return migration. The Inter-Governmental Authority on Drought and Development needs to become more active and establish better policies on nomadic and refugee movements and

  2. Traffic-Sensitive Live Migration of Virtual Machines

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

    Deshpande, Umesh; Keahey, Kate

    2015-01-01

    In this paper we address the problem of network contention between the migration traffic and the VM application traffic for the live migration of co-located Virtual Machines (VMs). When VMs are migrated with pre-copy, they run at the source host during the migration. Therefore the VM applications with predominantly outbound traffic contend with the outgoing migration traffic at the source host. Similarly, during post-copy migration, the VMs run at the destination host. Therefore the VM applications with predominantly inbound traffic contend with the incoming migration traffic at the destination host. Such a contention increases the total migration time of themore » VMs and degrades the performance of VM application. Here, we propose traffic-sensitive live VM migration technique to reduce the contention of migration traffic with the VM application traffic. It uses a combination of pre-copy and post-copy techniques for the migration of the co-located VMs, instead of relying upon any single pre-determined technique for the migration of all the VMs. We base the selection of migration techniques on VMs' network traffic profiles so that the direction of migration traffic complements the direction of the most VM application traffic. We have implemented a prototype of traffic-sensitive migration on the KVM/QEMU platform. In the evaluation, we compare traffic-sensitive migration against the approaches that use only pre-copy or only post-copy for VM migration. We show that our approach minimizes the network contention for migration, thus reducing the total migration time and the application degradation.« less

  3. S-Fms signalobody enhances myeloid cell growth and migration.

    PubMed

    Kawahara, Masahiro; Hitomi, Azusa; Nagamune, Teruyuki

    2014-07-01

    Since receptor tyrosine kinases (RTKs) control various cell fates in many types of cells, mimicry of RTK functions is promising for artificial control of cell fates. We have previously developed single-chain Fv (scFv)/receptor chimeras named signalobodies that can mimic receptor signaling in response to a specific antigen. While the RTK-based signalobodies enabled us to control cell growth and migration, further extension of applicability in another cell type would underlie the impact of the RTK-based signalobodies. In this study, we applied the scFv-c-Fms (S-Fms) signalobody in a murine myeloid progenitor cell line, FDC-P1. S-Fms transduced a fluorescein-conjugated BSA (BSA-FL)-dependent growth signal and activated downstream signaling molecules including MEK, ERK, Akt, and STAT3, which are major constituents of Ras/MAPK, PI3K/Akt, and JAK/STAT signaling pathways. In addition, S-Fms transduced a migration signal as demonstrated by the transwell-based migration assay. Direct real-time observation of the cells further confirmed that FDC/S-Fms cells underwent directional cell migration toward a positive gradient of BSA-FL. These results demonstrated the utility of the S-Fms signalobody for controlling growth and migration of myeloid cells. Further extension of our approach includes economical large-scale production of practically relevant blood cells as well as artificial control of cell migration for tissue regeneration and immune response. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Population and labour force projections for 27 European countries, 2002-052: impact of international migration on population ageing: Projections de population et de population active pour 27 pays européens 2002-052: impact de la migration internationale sur le vieillissement de la population.

    PubMed

    Bijak, Jakub; Kupiszewska, Dorota; Kupiszewski, Marek; Saczuk, Katarzyna; Kicinger, Anna

    2007-03-01

    Population and labour force projections are made for 27 selected European countries for 2002-052, focussing on the impact of international migration on population and labour force dynamics. Starting from single scenarios for fertility, mortality and economic activity, three sets of assumptions are explored regarding migration flows, taking into account probable policy developments in Europe following the enlargement of the EU. In addition to age structures, various support ratio indicators are analysed. The results indicate that plausible immigration cannot offset the negative effects of population and labour force ageing.

  5. Migration of refugees and non-refugees to Amman, 1948-1977.

    PubMed

    Samha, M

    1980-12-01

    The migration to the city of Amman, Jordan during periods of war and peace over the past 3 decades was studied in an attempt to discover patterns of migration to Amman, to better understand their nature, to determine the constraints of migration, and to discover its motivation by resorting in part to classification and in part to analysis. The data were derived from a household survey of the amman population that covered 1750 randomly selected households and was conducted in 1977. The study was confined to compulsory migration resulting from the events in Palestine in 1948 and from the occupation of the West Bank of Jordan in 1965 and to voluntary internal migration arising from the lack of equal social and economic opportunities in different parts of the country. The 1977 survey, which covered 1355 households that had migrated to Amman, revealed that 703 were refugee households, representing the equivalent of 52% of all migrant households. The occupation of Palestine in 1948 led to a sharp influx of refugees to Amman with refugees making up 34.4% of the total number of migrants to Amman. In 1967 refugees from Gaza and the West Bank constituted 59.2% of the total number of migrants to Amman. Around 23% of all refugees are refugees for the 2nd time. Most of the refugees went directly to Amman with only a small minority (14%) moving to the city in stages, and most of these were 1948 refugees. The size and trend of migration to Amman was linked to a great extent, to the movement of refugees, which represented more than 1/2 of the migration to the city. The occupation of Palestine in 1948 led to the concentration of economic activities in the East Bank of Jordan. This meant migration east as far as the refugees from occupied Palestine and the migrants from the West Bank were concerned. As a consequence, Amman became the major attraction. The sample icluded 532 households that had migrated internally to Amman. It represented the voluntary migration to Amman from the

  6. Lipid rafts sense and direct electric field-induced migration

    PubMed Central

    Lin, Bo-jian; Tsao, Shun-hao; Chen, Alex; Hu, Shu-Kai; Chao, Ling

    2017-01-01

    Endogenous electric fields (EFs) are involved in developmental regulation and wound healing. Although the phenomenon is known for more than a century, it is not clear how cells perceive the external EF. Membrane proteins, responding to electrophoretic and electroosmotic forces, have long been proposed as the sensing molecules. However, specific charge modification of surface proteins did not change cell migration motility nor directionality in EFs. Moreover, symmetric alternating current (AC) EF directs cell migration in a frequency-dependent manner. Due to their charge and ability to coalesce, glycolipids are therefore the likely primary EF sensor driving polarization of membrane proteins and intracellular signaling. We demonstrate that detergent-resistant membrane nanodomains, also known as lipid rafts, are the primary response element in EF sensing. The clustering and activation of caveolin and signaling proteins further stabilize raft structure and feed-forward downstream signaling events, such as rho and PI3K activation. Theoretical modeling supports the experimental results and predicts AC frequency-dependent cell and raft migration. Our results establish a fundamental mechanism for cell electrosensing and provide a role in lipid raft mechanotransduction. PMID:28739955

  7. Platelets Inhibit Migration of Canine Osteosarcoma Cells.

    PubMed

    Bulla, S C; Badial, P R; Silva, R C; Lunsford, K; Bulla, C

    2017-01-01

    The interaction between platelets and tumour cells is important for tumour growth and metastasis. Thrombocytopenia or antiplatelet treatment negatively impact on cancer metastasis, demonstrating potentially important roles for platelets in tumour progression. To our knowledge, there is no information regarding the role of platelets in cancer progression in dogs. This study was designed to test whether canine platelets affected the migratory behaviour of three canine osteosarcoma cell lines and to give insights of molecular mechanisms. Intact platelets, platelet lysate and platelet releasate inhibited the migration of canine osteosarcoma cell lines. Addition of blood leucocytes to the platelet samples did not alter the inhibitory effect on migration. Platelet treatment also significantly downregulated the transcriptional levels of SNAI2 and TWIST1 genes. The interaction between canine platelets or molecules released during platelet activation and these tumour cell lines inhibits their migration, which suggests that canine platelets might antagonize metastasis of canine osteosarcoma. This effect is probably due to, at least in part, downregulation of genes related to epithelial-mesenchymal transition. Copyright © 2016. Published by Elsevier Ltd.

  8. Bioacoustic monitoring of nocturnal songbird migration in a southern great lakes ecosystem

    NASA Astrophysics Data System (ADS)

    Sanders, Claire Elizabeth

    Many species of birds produce short vocalizations during nocturnal migration. My thesis uses bioacoustic monitoring of these night flight calls to study bird migration through a southern Great Lakes ecosystem. I deployed recording devices around western Lake Erie during spring and fall migrations. Analysis of thousands of hours of recordings revealed that night flight calls accurately predicted both the magnitude of migration, as well as the timing of migrant passage, as assessed by banding. The first arrival dates for 48 species of migratory birds were significantly earlier on Pelee Island than on mainland Ontario in the spring. More flight calls were detected over Pelee Island than over mainland comparison sites. These results suggest that many birds cross Lake Erie in spring and fall, and that islands are important for migratory birds. This research provides insight into the use of acoustics for monitoring birds in active migration.

  9. Method of migrating seismic records

    DOEpatents

    Ober, Curtis C.; Romero, Louis A.; Ghiglia, Dennis C.

    2000-01-01

    The present invention provides a method of migrating seismic records that retains the information in the seismic records and allows migration with significant reductions in computing cost. The present invention comprises phase encoding seismic records and combining the encoded seismic records before migration. Phase encoding can minimize the effect of unwanted cross terms while still allowing significant reductions in the cost to migrate a number of seismic records.

  10. The OPEN Migration Platform Architecture

    NASA Astrophysics Data System (ADS)

    Martin, Miquel

    This chapter establishes a common understanding of the meaning of migration, and introduces the OPEN functionalities, which enable application migration. We start by discussing the various definitions of migration, before focusing on the OPEN take on the concept. The chapter then covers our proposed architecture , as well as the functionality required, both from the server and the client side (i.e. the applications) in order to enable application migration.

  11. Pre-migration persecution, post-migration stressors and resources, and post-migration mental health: A study of severely traumatized U.S. Arab immigrant women

    PubMed Central

    Norris, Anne E.; Aroian, Karen J.; Nickerson, David

    2015-01-01

    Background Competing theories exist regarding the importance of pre-migration trauma as compared to post-migration stressors and resources with respect to the risk to immigrant mental health. Objective To examine how type of pre-migration trauma, post-migration stressors, and post-migration resources differentially predict PTSD and MDD symptomatology in Arab immigrant women who have been exposed to pre-migration trauma. Design Descriptive; using multinomial logistic regression to explain membership in one of four groups: (a) PTSD only (n = 14); (b) major depressive disorder (MDD) (n = 162), (c) Co-Morbid PTSD-MDD (n = 148), (d) Subclinical Symptoms (n = 209). Results Post-immigration related stressors (as measured by the Demands of Immigration (DI)) had the strongest effect: Parameter estimates indicated that a unit increase in DI scores was associated with a nearly 17 fold increase in the likelihood of being in the Co-morbid relative to the Subclinical group, and a nearly 2.5 increase in the likelihood of being in the Co-Morbid relative to the MDD only group (p < .05). Social support, age and type of pre-migration trauma had smaller effects and only differentiated between Subclinical and Co-Morbid PTSD-MDD groups (p < .05). Conclusion Post-migration stressors exert substantive effects on immigrant mental health outcomes. Nursing interventions are needed to reduce immigration related stressors. Screening Arab immigrant women for depression and PTSD is important given high levels observed in this community based sample. PMID:21835819

  12. Migration of fallout radiocaesium in a grassland soil from 1986 to 2001. Part I: activity-depth profiles of (134)Cs and (137)Cs.

    PubMed

    Schimmack, W; Schultz, W

    2006-09-15

    The temporal changes of the vertical distribution of (134)Cs (deposited by the Chernobyl fallout in 1986) and (137)Cs (deposited by the Chernobyl and the global fallout) in the soil were investigated at an undisturbed Bavarian grassland site in Germany. At ten sampling dates between 1986 and 2001, the activity density of (134)Cs and (137)Cs was determined in various soil layers down to 80 cm depth. In 2001, the small-scale spatial variability of the radiocaesium activity was determined by sampling five plots within 10 m(2) (coefficient of variation about 20% for the upper soil layers). Between 1987 and 1990, substantial changes of the activity-depth profiles were observed. The percentage depth distributions of (134)Cs and (137)Cs were rather similar. The 50%-depth of the accumulated activity increased from 2.4 cm in 1988 to 5.3 cm in 2001 for (134)Cs and from 2.7 to 5.8 cm for (137)Cs. This indicates that at the study site the migration data of Chernobyl-derived (137)Cs can be estimated by those of total (137)Cs. In the second part of this study, the activity-depth profiles will be evaluated by the convection-dispersion model [Schimmack, W, Feria Márquez, F. Migration of fallout radiocaesium in a grassland soil from 1986 to 2001. Part II: Evaluation of the activity-depth profiles by transport models. Sci Total Environ 2006-this issue].

  13. The Great Migration.

    ERIC Educational Resources Information Center

    Trotter, Joe William, Jr.

    2002-01-01

    Describes the migration of African Americans in the United States and the reasons why African Americans migrated from the south. Focuses on issues, such as the effect of World War I, the opportunities offered in the north, and the emergence of a black industrial working class. (CMK)

  14. Enterolactone Suppresses Proliferation, Migration and Metastasis of MDA-MB-231 Breast Cancer Cells Through Inhibition of uPA Induced Plasmin Activation and MMPs-Mediated ECM Remodeling

    PubMed Central

    Mali, Aniket V; Joshi, Asavari A; Hegde, Mahabaleshwar V; Kadam, Shivajirao S

    2017-01-01

    Background: To enhance their own survival, tumor cells can manipulate their microenvironment through remodeling of the extra cellular matrix (ECM). The urokinase-type plasminogen activator (uPA) system catalyzes plasmin production which further mediates activation of matrix metalloproteinases (MMPs) and plays an important role in breast cancer invasion and metastasis through ECM remodeling. This provides a potential target for therapeutic intervention of breast cancer treatment. Enterolactone (EL) is derived from dietary flax lignans in the human body and is known to have anti-breast cancer activity. We here investigated molecular and cellular mechanisms of EL action on the uPA-plasmin-MMPs system. Methods: MTT and trypan blue dye exclusion assays, anchorage-dependent clonogenic assays and wound healing assays were carried out to study effects on cell proliferation and viability, clonogenicity and migration capacity, respectively. Real-time PCR was employed to study gene expression and gelatin zymography was used to assess MMP-2 and MMP-9 activities. All data were statistically analysed and presented as mean ± SEM values. Results: All the findings collectively demonstrated anticancer and antimetastatic potential of EL with antiproliferative, antimigratory and anticlonogenic cellular mechanisms. EL was found to exhibit multiple control of plasmin activation by down-regulating uPA expression and also up-regulating its natural inhibitor, PAI-1, at the mRNA level. Further, EL was found to down-regulate expression of MMP-2 and MMP-9 genes, and up-regulate TIMP-1 and TIMP-2; natural inhibitors of MMP-2 and MMP-9, respectively. This may be as a consequence of inhibition of plasmin activation, resulting in robust control over migration and invasion of breast cancer cells during metastasis. Conclusions: EL suppresses proliferation, migration and metastasis of MDA-MB-231 breast cancer cells by inhibiting induced ECM remodeling by the ‘uPA-plasmin-MMPs system’. PMID

  15. 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

  16. Lamellipodin and the Scar/WAVE complex cooperate to promote cell migration in vivo

    PubMed Central

    Law, Ah-Lai; Vehlow, Anne; Kotini, Maria; Dodgson, Lauren; Soong, Daniel; Theveneau, Eric; Bodo, Cristian; Taylor, Eleanor; Navarro, Christel; Perera, Upamali; Michael, Magdalene; Dunn, Graham A.; Bennett, Daimark; Mayor, Roberto

    2013-01-01

    Cell migration is essential for development, but its deregulation causes metastasis. The Scar/WAVE complex is absolutely required for lamellipodia and is a key effector in cell migration, but its regulation in vivo is enigmatic. Lamellipodin (Lpd) controls lamellipodium formation through an unknown mechanism. Here, we report that Lpd directly binds active Rac, which regulates a direct interaction between Lpd and the Scar/WAVE complex via Abi. Consequently, Lpd controls lamellipodium size, cell migration speed, and persistence via Scar/WAVE in vitro. Moreover, Lpd knockout mice display defective pigmentation because fewer migrating neural crest-derived melanoblasts reach their target during development. Consistently, Lpd regulates mesenchymal neural crest cell migration cell autonomously in Xenopus laevis via the Scar/WAVE complex. Further, Lpd’s Drosophila melanogaster orthologue Pico binds Scar, and both regulate collective epithelial border cell migration. Pico also controls directed cell protrusions of border cell clusters in a Scar-dependent manner. Taken together, Lpd is an essential, evolutionary conserved regulator of the Scar/WAVE complex during cell migration in vivo. PMID:24247431

  17. Guidance signalling regulates leading edge behaviour during collective cell migration of cardiac cells in Drosophila.

    PubMed

    Raza, Qanber; Jacobs, J Roger

    2016-11-15

    Collective cell migration is the coordinated movement of cells, which organize tissues during morphogenesis, repair and some cancers. The motile cell membrane of the advancing front in collective cell migration is termed the Leading Edge. The embryonic development of the vertebrate and Drosophila hearts are both characterized by the coordinated medial migration of a bilateral cluster of mesodermal cells. In Drosophila, the cardioblasts form cohesive bilateral rows that migrate collectively as a unit towards the dorsal midline to form the dorsal vessel. We have characterized the collective cell migration of cardioblasts as an in vivo quantitative model to study the behaviour of the Leading Edge. We investigated whether guidance signalling through Slit and Netrin pathways plays a role in cell migration during heart development. Through time-lapse imaging and quantitative assessment of migratory behaviour of the cardioblasts in loss-of-function mutants, we demonstrate that both Slit and Netrin mediated signals are autonomously and concomitantly required to maximize migration velocity, filopodial and lamellipodial activities. Additionally, we show that another Slit and Netrin receptor, Dscam1, the role of which during heart development was previously unknown, is required for both normal migration of cardioblasts and luminal expansion. Leading edge behaviour analysis revealed a dosage dependent genetic interaction between Slit and Netrin receptors suggesting that downstream signalling through these receptors converge on a common output that increases leading edge activity of the cardioblasts. Finally, we found that guidance signalling maintains the balance between epithelial and mesenchymal characteristics of the migrating cardioblasts. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Analytical procedure for the determination of Ethyl Lauroyl Arginate (LAE) to assess the kinetics and specific migration from a new antimicrobial active food packaging.

    PubMed

    Pezo, Davinson; Navascués, Beatriz; Salafranca, Jesús; Nerín, Cristina

    2012-10-01

    Ethyl Lauroyl Arginate (LAE) is a cationic tensoactive compound, soluble in water, with a wide activity spectrum against moulds and bacteria. LAE has been incorporated as antimicrobial agent into packaging materials for food contact and these materials require to comply with the specific migration criteria. In this paper, one analytical procedure has been developed and optimized for the analysis of LAE in food simulants after the migrations tests. It consists of the formation of an ionic pair between LAE and the inorganic complex Co(SCN)(4)(2-) in aqueous solution, followed by a liquid-liquid extraction in a suitable organic solvent and further UV-Vis absorbance measurement. In order to evaluate possible interferences, the ionic pair has been also analyzed by high performance liquid chromatography with UV-Vis detection. Both procedures provided similar analytical characteristics, with linear ranges from 1.10 to 25.00 mg kg(-1), linearity higher than 0.9886, limits of detection and quantification of 0.33 and 1.10 mg kg(-1), respectively, accuracy better than 1% as relative error and precision better than 3.6% expressed as RSD. Optimization of analytical techniques, thermal and chemical stability of LAE, as well as migration kinetics of LAE from experimental active packaging are reported and discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Consequences of Out-Migration for Land Use in Rural Ecuador

    PubMed Central

    Gray, Clark L.; Bilsborrow, Richard E.

    2013-01-01

    In rural Ecuador and elsewhere in Latin America, the departure of migrants and the receipt of migrant remittances have led to declining rural populations and increasing cash incomes. It is commonly assumed that these processes will lead to agricultural abandonment and the regrowth of native vegetation, thus undermining traditional livelihoods and providing a boon for biodiversity conservation. However, an increasing number of household-level studies have found mixed and complex effects of out-migration and remittances on agriculture. We advance this literature by using household survey data and satellite imagery from three study areas in rural Ecuador to investigate the effects of migration and remittances on agricultural land use. Multivariate methods are used to disaggregate the effects of migration and remittances, to account for other influences on land use and to correct for the potential endogeneity of migration and remittances. Contrary to common assumptions but consistent with previous studies, we find that migrant departure has a positive effect on agricultural activities that is offset by migrant remittances. These results suggest that rural out-migration alone is not likely to lead to a forest transition in the study areas. PMID:24187416

  20. Global migration and health: ecofeminist perspectives.

    PubMed

    McGuire, S

    1998-12-01

    Global migration is occurring at an unprecedented rate. The phenomenon of migration is complex and poorly understood by most people in countries who host immigrants. People migrate for numerous reasons related to social, economic, political, cultural, and physical environmental conditions formed by historical antecedents. Migrating people, especially vulnerable women and children, are exposed to numerous health hazards, a situation calling for a response from nursing. To respond effectively nursing needs knowledge development of global migration and health that includes the precursors to migration in addition to the postmigration experience where nurses encounter immigrants. Ecofeminist perspectives allowing for reflection on historical determinants and interlocking socioeconomic, political, and environmental conditions are used as a prism to examine global migration and health.

