The effects of migration on the establishment of networks: caste disintegration and reformation among the Indians of Fiji.

PubMed

Grieco, E M

1998-01-01

"This article focuses on how migration auspices affect the formation of migrant networks and ethnic communities. Using ethnographic data and migration histories to focus on caste ¿reformation' in the subcommunities of the Indians of Fiji, the ability to reestablish and maintain subcaste group ¿extensions' in Fiji is shown as directly related to the migration auspices that originally established the community. By determining the characteristics of migrants, the reason for migrating, and the magnitude and duration of migration streams, migration auspices define a migration type. This migration type affects the strength and density of social ties present in migration streams. It also affects the strength and density of network ties that members of a migrant community can establish in a receiving society." excerpt

Chemokine guided angiogenesis directs coronary vasculature formation in zebrafish

PubMed Central

Harrison, Michael R.M.; Bussmann, Jeroen; Huang, Ying; Zhao, Long; Osorio, Arthela; Burns, C. Geoffrey; Burns, Caroline E.; Sucov, Henry M.; Siekmann, Arndt F.; Lien, Ching-Ling

2015-01-01

SUMMARY Interruption of coronary blood supply severely impairs heart function with often-fatal consequences for heart disease patients. However the formation and maturation of these coronary vessels is not fully understood. Here we provide a detailed analysis of coronary vessel development in zebrafish. We observe that coronary vessels form in zebrafish by angiogenic sprouting of arterial cells derived from the endocardium at the atrioventricular canal. Endothelial cells express the CXC-motif chemokine receptor Cxcr4a and migrate to vascularize the ventricle under the guidance of the myocardium-expressed ligand Cxcl12b. cxcr4a mutant zebrafish fail to form a vascular network, whereas ectopic expression of Cxcl12b ligand induces coronary vessel formation. Importantly, cxcr4a mutant zebrafish fail to undergo heart regeneration following injury. Our results suggest that chemokine-signaling has an essential role in coronary vessel formation by directing migration of endocardium-derived endothelial cells. Poorly developed vasculature in cxcr4a mutants likely underlies decreased regenerative potential in adults. PMID:26017769

Matching times of leading and following suggest cooperation through direct reciprocity during V-formation flight in ibis

PubMed Central

Voelkl, Bernhard; Portugal, Steven J.; Unsöld, Markus; Usherwood, James R.; Wilson, Alan M.; Fritz, Johannes

2015-01-01

One conspicuous feature of several larger bird species is their annual migration in V-shaped or echelon formation. When birds are flying in these formations, energy savings can be achieved by using the aerodynamic up-wash produced by the preceding bird. As the leading bird in a formation cannot profit from this up-wash, a social dilemma arises around the question of who is going to fly in front? To investigate how this dilemma is solved, we studied the flight behavior of a flock of juvenile Northern bald ibis (Geronticus eremita) during a human-guided autumn migration. We could show that the amount of time a bird is leading a formation is strongly correlated with the time it can itself profit from flying in the wake of another bird. On the dyadic level, birds match the time they spend in the wake of each other by frequent pairwise switches of the leading position. Taken together, these results suggest that bald ibis cooperate by directly taking turns in leading a formation. On the proximate level, we propose that it is mainly the high number of iterations and the immediacy of reciprocation opportunities that favor direct reciprocation. Finally, we found evidence that the animals' propensity to reciprocate in leading has a substantial influence on the size and cohesion of the flight formations. PMID:25646487

Matching times of leading and following suggest cooperation through direct reciprocity during V-formation flight in ibis.

PubMed

Voelkl, Bernhard; Portugal, Steven J; Unsöld, Markus; Usherwood, James R; Wilson, Alan M; Fritz, Johannes

2015-02-17

One conspicuous feature of several larger bird species is their annual migration in V-shaped or echelon formation. When birds are flying in these formations, energy savings can be achieved by using the aerodynamic up-wash produced by the preceding bird. As the leading bird in a formation cannot profit from this up-wash, a social dilemma arises around the question of who is going to fly in front? To investigate how this dilemma is solved, we studied the flight behavior of a flock of juvenile Northern bald ibis (Geronticus eremita) during a human-guided autumn migration. We could show that the amount of time a bird is leading a formation is strongly correlated with the time it can itself profit from flying in the wake of another bird. On the dyadic level, birds match the time they spend in the wake of each other by frequent pairwise switches of the leading position. Taken together, these results suggest that bald ibis cooperate by directly taking turns in leading a formation. On the proximate level, we propose that it is mainly the high number of iterations and the immediacy of reciprocation opportunities that favor direct reciprocation. Finally, we found evidence that the animals' propensity to reciprocate in leading has a substantial influence on the size and cohesion of the flight formations.

Establishment of substratum polarity in the blastocoel roof of the Xenopus embryo.

PubMed

Nagel, M; Winklbauer, R

1999-05-01

The fibronectin fibril matrix on the blastocoel roof of the Xenopus gastrula contains guidance cues that determine the direction of mesoderm cell migration. The underlying guidance-related polarity of the blastocoel roof is established in the late blastula under the influence of an instructive signal from the vegetal half of the embryo, in particular from the mesoderm. Formation of an oriented substratum depends on functional activin and FGF signaling pathways in the blastocoel roof. Besides being involved in tissue polarization, activin and FGF also affect fibronectin matrix assembly. Activin treatment of the blastocoel roof inhibits fibril formation, whereas FGF modulates the structure of the fibril network. The presence of intact fibronectin fibrils is permissive for directional mesoderm migration on the blastocoel roof extracellular matrix.

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

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

PubMed Central

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

2006-01-01

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

Phosphorylation of WAVE2 by MAP kinases regulates persistent cell migration and polarity

PubMed Central

Danson, Christopher M.; Pocha, Shirin M.; Bloomberg, Graham B.; Cory, Giles O.

2009-01-01

Summary The WAVE family of proteins has long been implicated in the stimulus-dependent generation of lamellipodia at the leading edge of migrating cells, with WAVE2 in particular implicated in the formation of peripheral ruffles and chemotactic migration. However, the lack of direct visualisation of cell migration in WAVE2 mutants or knockdowns has made defining the mechanisms of WAVE2 regulation during cell migration difficult. We have characterised three MAP kinase phosphorylation sites within WAVE2 and analysed fibroblast behaviour in a scratch-wound model following introduction of transgenes encoding phospho-defective WAVE2. The cells exhibited an increase in migration speed, a decrease in the persistence of migration, and disruption of polarisation of the Golgi apparatus. All these effects could be mimicked by acute knockdown of endogenous WAVE2 expression with RNAi, indicating that phosphorylation of WAVE2 by MAP kinases regulates cell polarity during migration. PMID:18032787

Phosphorylation of WAVE2 by MAP kinases regulates persistent cell migration and polarity.

PubMed

Danson, Christopher M; Pocha, Shirin M; Bloomberg, Graham B; Cory, Giles O

2007-12-01

The WAVE family of proteins has long been implicated in the stimulus-dependent generation of lamellipodia at the leading edge of migrating cells, with WAVE2 in particular implicated in the formation of peripheral ruffles and chemotactic migration. However, the lack of direct visualisation of cell migration in WAVE2 mutants or knockdowns has made defining the mechanisms of WAVE2 regulation during cell migration difficult. We have characterised three MAP kinase phosphorylation sites within WAVE2 and analysed fibroblast behaviour in a scratch-wound model following introduction of transgenes encoding phospho-defective WAVE2. The cells exhibited an increase in migration speed, a decrease in the persistence of migration, and disruption of polarisation of the Golgi apparatus. All these effects could be mimicked by acute knockdown of endogenous WAVE2 expression with RNAi, indicating that phosphorylation of WAVE2 by MAP kinases regulates cell polarity during migration.

Asymmetrical Macromolecular Complex Formation of Lysophosphatidic Acid Receptor 2 (LPA2) Mediates Gradient Sensing in Fibroblasts*

PubMed Central

Ren, Aixia; Moon, Changsuk; Zhang, Weiqiang; Sinha, Chandrima; Yarlagadda, Sunitha; Arora, Kavisha; Wang, Xusheng; Yue, Junming; Parthasarathi, Kaushik; Heil-Chapdelaine, Rick; Tigyi, Gabor; Naren, Anjaparavanda P.

2014-01-01

Chemotactic migration of fibroblasts toward growth factors relies on their capacity to sense minute extracellular gradients and respond to spatially confined receptor-mediated signals. Currently, mechanisms underlying the gradient sensing of fibroblasts remain poorly understood. Using single-particle tracking methodology, we determined that a lysophosphatidic acid (LPA) gradient induces a spatiotemporally restricted decrease in the mobility of LPA receptor 2 (LPA2) on chemotactic fibroblasts. The onset of decreased LPA2 mobility correlates to the spatial recruitment and coupling to LPA2-interacting proteins that anchor the complex to the cytoskeleton. These localized PDZ motif-mediated macromolecular complexes of LPA2 trigger a Ca2+ puff gradient that governs gradient sensing and directional migration in response to LPA. Disruption of the PDZ motif-mediated assembly of the macromolecular complex of LPA2 disorganizes the gradient of Ca2+ puffs, disrupts gradient sensing, and reduces the directional migration of fibroblasts toward LPA. Our findings illustrate that the asymmetric macromolecular complex formation of chemoattractant receptors mediates gradient sensing and provides a new mechanistic basis for models to describe gradient sensing of fibroblasts. PMID:25542932

Hippo kinases maintain polarity during directional cell migration in Caenorhabditis elegans.

PubMed

Feng, Guoxin; Zhu, Zhiwen; Li, Wen-Jun; Lin, Qirong; Chai, Yongping; Dong, Meng-Qiu; Ou, Guangshuo

2017-02-01

Precise positioning of cells is crucial for metazoan development. Despite immense progress in the elucidation of the attractive cues of cell migration, the repulsive mechanisms that prevent the formation of secondary leading edges remain less investigated. Here, we demonstrate that Caenorhabditis elegans Hippo kinases promote cell migration along the anterior-posterior body axis via the inhibition of dorsal-ventral (DV) migration. Ectopic DV polarization was also demonstrated in gain-of-function mutant animals for C. elegans RhoG MIG-2. We identified serine 139 of MIG-2 as a novel conserved Hippo kinase phosphorylation site and demonstrated that purified Hippo kinases directly phosphorylate MIG-2 S139 Live imaging analysis of genome-edited animals indicates that MIG-2 S139 phosphorylation impedes actin assembly in migrating cells. Intriguingly, Hippo kinases are excluded from the leading edge in wild-type cells, while MIG-2 loss induces uniform distribution of Hippo kinases. We provide evidence that Hippo kinases inhibit RhoG activity locally and are in turn restricted to the cell body by RhoG-mediated polarization. Therefore, we propose that the Hippo-RhoG feedback regulation maintains cell polarity during directional cell motility. © 2016 The Authors.

Lymphatic exosomes promote dendritic cell migration along guidance cues

PubMed Central

Brown, Markus; Johnson, Louise A.; Leone, Dario A.; Majek, Peter; Senfter, Daniel; Bukosza, Nora; Asfour, Gabriele; Langer, Brigitte; Parapatics, Katja; Hong, Young-Kwon; Bennett, Keiryn L.; Sixt, Michael

2018-01-01

Lymphatic endothelial cells (LECs) release extracellular chemokines to guide the migration of dendritic cells. In this study, we report that LECs also release basolateral exosome-rich endothelial vesicles (EEVs) that are secreted in greater numbers in the presence of inflammatory cytokines and accumulate in the perivascular stroma of small lymphatic vessels in human chronic inflammatory diseases. Proteomic analyses of EEV fractions identified >1,700 cargo proteins and revealed a dominant motility-promoting protein signature. In vitro and ex vivo EEV fractions augmented cellular protrusion formation in a CX3CL1/fractalkine-dependent fashion and enhanced the directional migratory response of human dendritic cells along guidance cues. We conclude that perilymphatic LEC exosomes enhance exploratory behavior and thus promote directional migration of CX3CR1-expressing cells in complex tissue environments. PMID:29650776

Direct contact with perivascular tumor cells enhances integrin αvβ3 signaling and migration of endothelial cells

PubMed Central

Burgett, Monica E.; Lathia, Justin D.; Roth, Patrick; Nowacki, Amy S.; Galileo, Deni S.; Pugacheva, Elena; Huang, Ping; Vasanji, Amit; Li, Meizhang; Byzova, Tatiana; Mikkelsen, Tom; Bao, Shideng; Rich, Jeremy N.; Weller, Michael; Gladson, Candece L.

2016-01-01

The secretion of soluble pro-angiogenic factors by tumor cells and stromal cells in the perivascular niche promotes the aggressive angiogenesis that is typical of glioblastoma (GBM). Here, we show that angiogenesis also can be promoted by a direct interaction between brain tumor cells, including tumor cells with cancer stem-like properties (CSCs), and endothelial cells (ECs). As shown in vitro, this direct interaction is mediated by binding of integrin αvβ3 expressed on ECs to the RGD-peptide in L1CAM expressed on CSCs. It promotes both EC network formation and enhances directed migration toward basic fibroblast growth factor. Activation of αvβ3 and bone marrow tyrosine kinase on chromosome X (BMX) is required for migration stimulated by direct binding but not for migration stimulated by soluble factors. RGD-peptide treatment of mice with established intracerebral GBM xenografts significantly reduced the percentage of Sox2-positive tumor cells and CSCs in close proximity to ECs, decreased integrin αvβ3 and BMX activation and p130CAS phosphorylation in the ECs, and reduced the vessel surface area. These results reveal a previously unrecognized aspect of the regulation of angiogenesis in GBM that can impact therapeutic anti-angiogenic targeting. PMID:27270311

Quantitative cell polarity imaging defines leader-to-follower transitions during collective migration and the key role of microtubule-dependent adherens junction formation.

PubMed

Revenu, Céline; Streichan, Sebastian; Donà, Erika; Lecaudey, Virginie; Hufnagel, Lars; Gilmour, Darren

2014-03-01

The directed migration of cell collectives drives the formation of complex organ systems. A characteristic feature of many migrating collectives is a 'tissue-scale' polarity, whereby 'leader' cells at the edge of the tissue guide trailing 'followers' that become assembled into polarised epithelial tissues en route. Here, we combine quantitative imaging and perturbation approaches to investigate epithelial cell state transitions during collective migration and organogenesis, using the zebrafish lateral line primordium as an in vivo model. A readout of three-dimensional cell polarity, based on centrosomal-nucleus axes, allows the transition from migrating leaders to assembled followers to be quantitatively resolved for the first time in vivo. Using live reporters and a novel fluorescent protein timer approach, we investigate changes in cell-cell adhesion underlying this transition by monitoring cadherin receptor localisation and stability. This reveals that while cadherin 2 is expressed across the entire tissue, functional apical junctions are first assembled in the transition zone and become progressively more stable across the leader-follower axis of the tissue. Perturbation experiments demonstrate that the formation of these apical adherens junctions requires dynamic microtubules. However, once stabilised, adherens junction maintenance is microtubule independent. Combined, these data identify a mechanism for regulating leader-to-follower transitions within migrating collectives, based on the relocation and stabilisation of cadherins, and reveal a key role for dynamic microtubules in this process.

Chemokine-Dependent pH Elevation at the Cell Front Sustains Polarity in Directionally Migrating Zebrafish Germ Cells.

PubMed

Tarbashevich, Katsiaryna; Reichman-Fried, Michal; Grimaldi, Cecilia; Raz, Erez

2015-04-20

Directional cell migration requires cell polarization with respect to the distribution of the guidance cue. Cell polarization often includes asymmetric distribution of response components as well as elements of the motility machinery. Importantly, the function and regulation of most of these molecules are known to be pH dependent. Intracellular pH gradients were shown to occur in certain cells migrating in vitro, but the functional relevance of such gradients for cell migration and for the response to directional cues, particularly in the intact organism, is currently unknown. In this study, we find that primordial germ cells migrating in the context of the developing embryo respond to the graded distribution of the chemokine Cxcl12 by establishing elevated intracellular pH at the cell front. We provide insight into the mechanisms by which a polar pH distribution contributes to efficient cell migration. Specifically, we show that Carbonic Anhydrase 15b, an enzyme controlling the pH in many cell types, including metastatic cancer cells, is expressed in migrating germ cells and is crucial for establishing and maintaining an asymmetric pH distribution within them. Reducing the level of the protein and thereby erasing the pH elevation at the cell front resulted in abnormal cell migration and impaired arrival at the target. The basis for the disrupted migration is found in the stringent requirement for pH conditions in the cell for regulating contractility, for the polarization of Rac1 activity, and hence for the formation of actin-rich structures at the leading edge of the migrating cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

The matrix protein CCN1 (CYR61) promotes proliferation, migration and tube formation of endothelial progenitor cells

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

Yu Yang; Gao Yu; Wang, Hong

Neovascularization and re-endothelialization relies on circulating endothelial progenitor cells (EPCs), but their recruitment and angiogenic roles are subjected to regulation by the vascular microenvironment, which remains largely unknown. The present study was designed to investigate the effects of mature ECs and matrix protein CCN1 on the properties of EPCs. In a coculture system, effects of ECs on proliferation, migration and participation in tube-like formation of EPCs were evaluated, and functional assays were employed to identify the exact role of CCN1 in EPCs vitality and function. We demonstrated that ECs, as an indispensable part of the cellular milieu, significantly promoted themore » proliferation, migration and tube formation activities of EPCs, and more importantly, CCN1 was potentially involved in such effects of ECs. Expression of CCN1 in EPCs was significantly increased by serum, VEGF, ECs-cocultivation and ECs conditioned medium. Moreover, Ad-CCN1-mediated overexpression of CCN1 directly enhanced migration and tube formation of EPCs, whereas silencing of endogenous CCN1 in EPCs inhibits cell functions. Furthermore, CCN1 induced the expressions of chemokines and growth factors, such as MCP-1 and VEGF, suggesting a complex interaction between those proangiogenic factors. Our data suggest that matrix protein CCN1 may play an important role in microenvironment-mediated biological properties of EPCs.« less

Effect of d electrons on defect properties in equiatomic NiCoCr and NiCoFeCr concentrated solid solution alloys

DOE PAGES

Zhao, Shijun; Egami, Takeshi; Stocks, G. Malcolm; ...

2018-01-01

Here, the role of d electrons in determining distributions of formation and migration energies for point defects in equiatomic NiCoCr and NiCoFeCr concentrated solid solution alloys (CSAs) are studied regarding electron density deformation flexibility based on first-principles calculations. The disordered state is taken into account by constructing special quasirandom structures. The migration barriers are determined by directly optimizing the saddle point. It is found that the formation energies of interstitials in CSAs are lower than those in pure Ni, whereas the formation energies of vacancies are higher. In both NiCoCr and NiCoFeCr, Co-related dumbbell interstitials exhibit lower formation energies. Notably,more » the distributions of migration energies for Cr interstitials and vacancies exhibit a remarkable overlap region. A detailed analysis of electronic properties reveals that the electronic charge deformation flexibility regarding e g to t 2g transition has a dominant effect on defect energetics for different elements in CSAs. Thus the electron deformation ability is suggested as a key factor in understanding the peculiar defect behavior in CSAs.« less

Effect of d electrons on defect properties in equiatomic NiCoCr and NiCoFeCr concentrated solid solution alloys

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

Zhao, Shijun; Egami, Takeshi; Stocks, G. Malcolm

Here, the role of d electrons in determining distributions of formation and migration energies for point defects in equiatomic NiCoCr and NiCoFeCr concentrated solid solution alloys (CSAs) are studied regarding electron density deformation flexibility based on first-principles calculations. The disordered state is taken into account by constructing special quasirandom structures. The migration barriers are determined by directly optimizing the saddle point. It is found that the formation energies of interstitials in CSAs are lower than those in pure Ni, whereas the formation energies of vacancies are higher. In both NiCoCr and NiCoFeCr, Co-related dumbbell interstitials exhibit lower formation energies. Notably,more » the distributions of migration energies for Cr interstitials and vacancies exhibit a remarkable overlap region. A detailed analysis of electronic properties reveals that the electronic charge deformation flexibility regarding e g to t 2g transition has a dominant effect on defect energetics for different elements in CSAs. Thus the electron deformation ability is suggested as a key factor in understanding the peculiar defect behavior in CSAs.« less

Vinculin is required for cell polarization, migration, and extracellular matrix remodeling in 3D collagen.

PubMed

Thievessen, Ingo; Fakhri, Nikta; Steinwachs, Julian; Kraus, Viola; McIsaac, R Scott; Gao, Liang; Chen, Bi-Chang; Baird, Michelle A; Davidson, Michael W; Betzig, Eric; Oldenbourg, Rudolf; Waterman, Clare M; Fabry, Ben

2015-11-01

Vinculin is filamentous (F)-actin-binding protein enriched in integrin-based adhesions to the extracellular matrix (ECM). Whereas studies in 2-dimensional (2D) tissue culture models have suggested that vinculin negatively regulates cell migration by promoting cytoskeleton-ECM coupling to strengthen and stabilize adhesions, its role in regulating cell migration in more physiologic, 3-dimensional (3D) environments is unclear. To address the role of vinculin in 3D cell migration, we analyzed the morphodynamics, migration, and ECM remodeling of primary murine embryonic fibroblasts (MEFs) with cre/loxP-mediated vinculin gene disruption in 3D collagen I cultures. We found that vinculin promoted 3D cell migration by increasing directional persistence. Vinculin was necessary for persistent cell protrusion, cell elongation, and stable cell orientation in 3D collagen, but was dispensable for lamellipodia formation, suggesting that vinculin-mediated cell adhesion to the ECM is needed to convert actin-based cell protrusion into persistent cell shape change and migration. Consistent with this finding, vinculin was necessary for efficient traction force generation in 3D collagen without affecting myosin II activity and promoted 3D collagen fiber alignment and macroscopical gel contraction. Our results suggest that vinculin promotes directionally persistent cell migration and tension-dependent ECM remodeling in complex 3D environments by increasing cell-ECM adhesion and traction force generation. © FASEB.

Directional cell migration in an extracellular pH gradient: a model study with an engineered cell line and primary microvascular endothelial cells.

PubMed

Paradise, Ranjani K; Whitfield, Matthew J; Lauffenburger, Douglas A; Van Vliet, Krystyn J

2013-02-15

Extracellular pH (pH(e)) gradients are characteristic of tumor and wound environments. Cell migration in these environments is critical to tumor progression and wound healing. While it has been shown previously that cell migration can be modulated in conditions of spatially invariant acidic pH(e) due to acid-induced activation of cell surface integrin receptors, the effects of pH(e) gradients on cell migration remain unknown. Here, we investigate cell migration in an extracellular pH(e) gradient, using both model α(v)β(3) CHO-B2 cells and primary microvascular endothelial cells. For both cell types, we find that the mean cell position shifts toward the acidic end of the gradient over time, and that cells preferentially polarize toward the acidic end of the gradient during migration. We further demonstrate that cell membrane protrusion stability and actin-integrin adhesion complex formation are increased in acidic pH(e), which could contribute to the preferential polarization toward acidic pH(e) that we observed for cells in pH(e) gradients. These results provide the first demonstration of preferential cell migration toward acid in a pH(e) gradient, with intriguing implications for directed cell migration in the tumor and wound healing environments. Copyright © 2012 Elsevier Inc. All rights reserved.

Anterior gradient 2 is induced in cutaneous wound and promotes wound healing through its adhesion domain.

PubMed

Zhu, Qi; Mangukiya, Hitesh Bhagavanbhai; Mashausi, Dhahiri Saidi; Guo, Hao; Negi, Hema; Merugu, Siva Bharath; Wu, Zhenghua; Li, Dawei

2017-09-01

Anterior gradient 2 (AGR2), a member of protein disulfide isomerase (PDI) family, is both located in cytoplasm and secreted into extracellular matrix. The orthologs of AGR2 have been linked to limb regeneration in newt and wound healing in zebrafish. In mammals, AGR2 influences multiple cell signaling pathways in tumor formation and in normal cell functions related to new tissue formation like angiogenesis. However, the function of AGR2 in mammalian wound healing remains unknown. This study aimed to investigate AGR2 expression and its function during skin wound healing and the possible application of external AGR2 in cutaneous wound to accelerate the healing process. Our results showed that AGR2 expression was induced in the migrating epidermal tongue and hyperplastic epidermis after skin excision. Topical application of recombinant AGR2 significantly accelerated wound-healing process by increasing the migration of keratinocytes (Kera.) and the recruitment of fibroblasts (Fibro.) near the wounded area. External AGR2 also promoted the migration of Kera. and Fibro. in vitro in a dose-dependent manner. The adhesion domain of AGR2 was required for the formation of focal adhesions in migrating Fibro., leading to the directional migration along AGR2 gradient. These results indicate that recombinant AGR2 accelerates skin wound healing through regulation of Kera. and Fibro. migration, thus demonstrating its potential utility as an alternative strategy of the therapeutics to accelerate the healing of acute or chronic skin wounds. © 2017 Federation of European Biochemical Societies.

Formation mechanism of gas bubble superlattice in UMo metal fuels: Phase-field modeling investigation

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

Hu, Shenyang; Burkes, Douglas E.; Lavender, Curt A.

2016-07-08

Nano-gas bubble superlattices are often observed in irradiated UMo nuclear fuels. However, the for- mation mechanism of gas bubble superlattices is not well understood. A number of physical processes may affect the gas bubble nucleation and growth; hence, the morphology of gas bubble microstructures including size and spatial distributions. In this work, a phase-field model integrating a first-passage Monte Carlo method to investigate the formation mechanism of gas bubble superlattices was devel- oped. Six physical processes are taken into account in the model: 1) heterogeneous generation of gas atoms, vacancies, and interstitials informed from atomistic simulations; 2) one-dimensional (1-D) migration of interstitials; 3) irradiation-induced dissolution of gas atoms; 4) recombination between vacancies and interstitials; 5) elastic interaction; and 6) heterogeneous nucleation of gas bubbles. We found that the elastic interaction doesn’t cause the gas bubble alignment, and fast 1-D migration of interstitials alongmore » $$\\langle$$110$$\\rangle$$ directions in the body-centered cubic U matrix causes the gas bubble alignment along $$\\langle$$110$$\\rangle$$ directions. It implies that 1-D interstitial migration along [110] direction should be the primary mechanism of a fcc gas bubble superlattice which is observed in bcc UMo alloys. Simulations also show that fission rates, saturated gas concentration, and elastic interaction all affect the morphology of gas bubble microstructures.« less

Linking the Primary Cilium to Cell Migration in Tissue Repair and Brain Development

PubMed Central

Veland, Iben Rønn; Lindbæk, Louise; Christensen, Søren Tvorup

2014-01-01

Primary cilia are unique sensory organelles that coordinate cellular signaling networks in vertebrates. Inevitably, defects in the formation or function of primary cilia lead to imbalanced regulation of cellular processes that causes multisystemic disorders and diseases, commonly known as ciliopathies. Mounting evidence has demonstrated that primary cilia coordinate multiple activities that are required for cell migration, which, when they are aberrantly regulated, lead to defects in organogenesis and tissue repair, as well as metastasis of tumors. Here, we present an overview on how primary cilia may contribute to the regulation of the cellular signaling pathways that control cyclic processes in directional cell migration. PMID:26955067

E-cadherin is required for cranial neural crest migration in Xenopus laevis.

PubMed

Huang, Chaolie; Kratzer, Marie-Claire; Wedlich, Doris; Kashef, Jubin

2016-03-15

The cranial neural crest (CNC) is a highly motile and multipotent embryonic cell population, which migrates directionally on defined routes throughout the embryo, contributing to facial structures including cartilage, bone and ganglia. Cadherin-mediated cell-cell adhesion is known to play a crucial role in the directional migration of CNC cells. However, migrating CNC co-express different cadherin subtypes, and their individual roles have yet to be fully explored. In previous studies, the expression of individual cadherin subtypes has been analysed using different methods with varying sensitivities, preventing the direct comparison of expression levels. Here, we provide the first comprehensive and comparative analysis of the expression of six cadherin superfamily members during different phases of CNC cell migration in Xenopus. By applying a quantitative RT-qPCR approach, we can determine the copy number and abundance of each expressed cadherin through different phases of CNC migration. Using this approach, we show for the first time expression of E-cadherin and XB/C-cadherin in CNC cells, adding them as two new members of cadherins co-expressed during CNC migration. Cadherin co-expression during CNC migration in Xenopus, in particular the constant expression of E-cadherin, contradicts the classical epithelial-mesenchymal transition (EMT) model postulating a switch in cadherin expression. Loss-of-function experiments further show that E-cadherin is required for proper CNC cell migration in vivo and also for cell protrusion formation in vitro. Knockdown of E-cadherin is not rescued by co-injection of other classical cadherins, pointing to a specific function of E-cadherin in mediating CNC cell migration. Finally, through reconstitution experiments with different E-cadherin deletion mutants in E-cadherin morphant embryos, we demonstrate that the extracellular domain, but not the cytoplasmic domain, of E-cadherin is sufficient to rescue CNC cell migration in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

Flow and diffusion in channel-guided cell migration.

PubMed

Marel, Anna-Kristina; Zorn, Matthias; Klingner, Christoph; Wedlich-Söldner, Roland; Frey, Erwin; Rädler, Joachim O

2014-09-02

Collective migration of mechanically coupled cell layers is a notable feature of wound healing, embryonic development, and cancer progression. In confluent epithelial sheets, the dynamics have been found to be highly heterogeneous, exhibiting spontaneous formation of swirls, long-range correlations, and glass-like dynamic arrest as a function of cell density. In contrast, the flow-like properties of one-sided cell-sheet expansion in confining geometries are not well understood. Here, we studied the short- and long-term flow of Madin-Darby canine kidney (MDCK) cells as they moved through microchannels. Using single-cell tracking and particle image velocimetry (PIV), we found that a defined averaged stationary cell current emerged that exhibited a velocity gradient in the direction of migration and a plug-flow-like profile across the advancing sheet. The observed flow velocity can be decomposed into a constant term of directed cell migration and a diffusion-like contribution that increases with density gradient. The diffusive component is consistent with the cell-density profile and front propagation speed predicted by the Fisher-Kolmogorov equation. To connect diffusion-mediated transport to underlying cellular motility, we studied single-cell trajectories and occurrence of vorticity. We discovered that the directed large-scale cell flow altered fluctuations in cellular motion at short length scales: vorticity maps showed a reduced frequency of swirl formation in channel flow compared with resting sheets of equal cell density. Furthermore, under flow, single-cell trajectories showed persistent long-range, random-walk behavior superimposed on drift, whereas cells in resting tissue did not show significant displacements with respect to neighboring cells. Our work thus suggests that active cell migration manifests itself in an underlying, spatially uniform drift as well as in randomized bursts of short-range correlated motion that lead to a diffusion-mediated transport. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

On the post-25 Ma geodynamic evolution of the western Mediterranean

NASA Astrophysics Data System (ADS)

Gueguen, Erwan; Doglioni, Carlo; Fernandez, Manuel

1998-11-01

During the Neogene and Quaternary western Mediterranean geodynamics were dominated by the `eastward' migration of the Apenninic arc and associated back-arc basins. The migration was controlled by retreat of the Apenninic slab and was associated with `boudinage' of the lithosphere in the back-arc area. Palaeo-reconstruction of the kinematics of the arc suggests about 775 km of migration from the Late Oligocene to present along a transect from the Gulf of Lions to Calabria. A maximum of 135 km of N-S converge occurred between Africa and Europe during the same time span. The western Mediterranean was thus mainly shaped by the migration of the slab related to west-directed subduction. It is hypothesized that minor N-S convergence deformed the arc but was not the cause of its formation.

From N-WASP to WAVE: key molecules for regulation of cortical actin organization.

PubMed

Takenawa, Tadaomi

2005-01-01

We first isolated N-WASP as one of the proteins bound to Ash/Grb2 SH3 domain. This protein has a VCA region (verplorin-like, cofilin-like, acidic region) at the C-terminus, which binds to G-actin and Arp2/3 complex, and several functional domains at the N-terminus, such as WHD (WASP homology domain) and GBD/CRIB domain. N-WASP activates Arp2/3 complex-dependent actin polymerization through the VCA region, leading to filopodium formation. Next, we found WAVE1, WAVE2 and WAVE3. All these proteins have also VCA regions at C-terminal areas and induce membrane ruffle formation. To clarify the different roles of WAVE1 and WAVE2, we established WAVE1- and WAVE2-deficient mouse embryonic fibroblasts (MEFs), because these two WAVEs are expressed in MEF. When wild-type MEFs are stimulated randomly by PDGF, two types of ruffles, peripheral and dorsal, are formed. However, dorsal ruffle formation does not occurin WAVE1-deficient MEFs. In contrast, peripheral ruffle formation is diminished in WAVE2-deficient MEFs. On the other hand, in MEFs migrating towards a chemoattractant gradient, only peripheral ruffles (lamellipodia) are formed. In this migration, WAVE1-deficient MEFs still could form lamellipodia but WAVE2-deficient MEFs could not. All these data show that WAVE2 but not WAVE1 is essential for lamellipodium formation and directed migration.

Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact

PubMed Central

Ray, Thomas A; Roy, Suva; Kozlowski, Christopher; Wang, Jingjing; Cafaro, Jon; Hulbert, Samuel W; Wright, Christopher V; Field, Greg D

2018-01-01

A common strategy by which developing neurons locate their synaptic partners is through projections to circuit-specific neuropil sublayers. Once established, sublayers serve as a substrate for selective synapse formation, but how sublayers arise during neurodevelopment remains unknown. Here, we identify the earliest events that initiate formation of the direction-selective circuit in the inner plexiform layer of mouse retina. We demonstrate that radially migrating newborn starburst amacrine cells establish homotypic contacts on arrival at the inner retina. These contacts, mediated by the cell-surface protein MEGF10, trigger neuropil innervation resulting in generation of two sublayers comprising starburst-cell dendrites. This dendritic scaffold then recruits projections from circuit partners. Abolishing MEGF10-mediated contacts profoundly delays and ultimately disrupts sublayer formation, leading to broader direction tuning and weaker direction-selectivity in retinal ganglion cells. Our findings reveal a mechanism by which differentiating neurons transition from migratory to mature morphology, and highlight this mechanism’s importance in forming circuit-specific sublayers. PMID:29611808

New Natural Pigment Fraction Isolated from Saw Palmetto: Potential for Adjuvant Therapy of Hepatocellular Carcinoma.

PubMed

Tan, Hor-Yue; Wang, Ning; Takahashi, Masao; Feng, Yigang; Li, Hongyun; Feng, Yibin

2016-08-05

For the first time, we discovered a small proportion of aqueous fraction from Saw Palmetto apart from the fatty acid-rich fraction exhibited pharmacological activity. Therefore, this study aims to explore the anti-tumor potential of red pigmented aqueous fraction of Saw Palmetto, NYG on human hepatocellular carcinoma and its possible targets. Subcutaneous xenograft and orthotopic implantation models of HCC were used to evaluate the tumor inhibitory effect of NYG. Human hepatocellular carcinoma (HCC) cell lines and human umbilical vein endothelial cells (HUVEC) were used as in vitro model. The mRNA expression was conducted by qPCR. Protein expression was monitored by immunoblotting and immunohistochemistry. Cell migration and blood vessel formation were determined by chamber assay and tube formation assay, respectively. Significant tumor inhibition of NYG in dose-dependent manner was observed on subcutaneous xenograft and orthotopic HCC model. NYG has no direct action on cell viability or VEGF secretion of HCC cells. However, NYG reduced in vitro migration and vessel formation activities of HUVEC cells, as well as in vivo intratumoral neovascularization. NYG attenuated extracellular signal-regulated kinases (ERK) activation in endothelial cells, which may be associated with the suppression of migration and tube formation of HUVEC. NYG suppressed tumor expansion of HCC via inhibiting neovascularization, and may be potential adjuvant treatment for HCC.

Physiological correlates of symbiont migration during bleaching of two octocoral species.