  1. Fisetin regulates astrocyte migration and proliferation in vitro

    PubMed Central

    Wang, Nan; Yao, Fang; Li, Ke; Zhang, Lanlan; Yin, Guo; Du, Mingjun; Wu, Bingyi

    2017-01-01

    Fisetin (3,3′,4′,7-tetrahydroxyflavone) is a plant flavonol found in fruits and vegetables that has been reported to inhibit migration and proliferation in several types of cancer. Reactive astrogliosis involves astrocyte migration and proliferation, and contributes to the formation of glial scars in central nervous system (CNS) disorders. However, the effect of fisetin on the migration and proliferation of astrocytes remains unclear. In this study, we found that fisetin inhibited astrocyte migration in a scratch-wound assay and diminished the phosphorylation of focal adhesion kinase (FAK; Tyr576/577 and paxillin (Tyr118). It also suppressed cell proliferation, as indicated by the decreased number of 5-ethynyl-2′-deoxyuridine (EdU)-positive cells, induced cell cycle arrest in the G1 phase, reduced the percentage of cells in the G2 and S phase (as measured by flow cytometry), and decreased cyclin D1 expression, but had no effect on apoptosis. Fisetin also decreased the phosphorylation levels of Akt and extracellular signal-regulated kinase (Erk)1/2, but had no effect on the phosphorylation of p38 mitogen-activated protein kinase (MAPK). These results indicate that fisetin inhibits aggressive cell phenotypes by suppressing cell migration and proliferation via the Akt/Erk signaling pathway. Fisetin may thus have potential for use as a therapeutic strategy targeting reactive astrocytes, which may lead to the inhibition of glial scar formation in vitro. PMID:28204814

  2. PLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration.

    PubMed

    Janjanam, Jagadeesh; Chandaka, Giri Kumar; Kotla, Sivareddy; Rao, Gadiparthi N

    2015-12-15

    Monocyte chemotactic protein 1 (MCP1) stimulates vascular smooth muscle cell (VSMC) migration in vascular wall remodeling. However, the mechanisms underlying MCP1-induced VSMC migration have not been understood. Here we identify the signaling pathway associated with MCP1-induced human aortic smooth muscle cell (HASMC) migration. MCP1, a G protein-coupled receptor agonist, activates phosphorylation of cortactin on S405 and S418 residues in a time-dependent manner, and inhibition of its phosphorylation attenuates MCP1-induced HASMC G-actin polymerization, F-actin stress fiber formation, and migration. Cortactin phosphorylation on S405/S418 is found to be critical for its interaction with WAVE2, a member of the WASP family of cytoskeletal regulatory proteins required for cell migration. In addition, the MCP1-induced cortactin phosphorylation is dependent on PLCβ3-mediated PKCδ activation, and siRNA-mediated down-regulation of either of these molecules prevents cortactin interaction with WAVE2, affecting G-actin polymerization, F-actin stress fiber formation, and HASMC migration. Upstream, MCP1 activates CCR2 and Gαq/11 in a time-dependent manner, and down-regulation of their levels attenuates MCP1-induced PLCβ3 and PKCδ activation, cortactin phosphorylation, cortactin-WAVE2 interaction, G-actin polymerization, F-actin stress fiber formation, and HASMC migration. Together these findings demonstrate that phosphorylation of cortactin on S405 and S418 residues is required for its interaction with WAVE2 in MCP1-induced cytoskeleton remodeling, facilitating HASMC migration. © 2015 Janjanam et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  3. CAPE suppresses migration and invasion of prostate cancer cells via activation of non-canonical Wnt signaling.

    PubMed

    Tseng, Jen-Chih; Lin, Ching-Yu; Su, Liang-Chen; Fu, Hsiao-Hui; Yang, Shiaw-Der; Chuu, Chih-Pin

    2016-06-21

    Prostate cancer (PCa) was the fifth most common cancer overall in the world. More than 80% of patients died from PCa developed bone metastases. Caffeic acid phenethyl ester (CAPE) is a main bioactive component of honeybee hive propolis. Transwell and wound healing assays demonstrated that CAPE treatment suppressed the migration and invasion of PC-3 and DU-145 PCa cells. Gelatin zymography and Western blotting indicated that CAPE treatment reduced the abundance and activity of MMP-9 and MMP-2. Analysis using Micro-Western Array (MWA), a high-throughput antibody-based proteomics platform with 264 antibodies detecting signaling proteins involved in important pathways indicated that CAPE treatment induced receptor tyrosine kinase-like orphan receptor 2 (ROR2) in non-canonical Wnt signaling pathway but suppressed abundance of β-catenin, NF-κB activity, PI3K-Akt signaling, and epithelial-mesenchymal transition (EMT). Overexpression or knockdown of ROR2 suppressed or enhanced cell migration of PC-3 cells, respectively. TCF-LEF promoter binding assay revealed that CAPE treatment reduced canonical Wnt signaling. Intraperitoneal injection of CAPE reduced the metastasis of PC-3 xenografts in tail vein injection nude mice model. Immunohistochemical staining demonstrated that CAPE treatment increased abundance of ROR2 and Wnt5a but decreased protein expression of Ki67, Frizzle 4, NF-κB p65, MMP-9, Snail, β-catenin, and phosphorylation of IκBα. Clinical evidences suggested that genes affected by CAPE treatment (CTNNB1, RELA, FZD5, DVL3, MAPK9, SNAl1, ROR2, SMAD4, NFKBIA, DUSP6, and PLCB3) correlate with the aggressiveness of PCa. Our study suggested that CAPE may be a potential therapeutic agent for patients with advanced PCa.

  4. Intracellular pH gradients in migrating cells.

    PubMed

    Martin, Christine; Pedersen, Stine F; Schwab, Albrecht; Stock, Christian

    2011-03-01

    Cell polarization along the axis of movement is required for migration. The localization of proteins and regulators of the migratory machinery to either the cell front or its rear results in a spatial asymmetry enabling cells to simultaneously coordinate cell protrusion and retraction. Protons might function as such unevenly distributed regulators as they modulate the interaction of focal adhesion proteins and components of the cytoskeleton in vitro. However, an intracellular pH (pH(i)) gradient reflecting a spatial asymmetry of protons has not been shown so far. One major regulator of pH(i), the Na(+)/H(+) exchanger NHE1, is essential for cell migration and accumulates at the cell front. Here, we test the hypothesis that the uneven distribution of NHE1 activity creates a pH(i) gradient in migrating cells. Using the pH-sensitive fluorescent dye BCECF, pH(i) was measured in five cell lines (MV3, B16V, NIH3T3, MDCK-F1, EA.hy926) along the axis of movement. Differences in pH(i) between the front and the rear end (ΔpH(i) front-rear) were present in all cell lines, and inhibition of NHE1 either with HOE642 or by absence of extracellular Na(+) caused the pH(i) gradient to flatten or disappear. In conclusion, pH(i) gradients established by NHE1 activity exist along the axis of movement.

  5. [International migration in the Americas: intraregional migration grows].

    PubMed

    Zlotnik, H

    1992-01-01

    The principal destinations for intraregional migrants in South America in recent decades have been Argentina, Brazil, and Venezuela, while in North America the U.S. has exerted a growing attraction since 1965. Intraregional migration in Latin America has been irregular and difficult to quantify, and reliable statistics on migratory flows are nonexistent. Census data indicate that most migration to Argentina and Brazil occurred before 1960, while most migration to Venezuela occurred during the 1970s. Between 1960 and 1980, the proportion of migrants from other Latin American countries showed a tendency to increase, despite decreases in the overall level of immigration. The effect of the economic crisis of the 1980s on immigration from Latin American countries will become more apparent as census data for the 1990s become available. Selectivity according to country of origin is an important characteristic of intraregional migration in South America. The U.S. has, however, been the principal destination of Latin American migrants for the past three decades. Between 1965 and 1991 the U.S. granted resident status to more than 7.4 million persons of Latin American and Caribbean origin, and they constituted 47% of immigrants during those years. The great majority of the Latin American immigrants in the U.S. are Mexican. The 3.5 million Mexicans admitted to the U.S. as immigrants between 1965 and 1991 accounted for 22% of all immigrants during this period.

  6. Tissue Factor-Factor VIIa Complex Triggers Protease Activated Receptor 2-Dependent Growth Factor Release and Migration in Ovarian Cancer

    PubMed Central

    Chanakira, Alice; Westmark, Pamela R.; Ong, Irene M.; Sheehan, John P.

    2017-01-01

    Objective Enhanced tissue factor (TF) expression in epithelial ovarian cancer (EOC) is associated with aggressive disease. Our objective was to evaluate the role of the TF-factor VIIa-protease-activated receptor-2 (PAR-2) pathway in human EOC. Methods TCGA RNAseq data from EOC databases were analyzed for PAR expression. Cell and microparticle (MP) associated TF protein expression (Western blot) and MP-associated coagulant activity were determined in human EOC (SKOV-3, OVCAR-3 and CaOV-3) and control cell lines. PAR-1 and PAR-2 protein expression were similarly examined. The PAR dependence of VEGF-A release (ELISA) and chemotactic migration in response to FVIIa and cellular proliferation in response to thrombin was evaluated with small molecule antagonists. Results Relative mRNA expression consistently demonstrated PAR-2>PAR-1≫PAR-3/4 in multiple EOC datasets. Human EOC cell line lysates confirmed expression of TF, PAR-1 and PAR-2 proteins. MPs isolated from EOC cell lines demonstrated markedly enhanced (4–10 fold) TF coagulant activity relative to control cell lines. FVIIa induced a dose-dependent increase in VEGF-A release (2.5-3 fold) from EOC cell lines that was abrogated by the PAR-2 antagonist ENMD-1068. FVIIa treatment of CaOV-3 and OVCAR-3 cells resulted in increased chemotactic migration that was abolished by ENMD-1068. Thrombin induced dose-dependent EOC cell line proliferation was completely reversed by the PAR-1 antagonist vorapaxar. Small molecule antagonists had no effect on these phenotypes without protease present. Conclusions Enhanced activity of the TF-FVIIa-PAR-2 axis may contribute to the EOC progression via PAR-2 dependent signaling that supports an angiogenic and invasive phenotype and local thrombin generation supporting PAR-1 dependent proliferation. PMID:28148395

  7. Beta-Adrenoceptor Activation Reduces Both Dermal Microvascular Endothelial Cell Migration via a cAMP-Dependent Mechanism and Wound Angiogenesis.

    PubMed

    O'Leary, Andrew P; Fox, James M; Pullar, Christine E

    2015-02-01

    Angiogenesis is an essential process during tissue regeneration; however, the amount of angiogenesis directly correlates with the level of wound scarring. Angiogenesis is lower in scar-free foetal wounds while angiogenesis is raised and abnormal in pathophysiological scarring such as hypertrophic scars and keloids. Delineating the mechanisms that modulate angiogenesis and could reduce scarring would be clinically useful. Beta-adrenoceptors (β-AR) are G protein-coupled receptors (GPCRs) expressed on all skin cell-types. They play a role in wound repair but their specific role in angiogenesis is unknown. In this study, a range of in vitro assays (single cell migration, scratch wound healing, ELISAs for angiogenic growth factors and tubule formation) were performed with human dermal microvascular endothelial cells (HDMEC) to investigate and dissect mechanisms underpinning β-AR-mediated modulation of angiogenesis in chick chorioallantoic membranes (CAM) and murine excisional skin wounds. β-AR activation reduced HDMEC migration via cyclic adenosine monophosphate (cAMP)-dependent and protein kinase A (PKA)-independent mechanisms as demonstrated through use of an EPAC agonist that auto-inhibited the cAMP-mediated β-AR transduced reduction in HDMEC motility; a PKA inhibitor was, conversely, ineffective. ELISA studies demonstrated that β-AR activation reduced pro-angiogenic growth factor secretion from HDMECs (fibroblast growth factor 2) and keratinocytes (vascular endothelial growth factor A) revealing possible β-AR-mediated autocrine and paracrine anti-angiogenic mechanisms. In more complex environments, β-AR activation delayed HDMEC tubule formation and decreased angiogenesis both in the CAM assay and in murine excisional skin wounds in vivo. β-AR activation reduced HDMEC function in vitro and angiogenesis in vivo; therefore, β-AR agonists could be promising anti-angiogenic modulators in skin. © 2014 The Authors. Journal of Cellular Physiology Published by

  8. ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site.

    PubMed

    Abbruzzese, Genevieve; Becker, Sarah F; Kashef, Jubin; Alfandari, Dominique

    2016-07-15

    The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell-cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo. Copyright © 2015. Published by Elsevier Inc.

  9. ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site

    PubMed Central

    Kashef, Jubin; Alfandari, Dominique

    2015-01-01

    The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell–cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo. PMID:26206614

  10. 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.

  11. KCa3.1 Modulates Neuroblast Migration Along the Rostral Migratory Stream (RMS) In Vivo

    PubMed Central

    Turner, Kathryn L.; Sontheimer, Harald

    2014-01-01

    From the subventricular zone (SVZ), neuronal precursor cells (NPCs), called neuroblasts, migrate through the rostral migratory stream (RMS) to become interneurons in the olfactory bulb (OB). Ion channels regulate neuronal migration during development, yet their role in migration through the adult RMS is unknown. To address this question, we utilized Nestin-CreERT2/R26R-YFP mice to fluorescently label neuroblasts in the adult. Patch-clamp recordings from neuroblasts reveal K+ currents that are sensitive to intracellular Ca2+ levels and blocked by clotrimazole and TRAM-34, inhibitors of intermediate conductance Ca2+-activated K+ (KCa3.1) channels. Immunolabeling and electrophysiology show KCa3.1 expression restricted to neuroblasts in the SVZ and RMS, but absent in OB neurons. Time-lapse confocal microscopy in situ showed inhibiting KCa3.1 prolonged the stationary phase of neuroblasts' saltatory migration, reducing migration speed by over 50%. Both migration and KCa3.1 currents could also be inhibited by blocking Ca2+ influx via transient receptor potential (TRP) channels, which, together with positive immunostaining for transient receptor potential canonical 1 (TRPC1), suggest that TRP channels are an important Ca2+ source modulating KCa3.1 activity. Finally, injecting TRAM-34 into Nestin-CreERT2/R26R-YFP mice significantly reduced the number of neuroblasts that reached the OB, suggesting an important role for KCa3.1 in vivo. These studies describe a previously unrecognized protein in migration of adult NPCs. PMID:23585521

  12. Singing behavior of fin whales in the Davis Strait with implications for mating, migration and foraging.

    PubMed

    Simon, Malene; Stafford, Kathleen M; Beedholm, Kristian; Lee, Craig M; Madsen, Peter T

    2010-11-01

    Most baleen whales undertake migrations between low-latitude breeding grounds and high-latitude feeding grounds. Though little is known about the timing of their migration from the Arctic, fin whales are assumed to undertake a similar migratory pattern. To address questions about habitat use and migrations, the acoustic activity of fin whales in Davis Strait, between Greenland and Canada, was monitored continuously for two years using three bottom-moored acoustic recorders. The acoustic power in the fin whale call frequencies peaked in November-December, showing that fin whales are present in Davis Strait much later in the year than previously expected. The closely timed peaks in song activity and conception time imply that not all fin whales migrate south to mate, but rather start mating at high latitudes rather than or before migrating. Singing activity was strongly linked to daylight hours, suggesting that fin whales might feed during the few daylight hours of the late fall and early Arctic winter. A negative correlation between the advancing sea ice front and power in fin whale frequencies indicates that future changes in sea ice conditions from global warming might change the distribution and migratory patterns of fin whales near the poles.

  13. Erk regulation of actin capping and bundling by Eps8 promotes cortex tension and leader bleb-based migration

    PubMed Central

    Logue, Jeremy S; Cartagena-Rivera, Alexander X; Baird, Michelle A; Davidson, Michael W; Chadwick, Richard S; Waterman, Clare M

    2015-01-01

    Within the confines of tissues, cancer cells can use blebs to migrate. Eps8 is an actin bundling and capping protein whose capping activity is inhibited by Erk, a key MAP kinase that is activated by oncogenic signaling. We tested the hypothesis that Eps8 acts as an Erk effector to modulate actin cortex mechanics and thereby mediate bleb-based migration of cancer cells. Cells confined in a non-adhesive environment migrate in the direction of a very large ‘leader bleb.’ Eps8 bundling activity promotes cortex tension and intracellular pressure to drive leader bleb formation. Eps8 capping and bundling activities act antagonistically to organize actin within leader blebs, and Erk mediates this effect. An Erk biosensor reveals concentrated kinase activity within leader blebs. Bleb contents are trapped by the narrow neck that separates the leader bleb from the cell body. Thus, Erk activity promotes actin bundling by Eps8 to enhance cortex tension and drive the bleb-based migration of cancer cells under non-adhesive confinement. DOI: http://dx.doi.org/10.7554/eLife.08314.001 PMID:26163656

  14. Arroyo channel head evolution in a flash-flood-dominated discontinuous ephemeral stream system

    USGS Publications Warehouse

    DeLong, Stephen B.; Johnson, Joel P.L.; Whipple, Kelin X.

    2014-01-01

    We study whether arroyo channel head retreat in dryland discontinuous ephemeral streams is driven by surface runoff, seepage erosion, mass wasting, or some combination of these hydrogeomorphic processes. We monitored precipitation, overland flow, soil moisture, and headcut migration over several seasonal cycles at two adjacent rangeland channel heads in southern Arizona. Erosion occurred by headward retreat of vertical to overhanging faces, driven dominantly by surface runoff. No evidence exists for erosion caused by shallow-groundwater–related processes, even though similar theater-headed morphologies are sometimes attributed to seepage erosion by emerging groundwater. At our field site, vertical variation in soil shear strength influenced the persistence of the characteristic theater-head form. The dominant processes of erosion included removal of grains and soil aggregates during even very shallow (1–3 cm) overland flow events by runoff on vertical to overhanging channel headwalls, plunge-pool erosion during higher-discharge runoff events, immediate postrunoff wet mass wasting, and minor intra-event dry mass wasting on soil tension fractures developing subparallel to the headwall. Multiple stepwise linear regression indicates that the migration rate is most strongly correlated with flow duration and total precipitation and is poorly correlated with peak flow depth or time-integrated flow depth. The studied channel heads migrated upslope with a self-similar morphologic form under a wide range of hydrological conditions, and the most powerful flash floods were not always responsible for the largest changes in landscape form in this environment. 

  15. HMEC-1 adopt the mixed amoeboid-mesenchymal migration type during EndMT.

    PubMed

    Kryczka, Jakub; Przygodzka, Patrycja; Bogusz, Helena; Boncela, Joanna

    2017-06-01

    The contribution of endothelial cells to scar and fibrotic tissue formation is undisputedly connected to their ability to undergo the endothelial-to-mesenchymal transition (EndMT) towards fibroblast phenotype-resembling cells. The migration model of fibroblasts and fibroblast-resembling cells is still not fully understood. It may be either a Rho/ROCK-independent, an integrin- and MMP-correlated ECM degradation-dependent, a mesenchymal model or Rho/ROCK-dependent, integrin adhesion- and MMP activity-independent, an amoeboid model. Here, we hypothesized that microvascular endothelial cells (HMEC-1) undergoing EndMT adopt an intermediate state of drifting migration model between the mesenchymal and amoeboid protrusive types in the early stages of fibrosis. We characterized the response of HMEC-1 to TGF-β2, a well-known mediator of EndMT within the microvasculature. We observed that TGF-β2 induces up to an intermediate mesenchymal phenotype in HMEC-1. In parallel, MMP-2 is upregulated and is responsible for most proteolytic activity. Interestingly, the migration of HMEC-1 undergoing EndMT is dependent on both ECM degradation and invadosome formation associated with MMP-2 proteolytic activity and Rho/ROCK cytoskeleton contraction. In conclusion, the transition from mesenchymal towards amoeboid movement highlights a molecular plasticity mechanism in endothelial cell migration in skin fibrosis. Copyright © 2017 Elsevier GmbH. All rights reserved.

  16. Statistical characteristics of dynamics for population migration driven by the economic interests

    NASA Astrophysics Data System (ADS)

    Huo, Jie; Wang, Xu-Ming; Zhao, Ning; Hao, Rui

    2016-06-01

    Population migration typically occurs under some constraints, which can deeply affect the structure of a society and some other related aspects. Therefore, it is critical to investigate the characteristics of population migration. Data from the China Statistical Yearbook indicate that the regional gross domestic product per capita relates to the population size via a linear or power-law relation. In addition, the distribution of population migration sizes or relative migration strength introduced here is dominated by a shifted power-law relation. To reveal the mechanism that creates the aforementioned distributions, a dynamic model is proposed based on the population migration rule that migration is facilitated by higher financial gains and abated by fewer employment opportunities at the destination, considering the migration cost as a function of the migration distance. The calculated results indicate that the distribution of the relative migration strength is governed by a shifted power-law relation, and that the distribution of migration distances is dominated by a truncated power-law relation. These results suggest the use of a power-law to fit a distribution may be not always suitable. Additionally, from the modeling framework, one can infer that it is the randomness and determinacy that jointly create the scaling characteristics of the distributions. The calculation also demonstrates that the network formed by active nodes, representing the immigration and emigration regions, usually evolves from an ordered state with a non-uniform structure to a disordered state with a uniform structure, which is evidenced by the increasing structural entropy.

  17. 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

  18. RSA migration of total knee replacements.

    PubMed

    Pijls, Bart G; Plevier, José W M; Nelissen, Rob G H H

    2018-06-01

    Purpose - We performed a systematic review and meta-analyses to evaluate the early and long-term migration patterns of tibial components of TKR of all known RSA studies. Methods - Migration pattern was defined as at least 2 postoperative RSA follow-up moments. Maximal total point motion (MTPM) at 6 weeks, 3 months, 6 months, 1 year, 2 years, 5 years, and 10 years were considered. Results - The literature search yielded 1,167 hits of which 53 studies were included, comprising 111 study groups and 2,470 knees. The majority of the early migration occurred in the first 6 months postoperatively followed by a period of stability, i.e., no or very little migration. Cemented and uncemented tibial components had different migration patterns. For cemented tibial components there was no difference in migration between all-poly and metal-backed components, between mobile bearing and fixed bearing, between cruciate retaining and posterior stabilized. Furthermore, no difference existed between TKR measured with model-based RSA or marker-based RSA methods. For uncemented TKR there was some variation in migration with the highest migration for uncoated TKR. Interpretation - The results from this meta-analysis on RSA migration of TKR are in line with both the survival analyses results from joint registries of these TKRs as well as revision rates results from meta-analyses, thus providing further proof for the association between early migration and late revision for loosening. The pooled migration patterns can be used both as benchmarks and for defining migration thresholds for future evaluation of new TKR.

  19. Focal Adhesion-Independent Cell Migration.

    PubMed

    Paluch, Ewa K; Aspalter, Irene M; Sixt, Michael

    2016-10-06

    Cell migration is central to a multitude of physiological processes, including embryonic development, immune surveillance, and wound healing, and deregulated migration is key to cancer dissemination. Decades of investigations have uncovered many of the molecular and physical mechanisms underlying cell migration. Together with protrusion extension and cell body retraction, adhesion to the substrate via specific focal adhesion points has long been considered an essential step in cell migration. Although this is true for cells moving on two-dimensional substrates, recent studies have demonstrated that focal adhesions are not required for cells moving in three dimensions, in which confinement is sufficient to maintain a cell in contact with its substrate. Here, we review the investigations that have led to challenging the requirement of specific adhesions for migration, discuss the physical mechanisms proposed for cell body translocation during focal adhesion-independent migration, and highlight the remaining open questions for the future.

  20. Nuclear Migration During Retinal Development

    PubMed Central

    Baye, Lisa M.; Link, Brian A.

    2009-01-01

    In this review we focus on the mechanisms, regulation, and cellular consequences of nuclear migration in the developing retina. In the nervous system, nuclear migration is prominent during both proliferative and post-mitotic phases of development. Interkinetic nuclear migration is the process where the nucleus oscillates from the apical to basal surfaces in proliferative neuroepithelia. Proliferative nuclear movement occurs in step with the cell cycle, with M-phase being confined to the apical surface and G1-, S-, and G2-phases occurring at more basal locations. Later, following cell cycle exit, some neuron precursors migrate by nuclear translocation. In this mode of cellular migration, nuclear movement is the driving force for motility. Following discussion of the key components and important regulators for each of these processes, we present an emerging model where interkinetic nuclear migration functions to distinguish cell fates among retinal neuroepithelia. PMID:17560964

  1. 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

  2. Dietary spices protect against hydrogen peroxide-induced DNA damage and inhibit nicotine-induced cancer cell migration.

    PubMed

    Jayakumar, R; Kanthimathi, M S

    2012-10-01

    Spices are rich sources of antioxidants due to the presence of phenols and flavonoids. In this study, the DNA protecting activity and inhibition of nicotine-induced cancer cell migration of 9 spices were analysed. Murine fibroblasts (3T3-L1) and human breast cancer (MCF-7) cells were pre-treated with spice extracts and then exposed to H₂O₂ and nicotine. The comet assay was used to analyse the DNA damage. Among the 9 spices, ginger, at 50 μg/ml protected against 68% of DNA damage in 3T3-L1 cells. Caraway, cumin and fennel showed statistically significant (p<0.05) DNA protecting activity. Treatment of MCF-7 cells with nicotine induced cell migration, whereas pre-treatment with spices reduced this migration. Pepper, long pepper and ginger exhibited a high rate of inhibition of cell migration. The results of this study prove that spices protect DNA and inhibit cancer cell migration. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Modular control of endothelial sheet migration

    PubMed Central

    Vitorino, Philip; Meyer, Tobias

    2008-01-01

    Growth factor-induced migration of endothelial cell monolayers enables embryonic development, wound healing, and angiogenesis. Although collective migration is widespread and therapeutically relevant, the underlying mechanism by which cell monolayers respond to growth factor, sense directional signals, induce motility, and coordinate individual cell movements is only partially understood. Here we used RNAi to identify 100 regulatory proteins that enhance or suppress endothelial sheet migration into cell-free space. We measured multiple live-cell migration parameters for all siRNA perturbations and found that each targeted protein primarily regulates one of four functional outputs: cell motility, directed migration, cell–cell coordination, or cell density. We demonstrate that cell motility regulators drive random, growth factor-independent motility in the presence or absence of open space. In contrast, directed migration regulators selectively transduce growth factor signals to direct cells along the monolayer boundary toward open space. Lastly, we found that regulators of cell–cell coordination are growth factor-independent and reorient randomly migrating cells inside the sheet when boundary cells begin to migrate. Thus, cells transition from random to collective migration through a modular control system, whereby growth factor signals convert boundary cells into pioneers, while cells inside the monolayer reorient and follow pioneers through growth factor-independent migration and cell–cell coordination. PMID:19056882

  4. Quantitative impedimetric monitoring of cell migration under the stimulation of cytokine or anti-cancer drug in a microfluidic chip

    PubMed Central

    Xiao, Xia; Lei, Kin Fong; Huang, Chia-Hao

    2015-01-01

    Cell migration is a cellular response and results in various biological processes such as cancer metastasis, that is, the primary cause of death for cancer patients. Quantitative investigation of the correlation between cell migration and extracellular stimulation is essential for developing effective therapeutic strategies for controlling invasive cancer cells. The conventional method to determine cell migration rate based on comparison of successive images may not be an objective approach. In this work, a microfluidic chip embedded with measurement electrodes has been developed to quantitatively monitor the cell migration activity based on the impedimetric measurement technique. A no-damage wound was constructed by microfluidic phenomenon and cell migration activity under the stimulation of cytokine and an anti-cancer drug, i.e., interleukin-6 and doxorubicin, were, respectively, investigated. Impedance measurement was concurrently performed during the cell migration process. The impedance change was directly correlated to the cell migration activity; therefore, the migration rate could be calculated. In addition, a good match was found between impedance measurement and conventional imaging analysis. But the impedimetric measurement technique provides an objective and quantitative measurement. Based on our technique, cell migration rates were calculated to be 8.5, 19.1, and 34.9 μm/h under the stimulation of cytokine at concentrations of 0 (control), 5, and 10 ng/ml. This technique has high potential to be developed into a powerful analytical platform for cancer research. PMID:26180566

  5. Carbon Ion Irradiation Inhibits Glioma Cell Migration Through Downregulation of Integrin Expression

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

    Rieken, Stefan, E-mail: Stefan.Rieken@med.uni-heidelberg.de; Habermehl, Daniel; Wuerth, Lena

    2012-05-01

    Purpose: To investigate the effect of carbon ion irradiation on glioma cell migration. Methods and Materials: U87 and Ln229 glioma cells were irradiated with photons and carbon ions. Migration was analyzed 24 h after irradiation. Fluorescence-activated cell sorting analysis was performed in order to quantify surface expression of integrins. Results: Single photon doses of 2 Gy and 10 Gy enhanced {alpha}{sub {nu}}{beta}{sub 3} and {alpha}{sub {nu}}{beta}{sub 5} integrin expression and caused tumor cell hypermigration on both vitronectin (Vn) and fibronectin (Fn). Compared to integrin expression in unirradiated cells, carbon ion irradiation caused decreased integrin expression and inhibited cell migration onmore » both Vn and Fn. Conclusion: Photon radiotherapy (RT) enhances the risk of tumor cell migration and subsequently promotes locoregional spread via photon induction of integrin expression. In contrast to photon RT, carbon ion RT causes decreased integrin expression and suppresses glioma cell migration on both Vn and Fn, thus promising improved local control.« less

  6. Initiation of migration and movement rates of Atlantic salmon smolts in fresh water

    USGS Publications Warehouse

    Stich, Daniel S.; Kinnison, Michael T.; Kocik, John F.; Zydlewski, Joseph D.

    2015-01-01

    Timing of ocean entry is critical for marine survival of both hatchery and wild Atlantic salmon (Salmo salar) smolts. Management practices and barriers to migration such as dams may constrain timing of smolt migrations resulting in suboptimal performance at saltwater entry. We modeled influences of stocking location, smolt development, and environmental conditions on (i) initiation of migration by hatchery-reared smolts and (ii) movement rate of hatchery- and wild-reared Atlantic salmon smolts in the Penobscot River, Maine, USA, from 2005 through 2014 using acoustic telemetry data. We also compared movement rates in free-flowing reaches with rates in reaches with hydropower dams and head ponds. We compared movement rates before and after (1) removal of two mainstem dams and (2) construction of new powerhouses. Initiation of movement by hatchery fish was influenced by smolt development, stocking location, and environmental conditions. Smolts with the greatest gill Na+, K+-ATPase (NKA) activity initiated migration 24 h sooner than fish with the lowest gill NKA activity. Fish with the greatest cumulative thermal experience initiated migration 5 days earlier than those with lowest cumulative thermal experience. Smolts released furthest from the ocean initiated migration earlier than those released downstream, but movement rate increased by fivefold closer to the ocean, indicating behavioral trade-offs between initiation and movement rate. Dams had a strong effect on movement rate. Movement rate increased from 2.8 to 5.4 km·h−1 in reaches where dams were removed, but decreased from 2.1 to 0.1 km·h−1 in reaches where new powerhouses were constructed. Movement rate varied throughout the migratory period and was inversely related to temperature. Fish moved slower at extreme high or low discharge. Responses in fish movement rates to dam removal indicate the potential scope of recovery for these activities.

  7. 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.

  8. F-spondin inhibits migration and differentiation of osteoclastic precursors.

    PubMed

    Oka, Hiroko; Mori, Maya; Kihara, Hisae

    2011-12-01

    Clinically, severe cemental resorption is a rare consequence of periodontitis, although alveolar bone resorption by osteoclasts is one of the main pathologic changes. F-spondin is a secreted neuronal glycoprotein that localizes to the cementum. F-spondin is among the cementum-specific factors in periodontal tissue that have been reported. However, the effects of F-spondin on osteoclastogenesis have not yet been established. We examined the effects of F-spondin on stages of osteoclastogenesis, migration, and differentiation in a mouse osteoclastic precursor model, RAW 264 cells. RAW 264 cells were treated with recombinant F-spondin. Macrophage colony stimulating factor (M-CSF)-induced cell migration was examined by migration assay performed with cell culture inserts. Osteoclastic differentiation was measured by counting tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. In a transmigration assay, F-spondin significantly downregulated M-CSF-induced cell migration. Further, F-spondin significantly reduced the number of receptor activator of nuclear factor-kappa B ligand-induced TRAP-positive multinucleated cells. The receptor-associated protein, an antagonist of the low-density lipoprotein (LDL) receptor family, blocked the effects of F-spondin on M-CSF-induced migration. The suppressive effect of F-spondin on M-CSF-induced cell migration was blocked by knockdown of LDL receptor-related protein 8 (LRP8), a member of the LDL receptor family. Our findings suggest that F-spondin downregulates recruitment to the root side of periodontal tissue via LRP8 and inhibits differentiation of osteoclastic precursors. It is suggested that F-spondin is essential to protect the root surface from resorption.

  9. Bromelain treatment decreases neutrophil migration to sites of inflammation.

    PubMed

    Fitzhugh, David J; Shan, Siqing; Dewhirst, Mark W; Hale, Laura P

    2008-07-01

    Bromelain, a mixture of proteases derived from pineapple stem, has been reported to have therapeutic benefits in a variety of inflammatory diseases, including murine inflammatory bowel disease. The purpose of this work was to understand potential mechanisms for this anti-inflammatory activity. Exposure to bromelain in vitro has been shown to remove a number of cell surface molecules that are vital to leukocyte trafficking, including CD128a/CXCR1 and CD128b/CXCR2 that serve as receptors for the neutrophil chemoattractant IL-8 and its murine homologues. We hypothesized that specific proteolytic removal of CD128 molecules by bromelain would inhibit neutrophil migration to IL-8 and thus decrease acute responses to inflammatory stimuli. Using an in vitro chemotaxis assay, we demonstrated a 40% reduction in migration of bromelain- vs. sham-treated human neutrophils in response to rhIL-8. Migration to the bacterial peptide analog fMLP was unaffected, indicating that bromelain does not induce a global defect in leukocyte migration. In vivo bromelain treatment generated a 50-85% reduction in neutrophil migration in 3 different murine models of leukocyte migration into the inflamed peritoneal cavity. Intravital microscopy demonstrated that although in vivo bromelain treatment transiently decreased leukocyte rolling, its primary long-term effect was abrogation of firm adhesion of leukocytes to blood vessels at the site of inflammation. These changes in adhesion were correlated with rapid re-expression of the bromelain-sensitive CD62L/L-selectin molecules that mediate rolling following in vivo bromelain treatment and minimal re-expression of CD128 over the time period studied. Taken together, these studies demonstrate that bromelain can effectively decrease neutrophil migration to sites of acute inflammation and support the specific removal of the CD128 chemokine receptor as a potential mechanism of action.

  10. Bromelain Treatment Decreases Neutrophil Migration to Sites of Inflammation

    PubMed Central

    Fitzhugh, David J.; Shan, Siqing; Dewhirst, Mark W.; Hale, Laura P.

    2008-01-01

    Bromelain, a mixture of proteases derived from pineapple stem, has been reported to have therapeutic benefits in a variety of inflammatory diseases, including murine inflammatory bowel disease. The purpose of this work was to understand potential mechanisms for this anti-inflammatory activity. Exposure to bromelain in vitro has been shown to remove a number of cell surface molecules that are vital to leukocyte trafficking, including CD128a/CXCR1 and CD128b/CXCR2 that serve as receptors for the neutrophil chemoattractant IL-8 and its murine homologues. We hypothesized that specific proteolytic removal of CD128 molecules by bromelain would inhibit neutrophil migration to IL-8 and thus decrease acute responses to inflammatory stimuli. Using an in vitro chemotaxis assay, we demonstrated a 40% reduction in migration of bromelain- vs. sham-treated human neutrophils in response to rhIL-8. Migration to the bacterial peptide analog fMLP was unaffected, indicating that bromelain does not induce a global defect in leukocyte migration. In vivo bromelain treatment generated a 50 – 85% reduction in neutrophil migration in 3 different murine models of leukocyte migration into the inflamed peritoneal cavity. Intravital microscopy demonstrated that although in vivo bromelain treatment transiently decreased leukocyte rolling, its primary long-term effect was abrogation of firm adhesion of leukocytes to blood vessels at the site of inflammation. These changes in adhesion were correlated with rapid re-expression of the bromelain-sensitive CD62L/L-selectin molecules that mediate rolling following in vivo bromelain treatment and minimal re-expression of CD128 over the time period studied. Taken together, these studies demonstrate that bromelain can effectively decrease neutrophil migration to sites of acute inflammation and support the specific removal of the CD128 chemokine receptor as a potential mechanism of action. PMID:18482869

  11. Transforming growth factor β induces bone marrow mesenchymal stem cell migration via noncanonical signals and N-cadherin.

    PubMed

    Dubon, Maria Jose; Yu, Jinyeong; Choi, Sanghyuk; Park, Ki-Sook

    2018-01-01

    Transforming growth factor-beta (TGF-β) induces the migration and mobilization of bone marrow-derived mesenchymal stem cells (BM-MSCs) to maintain bone homeostasis during bone remodeling and facilitate the repair of peripheral tissues. Although many studies have reported the mechanisms through which TGF-β mediates the migration of various types of cells, including cancer cells, the intrinsic cellular mechanisms underlying cellular migration, and mobilization of BM-MSCs mediated by TGF-β are unclear. In this study, we showed that TGF-β activated noncanonical signaling molecules, such as Akt, extracellular signal-regulated kinase 1/2 (ERK1/2), focal adhesion kinase (FAK), and p38, via TGF-β type I receptor in human BM-MSCs and murine BM-MSC-like ST2 cells. Inhibition of Rac1 by NSC23766 and Src by PP2 resulted in impaired TGF-β-mediated migration. These results suggested that the Smad-independent, noncanonical signals activated by TGF-β were necessary for migration. We also showed that N-cadherin-dependent intercellular interactions were required for TGF-β-mediated migration using functional inhibition of N-cadherin with EDTA treatment and a neutralizing antibody (GC-4 antibody) or siRNA-mediated knockdown of N-cadherin. However, N-cadherin knockdown did not affect the global activation of noncanonical signals in response to TGF-β. Therefore, these results suggested that the migration of BM-MSCs in response to TGF-β was mediated through N-cadherin and noncanonical TGF-β signals. © 2017 Wiley Periodicals, Inc.

  12. Direct observation of localized radial oxygen migration in functioning tantalum oxide memristors

    DOE PAGES

    Kumar, Suhas; Graves, Catherine E.; Strachan, John Paul; ...

    2016-02-02

    Oxygen migration in tantalum oxide, a promising next-generation storage material, is studied using in operando x-ray absorption spectromicroscopy and is used to microphysically describe accelerated evolution of conduction channel and device failure. Furthermore, the resulting ring-like patterns of oxygen concentration are modeled using thermophoretic forces and Fick diffusion, establishing the critical role of temperature-activated oxygen migration that has been under question lately.

  13. Biometrics and international migration.

    PubMed

    Redpath, Jillyanne

    2007-01-01

    This paper will focus on the impact of the rapid expansion in the use of biometric systems in migration management on the rights of individuals; it seeks to highlight legal issues for consideration in implementing such systems, taking as the starting point that the security interests of the state and the rights of the individual are not, and should not be, mutually exclusive. The first part of this paper briefly describes the type of biometric applications available, how biometric systems function, and those used in migration management. The second part examines the potential offered by biometrics for greater security in migration management, and focuses on developments in the use of biometrics as a result of September 11. The third part discusses the impact of the use of biometrics in the management of migration on the individual's right to privacy and ability to move freely and lawfully. The paper highlights the increasing need for domestic and international frameworks to govern the use of biometric applications in the migration/security context, and proposes a number of issues that such frameworks could address.

  14. 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

  15. 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.

  16. Migration and pension.

    PubMed

    Razin, A; Sadka, E

    1998-11-01

    "Migration has important implications for the financial soundness of the pension system.... While it is common sense to expect that young migrants, even if low-skilled, can help society pay the benefits to the currently elderly, it may nevertheless be reasonable to argue that these migrants would adversely affect current young since, after all, the migrants are net beneficiaries of the welfare state. In contrast to the adverse effects of low skilled migration in a static model, [the authors] show that in a Samuelsonian overlapping generations model...migration is a Pareto-improving measure. All the existing income (low and high) and age (young and old) groups living at the time of the migrant's arrival would be better off." excerpt

  17. Migration transition in small Northern and Eastern Caribbean states.

    PubMed

    Mcelroy, J L; De Albuquerque, K

    1988-01-01

    1 area of intra-Caribbean migration that has been overlooked is the "migration transition"--the transformation of rapidly modernizing societies from net labor exporters to net labor importers. This article assembles 8 case studies to 1) briefly present a spectrum of migration experiences in the Caribbean, 2) uncover some transitions under way, 3) pinpoint the forces that underlie the migration transition, and 4) point out some of the more important policy implications of labor migration reversals. The 8 island societies sampled for illustration purposes include 1) the Bahamas and the US Virgin Islands as post-migration transition societies (Zelinsky's advanced society), 2) the British Virgin Islands and the Cayman Islands as undergoing transition (Zelinsky's late transitional society), and 3) Anguilla, St. Kitts-Nevis, Turks and Caicos, and Montserrat as premigration transition societies (Zelinsky's early transitional society). Population data for the islands were derived primarily from the West Indian censuses and government statistics. These 8 historical sketches reveal certain commonalities. All are at various stages in a long-term economic restructuring to displace traditional staple crops with more income elastic, high value export services. In such societies, population growth and progress along the migration transition is an increasing function of this kind of successful export substitution. In addition, along the migration and economic transitions, such insular economies exhibit a relatively large public sector (20-30% of all activity), declining unemployment, increasing fiscal autonomy, and are committed to a development strategy remarkably similar to the "successful" model of the Bahamas and the US Virgin Islands. Cursory evidence suggests that, because of intersectoral competition for land and labor, there is an inverse relationship between farm effort/manufacturing employment and tourism intensity. This review suggests that small islands undergoing

  18. Monocarboxylate transporter 1 contributes to growth factor-induced tumor cell migration independent of transporter activity

    PubMed Central

    Gray, Alana L.; Coleman, David T.; Shi, Runhua; Cardelli, James A.