PubMed

Netherton, Sarah E; Scheer, Daniele M; Morrison, Patrick R; Parrin, Austin P; Blackstone, Neil W

2014-05-01

Perturbed colonies of Phenganax parrini and Sarcothelia sp. exhibit migration of symbionts of Symbiodinium spp. into the stolons. Densitometry and visual inspection indicated that polyps bleached while stolons did not. When migration was triggered by temperature, light and confinement, colonies of Sarcothelia sp. decreased rates of oxygen formation in the light (due to the effects of perturbation on photosynthesis and respiration) and increased rates of oxygen uptake in the dark (due to the effects of perturbation on respiration alone). Colonies of P. parrini, by contrast, showed no significant changes in either aspect of oxygen metabolism. When migration was triggered by light and confinement, colonies of Sarcothelia sp. showed decreased rates of oxygen formation in the light and increased rates of oxygen uptake in the dark, while colonies of P. parrini maintained the former and increased the latter. During symbiont migration into their stolons, colonies of both species showed dramatic increases in reactive oxygen species (ROS), as visualized with a fluorescent probe, with stolons of Sarcothelia sp. exhibiting a nearly immediate increase of ROS. Differences in symbiont type may explain the greater sensitivity of colonies of Sarcothelia sp. Using fluorescent probes, direct measurements of migrating symbionts in the stolons of Sarcothelia sp. showed higher levels of reactive nitrogen species and lower levels of ROS than the surrounding host tissue. As measured by native fluorescence, levels of NAD(P)H in the stolons were unaffected by perturbation. Symbiont migration thus correlates with dramatic physiological changes and may serve as a marker for coral condition.

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.

WAVE2 Protein Complex Coupled to Membrane and Microtubules.

PubMed

Takahashi, Kazuhide

2012-01-01

E-cadherin is one of the key molecules in the formation of cell-cell adhesion and interacts intracellularly with a group of proteins collectively named catenins, through which the E-cadherin-catenin complex is anchored to actin-based cytoskeletal components. Although cell-cell adhesion is often disrupted in cancer cells by either genetic or epigenetic alterations in cell adhesion molecules, disruption of cell-cell adhesion alone seems to be insufficient for the induction of cancer cell migration and invasion. A small GTP-binding protein, Rac1, induces the specific cellular protrusions lamellipodia via WAVE2, a member of WASP/WAVE family of the actin cytoskeletal regulatory proteins. Biochemical and pharmacological investigations have revealed that WAVE2 interacts with many proteins that regulate microtubule growth, actin assembly, and membrane targeting of proteins, all of which are necessary for directional cell migration through lamellipodia formation. These findings might have important implications for the development of effective therapeutic agents against cancer cell migration and invasion.

WAVE2 Protein Complex Coupled to Membrane and Microtubules

PubMed Central

Takahashi, Kazuhide

2012-01-01

E-cadherin is one of the key molecules in the formation of cell-cell adhesion and interacts intracellularly with a group of proteins collectively named catenins, through which the E-cadherin-catenin complex is anchored to actin-based cytoskeletal components. Although cell-cell adhesion is often disrupted in cancer cells by either genetic or epigenetic alterations in cell adhesion molecules, disruption of cell-cell adhesion alone seems to be insufficient for the induction of cancer cell migration and invasion. A small GTP-binding protein, Rac1, induces the specific cellular protrusions lamellipodia via WAVE2, a member of WASP/WAVE family of the actin cytoskeletal regulatory proteins. Biochemical and pharmacological investigations have revealed that WAVE2 interacts with many proteins that regulate microtubule growth, actin assembly, and membrane targeting of proteins, all of which are necessary for directional cell migration through lamellipodia formation. These findings might have important implications for the development of effective therapeutic agents against cancer cell migration and invasion. PMID:22315597

The fission yeast meiosis-specific Dmc1 recombinase mediates formation and branch migration of Holliday junctions by preferentially promoting strand exchange in a direction opposite to that of Rad51

PubMed Central

Murayama, Yasuto; Tsutsui, Yasuhiro; Iwasaki, Hiroshi

2011-01-01

Homologous recombination proceeds via the formation of several intermediates including Holliday junctions (HJs), which are important for creating crossover products. DNA strand exchange is a core reaction that produces these intermediates that is directly catalyzed by RecA family recombinases, of which there are two types in eukaryotes: universal Rad51 and meiosis-specific Dmc1. We demonstrated previously that Rad51 promotes four-strand exchange, mimicking the formation and branch migration of HJs. Here we show that Dmc1 from fission yeast has a similar activity, which requires ATP hydrolysis and is independent of an absolute requirement for the Swi5–Sfr1 complex. These features are critically different from three-strand exchange mediated by Dmc1, but similar to those of four-strand exchange mediated by Rad51, suggesting that strand exchange reactions between duplex–duplex and single-duplex DNAs are mechanistically different. Interestingly, despite similarities in protein structure and in reaction features, the preferential polarities of Dmc1 and Rad51 strand exchange are different (Dmc1 promotes exchange in the 5′-to-3′ direction and Rad51 promotes exchange in the 3′-to-5′ direction relative to the ssDNA region of the DNA substrate). The significance of the Dmc1 polarity is discussed within the context of the necessity for crossover production. PMID:21363965

RhoA regulates Activin B-induced stress fiber formation and migration of bone marrow-derived mesenchymal stromal cell through distinct signaling.

PubMed

Wang, Xueer; Tang, Pei; Guo, Fukun; Zhang, Min; Chen, Yinghua; Yan, Yuan; Tian, Zhihui; Xu, Pengcheng; Zhang, Lei; Zhang, Lu; Zhang, Lin

2017-01-01

In our previous study, Activin B induced actin stress fiber formation and cell migration in Bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. However, the underlying molecular mechanisms are not well studied. RhoA is recognized to play a critical role in the regulation of actomyosin cytoskeletal organization and cell migration. Pull-down assay was performed to investigate the activity of RhoA. The dominant-negative mutants of RhoA (RhoA(N19)) was used to determine whether RhoA has a role in Activin B-induced cytoskeleton organization and cell migration in BMSCs. Cytoskeleton organization was examined by fluorescence Rhodamine-phalloidin staining, and cell migration by transwell and cell scratching assay. Western blot was carried out to investigate downstream signaling cascade of RhoA. Inhibitor and siRNAs were used to detect the role of downstream signaling in stress fiber formation and/or cell migration. RhoA was activated by Activin B in BMSCs. RhoA(N19) blocked Activin B-induced stress fiber formation and cell migration. ROCK inhibitor blocked Activin B-induced stress fiber formation but enhanced BMSCs migration. Activin B induced phosphorylation of LIMK2 and Cofilin, which was abolished by ROCK inhibition. Both of siRNA LIMK2 and siRNA Cofilin inhibited Activin B-induced stress fiber formation. RhoA regulates Activin B-induced stress fiber formation and migration of BMSCs. A RhoA-ROCK-LIMK2-Cofilin signaling node exists and regulates actin stress fiber formation. RhoA regulates Activin B-induced cell migration independent of ROCK. Better understanding of the molecular mechanisms of BMSCs migration will help optimize therapeutic strategy to target BMSCs at injured tissues. Copyright © 2016 Elsevier B.V. All rights reserved.

The Outdoor Classroom. Experiencing Nature in the Elementary Curriculum.

ERIC Educational Resources Information Center

Alexander, Phyllis, Ed.; And Others

Through direct experience within natural settings, outdoor education allows students to learn about environmental concerns such as migration of birds, weather systems, wildlife habitats, watersheds, soil erosion, geological formations, food chains, and community resources. All subject areas in the present curriculum can be enriched through outdoor…

Nonautonomous Roles of MAB-5/Hox and the Secreted Basement Membrane Molecule SPON-1/F-Spondin in Caenorhabditis elegans Neuronal Migration.

PubMed

Josephson, Matthew P; Miltner, Adam M; Lundquist, Erik A

2016-08-01

Nervous system development and circuit formation requires neurons to migrate from their birthplaces to specific destinations.Migrating neurons detect extracellular cues that provide guidance information. In Caenorhabditis elegans, the Q right (QR) and Q left (QL) neuroblast descendants migrate long distances in opposite directions. The Hox gene lin-39 cell autonomously promotes anterior QR descendant migration, and mab-5/Hox cell autonomously promotes posterior QL descendant migration. Here we describe a nonautonomous role of mab-5 in regulating both QR and QL descendant migrations, a role masked by redundancy with lin-39 A third Hox gene, egl-5/Abdominal-B, also likely nonautonomously regulates Q descendant migrations. In the lin-39 mab-5 egl-5 triple mutant, little if any QR and QL descendant migration occurs. In addition to well-described roles of lin-39 and mab-5 in the Q descendants, our results suggest that lin-39, mab-5, and egl-5 might also pattern the posterior region of the animal for Q descendant migration. Previous studies showed that the spon-1 gene might be a target of MAB-5 in Q descendant migration. spon-1 encodes a secreted basement membrane molecule similar to vertebrate F-spondin. Here we show that spon-1 acts nonautonomously to control Q descendant migration, and might function as a permissive rather than instructive signal for cell migration. We find that increased levels of MAB-5 in body wall muscle (BWM) can drive the spon-1 promoter adjacent to the Q cells, and loss of spon-1 suppresses mab-5 gain of function. Thus, MAB-5 might nonautonomously control Q descendant migrations by patterning the posterior region of the animal to which Q cells respond. spon-1 expression from BWMs might be part of the posterior patterning necessary for directed Q descendant migration. Copyright © 2016 by the Genetics Society of America.

Nonautonomous Roles of MAB-5/Hox and the Secreted Basement Membrane Molecule SPON-1/F-Spondin in Caenorhabditis elegans Neuronal Migration

PubMed Central

Josephson, Matthew P.; Miltner, Adam M.; Lundquist, Erik A.

2016-01-01

Nervous system development and circuit formation requires neurons to migrate from their birthplaces to specific destinations.Migrating neurons detect extracellular cues that provide guidance information. In Caenorhabditis elegans, the Q right (QR) and Q left (QL) neuroblast descendants migrate long distances in opposite directions. The Hox gene lin-39 cell autonomously promotes anterior QR descendant migration, and mab-5/Hox cell autonomously promotes posterior QL descendant migration. Here we describe a nonautonomous role of mab-5 in regulating both QR and QL descendant migrations, a role masked by redundancy with lin-39. A third Hox gene, egl-5/Abdominal-B, also likely nonautonomously regulates Q descendant migrations. In the lin-39mab-5egl-5 triple mutant, little if any QR and QL descendant migration occurs. In addition to well-described roles of lin-39 and mab-5 in the Q descendants, our results suggest that lin-39, mab-5, and egl-5 might also pattern the posterior region of the animal for Q descendant migration. Previous studies showed that the spon-1 gene might be a target of MAB-5 in Q descendant migration. spon-1 encodes a secreted basement membrane molecule similar to vertebrate F-spondin. Here we show that spon-1 acts nonautonomously to control Q descendant migration, and might function as a permissive rather than instructive signal for cell migration. We find that increased levels of MAB-5 in body wall muscle (BWM) can drive the spon-1 promoter adjacent to the Q cells, and loss of spon-1 suppresses mab-5 gain of function. Thus, MAB-5 might nonautonomously control Q descendant migrations by patterning the posterior region of the animal to which Q cells respond. spon-1 expression from BWMs might be part of the posterior patterning necessary for directed Q descendant migration. PMID:27225683

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

Dong Subo; Katz, Boaz; Socrates, Aristotle

Upcoming direct-imaging experiments may detect a new class of long-period, highly luminous, tidally powered extrasolar gas giants. Even though they are hosted by {approx} Gyr-'old' main-sequence stars, they can be as 'hot' as young Jupiters at {approx}100 Myr, the prime targets of direct-imaging surveys. They are on years-long orbits and presently migrating to 'feed' the 'hot Jupiters'. They are expected from 'high-e' migration mechanisms, in which Jupiters are excited to highly eccentric orbits and then shrink semimajor axis by a factor of {approx}10-100 due to tidal dissipation at close periastron passages. The dissipated orbital energy is converted to heat, andmore » if it is deposited deep enough into the atmosphere, the planet likely radiates steadily at luminosity L {approx} 100-1000 L{sub Jup}(2 Multiplication-Sign 10{sup -7}-2 Multiplication-Sign 10{sup -6} L{sub Sun }) during a typical {approx} Gyr migration timescale. Their large orbital separations and expected high planet-to-star flux ratios in IR make them potentially accessible to high-contrast imaging instruments on 10 m class telescopes. {approx}10 such planets are expected to exist around FGK dwarfs within {approx}50 pc. Long-period radial velocity planets are viable candidates, and the highly eccentric planet HD 20782b at maximum angular separation {approx}0.''08 is a promising candidate. Directly imaging these tidally powered Jupiters would enable a direct test of high-e migration mechanisms. Once detected, the luminosity would provide a direct measurement of the migration rate, and together with mass (and possibly radius) estimate, they would serve as a laboratory to study planetary spectral formation and tidal physics.« less

Monocytes from HIV+ individuals show impaired cholesterol efflux and increased foam cell formation after transendothelial migration

PubMed Central

MAISA, Anna; HEARPS, Anna C.; ANGELOVICH, Thomas A.; PEREIRA, Candida F.; ZHOU, Jingling; SHI, Margaret D.Y.; PALMER, Clovis S.; MULLER, William A.; CROWE, Suzanne M.; JAWOROWSKI, Anthony

2016-01-01

Design HIV+ individuals have an increased risk of atherosclerosis and cardiovascular disease which is independent of antiretroviral therapy and traditional risk factors. Monocytes play a central role in the development of atherosclerosis, and HIV-related chronic inflammation and monocyte activation may contribute to increased atherosclerosis, but the mechanisms are unknown. Methods Using an in vitro model of atherosclerotic plaque formation, we measured the transendothelial migration of purified monocytes from age-matched HIV+ and uninfected donors and examined their differentiation into foam cells. Cholesterol efflux and the expression of cholesterol metabolism genes were also assessed. Results Monocytes from HIV+ individuals showed increased foam cell formation compared to controls (18.9% vs 0% respectively, p=0.004) and serum from virologically suppressed HIV+ individuals potentiated foam cell formation by monocytes from both uninfected and HIV+ donors. Plasma TNF levels were increased in HIV+ vs control donors (5.9 vs 3.5 pg/ml, p=0.02) and foam cell formation was inhibited by blocking antibodies to TNF receptors, suggesting a direct effect on monocyte differentiation to foam cells. Monocytes from virologically suppressed HIV+ donors showed impaired cholesterol efflux and decreased expression of key genes regulating cholesterol metabolism, including the cholesterol transporter ABCA1 (p=0.02). Conclusions Monocytes from HIV+ individuals show impaired cholesterol efflux and are primed for foam cell formation following trans-endothelial migration. Factors present in HIV+ serum, including elevated TNF levels, further enhance foam cell formation. The pro-atherogenic phenotype of monocytes persists in virologically suppressed HIV+ individuals and may contribute mechanistically to increased atherosclerosis in this population. PMID:26244384

Actin dynamics in cells on nanotopographical surfaces in competition with chemotaxis and electrotaxis

NASA Astrophysics Data System (ADS)

Schmidt, Sebastian

Directed cell migration can be guided by different types of gradients, for example chemotaxis. We use surfaces with nanotopographical ridges to examine a type of guidance called esotaxis on migration in the well-studied amoeba Dictyostelium Discoideum. In this work we compare chemotaxis with esotaxis on ridges as well as the influence of electrotaxis on the formation of the actin cytoskeleton on these nanotopographies. These esotactic surfaces have more guidance cues for cells than planar 2D cultures and can disrupt other guidance types like chemotaxis.

Directional cell elongation through filopodia-steered lamellipodial extension on patterned silk fibroin films.

PubMed

You, Renchuan; Li, Xiufang; Luo, Zuwei; Qu, Jing; Li, Mingzhong

2015-03-05

Micropatterned biomaterials have been used to direct cell alignment for specific tissue engineering applications. However, the understanding of how cells respond to guidance cues remains limited. Plasticity in protrusion formation has been proposed to enable cells to adapt their motility mode to microenvironment. In this study, the authors investigated the key role of protrusion response in cell guidance on patterned silk fibroin films. The results revealed that the ability to transform between filopodia and small lamellipodia played important roles in directional cell guidance. Filopodia did not show directional extension on patterned substrates prior to spreading, but they transduced topographical cues to the cell to trigger the formation of small lamellipodia along the direction of a microgrooved or parallel nanofiber pattern. The polar lamellipodia formation provided not only a path with directionality, but a driving force for directional cell elongation. Moreover, aligned nanofibers coating provided better mechanical support for the traction of filopodia and lamellipodia, promoting cell attachment, spreading, and migration. This study provides new insight into how cells respond to guidance cues and how filopodia and lamellipodia control cell contact guidance on micropatterned biomaterial surfaces.

Chimera Analysis Supports a Predominant Role of PDGFRβ in Promoting Smooth-Muscle Cell Chemotaxis after Arterial Injury

PubMed Central

Buetow, Bernard S.; Tappan, Kristen A.; Crosby, Jeffrey R.; Seifert, Ronald A.; Bowen-Pope, Daniel F.

2003-01-01

The carotid artery shows a common response to many forms of injury, including a rapid activation of smooth muscle cell (SMC) proliferation in the media and migration of SMCs into the intima to form a neointima. Platelet-derived growth factor (PDGF) is believed to play a role in this response to injury, but it has proven difficult to distinguish whether it is stimulating cell migration or cell proliferation, and whether the action is direct or indirect. To determine this, we created chimeric mice composed of both wild-type (WT) and marked PDGF receptor β (PDGFRβ)-deficient cells, and determined the consequences of PDGFRβ expression for SMC participation in response to ligation of the left common carotid artery. The proportion of PDGFRβ−/− SMCs increased 4.5-fold in the media and decreased 1.8-fold during formation of the neointima, consistent with migration of WT SMCs out of the media and into the intima, leaving the PDGFRβ−/− cells behind. The fibrotic reaction in the adventitia, which does not involve cell migration, did not result in any change in relative abundance of WT and PDGFRβ-deficient fibroblasts. We conclude that the most significant direct role of PDGFRβ is to mediate responses that involve cell migration rather than proliferation. PMID:12937138

New Natural Pigment Fraction Isolated from Saw Palmetto: Potential for Adjuvant Therapy of Hepatocellular Carcinoma

PubMed Central

Tan, Hor-Yue; Wang, Ning; Takahashi, Masao; Feng, Yigang; Li, Hongyun; Feng, Yibin

2016-01-01

For the first time, we discovered a small proportion of aqueous fraction from Saw Palmetto apart from the fatty acid-rich fraction exhibited pharmacological activity. Therefore, this study aims to explore the anti-tumor potential of red pigmented aqueous fraction of Saw Palmetto, NYG on human hepatocellular carcinoma and its possible targets. Subcutaneous xenograft and orthotopic implantation models of HCC were used to evaluate the tumor inhibitory effect of NYG. Human hepatocellular carcinoma (HCC) cell lines and human umbilical vein endothelial cells (HUVEC) were used as in vitro model. The mRNA expression was conducted by qPCR. Protein expression was monitored by immunoblotting and immunohistochemistry. Cell migration and blood vessel formation were determined by chamber assay and tube formation assay, respectively. Significant tumor inhibition of NYG in dose-dependent manner was observed on subcutaneous xenograft and orthotopic HCC model. NYG has no direct action on cell viability or VEGF secretion of HCC cells. However, NYG reduced in vitro migration and vessel formation activities of HUVEC cells, as well as in vivo intratumoral neovascularization. NYG attenuated extracellular signal-regulated kinases (ERK) activation in endothelial cells, which may be associated with the suppression of migration and tube formation of HUVEC. NYG suppressed tumor expansion of HCC via inhibiting neovascularization, and may be potential adjuvant treatment for HCC. PMID:27527161

Migration of cells in a social context

PubMed Central

Vedel, Søren; Tay, Savaş; Johnston, Darius M.; Bruus, Henrik; Quake, Stephen R.

2013-01-01

In multicellular organisms and complex ecosystems, cells migrate in a social context. Whereas this is essential for the basic processes of life, the influence of neighboring cells on the individual remains poorly understood. Previous work on isolated cells has observed a stereotypical migratory behavior characterized by short-time directional persistence with long-time random movement. We discovered a much richer dynamic in the social context, with significant variations in directionality, displacement, and speed, which are all modulated by local cell density. We developed a mathematical model based on the experimentally identified “cellular traffic rules” and basic physics that revealed that these emergent behaviors are caused by the interplay of single-cell properties and intercellular interactions, the latter being dominated by a pseudopod formation bias mediated by secreted chemicals and pseudopod collapse following collisions. The model demonstrates how aspects of complex biology can be explained by simple rules of physics and constitutes a rapid test bed for future studies of collective migration of individual cells. PMID:23251032

Migration of cells in a social context.

PubMed

Vedel, Søren; Tay, Savaş; Johnston, Darius M; Bruus, Henrik; Quake, Stephen R

2013-01-02

In multicellular organisms and complex ecosystems, cells migrate in a social context. Whereas this is essential for the basic processes of life, the influence of neighboring cells on the individual remains poorly understood. Previous work on isolated cells has observed a stereotypical migratory behavior characterized by short-time directional persistence with long-time random movement. We discovered a much richer dynamic in the social context, with significant variations in directionality, displacement, and speed, which are all modulated by local cell density. We developed a mathematical model based on the experimentally identified "cellular traffic rules" and basic physics that revealed that these emergent behaviors are caused by the interplay of single-cell properties and intercellular interactions, the latter being dominated by a pseudopod formation bias mediated by secreted chemicals and pseudopod collapse following collisions. The model demonstrates how aspects of complex biology can be explained by simple rules of physics and constitutes a rapid test bed for future studies of collective migration of individual cells.

Vinculin is required for cell polarization, migration, and extracellular matrix remodeling in 3D collagen

PubMed Central

Thievessen, Ingo; Fakhri, Nikta; Steinwachs, Julian; Kraus, Viola; McIsaac, R. Scott; Gao, Liang; Chen, Bi-Chang; Baird, Michelle A.; Davidson, Michael W.; Betzig, Eric; Oldenbourg, Rudolf; Waterman, Clare M.; Fabry, Ben

2015-01-01

Vinculin is filamentous (F)-actin-binding protein enriched in integrin-based adhesions to the extracellular matrix (ECM). Whereas studies in 2-dimensional (2D) tissue culture models have suggested that vinculin negatively regulates cell migration by promoting cytoskeleton–ECM coupling to strengthen and stabilize adhesions, its role in regulating cell migration in more physiologic, 3-dimensional (3D) environments is unclear. To address the role of vinculin in 3D cell migration, we analyzed the morphodynamics, migration, and ECM remodeling of primary murine embryonic fibroblasts (MEFs) with cre/loxP-mediated vinculin gene disruption in 3D collagen I cultures. We found that vinculin promoted 3D cell migration by increasing directional persistence. Vinculin was necessary for persistent cell protrusion, cell elongation, and stable cell orientation in 3D collagen, but was dispensable for lamellipodia formation, suggesting that vinculin-mediated cell adhesion to the ECM is needed to convert actin-based cell protrusion into persistent cell shape change and migration. Consistent with this finding, vinculin was necessary for efficient traction force generation in 3D collagen without affecting myosin II activity and promoted 3D collagen fiber alignment and macroscopical gel contraction. Our results suggest that vinculin promotes directionally persistent cell migration and tension-dependent ECM remodeling in complex 3D environments by increasing cell–ECM adhesion and traction force generation.—Thievessen, I., Fakhri, N., Steinwachs, J., Kraus, V., McIsaac, R. S., Gao, L., Chen, B.-C., Baird, M. A., Davidson, M. W., Betzig, E., Oldenbourg, R., Waterman, C., M., Fabry, B. Vinculin is required for cell polarization, migration, and extracellular matrix remodeling in 3D collagen. PMID:26195589

Manipulation of Schwann cell migration across the astrocyte boundary by polysialyltransferase-loaded superparamagnetic nanoparticles under magnetic field

PubMed Central

Xia, Bing; Huang, Liangliang; Zhu, Lei; Liu, Zhongyang; Ma, Teng; Zhu, Shu; Huang, Jinghui; Luo, Zhuojing

2016-01-01

Schwann cell (SC) transplantation is an attractive strategy for spinal cord injury (SCI). However, the efficacy of SC transplantation has been limited by the poor migratory ability of SCs in the astrocyte-rich central nervous system (CNS) environment and the inability to intermingle with the host astrocyte. In this study, we first magnetofected SCs by polysialyltransferase-functionalized superparamagnetic iron oxide nanoparticles (PST/SPIONs) to induce overexpression of polysialylation of neural cell adhesion molecule (PSA-NCAM) to enhance SC migration ability, before manipulating the direction of SC migration with the assistance of an applied magnetic field (MF). It was found that magnetofection with PST/SPIONs significantly upregulated the expression of PSA-NCAM in SCs, which significantly enhanced the migration ability of SCs, but without preferential direction in the absence of MF. The number and averaged maximum distance of SCs with PST/SPIONs migrating into the astrocyte domain were significantly enhanced by an applied MF. In a 300 μm row along the astrocyte boundary, the number of SCs with PST/SPIONs migrating into the astrocyte domain under an MF was 2.95 and 6.71 times higher than that in the absence of MF and the intact control SCs, respectively. More interestingly, a confrontation assay demonstrated that SCs with PST/SPIONs were in close contact with astrocytes and no longer formed boundaries in the presence of MF. In conclusion, SCs with PST/SPIONs showed enhanced preferential migration along the axis of a magnetic force, which might be beneficial for the formation of Büngner bands in the CNS. These findings raise the possibilities of enhancing the migration of transplanted SCs in astrocyte-rich CNS regions in a specific direction and creating an SC bridge in the CNS environment to guide regenerated axons to their distal destination in the treatment of SCI. PMID:28003748

Fast-crawling cell types migrate to avoid the direction of periodic substratum stretching

PubMed Central

Okimura, Chika; Ueda, Kazuki; Sakumura, Yuichi; Iwadate, Yoshiaki

2016-01-01

ABSTRACT To investigate the relationship between mechanical stimuli from substrata and related cell functions, one of the most useful techniques is the application of mechanical stimuli via periodic stretching of elastic substrata. In response to this stimulus, Dictyostelium discoideum cells migrate in a direction perpendicular to the stretching direction. The origins of directional migration, higher migration velocity in the direction perpendicular to the stretching direction or the higher probability of a switch of migration direction to perpendicular to the stretching direction, however, remain unknown. In this study, we applied periodic stretching stimuli to neutrophil-like differentiated HL-60 cells, which migrate perpendicular to the direction of stretch. Detailed analysis of the trajectories of HL-60 cells and Dictyostelium cells obtained in a previous study revealed that the higher probability of a switch of migration direction to that perpendicular to the direction of stretching was the main cause of such directional migration. This directional migration appears to be a strategy adopted by fast-crawling cells in which they do not migrate faster in the direction they want to go, but migrate to avoid a direction they do not want to go. PMID:26980079

Ingression-type cell migration drives vegetal endoderm internalisation in the Xenopus gastrula

PubMed Central

Wen, Jason WH

2017-01-01

During amphibian gastrulation, presumptive endoderm is internalised as part of vegetal rotation, a large-scale movement that encompasses the whole vegetal half of the embryo. It has been considered a gastrulation process unique to amphibians, but we show that at the cell level, endoderm internalisation exhibits characteristics reminiscent of bottle cell formation and ingression, known mechanisms of germ layer internalisation. During ingression proper, cells leave a single-layered epithelium. In vegetal rotation, the process occurs in a multilayered cell mass; we refer to it as ingression-type cell migration. Endoderm cells move by amoeboid shape changes, but in contrast to other instances of amoeboid migration, trailing edge retraction involves ephrinB1-dependent macropinocytosis and trans-endocytosis. Moreover, although cells are separated by wide gaps, they are connected by filiform protrusions, and their migration depends on C-cadherin and the matrix protein fibronectin. Cells move in the same direction but at different velocities, to rearrange by differential migration. PMID:28826499

Immigrant Families over the Life Course: Research Directions and Needs

ERIC Educational Resources Information Center

Clark, Rebecca L.; Glick, Jennifer E.; Bures, Regina M.

2009-01-01

Family researchers and policy makers are giving increasing attention to the consequences of immigration for families. Immigration affects the lives of family members who migrate as well as those who remain behind and has important consequences for family formation, kinship ties, living arrangements, and children's outcomes. We present a selective…

Cell Blebbing in Confined Microfluidic Environments

PubMed Central

Ibo, Markela; Srivastava, Vasudha; Robinson, Douglas N.; Gagnon, Zachary R.

2016-01-01

Migrating cells can extend their leading edge by forming myosin-driven blebs and F-actin-driven pseudopods. When coerced to migrate in resistive environments, Dictyostelium cells switch from using predominately pseudopods to blebs. Bleb formation has been shown to be chemotactic and can be influenced by the direction of the chemotactic gradient. In this study, we determine the blebbing responses of developed cells of Dictyostelium discoideum to cAMP gradients of varying steepness produced in microfluidic channels with different confining heights, ranging between 1.7 μm and 3.8 μm. We show that microfluidic confinement height, gradient steepness, buffer osmolarity and Myosin II activity are important factors in determining whether cells migrate with blebs or with pseudopods. Dictyostelium cells were observed migrating within the confines of microfluidic gradient channels. When the cAMP gradient steepness is increased from 0.7 nM/μm to 20 nM/μm, cells switch from moving with a mixture of blebs and pseudopods to moving only using blebs when chemotaxing in channels with confinement heights less than 2.4 μm. Furthermore, the size of the blebs increases with gradient steepness and correlates with increases in myosin-II localization at the cell cortex. Reduction of intracellular pressure by high osmolarity buffer or inhibition of myosin-II by blebbistatin leads to a decrease in bleb formation and bleb size. Together, our data reveal that the protrusion type formed by migrating cells can be influenced by the channel height and the steepness of the cAMP gradient, and suggests that a combination of confinement-induced myosin-II localization and cAMP-regulated cortical contraction leads to increased intracellular fluid pressure and bleb formation. PMID:27706201

Modeling biogenic gas bubbles formation and migration in coarse sand

NASA Astrophysics Data System (ADS)

Ye, S.

2011-12-01

Shujun Ye Department of Hydrosciences, School of Earth Sciences and Engineering, Nanjing University, Nanjing 210093, China; sjye@nju.edu.cn Brent E. Sleep Department of Civil Engineering, University of Toronto, Toronto, ON, M5S 1A4 CANADA; sleep@ecf.utoronto.ca Methane gas generation in porous media was investigated in an anaerobic two-dimensional sand-filled cell. Inoculation of the lower portion of the cell with a methanogenic culture and addition of methanol to the bottom of the cell led to biomass growth and formation of a gas phase. The formation, migration, distribution and saturation of gases in the cell were visualized by the charge-coupled device (CCD) camera. Gas generated at the bottom of the cell in the biologically active zone moved upwards in discrete fingers, so that gas phase saturations (gas-filled fraction of void space) in the biologically active zone at the bottom of the cell did not exceed 40-50%, while gas accumulation at the top of the cell produced gas phase saturations as high as 80%. Macroscopic invasion percolation (MIP) at near pore scale[Glass, et al., 2001; Kueper and McWhorter, 1992]was used to model gas bubbles growth in porous media. The nonwetting phase migration pathway can be yielded directly by MIP. MIP was adopted to simulate the expansion, fragmentation, and mobilization of gas clusters in the cell. The production of gas, and gas phash saturations were simulated by a continuum model - compositional simulator (COMPSIM) [Sleep and Sykes, 1993]. So a combination of a continuum model and a MIP model was used to simulate the formation, fragmentation and migration of biogenic gas bubbles. Key words: biogenic gas; two dimensional; porous media; MIP; COMPSIM

Migration behaviour of silicone moulds in contact with different foodstuffs.

PubMed

Helling, Ruediger; Kutschbach, Katja; Joachim Simat, Thomas

2010-03-01

Various foodstuffs were prepared in silicone baking moulds and analyzed for siloxane migration using a previously developed and validated (1)H-NMR method. Meat loaf significantly exceeded the overall migration limit of 60 mg kg(-1) (10 mg sdm(-1)) in the first and third experiment. The highest siloxane migration found in a meat loaf after preparation in a commercial mould was 177 mg kg(-1). In contrast, milk-based food showed very low or non-detectable migration (<2.4 mg kg(-1)), even containing high fat levels. Similar results were achieved using 50% ethanol as the simulant for milk-based products, as defined in the Plastics Directive 2007/19/EEC. After solvent extraction of the moulds in simulating long-term usage, no further migration into the food was detectable, indicating that there is no significant formation of low molecular weight, potentially migrating siloxanes from the elastomer. During repeated usage, the moulds showed a high uptake of fat: up to 8.0 g fat per kg elastomer. Proper tempering of the moulds had a major influence on the migration properties of siloxanes into different foodstuffs. Non-tempered moulds with a high level of volatile organic compounds (1.1%) were shown to have considerably higher migration than the equivalent tempered moulds.

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

Focal adhesion kinase-dependent focal adhesion recruitment of SH2 domains directs SRC into focal adhesions to regulate cell adhesion and migration

PubMed Central

Wu, Jui-Chung; Chen, Yu-Chen; Kuo, Chih-Ting; Wenshin Yu, Helen; Chen, Yin-Quan; Chiou, Arthur; Kuo, Jean-Cheng

2015-01-01

Directed cell migration requires dynamical control of the protein complex within focal adhesions (FAs) and this control is regulated by signaling events involving tyrosine phosphorylation. We screened the SH2 domains present in tyrosine-specific kinases and phosphatases found within FAs, including SRC, SHP1 and SHP2, and examined whether these enzymes transiently target FAs via their SH2 domains. We found that the SRC_SH2 domain and the SHP2_N-SH2 domain are associated with FAs, but only the SRC_SH2 domain is able to be regulated by focal adhesion kinase (FAK). The FAK-dependent association of the SRC_SH2 domain is necessary and sufficient for SRC FA targeting. When the targeting of SRC into FAs is inhibited, there is significant suppression of SRC-mediated phosphorylation of paxillin and FAK; this results in an inhibition of FA formation and maturation and a reduction in cell migration. This study reveals an association between FAs and the SRC_SH2 domain as well as between FAs and the SHP2_N-SH2 domains. This supports the hypothesis that the FAK-regulated SRC_SH2 domain plays an important role in directing SRC into FAs and that this SRC-mediated FA signaling drives cell migration. PMID:26681405

Focal adhesion kinase-dependent focal adhesion recruitment of SH2 domains directs SRC into focal adhesions to regulate cell adhesion and migration.

PubMed

Wu, Jui-Chung; Chen, Yu-Chen; Kuo, Chih-Ting; Wenshin Yu, Helen; Chen, Yin-Quan; Chiou, Arthur; Kuo, Jean-Cheng

2015-12-18

Directed cell migration requires dynamical control of the protein complex within focal adhesions (FAs) and this control is regulated by signaling events involving tyrosine phosphorylation. We screened the SH2 domains present in tyrosine-specific kinases and phosphatases found within FAs, including SRC, SHP1 and SHP2, and examined whether these enzymes transiently target FAs via their SH2 domains. We found that the SRC_SH2 domain and the SHP2_N-SH2 domain are associated with FAs, but only the SRC_SH2 domain is able to be regulated by focal adhesion kinase (FAK). The FAK-dependent association of the SRC_SH2 domain is necessary and sufficient for SRC FA targeting. When the targeting of SRC into FAs is inhibited, there is significant suppression of SRC-mediated phosphorylation of paxillin and FAK; this results in an inhibition of FA formation and maturation and a reduction in cell migration. This study reveals an association between FAs and the SRC_SH2 domain as well as between FAs and the SHP2_N-SH2 domains. This supports the hypothesis that the FAK-regulated SRC_SH2 domain plays an important role in directing SRC into FAs and that this SRC-mediated FA signaling drives cell migration.

Fine tuning cellular recognition: The function of the leucine rich repeat (LRR) trans-membrane protein, LRT, in muscle targeting to tendon cells.