    2016-01-01

    Tumor progression to metastatic disease contributes to the vast majority of incurable cancer. Understanding the processes leading to advanced stage cancer is important for the development of future therapeutic strategies. Here, we establish a connection between tumor cell migration, a prerequisite to metastasis, and monocarboxylate transporter 1 (MCT1). MCT1 transporter activity is known to regulate aspects of tumor progression and, as such, is a clinically relevant target for treating cancer. Knockdown of MCT1 expression caused decreased hepatocyte growth factor (HGF)-induced as well as epidermal growth factor (EGF)-induced tumor cell scattering and wound healing. Western blot analysis suggested that MCT1 knockdown (KD) hinders signaling through the HGF receptor (c-Met) but not the EGF receptor. Exogenous, membrane-permeable MCT1 substrates were not able to rescue motility in MCT1 KD cells, nor was pharmacologic inhibition of MCT1 able to recapitulate decreased cell motility as seen with MCT1 KD cells, indicating transporter activity of MCT1 was dispensable for EGF- and HGF-induced motility. These results indicate MCT1 expression, independent of transporter activity, is required for growth factor-induced tumor cell motility. The findings presented herein suggest a novel function for MCT1 in tumor progression independent of its role as a monocarboxylate transporter. PMID:27127175

  19. College Student Migration.

    ERIC Educational Resources Information Center

    Fenske, R. H.; And Others

    This study examines the background characteristics of two large national samples of first-time enrolled freshmen who (a) attended college within their state of residence but away from their home community, (b) migrated to a college in an adjacent state, (c) migrated to a college in a distant state, and (d) attended college in their home community.…

  20. Vitamin D binding protein-macrophage activating factor directly inhibits proliferation, migration, and uPAR expression of prostate cancer cells.

    PubMed

    Gregory, Kalvin J; Zhao, Bing; Bielenberg, Diane R; Dridi, Sami; Wu, Jason; Jiang, Weihua; Huang, Bin; Pirie-Shepherd, Steven; Fannon, Michael

    2010-10-18

    Vitamin D binding protein-macrophage activating factor (DBP-maf) is a potent inhibitor of tumor growth. Its activity, however, has been attributed to indirect mechanisms such as boosting the immune response by activating macrophages and inhibiting the blood vessel growth necessary for the growth of tumors. In this study we show for the first time that DBP-maf exhibits a direct and potent effect on prostate tumor cells in the absence of macrophages. DBP-maf demonstrated inhibitory activity in proliferation studies of both LNCaP and PC3 prostate cancer cell lines as well as metastatic clones of these cells. Flow cytometry studies with annexin V and propidium iodide showed that this inhibitory activity is not due to apoptosis or cell death. DBP-maf also had the ability to inhibit migration of prostate cancer cells in vitro. Finally, DBP-maf was shown to cause a reduction in urokinase plasminogen activator receptor (uPAR) expression in prostate tumor cells. There is evidence that activation of this receptor correlates with tumor metastasis. These studies show strong inhibitory activity of DBP-maf on prostate tumor cells independent of its macrophage activation.

  1. Vitamin D Binding Protein-Macrophage Activating Factor Directly Inhibits Proliferation, Migration, and uPAR Expression of Prostate Cancer Cells

    PubMed Central

    Bielenberg, Diane R.; Dridi, Sami; Wu, Jason; Jiang, Weihua; Huang, Bin; Pirie-Shepherd, Steven; Fannon, Michael

    2010-01-01

    Background Vitamin D binding protein-macrophage activating factor (DBP-maf) is a potent inhibitor of tumor growth. Its activity, however, has been attributed to indirect mechanisms such as boosting the immune response by activating macrophages and inhibiting the blood vessel growth necessary for the growth of tumors. Methods and Findings In this study we show for the first time that DBP-maf exhibits a direct and potent effect on prostate tumor cells in the absence of macrophages. DBP-maf demonstrated inhibitory activity in proliferation studies of both LNCaP and PC3 prostate cancer cell lines as well as metastatic clones of these cells. Flow cytometry studies with annexin V and propidium iodide showed that this inhibitory activity is not due to apoptosis or cell death. DBP-maf also had the ability to inhibit migration of prostate cancer cells in vitro. Finally, DBP-maf was shown to cause a reduction in urokinase plasminogen activator receptor (uPAR) expression in prostate tumor cells. There is evidence that activation of this receptor correlates with tumor metastasis. Conclusions These studies show strong inhibitory activity of DBP-maf on prostate tumor cells independent of its macrophage activation. PMID:20976141

  2. Process migration in UNIX environments

    NASA Technical Reports Server (NTRS)

    Lu, Chin; Liu, J. W. S.

    1988-01-01

    To support process migration in UNIX environments, the main problem is how to encapsulate the location dependent features of the system in such a way that a host independent virtual environment is maintained by the migration handlers on the behalf of each migrated process. An object-oriented approach is used to describe the interaction between a process and its environment. More specifically, environmental objects were introduced in UNIX systems to carry out the user-environment interaction. The implementation of the migration handlers is based on both the state consistency criterion and the property consistency criterion.

  3. Evaluation of the Indian Migration Study Physical Activity Questionnaire (IMS-PAQ): a cross-sectional study.

    PubMed

    Sullivan, Ruth; Kinra, Sanjay; Ekelund, Ulf; Bharathi, A V; Vaz, Mario; Kurpad, Anura; Collier, Tim; Reddy, K Srinath; Prabhakaran, Dorairaj; Ebrahim, Shah; Kuper, Hannah

    2012-02-09

    Socio-cultural differences for country-specific activities are rarely addressed in physical activity questionnaires. We examined the reliability and validity of the Indian Migration Study Physical Activity Questionnaire (IMS-PAQ) in urban and rural groups in India. A sub-sample of IMS participants (n = 479) was used to examine short term (≤ 1 month [n = 158]) and long term (> 1 month [n = 321]) IMS-PAQ reliability for levels of total, sedentary, light and moderate/vigorous activity (MVPA) intensity using intraclass correlation (ICC) and kappa coefficients (k). Criterion validity (n = 157) was examined by comparing the IMS-PAQ to a uniaxial accelerometer (ACC) worn ≥ 4 days, via Spearman's rank correlations (ρ) and k, using Bland-Altman plots to check for systematic bias. Construct validity (n = 7,000) was established using linear regression, comparing IMS-PAQ against theoretical constructs associated with physical activity (PA): BMI [kg/m2], percent body fat and pulse rate. IMS-PAQ reliability ranged from ICC 0.42-0.88 and k = 0.37-0.61 (≤ 1 month) and ICC 0.26 to 0.62; kappa 0.17 to 0.45 (> 1 month). Criterion validity was ρ = 0.18-0.48; k = 0.08-0.34. Light activity was underestimated and MVPA consistently and substantially overestimated for the IMS-PAQ vs. the accelerometer. Criterion validity was moderate for total activity and MVPA. Reliability and validity were comparable for urban and rural participants but lower in women than men. Increasing time spent in total activity or MVPA, and decreasing time in sedentary activity were associated with decreasing BMI, percent body fat and pulse rate, thereby demonstrating construct validity. IMS-PAQ reliability and validity is similar to comparable self-reported instruments. It is an appropriate tool for ranking PA of individuals in India. Some refinements may be required for sedentary populations and women in India.

  4. Clonorchis sinensis excretory-secretory products promote the migration and invasion of cholangiocarcinoma cells by activating the integrin β4-FAK/Src signaling pathway.

    PubMed

    Pak, Jhang Ho; Bashir, Qudsia; Kim, In Ki; Hong, Sung-Jong; Maeng, Sejung; Bahk, Young Yil; Kim, Tong-Soo

    2017-06-01

    Cholangiocarcinoma (CCA) is a slow-growing but highly metastatic cancer. Its metastatic potential largely explains its high mortality rate. A recognized risk factor for CCA development is infection with the liver flukes Opisthorchis viverrini and Clonorchis sinensis. We previously reported that the excretory-secretory products (ESPs) of C. sinensis promoted the three-dimensional aggregation and invasion of CCA cells. In the present study, a quantitative real-time PCR array of extracellular matrix (ECM) and adhesion molecules was used to examine the regulatory mechanism of ESP-mediated CCA cell migration and invasion. In particular, the expression levels of integrin α isoforms and β4 were upregulated in response to ESPs. Increased expression of integrin β4 was probably correlated with activation of focal adhesion kinase (FAK) and the steroid receptor coactivator (Src) family kinase and the subsequent activation of two downstream focal adhesion molecules, paxillin and vinculin. Moreover, inhibition of FAK/Src activation reduced paxillin and vinculin phosphorylation and attenuated ESP-induced CCA cell migration and invasion. These findings suggest that the integrin β4-FAK/Src signaling axis may play a crucial role in clonorchiasis-associated CCA metastasis during tumor progression. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Evolution with Stochastic Fitness and Stochastic Migration

    PubMed Central

    Rice, Sean H.; Papadopoulos, Anthony

    2009-01-01

    Background Migration between local populations plays an important role in evolution - influencing local adaptation, speciation, extinction, and the maintenance of genetic variation. Like other evolutionary mechanisms, migration is a stochastic process, involving both random and deterministic elements. Many models of evolution have incorporated migration, but these have all been based on simplifying assumptions, such as low migration rate, weak selection, or large population size. We thus have no truly general and exact mathematical description of evolution that incorporates migration. Methodology/Principal Findings We derive an exact equation for directional evolution, essentially a stochastic Price equation with migration, that encompasses all processes, both deterministic and stochastic, contributing to directional change in an open population. Using this result, we show that increasing the variance in migration rates reduces the impact of migration relative to selection. This means that models that treat migration as a single parameter tend to be biassed - overestimating the relative impact of immigration. We further show that selection and migration interact in complex ways, one result being that a strategy for which fitness is negatively correlated with migration rates (high fitness when migration is low) will tend to increase in frequency, even if it has lower mean fitness than do other strategies. Finally, we derive an equation for the effective migration rate, which allows some of the complex stochastic processes that we identify to be incorporated into models with a single migration parameter. Conclusions/Significance As has previously been shown with selection, the role of migration in evolution is determined by the entire distributions of immigration and emigration rates, not just by the mean values. The interactions of stochastic migration with stochastic selection produce evolutionary processes that are invisible to deterministic evolutionary theory

  6. Migration of health-care workers from developing countries: strategic approaches to its management.

    PubMed Central

    Stilwell, Barbara; Diallo, Khassoum; Zurn, Pascal; Vujicic, Marko; Adams, Orvill; Dal Poz, Mario

    2004-01-01

    Of the 175 million people (2.9% of the world's population) living outside their country of birth in 2000, 65 million were economically active. The rise in the number of people migrating is significant for many developing countries because they are losing their better-educated nationals to richer countries. Medical practitioners and nurses represent a small proportion of the highly skilled workers who migrate, but the loss for developing countries of human resources in the health sector may mean that the capacity of the health system to deliver health care equitably is significantly compromised. It is unlikely that migration will stop given the advances in global communications and the development of global labour markets in some fields, which now include nursing. The aim of this paper is to examine some key issues related to the international migration of health workers and to discuss strategic approaches to managing migration. PMID:15375449

  7. Migration of health-care workers from developing countries: strategic approaches to its management.

    PubMed

    Stilwell, Barbara; Diallo, Khassoum; Zurn, Pascal; Vujicic, Marko; Adams, Orvill; Dal Poz, Mario

    2004-08-01

    Of the 175 million people (2.9% of the world's population) living outside their country of birth in 2000, 65 million were economically active. The rise in the number of people migrating is significant for many developing countries because they are losing their better-educated nationals to richer countries. Medical practitioners and nurses represent a small proportion of the highly skilled workers who migrate, but the loss for developing countries of human resources in the health sector may mean that the capacity of the health system to deliver health care equitably is significantly compromised. It is unlikely that migration will stop given the advances in global communications and the development of global labour markets in some fields, which now include nursing. The aim of this paper is to examine some key issues related to the international migration of health workers and to discuss strategic approaches to managing migration.

  8. Migration of dispersive GPR data

    USGS Publications Warehouse

    Powers, M.H.; Oden, C.P.; ,

    2004-01-01

    Electrical conductivity and dielectric and magnetic relaxation phenomena cause electromagnetic propagation to be dispersive in earth materials. Both velocity and attenuation may vary with frequency, depending on the frequency content of the propagating energy and the nature of the relaxation phenomena. A minor amount of velocity dispersion is associated with high attenuation. For this reason, measuring effects of velocity dispersion in ground penetrating radar (GPR) data is difficult. With a dispersive forward model, GPR responses to propagation through materials with known frequency-dependent properties have been created. These responses are used as test data for migration algorithms that have been modified to handle specific aspects of dispersive media. When either Stolt or Gazdag migration methods are modified to correct for just velocity dispersion, the results are little changed from standard migration. For nondispersive propagating wavefield data, like deep seismic, ensuring correct phase summation in a migration algorithm is more important than correctly handling amplitude. However, the results of migrating model responses to dispersive media with modified algorithms indicate that, in this case, correcting for frequency-dependent amplitude loss has a much greater effect on the result than correcting for proper phase summation. A modified migration is only effective when it includes attenuation recovery, performing deconvolution and migration simultaneously.

  9. Regulation of Cell Migration in Breast Cancer

    DTIC Science & Technology

    2011-04-01

    the wound healing, assay by scarring and Oris plate migration assay, transwell migration assay and live - cell imaging studies. Cell migration capacity...evaluated by the use of techniques that include the wound healing assay by scarring and Oris plate migration assay, transwell migration assay and live - cell imaging studies

  10. Modeling keratinocyte wound healing dynamics: Cell-cell adhesion promotes sustained collective migration.

    PubMed

    Nardini, John T; Chapnick, Douglas A; Liu, Xuedong; Bortz, David M

    2016-07-07

    The in vitro migration of keratinocyte cell sheets displays behavioral and biochemical similarities to the in vivo wound healing response of keratinocytes in animal model systems. In both cases, ligand-dependent Epidermal Growth Factor Receptor (EGFR) activation is sufficient to elicit collective cell migration into the wound. Previous mathematical modeling studies of in vitro wound healing assays assume that physical connections between cells have a hindering effect on cell migration, but biological literature suggests a more complicated story. By combining mathematical modeling and experimental observations of collectively migrating sheets of keratinocytes, we investigate the role of cell-cell adhesion during in vitro keratinocyte wound healing assays. We develop and compare two nonlinear diffusion models of the wound healing process in which cell-cell adhesion either hinders or promotes migration. Both models can accurately fit the leading edge propagation of cell sheets during wound healing when using a time-dependent rate of cell-cell adhesion strength. The model that assumes a positive role of cell-cell adhesion on migration, however, is robust to changes in the leading edge definition and yields a qualitatively accurate density profile. Using RNAi for the critical adherens junction protein, α-catenin, we demonstrate that cell sheets with wild type cell-cell adhesion expression maintain migration into the wound longer than cell sheets with decreased cell-cell adhesion expression, which fails to exhibit collective migration. Our modeling and experimental data thus suggest that cell-cell adhesion promotes sustained migration as cells pull neighboring cells into the wound during wound healing. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Nuss bar migrations: occurrence and classification.

    PubMed

    Binkovitz, Lauren E; Zendejas, Benjamin; Moir, Christopher R; Binkovitz, Larry A

    2016-12-01

    Pectus excavatum results from dorsal deviation of the sternum causing narrowing of the anterior-posterior diameter of the chest. It can result in significant cosmetic deformities and cardiopulmonary compromise if severe. The Nuss procedure is a minimally invasive technique that involves placing a thin horizontally oriented metal bar below the dorsal sternal apex for correction of the pectus deformity. To identify the frequency and types of Nuss bar migrations, to present a new categorization of bar migrations, and to present examples of true migrations and pseudomigrations. We retrospectively reviewed the electronic medical records and all pertinent radiologic studies of 311 pediatric patients who underwent a Nuss procedure. We evaluated the frequency and type of bar migrations. Bar migration was demonstrated in 23 of 311 patients (7%) and occurred within a mean period of 26 days after surgery. Bar migrations were subjectively defined as deviation of the bar from the position demonstrated on the immediate postoperative radiographs and categorized as superior, inferior, rotation, lateral or flipped using a new classification system. Sixteen of the 23 migrations required re-operation. Nuss bar migration can be diagnosed with careful evaluation of serial radiographs. Nuss bar migration has a wide variety of appearances and requires exclusion of pseudomigration resulting from changes in patient positioning between radiologic examinations.

  12. Migration of antimony from PET trays into food simulant and food: determination of Arrhenius parameters and comparison of predicted and measured migration data

    PubMed Central

    Haldimann, M.; Alt, A.; Blanc, A.; Brunner, K.; Sager, F.; Dudler, V.

    2013-01-01

    Migration experiments with small sheets cut out from ovenable PET trays were performed in two-sided contact with 3% acetic acid as food simulant at various temperatures. The fraction of diffusible antimony (Sb) was estimated to be 62% in the PET sample under study. Apparent diffusion coefficients of Sb in PET trays were determined experimentally. Measurement of migration between 20 and 150°C yielded a linear Arrhenius plot over a wide temperature range from which the activation energy (Ea) of 188 ± 36 kJ mol−1 and the pre-exponential factor (D0) of 3.6 × 1014 cm2s−1 were determined for diffusing Sb species. Ea was similar to previously reported values for PET bottles obtained with a different experimental approach. Ea and D0 were applied as model parameters in migration modelling software for predicting the Sb transfer in real food. Ready meals intended for preparation in a baking oven were heated in the PET trays under study and the actual Sb migration into the food phase was measured by isotope dilution ICP-MS. It was shown that the predictive modelling reproduces correctly experimental data. PMID:23286325

  13. Migration of antimony from PET trays into food simulant and food: determination of Arrhenius parameters and comparison of predicted and measured migration data.

    PubMed

    Haldimann, M; Alt, A; Blanc, A; Brunner, K; Sager, F; Dudler, V

    2013-01-01

    Migration experiments with small sheets cut out from ovenable PET trays were performed in two-sided contact with 3% acetic acid as food simulant at various temperatures. The fraction of diffusible antimony (Sb) was estimated to be 62% in the PET sample under study. Apparent diffusion coefficients of Sb in PET trays were determined experimentally. Measurement of migration between 20 and 150°C yielded a linear Arrhenius plot over a wide temperature range from which the activation energy (E(a)) of 188 ± 36 kJ mol(-1) and the pre-exponential factor (D(0)) of 3.6 × 10(14) cm(2) s(-1) were determined for diffusing Sb species. E (a) was similar to previously reported values for PET bottles obtained with a different experimental approach. E (a) and D (0) were applied as model parameters in migration modelling software for predicting the Sb transfer in real food. Ready meals intended for preparation in a baking oven were heated in the PET trays under study and the actual Sb migration into the food phase was measured by isotope dilution ICP-MS. It was shown that the predictive modelling reproduces correctly experimental data.

  14. Zinc improves learning and memory abilities of fetal growth restriction rats and promotes trophoblast cell invasion and migration via enhancing STAT3-MMP-2/9 axis activity.

    PubMed

    Zong, Lu; Wei, Xiaohua; Gou, Wenli; Huang, Pu; Lv, Ye

    2017-12-29

    Fetal growth restriction (FGR) is a well-known risk factor for cognitive dysfunction, especially for learning and memory abilities. However, knowledge about prevention and treatment methods of learning and memory abilities of fetal are limit. Here, Morris water maze and passive avoidance tests showed zinc supplementation could protect the impairment of the learning and memory abilities caused by FGR. As accumulating evidence suggested that insufficiency of placental trophoblast cell invasion was closely related to FGR fetal neurodevelopmental dysplasia, we further explored the relationship between zinc supplementation during pregnancy and placental trophoblast. Microarray identified 346 differently expressed genes in placental tissues with and without zinc supplementation, and GO and KEGG analyses showed these differently expressed genes were highly enriched in cell invasion and migration and STAT3 pathway. Protein-protein interaction(PPI) analysis found that STAT3 interacted with matrix metalloproteinase-2/9 (MMP-2/9). In vivo , western blot results authenticated that the expression levels of phospho-STAT3, STAT3, MMP-2 and MMP-9 were up-regulated in placental tissues after zinc treatment. To validate whether zinc could promotes trophoblast cell invasion and migration via enhancing STAT3-MMP-2/9 activity. In vitro , Transwell assay was performed, and we observed that abilities of invasion and migration were obviously increased in zinc treated trophoblast cells. And phospho-STAT3, STAT3, MMP-2 and MMP-9 expression levels were correspondingly increased in zinc treated trophoblast cells, which were dose-dependent. Moreover, gain-of-function and loss-of-function of STAT3 confirmed that zinc promotes cell invasion and migration via regulating STAT3 mediated up-regulation of MMP-2/9 activity. We propose that activation of MMP-2/9 mediated by STAT3 may contribute to invasion and migration of trophoblast cells, which improved neurodevelopmental impairment of FGR rats

  15. 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.