PubMed

Gilsohn, Eli; Volk, Talila

2010-01-01

The formation of complex tissues during embryonic development is often accompanied by directed cellular migration towards a target tissue. Specific mutual recognition between the migrating cell and its target tissue leads to the arrest of the cell migratory behavior and subsequent contact formation between the two interacting cell types. Recent studies implicated a novel family of surface proteins containing a trans-membrane domain and single leucine-rich repeat (LRR) domain in inter-cellular recognition and the arrest of cell migration. Here, we describe the involvement of a novel LRR surface protein, LRT, in targeting migrating muscles towards their corresponding tendon cells in the Drosophila embryo. LRT is specifically expressed by the target tendon cells and is essential for arresting the migratory behavior of the muscle cells. Additional studies in Drosophila S2 cultured cells suggest that LRT forms a protein complex with the Roundabout (Robo) receptor, essential for guiding muscles towards their tendon partners. Genetic analysis supports a model in which LRT performs its activity non-autonomously through its interaction with the Robo receptors expressed on the muscle surfaces. These results suggest a novel mechanism of intercellular recognition through interactions between LRR family members and Robo receptors.

Tectonic-1 contributes to the growth and migration of prostate cancer cells in vitro

PubMed Central

WANG, ZHIJUN; GAO, YI; LIU, YUSHAN; CHEN, JIE; WANG, JUNKAI; GAN, SISHUN; XU, DANFENG; CUI, XINGANG

2015-01-01

Tectonic-1 (TCTN1) is an upstream gene involved in embryonic development. The aim of the present study was to investigate the effect of the TCTN1 gene on the viability and migration of prostate cancer cells. Lentivirus-mediated short hairpin RNA (shRNA) was constructed to silence the expression of TCTN1 in PC-3 and DU145 prostate cancer cells. Cell viability and proliferation were measured using MTT and colony formation assays, and the distribution of cells in phases of the cell cycle was determined using flow cytometry. Cell migration was detected using a Transwell assay. The results demonstrated that TCTN1 was widely expressed in several human prostate cancer cell lines. Knockdown of the TCTN1 gene by RNA interference markedly suppressed cell viability and colony formation in the PC-3 and DU145 cell lines. Cell cycle progression was also arrested by TCTN1 silencing. In addition, knockdown of the TCTN1 gene led to the inhibition of cell migration in the two cell lines. These findings confirmed the direct association between the TCTN1 gene and prostate cancer growth in vitro. With further understanding and clinical investigation, this indicates the potential for future development of a novel marker for early detection and gene therapy for prostate cancer. PMID:26310786

Venous-derived angioblasts generate organ-specific vessels during zebrafish embryonic development.

PubMed

Hen, Gideon; Nicenboim, Julian; Mayseless, Oded; Asaf, Lihee; Shin, Masahiro; Busolin, Giorgia; Hofi, Roy; Almog, Gabriella; Tiso, Natascia; Lawson, Nathan D; Yaniv, Karina

2015-12-15

Formation and remodeling of vascular beds are complex processes orchestrated by multiple signaling pathways. Although it is well accepted that vessels of a particular organ display specific features that enable them to fulfill distinct functions, the embryonic origins of tissue-specific vessels and the molecular mechanisms regulating their formation are poorly understood. The subintestinal plexus of the zebrafish embryo comprises vessels that vascularize the gut, liver and pancreas and, as such, represents an ideal model in which to investigate the early steps of organ-specific vessel formation. Here, we show that both arterial and venous components of the subintestinal plexus originate from a pool of specialized angioblasts residing in the floor of the posterior cardinal vein (PCV). Using live imaging of zebrafish embryos, in combination with photoconvertable transgenic reporters, we demonstrate that these angioblasts undergo two phases of migration and differentiation. Initially, a subintestinal vein forms and expands ventrally through a Bone Morphogenetic Protein-dependent step of collective migration. Concomitantly, a Vascular Endothelial Growth Factor-dependent shift in the directionality of migration, coupled to the upregulation of arterial markers, is observed, which culminates with the generation of the supraintestinal artery. Together, our results establish the zebrafish subintestinal plexus as an advantageous model for the study of organ-specific vessel development and provide new insights into the molecular mechanisms controlling its formation. More broadly, our findings suggest that PCV-specialized angioblasts contribute not only to the formation of the early trunk vasculature, but also to the establishment of late-forming, tissue-specific vascular beds. © 2015. Published by The Company of Biologists Ltd.

Bleb Expansion in Migrating Cells Depends on Supply of Membrane from Cell Surface Invaginations.

PubMed

Goudarzi, Mohammad; Tarbashevich, Katsiaryna; Mildner, Karina; Begemann, Isabell; Garcia, Jamie; Paksa, Azadeh; Reichman-Fried, Michal; Mahabaleshwar, Harsha; Blaser, Heiko; Hartwig, Johannes; Zeuschner, Dagmar; Galic, Milos; Bagnat, Michel; Betz, Timo; Raz, Erez

2017-12-04

Cell migration is essential for morphogenesis, organ formation, and homeostasis, with relevance for clinical conditions. The migration of primordial germ cells (PGCs) is a useful model for studying this process in the context of the developing embryo. Zebrafish PGC migration depends on the formation of cellular protrusions in form of blebs, a type of protrusion found in various cell types. Here we report on the mechanisms allowing the inflation of the membrane during bleb formation. We show that the rapid expansion of the protrusion depends on membrane invaginations that are localized preferentially at the cell front. The formation of these invaginations requires the function of Cdc42, and their unfolding allows bleb inflation and dynamic cell-shape changes performed by migrating cells. Inhibiting the formation and release of the invaginations strongly interfered with bleb formation, cell motility, and the ability of the cells to reach their target. Copyright © 2017 Elsevier Inc. All rights reserved.

Nitrosoureas inhibit the stathmin-mediated migration and invasion of malignant glioma cells.

PubMed

Liang, Xing-Jie; Choi, Yong; Sackett, Dan L; Park, John K

2008-07-01

Malignant gliomas are the most common primary intrinsic brain tumors and are highly lethal. The widespread migration and invasion of neoplastic cells from the initial site of tumor formation into the surrounding brain render these lesions refractory to definitive surgical treatment. Stathmin, a microtubule-destabilizing protein that mediates cell cycle progression, can also regulate directed cell movement. Nitrosoureas, traditionally viewed as DNA alkylating agents, can also covalently modify proteins such as stathmin. We therefore sought to establish a role for stathmin in malignant glioma cell motility, migration, and invasion and determine the effects of nitrosoureas on these cell movement-related processes. Scratch wound-healing recovery, Boyden chamber migration, Matrigel invasion, and organotypic slice invasion assays were performed before and after the down-regulation of cellular stathmin levels and in the absence and presence of sublethal nitrosourea ([1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea]; CCNU) concentrations. We show that decreases in stathmin expression lead to significant decreases in malignant glioma cell motility, migration, and invasion. CCNU, at a concentration of 10 micromol/L, causes similar significant decreases, even in the absence of any effects on cell viability. The direct inhibition of stathmin by CCNU is likely a contributing factor. These findings suggest that the inhibition of stathmin expression and function may be useful in limiting the spread of malignant gliomas within the brain, and that nitrosoureas may have therapeutic benefits in addition to their antiproliferative effects.

Golgi polarization plays a role in the directional migration of neonatal dermal fibroblasts induced by the direct current electric fields.

PubMed

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

2015-05-01

Directional cell migration requires cell polarization. The reorganization of the Golgi apparatus is an important phenomenon in the polarization and migration of many types of cells. Direct current electric fields (dc (EF) induced directional cell migration in a wide variety of cells. Here nHDFs migrated toward cathode under 1 V/cm dc EF, however 1 μM of brefeldin A (BFA) inhibited the dc EF induced directional migration. BFA (1 μM) did not cause the complete Golgi dispersal for 2 h. When the Golgi polarization maintained their direction of polarity, the direction of cell migration also kept toward the same direction of the Golgi polarization even though the dc EF was reversed. In this study, the importance of the Golgi polarization in the directional migration of nHDf under dc EF was identified. Copyright © 2015 Elsevier Inc. All rights reserved.

Uranium migration and favourable sites of potential radioelement concentrations in Gabal Umm Hammad area, Central Eastern Desert, Egypt

NASA Astrophysics Data System (ADS)

Youssef, Mohamed A. S.; Sabra, Mohamed Elsadek M.; Abdeldayem, Abdelaziz L.; Masoud, Alaa A.; Mansour, Salah A.

2017-12-01

Airborne gamma-ray spectrometric data, covering Gabal Umm Hammad area, near Quseir City, in the Eastern Desert of Egypt, has been utilized to identify the uranium migration path, and U, Th and K-favorability indices. The following of the uranium migration technique enabled estimation of the amount of migrated uranium, in and out of the rock units. Investigation of the Taref Formation, Nakhil Formation, Tarawan Formation and Dawi Formation shows large negative amount of uranium migration, indicating that uranium leaching is outward from the geologic body toward surrounding rock units. Moreover, calculation of the U, Th and K-favorability indices has been carried out for the various rock units to locate the rocks having the highest radioelement potentialities. The rock units that possess relatively major probability of uranium potentiality include Mu‧tiq Group, weakly deformed granitic rocks, and Trachyte plugs and sheets. Meanwhile, the rock units with major potential of Th-index are Taref Formation, Quseir Formation and Dawi Formation. The rock units with major potential of K-index are Dokhan volcanic and Mu‧tiq group.

Quantitative Analysis of Cell Migration Using Optical Flow

PubMed Central

Boric, Katica; Orio, Patricio; Viéville, Thierry; Whitlock, Kathleen

2013-01-01

Neural crest cells exhibit dramatic migration behaviors as they populate their distant targets. Using a line of zebrafish expressing green fluorescent protein (sox10:EGFP) in neural crest cells we developed an assay to analyze and quantify cell migration as a population, and use it here to characterize in detail the subtle defects in cell migration caused by ethanol exposure during early development. The challenge was to quantify changes in the in vivo migration of all Sox10:EGFP expressing cells in the visual field of time-lapse movies. To perform this analysis we used an Optical Flow algorithm for motion detection and combined the analysis with a fit to an affine transformation. Through this analysis we detected and quantified significant differences in the cell migrations of Sox10:EGFP positive cranial neural crest populations in ethanol treated versus untreated embryos. Specifically, treatment affected migration by increasing the left-right asymmetry of the migrating cells and by altering the direction of cell movements. Thus, by applying this novel computational analysis, we were able to quantify the movements of populations of cells, allowing us to detect subtle changes in cell behaviors. Because cranial neural crest cells contribute to the formation of the frontal mass these subtle differences may underlie commonly observed facial asymmetries in normal human populations. PMID:23936049

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

Xiong, W; Zhou, Yunshen; Hou, Wenjia

Direct formation of graphene with controlled number of graphitic layers on dielectric surfaces is highly desired for practical applications. Despite significant progress achieved in understanding the formation of graphene on metallic surfaces through chemical vapor deposition (CVD) of hydrocarbons, very limited research is available elucidating the graphene formation process via rapid thermal processing (RTP) of solid-state amorphous carbon, through which graphene is formed directly on dielectric surfaces accompanied by autonomous nickel evaporation. It is suggested that a metastable hexagonal nickel carbide (Ni 3C) intermediate phase plays a critical role in transforming amorphous carbon to 2D crystalline graphene and contributing tomore » the autonomous Ni evaporation. Temperature resolved carbon and nickel evolution in the RTP process is investigated using Auger electron spectroscopic (AES) depth profiling and glancing-angle X-ray diffraction (GAXRD). Formation, migration and decomposition of the hexagonal Ni 3C are confirmed to be responsible for the formation of graphene and the evaporation of Ni at 1100 °C. The Ni 3C-assisted graphene formation mechanism expands the understanding of Ni-catalyzed graphene formation, and provides insightful guidance for controlled growth of graphene through the solid-state transformation process.« less

The Development of a Novel High Throughput Computational Tool for Studying Individual and Collective Cellular Migration

PubMed Central

Chapnick, Douglas A.; Jacobsen, Jeremy; Liu, Xuedong

2013-01-01

Understanding how cells migrate individually and collectively during development and cancer metastasis can be significantly aided by a computation tool to accurately measure not only cellular migration speed, but also migration direction and changes in migration direction in a temporal and spatial manner. We have developed such a tool for cell migration researchers, named Pathfinder, which is capable of simultaneously measuring the migration speed, migration direction, and changes in migration directions of thousands of cells both instantaneously and over long periods of time from fluorescence microscopy data. Additionally, we demonstrate how the Pathfinder software can be used to quantify collective cell migration. The novel capability of the Pathfinder software to measure the changes in migration direction of large populations of cells in a spatiotemporal manner will aid cellular migration research by providing a robust method for determining the mechanisms of cellular guidance during individual and collective cell migration. PMID:24386097

Resonant structure, formation and stability of the planetary system HD155358

NASA Astrophysics Data System (ADS)

Silburt, Ari; Rein, Hanno

2017-08-01

Two Jovian-sized planets are orbiting the star HD155358 near exact mean motion resonance (MMR) commensurability. In this work, we re-analyse the radial velocity (RV) data previously collected by Robertson et al. Using a Bayesian framework, we construct two models - one that includes and the other that excludes gravitational planet-planet interactions (PPIs). We find that the orbital parameters from our PPI and no planet-planet interaction (noPPI) models differ by up to 2σ, with our noPPI model being statistically consistent with previous results. In addition, our new PPI model strongly favours the planets being in MMR, while our noPPI model strongly disfavours MMR. We conduct a stability analysis by drawing samples from our PPI model's posterior distribution and simulating them for 109 yr, finding that our best-fitting values land firmly in a stable region of parameter space. We explore a series of formation models that migrate the planets into their observed MMR. We then use these models to directly fit to the observed RV data, where each model is uniquely parametrized by only three constants describing its migration history. Using a Bayesian framework, we find that a number of migration models fit the RV data surprisingly well, with some migration parameters being ruled out. Our analysis shows that PPIs are important to take into account when modelling observations of multiplanetary systems. The additional information that one can gain from interacting models can help constrain planet migration parameters.

Nuclear translocation of phosphorylated STAT3 regulates VEGF-A-induced lymphatic endothelial cell migration and tube formation

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

Okazaki, Hideki; Tokumaru, Sho; Hanakawa, Yasushi

2011-09-02

Highlights: {yields} VEGF-A enhanced lymphatic endothelial cell migration and increased tube formation. {yields} VEGF-A treated lymphatic endothelial cell showed activation of STAT3. {yields} Dominant-negative STAT3 inhibited VEGF-A-induced lymphatic endothelial cell migration and tube formation. -- Abstract: Vascular endothelial growth factor (VEGF) is an endothelial cell-specific growth factor that regulates endothelial functions, and signal transducers and activators of transcription (STATs) are known to be important during VEGF receptor signaling. The aim of this study was to determine whether STAT3 regulates VEGF-induced lymphatic endothelial cell (LEC) migration and tube formation. VEGF-A (33 ng/ml) enhanced LEC migration by 2-fold and increased tube lengthmore » by 25% compared with the control, as analyzed using a Boyden chamber and Matrigel assay, respectively. Western blot analysis and immunostaining revealed that VEGF-A induced the nuclear translocation of phosphorylated STAT3 in LECs, and this translocation was blocked by the transfection of LECs with an adenovirus vector expressing a dominant-negative mutant of STAT3 (Ax-STAT3F). Transfection with Ax-STAT3F also almost completely inhibited VEGF-A-induced LEC migration and tube formation. These results indicate that STAT3 is essential for VEGF-A-induced LEC migration and tube formation and that STAT3 regulates LEC functions.« less

Collagen triple helix repeat containing 1 is a new promigratory marker of arthritic pannus.

PubMed

Shekhani, Mohammed Talha; Forde, Toni S; Adilbayeva, Altynai; Ramez, Mohamed; Myngbay, Askhat; Bexeitov, Yergali; Lindner, Volkhard; Adarichev, Vyacheslav A

2016-07-19

The formation of destructive hypercellular pannus is critical to joint damage in rheumatoid arthritis (RA). The collagen triple helix repeat containing 1 (CTHRC1) protein expressed by activated stromal cells of diverse origin has previously been implicated in tissue remodeling and carcinogenesis. We recently discovered that the synovial Cthrc1 mRNA directly correlates with arthritis severity in mice. This study characterizes the role of CTHRC1 in arthritic pannus formation. Synovial joints of mice with collagen antibody-induced arthritis (CAIA) and human RA-fibroblast-like synoviocytes (FLS) were immunostained for CTHRC1, FLS and macrophage-specific markers. CTHRC1 levels in plasma from patients with RA were measured using sandwich ELISA. The migratory response of fibroblasts was studied with a transwell migration assay and time-lapse microscopy. Velocity and directness of cell migration was analyzed by recording the trajectories of cells treated with rhCTHRC1. Immunohistochemical analysis of normal and inflamed synovium revealed highly inducible expression of CTHRC1 in arthritis (10.9-fold). At the tissue level, CTHRC1-expressing cells occupied the same niche as large fibroblast-like cells positive for α-smooth muscle actin (α-SMA) and cadherin 11 (CDH11). CTHRC1 was produced by activated FLS predominantly located at the synovial intimal lining and at the bone-pannus interface. Cultured RA-FLS expressed CDH11, α-SMA, and CTHRC1. Upon treatment with exogenous rhCTHRC1, embryonic fibroblasts and RA-FLS significantly increased migration velocity, directness, and cell length along the front-tail axis (1.4-fold, p < 0.01). CTHRC1 was established as a novel marker of activated synoviocytes in murine experimental arthritis and RA. The pro-migratory effect of CTHRC1 on synoviocytes is considered one of the mechanisms promoting hypercellularity of the arthritic pannus.

A low-molecular-weight galactofucan from the seaweed, Spatoglossum schröederi, binds fibronectin and inhibits capillary-like tube formation in vitro.

PubMed

Menezes, Maira Maria; Nobre, Leonardo Thiago Duarte Barreto; Rossi, Gustavo Rodrigues; Almeida-Lima, Jailma; Melo-Silveira, Raniere Fagundes; Franco, Celia Regina Cavichiolo; Trindade, Edvaldo Silva; Nader, Helena Bonciani; Rocha, Hugo Alexandre Oliveira

2018-05-01

A low-molecular-weight (LMW) heterofucan (designated fucan B) was obtained from the brown seaweed, Spatoglossum schröederi, and its activity as an inhibitor of capillary-like tube formation by endothelial cells (ECs) was analyzed. Chemical, infrared and electrophoretic analyses confirmed the identity of fucan B. In contrast to other LMW fucans, fucan B (0.012-0.1 mg/mL) inhibited ECs capillary-like tube formation in a concentration-dependent manner. In addition, fucan B (0.01-0.05 mg/mL) did not affect ECs proliferation. Fucan B also inhibited ECs migration on a fibronectin-coated surface, but not on laminin- or collagen-coated surfaces. Biotinylated fucan B was used as a probe to identify its localization. Confocal microscopy experiments revealed that biotinylated fucan did not bind to the cell surface, but rather only to fibronectin. Our findings suggest that fucan B inhibits ECs capillary-like tube formation and migration by binding directly to fibronectin and blocking fibronectin sites recognized by cell surface ligands. However, further studies are needed to evaluate the in vivo effects of fucan B. Copyright © 2018 Elsevier B.V. All rights reserved.

Moesin and myosin phosphatase confine neutrophil orientation in a chemotactic gradient

PubMed Central

Liu, Xiaowen; Yang, Tao; Suzuki, Koya; Tsukita, Sachiko; Ishii, Masaru; Zhou, Shuping; Wang, Gang; Cao, Luyang; Qian, Feng; Taylor, Shalina; Oh, Myung-Jin; Levitan, Irena; Ye, Richard D.; Carnegie, Graeme K.; Malik, Asrar B.

2015-01-01

Neutrophils respond to invading bacteria by adopting a polarized morphology, migrating in the correct direction, and engulfing the bacteria. How neutrophils establish and precisely orient this polarity toward pathogens remains unclear. Here we report that in resting neutrophils, the ERM (ezrin, radixin, and moesin) protein moesin in its active form (phosphorylated and membrane bound) prevented cell polarization by inhibiting the small GTPases Rac, Rho, and Cdc42. Attractant-induced activation of myosin phosphatase deactivated moesin at the prospective leading edge to break symmetry and establish polarity. Subsequent translocation of moesin to the trailing edge confined the formation of a prominent pseudopod directed toward pathogens and prevented secondary pseudopod formation in other directions. Therefore, both moesin-mediated inhibition and its localized deactivation by myosin phosphatase are essential for neutrophil polarization and effective neutrophil tracking of pathogens. PMID:25601651

Directional migration of leading-edge mesoderm generates physical forces: Implication in Xenopus notochord formation during gastrulation.

PubMed

Hara, Yusuke; Nagayama, Kazuaki; Yamamoto, Takamasa S; Matsumoto, Takeo; Suzuki, Makoto; Ueno, Naoto

2013-10-15

Gastrulation is a dynamic tissue-remodeling process occurring during early development and fundamental to the later organogenesis. It involves both chemical signals and physical factors. Although much is known about the molecular pathways involved, the roles of physical forces in regulating cellular behavior and tissue remodeling during gastrulation have just begun to be explored. Here, we characterized the force generated by the leading edge mesoderm (LEM) that migrates preceding axial mesoderm (AM), and investigated the contribution of LEM during Xenopus gastrulation. First, we constructed an assay system using micro-needle which could measure physical forces generated by the anterior migration of LEM, and estimated the absolute magnitude of the force to be 20-80nN. Second, laser ablation experiments showed that LEM could affect the force distribution in the AM (i.e. LEM adds stretch force on axial mesoderm along anterior-posterior axis). Third, migrating LEM was found to be necessary for the proper gastrulation cell movements and the establishment of organized notochord structure; a reduction of LEM migratory activity resulted in the disruption of mediolateral cell orientation and convergence in AM. Finally, we found that LEM migration cooperates with Wnt/PCP to form proper notochord. These results suggest that the force generated by the directional migration of LEM is transmitted to AM and assists the tissue organization of notochord in vivo independently of the regulation by Wnt/PCP. We propose that the LEM may have a mechanical role in aiding the AM elongation through the rearrangement of force distribution in the dorsal marginal zone. © 2013 Elsevier Inc. All rights reserved.

Vertical migration of motile phytoplankton chains through turbulence

NASA Astrophysics Data System (ADS)

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

2017-11-01

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

Self-formed meandering river created in the laboratory using an upstream migrating boundary

NASA Astrophysics Data System (ADS)

van Dijk, W. M.; van de Lageweg, W. I.; Kleinhans, M. G.

2010-12-01

Braided rivers are relatively easily formed in the laboratory, whereas self-formed meandering rivers in the lab have proven very difficult to form, indicating a lack of understanding of the necessary and sufficient conditions for meandering. Our objective is to create self-formed dynamic meandering rivers and floodplains in a laboratory. Early experiments attempted to initiate meandering with upstream inflow at a fixed angle different from the general flow direction. The resulting bends were fixed at one position, which is not the dynamic meandering observed in nature. Another important condition for meandering is to have banks stronger than the non-cohesive bed sediment, which has been attained by growing vegetation. Furthermore, finer or light-weight sediment has been used to let chute channels fill up where otherwise multi-thread channels would have evolved, which is braiding. Yet the fixed-angle inflow kept meander migration and channel belt width and complexity limited. We accomplished dynamic meandering in the laboratory by using an upstream migrating boundary, which simulates a meander migrating into the flume. Our experiments were conducted in a circulated flume of 11x6 meter, with a constant discharge and sediment feed consisting of a sediment mixture ranging from silt to fine gravel (Kleinhans et al., 2010, this conference). The downstream boundary is a lake into which the river built a branched fan delta (Van de Lageweg et al., 2010, this conference). The morphology was recorded by high-resolution (0.5 mm) line-laser scanning and digital Single Lens Reflex (SLR) camera used for channel-floodplain segmentation and particle size estimation, at an interval of 8 hours. Furthermore a large number of smaller-scale auxiliary experiments were conducted to explore meandering tendency in a large range of parameters. Initial alternate ‘forced’ bars were formed at fixed positions with low sinuosity when the upstream boundary was at one fixed position. Migration of the upstream boundary caused further erosion of the outer banks and formation of point bars in inner bends, so that sinuosity increased to about 1.25. When the upstream boundary reversed migration direction chute cut-offs formed and meander bends reformed in the opposite direction. Hence in the first meander sweep the reworked floodplain showed nodes and antinodes at a wave length in agreement with linear bar stability analysis. After 260 hours experimental time the floodplain had become much more complex, exhibiting meandering channels, point bars, chutes, abandoned and partially filled channels, and slightly cohesive floodplains similar to natural meandering gravel-bed rivers such as the Allier near Moulins (France) and the Rhine near Emmerich (Germany). The flow became even more confined to a single-thread channel when pulses of silica flour were fed during short flood events, which significantly enhanced cohesive floodplain formation. The strengthened floodplains decreased channel mobility, however. We conclude that the necessary and sufficient conditions for meandering are a dynamic upstream boundary and active floodplain formation by fines.

Novel role of apatinib as a multi-target RTK inhibitor in the direct suppression of hepatocellular carcinoma cells.

PubMed

Li, Xiaojin; Xu, Anjian; Li, Huihui; Zhang, Bei; Cao, Bangwei; Huang, Jian

2018-05-01

Although apatinib has been demonstrated with potential antitumor activity in multiple solid tumors, the underlying mechanism of apatinib for the treatment of hepatocellular carcinoma (HCC) remains unclear. In the present study, we explored if there are any direct suppression effects of apatinib on HCC cells and its relevant targets. We investigated the effect of apatinib on viability of five HCC cell lines and an intrahepatic cholangiocarcinoma cell line, and colony formation, apoptosis and migration of representative HCC cells in vitro; and HCC progression in a xenograft mouse model. Using a phospho-receptor tyrosine kinase pathway array with 49 different tyrosine kinases, we screened and verified the tyrosine kinase targets involved in apatinib response. Apatinib treatment significantly inhibited HCC cell viability, proliferation, colony formation, and migration, and enhanced cell apoptosis in a concentration-dependent manner (p < 0.05). Furthermore, apatinib showed a favorable anti-tumor growth effect (71% of inhibition ratio, p < 0.05) in an established human HCC xenograft mice model with good safety. RTK pathway arrays and western blots analysis demonstrated that apatinib significantly downregulated the phosphorylation levels of several tyrosine kinase receptors, particularly PDGFR-α and IGF-IR, and inhibited Akt phosphorylation. These data suggest that the apatinib may have a direct anti-HCC effect as a direct multi-target RTK inhibitor of HCC cells and a promising potentiality in HCC clinical therapies. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of directional migration on prisoner's dilemma game in a square domain

NASA Astrophysics Data System (ADS)

Cheng, Hongyan; Dai, Qionglin; Li, Haihong; Qian, Xiaolan; Zhang, Mei; Yang, Junzhong

2013-04-01

We introduce a new migration rule, the directional migration, into evolutionary prisoner's dilemma games defined in a square domain with periodic boundary conditions. We find that cooperation can be enhanced to a much higher level than the case in the absence of migration. Additionally, the presence of the directional migration has profound impact on the population structure: the directional migration drives individuals to form a number of dense clusters which resembles social cohesion. The evolutionary game theory incorporating the directional migration can reproduce some real characteristics of populations in human society and may shed light on the problem of social cohesion.

The formation of protoplanets in the planetesimal disk

NASA Astrophysics Data System (ADS)

Kominami, Junko; Tanaka, Hidekazu; Ida, Shigeru

We have performed N-body simulations on the stage of protoplanet formation from planetesimals. Generally accepted planet formation theory suggests that protoplanets are formed through accretion of ~km sized planetesimals. The formation process proceeds in the nebular disk. Hence the bodies in the disk suffer gas drag and interact tidally with the nebula. Such interaction triggers the type I migration. We found that the runaway protoplanet forms a gap in the planetesimal disk. It results in the slow down of the migration by factor of ~0.7, and the accretion rate. However, the shepherding does not last so long. Hence the overall migration time scale can not be changed by the formation of the gap in the planetesimal disk. However, if the depletion of the gas occurs from the inner region of the disk, the planets may survive from migration.

Nitrosoureas Inhibit the Stathmin Mediated Migration and Invasion of Malignant Glioma Cells

PubMed Central

Liang, Xing-Jie; Choi, Yong; Sackett, Dan L.; Park, John K.

2008-01-01

Malignant gliomas are the most common primary intrinsic brain tumors and are highly lethal. The widespread migration and invasion of neoplastic cells from the initial site of tumor formation into the surrounding brain render these lesions refractory to definitive surgical treatment. Stathmin, a microtubule destabilizing protein that mediates cell cycle progression, can also regulate directed cell movement. Nitrosoureas, traditionally viewed as DNA alkylating agents, can also covalently modify proteins such as stathmin. We therefore sought to establish a role for stathmin in malignant glioma cell motility, migration, and invasion and determine the effects of nitrosoureas on these cell movement related processes. Scratch-wound healing recovery, Boyden chamber migration, Matrigel invasion, and organotypic slice invasion assays were performed before and after the down regulation of cellular stathmin levels and in the absence and presence of sub-lethal nitrosourea (CCNU; [1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea]) concentrations. We demonstrate that decreases in stathmin expression lead to significant decreases in malignant glioma cell motility, migration, and invasion. CCNU, at a concentration of 10 μM, causes similar significant decreases, even in the absence of any effects on cell viability. The direct inhibition of stathmin by CCNU is likely a contributing factor. These findings suggest that the inhibition of stathmin expression and function may be useful in limiting the spread of malignant gliomas within the brain and that nitrosoureas may have therapeutic benefits in addition to their anti-proliferative effects. PMID:18593927

Disruption of neural progenitors along the ventricular and subventricular zones in periventricular heterotopia

PubMed Central

Ferland, Russell J.; Batiz, Luis Federico; Neal, Jason; Lian, Gewei; Bundock, Elizabeth; Lu, Jie; Hsiao, Yi-Chun; Diamond, Rachel; Mei, Davide; Banham, Alison H.; Brown, Philip J.; Vanderburg, Charles R.; Joseph, Jeffrey; Hecht, Jonathan L.; Folkerth, Rebecca; Guerrini, Renzo; Walsh, Christopher A.; Rodriguez, Esteban M.; Sheen, Volney L.

2009-01-01

Periventricular heterotopia (PH) is a disorder characterized by neuronal nodules, ectopically positioned along the lateral ventricles of the cerebral cortex. Mutations in either of two human genes, Filamin A (FLNA) or ADP-ribosylation factor guanine exchange factor 2 (ARFGEF2), cause PH (Fox et al. in ‘Mutations in filamin 1 prevent migration of cerebral cortical neurons in human periventricular heterotopia'. Neuron, 21, 1315–1325, 1998; Sheen et al. in ‘Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex'. Nat. Genet., 36, 69–76, 2004). Recent studies have shown that mutations in mitogen-activated protein kinase kinase kinase-4 (Mekk4), an indirect interactor with FlnA, also lead to periventricular nodule formation in mice (Sarkisian et al. in ‘MEKK4 signaling regulates filamin expression and neuronal migration'. Neuron, 52, 789–801, 2006). Here we show that neurons in post-mortem human PH brains migrated appropriately into the cortex, that periventricular nodules were primarily composed of later-born neurons, and that the neuroependyma was disrupted in all PH cases. As studied in the mouse, loss of FlnA or Big2 function in neural precursors impaired neuronal migration from the germinal zone, disrupted cell adhesion and compromised neuroepithelial integrity. Finally, the hydrocephalus with hop gait (hyh) mouse, which harbors a mutation in Napa [encoding N-ethylmaleimide-sensitive factor attachment protein alpha (α-SNAP)], also develops a progressive denudation of the neuroepithelium, leading to periventicular nodule formation. Previous studies have shown that Arfgef2 and Napa direct vesicle trafficking and fusion, whereas FlnA associates dynamically with the Golgi membranes during budding and trafficking of transport vesicles. Our current findings suggest that PH formation arises from a final common pathway involving disruption of vesicle trafficking, leading to impaired cell adhesion and loss of neuroependymal integrity. PMID:18996916

Beach cusp destruction, formation, and evolution during and subsequent to an extratropical storm, Duck, North Carolina

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

Miller, J.R.; Miller, S.M.O.; Torzynski, C.A.

Many studies have debated whether beach cusps are erosional or depositional features. The April 12-14, 1988, extratropical storm provided an opportunity to view the direct effects of one of the largest storms of the past decade upon beach sedimentology and morphology on barrier islands near Duck, North Carolina. Prior to the storm, the beach at Duck was characterized by a well-defined pattern of beach cusps with horn-to-horn spacings averaging 35 m. Storm-induced alterations were dominated by an initial period of beach erosion that remobilized the upper 30 to 50 cm of beach sediment, followed by aggradation. Net aggradation was mostmore » prominent along the middle beachface and within the pre-storm cusp bays. These morphologic adjustments resulted in the destruction of cusps, which were replaced with a post-storm planar beachface composed of horizontally bedded fine- to coarse-grained sediments. Within 24 hrs of storm subsidence, new beach cusps formed sequentially along the coast in the direction of longshore transport. Initial cusp formation resulted from beach erosion and the creation of bays in the planar storm-beach surface at positions of preferential post-storm runup. The initial cusp horns were composed of truncated horizontal beds of the planar beach accreted during the storm. After their formation, the cusps sequentially migrated downdrift. Migrating horns were composed of a coarse-grained sediment wedge that thickened toward horn crests, suggesting formation by deposition. It is concluded from these observations that beach cusps are both erosional and depositional in nature.« less

The Crataegus extract WS 1442 inhibits balloon catheter-induced intimal hyperplasia in the rat carotid artery by directly influencing PDGFR-beta.

PubMed

Fürst, Robert; Zirrgiebel, Ute; Totzke, Frank; Zahler, Stefan; Vollmar, Angelika M; Koch, Egon

2010-08-01

Effective systemic drugs against restenosis upon percutaneous transluminal coronary angioplasty (PTCA) are largely lacking. Polyphenols have been suggested to ameliorate post-angioplasty restenosis. Hawthorn (Crataegus spp.) extracts, which are among the most frequently used herbal medicinal products against mild forms of congestive heart failure, contain polyphenols, but have not been investigated in this context. We aimed to assess the potential of the hawthorn extract WS 1442 to prevent balloon catheter-induced intimal hyperplasia and to elucidate the underlying mechanisms. We analyzed the effects of WS 1442 on serum-induced vascular smooth muscle cell (VSMC) and endothelial cell (EC) growth and migration, growth factor-induced proliferation, growth factor receptor activity, and neointima formation in the rat carotid artery model. WS 1442 (100 microg/ml) decreased VSMC migration by 38% and proliferation by 44%, whereas EC migration and proliferation were unaltered. The extract inhibited VSMC DNA synthesis induced by platelet-derived growth factor (PDGF) (IC(50): 47 microg/ml), but not that of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). Along this line, WS 1442 blocked recombinant human PDGF receptor (PDGFR)-beta kinase activity (IC(50): 1.4 microg/ml) and decreased PDGFR-beta activation and extracellular signal-regulated kinase (ERK) activation in VSMCs. In rats, orally administered WS 1442 significantly reduced neointima formation after balloon catheter dilatation of the carotid artery. WS 1442 inhibits migration and proliferation of VSMCs, but not of ECs, and reduces balloon catheter-evoked neointima formation probably through inhibition of PDGFR-beta. Thus, the present study suggests a novel adjunct pharmacological strategy to prevent angioplasty-related restenosis. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

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.

Formation of Ice Giant Satellites During Thommes Model Mirgration

NASA Astrophysics Data System (ADS)

Fuse, Christopher; Spiegelberg, Josephine

2018-01-01

Inconsistencies between ice giant planet characteristics and classic planet formation theories have led to a re-evaluation of the formation of the outer Solar system. Thommes model migration delivers proto-Uranus and Neptune from orbits interior to Saturn to their current locations. The Thommes model has also been able to reproduce the large Galilean and Saturnian moons via interactions between the proto-ice giants and the gas giant moon disks.As part of a series of investigations examining the effects of Thommes model migration on the formation of moons, N-body simulations of the formation of the Uranian and Neptunian satellite systems were performed. Previous research has yielded conflicting results as to whether satellite systems are stable during planetary migration. Some studies, such as Beaugé (2002) concluded that the system was not stable over the proposed duration of migration. Conversely, Fuse and Neville (2011) and Yokoyama et al. (2011) found that moons were retained, though the nature of the resulting system was heavily influenced by interactions with planetesimals and other large objects. The results of the current study indicate that in situ simulations of the Uranus and Neptune systems can produce stable moons. Whether with current orbital parameters or located at pre-migration, inner Solar system semi-major axes, the simulations end with 5.8 ± 0.15 or 5.9 ± 0.7 regular satellites around Uranus and Neptune, respectively. Preliminary simulations of a proto-moon disk around a single planet migrating via the Thommes model have failed to retain moons. Furthermore, simulations of ejection of the current Uranian satellite system retained at most one moon. Thus, for the Thommes model to be valid, it is likely that moon formation did not begin until after migration ended. Future work will examine the formation of gas and ice giant moons through other migration theories, such as the Nice model (Tsiganis et al. 2006).

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.

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.

Novel role of copper transport protein antioxidant-1 in neointimal formation after vascular injury.

PubMed

Kohno, Takashi; Urao, Norifumi; Ashino, Takashi; Sudhahar, Varadarajan; McKinney, Ronald D; Hamakubo, Takao; Iwanari, Hiroko; Ushio-Fukai, Masuko; Fukai, Tohru

2013-04-01

Vascular smooth muscle cell (VSMC) migration is critically important for neointimal formation after vascular injury and atherosclerosis lesion formation. Copper (Cu) chelator inhibits neointimal formation, and we previously demonstrated that Cu transport protein antioxidant-1 (Atox1) is involved in Cu-induced cell growth. However, role of Atox1 in VSMC migration and neointimal formation after vascular injury is unknown. Here, we show that Atox1 expression is upregulated in injured vessel, and it is colocalized with the Cu transporter ATP7A, one of the downstream targets of Atox1, mainly in neointimal VSMCs at day 14 after wire injury. Atox1(-/-) mice show inhibition of neointimal formation and extracellular matrix expansion, which is associated with a decreased VSMCs accumulation within neointima and lysyl oxidase activity. Mechanistically, in cultured VSMC, Atox1 depletion with siRNA inhibits platelet-derived growth factor-induced Cu-dependent VSMC migration by preventing translocation of ATP7A and small G protein Rac1 to the leading edge, as well as Cu- and Rac1-dependent lamellipodia formation. Furthermore, Atox1(-/-) mice show decreased perivascular macrophage infiltration in wire-injured vessels, as well as thioglycollate-induced peritoneal macrophage recruitment. Atox1 is involved in neointimal formation after vascular injury through promoting VSMC migration and inflammatory cell recruitment in injured vessels. Thus, Atox1 is a potential therapeutic target for VSMC migration and inflammation-related vascular diseases.

Direct visualization and in-depth physical study of metal filament formation in percolated high-κ dielectrics

NASA Astrophysics Data System (ADS)

Li, X.; Pey, K. L.; Bosman, M.; Liu, W. H.; Kauerauf, T.

2010-01-01

The migration of Ta atoms from a transistor gate electrode into the percolated high-κ (HK) gate dielectrics is directly shown using transmission electron microscopy analysis. A nanoscale metal filament that formed under high current injection is identified to be the physical defect responsible for the ultrafast transient breakdown (BD) of the metal-gate/high-κ (MG/HK) gate stacks. This highly conductive metal filament poses reliability concerns for MG/HK gate stacks as it significantly reduces the post-BD reliability margin of a transistor.

Supercritical CO2 Migration under Cross-Bedded Structures: Outcrop Analog from the Jurassic Navajo Sandstone

NASA Astrophysics Data System (ADS)

Lee, S.; Allen, J.; Han, W.; Lu, C.; McPherson, B. J.

2011-12-01

Jurassic aeolian sandstones (e.g. Navajo and White Rim Sandstones) on the Colorado Plateau of Utah have been considered potential sinks for geologic CO2 sequestration due to their regional lateral continuity, thickness, high porosity and permeability, presence of seal strata and proximity to large point sources of anthropogenic CO2. However, aeolian deposits usually exhibit inherent internal complexities induced by migrating bedforms of different sizes and their resulting bounding surfaces. Therefore, CO2 plume migration in such complex media should be well defined and successively linked in models for better characterization of the plume behavior. Based on an outcrop analog of the upper Navajo Sandstone in the western flank of the San Rafael Swell, Utah, we identified five different bedform types with dune and interdune facies to represent the spatial continuity of lithofacies units. Using generated 3D geometrical facies patterns of cross-bedded structures in the Navajo Sandstone, we performed numerical simulations to understand the detailed behavior of CO2 plume migration under the different cross-bedded bedforms. Our numerical simulation results indicate that cross-bedded structures (bedform types) play an important role on governing the rate and directionality of CO2 migration, resulting in changes of imbibition processes of CO2. CO2 migration tends to follow wind ripple laminations and reactivation surfaces updip. Our results suggest that geologically-based upscaling of CO2 migration is crucial in cross-bedded formations as part of reservoir or basin scale models. Furthermore, comparative modeling studies between 3D models and 2D cross-sections extracted from 3D models showed the significant three-dimensional interplay in a cross-bedded structure and the need to correctly capture the geologic heterogeneity to predict realistic CO2 plume behavior. Our outcrop analog approach presented in this study also demonstrates an alternative method for assessing geologic CO2 storage in deep formations when scarce data is available.

Restore the change process of Longmaxi shale pore structure during the diagenesis by the potassium and the magnesium

NASA Astrophysics Data System (ADS)

Zhou, W.

2016-12-01

The pore structure of Longmaxi shale was changing during the diagenetic process, mainly caused by the illitization and serpentinzation. The evolution of shale pore structure mainly relates to the element migration. Based on the result of electron microprobe analyser (EMPA), it is possible to find the distribution of element in shale directly and to distinguish the destroyed primary pore structure as element will remain in the migration way. The migration of potassium in Longmaxi shale mainly happened during early diagenesis phase to middle diagenesis phase (Geothermal temperature: 60°-140°). During the illitization, potassium mainly came from potassium feldspar, migrated though the connected pore structure and reacted with smectite. Illite and illite/smectite in Longmaxi shale distribute continuously in 10micron-level flocculent formation, which means that primary connective pore structure in Longmaxi shale has a same scale. The concentration of potassium has an obvious gradient that potassium content in middle of flocculation of Illite/smectite is about 6.8% and 4.8% in the boundary parts (Fig.). In addition, as SiO2 was generated during the illitization, which makes Longmaxi shale very compacted. The migration of magnesium in Longmaxi shale happened during low temperature serpentinization (Geothermal temperature: 140°-350°). Magnesium mainly came from dolomite and migrated in primary pores. According to the result of EMPA, it can be recognized that the migration path of magnesium is much simpler than potassium, which is caused as serpentinization do not have much reaction with clay minerals around (Fig.). Serpentine jams the primary pores of Longmaxi shale too. As reaction temperature of serpentinization is higher than illitization and serpentine is inserts in illite/smectite, the formation process of Longmaxi shale pore structure can be mainly divided into two phases: geothermal temperature˜140° and˜140°.

Electronic structure and O vacancy formation/migration in La0.825(Mg/Ca/Ba)0.125CoO3

NASA Astrophysics Data System (ADS)

Omotayo Akande, Salawu; Gan, Li-Yong; Schwingenschlögl, Udo

2016-04-01

The effect of A-site hole doping (Mg2+, Ca2+ or Ba2+) on the electronic and magnetic properties as well as the O vacancy formation and migration in perovskite LaCoO3 is studied using first-principles calculations. All three dopants are found to facilitate O vacancy formation. Substitution of La3+ with Ba2+/Mg2+ yields the lowest O vacancy formation energy for low/intermediate spin Co, implying that not only the structure but also the spin state of Co is a key parameter. Only for low spin Co the ionic radius is correlated with the O migration barrier. Enhanced migration for intermediate spin Co is ascribed to the availability of additional space at the transition state.

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 OPN. We further suggest that the initiation of the migration process occurs predominant through direct activation of the P2Y{sub 2} by Up{sub 4}A and via transactivation of the PDGFR.« less

[Study on the effect of phloretin on inhibiting malignant pheotype of BEL-7402 cells].

PubMed

Luo, Hui; Wang, Ya-Jun; Chen, Jie; Liu, Jiang-Qin

2008-07-01

To investigate the effect of phloretin on inhibiting BEL-7402 cells' growth, invasive, migration and adhesion ability and the rate of colony formation. BEL-7402 cells' growth, invasive, migration and adhesion ability and the rate of colony formation were examined with MIT method and Costar Transwell. Phloretin inhibited the growth, invasive, migration and adhesion ability of BEL-7402 cells and reduced the rate of colony formation in dose-dependent. Phloretin can inhibit BEL-7402 cells' malignant pheotype.

Solid-state graphene formation via a nickel carbide intermediate phase [Nickel carbide (Ni 3C) as an intermediate phase for graphene formation

DOE PAGES

Xiong, W; Zhou, Yunshen; Hou, Wenjia; ...

2015-11-10

Direct formation of graphene with controlled number of graphitic layers on dielectric surfaces is highly desired for practical applications. Despite significant progress achieved in understanding the formation of graphene on metallic surfaces through chemical vapor deposition (CVD) of hydrocarbons, very limited research is available elucidating the graphene formation process via rapid thermal processing (RTP) of solid-state amorphous carbon, through which graphene is formed directly on dielectric surfaces accompanied by autonomous nickel evaporation. It is suggested that a metastable hexagonal nickel carbide (Ni 3C) intermediate phase plays a critical role in transforming amorphous carbon to 2D crystalline graphene and contributing tomore » the autonomous Ni evaporation. Temperature resolved carbon and nickel evolution in the RTP process is investigated using Auger electron spectroscopic (AES) depth profiling and glancing-angle X-ray diffraction (GAXRD). Formation, migration and decomposition of the hexagonal Ni 3C are confirmed to be responsible for the formation of graphene and the evaporation of Ni at 1100 °C. The Ni 3C-assisted graphene formation mechanism expands the understanding of Ni-catalyzed graphene formation, and provides insightful guidance for controlled growth of graphene through the solid-state transformation process.« less

Dissecting GRB7-mediated signals for proliferation and migration in HER2 overexpressing breast tumor cells: GTP-ase rules.

PubMed

Pradip, De; Bouzyk, Mark; Dey, Nandini; Leyland-Jones, Brian

2013-01-01

Amplification of human Her2 and its aberrant signaling in 20-30% of early breast cancer patients is responsible for highly aggressive tumors with poor outcome. Grb7 is reported to be co-amplified with Her2. We report a concurrent high expression of mRNA (from FFPE tumor samples; mRNA correlation, Pearson r(2)= 0.806), and high levels of GRB7 protein (immunoblot) in HER2+ breast cancer cell lines. We demonstrated the signaling mechanism of HER2 and downstream effectors that contributes to proliferation and migration. Using HER2+ and trastuzumab-resistant breast cancer cell lines, we identified the interaction between GRB7 and HER2 in the control of HER2+ cell proliferation. Our co-IP data show that GRB7 recruits SHC into the HER2-GRB7 signaling complex. This complex formation leads to activation of RAS-GTP. We also observed that following integrin engagement, GRB7 is phosphorylated at tyrosine in a p-FAK (Y397) dependent manner. This FAK-GRB7 complex leads to downstream activation of RAC1-GTP (responsible for migration) probably through the recruitment of VAV2. Our CO-IP data demonstrate that GRB7 directly binds with VAV2 following fibronectin engagement in HER2+ cells. To address whether GRB7 could serve as a pathway specific therapeutic target, we used siRNA to suppress GRB7 expression. Knockdown of GRB7 expression in the HER2+ breast cancer cell lines decreases RAS activation, cell proliferation, 2D and 3D colony formation and also blocked integrin-mediated RAC1 activation along with integrin-directed cell migration. These findings dissected the HER2-mediated signaling cascade into (1) HER2+ cell proliferation (HER2-GRB7-SHC-RAS) and (2) HER2+ cell migration (alpha5 beta1/alpha4 beta1-FAK-GRB7-VAV2-RAC1). Our data clearly demonstrate that a coupling of GRB7 with HER2 is required for the proliferative and migratory signals in HER2+ breast tumor cells.

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

Functional interplay between endothelial nitric oxide synthase and membrane type 1–matrix metalloproteinase in migrating endothelial cells

PubMed Central

Genís, Laura; Gonzalo, Pilar; Tutor, Antonio S.; Gálvez, Beatriz G.; Martínez-Ruiz, Antonio; Zaragoza, Carlos; Lamas, Santiago; Tryggvason, Karl; Apte, Suneel S.

2007-01-01

Nitric oxide (NO) is essential for vascular homeostasis and is also a critical modulator of angiogenesis; however, the molecular mechanisms of NO action during angiogenesis remain elusive. We have investigated the potential relationship between NO and membrane type 1–matrix metalloproteinase (MT1-MMP) during endothelial migration and capillary tube formation. Endothelial NO synthase (eNOS) colocalizes with MT1-MMP at motility-associated structures in migratory human endothelial cells (ECs); moreover, NO is produced at these structures and is released into the medium during EC migration. We have therefore addressed 2 questions: (1) the putative regulation of MT1-MMP by NO in migratory ECs; and (2) the requirement for MT1-MMP in NO-induced EC migration and tube formation. NO upregulates MT1-MMP membrane clustering on migratory human ECs, and this is accompanied by increased degradation of type I collagen substrate. MT1-MMP membrane expression and localization are impaired in lung ECs from eNOS-deficient mice, and these cells also show impaired migration and tube formation in vitro. Inhibition of MT1-MMP with a neutralizing antibody impairs NOinduced tube formation by human ECs, and NO-induced endothelial migration and tube formation are impaired in lung ECs from mice deficient in MT1-MMP. MT1-MMP thus appears to be a key molecular effector of NO during the EC migration and angiogenic processes, and is a potential therapeutic target for NO-associated vascular disorders. PMID:17606763

Jupiter's decisive role in the inner Solar System's early evolution.

PubMed

Batygin, Konstantin; Laughlin, Greg

2015-04-07

The statistics of extrasolar planetary systems indicate that the default mode of planet formation generates planets with orbital periods shorter than 100 days and masses substantially exceeding that of the Earth. When viewed in this context, the Solar System is unusual. Here, we present simulations which show that a popular formation scenario for Jupiter and Saturn, in which Jupiter migrates inward from a > 5 astronomical units (AU) to a ≈ 1.5 AU before reversing direction, can explain the low overall mass of the Solar System's terrestrial planets, as well as the absence of planets with a < 0.4 AU. Jupiter's inward migration entrained s ≳ 10-100 km planetesimals into low-order mean motion resonances, shepherding and exciting their orbits. The resulting collisional cascade generated a planetesimal disk that, evolving under gas drag, would have driven any preexisting short-period planets into the Sun. In this scenario, the Solar System's terrestrial planets formed from gas-starved mass-depleted debris that remained after the primary period of dynamical evolution.

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

DOEpatents

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

2010-11-30

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

Gaussian Curvature Directs Stress Fiber Orientation and Cell Migration.

PubMed

Bade, Nathan D; Xu, Tina; Kamien, Randall D; Assoian, Richard K; Stebe, Kathleen J

2018-03-27

We show that substrates with nonzero Gaussian curvature influence the organization of stress fibers and direct the migration of cells. To study the role of Gaussian curvature, we developed a sphere-with-skirt surface in which a positive Gaussian curvature spherical cap is seamlessly surrounded by a negative Gaussian curvature draping skirt, both with principal radii similar to cell-length scales. We find significant reconfiguration of two subpopulations of stress fibers when fibroblasts are exposed to these curvatures. Apical stress fibers in cells on skirts align in the radial direction and avoid bending by forming chords across the concave gap, whereas basal stress fibers bend along the convex direction. Cell migration is also strongly influenced by the Gaussian curvature. Real-time imaging shows that cells migrating on skirts repolarize to establish a leading edge in the azimuthal direction. Thereafter, they migrate in that direction. This behavior is notably different from migration on planar surfaces, in which cells typically migrate in the same direction as the apical stress fiber orientation. Thus, this platform reveals that nonzero Gaussian curvature not only affects the positioning of cells and alignment of stress fiber subpopulations but also directs migration in a manner fundamentally distinct from that of migration on planar surfaces. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

EphA2/Ephrin-A1 Mediate Corneal Epithelial Cell Compartmentalization via ADAM10 Regulation of EGFR Signaling

PubMed Central

Kaplan, Nihal; Ventrella, Rosa; Peng, Han; Pal-Ghosh, Sonali; Arvanitis, Constadina; Rappoport, Joshua Z.; Mitchell, Brian J.; Stepp, Mary Ann; Lavker, Robert M.

2018-01-01

Purpose Progenitor cells of the limbal epithelium reside in a discrete area peripheral to the more differentiated corneal epithelium and maintain tissue homeostasis. What regulates the limbal–corneal epithelial boundary is a major unanswered question. Ephrin-A1 ligand is enriched in the limbal epithelium, whereas EphA2 receptor is concentrated in the corneal epithelium. This reciprocal pattern led us to assess the role of ephrin-A1 and EphA2 in limbal–corneal epithelial boundary organization. Methods EphA2-expressing corneal epithelial cells engineered to express ephrin-A1 were used to study boundary formation in vitro in a manner that mimicked the relative abundance of these juxtamembrane signaling proteins in the limbal and corneal epithelium in vivo. Interaction of these two distinct cell populations following initial seeding into discrete culture compartments was assessed by live cell imaging. Immunofluoresence and immunoblotting was used to evaluate the contribution of downstream growth factor signaling and cell–cell adhesion systems to boundary formation at sites of heterotypic contact between ephrin-A1 and EphA2 expressing cells. Results Ephrin-A1–expressing cells impeded and reversed the migration of EphA2-expressing corneal epithelial cells upon heterotypic contact formation leading to coordinated migration of the two cell populations in the direction of an ephrin-A1–expressing leading front. Genetic silencing and pharmacologic inhibitor studies demonstrated that the ability of ephrin-A1 to direct migration of EphA2-expressing cells depended on an a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) and epidermal growth factor receptor (EGFR) signaling pathway that limited E-cadherin–mediated adhesion at heterotypic boundaries. Conclusions Ephrin-A1/EphA2 signaling complexes play a key role in limbal–corneal epithelial compartmentalization and the response of these tissues to injury. PMID:29351356

EphA2/Ephrin-A1 Mediate Corneal Epithelial Cell Compartmentalization via ADAM10 Regulation of EGFR Signaling.

PubMed

Kaplan, Nihal; Ventrella, Rosa; Peng, Han; Pal-Ghosh, Sonali; Arvanitis, Constadina; Rappoport, Joshua Z; Mitchell, Brian J; Stepp, Mary Ann; Lavker, Robert M; Getsios, Spiro

2018-01-01

Progenitor cells of the limbal epithelium reside in a discrete area peripheral to the more differentiated corneal epithelium and maintain tissue homeostasis. What regulates the limbal-corneal epithelial boundary is a major unanswered question. Ephrin-A1 ligand is enriched in the limbal epithelium, whereas EphA2 receptor is concentrated in the corneal epithelium. This reciprocal pattern led us to assess the role of ephrin-A1 and EphA2 in limbal-corneal epithelial boundary organization. EphA2-expressing corneal epithelial cells engineered to express ephrin-A1 were used to study boundary formation in vitro in a manner that mimicked the relative abundance of these juxtamembrane signaling proteins in the limbal and corneal epithelium in vivo. Interaction of these two distinct cell populations following initial seeding into discrete culture compartments was assessed by live cell imaging. Immunofluoresence and immunoblotting was used to evaluate the contribution of downstream growth factor signaling and cell-cell adhesion systems to boundary formation at sites of heterotypic contact between ephrin-A1 and EphA2 expressing cells. Ephrin-A1-expressing cells impeded and reversed the migration of EphA2-expressing corneal epithelial cells upon heterotypic contact formation leading to coordinated migration of the two cell populations in the direction of an ephrin-A1-expressing leading front. Genetic silencing and pharmacologic inhibitor studies demonstrated that the ability of ephrin-A1 to direct migration of EphA2-expressing cells depended on an a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) and epidermal growth factor receptor (EGFR) signaling pathway that limited E-cadherin-mediated adhesion at heterotypic boundaries. Ephrin-A1/EphA2 signaling complexes play a key role in limbal-corneal epithelial compartmentalization and the response of these tissues to injury.

Co-Regulation of Cell Polarization and Migration by Caveolar Proteins PTRF/Cavin-1 and Caveolin-1

PubMed Central

Hill, Michelle M.; Daud, Noor Huda; Aung, Cho Sanda; Loo, Dorothy; Martin, Sally; Murphy, Samantha; Black, Debra M.; Barry, Rachael; Simpson, Fiona; Liu, Libin; Pilch, Paul F.; Hancock, John F.; Parat, Marie-Odile; Parton, Robert G.

2012-01-01

Caveolin-1 and caveolae are differentially polarized in migrating cells in various models, and caveolin-1 expression has been shown to quantitatively modulate cell migration. PTRF/cavin-1 is a cytoplasmic protein now established to be also necessary for caveola formation. Here we tested the effect of PTRF expression on cell migration. Using fluorescence imaging, quantitative proteomics, and cell migration assays we show that PTRF/cavin-1 modulates cellular polarization, and the subcellular localization of Rac1 and caveolin-1 in migrating cells as well as PKCα caveola recruitment. PTRF/cavin-1 quantitatively reduced cell migration, and induced mesenchymal epithelial reversion. Similar to caveolin-1, the polarization of PTRF/cavin-1 was dependent on the migration mode. By selectively manipulating PTRF/cavin-1 and caveolin-1 expression (and therefore caveola formation) in multiple cell systems, we unveil caveola-independent functions for both proteins in cell migration. PMID:22912783

Human plasminogen kringle 1-5 inhibits angiogenesis and induces thrombomodulin degradation in a protein kinase A-dependent manner.

PubMed

Cho, Chia-Fong; Chen, Po-Ku; Chang, Po-Chiao; Wu, Hau-Lin; Shi, Guey-Yueh

2013-10-01

Kringle 1-5 (K1-5), an endogenous proteolytic fragment of human plasminogen (Plg), is an angiostatin-related protein that inhibits angiogenesis. Many angiostatin-related proteins have been identified, but the detailed molecular mechanisms underlying their antiangiogenic effects remain unclear. Thrombomodulin (TM) is a transmembrane glycoprotein that plays a major role in the anticoagulation process in endothelial cells. Previously, we demonstrated that recombinant TM could interact with Plg to enhance Plg activation. In the present study, we investigated the interaction between TM and K1-5, and their functions in endothelial cells. We found that K1-5 colocalized with TM and directly interacted with TM through the TM lectin-like domain. After K1-5 interacted with TM, it induced TM internalization and degradation. In addition, the K1-5-induced TM internalization and degradation in proteasomes after ubiquitin modification were dependent on protein kinase A (PKA). Moreover, a PKA-specific inhibitor reversed the effects of K1-5 on cell migration and tube formation. Consistent with these findings, TM overexpression resulted in increased cell migration; moreover, K1-5 inhibited the increase of TM-mediated cell migration in a PKA-dependent manner. We determined that TM acts as a K1-5 receptor and that K1-5 induces TM internalization, ubiquitination, and degradation through the PKA pathway, by which K1-5 may inhibit endothelial cell migration and tube formation. © 2013. Published by Elsevier Ltd. All rights reserved.

Petroleum systems of Zhu III depression in Pearl River Mouth Basin, South China Sea

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

Weilin, Zhu; Li Mingbi; Wu Peikang

Zhu III depression is located in the west part of Pearl River Mouth Basin, and covers an area of 11,000 sq km. Until now more than twenty wells have been drilled in the depression and its surrounding area, and all oil-gas fields and oil-gas discoveries are concentrated inside the depression. Integrated study indicates that there are two petroleum systems in Zhu III depression. One is Wenchang - Zhuhai, Zhujiang oil system which is mainly distributed in Wenchang B sag in the southwest part of the depression. Its source rock, the Wenchang formation is mainly composed of dark mudstone of lacustrinemore » facies, with thicknesses up to more than 1000 m. Its reservoir includes tidal sandstone of transitional facies of Zhuhai formation and neritic sandstone of the lower part of Zhujiang formation. Through bounding faults and margin coarse sediment zone, oil generated from the Wenchang formation migrated into overlying sandstone of Zhuhai formation, which was overlaid by mudstone beds of bay facies of Zhuhai formation or neritic facies of Zhujiang formation, and formed oil accumulations. The other system is Enping - Zhuhai gas system, distributed in Wenchang A sag in the northeast part of the depression, whose source rock in the Enping formation deposited in the contracting stage of the lake, dominated by swamp coal measure in lithology and terrestrial plant clastics in kerogen components. The gas generated from Enping formation directly migrated into overlying tidal sandstone of Zhuhai formation and formed gas accumulations. Therefore, exploration in Wenchang A sag in the northeast part of the depression is for gas accumulations, and oil accumulations in Wenchang B sag in the southwest part of the depression, while oil-gas mixed accumulations are likely to be found in the transitional area of two systems.« less

Novel Role of Copper Transport Protein Antioxidant-1 in Neointimal Formation Following Vascular Injury

PubMed Central

Kohno, Takashi; Urao, Norifumi; Ashino, Takashi; Sudhahar, Varadarajan; McKinney, Ronald D.; Hamakubo, Takao; Iwanari, Hiroko; Ushio-Fukai, Masuko; Fukai, Tohru

2013-01-01

Objective Vascular smooth muscle cell (VSMC) migration is critically important for neointimal formation following vascular injury and atherosclerosis lesion formation. Copper (Cu) chelator inhibits neointimal formation, and we previously demonstrated that Cu transport protein Antioxidant-1 (Atox1) is involved in Cu-induced cell growth. However, role of Atox1 in VSMC migration and neointimal formation after vascular injury is unknown. Approach and Results Here we show that Atox1 expression is upregulated in injured vessel, and it is colocalized with the Cu transporter ATP7A, one of downstream targets of Atox1, mainly in neointimal VSMCs at day 14 after wire injury. Atox1−/− mice show inhibition of neointimal formation and extracellular matrix expansion, which is associated with a decreased VSMCs accumulation within neointima and lysyl oxidase activity. Mechanistically, in cultured VSMC, Atox1 depletion with siRNA inhibits platelet-derived growth factor (PDGF)-induced Cu-dependent VSMC migration by preventing translocation of ATP7A and small G protein Rac1 to the leading edge as well as Cu- and Rac1-dependent lamellipodia formation. Furthermore, Atox1−/− mice show decreased perivascular macrophage infiltration in wire-injured vessels as well as thioglycollate-induced peritoneal macrophage recruitment. Conclusions Atox1 is involved in neointimal formation after vascular injury through promoting VSMC migration and inflammatory cell recruitment in injured vessels. Thus, Atox1 is a potential therapeutic target for VSMC migration and inflammation-related vascular diseases. PMID:23349186

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

Rohde, Magdalena; Sievers, Elisabeth; Janzer, Andreas

Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing, immune responses and invasive tumors all require the orchestrated movement of cells to specific locations. Histone demethylase proteins alter transcription by regulating the chromatin state at specific gene loci. FBXL10 is a conserved and ubiquitously expressed member of the JmjC domain-containing histone demethylase family and is implicated in the demethylation of H3K4me3 and H3K36me2 and thereby removing active chromatin marks. However, the physiological role of FBXL10 in vivo remains largely unknown. Therefore, we established an inducible gain of functionmore » model to analyze the role of Fbxl10 and compared wild-type with Fbxl10 overexpressing mouse embryonic fibroblasts (MEFs). Our study shows that overexpression of Fbxl10 in MEFs doesn’t influence the proliferation capability but leads to an enhanced migration capacity in comparison to wild-type MEFs. Transcriptome and ChIP-seq experiments demonstrated that Fbxl10 binds to genes involved in migration like Areg, Mdk, Lmnb1, Thbs1, Mgp and Cxcl12. Taken together, our results strongly suggest that Fbxl10 plays a critical role in migration by binding to the promoter region of migration-associated genes and thereby might influences cell behaviour to a possibly more aggressive phenotype. - Highlights: • Migration capability of MEFs is enhanced after Fbxl10 upregulation. • Overexpression of Fbxl10 induced migration-associated genes. • Fbxl10 binds directly to migration-associated genes.« less

Cdk5 phosphorylation of WAVE2 regulates oligodendrocyte precursor cell migration through nonreceptor tyrosine kinase Fyn.

PubMed

Miyamoto, Yuki; Yamauchi, Junji; Tanoue, Akito

2008-08-13

Myelin formation of the CNS is a complex and dynamic process. Before the onset of myelination, oligodendrocytes (OLs), the myelin-forming glia of the CNS, proliferate and migrate along axons. Little is known about the molecular mechanisms underlying the early myelination processes. Here, we show that platelet-derived growth factor (PDGF), the crucial physiological ligand in early OL development, controls the migration of oligodendrocyte precursor cells (OPCs) through cyclin-dependent kinase 5 (Cdk5). PDGF stimulates Cdk5 activity in a time-dependent manner, whereas suppression of Cdk5 by the specific inhibitor roscovitine or by the retrovirus encoding short-hairpin RNA for Cdk5 impairs PDGF-dependent OPC migration. The activation of Cdk5 by PDGF is mediated by the phosphorylation of the nonreceptor tyrosine kinase, Fyn, whose inhibition reduces PDGF-dependent OPC migration. Furthermore, Cdk5 regulates PDGF-dependent OPC migration through the direct phosphorylation of WASP (Wiskott-Aldrich syndrome protein)-family verprolin-homologous protein 2 (WAVE2). Cdk5 phosphorylates WAVE2 at Ser-137 in vitro. Infection of the WAVE2 construct harboring the Ser-137-to-Ala reduces PDGF-dependent migration. Together, PDGF regulates OPC migration through an as-yet-unidentified signaling cascade coupling Fyn kinase to Cdk5 phosphorylation of WAVE2. These results provide new insights into both the role of Cdk5 in glial cells and the molecular mechanisms controlling the early developmental stage of OLs.

Evolutionary modification of mesenchyme cells in sand dollars in the transition from indirect to direct development.

PubMed

Yajima, Mamiko

2007-01-01

Peronella japonica, an intermediate type of direct-developing sand dollar, forms an abbreviated pluteus, followed by metamorphosis within 3 days without feeding. In this species, ingression of mesenchyme cells starts before hatching and continues until gastrulation, but no typical secondary mesenchyme cells (SMCs) migrate from the tip of the archenteron. Here, I investigated the cell lineage of mesenchyme cells through metamorphosis in P. japonica and found that mesenchyme cells migrating before hatching (early mesenchyme cells [EMCs]) were exclusively derived from micromeres and became larval skeletogenic cells, whereas cells migrating after hatching (late mesenchyme cells [LMCs]) appeared to contain several nonskeletogenic cells. Thus, it is likely that EMCs are homologous to primary mesenchyme cells (PMCs) and LMCs are similar to the SMCs of typical indirect developers, suggesting that heterochrony in the timing of mesenchyme cell ingression may have occurred in this species. EMCs disappeared after metamorphosis and LMCs were involved in adult skeletogenesis. Embryos from which micromeres were removed at the 16-cell stage formed armless plutei that went on to form adult skeletons and resulted in juveniles with normal morphology. These results suggest that in P. japonica, LMCs form adult skeletal elements, whereas EMCs are specialized for larval spicule formation. The occurrence of evolutionary modifications in mesenchyme cells in the transition from indirect to direct development of sand dollars is discussed.

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

New Skills, New Jobs: Return Migration, Skill Transfers, and Business Formation in Mexico.

PubMed

Hagan, Jacqueline Maria; Wassink, Joshua

2016-11-01

Numerous studies have documented a high propensity for self-employment and business formation among return migrants relative to non-migrants. The literature points to the importance of remitted savings, migration duration, and number and types of jobs abroad for business formation upon return. Implicit in this scholarship is the assumption that migrants acquire not only financial capital, but also human capital, which expands their opportunities upon return. Empirical work has demonstrated how the transfer of formal human capital, such as language skills and professional credentials, influences the mobility pathways of professional return migrants. More recent research has also found that the transfer of informal human capital, such as social and technical skills learned on the job, shape the mobility pathways of return migrants with little schooling. Absent from this scholarship, however, are studies that directly test the relationship between the transfer of informal human capital and the odds of business formation among return migrants. In this paper, we address this gap. Using a multidimensional skills variable, which includes social, technical, and English language competences, we measure and test the relationship between skill acquisition and transfer and business formation among return migrants. Drawing on findings from a survey of 200 return migrants and 200 non-migrants in Mexico, we show that return migrants who successfully acquire and transfer new skills across the migratory circuit often leverage their new knowledge to launch businesses. Our findings have wide implications for how social scientists conceptualize and measure human capital formation across the migratory circuit.

The Exoplant Migration Timescale from K2 Young Clusters

NASA Astrophysics Data System (ADS)

Rizzuto, Aaron C.; Mann, Andrew; Kraus, Adam L.; Ireland, Michael

2017-01-01

Planetary Migration models for close-in exoplanets(a < 0.1 AU, P < 20 days) can be loosely divided into three categories: Disk-driven migration, binary-star planet interaction, and planet-planet interaction. Disk migration, occurs over the lifetime of the protoplanetary disk (<5 Myr), while migration involving dynamical multi-body interactions operate on timescales of ~100’s of Myr to ~1Gyr, a lengthier process than disk migration. It is unclear which of these is the dominating mechanism.The K2 mission has measured planet formation timescales and migration pathways by sampling groups of stars at key pre-main-sequence ages: Over the past 10 campaigns, multiple groups of young stars have been observed by K2, ranging from the 10 Myr Upper Scorpius OB association, through the ˜120 Myr Pleiades, the ˜600-800 Myr Hyades and Praesepe moving groups, to the original Kepler Field. The frequency, orbital and compositional properties of the exoplanet population in these samples of different age, with careful treatment of detection completeness, will be sufficient to address the question of exoplanet migration as their host stars are settling onto the main sequence.We will present the initial results of a program to directly address the question of planet migration with a uniform injection-recovery tests on a new K2 detrending pipeline that is optimized for the particular case of young, rotationally variable stars in K2 to robustly measure the detectability of planets of differing size and orbit. Initial results point towards a migration timescale of 200-700 Myr, which is consistent with the slower planet-planet scattering or Kozai migration models.

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.

Multi-Cellular Logistics of Collective Cell Migration

PubMed Central

Yamao, Masataka; Naoki, Honda; Ishii, Shin

2011-01-01

During development, the formation of biological networks (such as organs and neuronal networks) is controlled by multicellular transportation phenomena based on cell migration. In multi-cellular systems, cellular locomotion is restricted by physical interactions with other cells in a crowded space, similar to passengers pushing others out of their way on a packed train. The motion of individual cells is intrinsically stochastic and may be viewed as a type of random walk. However, this walk takes place in a noisy environment because the cell interacts with its randomly moving neighbors. Despite this randomness and complexity, development is highly orchestrated and precisely regulated, following genetic (and even epigenetic) blueprints. Although individual cell migration has long been studied, the manner in which stochasticity affects multi-cellular transportation within the precisely controlled process of development remains largely unknown. To explore the general principles underlying multicellular migration, we focus on the migration of neural crest cells, which migrate collectively and form streams. We introduce a mechanical model of multi-cellular migration. Simulations based on the model show that the migration mode depends on the relative strengths of the noise from migratory and non-migratory cells. Strong noise from migratory cells and weak noise from surrounding cells causes “collective migration,” whereas strong noise from non-migratory cells causes “dispersive migration.” Moreover, our theoretical analyses reveal that migratory cells attract each other over long distances, even without direct mechanical contacts. This effective interaction depends on the stochasticity of the migratory and non-migratory cells. On the basis of these findings, we propose that stochastic behavior at the single-cell level works effectively and precisely to achieve collective migration in multi-cellular systems. PMID:22205934

A family affair: A Ral-exocyst-centered network links Ras, Rac, Rho signaling to control cell migration.