  16. 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

  17. PP2A regulates SCF-induced cardiac stem cell migration through interaction with p38 MAPK.

    PubMed

    Wang, Ying; Xia, Yanli; Kuang, Dong; Duan, Yaqi; Wang, Guoping

    2017-12-15

    Previous studies have shown that stem cell factor (SCF) induces the migration of cardiac stem cells (CSCs) and helps to repair myocardial infarctions. Earlier studies on the migration mechanism only focused on the activation of kinases; here, we aimed to explore the functional role of protein phosphatase 2A (PP2A) in SCF-induced CSC migration. CSCs were treated with SCF, PP2A enzymatic activity was measured, the phosphorylation levels of PP2A, p38 MAPK and cofilin were evaluated using western blot. Transwell assay was used to determine the migratory ability of CSCs. In vitro, SCF induced the phosphorylation of p38 MAPK and cofilin, leading to the migration of CSCs. Cofilin acted as a downstream signal of p38 MAPK. PP2A was involved in this process. Further studies revealed that PP2A was inactivated via phosphorylation at Tyr307 by SCF and the inactivation/phosphorylation was mediated by activated p38 MAPK, as p38 MAPK inhibitor SB203580 or siRNA prevented SCF-induced inactivation and phosphorylation of PP2A. When CSCs were pretreated with PP2A inhibitor (okadaic acid, OA), SCF-induced CSC migration and the downstream signals were enhanced, and the enhancement was reversed when p38 MAPK was blocked. Additionally, co-immunoprecipitation showed a direct interaction of PP2A with p38 MAPK. Our results indicated that PP2A regulated the SCF-induced activation of p38 MAPK/cofilin signaling pathway and subsequent migration of CSCs by interaction with p38 MAPK. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Cigarette smoke induces β2-integrin-dependent neutrophil migration across human endothelium

    PubMed Central

    2011-01-01

    Background Cigarette smoking induces peripheral inflammatory responses in all smokers and is the major risk factor for neutrophilic lung disease such as chronic obstructive pulmonary disease. The aim of this study was to investigate the effect of cigarette smoke on neutrophil migration and on β2-integrin activation and function in neutrophilic transmigration through endothelium. Methods and results Utilizing freshly isolated human PMNs, the effect of cigarette smoke on migration and β2-integrin activation and function in neutrophilic transmigration was studied. In this report, we demonstrated that cigarette smoke extract (CSE) dose dependently induced migration of neutrophils in vitro. Moreover, CSE promoted neutrophil adherence to fibrinogen. Using functional blocking antibodies against CD11b and CD18, it was demonstrated that Mac-1 (CD11b/CD18) is responsible for the cigarette smoke-induced firm adhesion of neutrophils to fibrinogen. Furthermore, neutrophils transmigrated through endothelium by cigarette smoke due to the activation of β2-integrins, since pre-incubation of neutrophils with functional blocking antibodies against CD11b and CD18 attenuated this transmigration. Conclusion This is the first study to describe that cigarette smoke extract induces a direct migratory effect on neutrophils and that CSE is an activator of β2-integrins on the cell surface. Blocking this activation of β2-integrins might be an important target in cigarette smoke induced neutrophilic diseases. PMID:21651795

  19. Examining Pre-migration Health Among Filipino Nurses

    PubMed Central

    de Castro, A. B.; Gee, Gilbert; Fujishiro, Kaori; Rue, Tessa

    2014-01-01

    The healthy immigrant hypothesis asserts that immigrants arrive in the receiving country healthier than same race/ethnic counterparts born there. Contemporary research, however, has not evaluated pre-migration health among migrants, nor has explicitly considered comparisons with non-migrants in the country of origin. Pre-migration health was examined among 621 Filipino nurses, including self-reported physical health, mental health, health behaviors, and social stress. Measures were compared by intention to migrate and also tested as predictors of actual migration using time-to-event analysis. Nurses intending to migrate had higher proportion of depression and reported higher general perceived stress compared to those not. Predictors of actual migration included age, mentally unhealthy days, social strain, and social support. Physical health and health behavior measures had no association with migration intention or actual migration. Findings suggest that, relative to those not intending to migrate, nurses intending to migrate have worse mental health status and social stress; and, do not have a physical health advantage. Future research must span the pre- to post-migration continuum to better understand the impact of moving from one country to another on health and well-being. PMID:25385090

  20. Examining Pre-migration Health Among Filipino Nurses.

    PubMed

    de Castro, A B; Gee, Gilbert; Fujishiro, Kaori; Rue, Tessa

    2015-12-01

    The healthy immigrant hypothesis asserts that immigrants arrive in the receiving country healthier than same race/ethnic counterparts born there. Contemporary research, however, has not evaluated pre-migration health among migrants, nor has explicitly considered comparisons with non-migrants in the country of origin. Pre-migration health was examined among 621 Filipino nurses, including self-reported physical health, mental health, health behaviors, and social stress. Measures were compared by intention to migrate and also tested as predictors of actual migration using time-to-event analysis. Nurses intending to migrate had higher proportion of depression and reported higher general perceived stress compared to those not. Predictors of actual migration included age, mentally unhealthy days, social strain, and social support. Physical health and health behavior measures had no association with migration intention or actual migration. Findings suggest that, relative to those not intending to migrate, nurses intending to migrate have worse mental health status and social stress; and, do not have a physical health advantage. Future research must span the pre- to post-migration continuum to better understand the impact of moving from one country to another on health and well-being.

  1. Blockade by fenspiride of endotoxin-induced neutrophil migration in the rat.

    PubMed

    Cunha, F Q; Boukili, M A; da Motta, J I; Vargaftig, B B; Ferreira, S H

    1993-07-06

    Fenspiride, an antiinflammatory drug with low anti-cyclooxygenase activity, administered orally at 60-200 mg/kg inhibited neutrophil migration into peritoneal and air pouches cavities as well as exudation into peritoneal cavities induced by endotoxin but not induced by carrageenin. Up to 100 microM, fenspiride failed to inhibit the in vitro release of a neutrophil chemotactic activity by endotoxin-stimulated macrophages and the in vivo migration into the peritoneal cavities induced by the supernatant of those macrophages. The release of tumour necrosis factor by stimulated macrophages was inhibited by fenspiride in a dose-dependent manner. These results suggest that the antiinflammatory effects of fenspiride are associated with the inhibition of the tumour necrosis factor release by resident macrophages.

  2. Systematic Analysis of the Transcriptional Switch Inducing Migration of Border Cells

    PubMed Central

    Borghese, Lodovica; Fletcher, Georgina; Mathieu, Juliette; Atzberger, Ann; Eades, William C.; Cagan, Ross L.; Rørth, Pernille

    2010-01-01

    Summary Cell migration within a natural context is tightly controlled, often by specific transcription factors. However, the switch from stationary to migratory behavior is poorly understood. Border cells perform a spatially and temporally controlled invasive migration during Drosophila oogenesis. Slbo, a C/EBP family transcriptional activator, is required for them to become migratory. We purified wild-type and slbo mutant border cells as well as nonmigratory follicle cells and performed comparative whole-genome expression profiling, followed by functional tests of the contributions of identified targets to migration. About 300 genes were significantly upregulated in border cells, many dependent on Slbo. Among these, the microtubule regulator Stathmin was strongly upregulated and was required for normal migration. Actin cytoskeleton regulators were also induced, including, surprisingly, a large cluster of “muscle-specific” genes. We conclude that Slbo induces multiple cytoskeletal effectors, and that each contributes to the behavioral changes in border cells. PMID:16580994

  3. Transcription factor activity of estrogen receptor α activation upon nonylphenol or bisphenol A treatment enhances the in vitro proliferation, invasion, and migration of neuroblastoma cells

    PubMed Central

    Ma, Hongda; Yao, Yao; Wang, Changli; Zhang, Liyu; Cheng, Long; Wang, Yiren; Wang, Tao; Liang, Erguang; Jia, Hui; Ye, Qinong; Hou, Mingxiao; Feng, Fan

    2016-01-01

    Many kinds of endocrine-disrupting chemicals (EDCs), for example, the environmental estrogens bisphenol A and nonylphenol, may regulate the activity of estrogen receptor α (ERα) and therefore induce potential disruption of normal endocrine function. However, the involvement of EDCs in human cancers, especially in endocrine-related cancer neuroblastoma regulation, is not very clear. In this work, results showed that upon bisphenol A or nonylphenol treatment, the transcription factor activity of ERα was significantly increased in neuroblastoma cell line SH-SY5Y. Bisphenol A and nonylphenol could enhance ERα activity via recruiting it to the target gene promoter. Furthermore, treatment of bisphenol A and nonylphenol enhanced the in vitro proliferation, invasion, and migration ability of neuroblastoma cells. By investigating the role of EDC-induced ERα upregulation, our data extend the understanding of the function of EDCs and further suggest that ERα might be a potential therapeutic target in human neuroblastoma treatment. PMID:27366082

  4. Pre-migration Trauma Exposure and Psychological Distress for Asian American Immigrants: Linking the Pre- and Post-migration Contexts.

    PubMed

    Li, Miao; Anderson, James G

    2016-08-01

    Drawing on the life course perspective and the assumptive world theory, this paper examines whether pre-migration trauma exposure is associated with psychological distress through post-migration perceived discrimination for Asian American immigrants. The study is based on cross-sectional data from the National Latino and Asian American Study (N = 1639). Structural equation model is used to estimate the relationship between pre-migration trauma, post-migration perceived discrimination, and psychological distress. Additional models are estimated to explore possible variations across ethnic groups as well as across different types of pre-migration trauma experience. Pre-migration trauma exposure is associated with higher levels of psychological distress, both directly and indirectly through higher level of perceived discrimination, even after controlling for demographic/acculturative factors and post-migration trauma exposure. This pattern holds for the following sub-types of pre-migration trauma: political trauma, crime victimization, physical violence, accidental trauma, and relational trauma. Multi-group analyses show that this pattern holds for all Asian immigrant subgroups except the Vietnamese. Studies of immigrant mental health primarily focus on post-migration stressors. Few studies have considered the link between pre- and post-migration contexts in assessing mental health outcomes. The study illustrates the usefulness of bridging the pre- and post-migration context in identifying the mental health risks along the immigrant life course.

  5. Lamellipodia-based migrations of larval epithelial cells are required for normal closure of the adult epidermis of Drosophila

    PubMed Central

    Bischoff, Marcus

    2012-01-01

    Cell migrations are an important feature of animal development. They are, furthermore, essential to wound healing and tumour progression. Despite recent progress, it is still mysterious how cell migration is spatially and temporally regulated during morphogenesis and how cell migration is coordinated with other cellular behaviours to shape tissues and organs. The formation of the abdominal epithelium of Drosophila during metamorphosis provides an attractive system to study morphogenesis. Here, the diploid adult histoblasts replace the polyploid larval epithelial cells (LECs). Using in vivo 4D microscopy, I show that, besides apical constriction and apoptosis, the LECs undergo extensive coordinated migrations. The migrations follow a transition from a stationary (epithelial) to a migratory mode. The migratory behaviour is stimulated by autocrine Dpp signalling. Directed apical lamellipodia-like protrusions propel the cells. Initially, planar cell polarity determines the orientation of LEC migration. While LECs are migrating they also constrict apically, and changes in activity of the small GTPase Rho1 can favour one behaviour over the other. This study shows that the LECs play a more active role in morphogenesis than previously thought, with their migrations contributing to abdominal closure. It furthermore provides insights into how the migratory behaviour of cells is regulated during morphogenesis. PMID:22230614

  6. The mechanisms of substance P-mediated migration of bone marrow-derived mesenchymal stem cell-like ST2 cells.

    PubMed

    Dubon, Maria Jose; Park, Ki-Sook

    2016-04-01

    Substance P (SP) is known to induce the mobilization of bone marrow-derived mesenchymal stem cells (BM-MSCs) and thus participates in wound repair. However, the cellular and molecular mechanisms responsible for the SP-mediated migration of BM-MSCs were not fully understood. In the present study, we studied the molecular mechanisms that mediate the migration of the BM-derived MSC-like cell line ST2 in response to SP. Using a migration assay and western blot analysis, we noted that SP induced the chemotactic migration of ST2 cells through the intrinsic activation of extracellular signal-regulated kinases (ERKs) and protein kinase B (Akt), the phosphorylated expression levels of which were increased. We noted that Src is involved in the SP-mediated migration of ST2 cells and that focal adhesion kinase (FAK) was activated in the ST2 cells following SP treatment. Membrane ruffling increased in the ST2 cells after SP treatment, as was clearly demonstrated by immunocytochemical analysis. Importantly, using a blocking antibody against N-cadherin (GC-4), we studied cell migration and noted that SP mediated the migration of the ST2 cells through N-cadherin. The present study thus advanced our understanding of the mechanisms through which SP induces BM-MSC migration.

  7. The migration policy of developed Socialist society: problems of improvement.

    PubMed

    Khomra, A

    1982-10-01

    In the USSR the need for migration policy stems from objective processes in the development of socialist production and from its constant structural and territorial modifications, which are particularly palpable under current conditions, at a time when vast new regions are undergoing intensive development. Migration policy, to play the part of an effective instrument for exerting a purposeful influence on migration processes, must be stable in its basic directions and relatively flexible when it is necessary to react quickly to changes in various relatively local circumstances. The determination of criteria of optimization of migration processes is of paramount significance for the solution of problems of migration policy. The improvement of migration policy under the conditions of developed socialism must be based on the known patterns of reproduction of the population. At the same time it is necessary to consider the fact that the migration of the population proper can be considered as the source of regional differences in this reproduction and simultaneously is their consequence to a considerable degree. Consequently, 1 of the approaches to the elaboration of migration policy measures is oriented toward the equalization of conditions of population reproduction at the settlement and regional level. Many investigators of the problem of retaining youth in the countryside and of attracting skilled persons to rural areas believe the optimization of the productive and nonproductive spheres of activity to be the solution. Migration policy is implemented at 3 levels: the population as a whole; the collective; and the individual. Migration policy measures are divided according to the nature of their impact on the population into economic, moral, and administrative categories with the leading role assigned to economic measures. Among the economic measures that stimulate migration, a leading role is played by cash payments in the form of wage increases and one time grants

  8. Angiotensin Converting Enzyme Regulates Cell Proliferation and Migration

    PubMed Central

    Carvalho, Clarissa Coelho; Florentino, Rodrigo Machado; França, Andressa; Matias, Eveline; Guimarães, Paola Bianchi; Batista, Carolina; Freire, Valder; Carmona, Adriana Karaoglanovic; Pesquero, João Bosco; de Paula, Ana Maria; Foureaux, Giselle; Leite, Maria de Fatima

    2016-01-01

    Background The angiotensin-I converting enzyme (ACE) plays a central role in the renin-angiotensin system, acting by converting the hormone angiotensin-I to the active peptide angiotensin-II (Ang-II). More recently, ACE was shown to act as a receptor for Ang-II, and its expression level was demonstrated to be higher in melanoma cells compared to their normal counterparts. However, the function that ACE plays as an Ang-II receptor in melanoma cells has not been defined yet. Aim Therefore, our aim was to examine the role of ACE in tumor cell proliferation and migration. Results We found that upon binding to ACE, Ang-II internalizes with a faster onset compared to the binding of Ang-II to its classical AT1 receptor. We also found that the complex Ang-II/ACE translocates to the nucleus, through a clathrin-mediated process, triggering a transient nuclear Ca2+ signal. In silico studies revealed a possible interaction site between ACE and phospholipase C (PLC), and experimental results in CHO cells, demonstrated that the β3 isoform of PLC is the one involved in the Ca2+ signals induced by Ang-II/ACE interaction. Further studies in melanoma cells (TM-5) showed that Ang-II induced cell proliferation through ACE activation, an event that could be inhibited either by ACE inhibitor (Lisinopril) or by the silencing of ACE. In addition, we found that stimulation of ACE by Ang-II caused the melanoma cells to migrate, at least in part due to decreased vinculin expression, a focal adhesion structural protein. Conclusion ACE activation regulates melanoma cell proliferation and migration. PMID:27992423

  9. PCP Signaling between Migrating Neurons and their Planar-Polarized Neuroepithelial Environment Controls Filopodial Dynamics and Directional Migration

    PubMed Central

    Moens, Cecilia B.

    2016-01-01

    The planar cell polarity (PCP) pathway is a cell-contact mediated mechanism for transmitting polarity information between neighboring cells. PCP “core components” (Vangl, Fz, Pk, Dsh, and Celsr) are essential for a number of cell migratory events including the posterior migration of facial branchiomotor neurons (FBMNs) in the plane of the hindbrain neuroepithelium in zebrafish and mice. While the mechanism by which PCP signaling polarizes static epithelial cells is well understood, how PCP signaling controls highly dynamic processes like neuronal migration remains an important outstanding question given that PCP components have been implicated in a range of directed cell movements, particularly during vertebrate development. Here, by systematically disrupting PCP signaling in a rhombomere-restricted manner we show that PCP signaling is required both within FBMNs and the hindbrain rhombomere 4 environment at the time when they initiate their migration. Correspondingly, we demonstrate planar polarized localization of PCP core components Vangl2 and Fzd3a in the hindbrain neuroepithelium, and transient localization of Vangl2 at the tips of retracting FBMN filopodia. Using high-resolution timelapse imaging of FBMNs in genetic chimeras we uncover opposing cell-autonomous and non-cell-autonomous functions for Fzd3a and Vangl2 in regulating FBMN protrusive activity. Within FBMNs, Fzd3a is required to stabilize filopodia while Vangl2 has an antagonistic, destabilizing role. However, in the migratory environment Fzd3a acts to destabilize FBMN filopodia while Vangl2 has a stabilizing role. Together, our findings suggest a model in which PCP signaling between the planar polarized neuroepithelial environment and FBMNs directs migration by the selective stabilization of FBMN filopodia. PMID:26990447

  10. 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

  11. Repeat migration and disappointment.

    PubMed

    Grant, E K; Vanderkamp, J

    1986-01-01

    This article investigates the determinants of repeat migration among the 44 regions of Canada, using information from a large micro-database which spans the period 1968 to 1971. The explanation of repeat migration probabilities is a difficult task, and this attempt is only partly successful. May of the explanatory variables are not significant, and the overall explanatory power of the equations is not high. In the area of personal characteristics, the variables related to age, sex, and marital status are generally significant and with expected signs. The distance variable has a strongly positive effect on onward move probabilities. Variables related to prior migration experience have an important impact that differs between return and onward probabilities. In particular, the occurrence of prior moves has a striking effect on the probability of onward migration. The variable representing disappointment, or relative success of the initial move, plays a significant role in explaining repeat migration probabilities. The disappointment variable represents the ratio of actural versus expected wage income in the year after the initial move, and its effect on both repeat migration probabilities is always negative and almost always highly significant. The repeat probabilities diminish after a year's stay in the destination region, but disappointment in the most recent year still has a bearing on the delayed repeat probabilities. While the quantitative impact of the disappointment variable is not large, it is difficult to draw comparisons since similar estimates are not available elsewhere.

  12. CCL11 promotes migration and proliferation of mouse neural progenitor cells.

    PubMed

    Wang, Feifei; Baba, Nobuyasu; Shen, Yuan; Yamashita, Tatsuyuki; Tsuru, Emi; Tsuda, Masayuki; Maeda, Nagamasa; Sagara, Yusuke

    2017-02-07

    Neonatal hypoxia-ischemia induces massive brain damage during the perinatal period, resulting in long-term consequences to central nervous system structural and functional maturation. Although neural progenitor cells (NPCs) migrate through the parenchyma and home in to injury sites in the rodent brain, the molecular mechanisms are unknown. We examined the role of chemokines in mediating NPC migration after neonatal hypoxic-ischemic brain injury. Nine-day-old mice were exposed to a 120-minute hypoxia following unilateral carotid occlusion. Chemokine levels were quantified in mouse brain extract. Migration and proliferation assays were performed using embryonic and infant mouse NPCs. The neonatal hypoxic-ischemic brain injury resulted in an ipsilateral lesion, which was extended to the cortical and striatal areas. NPCs migrated toward an injured area, where a marked increase of CC chemokines was detected. In vitro studies showed that incubation of NPCs with recombinant mouse CCL11 promoted migration and proliferation. These effects were partly inhibited by a CCR3 antagonist, SB297006. Our data implicate an important effect of CCL11 for mouse NPCs. The effective activation of NPCs may offer a promising strategy for neuroregeneration in neonatal hypoxic-ischemic brain injury.