PubMed

Zago, Giulia; Biondini, Marco; Camonis, Jacques; Parrini, Maria Carla

2017-05-12

Cell migration is central to many developmental, physiologic and pathological processes, including cancer progression. The Ral GTPases (RalA and RalB) which act down-stream the Ras oncogenes, are key players in the coordination between membrane trafficking and actin polymerization. A major direct effector of Ral, the exocyst complex, works in polarized exocytosis and is at the center of multiple protein-protein interactions that support cell migration by promoting protrusion formation, front-rear polarization, and extra-cellular matrix degradation. In this review we describe the recent advancements in deciphering the molecular mechanisms underlying this role of Ral via exocyst on cell migration. Among others, we will discuss the recently identified cross-talk between Ral and Rac1 pathways: exocyst binds to a negative regulator (the RacGAP SH3BP1) and to the major effector (the Wave Regulatory Complex, WRC) of Rac1, the master regulator of protrusions. Next challenge will be to better characterize the dynamics in space and in time of these molecular interplays, to better understand the pleiotropic functions of Ral in both normal and cancer cells.

TRPM8 inhibits endothelial cell migration via a non-channel function by trapping the small GTPase Rap1

PubMed Central

Grolez, Guillaume P.; Bernardini, Michela; Richard, Elodie; Scianna, Marco; Lemonnier, Loic; Munaron, Luca; Mattot, Virginie; Prevarskaya, Natalia; Gkika, Dimitra

2017-01-01

Endothelial cell adhesion and migration are critical steps of the angiogenic process, whose dysfunction is associated with tumor growth and metastasis. The TRPM8 channel has recently been proposed to play a protective role in prostate cancer by impairing cell motility. However, the mechanisms by which it could influence vascular behavior are unknown. Here, we reveal a novel non-channel function for TRPM8 that unexpectedly acts as a Rap1 GTPase inhibitor, thereby inhibiting endothelial cell motility, independently of pore function. TRPM8 retains Rap1 intracellularly through direct protein–protein interaction, thus preventing its cytoplasm–plasma membrane trafficking. In turn, this mechanism impairs the activation of a major inside-out signaling pathway that triggers the conformational activation of integrin and, consequently, cell adhesion, migration, in vitro endothelial tube formation, and spheroid sprouting. Our results bring to light a novel, pore-independent molecular mechanism by which endogenous TRPM8 expression inhibits Rap1 GTPase and thus plays a critical role in the behavior of vascular endothelial cells by inhibiting migration. PMID:28550110

Periodic Colony Formation of Bacteria Due to their Cell Reproduction and Movement

NASA Astrophysics Data System (ADS)

Itoh, H.; Wakita, J.; Watanabe, K.; Matsuyama, T.; Matsushita, M.

We have experimentally investigated periodic pattern formation produced by bacterial species Proteus mirabilis, which forms concentric-ring-like colonies by repeating migration and rest alternately on the surface of a solid agar medium. We distinguish three phases (initial lag phase, the following migration and consolidation phases that appear alternately) for the colony growth. Here we mainly used physical approaches in order to try to understand the formation of concentric-ring-like colonies, such as cutting the part of a colony during its growth. Global chemical signals governing the colony formation from the center were not found. We also checked phase entrainment quantitatively by letting two colonies collide with each other and confirmed that it does not take place in macroscopic scales. When we cut a colony just behind the migrating front shortly after the migration started, the migration ended earlier and the following consolidation lasted longer. However, the following cycles were not influenced by the cut, i.e., the following migration and consolidation phases were both found to return normal. The cut results in the stop of supply of cell population to the migrating front by internal waves. In fact the cell population on the new terrace during the first migration after the cut was less than that without cut. Furthermore, the cell population density was found to be recovered to the ordinary value by the end of the consolidation. All these experimental results suggest that the most important factor for the repetition of migration and consolidation phases is the cell population density.

Defect energetics of concentrated solid-solution alloys from ab initio calculations: Ni 0.5Co 0.5, Ni 0.5Fe 0.5, Ni 0.8Fe 0.2 and Ni 0.8Cr 0.2

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

Zhao, Shijun; Stocks, George Malcolm; Zhang, Yanwen

2016-08-03

It has been shown that concentrated solid solution alloys possess unusual electronic, magnetic, transport, mechanical and radiation-resistant properties that are directly related to underlying chemical complexity. Because every atom experiences a different local atomic environment, the formation and migration energies of vacancies and interstitials in these alloys exhibit a distribution, rather than a single value as in a pure metal or dilute alloy. In this study, using ab initio calculations based on density functional theory and special quasirandom structure, we have characterized the distribution of defect formation energy and migration barrier in four Ni-based solid-solution alloys: Ni 0.5Co 0.5, Nimore » 0.5Fe 0.5, Ni 0.8Fe 0.2 and Ni 0.8Cr 0.2. As defect formation energies in finite-size models depend sensitively on the elemental chemical potential, we have developed a computationally efficient method for determining it which takes into account the global composition and the local short-range order. In addition we have compared the results of our ab initio calculations to those obtained from available embedded atom method (EAM) potentials. Our results indicate that the defect formation and migration energies are closely related to the specific atomic size in the structure, which further determines the elemental diffusion properties. In conclusion, different EAM potentials yield different features of defect energetics in concentrated alloys, pointing to the need for additional potential development efforts in order to allow spatial and temporal scale-up of defect and simulations, beyond those accessible to ab initio methods.« less

Defect energetics of concentrated solid-solution alloys from ab initio calculations: Ni0.5Co0.5, Ni0.5Fe0.5, Ni0.8Fe0.2 and Ni0.8Cr0.2.

PubMed

Zhao, Shijun; Stocks, G Malcolm; Zhang, Yanwen

2016-09-14

It has been shown that concentrated solid solution alloys possess unusual electronic, magnetic, transport, mechanical and radiation-resistant properties that are directly related to underlying chemical complexity. Because every atom experiences a different local atomic environment, the formation and migration energies of vacancies and interstitials in these alloys exhibit a distribution, rather than a single value as in a pure metal or dilute alloy. Using ab initio calculations based on density functional theory and special quasirandom structures, we have characterized the distribution of defect formation energy and migration barrier in four Ni-based solid-solution alloys: Ni0.5Co0.5, Ni0.5Fe0.5, Ni0.8Fe0.2, and Ni0.8Cr0.2. As defect formation energies in finite-size models depend sensitively on the elemental chemical potential, we have developed a computationally efficient method for determining it which takes into account the global composition and the local short-range order. In addition we have compared the results of our ab initio calculations to those obtained from available embedded atom method (EAM) potentials. Our results indicate that the defect formation and migration energies are closely related to the specific atoms in the structure, which further determines the elemental diffusion properties. Different EAM potentials yield different features of defect energetics in concentrated alloys, pointing to the need for additional potential development efforts in order to allow spatial and temporal scale-up of defect and simulations, beyond those accessible to ab initio methods.

The formation of low-angle eolian stratification through the migration of protodunes

NASA Astrophysics Data System (ADS)

Ewing, R. C.; Phillips, J. D.; Weymer, B. A.; Barrineaux, P.; Bowling, R.; Nittrouer, J. A.

2017-12-01

Protodunes are low-relief, slipfaceless migrating bed forms that represent the emergent form of eolian sand dunes. Protodunes develop as cm-scale topography out of a flat bed of sand and evolve spatially and temporally into dunes with angle-of-repose slipfaces. Protodunes at White Sands Dune Field in New Mexico form at the upwind, trailing margin of the field, on dune stoss slopes, and in interdune areas. Here we analyze protodunes at the upwind margin of White Sands by coupling 200 mHz ground penetrating radar (GPR) with time-series high-resolution topography to characterize the origin and evolution of protodune stratification and the stratigraphic transition into fully developed dunes. We surveyed a 780m transect in the resultant transport direction of the dune field from SW to NE from sand patches through protodunes and into the first dune. We used airborne lidar surveys and structure-from-motion photogrammetry from 2007, 2008, 2009, 2010, 2015, and 2016. We find that protodune stratification forms at angles between 0-10 degrees by protodune migration. Dip angles increase as protodune amplitude increases along the transect. Accumulation of low-angle stratification increases across the first 650m and ranges from none to subcritical. Nearly aggradational accumulation of low-angle stratification occurs over the last 100m and is a precursor to angle-of-repose slipface formation. The origins of the aggradation and slipface development appear to be linked to protodune merging, dune interactions, and possibly to the development of a dune field-scale boundary layer. Protodunes and the formation of low-angle stratification at the upwind margin of White Sands are a good analog to the initiation of dune field development from sand sheets and the formation of low-angle stratification found at the base of eolian successions in the stratigraphic record.

Turning behaviors of T cells climbing up ramp-like structures are regulated by myosin light chain kinase activity and lamellipodia formation.

PubMed

Song, Kwang Hoon; Lee, Jaehyun; Jung, Hong-Ryul; Park, HyoungJun; Doh, Junsang

2017-09-14

T cells navigate diverse microenvironments to perform immune responses. Micro-scale topographical structures within the tissues, which may inherently exist in normal tissues or may be formed by inflammation or injury, can influence T cell migration, but how T cell migration is affected by such topographical structures have not been investigated. In this study, we fabricated ramp-like structures with a 5 μm height and various slopes, and observed T cells climbing up the ramp-like structures. T cells encountering the ramp-like structures exhibited MLC accumulation near head-tail junctions contacting the ramp-like structures, and made turns to the direction perpendicular to the ramp-like structures. Pharmacological study revealed that lamellipodia formation mediated by arp2/3 and contractility regulated by myosin light chain kinase (MLCK) were responsible for the intriguing turning behavior of T cells climbing the ramp-like structures. Arp2/3 or MLCK inhibition substantially reduced probability of T cells climbing sharp-edged ramp-like structures, indicating intriguing turning behavior of T cells mediated by lamellipodia formation and MLCK activity may be important for T cells to access inflamed or injured tissues with abrupt topographical changes.

Loss of miR-100 enhances migration, invasion, epithelial-mesenchymal transition and stemness properties in prostate cancer cells through targeting Argonaute 2.

PubMed

Wang, Min; Ren, Dong; Guo, Wei; Wang, Zeyu; Huang, Shuai; Du, Hong; Song, Libing; Peng, Xinsheng

2014-07-01

Evidence in literature has demonstrated that some microRNAs (miRNAs) play a pivotal role in most solid tumor metastasis. Previous studies have showed that miR-100 is downregulated in human prostate cancer tissue compared to normal prostate and also significantly decreased in bone metastatic prostate cancer samples compared with primary prostate cancer. Argonaute 2 (AGO2) is the core effector protein of the miRNA-induced silencing complex and overexpression of AGO2 might enhance tumor metastasis. However, it is unknown whether and how miR-100 and AGO2 regulates metastasis of prostate cancer. Here, we report that miR-100 negatively regulated migration, invasion, epithelial-mesenchymal transition (EMT), colony formation, spheroid formation and expression of the stemness factors c-Myc, Oct4 and Klf4 in PC-3 and DU145 cells. Furthermore, miR-100 expression was negatively correlated with bone metastasis of prostate cancer patients. Notably, luciferase assay showed that AGO2 was a direct target of miR-100. Downregulation of AGO2 repressed migration, invasion, EMT and stemness of prostate cancer cells, and reversed the effects seen with miR-100 downregulation. Downregulation of AGO2 enhanced expression of miR-34a and miR-125b which can suppress migration, invasion, EMT and stemness of cancer cells. Taken together, our findings indicate that loss of miR-100 promotes the metastatic ability of prostate cancer cells at least partially by upregulating AGO2 expression through modulating migration, invasion, EMT and stemness of cancer cells, and suggest that miR-100/AGO2 may play an important role in regulating the metastasis of prostate cancer and is a potential target of prevention and therapy.

Jin Fu Kang Oral Liquid Inhibits Lymphatic Endothelial Cells Formation and Migration

PubMed Central

Wang, Dan; Tang, Jie

2016-01-01

Lung cancer is the leading cause of cancer-related deaths worldwide. Jin Fu Kang (JFK), an oral liquid prescription of Chinese herbal drugs, has been clinically available for the treatment of non-small cell lung cancer (NSCLC). Lymphangiogenesis is a primary event in the process of cancer development and metastasis, and the formation and migration of lymphatic endothelial cells (LECs) play a key role in the lymphangiogenesis. To assess the activity of stromal cell-derived factor-1 (SDF-1) and the coeffect of SDF-1 and vascular endothelial growth factor-C (VEGF-C) on the formation and migration of LECs and clarify the inhibitory effects of JFK on the LECs, the LECs were differentiated from CD34+/VEGFR-3+ endothelial progenitor cells (EPCs), and JFK-containing serums were prepared from rats. SDF-1 and VEGF-C both induced the differentiation of CD34+/VEGFR-3+ EPCs towards LECs and enhanced the LECs migration. Couse of SDF-1 and VEGF-C displayed an additive effect on the LECs formation but not on their migration. JFK inhibited the formation and migration of LECs, and the inhibitory effects were most probably via regulation of the SDF-1/CXCR4 and VEGF-C/VEGFR-3 axes. The current finding suggested that JFK might inhibit NSCLC through antilymphangiogenesis and also provided a potential to discover antilymphangiogenesis agents from natural resources. PMID:27698675

Jin Fu Kang Oral Liquid Inhibits Lymphatic Endothelial Cells Formation and Migration.

PubMed

He, Hai-Lang; Wang, Dan; Tang, Jie; Zhou, Xian-Mei; Li, Jian-Xin; Xu, Ling

2016-01-01

Lung cancer is the leading cause of cancer-related deaths worldwide. Jin Fu Kang (JFK), an oral liquid prescription of Chinese herbal drugs, has been clinically available for the treatment of non-small cell lung cancer (NSCLC). Lymphangiogenesis is a primary event in the process of cancer development and metastasis, and the formation and migration of lymphatic endothelial cells (LECs) play a key role in the lymphangiogenesis. To assess the activity of stromal cell-derived factor-1 (SDF-1) and the coeffect of SDF-1 and vascular endothelial growth factor-C (VEGF-C) on the formation and migration of LECs and clarify the inhibitory effects of JFK on the LECs, the LECs were differentiated from CD34 + /VEGFR-3 + endothelial progenitor cells (EPCs), and JFK-containing serums were prepared from rats. SDF-1 and VEGF-C both induced the differentiation of CD34 + /VEGFR-3 + EPCs towards LECs and enhanced the LECs migration. Couse of SDF-1 and VEGF-C displayed an additive effect on the LECs formation but not on their migration. JFK inhibited the formation and migration of LECs, and the inhibitory effects were most probably via regulation of the SDF-1/CXCR4 and VEGF-C/VEGFR-3 axes. The current finding suggested that JFK might inhibit NSCLC through antilymphangiogenesis and also provided a potential to discover antilymphangiogenesis agents from natural resources.

Southward autumn migration of waterfowl facilitates cross-continental transmission of the highly pathogenic avian influenza H5N1 virus

NASA Astrophysics Data System (ADS)

Xu, Yanjie; Gong, Peng; Wielstra, Ben; Si, Yali

2016-08-01

The highly pathogenic avian influenza subtype H5N1 (HPAI H5N1) is a worldwide zoonotic infectious disease, threatening humans, poultry and wild birds. The role of wild birds in the spread of HPAI H5N1 has previously been investigated by comparing disease spread patterns with bird migration routes. However, the different roles that the southward autumn and northward spring migration might play in virus transmission have hardly been explored. Using direction analysis, we analyze HPAI H5N1 transmission directions and angular concentration of currently circulating viral clades, and compare these with waterfowl seasonal migration directions along major waterfowl flyways. Out of 22 HPAI H5N1 transmission directions, 18 had both a southward direction and a relatively high concentration. Differences between disease transmission and waterfowl migration directions were significantly smaller for autumn than for spring migration. The four northward transmission directions were found along Asian flyways, where the initial epicenter of the virus was located. We suggest waterfowl first picked up the virus from East Asia, then brought it to the north via spring migration, and then spread it to other parts of world mainly by autumn migration. We emphasize waterfowl autumn migration plays a relatively important role in HPAI H5N1 transmission compared to spring migration.

Platelet rich plasma promotes skeletal muscle cell migration in association with up-regulation of FAK, paxillin, and F-Actin formation.

PubMed

Tsai, Wen-Chung; Yu, Tung-Yang; Lin, Li-Ping; Lin, Mioa-Sui; Tsai, Ting-Ta; Pang, Jong-Hwei S

2017-11-01

Platelet rich plasma (PRP) contains various cytokines and growth factors which may be beneficial to the healing process of injured muscle. The aim of this study was to investigate the effect and molecular mechanism of PRP on migration of skeletal muscle cells. Skeletal muscle cells intrinsic to Sprague-Dawley rats were treated with PRP. The cell migration was evaluated by transwell filter migration assay and electric cell-substrate impedance sensing. The spreading of cells was evaluated microscopically. The formation of filamentous actin (F-actin) cytoskeleton was assessed by immunofluorescence staining. The protein expressions of paxillin and focal adhesion kinase (FAK) were assessed by Western blot analysis. Transfection of paxillin small-interfering RNA (siRNAs) to muscle cells was performed to validate the role of paxillin in PRP-mediated promotion of cell migration. Dose-dependently PRP promotes migration of and spreading and muscle cells. Protein expressions of paxillin and FAK were up-regulated dose-dependently. F-actin formation was also enhanced by PRP treatment. Furthermore, the knockdown of paxillin expression impaired the effect of PRP to promote cell migration. It was concluded that PRP promoting migration of muscle cells is associated with up-regulation of proteins expression of paxillin and FAK as well as increasing F-actin formation. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2506-2512, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Magnolol inhibits migration of vascular smooth muscle cells via cytoskeletal remodeling pathway to attenuate neointima formation

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

Karki, Rajendra; Department of Oriental Medicine Resources, Mokpo National University; Kim, Seong-Bin

Background: Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. The objective of this study was to investigate the effect of magnolol on VSMC migration. Methods: The proteolytic activity of matrix metalloproteinases (MMPs) in tumor necrosis factor alpha (TNF-α) stimulated VSMCs was performed by gelatin zymography. VSMC migration was assessed by wound healing and Boyden chamber methods. Collagen induced VSMC adhesion was determined by spectrofluorimeter and stress fibers formation was evaluated by fluorescence microscope. The expression of signaling molecules involved in stress fibers formation was determined by westernmore » blot. The phosphorylation of myosin light chain (MLC20) was determined by urea-glycerol polyacrylamide gel electrophoresis. Immunohistochemistry was performed to determine the expression of β1-integrin and collagen type I in the injured carotid arteries of rats on day 35 after vascular injury. Results: VSMC migration was strongly inhibited by magnolol without affecting MMPs expression. Also, magnolol inhibited β1-integrin expression, FAK phosphorylation and RhoA and Cdc42 activation to inhibit the collagen induced stress fibers formation. Moreover, magnolol inhibited the phosphorylation of MLC20. Our in vivo results showed that magnolol inhibited β1-integrin expression, collagen type I deposition and FAK phosphorylation in injured carotid arteries without affecting MMP-2 activity. Conclusions: Magnolol inhibited VSMC migration via inhibition of cytoskeletal remodeling pathway to attenuate neointima formation. General significance: This study provides a rationale for further evaluation of magnolol for the management of atherosclerosis and restenosis. - Highlights: • Magnolol strongly inhibited migration of VSMCs. • Magnolol inhibited stress fibers formation. • MLC20 phosphorylation was also inhibited by magnolol. • Anti-migratory effect of magnolol was cytoskeletal dependent. • Magnolol inhibited β1-integrin and collagen expression in vivo.« less

Membrane Tension Acts Through PLD2 and mTORC2 to Limit Actin Network Assembly During Neutrophil Migration

PubMed Central

Diz-Muñoz, Alba; Thurley, Kevin; Chintamen, Sana; Altschuler, Steven J.; Fletcher, Daniel A.; Weiner, Orion D.

2016-01-01

For efficient polarity and migration, cells need to regulate the magnitude and spatial distribution of actin assembly. This process is coordinated by reciprocal interactions between the actin cytoskeleton and mechanical forces. Actin polymerization-based protrusion increases tension in the plasma membrane, which in turn acts as a long-range inhibitor of actin assembly. These interactions form a negative feedback circuit that limits the magnitude of membrane tension in neutrophils and prevents expansion of the existing front and the formation of secondary fronts. It has been suggested that the plasma membrane directly inhibits actin assembly by serving as a physical barrier that opposes protrusion. Here we show that efficient control of actin polymerization-based protrusion requires an additional mechanosensory feedback cascade that indirectly links membrane tension with actin assembly. Specifically, elevated membrane tension acts through phospholipase D2 (PLD2) and the mammalian target of rapamycin complex 2 (mTORC2) to limit actin nucleation. In the absence of this pathway, neutrophils exhibit larger leading edges, higher membrane tension, and profoundly defective chemotaxis. Mathematical modeling suggests roles for both the direct (mechanical) and indirect (biochemical via PLD2 and mTORC2) feedback loops in organizing cell polarity and motility—the indirect loop is better suited to enable competition between fronts, whereas the direct loop helps spatially organize actin nucleation for efficient leading edge formation and cell movement. This circuit is essential for polarity, motility, and the control of membrane tension. PMID:27280401

Fishing out collective memory of migratory schools

PubMed Central

De Luca, Giancarlo; Mariani, Patrizio; MacKenzie, Brian R.; Marsili, Matteo

2014-01-01

Animals form groups for many reasons, but there are costs and benefits associated with group formation. One of the benefits is collective memory. In groups on the move, social interactions play a crucial role in the cohesion and the ability to make consensus decisions. When migrating from spawning to feeding areas, fish schools need to retain a collective memory of the destination site over thousands of kilometres, and changes in group formation or individual preference can produce sudden changes in migration pathways. We propose a modelling framework, based on stochastic adaptive networks, that can reproduce this collective behaviour. We assume that three factors control group formation and school migration behaviour: the intensity of social interaction, the relative number of informed individuals and the strength of preference that informed individuals have for a particular migration area. We treat these factors independently and relate the individuals’ preferences to the experience and memory for certain migration sites. We demonstrate that removal of knowledgeable individuals or alteration of individual preference can produce rapid changes in group formation and collective behaviour. For example, intensive fishing targeting the migratory species and also their preferred prey can reduce both terms to a point at which migration to the destination sites is suddenly stopped. The conceptual approaches represented by our modelling framework may therefore be able to explain large-scale changes in fish migration and spatial distribution. PMID:24647905

Fishing out collective memory of migratory schools.

PubMed

De Luca, Giancarlo; Mariani, Patrizio; MacKenzie, Brian R; Marsili, Matteo

2014-06-06

Animals form groups for many reasons, but there are costs and benefits associated with group formation. One of the benefits is collective memory. In groups on the move, social interactions play a crucial role in the cohesion and the ability to make consensus decisions. When migrating from spawning to feeding areas, fish schools need to retain a collective memory of the destination site over thousands of kilometres, and changes in group formation or individual preference can produce sudden changes in migration pathways. We propose a modelling framework, based on stochastic adaptive networks, that can reproduce this collective behaviour. We assume that three factors control group formation and school migration behaviour: the intensity of social interaction, the relative number of informed individuals and the strength of preference that informed individuals have for a particular migration area. We treat these factors independently and relate the individuals' preferences to the experience and memory for certain migration sites. We demonstrate that removal of knowledgeable individuals or alteration of individual preference can produce rapid changes in group formation and collective behaviour. For example, intensive fishing targeting the migratory species and also their preferred prey can reduce both terms to a point at which migration to the destination sites is suddenly stopped. The conceptual approaches represented by our modelling framework may therefore be able to explain large-scale changes in fish migration and spatial distribution.

Magnolol inhibits migration of vascular smooth muscle cells via cytoskeletal remodeling pathway to attenuate neointima formation.

PubMed

Karki, Rajendra; Kim, Seong-Bin; Kim, Dong-Wook

2013-12-10

Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. The objective of this study was to investigate the effect of magnolol on VSMC migration. The proteolytic activity of matrix metalloproteinases (MMPs) in tumor necrosis factor alpha (TNF-α) stimulated VSMCs was performed by gelatin zymography. VSMC migration was assessed by wound healing and Boyden chamber methods. Collagen induced VSMC adhesion was determined by spectrofluorimeter and stress fibers formation was evaluated by fluorescence microscope. The expression of signaling molecules involved in stress fibers formation was determined by western blot. The phosphorylation of myosin light chain (MLC20) was determined by urea-glycerol polyacrylamide gel electrophoresis. Immunohistochemistry was performed to determine the expression of β1-integrin and collagen type I in the injured carotid arteries of rats on day 35 after vascular injury. VSMC migration was strongly inhibited by magnolol without affecting MMPs expression. Also, magnolol inhibited β1-integrin expression, FAK phosphorylation and RhoA and Cdc42 activation to inhibit the collagen induced stress fibers formation. Moreover, magnolol inhibited the phosphorylation of MLC20. Our in vivo results showed that magnolol inhibited β1-integrin expression, collagen type I deposition and FAK phosphorylation in injured carotid arteries without affecting MMP-2 activity. Magnolol inhibited VSMC migration via inhibition of cytoskeletal remodeling pathway to attenuate neointima formation. This study provides a rationale for further evaluation of magnolol for the management of atherosclerosis and restenosis. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Substrate engagement of integrins α5β1 and αvβ3 is necessary, but not sufficient, for high directional persistence in migration on fibronectin

PubMed Central

Missirlis, Dimitris; Haraszti, Tamás; Scheele, Catharina v. C.; Wiegand, Tina; Diaz, Carolina; Neubauer, Stefanie; Rechenmacher, Florian; Kessler, Horst; Spatz, Joachim P.

2016-01-01

The interplay between specific integrin-mediated matrix adhesion and directional persistence in cell migration is not well understood. Here, we characterized fibroblast adhesion and migration on the extracellular matrix glycoproteins fibronectin and vitronectin, focusing on the role of α5β1 and αvβ3 integrins. Fibroblasts manifested high directional persistence in migration on fibronectin-, but not vitronectin-coated substrates, in a ligand density-dependent manner. Fibronectin stimulated α5β1-dependent organization of the actin cytoskeleton into oriented, ventral stress fibers, and assembly of dynamic, polarized protrusions, characterized as regions free of stress fibers and rich in nascent adhesions at their edge. Such protrusions correlated with persistent, local leading edge advancement, but were not sufficient, nor necessary for directional migration over longer times. Selective blocking of αvβ3 or α5β1 integrins using small molecule integrin antagonists reduced directional persistence on fibronectin, indicating integrin cooperativity in maintaining directionality. On the other hand, patterned substrates, designed to selectively engage either integrin, or their combination, were not sufficient to establish directional migration. Overall, our study demonstrates adhesive coating-dependent regulation of directional persistence in fibroblast migration and challenges the generality of the previously suggested role of β1 and β3 integrins in directional migration. PMID:26987342

Planet Formation

NASA Astrophysics Data System (ADS)

Klahr, Hubert; Brandner, Wolfgang

2011-02-01

1. Historical notes on planet formation Bodenheimer; 2. The formation and evolution of planetary systems Bouwman et al.; 3. Destruction of protoplanetary disks by photoevaporation Richling, Hollenbach and Yorke; 4. Turbulence in protoplanetary accretion disks Klahr, Rozyczka, Dziourkevitch, Wunsch and Johansen; 5. The origin of solids in the early solar system Trieloff and Palme; 6. Experiments on planetesimal formation Wurm and Blum; 7. Dust coagulation in protoplanetary disks Henning, Dullemond, Wolf and Dominik; 8. The accretion of giant planet cores Thommes and Duncan; 9. Planetary transits: direct vision of extrasolar planets Lecavelier des Etangs and Vidal-Madjar; 10. The core accretion - gas capture model Hubickyj; 11. Properties of exoplanets Marcy, Fischer, Butler and Vogt; 12. Giant planet formation: theories meet observations Boss; 13. From hot Jupiters to hot Neptures … and below Lovis, Mayor and Udry; 14. Disk-planet interaction and migration Masset and Kley; 15. The Brown Dwarf - planet relation Bate; 16. From astronomy to astrobiology Brandner; 17. Overview and prospective Lin.

Myosin-II-Mediated Directional Migration of Dictyostelium Cells in Response to Cyclic Stretching of Substratum

PubMed Central

Iwadate, Yoshiaki; Okimura, Chika; Sato, Katsuya; Nakashima, Yuta; Tsujioka, Masatsune; Minami, Kazuyuki

2013-01-01

Living cells are constantly subjected to various mechanical stimulations, such as shear flow, osmotic pressure, and hardness of substratum. They must sense the mechanical aspects of their environment and respond appropriately for proper cell function. Cells adhering to substrata must receive and respond to mechanical stimuli from the substrata to decide their shape and/or migrating direction. In response to cyclic stretching of the elastic substratum, intracellular stress fibers in fibroblasts and endothelial, osteosarcoma, and smooth muscle cells are rearranged perpendicular to the stretching direction, and the shape of those cells becomes extended in this new direction. In the case of migrating Dictyostelium cells, cyclic stretching regulates the direction of migration, and not the shape, of the cell. The cells migrate in a direction perpendicular to that of the stretching. However, the molecular mechanisms that induce the directional migration remain unknown. Here, using a microstretching device, we recorded green fluorescent protein (GFP)-myosin-II dynamics in Dictyostelium cells on an elastic substratum under cyclic stretching. Repeated stretching induced myosin II localization equally on both stretching sides in the cells. Although myosin-II-null cells migrated randomly, myosin-II-null cells expressing a variant of myosin II that cannot hydrolyze ATP migrated perpendicular to the stretching. These results indicate that Dictyostelium cells accumulate myosin II at the portion of the cell where a large strain is received and migrate in a direction other than that of the portion where myosin II accumulated. This polarity generation for migration does not require the contraction of actomyosin. PMID:23442953

Direct observation of oxygen vacancy-driven structural and resistive phase transitions in La2/3Sr1/3MnO3

NASA Astrophysics Data System (ADS)

Yao, Lide; Inkinen, Sampo; van Dijken, Sebastiaan

2017-02-01

Resistive switching in transition metal oxides involves intricate physical and chemical behaviours with potential for non-volatile memory and memristive devices. Although oxygen vacancy migration is known to play a crucial role in resistive switching of oxides, an in-depth understanding of oxygen vacancy-driven effects requires direct imaging of atomic-scale dynamic processes and their real-time impact on resistance changes. Here we use in situ transmission electron microscopy to demonstrate reversible switching between three resistance states in epitaxial La2/3Sr1/3MnO3 films. Simultaneous high-resolution imaging and resistance probing indicate that the switching events are caused by the formation of uniform structural phases. Reversible horizontal migration of oxygen vacancies within the manganite film, driven by combined effects of Joule heating and bias voltage, predominantly triggers the structural and resistive transitions. Our findings open prospects for ionotronic devices based on dynamic control of physical properties in complex oxide nanostructures.

Mena binds α5 integrin directly and modulates α5β1 function.

PubMed

Gupton, Stephanie L; Riquelme, Daisy; Hughes-Alford, Shannon K; Tadros, Jenny; Rudina, Shireen S; Hynes, Richard O; Lauffenburger, Douglas; Gertler, Frank B

2012-08-20

Mena is an Ena/VASP family actin regulator with roles in cell migration, chemotaxis, cell-cell adhesion, tumor cell invasion, and metastasis. Although enriched in focal adhesions, Mena has no established function within these structures. We find that Mena forms an adhesion-regulated complex with α5β1 integrin, a fibronectin receptor involved in cell adhesion, motility, fibronectin fibrillogenesis, signaling, and growth factor receptor trafficking. Mena bound directly to the carboxy-terminal portion of the α5 cytoplasmic tail via a 91-residue region containing 13 five-residue "LERER" repeats. In fibroblasts, the Mena-α5 complex was required for "outside-in" α5β1 functions, including normal phosphorylation of FAK and paxillin and formation of fibrillar adhesions. It also supported fibrillogenesis and cell spreading and controlled cell migration speed. Thus, fibroblasts require Mena for multiple α5β1-dependent processes involving bidirectional interactions between the extracellular matrix and cytoplasmic focal adhesion proteins.

Mena binds α5 integrin directly and modulates α5β1 function

PubMed Central

Riquelme, Daisy; Hughes-Alford, Shannon K.; Tadros, Jenny; Rudina, Shireen S.; O.Hynes, Richard; Lauffenburger, Douglas

2012-01-01

Mena is an Ena/VASP family actin regulator with roles in cell migration, chemotaxis, cell–cell adhesion, tumor cell invasion, and metastasis. Although enriched in focal adhesions, Mena has no established function within these structures. We find that Mena forms an adhesion-regulated complex with α5β1 integrin, a fibronectin receptor involved in cell adhesion, motility, fibronectin fibrillogenesis, signaling, and growth factor receptor trafficking. Mena bound directly to the carboxy-terminal portion of the α5 cytoplasmic tail via a 91-residue region containing 13 five-residue “LERER” repeats. In fibroblasts, the Mena–α5 complex was required for “outside-in” α5β1 functions, including normal phosphorylation of FAK and paxillin and formation of fibrillar adhesions. It also supported fibrillogenesis and cell spreading and controlled cell migration speed. Thus, fibroblasts require Mena for multiple α5β1-dependent processes involving bidirectional interactions between the extracellular matrix and cytoplasmic focal adhesion proteins. PMID:22908313

Sonic hedgehog acts cell-autonomously on muscle precursor cells to generate limb muscle diversity

PubMed Central

Anderson, Claire; Williams, Victoria C.; Moyon, Benjamin; Daubas, Philippe; Tajbakhsh, Shahragim; Buckingham, Margaret E.; Shiroishi, Toshihiko; Hughes, Simon M.; Borycki, Anne-Gaëlle

2012-01-01

How muscle diversity is generated in the vertebrate body is poorly understood. In the limb, dorsal and ventral muscle masses constitute the first myogenic diversification, as each gives rise to distinct muscles. Myogenesis initiates after muscle precursor cells (MPCs) have migrated from the somites to the limb bud and populated the prospective muscle masses. Here, we show that Sonic hedgehog (Shh) from the zone of polarizing activity (ZPA) drives myogenesis specifically within the ventral muscle mass. Shh directly induces ventral MPCs to initiate Myf5 transcription and myogenesis through essential Gli-binding sites located in the Myf5 limb enhancer. In the absence of Shh signaling, myogenesis is delayed, MPCs fail to migrate distally, and ventral paw muscles fail to form. Thus, Shh production in the limb ZPA is essential for the spatiotemporal control of myogenesis and coordinates muscle and skeletal development by acting directly to regulate the formation of specific ventral muscles. PMID:22987640

Ischemic mass effect from biliary surgical clips.

PubMed

Mateo, Rod; Tsai, Steven; Stapfer, Maria V; Sher, Linda S; Selby, Rick; Genyk, Yuri S

2008-02-01

Migrating surgical clips in the hepatic hilum are known causes of biliary stricture or obstruction, most often due to direct intraluminal obstruction or secondary stone formation. Two cases are reported on patients with previous cholecystectomies presenting with delayed symptoms of biliary tract stricture. Both patients were successfully treated with a resection of the strictured area and a Roux-en-Y hepatico-jejunostomy. Resected specimens grossly demonstrated surgical clips adjacent to the stricture, but not directly within the lumen, suggestive of an ischemic mass effect, which was supported by histology. In addition to the direct intraluminal obstruction and lithogenic effects of migratory surgical clips, "clipomas" due to an ischemic mass effect can also lead to biliary tract strictures.

Inhibition of IGF-1-Mediated Cellular Migration and Invasion by Migracin A in Ovarian Clear Cell Carcinoma Cells.

PubMed

Ukaji, Tamami; Lin, Yinzhi; Banno, Kouji; Okada, Shoshiro; Umezawa, Kazuo

2015-01-01

Previously we isolated migracin A from a Streptomyces culture filtrate as an inhibitor of cancer cell migration. In the present research, we found that migracin A inhibited migration and invasion of ovarian clear cell carcinoma ES-2 cells. In the course of our mechanistic study, migracin A was shown to enhance vasohibin-1 expression in an angiogenesis array. We also confirmed that it increased the mRNA expression of this protein. Moreover, overexpression of vasohibin-1 lowered the migration but not the invasion of ES-2 cells. Then, we looked for another target protein employing a motility array, and found that migracin A lowered the IGF-1 expression. Knockdown of IGF-1 by siRNA decreased the migration and invasion of ES-2 cells. Migracin A also decreased Akt phosphorylation involved in the downstream signaling. Crosstalk analysis indicated that overexpression of vasohibin-1 decreased the IGF-1 expression. On the other hand, it showed no direct anticancer activity in terms of the ES-2 growth in agar. Migracin A inhibited the migration and IGF-1 expression in not only ES-2 but also another ovarian clear cell carcinoma JHOC-5 cells. In addition, it also inhibited capillary tube formation of human umbilical vein endothelial cells. Since its cytotoxicity is very low, migracin A may be a candidate for an anti-metastasis agent not exhibiting prominent toxicity.

Rear-polarized Wnt5a-receptor-actin-myosin-polarity (WRAMP) structures promote the speed and persistence of directional cell migration

PubMed Central

Connacher, Mary Katherine; Tay, Jian Wei; Ahn, Natalie G.

2017-01-01

In contrast to events at the cell leading edge, rear-polarized mechanisms that control directional cell migration are poorly defined. Previous work described a new intracellular complex, the Wnt5a-receptor-actomyosin polarity (WRAMP) structure, which coordinates the polarized localization of MCAM, actin, and myosin IIB in a Wnt5a-induced manner. However, the polarity and function for the WRAMP structure during cell movement were not determined. Here we characterize WRAMP structures during extended cell migration using live-cell imaging. The results demonstrate that cells undergoing prolonged migration show WRAMP structures stably polarized at the rear, where they are strongly associated with enhanced speed and persistence of directional movement. Strikingly, WRAMP structures form transiently, with cells displaying directional persistence during periods when they are present and cells changing directions randomly when they are absent. Cells appear to pause locomotion when WRAMP structures disassemble and then migrate in new directions after reassembly at a different location, which forms the new rear. We conclude that WRAMP structures represent a rear-directed cellular mechanism to control directional migration and that their ability to form dynamically within cells may control changes in direction during extended migration. PMID:28592632

Giant Planets in Open Clusters

NASA Astrophysics Data System (ADS)

Quinn, S. N.; White, R. J.; Latham, D. W.

2015-10-01

Two decades after the discovery of 51 Peg b, more than 200 hot Jupiters have now been confirmed, but the details of their inward migration remain uncertain. While it is widely accepted that short period giant planets could not have formed in situ, several different mechanisms (e.g., Type II migration, planet-planet scattering, Kozai-Lidov cycles) may contribute to shrinking planetary orbits, and the relative importance of each is not well-constrained. Migration through the gas disk is expected to preserve circular, coplanar orbits and must occur quickly (within ˜ 10 Myr), whereas multi-body processes should initially excite eccentricities and inclinations and may take hundreds of millions of years. Subsequent evolution of the system (e.g., orbital circularization and inclination damping via tidal interaction with the host star) may obscure these differences, so observing hot Jupiters soon after migration occurs can constrain the importance of each mechanism. Fortunately, the well-characterized stars in young and adolescent open clusters (with known ages and compositions) provide natural laboratories for such studies, and recent surveys have begun to take advantage of this opportunity. We present a review of the discoveries in this emerging realm of exoplanet science, discuss the constraints they provide for giant planet formation and migration, and reflect on the future direction of the field.

Cadherin-2 Is Required Cell Autonomously for Collective Migration of Facial Branchiomotor Neurons.

PubMed

Rebman, Jane K; Kirchoff, Kathryn E; Walsh, Gregory S

2016-01-01

Collective migration depends on cell-cell interactions between neighbors that contribute to their overall directionality, yet the mechanisms that control the coordinated migration of neurons remains to be elucidated. During hindbrain development, facial branchiomotor neurons (FBMNs) undergo a stereotypic tangential caudal migration from their place of birth in rhombomere (r)4 to their final location in r6/7. FBMNs engage in collective cell migration that depends on neuron-to-neuron interactions to facilitate caudal directionality. Here, we demonstrate that Cadherin-2-mediated neuron-to-neuron adhesion is necessary for directional and collective migration of FBMNs. We generated stable transgenic zebrafish expressing dominant-negative Cadherin-2 (Cdh2ΔEC) driven by the islet1 promoter. Cell-autonomous inactivation of Cadherin-2 function led to non-directional migration of FBMNs and a defect in caudal tangential migration. Additionally, mosaic analysis revealed that Cdh2ΔEC-expressing FBMNs are not influenced to migrate caudally by neighboring wild-type FBMNs due to a defect in collective cell migration. Taken together, our data suggest that Cadherin-2 plays an essential cell-autonomous role in mediating the collective migration of FBMNs.

Strain effects on oxygen vacancy energetics in KTaO 3

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

Xi, Jianqi; Xu, Haixuan; Zhang, Yanwen

Due to lattice mismatch between epitaxial films and substrates, in-plane strain fields are produced in the thin films, with accompanying structural distortions, and ion implantation can be used to controllably engineer the strain throughout the film. Because of the strain profile, local defect energetics are changed. In this study, the effects of in-plane strain fields on the formation and migration of oxygen vacancies in KTaO 3 are investigated using first-principles calculations. In particular, the doubly positive charged oxygen vacancy (V 2+O) is studied, which is considered to be the main charge state of the oxygen vacancy in KTaO 3. Wemore » find that the formation energies for oxygen vacancies are sensitive to in-plane strain and oxygen position. The local atomic configuration is identified, and strong relaxation of local defect structure is mainly responsible for the formation characteristics of these oxygen vacancies. Based on the computational results, formation-dependent site preferences for oxygen vacancies are expected to occur under epitaxial strain, which can result in orders of magnitude differences in equilibrium vacancy concentrations on different oxygen sites. In addition, all possible migration pathways, including intra- and inter-plane diffusions, are considered. In contrast to the strain-enhanced intra-plane diffusion, the diffusion in the direction normal to the strained plane is impeded under the epitaxial strain field. Lastly, these anisotropic diffusion processes can further enhance site preferences.« less

Strain effects on oxygen vacancy energetics in KTaO 3

DOE PAGES

Xi, Jianqi; Xu, Haixuan; Zhang, Yanwen; ...

2017-02-07

Due to lattice mismatch between epitaxial films and substrates, in-plane strain fields are produced in the thin films, with accompanying structural distortions, and ion implantation can be used to controllably engineer the strain throughout the film. Because of the strain profile, local defect energetics are changed. In this study, the effects of in-plane strain fields on the formation and migration of oxygen vacancies in KTaO 3 are investigated using first-principles calculations. In particular, the doubly positive charged oxygen vacancy (V 2+O) is studied, which is considered to be the main charge state of the oxygen vacancy in KTaO 3. Wemore » find that the formation energies for oxygen vacancies are sensitive to in-plane strain and oxygen position. The local atomic configuration is identified, and strong relaxation of local defect structure is mainly responsible for the formation characteristics of these oxygen vacancies. Based on the computational results, formation-dependent site preferences for oxygen vacancies are expected to occur under epitaxial strain, which can result in orders of magnitude differences in equilibrium vacancy concentrations on different oxygen sites. In addition, all possible migration pathways, including intra- and inter-plane diffusions, are considered. In contrast to the strain-enhanced intra-plane diffusion, the diffusion in the direction normal to the strained plane is impeded under the epitaxial strain field. Lastly, these anisotropic diffusion processes can further enhance site preferences.« less

Connective Tissue Growth Factor (CTGF/CCN2) mediates angiogenic effect of S1P in human dermal microvascular endothelial cells

PubMed Central

MARKIEWICZ, MAGARET; NAKERAKANTI, SASHIDHAR S.; KAPANADZE, BAGRAT; GHATNEKAR, ANGELA; TROJANOWSKA, MARIA

2010-01-01

Objective The primary objective of this study was to examine the potential interaction between sphingosine-1-phosphate (S1P), a pleiotropic lipid mediator, and CTGF/CCN2 a secreted multimodular protein, in the process of endothelial cell migration. The second objective was to determine whether C- and N-terminal domains of CTGF/CCN2 have specific function in cell migration. Materials and Methods Migration of human dermal microvascular endothelial cells (HDMECs) was examined in monolayer wound healing “scratch” assay, while capillary-like tube formation was examined in 3 dimensional collagen co-culture assays. Results We observed that S1P stimulates HDMECs migration concomitant with upregulation of CTGF/CCN2 expression. Furthermore, the blockade of endogenous CTGF/CCN2 via siRNA abrogated S1P induced HDMECs migration and capillary-like tube formation. Full length CTGF induced cell migration and capillary-like tube formation with potency similar to that of S1P, while C-terminal domain of CTGF was slightly less effective. However; N-terminal domain had only a residual activity in inducing capillary-like tube formation. Conclusions This study revealed that CTGF/CCN2 is required for the S1P induced endothelial cell migration, which suggests that CTGF/CCN2 may be an important mediator of S1P induced physiological and pathological angiogenesis. Moreover, this study shows that the pro-migratory activity of CTGF/CCN2 is located in the C-terminal domain. PMID:21166920

Connective tissue growth factor (CTGF/CCN2) mediates angiogenic effect of S1P in human dermal microvascular endothelial cells.

PubMed

Markiewicz, Margaret; Nakerakanti, Sashidhar S; Kapanadze, Bagrat; Ghatnekar, Angela; Trojanowska, Maria

2011-01-01

The primary objective of this study was to examine the potential interaction between S1P, a pleiotropic lipid mediator, and CTGF/CCN2, a secreted multimodular protein, in the process of endothelial cell migration. The secondary objective was to determine whether C- and N-terminal domains of CTGF/CCN2 have a specific function in cell migration. Migration of HDMECs was examined in monolayer wound healing "scratch" assay, whereas capillary-like tube formation was examined in three-dimensional collagen co-culture assays. We observed that S1P stimulates migration of HDMECs concomitant with upregulation of CTGF/CCN2 expression. Furthermore, the blockade of endogenous CTGF/CCN2 via siRNA abrogated S1P-induced HDMEC migration and capillary-like tube formation. Full-length CTGF induced cell migration and capillary-like tube formation with a potency similar to that of S1P, while C-terminal domain of CTGF was slightly less effective. However, N-terminal domain had only a residual activity in inducing capillary-like tube formation. This study revealed that CTGF/CCN2 is required for the S1P-induced endothelial cell migration, which suggests that CTGF/CCN2 may be an important mediator of S1P-induced physiological and pathological angiogenesis. Moreover, this study shows that the pro-migratory activity of CTGF/CCN2 is located in the C-terminal domain. © 2010 John Wiley & Sons Ltd.

Modeling Sr-90 Retardation by Fractured Rocks Based on the Results of In Situ and Laboratory Research

NASA Astrophysics Data System (ADS)

Samsanova, L.; Kotchergina, N. V.; Glinsky, M.; Zinin, A.; Ivanov, I.

2001-12-01

Industrial solutions from the surface storage of liquid radioactive wastes in Lake Karachay have been migrating in groundwaters for 50 years. Interaction of industrial solutions with fractured water-bearing rocks results in the formation of a plume body of contaminated rocks due to a partial retardation of the migrating radionuclides. In conducting research of the fractured rocks core samples from the wells located within the contaminated ground water plume, we have obtained empirical estimations of the retardation parameter (Sr-90 interphase distribution factor, Kd). To interpret the experimental data on Sr-90 Kd, a method of modeling of strontium-90 retardation by fractured rocks has been developed. The process of transient filtration for a flow fragment from Lake Karachay was reconstructed. Epignose modeling of the industrial solution's main flow migrating from Lake Karachay in south direction was performed. By solving the inverse tasks Kd of strontium-90 was estimated for the fractured rocks.

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

NASA Astrophysics Data System (ADS)

Pfunt, Helena; Houben, Georg; Himmelsbach, Thomas

2016-09-01

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

New Skills, New Jobs: Return Migration, Skill Transfers, and Business Formation in Mexico

PubMed Central

Wassink, Joshua

2017-01-01

Numerous studies have documented a high propensity for self-employment and business formation among return migrants relative to non-migrants. The literature points to the importance of remitted savings, migration duration, and number and types of jobs abroad for business formation upon return. Implicit in this scholarship is the assumption that migrants acquire not only financial capital, but also human capital, which expands their opportunities upon return. Empirical work has demonstrated how the transfer of formal human capital, such as language skills and professional credentials, influences the mobility pathways of professional return migrants. More recent research has also found that the transfer of informal human capital, such as social and technical skills learned on the job, shape the mobility pathways of return migrants with little schooling. Absent from this scholarship, however, are studies that directly test the relationship between the transfer of informal human capital and the odds of business formation among return migrants. In this paper, we address this gap. Using a multidimensional skills variable, which includes social, technical, and English language competences, we measure and test the relationship between skill acquisition and transfer and business formation among return migrants. Drawing on findings from a survey of 200 return migrants and 200 non-migrants in Mexico, we show that return migrants who successfully acquire and transfer new skills across the migratory circuit often leverage their new knowledge to launch businesses. Our findings have wide implications for how social scientists conceptualize and measure human capital formation across the migratory circuit. PMID:28316348

Notch1-Dll4 signaling and mechanical force regulate leader cell formation during collective cell migration

PubMed Central

Riahi, Reza; Sun, Jian; Wang, Shue; Long, Min; Zhang, Donna D.; Wong, Pak Kin

2015-01-01

At the onset of collective cell migration, a subset of cells within an initially homogenous population acquires a distinct “leader” phenotype with characteristic morphology and motility. However, the factors driving leader cell formation as well as the mechanisms regulating leader cell density during the migration process remain to be determined. Here, we use single cell gene expression analysis and computational modeling to show that leader cell identity is dynamically regulated by Dll4 signaling through both Notch1 and cellular stress in a migrating epithelium. Time-lapse microscopy reveals that Dll4 is induced in leader cells after the creation of the cell-free region and leader cells are regulated via Notch1-Dll4 lateral inhibition. Furthermore, mechanical stress inhibits Dll4 expression and leader cell formation in the monolayer. Collectively, our findings suggest that a reduction of mechanical force near the boundary promotes Notch1-Dll4 signaling to dynamically regulate the density of leader cells during collective cell migration. PMID:25766473

Epithelial sheet folding induces lumen formation by Madin-Darby canine kidney cells in a collagen gel.

PubMed

Ishida, Sumire; Tanaka, Ryosuke; Yamaguchi, Naoya; Ogata, Genki; Mizutani, Takeomi; Kawabata, Kazushige; Haga, Hisashi

2014-01-01

Lumen formation is important for morphogenesis; however, an unanswered question is whether it involves the collective migration of epithelial cells. Here, using a collagen gel overlay culture method, we show that Madin-Darby canine kidney cells migrated collectively and formed a luminal structure in a collagen gel. Immediately after the collagen gel overlay, an epithelial sheet folded from the periphery, migrated inwardly, and formed a luminal structure. The inhibition of integrin-β1 or Rac1 activity decreased the migration rate of the peripheral cells after the sheets folded. Moreover, lumen formation was perturbed by disruption of apical-basolateral polarity induced by transforming growth factor-β1. These results indicate that cell migration and cell polarity play an important role in folding. To further explore epithelial sheet folding, we developed a computer-simulated mechanical model based on the rigidity of the extracellular matrix. It indicated a soft substrate is required for the folding movement.

Silk Film Topography Directs Collective Epithelial Cell Migration

PubMed Central

Rosenblatt, Mark I.

2012-01-01

The following study provides new insight into how surface topography dictates directed collective epithelial cell sheet growth through the guidance of individual cell movement. Collective cell behavior of migrating human corneal limbal-epithelial cell sheets were studied on highly biocompatible flat and micro-patterned silk film surfaces. The silk film edge topography guided the migratory direction of individual cells making up the collective epithelial sheet, which resulted in a 75% increase in total culture elongation. This was due to a 3-fold decrease in cell sheet migration rate efficiency for movement perpendicular to the topography edge. Individual cell migration direction is preferred in the parallel approach to the edge topography where localization of cytoskeletal proteins to the topography’s edge region is reduced, which results in the directed growth of the collective epithelial sheet. Findings indicate customized biomaterial surfaces may be created to direct both the migration rate and direction of tissue epithelialization. PMID:23185573

Exoplanet Orbits Youthful Star (Artist Concept)

NASA Image and Video Library

2016-06-20

K2-33b, shown in this illustration, is one of the youngest exoplanets detected to date using NASA Kepler Space Telescope. It makes a complete orbit around its star in about five days. These two characteristics combined provide exciting new directions for planet-formation theories. K2-33b could have formed on a farther out orbit and quickly migrated inward. Alternatively, it could have formed in situ, or in place. http://photojournal.jpl.nasa.gov/catalog/PIA20690

Effects of ROCK inhibitor Y-27632 on cell fusion through a microslit.

PubMed

Wada, Ken-Ichi; Hosokawa, Kazuo; Ito, Yoshihiro; Maeda, Mizuo

2015-11-01

We previously reported a direct cytoplasmic transfer method using a microfluidic device, in which cell fusion was induced through a microslit (slit-through-fusion) by the Sendai virus envelope (HVJ-E) to prevent nuclear mixing. However, the method was impractical due to low efficiency of slit-through-fusion formation and insufficient prevention of nuclear mixing. The purpose of this study was to establish an efficient method for inducing slit-through-fusion without nuclear mixing. We hypothesized that modulation of cytoskeletal component can decrease nuclear migration through the microslit considering its functions. Here we report that supplementation with Y-27632, a specific ROCK inhibitor, significantly enhances cell fusion induction and prevention of nuclear mixing. Supplementation with Y-27632 increased the formation of slit-through-fusion efficiency by more than twofold. Disruption of F-actin by Y-27632 prevented nuclear migration between fused cells through the microslit. These two effects of Y-27632 led to promotion of the slit-through-fusion without nuclear mixing with a 16.5-fold higher frequency compared to our previous method (i.e., cell fusion induction by HVJ-E without supplementation with Y-27632). We also confirmed that mitochondria were successfully transferred to the fusion partner under conditions of Y-27632 supplementation. These findings demonstrate the practicality of our cell fusion system in producing direct cytoplasmic transfer between live cells. © 2015 Wiley Periodicals, Inc.

Assembly of the Escherichia coli RuvABC resolvasome directs the orientation of Holliday junction resolution

PubMed Central

van Gool, Alain J.; Hajibagheri, Nasser M.A.; Stasiak, Andrzej; West, Stephen C.

1999-01-01

Genetic recombination can lead to the formation of intermediates in which DNA molecules are linked by Holliday junctions. Movement of a junction along DNA, by a process known as branch migration, leads to heteroduplex formation, whereas resolution of a junction completes the recombination process. Holliday junctions can be resolved in either of two ways, yielding products in which there has, or has not, been an exchange of flanking markers. The ratio of these products is thought to be determined by the frequency with which the two isomeric forms (conformers) of the Holliday junction are cleaved. Recent studies with enzymes that process Holliday junctions in Escherichia coli, the RuvABC proteins, however, indicate that protein binding causes the junction to adopt an open square-planar configuration. Within such a structure, DNA isomerization can have little role in determining the orientation of resolution. To determine the role that junction-specific protein assembly has in determining resolution bias, a defined in vitro system was developed in which we were able to direct the assembly of the RuvABC resolvasome. We found that the bias toward resolution in one orientation or the other was determined simply by the way in which the Ruv proteins were positioned on the junction. Additionally, we provide evidence that supports current models on RuvABC action in which Holliday junction resolution occurs as the resolvasome promotes branch migration. PMID:10421637

Star-disc interaction in galactic nuclei: formation of a central stellar disc

NASA Astrophysics Data System (ADS)

Panamarev, Taras; Shukirgaliyev, Bekdaulet; Meiron, Yohai; Berczik, Peter; Just, Andreas; Spurzem, Rainer; Omarov, Chingis; Vilkoviskij, Emmanuil

2018-05-01

We perform high-resolution direct N-body simulations to study the effect of an accretion disc on stellar dynamics in an active galactic nucleus (AGN). We show that the interaction of the nuclear stellar cluster (NSC) with the gaseous accretion disc (AD) leads to formation of a stellar disc in the central part of the NSC. The accretion of stars from the stellar disc on to the super-massive black hole is balanced by the capture of stars from the NSC into the stellar disc, yielding a stationary density profile. We derive the migration time through the AD to be 3 per cent of the half-mass relaxation time of the NSC. The mass and size of the stellar disc are 0.7 per cent of the mass and 5 per cent of the influence radius of the super-massive black hole. An AD lifetime shorter than the migration time would result in a less massive nuclear stellar disc. The detection of such a stellar disc could point to past activity of the hosting galactic nucleus.

Jupiter’s decisive role in the inner Solar System’s early evolution

PubMed Central

Batygin, Konstantin; Laughlin, Greg

2015-01-01

The statistics of extrasolar planetary systems indicate that the default mode of planet formation generates planets with orbital periods shorter than 100 days and masses substantially exceeding that of the Earth. When viewed in this context, the Solar System is unusual. Here, we present simulations which show that a popular formation scenario for Jupiter and Saturn, in which Jupiter migrates inward from a > 5 astronomical units (AU) to a ≈ 1.5 AU before reversing direction, can explain the low overall mass of the Solar System’s terrestrial planets, as well as the absence of planets with a < 0.4 AU. Jupiter’s inward migration entrained s ≳ 10−100 km planetesimals into low-order mean motion resonances, shepherding and exciting their orbits. The resulting collisional cascade generated a planetesimal disk that, evolving under gas drag, would have driven any preexisting short-period planets into the Sun. In this scenario, the Solar System’s terrestrial planets formed from gas-starved mass-depleted debris that remained after the primary period of dynamical evolution. PMID:25831540

Effect of Granulocyte-Colony Stimulating Factor on Endothelial Cells and Osteoblasts

PubMed Central

Liu, Xi Ling; Hu, Xiang; Cai, Wei Xin; Lu, Weijia William; Zheng, Li Wu

2016-01-01

Objectives. Some animal studies showed that granulocyte-colony stimulating factor (G-CSF) provides beneficial environment for bone healing. It has been well documented that endothelial cells and osteoblasts play critical roles in multiple phases of bone healing. However, the biological effects of G-CSF on these cells remain controversial. This study aimed to investigate the influence of G-CSF at various concentrations on endothelial cells and osteoblasts. Materials and Methods. Human umbilical vein endothelial cells (HUVECs) and human osteoblasts (hOBs) were treated with G-CSF at 1000, 100, 10, and 0 ng/mL, respectively. The capacity of cell proliferation, migration, and tube formation of HUVECs was evaluated at 72, 8, and 6 hours after treatment, respectively. The capacity of proliferation, differentiation, and mineralization of hOBs was evaluated at 24 hours, 72 hours, and 21 days after treatment, respectively. Results. HUVECs treated with 100 and 1000 ng/mL G-CSF showed a significantly higher value comparing with controls in migration assay (p < 0.001, p < 0.01, resp.); the group treated with 1000 ng/mL G-CSF showed a significantly lower value on tube formation. No significant difference was detected in groups of hOBs. Conclusions. G-CSF showed favorable effects only on the migration of HUVECs, and no direct influence was found on hOBs. PMID:27006951

MicroRNA-584-3p, a novel tumor suppressor and prognostic marker, reduces the migration and invasion of human glioma cells by targeting hypoxia-induced ROCK1

PubMed Central

Xue, Hao; Guo, Xing; Han, Xiao; Yan, Shaofeng; Zhang, Jinsen; Xu, Shugang; Li, Tong; Guo, Xiaofan; Zhang, Ping; Gao, Xiao; Liu, Qinglin; Li, Gang

2016-01-01

Here, we report that microRNA-584-3p (miR-584-3p) is up-regulated in hypoxic glioma cells and in high-grade human glioma tumors (WHO grades III–IV) relative to normoxic cells and to low-grade tumors (WHO grades I–II), respectively. The postoperative survival time was significantly prolonged in the high-grade glioma patients with high miR-584-3p expression compared with those with low miR-584-3p expression. miR-584-3p may function as a potent tumor suppressor and as a prognostic biomarker for malignant glioma. However, the molecular mechanisms underlying these properties remain poorly understood. Our mechanistic studies revealed that miR-584-3p suppressed the migration and invasion of glioma cells by disrupting hypoxia-induced stress fiber formation. Specifically, we have found that ROCK1 is a direct and functionally relevant target of miR-584-3p in glioma cells. Our results have demonstrated a tumor suppressive function of miR-584-3p in glioma, in which it inhibits the migration and invasion of tumor cells by antagonizing hypoxia-induced, ROCK1-dependent stress fiber formation. Our findings have potential implications for glioma gene therapy and suggest that miR-584-3p could represent a prognostic indicator for glioma. PMID:26715733

INSIDE-OUT PLANET FORMATION. III. PLANET–DISK INTERACTION AT THE DEAD ZONE INNER BOUNDARY

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

Hu, Xiao; Tan, Jonathan C.; Chatterjee, Sourav

The Kepler mission has discovered more than 4000 exoplanet candidates. Many of them are in systems with tightly packed inner planets. Inside-out planet formation (IOPF) has been proposed as a scenario to explain these systems. It involves sequential in situ planet formation at the local pressure maximum of a retreating dead zone inner boundary (DZIB). Pebbles accumulate at this pressure trap, which builds up a pebble ring and then a planet. The planet is expected to grow in mass until it opens a gap, which helps to both truncate pebble accretion and also induce DZIB retreat that sets the location ofmore » formation of the next planet. This simple scenario may be modified if the planet undergoes significant migration from its formation location. Thus, planet–disk interactions play a crucial role in the IOPF scenario. Here we present numerical simulations that first assess the degree of migration for planets of various masses that are forming at the DZIB of an active accretion disk, where the effective viscosity is undergoing a rapid increase in the radially inward direction. We find that torques exerted on the planet by the disk tend to trap the planet at a location very close to the initial pressure maximum where it formed. We then study gap opening by these planets to assess at what mass a significant gap is created. Finally, we present a simple model for DZIB retreat due to penetration of X-rays from the star to the disk midplane. Overall, these simulations help to quantify both the mass scale of first (“Vulcan”) planet formation and the orbital separation to the location of second planet formation.« less

Inside-out Planet Formation. III. Planet-Disk Interaction at the Dead Zone Inner Boundary

NASA Astrophysics Data System (ADS)

Hu, Xiao; Zhu, Zhaohuan; Tan, Jonathan C.; Chatterjee, Sourav

2016-01-01

The Kepler mission has discovered more than 4000 exoplanet candidates. Many of them are in systems with tightly packed inner planets. Inside-out planet formation (IOPF) has been proposed as a scenario to explain these systems. It involves sequential in situ planet formation at the local pressure maximum of a retreating dead zone inner boundary (DZIB). Pebbles accumulate at this pressure trap, which builds up a pebble ring and then a planet. The planet is expected to grow in mass until it opens a gap, which helps to both truncate pebble accretion and also induce DZIB retreat that sets the location of formation of the next planet. This simple scenario may be modified if the planet undergoes significant migration from its formation location. Thus, planet-disk interactions play a crucial role in the IOPF scenario. Here we present numerical simulations that first assess the degree of migration for planets of various masses that are forming at the DZIB of an active accretion disk, where the effective viscosity is undergoing a rapid increase in the radially inward direction. We find that torques exerted on the planet by the disk tend to trap the planet at a location very close to the initial pressure maximum where it formed. We then study gap opening by these planets to assess at what mass a significant gap is created. Finally, we present a simple model for DZIB retreat due to penetration of X-rays from the star to the disk midplane. Overall, these simulations help to quantify both the mass scale of first (“Vulcan”) planet formation and the orbital separation to the location of second planet formation.

MIGRATION TRAPS IN DISKS AROUND SUPERMASSIVE BLACK HOLES

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

Bellovary, Jillian M.; Low, Mordecai-Mark Mac; McKernan, Barry

Accretion disks around supermassive black holes (SMBHs) in active galactic nuclei (AGNs) contain stars, stellar mass black holes, and other stellar remnants, which perturb the disk gas gravitationally. The resulting density perturbations exert torques on the embedded masses causing them to migrate through the disk in a manner analogous to planets in protoplanetary disks. We determine the strength and direction of these torques using an empirical analytic description dependent on local disk gradients, applied to two different analytic, steady-state disk models of SMBH accretion disks. We find that there are radii in such disks where the gas torque changes sign,more » trapping migrating objects. Our analysis shows that major migration traps generally occur where the disk surface density gradient changes sign from positive to negative, around 20–300R{sub g}, where R{sub g} = 2GM/c{sup 2} is the Schwarzschild radius. At these traps, massive objects in the AGN disk can accumulate, collide, scatter, and accrete. Intermediate mass black hole formation is likely in these disk locations, which may lead to preferential gap and cavity creation at these radii. Our model thus has significant implications for SMBH growth as well as gravitational wave source populations.« less

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

Forced migration, adolescence, and identity formation.

PubMed

Anagnostopoulos, Dimitris C; Vlassopoulos, Maria; Lazaratou, Helen

2006-09-01

Adolescence is a complex biopsychosocial phenomenon. All the inner-subjective changes in adolescents take place within the context of a specific social environment, which offers the necessary ideological setting that adolescents must confront in the course of their identity formation. Forced migration creates conditions under which the adolescent Ego may be traumatized more easily, resulting in the development of defensive mechanisms, which may interfere with the natural process of identity formation. The aim of this paper is to investigate how a traumatic situation such as forced migration may affect the mechanisms of identity formation in adolescence. For this purpose, clinical material, consisting of two cases of psychoanalytical psychotherapy of adolescents who were forced to immigrate to Greece, is presented and discussed in a psychoanalytical theoretical framework, along with the historical-sociological background.

Absence of bundle structure in the neocortex of the reeler mouse at the embryonic stage. Studies by scanning electron microscopic fractography.

PubMed

Mikoshiba, K; Nishimura, Y; Tsukada, Y

The reeler mutant mouse is characterized by a derangement of the cerebral cortical structure due to abnormalities during the migration step at the embryonic stage. We have analyzed both the control and reeler cerebral cortex by means of scanning electron microscopic fractography. In the control cerebral cortex, the bundle formation was composed of fine fibers on which the migrating neuroblasts were attached perpendicular to the pial surface, whereas no bundle formation was observed in the reeler; instead, there was a fine meshwork of fibers surrounding the neuroblasts. The possible role of bundle formation in the normal cerebral cortex and the correlation between the inability of cells to migrate and the absence of bundle formation in the reeler is discussed.

Japanese direct investment and its impact on migration in the ASEAN 4.

PubMed

Ito, S; Iguchi, Y

1994-01-01

"The purpose of this article is to show the relationship among Japanese direct investment...,domestic labor markets, and international labor migration in ASEAN-4 countries (Indonesia, Malaysia, Philippines, and Thailand). The effects of foreign direct investment on skilled labor migration are also considered." excerpt

Deformation-related recrystallization processes

NASA Astrophysics Data System (ADS)

Drury, Martyn R.; Urai, Janos L.

1990-02-01

Recrystallization is a common microstructural transformation that occurs during deformation, metamorphism and diagenesis of rocks. Studies on minerals and rock analogues have demonstrated that a wide range of recrystallization mechanisms can occur. The range of mechanisms is related to the various ways in which two basic processes, grain boundary migration and new grain boundary formation combine to transform the microstructure. Two recent papers (Drury et al., 1985; Urai et al., 1986) have proposed different schemes for the description of recrystallization mechanisms. The purpose of this paper is to provide a unified framework for the description of mechanisms. Recrystallization mechanisms are divided into three main types; rotation mechanisms which principally involve the formation of new grain boundaries; migration mechanisms which principally involve grain boundary migration; and general mechanisms which involve both basic processes. A further distinction is made on the basis of the continuity of the microstructural transformation with respect to time. Each of the three main types of mechanism can be divided into a number of sub-types depending on whether the processes of grain boundary migration, new grain boundary formation and new grain formation occur in a discontinuous or continuous manner with respect to time. As the terms continuous and discontinuous have been used in the metallurgical literature to signify the spatial continuity of the microstructural transformation, the terms discontinuai and continual are used to refer to the temporal continuity of the transformation. It is recommended that the following aspects should be specified, if possible, in a general description of recrystallization mechanisms: (1) How do the basic processes combine to transform the microstructure. (2) If new grain development occurs, what is the development mechanism, and does new grain formation occur in a continual or discontinuai manner. (3) If grain boundary migration is involved in the transformation, what is the migration mechanism (i.e. fast solute escape migration, slow solute loaded migration, fluid assisted migration, etc.), and is migration a continual or discontinuai process. The application of the unified scheme is illustrated by reviewing studies that have provided detailed information on the recrystallization mechanisms involved. The complicating effects of solid solution impurities, dispersed second phase particles and grain boundary fluid films are also considered and it is demonstrated that variations in content of these types of impurity can significantly effect the types of recrystallization that occur in a given material.

Spatial distribution of filament elasticity determines the migratory behaviors of a cell

PubMed Central

Harn, Hans I-Chen; Hsu, Chao-Kai; Wang, Yang-Kao; Huang, Yi-Wei; Chiu, Wen-Tai; Lin, Hsi-Hui; Cheng, Chao-Min; Tang, Ming-Jer

2016-01-01

ABSTRACT Any cellular response leading to morphological changes is highly tuned to balance the force generated from structural reorganization, provided by actin cytoskeleton. Actin filaments serve as the backbone of intracellular force, and transduce external mechanical signal via focal adhesion complex into the cell. During migration, cells not only undergo molecular changes but also rapid mechanical modulation. Here we focus on determining, the role of spatial distribution of mechanical changes of actin filaments in epithelial, mesenchymal, fibrotic and cancer cells with non-migration, directional migration, and non-directional migration behaviors using the atomic force microscopy. We found 1) non-migratory cells only generated one type of filament elasticity, 2) cells generating spatially distributed two types of filament elasticity showed directional migration, and 3) pathologic cells that autonomously generated two types of filament elasticity without spatial distribution were actively migrating non-directionally. The demonstration of spatial regulation of filament elasticity of different cell types at the nano-scale highlights the coupling of cytoskeletal function with physical characters at the sub-cellular level, and provides new research directions for migration related disease. PMID:26919488

First-Time Migration in Juvenile Common Cuckoos Documented by Satellite Tracking

PubMed Central

Willemoes, Mikkel; Thomson, Robert L.; Tolvanen, Jere; Rutila, Jarkko; Samaš, Peter; Strandberg, Roine; Grim, Tomáš; Fossøy, Frode; Stokke, Bård Gunnar; Thorup, Kasper

2016-01-01

Being an obligate parasite, juvenile common cuckoos Cuculus canorus are thought to reach their African wintering grounds from Palearctic breeding grounds without guidance from experienced conspecifics but this has not been documented. We used satellite tracking to study naïve migrating common cuckoos. Juvenile cuckoos left breeding sites in Finland moving slowly and less consistently directed than adult cuckoos. Migration of the juveniles (N = 5) was initiated later than adults (N = 20), was directed toward the southwest–significantly different from the initial southeast direction of adults–and included strikingly long Baltic Sea crossings (N = 3). After initial migration of juvenile cuckoos toward Poland, the migration direction changed and proceeded due south, directly toward the winter grounds, as revealed by a single tag transmitting until arrival in Northwest Angola where northern adult cuckoos regularly winter. Compared to adults, the juvenile travelled straighter and faster, potentially correcting for wind drift along the route. That both migration route and timing differed from adults indicates that juvenile cuckoos are able to reach proper wintering grounds independently, guided only by their innate migration programme. PMID:28005960

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

Capillary Assembly of Colloids: Interactions on Planar and Curved Interfaces

NASA Astrophysics Data System (ADS)

Liu, Iris B.; Sharifi-Mood, Nima; Stebe, Kathleen J.