  13. The poleward migration of the location of tropical cyclone maximum intensity.

    PubMed

    Kossin, James P; Emanuel, Kerry A; Vecchi, Gabriel A

    2014-05-15

    Temporally inconsistent and potentially unreliable global historical data hinder the detection of trends in tropical cyclone activity. This limits our confidence in evaluating proposed linkages between observed trends in tropical cyclones and in the environment. Here we mitigate this difficulty by focusing on a metric that is comparatively insensitive to past data uncertainty, and identify a pronounced poleward migration in the average latitude at which tropical cyclones have achieved their lifetime-maximum intensity over the past 30 years. The poleward trends are evident in the global historical data in both the Northern and the Southern hemispheres, with rates of 53 and 62 kilometres per decade, respectively, and are statistically significant. When considered together, the trends in each hemisphere depict a global-average migration of tropical cyclone activity away from the tropics at a rate of about one degree of latitude per decade, which lies within the range of estimates of the observed expansion of the tropics over the same period. The global migration remains evident and statistically significant under a formal data homogenization procedure, and is unlikely to be a data artefact. The migration away from the tropics is apparently linked to marked changes in the mean meridional structure of environmental vertical wind shear and potential intensity, and can plausibly be linked to tropical expansion, which is thought to have anthropogenic contributions.

  14. C-C motif ligand 5 promotes migration of prostate cancer cells in the prostate cancer bone metastasis microenvironment.

    PubMed

    Urata, Satoko; Izumi, Kouji; Hiratsuka, Kaoru; Maolake, Aerken; Natsagdorj, Ariunbold; Shigehara, Kazuyoshi; Iwamoto, Hiroaki; Kadomoto, Suguru; Makino, Tomoyuki; Naito, Renato; Kadono, Yoshifumi; Lin, Wen-Jye; Wufuer, Guzailinuer; Narimoto, Kazutaka; Mizokami, Atsushi

    2018-03-01

    Chemokines and their receptors have key roles in cancer progression. The present study investigated chemokine activity in the prostate cancer bone metastasis microenvironment. Growth and migration of human prostate cancer cells were assayed in cocultures with bone stromal cells. The migration of LNCaP cells significantly increased when co-cultured with bone stromal cells isolated from prostate cancer bone metastases. Cytokine array analysis of conditioned medium from bone stromal cell cultures identified CCL5 as a concentration-dependent promoter of LNCaP cell migration. The migration of LNCaP cells was suppressed when C-C motif ligand 5 (CCL5) neutralizing antibody was added to cocultures with bone stromal cells. Knockdown of androgen receptor with small interfering RNA increased the migration of LNCaP cells compared with control cells, and CCL5 did not promote the migration of androgen receptor knockdown LNCaP. Elevated CCL5 secretion in bone stromal cells from metastatic lesions induced prostate cancer cell migration by a mechanism consistent with CCL5 activity upstream of androgen receptor signaling. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  15. Probabilistic migration modelling focused on functional barrier efficiency and low migration concepts in support of risk assessment.

    PubMed

    Brandsch, Rainer

    2017-10-01

    Migration modelling provides reliable migration estimates from food-contact materials (FCM) to food or food simulants based on mass-transfer parameters like diffusion and partition coefficients related to individual materials. In most cases, mass-transfer parameters are not readily available from the literature and for this reason are estimated with a given uncertainty. Historically, uncertainty was accounted for by introducing upper limit concepts first, turning out to be of limited applicability due to highly overestimated migration results. Probabilistic migration modelling gives the possibility to consider uncertainty of the mass-transfer parameters as well as other model inputs. With respect to a functional barrier, the most important parameters among others are the diffusion properties of the functional barrier and its thickness. A software tool that accepts distribution as inputs and is capable of applying Monte Carlo methods, i.e., random sampling from the input distributions of the relevant parameters (i.e., diffusion coefficient and layer thickness), predicts migration results with related uncertainty and confidence intervals. The capabilities of probabilistic migration modelling are presented in the view of three case studies (1) sensitivity analysis, (2) functional barrier efficiency and (3) validation by experimental testing. Based on the predicted migration by probabilistic migration modelling and related exposure estimates, safety evaluation of new materials in the context of existing or new packaging concepts is possible. Identifying associated migration risk and potential safety concerns in the early stage of packaging development is possible. Furthermore, dedicated material selection exhibiting required functional barrier efficiency under application conditions becomes feasible. Validation of the migration risk assessment by probabilistic migration modelling through a minimum of dedicated experimental testing is strongly recommended.

  16. Glossary: migration and health.

    PubMed

    Urquia, Marcelo L; Gagnon, Anita J

    2011-05-01

    The literature on migration and health is quite heterogeneous in how migrants are labelled and how the relation between migration and health is conceptualised. A narrative review has been carried out. This glossary presents the most commonly used terms in the field of migration and health, along with synonyms and related concepts, and discusses the suitability of their use in epidemiological studies. The terminology used in migrant health is ambiguous in many cases. Studies on migrant health should avoid layman terms and strive to use internationally defined concepts.

  17. Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions

    NASA Astrophysics Data System (ADS)

    Doyle, Andrew D.; Carvajal, Nicole; Jin, Albert; Matsumoto, Kazue; Yamada, Kenneth M.

    2015-11-01

    The physical properties of two-dimensional (2D) extracellular matrices (ECMs) modulate cell adhesion dynamics and motility, but little is known about the roles of local microenvironmental differences in three-dimensional (3D) ECMs. Here we generate 3D collagen gels of varying matrix microarchitectures to characterize their regulation of 3D adhesion dynamics and cell migration. ECMs containing bundled fibrils demonstrate enhanced local adhesion-scale stiffness and increased adhesion stability through balanced ECM/adhesion coupling, whereas highly pliable reticular matrices promote adhesion retraction. 3D adhesion dynamics are locally regulated by ECM rigidity together with integrin/ECM association and myosin II contractility. Unlike 2D migration, abrogating contractility stalls 3D migration regardless of ECM pore size. We find force is not required for clustering of activated integrins on 3D native collagen fibrils. We propose that efficient 3D migration requires local balancing of contractility with ECM stiffness to stabilize adhesions, which facilitates the detachment of activated integrins from ECM fibrils.

  18. Interaction between p68 RNA helicase and Ca2+-calmodulin promotes cell migration and metastasis

    PubMed Central

    Wang, Haizhen; Gao, Xueliang; Yang, Jenny J.; Liu, Zhi-Ren

    2012-01-01

    Summary p68 RNA helicase is a prototypical RNA helicase. Here we present evidence to show that, by interacting with Ca-calmodulin (CaM), p68 plays a role in cancer metastasis and cell migration. A peptide fragment that spans the IQ motif of p68 strongly inhibits cancer metastasis in two different animal models. The peptide interrupts p68 and CaM interaction and inhibits cell migration. Our results demonstrate that the p68-CaM interaction is essential for the formation of lamellipodia and filopodia in migrating cells. p68 interacts with microtubules in the presence of CaM. Our experiments show that interaction with microtubules stimulates p68 ATPase activity. Further, microtubule gliding assays demonstrate that p68, in the presence of CaM, can function as a microtubule motor. This motor activity may allow p68 to transport CaM to the leading edge of migrating cells. PMID:23322042

  19. 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.

  20. Emerging role of ILK and ELMO2 in the integration of adhesion and migration pathways

    PubMed Central

    Ho, Ernest; Dagnino, Lina

    2012-01-01

    Integrins and their associated proteins are essential components of the cellular machinery that modulates adhesion and migration. In particular, integrin-linked kinase (ILK), which binds to the cytoplasmic tail of β1 integrins, is required for migration in a variety of cell types. We previously identified engulfment and motility 2 (ELMO2) as an ILK-binding protein in epidermal keratinocytes. Recently, we investigated the biological role of the ILK/ELMO2 complexes, and found that they exist in the cytoplasm. ILK/ELMO2 species are recruited by active RhoG to the plasma membrane, where they induce Rac1 activation and formation of lamellipodia at the leading edge of migrating cells. A large number of growth factors and cytokines induce keratinocyte migration. However, we found that formation of RhoG/ELMO2/ILK complexes occurs selectively upon stimulation by epidermal growth factor, but not by transforming growth factor-β1 or keratinocyte growth factor. Herein we discuss the relevance of these complexes to our understanding of the molecular mechanisms involved in cell migration, as well as their potential functions in morphogenesis and tissue regeneration following injury. PMID:22568984

  1. Emerging role of ILK and ELMO2 in the integration of adhesion and migration pathways.

    PubMed

    Ho, Ernest; Dagnino, Lina

    2012-01-01

    Integrins and their associated proteins are essential components of the cellular machinery that modulates adhesion and migration. In particular, integrin-linked kinase (ILK), which binds to the cytoplasmic tail of β1 integrins, is required for migration in a variety of cell types. We previously identified engulfment and motility 2 (ELMO2) as an ILK-binding protein in epidermal keratinocytes. Recently, we investigated the biological role of the ILK/ELMO2 complexes, and found that they exist in the cytoplasm. ILK/ELMO2 species are recruited by active RhoG to the plasma membrane, where they induce Rac1 activation and formation of lamellipodia at the leading edge of migrating cells. A large number of growth factors and cytokines induce keratinocyte migration. However, we found that formation of RhoG/ELMO2/ILK complexes occurs selectively upon stimulation by epidermal growth factor, but not by transforming growth factor-β1 or keratinocyte growth factor. Herein we discuss the relevance of these complexes to our understanding of the molecular mechanisms involved in cell migration, as well as their potential functions in morphogenesis and tissue regeneration following injury.

  2. Cell surface GRP78 facilitates hepatoma cells proliferation and migration by activating IGF-IR.

    PubMed

    Yin, Yancun; Chen, Chen; Chen, Jinliang; Zhan, Renhui; Zhang, Qiang; Xu, Xiaoyan; Li, Defang; Li, Minjing

    2017-07-01

    The 78kDa glucose regulated protein (GRP78) is a multifunctional chaperone that is involved in a variety of cellular processes. Insulin like growth factor I receptor (IGF-IR) often aberrant expresses in many types of tumor cells. The IGF-IR signaling plays key roles in carcinogenesis and maintenance of the malignant phenotype. The crosstalk between GRP78 and IGF-IR molecules has not well been illuminated. Here, we demonstrated a reciprocal regulation of GRP78 expression and IGF-IR pathway activation. IGF-I induced GRP78 expression in hepatoma cells. IGF-IR knockdown or IGF-IR inhibitor repressed GRP78 expression. Both phosphatidylinositol 3-kianase (PI3K) and mitogen-activated protein kinase (MAPK) pathways involved in IGF-I induction of GRP78 expression. Interestingly, treatment of hepatoma cells with IGF-I re-distributes GRP78 from endoplasmic reticulum (ER) to cell surface and promotes its physical interaction with IGF-IR. Also, GRP78 promotes IGF-IR phosphorylation and activation. Blocked of GRP78 by small interfering RNA or inhibition of GRP78 function by (-)-epigallocatechin gallate (EGCG) blocks IGF-I induced IGF-IR phosphorylation and its downstream signaling. Further, blocked cell surface GRP78 with antibody inhibits IGF-I stimulated cellular proliferation and migration. These data reveal an essential role for the molecular chaperone GRP78 in IGF-IR signaling and implicate the use of GRP78 inhibitors in blocking IGF-IR signaling in hepatoma cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Determinants of the Egyptian labour migration.

    PubMed

    Kandil, M; Metwally, M

    1992-03-01

    The objective is to summarize the pattern of Egyptian migration to Arab oil-producing countries (AOPC), to review some factors that are important determinants of labor movement based on theory, and to empirically model the migration rate to AOPC and to Saudi Arabia. Factors are differentiated as to their relative importance. Push factors are the low wages, high inflation rate, and high population density in Egypt; pull factors are higher wages. It is predicted that an increase in income from destination countries has a significant positive impact on the migration rate. An increase in population density stimulates migration. An increase in inflation acts to increase out-migration with a 2-year lag, which accommodates departure preparation. Egypt's experience with labor migration is described for the pre-oil boom, and the post-oil boom. Several estimates of labor migration are given. Government policy toward migration is positive. Theory postulates migration to be determined by differences in the availability of labor, labor rewards between destination and origin, and the cost of migration. In the empirical model, push factors are population density, the current inflation rate, and the ratio of income/capita in AOPC to Egypt. The results indicate that the ratio of income/capita had a strong pull impact and population density had a strong push impact. The inflation rate has a positive impact with a lag estimated at 2 years. Prior to the Camp David Accord, there was a significant decrease in the number of Egyptian migrants due to political tension. The findings support the classical theory of factor mobility. The consequences of migration on the Egyptian economy have been adverse. Future models should disaggregate data because chronic shortages exist in some parts of the labor market. Manpower needs assessment would be helpful for policy makers.

  4. WASP family proteins and formins compete in pseudopod- and bleb-based migration

    PubMed Central

    2018-01-01

    Actin pseudopods induced by SCAR/WAVE drive normal migration and chemotaxis in eukaryotic cells. Cells can also migrate using blebs, in which the edge is driven forward by hydrostatic pressure instead of actin. In Dictyostelium discoideum, loss of SCAR is compensated by WASP moving to the leading edge to generate morphologically normal pseudopods. Here we use an inducible double knockout to show that cells lacking both SCAR and WASP are unable to grow, make pseudopods or, unexpectedly, migrate using blebs. Remarkably, amounts and dynamics of actin polymerization are normal. Pseudopods are replaced in double SCAR/WASP mutants by aberrant filopods, induced by the formin dDia2. Further disruption of the gene for dDia2 restores cells’ ability to initiate blebs and thus migrate, though pseudopods are still lost. Triple knockout cells still contain near-normal F-actin levels. This work shows that SCAR, WASP, and dDia2 compete for actin. Loss of SCAR and WASP causes excessive dDia2 activity, maintaining F-actin levels but blocking pseudopod and bleb formation and migration. PMID:29191847

  5. Cohort profile: internal migration in sub-Saharan Africa—The Migration and Health in Malawi (MHM) study

    PubMed Central

    Anglewicz, Philip; VanLandingham, Mark; Manda-Taylor, Lucinda; Kohler, Hans-Peter

    2017-01-01

    Purpose The Migration and Health in Malawi (MHM) study focuses on a key challenge in migration research: although it has long been established that migration and health are closely linked, identifying the effect of migration on various health outcomes is complicated by methodological challenges. The MHM study uses a longitudinal panel premigration and postmigration study design (with a non-migrant comparison group) to measure and/or control for important characteristics that affect both migration and health outcomes. Participants Data are available for two waves. The MHM interviewed 398 of 715 migrants in 2007 (55.7%) and 722 of 1013 in 2013 (71.3%); as well as 604 of 751 (80.4%) for a non-migrant reference group in 2013. The total interviewed sample size for the MHM in both waves is 1809. These data include extensive information on lifetime migration, socioeconomic and demographic characteristics, sexual behaviours, marriage, household/family structure, social networks and social capital, HIV/AIDS biomarkers and other dimensions of health. Findings to date Our result for the relationship between migration and health differs by health measure and analytic approach. Migrants in Malawi have a significantly higher HIV prevalence than non-migrants, which is primarily due to the selection of HIV-positive individuals into migration. We find evidence for health selection; physically healthier men and women are more likely to move, partly because migration selects younger individuals. However, we do not find differences in physical or mental health between migrants and non-migrants after moving. Future plans We are preparing a third round of data collection for these (and any new) migrants, which will take place in 2018. This cohort will be used to examine the effect of migration on various health measures and behaviours, including general mental and physical health, smoking and alcohol use, access to and use of health services and use of antiretroviral therapy. PMID

  6. The geomorphic legacy of water and sediment control structures in a semiarid rangeland watershed

    USDA-ARS?s Scientific Manuscript database

    An inventory of water and sediment control structures remnant of historic cattle ranching was assembled for the Buenos Aires National Wildlife Refuge (BANWR) in southern Arizona, USA. An assessment of structural condition based on aerial imagery identified headcut initiation and channel incision as...

  7. Fisetin regulates astrocyte migration and proliferation in vitro.

    PubMed

    Wang, Nan; Yao, Fang; Li, Ke; Zhang, Lanlan; Yin, Guo; Du, Mingjun; Wu, Bingyi

    2017-04-01

    Fisetin (3,3',4',7-tetrahydroxyflavone) is a plant flavonol found in fruits and vegetables that has been reported to inhibit migration and proliferation in several types of cancer. Reactive astrogliosis involves astrocyte migration and proliferation, and contributes to the formation of glial scars in central nervous system (CNS) disorders. However, the effect of fisetin on the migration and proliferation of astrocytes remains unclear. In this study, we found that fisetin inhibited astrocyte migration in a scratch-wound assay and diminished the phosphorylation of focal adhesion kinase (FAK; Tyr576/577 and paxillin (Tyr118). It also suppressed cell proliferation, as indicated by the decreased number of 5-ethynyl-2'-deoxyuridine (EdU)-positive cells, induced cell cycle arrest in the G1 phase, reduced the percentage of cells in the G2 and S phase (as measured by flow cytometry), and decreased cyclin D1 expression, but had no effect on apoptosis. Fisetin also decreased the phosphorylation levels of Akt and extracellular signal-regulated kinase (Erk)1/2, but had no effect on the phosphorylation of p38 mitogen-activated protein kinase (MAPK). These results indicate that fisetin inhibits aggressive cell phenotypes by suppressing cell migration and proliferation via the Akt/Erk signaling pathway. Fisetin may thus have potential for use as a therapeutic strategy targeting reactive astrocytes, which may lead to the inhibition of glial scar formation in vitro.

  8. Some issues in Middle Eastern international migration.

    PubMed

    Sirageldin, I

    1983-01-01

    2 controversial issues related to the consequences of Middle Eastern international migration were examined: its effect on the development policies of the labor importing countries with a special reference to the case of Kuwait; and its effect on the growth potential of the labor exporting countries with special reference to recent development in Egypt's agricultural reproductivity. A preliminary note comments on the analytical nature of international labor migration in the Middle East and on the public view of emigrants as export commodities. The basic parameters of a desired population parity are interrelated. It is possible to influence the labor ratio (R2) as well as the nonKuwait crude labor participation rate (R3) through a migration policy. Thus, given a policy objective of some desired balance stated in trms of 1 or more of the identified parameters, it is possible to analyze the consequences of alternative migration strategies. It is important to consider the role of relative productivity (R6). An attempt to change R6 has implications for both the design of a migration policy and a national policy of human capital formation. Other factors may not be immediately related to a migration policy. The question then is whether these ratios are sensitive to policy intervention. In a simulation exercise it was assumed that the Kuwaiti crude labor force participation rate (R4) will increase by 13% during a period of 10 years. R4 increases if relatively more people work. Women are 1 segment of the labor force that is not adequately represented, partly because of traditions, lack of skills, and the presence of high fertility. None of these can change in the short run without an active policy of social reform. Yet, the assumption seems to be in the right direction. A policy that attempts to reduce R4 through increasing fertility in Kuwait is clearly against the tide. In sum, the labor importing countries faced with recent unfavorable demographic realities will actively

  9. CNTs-Modified Nb3O7F Hybrid Nanocrystal towards Faster Carrier Migration, Lower Bandgap and Higher Photocatalytic Activity.

    PubMed

    Huang, Fei; Li, Zhen; Yan, Aihua; Zhao, Hui; Liang, Huagen; Gao, Qingyu; Qiang, Yinghuai

    2017-01-06

    Novel semiconductor photocatalysts have been the research focus and received much attention in recent years. The key issues for novel semiconductor photocatalysts are to effectively harvest solar energy and enhance the separation efficiency of the electron-hole pairs. In this work, novel Nb 3 O 7 F/CNTs hybrid nanocomposites with enhanced photocatalytic activity have been successfully synthesized by a facile hydrothermal plus etching technique. The important finding is that appropriate pH values lead to the formation of Nb 3 O 7 F nanocrystal directly. A general strategy to introdue interaction between Nb 3 O 7 F and CNTs markedly enhances the photocatalytic activity of Nb 3 O 7 F. Comparatively, Nb 3 O 7 F/CNTs nanocomposites exhibit higher photodegradation efficiency and faster photodegradation rate in the solution of methylene blue (MB) under visible-light irradiation. The higher photocatalytic activity may be attributed to more exposed active sites, higher carrier migration and narrower bandgap because of good synergistic effect. The results here may inspire more engineering, new design and facile fabrication of novel photocatalysts with highly photocatalytic activity.

  10. CNTs-Modified Nb3O7F Hybrid Nanocrystal towards Faster Carrier Migration, Lower Bandgap and Higher Photocatalytic Activity

    PubMed Central

    Huang, Fei; Li, Zhen; Yan, Aihua; Zhao, Hui; Liang, Huagen; Gao, Qingyu; Qiang, Yinghuai

    2017-01-01

    Novel semiconductor photocatalysts have been the research focus and received much attention in recent years. The key issues for novel semiconductor photocatalysts are to effectively harvest solar energy and enhance the separation efficiency of the electron-hole pairs. In this work, novel Nb3O7F/CNTs hybrid nanocomposites with enhanced photocatalytic activity have been successfully synthesized by a facile hydrothermal plus etching technique. The important finding is that appropriate pH values lead to the formation of Nb3O7F nanocrystal directly. A general strategy to introdue interaction between Nb3O7F and CNTs markedly enhances the photocatalytic activity of Nb3O7F. Comparatively, Nb3O7F/CNTs nanocomposites exhibit higher photodegradation efficiency and faster photodegradation rate in the solution of methylene blue (MB) under visible-light irradiation. The higher photocatalytic activity may be attributed to more exposed active sites, higher carrier migration and narrower bandgap because of good synergistic effect. The results here may inspire more engineering, new design and facile fabrication of novel photocatalysts with highly photocatalytic activity. PMID:28059123

  11. Nucleus and nucleus-cytoskeleton connections in 3D cell migration

    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

    Cell migration plays an important role in many physiological and pathological settings, ranging from embryonic development to cancer metastasis. Currently, accumulating data suggest that cells migrating in three-dimensional (3D) environments show well-defined differences compared to their well-established two-dimensional (2D) counterparts. During 3D migration, the cell body and nucleus must deform to allow cellular passage through the available spaces, and the deformability of the relatively rigid nucleus may constitute a limiting step. Here, we highlight the key evidence regarding the role of the nuclear mechanics in 3D migration, including the molecular components that govern the stiffness of the nucleus and reviewmore » how the nuclear dynamics are connected to and controlled by cytoskeleton-based migration machinery. Intriguingly, nuclear movement must be coordinated with the cytoskeletal dynamics at the leading and trailing edges, which in turn impact the cytoplasmic dynamics that affect the migration efficiency. Thus, we suggest that alterations in the nuclear structure may facilitate cellular reorganizations that are necessary for efficient migration. - Graphical abstract: Schematic representations of a cell migrating on a 2D substrate and a cell migrating in a 3D extracellular matrix environment. (A) Nucleus-cytoskeleton connections are essential to 3D migration. Mechanical signals are transduced by integrins at the cell surface and channeled to cytoskeletal proteins, which generates prestress. The nucleus-cytoskeleton connections can either act as a stable skeleton to anchor the nuclei or provide active force to move the nuclei. The LINC complex is responsible for the nucleo-cytoskeletal coupling. Nesprins connect the cytoskeletal proteins to the inner nuclear membrane proteins SUN1 and SUN2. The SUN proteins connect to the lamins that form the lamina, which attaches to the chromatin. This physical connectivity transmits the mechanical signals from

  12. Functional characterization of the turkey macrophage migration inhibitory factor.

    PubMed

    Park, Myeongseon; Kim, Sungwon; Fetterer, Raymond H; Dalloul, Rami A

    2016-08-01

    Macrophage migration inhibitory factor (MIF) is a soluble protein that inhibits the random migration of macrophages and plays a pivotal immunoregulatory function in innate and adaptive immunity. The aim of this study was to clone the turkey MIF (TkMIF) gene, express the active protein, and characterize its basic function. The full-length TkMIF gene was amplified from total RNA extracted from turkey spleen, followed by cloning into a prokaryotic (pET11a) expression vector. Sequence analysis revealed that TkMIF consists of 115 amino acids with 12.5 kDa molecular weight. Multiple sequence alignment revealed 100%, 65%, 95% and 92% identity with chicken, duck, eagle and zebra finch MIFs, respectively. Recombinant TkMIF (rTkMIF) was expressed in Escherichia coli and purified through HPLC and endotoxin removal. SDS-PAGE analysis revealed an approximately 13.5 kDa of rTkMIF monomer containing T7 tag in soluble form. Western blot analysis showed that anti-chicken MIF (ChMIF) polyclonal antisera detected a monomer form of TkMIF at approximately 13.5 kDa size. Further functional analysis revealed that rTkMIF inhibits migration of both mononuclear cells and splenocytes in a dose-dependent manner, but was abolished by the addition of anti-ChMIF polyclonal antisera. qRT-PCR analysis revealed elevated transcripts of pro-inflammatory cytokines by rTkMIF in LPS-stimulated monocytes. rTkMIF also led to increased levels of IFN-γ and IL-17F transcripts in Con A-activated splenocytes, while IL-10 and IL-13 transcripts were decreased. Overall, the sequences of both the turkey and chicken MIF have high similarity and comparable biological functions with respect to migration inhibitory activities of macrophages and enhancement of pro-inflammatory cytokine expression, suggesting that turkey and chicken MIFs would be biologically cross-reactive. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. MMP20 Overexpression Disrupts Molar Ameloblast Polarity and Migration.

    PubMed

    Shin, M; Chavez, M B; Ikeda, A; Foster, B L; Bartlett, J D

    2018-07-01

    Ameloblasts responsible for enamel formation express matrix metalloproteinase 20 (MMP20), an enzyme that cleaves enamel matrix proteins, including amelogenin (AMELX) and ameloblastin (AMBN). Previously, we showed that continuously erupting incisors from transgenic mice overexpressing active MMP20 had a massive cell infiltrate present within their enamel space, leading to enamel mineralization defects. However, effects of MMP20 overexpression on mouse molars were not analyzed, although these teeth more accurately represent human odontogenesis. Therefore, MMP20-overexpressing mice ( Mmp20 +/+ Tg + ) were assessed by multiscale analyses, combining several approaches from high-resolution micro-computed tomography to enamel organ immunoblots. During the secretory stage at postnatal day 6 (P6), Mmp20 +/+ Tg + mice had a discontinuous ameloblast layer and, unlike incisors, molar P12 maturation stage ameloblasts abnormally migrated away from the enamel layer into the stratum intermedium/stellate reticulum. TOPflash assays performed in vitro demonstrated that MMP20 expression promoted β-catenin nuclear localization and that MMP20 expression promoted invasion through Matrigel-coated filters. However, for both assays, significant differences were eliminated in the presence of the β-catenin inhibitor ICG-001. This suggests that MMP20 activity promotes cell migration via the Wnt pathway. In vivo, the unique molar migration of amelogenin-expressing ameloblasts was associated with abnormal deposition of ectopic calcified nodules surrounding the adherent enamel layer. Enamel content was assessed just prior to eruption at P15. Compared to wild-type, Mmp20 +/+ Tg + molars exhibited significant reductions in enamel thickness (70%), volume (60%), and mineral density (40%), and MMP20 overexpression resulted in premature cleavage of AMBN, which likely contributed to the severe defects in enamel mineralization. In addition, Mmp20 +/+ Tg + mouse molar enamel organs had increased levels

  14. Pinoresinol-4,4'-di-O-beta-D-glucoside from Valeriana officinalis root stimulates calcium mobilization and chemotactic migration of mouse embryo fibroblasts.

    PubMed

    Do, Kee Hun; Choi, Young Whan; Kim, Eun Kyoung; Yun, Sung Ji; Kim, Min Sung; Lee, Sun Young; Ha, Jung Min; Kim, Jae Ho; Kim, Chi Dae; Son, Beung Gu; Kang, Jum Soon; Khan, Ikhlas A; Bae, Sun Sik

    2009-06-01

    Lignans are major constituents of plant extracts and have important pharmacological effects on mammalian cells. Here we showed that pinoresinol-4,4'-di-O-beta-D-glucoside (PDG) from Valeriana officinalis induced calcium mobilization and cell migration through the activation of lysophosphatidic acid (LPA) receptor subtypes. Stimulation of mouse embryo fibroblast (MEF) cells with 10 microM PDG resulted in strong stimulation of MEF cell migration and the EC(50) was about 2 microM. Pretreatment with pertussis toxin (PTX), an inhibitor of G(i) protein, completely blocked PDG-induced cell migration demonstrating that PDG evokes MEF cell migration through the activation of the G(i)-coupled receptor. Furthermore, pretreatment of MEF cells with Ki16425 (10 microM), which is a selective antagonist for LPA(1) and LPA(3) receptors, completely blocked PDG-induced cell migration. Likewise, PDG strongly induced calcium mobilization, which was also blocked by Ki16425 in a dose-dependent manner. Prior occupation of the LPA receptor with LPA itself completely blocked PDG-induced calcium mobilization. Finally, PDG-induced MEF cell migration was attenuated by pretreatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor such as LY294002. Cells lacking downstream mediator of PI3K such as Akt1 and Akt2 (DKO cells) showed loss of PDG-induced migration. Re-expression of Akt1 (but not Akt2) completely restored PDG-induced DKO cell migration. Given these results, we conclude that PDG is a strong inducer of cell migration. We suggest that the pharmacological action of PDG may occur through the activation of an LPA receptor whereby activation of PI3K/Akt signaling pathway mediates PDG-induced MEF cell migration.

  15. Return Migration as Failure or Success?: The Determinants of Return Migration Intentions Among Moroccan Migrants in Europe.

    PubMed

    de Haas, Hein; Fokkema, Tineke; Fihri, Mohamed Fassi

    Different migration theories generate competing hypotheses with regard to determinants of return migration. While neoclassical migration theory associates migration to the failure to integrate at the destination, the new economics of labour migration sees return migration as the logical stage after migrants have earned sufficient assets and knowledge and to invest in their origin countries. The projected return is then likely to be postponed for sustained or indefinite periods if integration is unsuccessful. So, from an indication or result of integration failure return is rather seen as a measure of success. Drawing on recent survey data ( N  = 2,832), this article tests these hypotheses by examining the main determinants of return intention among Moroccan migrants across Europe. The results indicate that structural integration through labour market participation, education and the maintenance of economic and social ties with receiving countries do not significantly affect return intentions. At the same time, investments and social ties to Morocco are positively related, and socio-cultural integration in receiving countries is negatively related to return migration intentions. The mixed results corroborate the idea that there is no uniform process of (return) migration and that competing theories might therefore be partly complementary.

  16. Microseismic source locations with deconvolution migration

    NASA Astrophysics Data System (ADS)

    Wu, Shaojiang; Wang, Yibo; Zheng, Yikang; Chang, Xu

    2018-03-01

    Identifying and locating microseismic events are critical problems in hydraulic fracturing monitoring for unconventional resources exploration. In contrast to active seismic data, microseismic data are usually recorded with unknown source excitation time and source location. In this study, we introduce deconvolution migration by combining deconvolution interferometry with interferometric cross-correlation migration (CCM). This method avoids the need for the source excitation time and enhances both the spatial resolution and robustness by eliminating the square term of the source wavelets from CCM. The proposed algorithm is divided into the following three steps: (1) generate the virtual gathers by deconvolving the master trace with all other traces in the microseismic gather to remove the unknown excitation time; (2) migrate the virtual gather to obtain a single image of the source location and (3) stack all of these images together to get the final estimation image of the source location. We test the proposed method on complex synthetic and field data set from the surface hydraulic fracturing monitoring, and compare the results with those obtained by interferometric CCM. The results demonstrate that the proposed method can obtain a 50 per cent higher spatial resolution image of the source location, and more robust estimation with smaller errors of the localization especially in the presence of velocity model errors. This method is also beneficial for source mechanism inversion and global seismology applications.

  17. A potential inhibitory function of draxin in regulating mouse trunk neural crest migration.

    PubMed

    Zhang, Sanbing; Su, Yuhong; Gao, Jinbao; Zhang, Chenbing; Tanaka, Hideaki

    2017-01-01

    Draxin is a repulsive axon guidance protein that plays important roles in the formation of three commissures in the central nervous system and dorsal interneuron 3 (dI3) in the chick spinal cord. In the present study, we report the expression pattern of mouse draxin in the embryonic mouse trunk spinal cord. In the presence of draxin, the longest net migration length of a migrating mouse trunk neural crest cell was significantly reduced. In addition, the relative number of apolar neural crest cells increased as the draxin treatment time increased. Draxin caused actin cytoskeleton rearrangement in the migrating trunk neural crest cells. Our data suggest that draxin may regulate mouse trunk neural crest cell migration by the rearrangement of cell actin cytoskeleton and by reducing the polarization activity of these cells subsequently.

  18. Characterizing and modelling river channel migration rates at a regional scale: Case study of south-east France.

    PubMed

    Alber, Adrien; Piégay, Hervé

    2017-11-01

    An increased awareness by river managers of the importance of river channel migration to sediment dynamics, habitat complexity and other ecosystem functions has led to an advance in the science and practice of identifying, protecting or restoring specific erodible corridors across which rivers are free to migrate. One current challenge is the application of these watershed-specific goals at the regional planning scales (e.g., the European Water Framework Directive). This study provides a GIS-based spatial analysis of the channel migration rates at the regional-scale. As a case study, 99 reaches were sampled in the French part of the Rhône Basin and nearby tributaries of the Mediterranean Sea (111,300 km 2 ). We explored the spatial correlation between the channel migration rate and a set of simple variables (e.g., watershed area, channel slope, stream power, active channel width). We found that the spatial variability of the channel migration rates was primary explained by the gross stream power (R 2  = 0.48) and more surprisingly by the active channel width scaled by the watershed area. The relationship between the absolute migration rate and the gross stream power is generally consistent with the published empirical models for freely meandering rivers, whereas it is less significant for the multi-thread reaches. The discussion focused on methodological constraints for a regional-scale modelling of the migration rates, and the interpretation of the empirical models. We hypothesize that the active channel width scaled by the watershed area is a surrogate for the sediment supply which may be a more critical factor than the bank resistance for explaining the regional-scale variability of the migration rates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Mental health of newly arrived Burmese refugees in Australia: contributions of pre-migration and post-migration experience.

    PubMed

    Schweitzer, Robert D; Brough, Mark; Vromans, Lyn; Asic-Kobe, Mary

    2011-04-01

    This study documents the mental health status of people from Burmese refugee backgrounds recently arrived in Australia, then examines the contributions of gender, pre-migration and post-migration factors in predicting mental health. Structured interviews, including a demographic questionnaire, the Harvard Trauma Questionnaire, the Post-migration Living Difficulties Checklist and Hopkins Symptom Checklist assessed pre-migration trauma, post-migration living difficulties, depression, anxiety, somatization and traumatization symptoms in a sample of 70 adults across five Burmese ethnic groups. Substantial proportions of participants reported psychological distress in symptomatic ranges including: post-traumatic stress disorder (9%), anxiety (20%) and depression (36%), as well as significant symptoms of somatization (37%). Participants reported multiple and severe pre-migration traumas. Post-migration living difficulties of greatest concern included communication problems and worry about family not in Australia. Gender did not predict mental health. Level of exposure to traumatic events and post-migration living difficulties each made unique and relatively equal contributions to traumatization symptoms. Post-migration living difficulties made unique contributions to depression, anxiety and somatization symptoms. While exposure to traumatic events impacted on participants' mental well-being, post-migration living difficulties had greater salience in predicting mental health outcomes of people from Burmese refugee backgrounds. Reported rates of post-traumatic stress disorder symptoms were consistent with a large review of adults across seven western countries. High levels of somatization point to a nuanced expression of distress. Findings have implications for service provision in terms of implementing appropriate interventions to effectively meet the needs of this newly arrived group in Australia.

  20. The health impacts of climate-related migration.

    PubMed

    Schwerdtle, Patricia; Bowen, Kathryn; McMichael, Celia

    2017-12-11

    Changes in climate, in conjunction with other drivers of mobility, shape human migration. While there is an increasing focus on the adaptive potential of migration, the health impacts of climate-related migration, including planned relocation and forced displacement, have not been thoroughly examined. The Intergovernmental Panel on Climate Change stated that migration is currently, and will increasingly be, influenced by environmental degradation and climate change, and that it needs to be addressed in a focused and coordinated manner. This paper examines the links between climate change, migration, and health, considering diverse migration responses, including immobility, forced displacement and planned migration, as well as the associated health risks and opportunities in different contexts. Using case studies, the paper illustrates strategies to reduce the health risks associated with climate change-related migration. While there is an increasing body of research examining the climate change-migration nexus, a dual approach is now required. This approach must include debate and further research regarding the health consequences and responses associated with climate migration as well as immediate strengthening of health systems to make them both climate resilient and migrant inclusive.

  1. [The regional context of migration: the case of Tabasco].

    PubMed

    Lezama, J L

    1991-09-01

    This work contains reflections on regional influences in determination of migratory processes, as distinct from economic and political influences at the national level. The relationship between migration and region implies discussion of the concept of regions and regional hierarchies in relation to the national level. The economic structure of a region and its influence on migration for example is related to characteristics of the same phenomenon at the national level. Migration to Mexico City and Monterrey represents a process of social change that affects all of Mexican society, both because of the regional diversity and large volume of migrants to the 2 cities and because of their importance in Mexico's economic and social development. Migration at the regional level may be determined by forces within that region or by processes at the national or even international level that are beyond local control. The particular mix of resources available in a region and the level of its development compared to other places within the nation strongly affect migratory potential. The concrete case of petroleum activity in the state of Tabasco is an example of the lack of participation at the regional level in design of investment policy. The petroleum boom of the 1960s in Tabasco produced profound economic changes in the region and caused changes in the local power structure. Particularities in the case of Tabasco included a state economy dominated by petroleum activity, deterioration in the agricultural sector accompanied by increased livestock raising, expansion of zones of population expulsion especially where livestock were most dominant, and consolidation of strong migratory flows toward the petroleum zones. External factors in the regional socioeconomic situation included the impacts generated by petroleum activity, while internal factors included the increasing importance of livestock and eclipse of agriculture even before the petroleum boom. Census and survey data

  2. Gendered Patterns of Migration in Rural South Africa

    PubMed Central

    Camlin, Carol S.; Snow, Rachel C.; Hosegood, Victoria

    2013-01-01

    Gender is increasingly recognized as fundamental to understanding migration processes, causes and consequences. In South Africa, it is intrinsic to the social transformations fueling high levels of internal migration and complex forms of mobility. While female migration in Africa has often been characterized as less prevalent than male migration, and primarily related to marriage, in South Africa a feminization of internal migration is underway, fueled by women’s increasing labor market participation. In this paper, we report sex differences in patterns, trends and determinants of internal migration based on data collected in a demographic surveillance system between 2001 and 2006 in rural KwaZulu-Natal. We show that women were somewhat more likely than men to undertake any migration, but sex differences in migration trends differed by migration flow, with women more likely to migrate into the area than men, and men more likely to out-migrate. Out-migration was suppressed by marriage particularly for women, but most women were not married; both men’s and women’s out-migrations were undertaken mainly for purposes of employment. Over half of female out-migrations (versus 35% of male out-migrations) were to nearby rural areas. The findings highlight the high mobility of this population and the extent to which gender is intimately related to the processes determining migration. We consider the implications of these findings for the measurement of migration and mobility, in particular for health and social policy and research among highly mobile populations in southern Africa. PMID:25332690

  3. Impact of Tumor Cell Cytoskeleton Organization on Invasiveness and Migration: A Microchannel-Based Approach

    PubMed Central

    Rolli, Claudio G.; Seufferlein, Thomas; Kemkemer, Ralf; Spatz, Joachim P.

    2010-01-01

    Cell migration is a fundamental feature of the interaction of cells with their surrounding. The cell's stiffness and ability to deform itself are two major characteristics that rule migration behavior especially in three-dimensional tissue. We simulate this situation making use of a micro-fabricated migration chip to test the active invasive behavior of pancreatic cancer cells (Panc-1) into narrow channels. At a channel width of 7 µm cell migration through the channels was significantly impeded due to size exclusion. A striking increase in cell invasiveness was observed once the cells were treated with the bioactive lipid sphingosylphosphorylcholine (SPC) that leads to a reorganization of the cell's keratin network, an enhancement of the cell's deformability, and also an increase in the cell's migration speed on flat surfaces. The migration speed of the highly deformed cells inside the channels was three times higher than of cells on flat substrates but was not affected upon SPC treatment. Cells inside the channels migrated predominantly by smooth sliding while maintaining constant cell length. In contrast, cells on adhesion mediating narrow lines moved in a stepwise way, characterized by fluctuations in cell length. Taken together, with our migration chip we demonstrate that the dimensionality of the environment strongly affects the migration phenotype and we suggest that the spatial cytoskeletal keratin organization correlates with the tumor cell's invasive potential. PMID:20090950

  4. Ocean-wide Drivers of Migration Strategies and Their Influence on Population Breeding Performance in a Declining Seabird.

    PubMed

    Fayet, Annette L; Freeman, Robin; Anker-Nilssen, Tycho; Diamond, Antony; Erikstad, Kjell E; Fifield, Dave; Fitzsimmons, Michelle G; Hansen, Erpur S; Harris, Mike P; Jessopp, Mark; Kouwenberg, Amy-Lee; Kress, Steve; Mowat, Stephen; Perrins, Chris M; Petersen, Aevar; Petersen, Ib K; Reiertsen, Tone K; Robertson, Gregory J; Shannon, Paula; Sigurðsson, Ingvar A; Shoji, Akiko; Wanless, Sarah; Guilford, Tim

    2017-12-18

    Which factors shape animals' migration movements across large geographical scales, how different migratory strategies emerge between populations, and how these may affect population dynamics are central questions in the field of animal migration [1] that only large-scale studies of migration patterns across a species' range can answer [2]. To address these questions, we track the migration of 270 Atlantic puffins Fratercula arctica, a red-listed, declining seabird, across their entire breeding range. We investigate the role of demographic, geographical, and environmental variables in driving spatial and behavioral differences on an ocean-basin scale by measuring puffins' among-colony differences in migratory routes and day-to-day behavior (estimated with individual daily activity budgets and energy expenditure). We show that competition and local winter resource availability are important drivers of migratory movements, with birds from larger colonies or with poorer local winter conditions migrating further and visiting less-productive waters; this in turn led to differences in flight activity and energy expenditure. Other behavioral differences emerge with latitude, with foraging effort and energy expenditure increasing when birds winter further north in colder waters. Importantly, these ocean-wide migration patterns can ultimately be linked with breeding performance: colony productivity is negatively associated with wintering latitude, population size, and migration distance, which demonstrates the cost of competition and migration on future breeding and the link between non-breeding and breeding periods. Our results help us to understand the drivers of animal migration and have important implications for population dynamics and the conservation of migratory species. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. The reorientation of cell nucleus promotes the establishment of front-rear polarity in migrating fibroblasts.