2018-03-01

In directed assembly, small building blocks are assembled into an organized structure under the influence of guiding fields. Capillary interactions provide a versatile route for structure formation. Colloids adsorbed on fluid interfaces distort the interface, which creates an associated energy field. When neighboring distortions overlap, colloids interact to minimize interfacial area. Contact line pinning, particle shape, and surface chemistry play important roles in structure formation. Interface curvature acts like an external field; particles migrate and assemble in patterns dictated by curvature gradients. We review basic analysis and recent findings in this rapidly evolving literature. Understanding the roles of assembly is essential for tuning the mechanical, physical, and optical properties of the structure.

High Altitude Bird Migration at Temperate Latitudes: A Synoptic Perspective on Wind Assistance

PubMed Central

Dokter, Adriaan M.; Shamoun-Baranes, Judy; Kemp, Michael U.; Tijm, Sander; Holleman, Iwan

2013-01-01

At temperate latitudes the synoptic patterns of bird migration are strongly structured by the presence of cyclones and anticyclones, both in the horizontal and altitudinal dimensions. In certain synoptic conditions, birds may efficiently cross regions with opposing surface wind by choosing a higher flight altitude with more favourable wind. We observed migratory passerines at mid-latitudes that selected high altitude wind optima on particular nights, leading to the formation of structured migration layers at varying altitude up to 3 km. Using long-term vertical profiling of bird migration by C-band Doppler radar in the Netherlands, we find that such migration layers occur nearly exclusively during spring migration in the presence of a high-pressure system. A conceptual analytic framework providing insight into the synoptic patterns of wind assistance for migrants that includes the altitudinal dimension has so far been lacking. We present a simple model for a baroclinic atmosphere that relates vertical profiles of wind assistance to the pressure and temperature patterns occurring at temperate latitudes. We show how the magnitude and direction of the large scale horizontal temperature gradient affects the relative gain in wind assistance that migrants obtain through ascending. Temperature gradients typical for northerly high-pressure systems in spring are shown to cause high altitude wind optima in the easterly sectors of anticyclones, thereby explaining the frequent observations of high altitude migration in these synoptic conditions. Given the recurring synoptic arrangements of pressure systems across temperate continents, the opportunities for exploiting high altitude wind will differ between flyways, for example between easterly and westerly oceanic coasts. PMID:23300969

High altitude bird migration at temperate latitudes: a synoptic perspective on wind assistance.

PubMed

Dokter, Adriaan M; Shamoun-Baranes, Judy; Kemp, Michael U; Tijm, Sander; Holleman, Iwan

2013-01-01

At temperate latitudes the synoptic patterns of bird migration are strongly structured by the presence of cyclones and anticyclones, both in the horizontal and altitudinal dimensions. In certain synoptic conditions, birds may efficiently cross regions with opposing surface wind by choosing a higher flight altitude with more favourable wind. We observed migratory passerines at mid-latitudes that selected high altitude wind optima on particular nights, leading to the formation of structured migration layers at varying altitude up to 3 km. Using long-term vertical profiling of bird migration by C-band Doppler radar in the Netherlands, we find that such migration layers occur nearly exclusively during spring migration in the presence of a high-pressure system. A conceptual analytic framework providing insight into the synoptic patterns of wind assistance for migrants that includes the altitudinal dimension has so far been lacking. We present a simple model for a baroclinic atmosphere that relates vertical profiles of wind assistance to the pressure and temperature patterns occurring at temperate latitudes. We show how the magnitude and direction of the large scale horizontal temperature gradient affects the relative gain in wind assistance that migrants obtain through ascending. Temperature gradients typical for northerly high-pressure systems in spring are shown to cause high altitude wind optima in the easterly sectors of anticyclones, thereby explaining the frequent observations of high altitude migration in these synoptic conditions. Given the recurring synoptic arrangements of pressure systems across temperate continents, the opportunities for exploiting high altitude wind will differ between flyways, for example between easterly and westerly oceanic coasts.

The distinct roles of the nucleus and nucleus-cytoskeleton connections in three-dimensional cell migration

PubMed Central

Khatau, Shyam B.; Bloom, Ryan J.; Bajpai, Saumendra; Razafsky, David; Zang, Shu; Giri, Anjil; Wu, Pei-Hsun; Marchand, Jorge; Celedon, Alfredo; Hale, Christopher M.; Sun, Sean X.; Hodzic, Didier; Wirtz, Denis

2012-01-01

Cells often migrate in vivo in an extracellular matrix that is intrinsically three-dimensional (3D) and the role of actin filament architecture in 3D cell migration is less well understood. Here we show that, while recently identified linkers of nucleoskeleton to cytoskeleton (LINC) complexes play a minimal role in conventional 2D migration, they play a critical role in regulating the organization of a subset of actin filament bundles – the perinuclear actin cap - connected to the nucleus through Nesprin2giant and Nesprin3 in cells in 3D collagen I matrix. Actin cap fibers prolong the nucleus and mediate the formation of pseudopodial protrusions, which drive matrix traction and 3D cell migration. Disruption of LINC complexes disorganizes the actin cap, which impairs 3D cell migration. A simple mechanical model explains why LINC complexes and the perinuclear actin cap are essential in 3D migration by providing mechanical support to the formation of pseudopodial protrusions. PMID:22761994

Collisions of deformable cells lead to collective migration

NASA Astrophysics Data System (ADS)

Löber, Jakob; Ziebert, Falko; Aranson, Igor S.

2015-03-01

Collective migration of eukaryotic cells plays a fundamental role in tissue growth, wound healing and immune response. The motion, arising spontaneously or in response to chemical and mechanical stimuli, is also important for understanding life-threatening pathologies, such as cancer and metastasis formation. We present a phase-field model to describe the movement of many self-organized, interacting cells. The model takes into account the main mechanisms of cell motility - acto-myosin dynamics, as well as substrate-mediated and cell-cell adhesion. It predicts that collective cell migration emerges spontaneously as a result of inelastic collisions between neighboring cells: collisions lead to a mutual alignment of the cell velocities and to the formation of coherently-moving multi-cellular clusters. Small cell-to-cell adhesion, in turn, reduces the propensity for large-scale collective migration, while higher adhesion leads to the formation of moving bands. Our study provides valuable insight into biological processes associated with collective cell motility.

Periodic Pattern Formation of Bacterial Colonies

NASA Astrophysics Data System (ADS)

Itoh, Hiroto; Wakita, Jun-ichi; Matsuyama, Tohey; Matsushita, Mitsugu

1999-04-01

We have experimentally investigated pattern formation of colonies ofbacterial species Proteus mirabilis, which is famous forforming concentric-ring-like colonies.The colony grows cyclically with the interface repeating an advance anda stop alternately on a surface of a solid agar medium.We distinguish three phases (initial lag phase, the followingmigration and consolidation phases that appear alternately) for the colony growth.When we cut a colony just behind a migrating front shortly after the migrationstarted, the migration ended earlier and the following consolidationlasted longer.However, the following cycles were not influenced by the cut, i.e., thephases of the migration and consolidation were not affected.Global chemical signals governing the colony formation from thecenter were not found to exist.We also quantitatively checked phase entrainment by letting two coloniescollide with each other and found that it does not take place in macroscopic scales.All these experimental results suggest that the most important factorfor the migration is the cell population density.

Cancer-associated fibroblasts promote directional cancer cell migration by aligning fibronectin.

PubMed

Erdogan, Begum; Ao, Mingfang; White, Lauren M; Means, Anna L; Brewer, Bryson M; Yang, Lijie; Washington, M Kay; Shi, Chanjuan; Franco, Omar E; Weaver, Alissa M; Hayward, Simon W; Li, Deyu; Webb, Donna J

2017-11-06

Cancer-associated fibroblasts (CAFs) are major components of the carcinoma microenvironment that promote tumor progression. However, the mechanisms by which CAFs regulate cancer cell migration are poorly understood. In this study, we show that fibronectin (Fn) assembled by CAFs mediates CAF-cancer cell association and directional migration. Compared with normal fibroblasts, CAFs produce an Fn-rich extracellular matrix with anisotropic fiber orientation, which guides the cancer cells to migrate directionally. CAFs align the Fn matrix by increasing nonmuscle myosin II- and platelet-derived growth factor receptor α-mediated contractility and traction forces, which are transduced to Fn through α5β1 integrin. We further show that prostate cancer cells use αv integrin to migrate efficiently and directionally on CAF-derived matrices. We demonstrate that aligned Fn is a prominent feature of invasion sites in human prostatic and pancreatic carcinoma samples. Collectively, we present a new mechanism by which CAFs organize the Fn matrix and promote directional cancer cell migration. © 2017 Erdogan et al.

Cancer-associated fibroblasts promote directional cancer cell migration by aligning fibronectin

PubMed Central

Ao, Mingfang; White, Lauren M.; Means, Anna L.; Yang, Lijie; Washington, M. Kay; Franco, Omar E.; Li, Deyu; Webb, Donna J.

2017-01-01

Cancer-associated fibroblasts (CAFs) are major components of the carcinoma microenvironment that promote tumor progression. However, the mechanisms by which CAFs regulate cancer cell migration are poorly understood. In this study, we show that fibronectin (Fn) assembled by CAFs mediates CAF–cancer cell association and directional migration. Compared with normal fibroblasts, CAFs produce an Fn-rich extracellular matrix with anisotropic fiber orientation, which guides the cancer cells to migrate directionally. CAFs align the Fn matrix by increasing nonmuscle myosin II- and platelet-derived growth factor receptor α–mediated contractility and traction forces, which are transduced to Fn through α5β1 integrin. We further show that prostate cancer cells use αv integrin to migrate efficiently and directionally on CAF-derived matrices. We demonstrate that aligned Fn is a prominent feature of invasion sites in human prostatic and pancreatic carcinoma samples. Collectively, we present a new mechanism by which CAFs organize the Fn matrix and promote directional cancer cell migration. PMID:29021221

DDA3 associates with microtubule plus ends and orchestrates microtubule dynamics and directional cell migration

PubMed Central

Zhang, Liangyu; Shao, Hengyi; Zhu, Tongge; Xia, Peng; Wang, Zhikai; Liu, Lifang; Yan, Maomao; Hill, Donald L.; Fang, Guowei; Chen, Zhengjun; Wang, Dongmei; Yao, Xuebiao

2013-01-01

Cell motility and adhesion involve orchestrated interaction of microtubules (MTs) with their plus-end tracking proteins (+TIPs). However, the mechanisms underlying regulations of MT dynamics and directional cell migration are still elusive. Here, we show that DDA3-EB1 interaction orchestrates MT plus-end dynamics and facilitates directional cell migration. Biochemical characterizations reveal that DDA3 interacts with EB1 via its SxIP motif within the C-terminal Pro/Ser-rich region. Time-lapse and total internal reflection fluorescence (TIRF) microscopic assays demonstrate that DDA3 exhibits EB1-dependent, MT plus-end loading and tracking. The EB1-based loading of DDA3 is responsible for MT plus-ends stabilization at the cell cortex, which in turn orchestrates directional cell migration. Interestingly, the DDA3-EB1 interaction is potentially regulated by EB1 acetylation, which may account for physiological regulation underlying EGF-elicited cell migration. Thus, the EB1-based function of DDA3 links MT dynamics to directional cell migration. PMID:23652583

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

* Central Growth Factor Loaded Depots in Bone Tissue Engineering Scaffolds for Enhanced Cell Attraction.

PubMed

Quade, Mandy; Knaack, Sven; Akkineni, Ashwini Rahul; Gabrielyan, Anastasia; Lode, Anja; Rösen-Wolff, Angela; Gelinsky, Michael

2017-08-01

Tissue engineering, the application of stem and progenitor cells in combination with an engineered extracellular matrix, is a promising strategy for bone regeneration. However, its success is limited by the lack of vascularization after implantation. The concept of in situ tissue engineering envisages the recruitment of cells necessary for tissue regeneration from the host environment foregoing ex vivo cell seeding of the scaffold. In this study, we developed a novel scaffold system for enhanced cell attraction, which is based on biomimetic mineralized collagen scaffolds equipped with a central biopolymer depot loaded with chemotactic agents. In humid milieu, as after implantation, the signaling factors are expected to slowly diffuse out of the central depot forming a gradient that stimulates directed cell migration toward the scaffold center. Heparin, hyaluronic acid, and alginate have been shown to be capable of depot formation. By using vascular endothelial growth factor (VEGF) as model factor, it was demonstrated that the release kinetics can be adjusted by varying the depot composition. While alginate and hyaluronic acid are able to reduce the initial burst and prolong the release of VEGF, the addition of heparin led to a much stronger retention that resulted in an almost linear release over 28 days. The biological activity of released VEGF was proven for all variants using an endothelial cell proliferation assay. Furthermore, migration experiments with endothelial cells revealed a relationship between the degree of VEGF retention and migration distance: cells invaded deepest in scaffolds containing a heparin-based depot indicating that the formation of a steep gradient is crucial for cell attraction. In conclusion, this novel in situ tissue engineering approach, specifically designed to recruit and accommodate endogenous cells upon implantation, appeared highly promising to stimulate cell invasion, which in turn would promote vascularization and finally new bone formation.

Tracking the evolution of a hydrothermal event plume with a RAFOS neutrally buoyant drifter

PubMed

Lupton; Baker; Garfield; Massoth; Feely; Cowen; Greene; Rago

1998-05-15

The migration and evolution of a deep ocean hydrothermal event plume were tracked with a neutrally buoyant RAFOS float. The float remained entrained in the plume for 60 days, and the plume vorticity was calculated directly from the anticyclonic motion of the float. Concentrations of suspended particles, particulate iron, and dissolved manganese in the plume did not decay significantly during the 60 days, which indicates that event plumes would be easily detectable a year after formation.

Impaired SIRT1 promotes the migration of vascular smooth muscle cell-derived foam cells.

PubMed

Zhang, Ming-Jie; Zhou, Yi; Chen, Lei; Wang, Xu; Pi, Yan; Long, Chun-Yan; Sun, Meng-Jiao; Chen, Xue; Gao, Chang-Yue; Li, Jing-Cheng; Zhang, Li-Li

2016-07-01

The formation of fat-laden foam cells, contributing to the fatty streaks of the plaques of atheroma, is the critical early process in atherosclerosis. The previous study demonstrated that vascular smooth muscle cells (VSMCs) contain a much larger burden of the excess cholesterol in comparison with monocyte-derived macrophages in human coronary atherosclerosis, as the main origin of foam cells. It is noteworthy that VSMC-derived foam cells are deposited in subintima but not media, where VSMCs normally deposit in. Therefore, migration from media to intima is an indispensable step for a VSMC to accrue neutral lipids and form foam cell. Whether this migration occurs paralleled with or prior to the formation of foam cell is still unclear. Herein, the present study was designed to test the VSMC migratory capability in the process of foam cell formation induced by oxidized low-density lipoprotein (oxLDL). In conclusion, we provide evidence that oxLDL induces the VSMC-derived foam cells formation with increased migration ability and MMP-9 expression, which were partly attributed to the impaired SIRT1 and enhanced nuclear factor-kappa B (NF-κB) activity. As activation of transient receptor potential vanilloid type 1 (TRPV1) has been reported to have anti-atherosclerotic effects, we investigated its role in oxLDL-treated VSMC migration. It is found that activating TRPV1 by capsaicin inhibits VSMC foam cell formation and the accompanied migration through rescuing the SIRT1 and suppressing NF-κB signaling. The present study provides evidence that SIRT1 may be a promising intervention target of atherosclerosis, and raises the prospect of TRPV1 in prevention and treatment of atherosclerosis.

MicroRNA-510 promotes cell and tumor growth by targeting peroxiredoxin1 in breast cancer

PubMed Central

2013-01-01

Introduction MicroRNAs are small non-coding RNAs that are involved in the post-transcriptional negative regulation of mRNAs. MicroRNA 510 (miR-510) was initially shown to have a potential oncogenic role in breast cancer by the observation of its elevated levels in human breast tumor samples when compared to matched non-tumor samples. Few targets have been identified for miR-510. However, as microRNAs function through the negative regulation of their direct targets, the identification of those targets is critical for the understanding of their functional role in breast cancer. Methods Breast cancer cell lines were transfected with pre-miR-510 or antisense miR-510 and western blotting and quantitative real time PCR were performed. Functional assays performed included cell growth, migration, invasion, colony formation, cytotoxicity and in vivo tumor growth. We performed a PCR assay to identify novel direct targets of miR-510. The study focused on peroxiredoxin 1 (PRDX1) as it was identified through our screen and was bioinformatically predicted to contain a miR-510 seed site in its 3' untranslated region (3'UTR). Luciferase reporter assays and site-directed mutagenesis were performed to confirm PRDX1 as a direct target. The Student's two-sided, paired t-test was used and a P-value less than 0.05 was considered significant. Results We show that miR-510 overexpression in non-transformed and breast cancer cells can increase their cell growth, migration, invasion and colony formation in vitro. We also observed increased tumor growth when miR-510 was overexpressed in vivo. We identified PRDX1 through a novel PCR screen and confirmed it as a direct target using luciferase reporter assays. The reintroduction of PRDX1 into breast cancer cell lines without its regulatory 3'UTR confirmed that miR-510 was mediating its migratory phenotype at least in part through the negative regulation of PRDX1. Furthermore, the PI3K/Akt pathway was identified as a positive regulator of miR-510 both in vitro and in vivo. Conclusions In this study, we provide evidence to support a role for miR-510 as a novel oncomir. We show that miR-510 directly binds to the 3'UTR of PRDX1 and blocks its protein expression, thereby suppressing migration of human breast cancer cells. Taken together, these data support a pivotal role for miR-510 in breast cancer progression and suggest it as a potential therapeutic target in breast cancer patients. PMID:23971998

MicroRNA-510 promotes cell and tumor growth by targeting peroxiredoxin1 in breast cancer.

PubMed

Guo, Qi J; Mills, Jamie N; Bandurraga, Savannah G; Nogueira, Lourdes M; Mason, Natalie J; Camp, E Ramsay; Larue, Amanda C; Turner, David P; Findlay, Victoria J

2013-01-01

MicroRNAs are small non-coding RNAs that are involved in the post-transcriptional negative regulation of mRNAs. MicroRNA 510 (miR-510) was initially shown to have a potential oncogenic role in breast cancer by the observation of its elevated levels in human breast tumor samples when compared to matched non-tumor samples. Few targets have been identified for miR-510. However, as microRNAs function through the negative regulation of their direct targets, the identification of those targets is critical for the understanding of their functional role in breast cancer. Breast cancer cell lines were transfected with pre-miR-510 or antisense miR-510 and western blotting and quantitative real time PCR were performed. Functional assays performed included cell growth, migration, invasion, colony formation, cytotoxicity and in vivo tumor growth. We performed a PCR assay to identify novel direct targets of miR-510. The study focused on peroxiredoxin 1 (PRDX1) as it was identified through our screen and was bioinformatically predicted to contain a miR-510 seed site in its 3' untranslated region (3'UTR). Luciferase reporter assays and site-directed mutagenesis were performed to confirm PRDX1 as a direct target. The Student's two-sided, paired t-test was used and a P-value less than 0.05 was considered significant. We show that miR-510 overexpression in non-transformed and breast cancer cells can increase their cell growth, migration, invasion and colony formation in vitro. We also observed increased tumor growth when miR-510 was overexpressed in vivo. We identified PRDX1 through a novel PCR screen and confirmed it as a direct target using luciferase reporter assays. The reintroduction of PRDX1 into breast cancer cell lines without its regulatory 3'UTR confirmed that miR-510 was mediating its migratory phenotype at least in part through the negative regulation of PRDX1. Furthermore, the PI3K/Akt pathway was identified as a positive regulator of miR-510 both in vitro and in vivo. In this study, we provide evidence to support a role for miR-510 as a novel oncomir. We show that miR-510 directly binds to the 3'UTR of PRDX1 and blocks its protein expression, thereby suppressing migration of human breast cancer cells. Taken together, these data support a pivotal role for miR-510 in breast cancer progression and suggest it as a potential therapeutic target in breast cancer patients.

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

The Comparison Study of gas source between two hydrate expeditions in ShenHu area, SCS

NASA Astrophysics Data System (ADS)

Cong, X. R.

2016-12-01

Two gas hydrate expeditions (GMGS 01&03) were conducted in the Pearl River Mouth Basin, SCS, which were organized by Guangzhou Marine Geological Survey in 2007 and 2015, respectively. Compared with the drilling results of "mixed bio-thermogenic gas and generally dominated by biogenic gas" in 2007, hydrocarbon component measurements revealed a higher content of ethane and propane in 2015 drilling, providing direct evidence that deep thermogenic gas was the source for shallow hydrate formation. According to the geochemical analyses of the results obtained from the industrial boreholes in Baiyun sag, the deep hydrocarbon gas obviously leaked from the reservoir as escape caused by Dongsha movement in the late Miocene, as a result thermogenic gas from Wenchang, Enping and Zhuhai hydrocarbon source rocks migrated to late Miocene shallow strata through faults, diapirs and gas chimney vertically migration. In this paper we report the differences in fluid migration channel types and discuss their effect in fluid vertical migration efficiency in the two Shenhu hydrate drilling areas. For the drilling area in 2007,when the limited deep thermogenic gas experienced long distance migration process from bottom to up along inefficient energy channel, the gas composition might have changed and the carbon isotope fractionation might have happened, which were reflected in the results of higher C1/C2 ratios and lighter carbon isotope in gas hydrate bearing sediments. As a result the gas is with more "biogenic gas" features. It means thermogenic gases in the deep to contributed the formation of shallow gas hydrate indirectly in 2007 Shenhu drill area. On another hand, the gases were transported to the shallow sediment layers efficiently, where gas hydrate formed, through faults and fractures from deep hydrocarbon reservoirs, and as the result they experienced less changes in both components and isotopes in 2015 drilling site.

CD44 regulates cell migration in human colon cancer cells via Lyn kinase and AKT phosphorylation.

PubMed

Subramaniam, Venkateswaran; Vincent, Isabella R; Gardner, Helena; Chan, Emily; Dhamko, Helena; Jothy, Serge

2007-10-01

Colon cancer is among the leading causes of cancer death in North America. CD44, an adhesion and antiapoptotic molecule is overexpressed in colon cancer. Cofilin is involved in the directional motility of cells. In the present study, we looked at how CD44 might modulate cell migration in human colon cancer via cofilin. We used a human colon cancer cell line, HT29, which expresses CD44, HT29 where CD44 expression was knocked down by siRNA, SW620, a human colon cancer cell line which does not express CD44, stably transfected exons of CD44 in SW620 cells and the colon from CD44 knockout and wild-type mouse. Western blot analysis of siRNA CD44 lysates showed increased level of AKT phosphorylation and decreased level of cofilin expression. Similar results were also observed with SW620 cells and CD44 knockout mouse colon lysates. Experiments using the AKT phosphorylation inhibitor LY294002 indicate that AKT phosphorylation downregulates cofilin. Immunoprecipitation studies showed CD44 complex formation with Lyn, providing an essential link between CD44 and AKT phosphorylation. LY294002 also stabilized Lyn from phosphorylated AKT, suggesting an interaction between Lyn and AKT phosphorylation. Immunocytochemistry showed that cofilin and Lyn expression were downregulated in siRNA CD44 cells and CD44 knockout mouse colon. siRNA CD44 cells had significantly less migration compared to HT29 vector. Given the well-defined roles of CD44, phosphorylated AKT in apoptosis and cancer, these results indicate that CD44-induced cell migration is dependent on its complex formation with Lyn and its consequent regulation of AKT phosphorylation and cofilin expression.

miR-27a induced by colon cancer cells in HLECs promotes lymphangiogenesis by targeting SMAD4

PubMed Central

Zhang, Chen-Peng; Xiao, Qian; Lin, Xiao-Lin

2017-01-01

Aim Metastasis of tumor cells occurs through lymphatic vessels, blood vessels and transcoelomic spreading. Growing evidence from in vivo and in vitro studies has indicated that tumor lymphangiogenesis facilitates metastasis. However, the regulation of lymphangiogenesis in colon cancer remains unclear. The aims of this study were to identify key miRNAs in colon cancer lymphangiogenesis and to investigate its target and mechanism. Methods miRNA microarray analysis was conducted to identify miRNAs in human lymphatic endothelial cells (HLECs) that were regulated by co-cultured human colon cancer cells. Gain- and loss-of-function studies were performed to determine the function of miR-27a, a top hint, on lymphangiogenesis and migration in HLECs. Furthermore, bioinformatics prediction and experimental validation were performed to identify miR-27a target genes in lymphangiogenesis. Results We found that expression of miR-27a in HLECs was induced by co-culturing with colon cancer cells. Over-expression of miR-27a in HLECs enhanced lymphatic tube formation and migration, whereas inhibition of miR-27a reduced lymphatic tube formation and migration. Luciferase reporter assays showed that miR-27a directly targeted SMAD4, a pivotal component of the TGF-β pathway. In addition, gain-of-function and loss-of-function experiments showed that SMAD4 negatively regulated the length of lymphatic vessels formed by HLECs and migration. Conclusions Our data indicated that colon cancer cell induced the expression of miR-27a in HLECs, which promoted lymphangiogenesis by targeting SMAD4. Our finding implicated miR-27a as a potential target for new anticancer therapies in colon cancer. PMID:29065177

A WAVE2-Abi1 complex mediates CSF-1-induced F-actin-rich membrane protrusions and migration in macrophages.

PubMed

Kheir, Wassim Abou; Gevrey, Jean-Claude; Yamaguchi, Hideki; Isaac, Beth; Cox, Dianne

2005-11-15

Colony-stimulating factor 1 (CSF-1) is an important physiological chemoattractant for macrophages. The mechanisms by which CSF-1 elicits the formation of filamentous actin (F-actin)-rich membrane protrusions and induces macrophage migration are not fully understood. In particular, very little is known regarding the contribution of the different members of the Wiskott-Aldrich Syndrome protein (WASP) family of actin regulators in response to CSF-1. Although a role for WASP itself in macrophage chemotaxis has been previously identified, no data was available regarding the function of WASP family verprolin-homologous (WAVE) proteins in this cell type. We found that WAVE2 was the predominant isoform to be expressed in primary macrophages and in cells derived from the murine monocyte/macrophage RAW264.7 cell line (RAW/LR5). CSF-1 treatment of macrophages resulted in WAVE2 accumulation in F-actin-rich protrusions induced by CSF-1. Inhibition of WAVE2 function by expressing a dominant-negative mutant or introducing anti-WAVE2 antibodies in RAW/LR5 cells, as well as reduction of endogenous WAVE2 expression by RNA-mediated interference (RNAi), resulted in a significant reduction of CSF-1-elicited F-actin protrusions. WAVE2 was found in a protein complex together with Abelson kinase interactor 1 (Abi1) in resting or stimulated cells. Both WAVE2 and Abi1 were recruited to and necessary for the formation of F-actin protrusions in response to CSF-1. Reducing the levels of WAVE2, directly or by targeting Abi1, resulted in an impaired cell migration to CSF-1. Altogether these data identify a WAVE2-Abi1 complex crucial for the normal actin cytoskeleton reorganization and migration of macrophages in response to CSF-1.

Cdc42 is required in a genetically distinct subset of cardiac cells during Drosophila dorsal vessel closure

PubMed Central

Swope, David; Kramer, Joseph; King, Tiffany R.; Cheng, Yi-Shan; Kramer, Sunita G.

2017-01-01

The embryonic heart tube is formed by the migration and subsequent midline convergence of two bilateral heart fields. In Drosophila the heart fields are organized into two rows of cardioblasts (CBs). While morphogenesis of the dorsal ectoderm, which lies directly above the Drosophila dorsal vessel (DV), has been extensively characterized, the migration and concomitant fundamental factors facilitating DV formation remain poorly understood. Here we provide evidence that DV closure occurs at multiple independent points along the A-P axis of the embryo in a “buttoning” pattern, divergent from the zippering mechanism observed in the overlying epidermis during dorsal closure. Moreover, we demonstrate that a genetically distinct subset of CBs is programmed to make initial contact with the opposing row. To elucidate the cellular mechanisms underlying this process, we examined the role of Rho GTPases during cardiac migration using inhibitory and overexpression approaches. We found that Cdc42 shows striking cell-type specificity during DV formation. Disruption of Cdc42 function specifically prevents CBs that express the homeobox gene tinman from completing their dorsal migration, resulting in a failure to make connections with their partnering CBs. Conversely, neighboring CBs that express the orphan nuclear receptor, seven-up, are not sensitive to Cdc42 inhibition. Furthermore, this phenotype was specific to Cdc42 and was not observed upon perturbation of Rac or Rho function. Together with the observation that DV closure occurs through the initial contralateral pairing of tinman-expressing CBs, our studies suggest that the distinct buttoning mechanism we propose for DV closure is elaborated through signaling pathways regulating Cdc42 activity in this cell type. PMID:24949939

An improved alkaline direct formate paper microfluidic fuel cell.

PubMed

Galvan, Vicente; Domalaon, Kryls; Tang, Catherine; Sotez, Samantha; Mendez, Alex; Jalali-Heravi, Mehdi; Purohit, Krutarth; Pham, Linda; Haan, John; Gomez, Frank A

2016-02-01

Paper-based microfluidic fuel cells (MFCs) are a potential replacement for traditional FCs and batteries due to their low cost, portability, and simplicity to operate. In MFCs, separate solutions of fuel and oxidant migrate through paper due to capillary action and laminar flow and, upon contact with each other and catalyst, produce electricity. In the present work, we describe an improved microfluidic paper-based direct formate FC (DFFC) employing formate and hydrogen peroxide as the anode fuel and cathode oxidant, respectively. The dimensions of the lateral column, current collectors, and cathode were optimized. A maximum power density of 2.53 mW/cm(2) was achieved with a DFFC of surface area 3.0 cm(2) , steel mesh as current collector, 5% carbon to paint mass ratio for cathode electrode and, 30% hydrogen peroxide. The longevity of the MFC's detailed herein is greater than eight hours with continuous flow of streams. In a series configuration, the MFCs generate sufficient energy to power light-emitting diodes and a handheld calculator. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Determination of diffusion and partition coefficients of model migrants by direct contact and vapour phase transfer from low-density polyethylene films into cake.

PubMed

Paseiro-Cerrato, Rafael; Rodríguez-Bernaldo de Quirós, Ana; Otero-Pazos, Pablo; Sendón, Raquel; Paseiro-Losada, Perfecto

2018-03-01

The aim of the present study was to determine the migration kinetics of one photoinitiator, benzophenone, and two optical brighteners, Uvitex OB and 1,4-diphenyl-1,3-butadiene (DPBD), from low-density polyethylene (LDPE) films into cake. Transfer was assessed by both direct contact and also the vapour phase. To perform the migration tests by direct contact, plastic films enriched with the additives were placed between two cake slices. To evaluate the migration through the gas phase, cake and the fortified LDPE film were placed with no direct contact in a glass container that was hermetically closed. Samples were stored at different time-temperature conditions. Target compounds were extracted from the films with ethanol (70°C, 24 h) and analysed by HPLC-DAD. Relevant parameters such as partition and diffusion coefficients between food and plastic film were calculated. The Arrhenius equation was applied to estimate the diffusion coefficient at any temperature. The data indicate that migration of benzophenone occurs in a significant extent into cake by both direct contact and through the gas phase (no direct contact). Conversely, very little migration occurred for Uvitex OB by direct contact and none through the gas phase. Results for benzophenone suggest that migration through the gas phase should be considered when evaluating migration from food packaging materials into food.

Towards an understanding of the role of clay minerals in crude oil formation, migration and accumulation

NASA Astrophysics Data System (ADS)

Wu, Lin Mei; Zhou, Chun Hui; Keeling, John; Tong, Dong Shen; Yu, Wei Hua

2012-12-01

This article reviews progress in the understanding of the role of clay minerals in crude oil formation, migration and accumulation. Clay minerals are involved in the formation of kerogen, catalytic cracking of kerogen into petroleum hydrocarbon, the migration of crude oil, and the continued change to hydrocarbon composition in underground petroleum reservoirs. In kerogen formation, clay minerals act as catalysts and sorbents to immobilize organic matter through ligand exchange, hydrophobic interactions and cation bridges by the mechanisms of Maillard reactions, polyphenol theory, selective preservation and sorptive protection. Clay minerals also serve as catalysts in acid-catalyzed cracking of kerogen into petroleum hydrocarbon through Lewis and Brønsted acid sites on the clay surface. The amount and type of clay mineral affect the composition of the petroleum. Brønsted acidity of clay minerals is affected by the presence and state of interlayer water, and displacement of this water is a probable driver in crude oil migration from source rocks. During crude oil migration and accumulation in reservoirs, the composition of petroleum is continually modified by interaction with clay minerals. The clays continue to function as sorbents and catalysts even while they are being transformed by diagenetic processes. The detail of chemical interactions and reaction mechanisms between clay minerals and crude oil formation remains to be fully explained but promises to provide insights with broader application, including catalytic conversion of biomass as a source of sustainable energy into the future.

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.

Directional Cell Migration in Response to Repeated Substratum Stretching

NASA Astrophysics Data System (ADS)

Okimura, Chika; Iwadate, Yoshiaki

2017-10-01

Crawling migration plays an essential role in a variety of biological phenomena, including development, wound healing, and immune system function. Migration properties such as anterior-posterior polarity, directionality, and velocity are regulated not only by the reception of a chemoattractant but also by sensing mechanical inputs from the external environment. In this review, we describe the mechanical response of migrating cells, particularly under repeated stretching of the elastic substratum, highlighting the fact that there appear to be two independent mechanosensing systems that generate the polarity needed for migration. Cells that have no stress fibers, such as Dictyostelium cells and neutrophil-like differentiated HL-60 cells, migrate perpendicular to the stretching direction via myosin II localization. Cells that do possess stress fibers, however, such as fish keratocytes, migrate parallel to the stretching via a stress-fiber-dependent process.

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

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

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

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

Adipose tissue-derived stem cells inhibit neointimal formation in a paracrine fashion in rat femoral artery.

PubMed

Takahashi, Masao; Suzuki, Etsu; Oba, Shigeyoshi; Nishimatsu, Hiroaki; Kimura, Kenjiro; Nagano, Tetsuo; Nagai, Ryozo; Hirata, Yasunobu

2010-02-01

Subcutaneous adipose tissue contains a lot of stem cells [adipose-derived stem cells (ASCs)] that can differentiate into a variety of cell lineages. In this study, we isolated ASCs from Wistar rats and examined whether ASCs would efficiently differentiate into vascular endothelial cells (ECs) in vitro. We also administered ASCs in a wire injury model of rat femoral artery and examined their effects. ASCs expressed CD29 and CD90, but not CD34, suggesting that ASCs resemble bone marrow-derived mesenchymal stem cells. When induced to differentiate into ECs with endothelial growth medium (EGM), ASCs expressed Flt-1, but not Flk-1 or mature EC markers such as CD31 and vascular endothelial cadherin. ASCs produced angiopoietin-1 when they were cultured in EGM. ASCs stimulated the migration of EC, as assessed by chemotaxis assay. When ASCs that were cultured in EGM were injected in the femoral artery, the ASCs potently and significantly inhibited neointimal formation without being integrated in the endothelial layer. EGM-treated ASCs significantly suppressed neointimal formation even when they were administered from the adventitial side. ASC administration significantly promoted endothelial repair. These results suggested that although ASCs appear to have little capacity to differentiate into mature ECs, ASCs have the potential to secrete paracrine factors that stimulate endothelial repair. Our results also suggested that ASCs inhibited neointimal formation via their paracrine effect of stimulation of EC migration in situ rather than the direct integration into the endothelial layer.

Mechanisms of ripple migration on a natural sand bed under waves

NASA Astrophysics Data System (ADS)

Carlson, E.; Foster, D. L.