    PubMed

    Maninová, Miloslava; Klímová, Zuzana; Parsons, J Thomas; Weber, Michael J; Iwanicki, Marcin P; Vomastek, Tomáš

    2013-06-12

    The establishment of cell polarity is an essential step in the process of cell migration. This process requires precise spatiotemporal coordination of signaling pathways that in most cells create the typical asymmetrical profile of a polarized cell with nucleus located at the cell rear and the microtubule organizing center (MTOC) positioned between the nucleus and the leading edge. During cell polarization, nucleus rearward positioning promotes correct microtubule organizing center localization and thus the establishment of front-rear polarity and directional migration. We found that cell polarization and directional migration require also the reorientation of the nucleus. Nuclear reorientation is manifested as temporally restricted nuclear rotation that aligns the nuclear axis with the axis of cell migration. We also found that nuclear reorientation requires physical connection between the nucleus and cytoskeleton mediated by the LINC (linker of nucleoskeleton and cytoskeleton) complex. Nuclear reorientation is controlled by coordinated activity of lysophosphatidic acid (LPA)-mediated activation of GTPase Rho and the activation of integrin, FAK (focal adhesion kinase), Src, and p190RhoGAP signaling pathway. Integrin signaling is spatially induced at the leading edge as FAK and p190RhoGAP are predominantly activated or localized at this location. We suggest that integrin activation within lamellipodia defines cell front, and subsequent FAK, Src, and p190RhoGAP signaling represents the polarity signal that induces reorientation of the nucleus and thus promotes the establishment of front-rear polarity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Migration of the CERN IT Data Centre Support System to ServiceNow

    NASA Astrophysics Data System (ADS)

    Alvarez Alonso, R.; Arneodo, G.; Barring, O.; Bonfillou, E.; Coelho dos Santos, M.; Dore, V.; Lefebure, V.; Fedorko, I.; Grossir, A.; Hefferman, J.; Mendez Lorenzo, P.; Moller, M.; Pera Mira, O.; Salter, W.; Trevisani, F.; Toteva, Z.

    2014-06-01

    The large potential and flexibility of the ServiceNow infrastructure based on "best practises" methods is allowing the migration of some of the ticketing systems traditionally used for the monitoring of the servers and services available at the CERN IT Computer Centre. This migration enables the standardization and globalization of the ticketing and control systems implementing a generic system extensible to other departments and users. One of the activities of the Service Management project together with the Computing Facilities group has been the migration of the ITCM structure based on Remedy to ServiceNow within the context of one of the ITIL processes called Event Management. The experience gained during the first months of operation has been instrumental towards the migration to ServiceNow of other service monitoring systems and databases. The usage of this structure is also extended to the service tracking at the Wigner Centre in Budapest.

  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. Repeated, long-distance migrations by a philopatric predator targeting highly contrasting ecosystems

    PubMed Central

    Lea, James S. E.; Wetherbee, Bradley M.; Queiroz, Nuno; Burnie, Neil; Aming, Choy; Sousa, Lara L.; Mucientes, Gonzalo R.; Humphries, Nicolas E.; Harvey, Guy M.; Sims, David W.; Shivji, Mahmood S.

    2015-01-01

    Long-distance movements of animals are an important driver of population spatial dynamics and determine the extent of overlap with area-focused human activities, such as fishing. Despite global concerns of declining shark populations, a major limitation in assessments of population trends or spatial management options is the lack of information on their long-term migratory behaviour. For a large marine predator, the tiger shark Galeocerdo cuvier, we show from individuals satellite-tracked for multiple years (up to 1101 days) that adult males undertake annually repeated, round-trip migrations of over 7,500 km in the northwest Atlantic. Notably, these migrations occurred between the highly disparate ecosystems of Caribbean coral reef regions in winter and high latitude oceanic areas in summer, with strong, repeated philopatry to specific overwintering insular habitat. Partial migration also occurred, with smaller, immature individuals displaying reduced migration propensity. Foraging may be a putative motivation for these oceanic migrations, with summer behaviour showing higher path tortuosity at the oceanic range extremes. The predictable migratory patterns and use of highly divergent ecosystems shown by male tiger sharks appear broadly similar to migrations seen in birds, reptiles and mammals, and highlight opportunities for dynamic spatial management and conservation measures of highly mobile sharks. PMID:26057337

  9. Repeated, long-distance migrations by a philopatric predator targeting highly contrasting ecosystems.

    PubMed

    Lea, James S E; Wetherbee, Bradley M; Queiroz, Nuno; Burnie, Neil; Aming, Choy; Sousa, Lara L; Mucientes, Gonzalo R; Humphries, Nicolas E; Harvey, Guy M; Sims, David W; Shivji, Mahmood S

    2015-06-09

    Long-distance movements of animals are an important driver of population spatial dynamics and determine the extent of overlap with area-focused human activities, such as fishing. Despite global concerns of declining shark populations, a major limitation in assessments of population trends or spatial management options is the lack of information on their long-term migratory behaviour. For a large marine predator, the tiger shark Galeocerdo cuvier, we show from individuals satellite-tracked for multiple years (up to 1101 days) that adult males undertake annually repeated, round-trip migrations of over 7,500 km in the northwest Atlantic. Notably, these migrations occurred between the highly disparate ecosystems of Caribbean coral reef regions in winter and high latitude oceanic areas in summer, with strong, repeated philopatry to specific overwintering insular habitat. Partial migration also occurred, with smaller, immature individuals displaying reduced migration propensity. Foraging may be a putative motivation for these oceanic migrations, with summer behaviour showing higher path tortuosity at the oceanic range extremes. The predictable migratory patterns and use of highly divergent ecosystems shown by male tiger sharks appear broadly similar to migrations seen in birds, reptiles and mammals, and highlight opportunities for dynamic spatial management and conservation measures of highly mobile sharks.

  10. Repeated, long-distance migrations by a philopatric predator targeting highly contrasting ecosystems

    NASA Astrophysics Data System (ADS)

    Lea, James S. E.; Wetherbee, Bradley M.; Queiroz, Nuno; Burnie, Neil; Aming, Choy; Sousa, Lara L.; Mucientes, Gonzalo R.; Humphries, Nicolas E.; Harvey, Guy M.; Sims, David W.; Shivji, Mahmood S.

    2015-06-01

    Long-distance movements of animals are an important driver of population spatial dynamics and determine the extent of overlap with area-focused human activities, such as fishing. Despite global concerns of declining shark populations, a major limitation in assessments of population trends or spatial management options is the lack of information on their long-term migratory behaviour. For a large marine predator, the tiger shark Galeocerdo cuvier, we show from individuals satellite-tracked for multiple years (up to 1101 days) that adult males undertake annually repeated, round-trip migrations of over 7,500 km in the northwest Atlantic. Notably, these migrations occurred between the highly disparate ecosystems of Caribbean coral reef regions in winter and high latitude oceanic areas in summer, with strong, repeated philopatry to specific overwintering insular habitat. Partial migration also occurred, with smaller, immature individuals displaying reduced migration propensity. Foraging may be a putative motivation for these oceanic migrations, with summer behaviour showing higher path tortuosity at the oceanic range extremes. The predictable migratory patterns and use of highly divergent ecosystems shown by male tiger sharks appear broadly similar to migrations seen in birds, reptiles and mammals, and highlight opportunities for dynamic spatial management and conservation measures of highly mobile sharks.

  11. Podosomes, But Not the Maturation Status, Determine the Protease-Dependent 3D Migration in Human Dendritic Cells.

    PubMed

    Cougoule, Céline; Lastrucci, Claire; Guiet, Romain; Mascarau, Rémi; Meunier, Etienne; Lugo-Villarino, Geanncarlo; Neyrolles, Olivier; Poincloux, Renaud; Maridonneau-Parini, Isabelle

    2018-01-01

    Dendritic cells (DC) are professional Antigen-Presenting Cells scattered throughout antigen-exposed tissues and draining lymph nodes, and survey the body for pathogens. Their ability to migrate through tissues, a 3D environment, is essential for an effective immune response. Upon infection, recognition of Pathogen-Associated Molecular Patterns (PAMP) by Toll-like receptors (TLR) triggers DC maturation. Mature DC (mDC) essentially use the protease-independent, ROCK-dependent amoeboid mode in vivo , or in collagen matrices in vitro . However, the mechanisms of 3D migration used by human immature DC (iDC) are still poorly characterized. Here, we reveal that human monocyte-derived DC are able to use two migration modes in 3D. In porous matrices of fibrillar collagen I, iDC adopted the amoeboid migration mode. In dense matrices of gelled collagen I or Matrigel, iDC used the protease-dependent, ROCK-independent mesenchymal migration mode. Upon TLR4 activation by LPS, mDC-LPS lose the capacity to form podosomes and degrade the matrix along with impaired mesenchymal migration. TLR2 activation by Pam 3 CSK 4 resulted in DC maturation, podosome maintenance, and efficient mesenchymal migration. Under all these conditions, when DC used the mesenchymal mode in dense matrices, they formed 3D podosomes at the tip of cell protrusions. Using PGE 2 , known to disrupt podosomes in DC, we observed that the cells remained in an immature status and the mesenchymal migration mode was abolished. We also observed that, while CCL5 (attractant of iDC) enhanced both amoeboid and mesenchymal migration of iDC, CCL19 and CCL21 (attractants of mDC) only enhanced mDC-LPS amoeboid migration without triggering mesenchymal migration. Finally, we examined the migration of iDC in tumor cell spheroids, a tissue-like 3D environment. We observed that iDC infiltrated spheroids of tumor cells using both migration modes. Altogether, these results demonstrate that human DC adopt the mesenchymal mode to

  12. Vulnerable to HIV / AIDS. Migration.

    PubMed

    Fernandez, I

    1998-01-01

    This special report discusses the impact of globalization, patterns of migration in Southeast Asia, gender issues in migration, the links between migration and HIV/AIDS, and spatial mobility and social networks. Migrants are particularly marginalized in countries that blame migrants for transmission of infectious and communicable diseases and other social ills. Effective control of HIV/AIDS among migrant and native populations requires a multisectoral approach. Programs should critically review the privatization of health care services and challenge economic models that polarize the rich and the poor, men and women, North and South, and migrant and native. Programs should recognize the equality between locals and migrants in receipt of health services. Countermeasures should have input from migrants in order to reduce the conditions that increase vulnerability to HIV/AIDS. Gender-oriented research is needed to understand women's role in migration. Rapid assessment has obscured the human dimension of migrants' vulnerability to HIV. Condom promotion is not enough. Migration is a major consequence of globalization, which holds the promise, real or imagined, of prosperity for all. Mass migration can be fueled by explosive regional developments. In Southeast Asia, migration has been part of the process of economic development. The potential to emigrate increases with greater per capita income. "Tiger" economies have been labor importers. Safe sex is not practiced in many Asian countries because risk is not taken seriously. Migrants tend to be used as economic tools, without consideration of social adjustment and sex behavior among singles.

  13. Cell Migration in Tissues: Explant Culture and Live Imaging.

    PubMed

    Staneva, Ralitza; Barbazan, Jorge; Simon, Anthony; Vignjevic, Danijela Matic; Krndija, Denis

    2018-01-01

    Cell migration is a process that ensures correct cell localization and function in development and homeostasis. In disease such as cancer, cells acquire an upregulated migratory capacity that leads to their dissemination throughout the body. Live imaging of cell migration allows for better understanding of cell behaviors in development, adult tissue homeostasis and disease. We have optimized live imaging procedures to track cell migration in adult murine tissue explants derived from: (1) healthy gut; (2) primary intestinal carcinoma; and (3) the liver, a common metastatic site. To track epithelial cell migration in the gut, we generated an inducible fluorescent reporter mouse, enabling us to visualize and track individual cells in unperturbed gut epithelium. To image intratumoral cancer cells, we use a spontaneous intestinal cancer model based on the activation of Notch1 and deletion of p53 in the mouse intestinal epithelium, which gives rise to aggressive carcinoma. Interaction of cancer cells with a metastatic niche, the mouse liver, is addressed using a liver colonization model. In summary, we describe a method for long-term 3D imaging of tissue explants by two-photon excitation microscopy. Explant culturing and imaging can help understand dynamic behavior of cells in homeostasis and disease, and would be applicable to various tissues.

  14. Connective tissue growth factor is activated by gastrin and involved in gastrin-induced migration and invasion.

    PubMed

    Bhandari, Sabin; Bakke, Ingunn; Kumar, J; Beisvag, Vidar; Sandvik, Arne K; Thommesen, Liv; Varro, Andrea; Nørsett, Kristin G

    2016-06-17

    Connective tissue growth factor (CTGF) has been reported in gastric adenocarcinoma and in carcinoid tumors. The aim of this study was to explore a possible link between CTGF and gastrin in gastric epithelial cells and to study the role of CTGF in gastrin induced migration and invasion of AGS-GR cells. The effects of gastrin were studied using RT-qPCR, Western blot and assays for migration and invasion. We report an association between serum gastrin concentrations and CTGF abundancy in the gastric corpus mucosa of hypergastrinemic subjects and mice. We found a higher expression of CTGF in gastric mucosa tissue adjacent to tumor compared to normal control tissue. We showed that gastrin induced expression of CTGF in gastric epithelial AGS-GR cells via MEK, PKC and PKB/AKT pathways. CTGF inhibited gastrin induced migration and invasion of AGS-GR cells. We conclude that CTGF expression is stimulated by gastrin and involved in remodeling of the gastric epithelium. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Effect of acetaminophen on osteoblastic differentiation and migration of MC3T3-E1 cells.

    PubMed

    Nakatsu, Yoshihiro; Nakagawa, Fumio; Higashi, Sen; Ohsumi, Tomoko; Shiiba, Shunji; Watanabe, Seiji; Takeuchi, Hiroshi

    2018-02-01

    N-acetyl-p-aminophenol (APAP, acetaminophen, paracetamol) is a widely used analgesic/antipyretic with weak inhibitory effects on cyclooxygenase (COX) compared to non-steroidal anti-inflammatory drugs (NSAIDs). The mechanism of action of APAP is mediated by its metabolite that activates transient receptor potential channels, including transient receptor potential vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) or the cannabinoid receptor type 1 (CB1). However, the exact molecular mechanism and target underlying the cellular actions of APAP remain unclear. Therefore, we investigated the effect of APAP on osteoblastic differentiation and cell migration, with a particular focus on TRP channels and CB1. Effects of APAP on osteoblastic differentiation and cell migration of MC3T3-E1, a mouse pre-osteoblast cell line, were assessed by the increase in alkaline phosphatase (ALP) activity, and both wound-healing and transwell-migration assays, respectively. APAP dose-dependently inhibited osteoblastic differentiation, which was well correlated with the effects on COX activity compared with other NSAIDs. In contrast, cell migration was promoted by APAP, and this effect was not correlated with COX inhibition. None of the agonists or antagonists of TRP channels and the CB receptor affected the APAP-induced cell migration, while the effect of APAP on cell migration was abolished by down-regulating TRPV4 gene expression. APAP inhibited osteoblastic differentiation via COX inactivation while it promoted cell migration independently of previously known targets such as COX, TRPV1, TRPA1 channels, and CB receptors, but through the mechanism involving TRPV4. APAP may have still unidentified molecular targets that modify cellular functions. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

  16. 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

  17. Arrested α-hydride migration activates a phosphido ligand for C–H insertion

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

    Hickey, Anne K.; Muñoz, Salvador B.; Lutz, Sean A.

    Bulky tris(carbene)borate ligands provide access to high spin iron(II) phosphido complexes. The complex PhB(MesIm) 3FeP(H)Ph is thermally unstable, and we observed [PPh] group insertion into a C–H bond of the supporting ligand. An arrested α-hydride migration mechanism suggests increased nucleophilicity of the phosphorus atom facilitates [PPh] group transfer reactivity.

  18. 6-Phosphogluconate dehydrogenase regulates tumor cell migration in vitro by regulating receptor tyrosine kinase c-Met

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

    Chan, Barden, E-mail: cchan@bidmc.harvard.edu; VanderLaan, Paul A.; Sukhatme, Vikas P.

    2013-09-20

    Highlights: •Expression of 6PGD positively correlates with advancing stage of lung carcinoma. •Knockdown of 6PGD by shRNA potently inhibits c-Met tyrosine phosphorylation. •Exogenous HGF fails to restore c-Met phosphorylation in cells with 6PGD knocked down. •6PGD knockdown results in inhibition of cell migration in vitro. •Constitutively active TPR-cMet significantly restores migration of cells without 6PGD. -- Abstract: 6-Phosphogluconate dehydrogenase (6PGD) is the third enzyme in the oxidative pentose phosphate pathway (PPP). Recently, we reported that knockdown of 6PGD inhibited lung tumor growth in vitro and in a xenograft model in mice. In this study, we continued to examine the functionalmore » role of 6PGD in cancer. We show that 6PGD expression positively correlates with advancing stage of lung carcinoma. In search of functional signals related to 6PGD, we discovered that knockdown of 6PGD significantly inhibited phosphorylation of c-Met at tyrosine residues known to be critical for activity. This downregulation of c-Met phosphorylation correlated with inhibition of cell migration in vitro. Overexpression of a constitutively active c-Met specifically rescued the migration but not proliferation phenotype of 6PGD knockdown. Therefore, 6PGD appears to be required for efficient c-Met signaling and migration of tumor cells in vitro.« less

  19. Impacts of ontogenetically migrating copepods on downward carbon flux in the western subarctic Pacific Ocean

    NASA Astrophysics Data System (ADS)

    Kobari, Toru; Steinberg, Deborah K.; Ueda, Ai; Tsuda, Atsushi; Silver, Mary W.; Kitamura, Minoru

    2008-07-01

    To evaluate the impacts of ontogenetically (seasonally) migrating copepods on carbon transport to the mesopelagic zone, we investigated depth distribution, population structure, and feeding activity of the ontogentic copepod community in the western subarctic Pacific Ocean from day-night pairs of zooplankton samples down to 1000 m during the VERtical Transport In the Global Ocean (VERTIGO) program. Over the 31 July-16 August 2005 study period, the biomass of Neocalanus cristatus and Neocalanus plumchrus predominated in the near surface waters, while Neocalanus flemingeri was already dormant at depth. We observed a strong diel migration for Metridia pacifica, and a seasonal downward migration for Eucalanus bungii. Based on gut pigment analysis, ingestion rate of the copepod community was 214-375 mg C m -2 day -1, which was equal to 26-37% of the concurrent primary production. However, comparison of grazing estimated from gut pigments to calculated carbon demand of the copepod community indicates that phytoplankton comprised 37-59% of the ingested carbon. Thus, the copepod community appears to have also relied on detritus and microzooplankton for their nutrition, likely because primary production during this time was dominated by picophytoplankton too small to be grazed by these large copepods. Fecal pellet flux by the copepod community was estimated to account for 141-223% of the sedimentary particulate organic carbon (POC) flux at 150 m, suggesting considerable fragmentation and consumption of pellets in the upper layers. Fecal pellets alone were adequate to meet copepod carbon demand in the surface 0-150 m layer. Active carbon flux by diel migration of M. pacifica (respiration, egestion, and mortality) was 4-17 mg C m -2 day -1, equal to 6-44% of sedimentary POC flux at 150 m. Active carbon flux by N. flemingeri ontogenetic migration (i.e., respiration and mortality at depth) contributed 246 mg C m -2 year -1, equal to 9% of sedimentary POC flux at 1000 m. The

  20. Individual versus Household Migration Decision Rules: Gender and Marital Status Differences in Intentions to Migrate in South Africa.

    PubMed

    Gubhaju, Bina; De Jong, Gordon F

    2009-03-01

    This research tests the thesis that the neoclassical micro-economic and the new household economic theoretical assumptions on migration decision-making rules are segmented by gender, marital status, and time frame of intention to migrate. Comparative tests of both theories within the same study design are relatively rare. Utilizing data from the Causes of Migration in South Africa national migration survey, we analyze how individually held "own-future" versus alternative "household well-being" migration decision rules effect the intentions to migrate of male and female adults in South Africa. Results from the gender and marital status specific logistic regressions models show consistent support for the different gender-marital status decision rule thesis. Specifically, the "maximizing one's own future" neoclassical microeconomic theory proposition is more applicable for never married men and women, the "maximizing household income" proposition for married men with short-term migration intentions, and the "reduce household risk" proposition for longer time horizon migration intentions of married men and women. Results provide new evidence on the way household strategies and individual goals jointly affect intentions to move or stay.