2016-02-01

In nearshore environments, the wave bottom boundary layer is of particular importance to bedform migration and evolution as it is the location of energy transfer from the water column to the bed. This effort examines the mechanisms responsible for bedform evolution and migration. In a field scale laboratory study, sand ripple dynamics were measured using particle image velocimetry. Both monotonic (T = 4 s, 8 s), bimodal (wave pair T = 3.7, 4.3 s), and solitary wave cases were examined. Bedform states included orbital and anorbital rippled beds with wavelengths ranging from 5 to 15 cm. During cases of moderately high energy, time series of instantaneous ripple migration rates oscillated with the same frequency as the surface waves. The oscillatory ripple migration signature was asymmetric, with higher amplitudes during onshore directed movement. This asymmetry leads to a net onshore migration, ranging from 0.1 to 0.6 cm/min in the wave conditions mentioned. The cyclic motion of the ripple field was compared to concomitant transfer mechanisms affecting the boundary layer dynamics including: bed shear stress, coherent structure generation, and free stream velocity. Coherent structures were identified using the swirling strength criterion, and were present during each half wave developing in the ripple troughs. Two estimates of bed shear stress were made: 1) Meyer-Peter Muller method using the bed migration to determine the necessary stress and 2) double averaging of the velocity field and partitioning into components of stress, following the methods of Rodriguez-Abudo and Foster (2014). Peak ripple migration rates occurred during strengthening onshore flow, which coincides with peak bed shear stresses and the onset of coherent structure formation. Higher energy bimodal wave groups caused periods of high suspension which were coincident with peak onshore migrations, during the low velocity periods of the bimodal forcing the bed did not migrate.

Are migrating raptors guided by a geomagnetic compass?

USGS Publications Warehouse

Thorup, Kasper; Fuller, Mark R.; Alerstam, T.; Hake, M.; Kjellen, N.; Standberg, R.

2006-01-01

We tested whether routes of raptors migrating over areas with homogeneous topography follow constant geomagnetic courses more or less closely than constant geographical courses. We analysed the routes taken over land of 45 individual raptors tracked by satellite-based radiotelemetry: 25 peregrine falcons, Falco peregrinus, on autumn migration between North and South America, and seven honey buzzards, Pernis apivorus, and 13 ospreys, Pandion haliaetus, on autumn migration between Europe and Africa. Overall, migration directions showed a better agreement with constant geographical than constant geomagnetic courses. Tracks deviated significantly from constant geomagnetic courses, but were not significantly different from geographical courses. After we removed movements directed far from the mean direction, which may not be migratory movements, migration directions still showed a better agreement with constant geographical than constant geomagnetic courses, but the directions of honey buzzards and ospreys were not significantly different from constant geomagnetic courses either. That migration routes of raptors followed by satellite telemetry are in closer accordance with constant geographical compass courses than with constant geomagnetic compass courses may indicate that geographical (e.g. based on celestial cues) rather than magnetic compass mechanisms are of dominating importance for the birds' long-distance orientation.

Dust production by collisional grinding during Planetesimal-Driven Migration

NASA Astrophysics Data System (ADS)

Salmon, Julien; Walsh, Kevin J.; Levison, Harold F.

2017-10-01

Many main-sequence stars are surrounded by optically thin disks of dust in the absence of any detectable gas (e.g. Su et al. 2006, Meyer et al. 2008). IR and sub-millimeter observations suggest that most of the observed emission comes from grains with sizes between 1-100 microns. Since radiation forces are expected to remove these grains on timescales much shorter than the age of the parent stars (Backman & Parsce 1993, Wyatt 2008), it implies that some process is replenishing the dust, such as collisional grinding. The latter requires large impact velocities between planetesimals, which can be achieved if large objects are dynamically exciting a disk of 1-10km planetesimals. Such debris disks could be hosting ongoing planet formation, and present a powerful tool to test planet formation theories.If a planet is embedded in a gas-free planetesimal disk, the mutual gravitational interactions will force the planet to migrate (e.g. Fernandez & Ip 1984). Planetesimals situated along the direction of migration can be trapped in mean motion resonances (MMRs) with the planet (Malhotra 1993, 1995, Hahn & Malholtra 1999). Planetesimals trapped in such resonances will have their eccentricities pumped to large values as the planet continues to migrate, thereby leading to energetic collisions and dust production (Wyatt 2003, Reche et al. 2008, Mustill & Wyatt 2011).We have performed an extensive suite of simulations in which we explore the likelihood that a given set of disk parameters (mass, surface density slope, number of planetesimals) can sustain planetesimal-driven migration (PDM). We confirm the strong dependence on resolution found in previous works (e.g. Kirsch et al 2009), and find that an embryo to planetesimal mass ratio of 400 is necessary to mitigate the effects of stochasticity, which may cause migration to stall and/or reverse. After having identified disks suitable for sustained PDM, we model their evolution using LIPAD (Levison et al. 2012) taking into account collisional grinding. We will present results on the dust signatures that can be expected from such systems.

Structural Evolution of Transform Fault Zones in Thick Oceanic Crust of Iceland

NASA Astrophysics Data System (ADS)

Karson, J. A.; Brandsdottir, B.; Horst, A. J.; Farrell, J.

2017-12-01

Spreading centers in Iceland are offset from the regional trend of the Mid-Atlantic Ridge by the Tjörnes Fracture Zone (TFZ) in the north and the South Iceland Seismic Zone (SISZ) in the south. Rift propagation away from the center of the Iceland hotspot, has resulted in migration of these transform faults to the N and S, respectively. As they migrate, new transform faults develop in older crust between offset spreading centers. Active transform faults, and abandoned transform structures left in their wakes, show features that reflect different amounts (and durations) of slip that can be viewed as a series of snapshots of different stages of transform fault evolution in thick, oceanic crust. This crust has a highly anisotropic, spreading fabric with pervasive zones of weakness created by spreading-related normal faults, fissures and dike margins oriented parallel to the spreading centers where they formed. These structures have a strong influence on the mechanical properties of the crust. By integrating available data, we suggest a series of stages of transform development: 1) Formation of an oblique rift (or leaky transform) with magmatic centers, linked by bookshelf fault zones (antithetic strike-slip faults at a high angle to the spreading direction) (Grimsey Fault Zone, youngest part of the TFZ); 2) broad zone of conjugate faulting (tens of km) (Hreppar Block N of the SISZ); 3) narrower ( 20 km) zone of bookshelf faulting aligned with the spreading direction (SISZ); 4) mature, narrow ( 1 km) through-going transform fault zone bounded by deformation (bookshelf faulting and block rotations) distributed over 10 km to either side (Húsavík-Flatey Fault Zone in the TFZ). With progressive slip, the transform zone becomes progressively narrower and more closely aligned with the spreading direction. The transform and non-transform (beyond spreading centers) domains may be truncated by renewed propagation and separated by subsequent spreading. This perspective provides an analog for the evolution of migrating transforms along mid-ocean ridge spreading centers or other places where plate boundary rearrangements result in the formation of a new transform fault in highly anisotropic oceanic crust.

Dynamics of radiocesium exchange and interstratification in anhydrous clay interlayers: Bridging the atom and single crystal scales

NASA Astrophysics Data System (ADS)

Lammers, L. N.; Pestana, L. R.; Schaettle, K. B.; Head-Gordon, T.

2016-12-01

High structural charge clay minerals govern the transport and retention of radiocesium in soils and clay-rich geologic repositories. Cation exchange capacities in these phases are typically assumed to be limited to fast-exchanging basal and high-affinity edge sites, while ions in anhydrous interlayers, usually K+, are considered non-exchangeable. However, recent high resolution imaging and spectroscopic studies have demonstrated that Cs ions can in fact exchange with interlayer K without the formation of a hydrated intermediate.1,2 These exchange reactions result in sharp exchange fronts wherein K+ ions are completely replaced by Cs+ at the exchange interface, and the rate of exchange varies from layer to layer, resulting in the formation of interstratified structures (i.e., randomly alternating layers of exchanged and pristine interlayers). Currently, this process cannot be explained by any known exchange mechanism, and consequently, no kinetic expressions are available to account for this phenomenon in models of subsurface radiocesium fate and transport. We present a mesoscale model for direct exchange in anhydrous clay interlayers that is based on the kinetics of single ion migration events. Single atom migration kinetics derived from density functional theory (DFT) calculations are used as inputs to kinetic Monte Carlo (kMC) simulations, which capture the collective dynamics of the exchange process over length- and timescales relevant for implementation in reactive transport models. Potential energy surfaces derived from DFT demonstrate that exchange of Cs+ for K+ in anhydrous interlayers lowers the energy barrier to K ion migration by 145 kJ/mol, leading to a positive feedback mechanism that generates atomically sharp exchange fronts. Our work demonstrates the application of "coarse-graining" techniques to develop models for processes with characteristic length- and timescales not accessible by direct atomistic simulation. 1 Okumura T. et al. (2014) Direct observation of cesium at the interlayer region in phlogopite mica. Microscopy 63(1), 65-72. 2 Fuller A. J. et al. (2015) Caesium incorporation and retention in illite interlayers. Appl. Clay Sci. 108, 128-134.

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

Luteolin suppresses angiogenesis and vasculogenic mimicry formation through inhibiting Notch1-VEGF signaling in gastric cancer.

PubMed

Zang, Mingde; Hu, Lei; Zhang, Baogui; Zhu, Zhenglun; Li, Jianfang; Zhu, Zhenggang; Yan, Min; Liu, Bingya

2017-08-26

Gastric cancer is a great threat to the health of the people worldwide and lacks effective therapeutic regimens. Luteolin is one of Chinese herbs and presents in many fruits and green plants. In our previous study, we observed that luteolin inhibited cell migration and promoted cell apoptosis in gastric cancer. In the present study, luteolin significantly inhibited tube formation of human umbilical vein endothelial cells (HUVECs) through decreasing cell migration and proliferation of HUVECs in a dose-dependent manner. Vasculogenic mimicry (VM) tubes formed by gastric cancer cells were also inhibited with luteolin treatment. To explore how luteolin inhibited tubes formation, ELISA assay for VEGF was performed. Both of the VEGF secretion from Hs-746T cells and HUVECs were significantly decreased subsequent to luteolin treatment. In addition, cell migration was increased with the interaction between gastric cancer cells and HUVECs in co-culture assays. However, the promoting effects were abolished subsequent to luteolin treatment. Furthermore, luteolin inhibited VEGF secretion through suppressing Notch1 expression in gastric cancer. Overexpression of Notch1 in gastric cancer cells partially rescued the effects on cell migration, proliferation, HUVECs tube formation, and VM formation induced by luteolin treatment. In conclusion, luteolin inhibits angiogenesis and VM formation in gastric cancer through suppressing VEGF secretion dependent on Notch1 expression. Copyright © 2017 Elsevier Inc. All rights reserved.

Texture Development and Material Flow Behavior During Refill Friction Stir Spot Welding of AlMgSc

NASA Astrophysics Data System (ADS)

Shen, Junjun; Lage, Sara B. M.; Suhuddin, Uceu F. H.; Bolfarini, Claudemiro; dos Santos, Jorge F.

2018-01-01

The microstructural evolution during refill friction stir spot welding of an AlMgSc alloy was studied. The primary texture that developed in all regions, with the exception of the weld center, was determined to be 〈110〉 fibers and interpreted as a simple shear texture with the 〈110〉 direction aligned with the shear direction. The material flow is mainly driven by two components: the simple shear acting on the horizontal plane causing an inward-directed spiral flow and the extrusion acting on the vertical plane causing an upward-directed or downward-directed flow. Under such a complex material flow, the weld center, which is subjected to minimal local strain, is the least recrystallized. In addition to the geometric effects of strain and grain subdivision, thermally activated high-angle grain boundary migration, particularly continuous dynamic recrystallization, drives the formation of refined grains in the stirred zone.

Influence of the intensity and loading time of direct current electric field on the directional migration of rat bone marrow mesenchymal stem cells.

PubMed

Wang, Xiaoyu; Gao, Yuxuan; Shi, Haigang; Liu, Na; Zhang, Wei; Li, Hongbo

2016-09-01

Exogenic electric fields can effectively accelerate bone healing and remodeling through the enhanced migration of bone marrow mesenchymal stem cells (BMSCs) toward the injured area. This study aimed to determine the following: (1) the direction of rat BMSC (rBMSC) migration upon exposure to a direct current electric field (DCEF), (2) the optimal DCEF intensity and duration, and (3) the possible regulatory role of SDF-1/CXCR4 axis in rBMSC migration as induced by DCEF. Results showed that rBMSCs migrated to the positive electrode of the DCEF, and that the DCEF of 200 mV/mm for 4 h was found to be optimal in enhancing rBMSC migration. This DCEF strength and duration also upregulated the expression of osteoblastic genes, including ALP and OCN, and upregulated the expression of ALP and Runx2 proteins. Moreover, when CXCR4 was inhibited, rBMSC migration due to DCEF was partially blocked. These findings indicated that DCEF can effectively induce rBMSC migration. A DCEF of 200 mV/mm for 4 h was recommended because of its ability to promote rBMSC migration, proliferation, and osteogenic differentiation. The SDF-1/CXCR4 signaling pathway may play an important role in regulating the DCEF-induced migration of rBMSCs.

Drops and Bubble in Materials Science

NASA Technical Reports Server (NTRS)

Doremus, R. H.

1982-01-01

The formation of extended p-n junctions in semiconductors by drop migration, mechanisms and morphologies of migrating drops and bubbles in solids and nucleation and corrections to the Volmer-Weber equations are discussed. Bubble shrinkage in the processing of glass, the formation of glass microshells as laser-fusion targets, and radiation-induced voids in nuclear reactors were examined.

Space-variant filtering for correction of wavefront curvature effects in spotlight-mode SAR imagery formed via polar formatting

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

Jakowatz, C.V. Jr.; Wahl, D.E.; Thompson, P.A.

1996-12-31

Wavefront curvature defocus effects can occur in spotlight-mode SAR imagery when reconstructed via the well-known polar formatting algorithm (PFA) under certain scenarios that include imaging at close range, use of very low center frequency, and/or imaging of very large scenes. The range migration algorithm (RMA), also known as seismic migration, was developed to accommodate these wavefront curvature effects. However, the along-track upsampling of the phase history data required of the original version of range migration can in certain instances represent a major computational burden. A more recent version of migration processing, the Frequency Domain Replication and Downsampling (FReD) algorithm, obviatesmore » the need to upsample, and is accordingly more efficient. In this paper the authors demonstrate that the combination of traditional polar formatting with appropriate space-variant post-filtering for refocus can be as efficient or even more efficient than FReD under some imaging conditions, as demonstrated by the computer-simulated results in this paper. The post-filter can be pre-calculated from a theoretical derivation of the curvature effect. The conclusion is that the new polar formatting with post filtering algorithm (PF2) should be considered as a viable candidate for a spotlight-mode image formation processor when curvature effects are present.« less

Prohibitin, relocated to the front ends, can control the migration directionality of colorectal cancer cells

PubMed Central

Guo, Li-Li; Hu, Chun-Ting; Huang, Ying-Xin; Huang, Guan; Jing, Fang-Yan; Liu, Chao; Li, Zhuo-Yi; Zhou, Na; Yan, Qian-Wen; Lei, Yan; Zhu, Shi-Jie; Cheng, Zhi-Qiang; Cao, Guang-Wen; Deng, Yong-Jian; Ding, Yan-Qing

2017-01-01

Directional migration is a cost-effective movement allowing invasion and metastatic spread of cancer cells. Although migration related to cytoskeletal assembly and microenvironmental chemotaxis has been elucidated, little is known about interaction between extracellular and intracellular molecules for controlling the migrational directionality. A polarized expression of prohibitin (PHB) in the front ends of CRC cells favors metastasis and is correlated with poor prognosis for 545 CRC patients. A high level of vascular endothelial growth factor (VEGF) in the interstitial tissue of CRC patients is associated with metastasis. VEGF bound to its receptor, neuropilin-1, can stimulate the activation of cell division cycle 42, which recruits intra-mitochondrial PHB to the front end of a CRC cell. This intracellular relocation of PHB results in the polymerization and reorganization of filament actin extending to the front end of the cell. As a result, the migration directionality of CRC cells is targeted towards VEGF. Together, these findings identify PHB as a key modulator of directional migration of CRC cells and a target for metastasis. PMID:29100316

Polarised Clathrin-Mediated Endocytosis of EGFR During Chemotactic Invasion

PubMed Central

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

2014-01-01

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

Effects of direct current electric-field using ITO plate on breast cancer cell migration.

PubMed

Kim, Min Sung; Lee, Mi Hee; Kwon, Byeong-Ju; Seo, Hyok Jin; Koo, Min-Ah; You, Kyung Eun; Kim, Dohyun; Park, Jong-Chul

2014-01-01

Cell migration is an essential activity of the cells in various biological phenomena. The evidence that electrotaxis plays important roles in many physiological phenomena is accumulating. In electrotaxis, cells move with a directional tendency toward the anode or cathode under direct-current electric fields. Indium tin oxide, commonly referred to as ITO has high luminous transmittance, high infrared reflectance, good electrical conductivity, excellent substrate adherence, hardness and chemical inertness and hence, have been widely and intensively studied for many years. Because of these properties of ITO films, the electrotaxis using ITO plate was evaluated. Under the 0 V/cm condition, MDA-MB-231 migrated randomly in all directions. When 1 V/cm of dc EF was applied, cells moved toward anode. The y forward migration index was -0.046 ± 0.357 under the 0 V/cm and was 0.273 ± 0.231 under direct-current electric field of 1 V/cm. However, the migration speed of breast cancer cell was not affected by direct-current electric field using ITO plate. In this study, we designed a new electrotaxis system using an ITO coated glass and observed the migration of MDA-MB-231 on direct current electric-field of the ITO glass.

[Effects of ezrin silencing on pancreatic cancer cell line Panc-1].

PubMed

Meng, Yun-xiao; Yu, Shuang-ni; Lu, Zhao-hui; Chen, Jie

2012-12-01

To explore the effects of ezrin silencing on pancreatic cancer cell line Panc-1. Pancreatic cancer cell line Panc-1 was transfected with ezrin silencing plasmid. The proliferation and the cell cycle status were determined by CCK-8 assay and flow cytometry analysis, respectively. Cellular membrane protrusions/microvilli formation were visualized by scanning election microscopy. Colony formation assay was used to determine the cell anchor-independent growth ability in vitro. Trans-filter migration and invasion assays were performed with 8 µm pore inserts in a 24-well BioCoat chamber with/without Matrigel. Ezrin silencing decreased cellular protrusions/microvilli formation, anchorage-independent growth, cell migration and invasion, but had no effects on cell proliferation in vitro and cell cycle, in pancreatic cancer cell line Panc-1. Ezrin expression affects the cellular protrusions/microvilli formation, anchorage-independent growth, cell migration and invasion in pancreatic cancer cell line Panc-1.

Transforming growth factor β-regulated microRNA-29a promotes angiogenesis through targeting the phosphatase and tensin homolog in endothelium.

PubMed

Wang, Jun; Wang, Youliang; Wang, Yu; Ma, Ying; Lan, Yu; Yang, Xiao

2013-04-12

The TGF-β pathway plays an important role in physiological and pathological angiogenesis. MicroRNAs (miRNAs) are a class of 18- to 25-nucleotide, small, noncoding RNAs that function by regulating gene expression. A number of miRNAs have been found to be regulated by the TGF-β pathway. However, the role of endothelial miRNAs in the TGF-β-mediated control of angiogenesis is still largely unknown. Here we investigated the regulation of endothelial microRNA-29a (miR-29a) by TGF-β signaling and the potential role of miR-29a in angiogenesis. MiR-29a was directly up-regulated by TGF-β/Smad4 signaling in human and mice endothelial cells. In a chick chorioallantoic membrane assay, miR-29a overexpression promoted the formation of new blood vessels, and miR-29a suppression completely blocked TGF-β1-stimulated angiogenesis. Consistently, miR-29a overexpression increased tube formation and migration in endothelial cultures. Mechanistically, miR-29a directly targeted the phosphatase and tensin homolog (PTEN) in endothelial cells, leading to activation of the AKT pathway. PTEN knockdown recapitulated the role of miR-29a in endothelial migration, whereas AKT inhibition completely attenuated the stimulating role of miR-29a in angiogenesis. Taken together, these results reveal a crucial role of a TGF-β-regulated miRNA in promoting angiogenesis by targeting PTEN to stimulate AKT activity.

Basinwide sedimentation and the continuum of paleoflow in an ancient river system: Kayenta Formation (Lower Jurassic), central portion Colorado Plateau

NASA Astrophysics Data System (ADS)

Luttrell, Patty Rubick

1993-05-01

Utilizing detailed documentation of alluvial architecture to reconstruct the continuum of paleoflow (perennial, intermittent, ephemeral), a basinwide study of the Kayenta Formation (Lower Jurassic) reveals that the northern half of the basin is characterized by sandy, low-sinuosity fluvial systems which exhibit perennial (Assoc. 1) to intermittent (Assoc. 2) discharge indicators. The rivers had headwaters east of the Uncompahgre Highlands (western Colorado) and flowed southwest across the basin depositing a braidplain of channel sands with well-preserved 3-dimensional macroforms. One significant aspect of the macroform architecture is documentation of macroform climb in both an upstream and downstream direction. The macroforms aggrade vertically by climbing (maximum 10° dip in an upstream direction) and migrating over the backs (upstream ends) of underlying macroforms. The process of macroform climb records a minimum water depth of 8 m and a maximum of 16 m which places the Kayenta perennial waterways (Assoc. 1) within a mesothermal hydrologic regime. The southern portion of the basin contains intermittent (Assoc. 2) to ephemeral (Assoc. 3) fluvial deposits, extensive floodplain preservation and eolian dune and interdune/sandsheet deposition (Assoc. 4). A tributary drainage pattern to the northwest was established by smaller, low- to moderately-sinuous streams. Eolian dune and interdune deposits migrated across this more arid windswept portion of the basin. The range of alluvial architecture present in the Kayenta attests to the diversity that can be found in a small continental sedimentary basin.

TOWARD CHEMICAL CONSTRAINTS ON HOT JUPITER MIGRATION

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

Madhusudhan, Nikku; Amin, Mustafa A.; Kennedy, Grant M., E-mail: nmadhu@ast.cam.ac.uk

The origin of hot Jupiters—gas giant exoplanets orbiting very close to their host stars—is a long-standing puzzle. Planet formation theories suggest that such planets are unlikely to have formed in situ but instead may have formed at large orbital separations beyond the snow line and migrated inward to their present orbits. Two competing hypotheses suggest that the planets migrated either through interaction with the protoplanetary disk during their formation, or by disk-free mechanisms such as gravitational interactions with a third body. Observations of eccentricities and spin-orbit misalignments of hot Jupiter systems have been unable to differentiate between the two hypotheses.more » In the present work, we suggest that chemical depletions in hot Jupiter atmospheres might be able to constrain their migration mechanisms. We find that sub-solar carbon and oxygen abundances in Jovian-mass hot Jupiters around Sun-like stars are hard to explain by disk migration. Instead, such abundances are more readily explained by giant planets forming at large orbital separations, either by core accretion or gravitational instability, and migrating to close-in orbits via disk-free mechanisms involving dynamical encounters. Such planets also contain solar or super-solar C/O ratios. On the contrary, hot Jupiters with super-solar O and C abundances can be explained by a variety of formation-migration pathways which, however, lead to solar or sub-solar C/O ratios. Current estimates of low oxygen abundances in hot Jupiter atmospheres may be indicative of disk-free migration mechanisms. We discuss open questions in this area which future studies will need to investigate.« less

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

Qiu, Mingning, E-mail: lcuzfy@163.com; Liu, Lei, E-mail: leiliulab@163.com; Chen, Lieqian, E-mail: lieqianchen@163.com

Highlights: • miR-183 was up-regulated in renal cancer tissues. • Inhibition of endogenous miR-183 suppressed renal cancer cell growth and metastasis. • miR-183 increased cell growth and metastasis. • miR-183 regulated renal cancer cell growth and metastasis via directly targeting tumor suppressor protein phosphatase 2A. - Abstract: The aim of this study was to investigate the function of miR-183 in renal cancer cells and the mechanisms miR-183 regulates this process. In this study, level of miR-183 in clinical renal cancer specimens was detected by quantitative real-time PCR. miR-183 was up- and down-regulated in two renal cancer cell lines ACHN andmore » A498, respectively, and cell proliferation, Caspase 3/7 activity, colony formation, in vitro migration and invasion were measured; and then the mechanisms of miR-183 regulating was analyzed. We found that miR-183 was up-regulated in renal cancer tissues; inhibition of endogenous miR-183 suppressed in vitro cell proliferation, colony formation, migration, and invasion and stimulated Caspase 3/7 activity; up-regulated miR-183 increased cell growth and metastasis and suppressed Caspase 3/7 activity. We also found that miR-183 directly targeted tumor suppressor, specifically the 3′UTR of three subunits of protein phosphatase 2A (PP2A-Cα, PP2A-Cβ, and PP2A-B56-γ) transcripts, inhibiting their expression and regulated the downstream regulators p21, p27, MMP2/3/7 and TIMP1/2/3/4. These results revealed the oncogenes role of miR-183 in renal cancer cells via direct targeting protein phosphatase 2A.« less

Rh(V) -Nitrenoid as a Key Intermediate in Rh(III) -Catalyzed Heterocyclization by C-H Activation: A Computational Perspective on the Cycloaddition of Benzamide and Diazo Compounds.

PubMed

Zhou, Tao; Guo, Wei; Xia, Yuanzhi

2015-06-15

A mechanistic study of the substituent-dependent ring formations in Rh(III) -catalyzed C-H activation/cycloaddition of benzamide and diazo compounds was carried out by using DFT calculations. The results indicated that the decomposition of the diazo is facilitated upon the formation of the five-membered rhodacycle, in which the Rh(III) center is more electrophilic. The insertion of carbenoid into Rh-C(phenyl) bond occurs readily and forms a 6-membered rhodacycle, however, the following C-N bond formation is difficult both kinetically and thermodynamically by reductive elimination from the Rh(III) species. Instead, the Rh(V) -nitrenoid intermediate could be formed by migration of the pivalate from N to Rh, which undergoes the heterocyclization much more easily and complementary ring-formations could be modulated by the nature of the substituent at the α-carbon. When a vinyl is attached, the stepwise 1,3-allylic migration occurs prior to the pivalate migration and the 8-membered ring product will be formed. On the other hand, the pivalate migration becomes more favorable for the phenyl-contained intermediate because of the difficult 1,3-allylic migration accompanied by dearomatization, thus the 5-membered ring product was formed selectively. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stanniocalcin-1 regulates re-epithelialization in human keratinocytes.

PubMed

Yeung, Bonnie H Y; Wong, Chris K C

2011-01-01

Stanniocalcin-1 (STC1), a glycoprotein hormone, is believed to be involved in various biological processes such as inflammation, oxidative responses and cell migration. Riding on these emerging evidences, we hypothesized that STC1 may participate in the re-epithelialization during wound healing. Re-epithelialization is a critical step that involves keratinocyte lamellipodia (e-lam) formation, followed by cell migration. In this study, staurosporine (STS) treatment induced human keratinocyte (HaCaT) e-lam formation on fibronectin matrix and migration via the activation of focal adhesion kinase (FAK), the surge of intracellular calcium level [Ca²⁺]i and the inactivation of Akt. In accompanied with these migratory features, a time- and dose-dependent increase in STC1 expression was detected. STC1 gene expression was found not the downstream target of FAK-signaling as illustrated by FAK inhibition using PF573228. The reduction of [Ca²⁺]i by BAPTA/AM blocked the STS-mediated keratinocyte migration and STC1 gene expression. Alternatively the increase of [Ca²⁺]i by ionomycin exerted promotional effect on STS-induced STC1 gene expression. The inhibition of Akt by SH6 and GSK3β by lithium chloride (LiCl) could respectively induce and inhibit the STS-mediated e-lam formation, cell migration and STC1 gene expression. The STS-mediated e-lam formation and cell migration were notably hindered or induced respectively by STC1 knockdown or overexpression. This notion was further supported by the scratched wound assay. Collectively the findings provide the first evidence that STC1 promotes re-epithelialization in wound healing.

Methods of quantitative and qualitative analysis of bird migration with a tracking radar

NASA Technical Reports Server (NTRS)

Bruderer, B.; Steidinger, P.

1972-01-01

Methods of analyzing bird migration by using tracking radar are discussed. The procedure for assessing the rate of bird passage is described. Three topics are presented concerning the grouping of nocturnal migrants, the velocity of migratory flight, and identification of species by radar echoes. The height and volume of migration under different weather conditions are examined. The methods for studying the directions of migration and the correlation between winds and the height and direction of migrating birds are presented.

The group migration of Dictyostelium cells is regulated by extracellular chemoattractant degradation.

PubMed

Garcia, Gene L; Rericha, Erin C; Heger, Christopher D; Goldsmith, Paul K; Parent, Carole A

2009-07-01

Starvation of Dictyostelium induces a developmental program in which cells form an aggregate that eventually differentiates into a multicellular structure. The aggregate formation is mediated by directional migration of individual cells that quickly transition to group migration in which cells align in a head-to-tail manner to form streams. Cyclic AMP acts as a chemoattractant and its production, secretion, and degradation are highly regulated. A key protein is the extracellular phosphodiesterase PdsA. In this study we examine the role and localization of PdsA during chemotaxis and streaming. We find that pdsA(-) cells respond chemotactically to a narrower range of chemoattractant concentrations compared with wild-type (WT) cells. Moreover, unlike WT cells, pdsA(-) cells do not form streams at low cell densities and form unusual thick and transient streams at high cell densities. We find that the intracellular pool of PdsA is localized to the endoplasmic reticulum, which may provide a compartment for storage and secretion of PdsA. Because we find that cAMP synthesis is normal in cells lacking PdsA, we conclude that signal degradation regulates the external cAMP gradient field generation and that the group migration behavior of these cells is compromised even though their signaling machinery is intact.

The Group Migration of Dictyostelium Cells Is Regulated by Extracellular Chemoattractant Degradation

PubMed Central

Garcia, Gene L.; Rericha, Erin C.; Heger, Christopher D.; Goldsmith, Paul K.

2009-01-01

Starvation of Dictyostelium induces a developmental program in which cells form an aggregate that eventually differentiates into a multicellular structure. The aggregate formation is mediated by directional migration of individual cells that quickly transition to group migration in which cells align in a head-to-tail manner to form streams. Cyclic AMP acts as a chemoattractant and its production, secretion, and degradation are highly regulated. A key protein is the extracellular phosphodiesterase PdsA. In this study we examine the role and localization of PdsA during chemotaxis and streaming. We find that pdsA− cells respond chemotactically to a narrower range of chemoattractant concentrations compared with wild-type (WT) cells. Moreover, unlike WT cells, pdsA− cells do not form streams at low cell densities and form unusual thick and transient streams at high cell densities. We find that the intracellular pool of PdsA is localized to the endoplasmic reticulum, which may provide a compartment for storage and secretion of PdsA. Because we find that cAMP synthesis is normal in cells lacking PdsA, we conclude that signal degradation regulates the external cAMP gradient field generation and that the group migration behavior of these cells is compromised even though their signaling machinery is intact. PMID:19477920

Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway

PubMed Central

Li, Shang; Dang, Yuanye; Zhou, Xuelin; Huang, Bin; Huang, Xiaohui; Zhang, Zherui; Kwan, Yiu Wa; Chan, Shun Wan; Leung, George Pak Heng; Lee, Simon Ming Yuen; Hoi, Maggie Pui Man

2015-01-01

Formononetin is an isoflavone that has been shown to display estrogenic properties and induce angiogenesis activities. However, the interrelationship between the estrogenic properties and angiogenesis activities of formononetin are not well defined. In the present study, docking and enzymatic assay demonstrated that formononetin displayed direct binding to the ligand-binding domain (LBD) of estrogen receptor alpha (ERα) with an agonistic property. Results from Human Umbilical Vein Endothelial Cells (HUVEC) by using real-time migration xCELLigence system, immunofluorescence and western blotting provided strong evidences of formononetin induced endothelial cell migration and dramatic actin cytoskeleton spatial modification through ERα-enhanced-ROCK-II/MMP2/9 signaling pathways. In addition, results from co-immunoprecipitation suggested formononetin induced cell migration via recruiting of ERα/ROCK-II activated complex formation. More interestingly, in zebrafish embryo we observed that formononetin significantly promoted angiogenic sproutings in the subintestinal vessels (SIVs) that could be completely abolished by ROCK inhibitor. In this study, we elucidated the underlying mechanisms that formononetin produced proangiogenesis effects through an ERα-enhanced ROCK-II signaling pathways. Results from the present study also expand our knowledge about the enigmatic underlying mechanisms of phytoestrogenic compounds in the promotion of angiogenesis in relation to ERα and ROCK interaction in endothelial cells and their relationship with actin assembly and cell migration. PMID:26568398

Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway.

PubMed

Li, Shang; Dang, Yuanye; Zhou, Xuelin; Huang, Bin; Huang, Xiaohui; Zhang, Zherui; Kwan, Yiu Wa; Chan, Shun Wan; Leung, George Pak Heng; Lee, Simon Ming Yuen; Hoi, Maggie Pui Man

2015-11-16

Formononetin is an isoflavone that has been shown to display estrogenic properties and induce angiogenesis activities. However, the interrelationship between the estrogenic properties and angiogenesis activities of formononetin are not well defined. In the present study, docking and enzymatic assay demonstrated that formononetin displayed direct binding to the ligand-binding domain (LBD) of estrogen receptor alpha (ERα) with an agonistic property. Results from Human Umbilical Vein Endothelial Cells (HUVEC) by using real-time migration xCELLigence system, immunofluorescence and western blotting provided strong evidences of formononetin induced endothelial cell migration and dramatic actin cytoskeleton spatial modification through ERα-enhanced-ROCK-II/MMP2/9 signaling pathways. In addition, results from co-immunoprecipitation suggested formononetin induced cell migration via recruiting of ERα/ROCK-II activated complex formation. More interestingly, in zebrafish embryo we observed that formononetin significantly promoted angiogenic sproutings in the subintestinal vessels (SIVs) that could be completely abolished by ROCK inhibitor. In this study, we elucidated the underlying mechanisms that formononetin produced proangiogenesis effects through an ERα-enhanced ROCK-II signaling pathways. Results from the present study also expand our knowledge about the enigmatic underlying mechanisms of phytoestrogenic compounds in the promotion of angiogenesis in relation to ERα and ROCK interaction in endothelial cells and their relationship with actin assembly and cell migration.

Defective neuronal migration and inhibition of bipolar to multipolar transition of migrating neural cells by Mesoderm-Specific Transcript, Mest, in the developing mouse neocortex.

PubMed

Ji, Liting; Bishayee, Kausik; Sadra, Ali; Choi, Seunghyuk; Choi, Wooyul; Moon, Sungho; Jho, Eek-Hoon; Huh, Sung-Oh

2017-07-04

Brain developmental disorders such as lissencephaly can result from faulty neuronal migration and differentiation during the formation of the mammalian neocortex. The cerebral cortex is a modular structure, where developmentally, newborn neurons are generated as a neuro-epithelial sheet and subsequently differentiate, migrate and organize into their final positions in the cerebral cortical plate via a process involving both tangential and radial migration. The specific role of Mest, an imprinted gene, in neuronal migration has not been previously studied. In this work, we reduced expression of Mest with in utero electroporation of neuronal progenitors in the developing embryonic mouse neocortex. Reduction of Mest levels by shRNA significantly reduced the number of neurons migrating to the cortical plate. Also, Mest-knockdown disrupted the transition of bipolar neurons into multipolar neurons migrating out of the sub-ventricular zone region. The migrating neurons also adopted a more tangential migration pattern upon knockdown of the Mest message, losing their potential to attach to radial glia cells, required for radial migration. The differentiation and migration properties of neurons via Wnt-Akt signaling were affected by Mest changes. In addition, miR-335, encoded in a Mest gene intron, was identified as being responsible for blocking the default tangential migration of the neurons. Our results suggest that Mest and its intron product, miR-335, play important roles in neuronal migration with Mest regulating the morphological transition of primary neurons required in the formation of the mammalian neocortex. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Investigating the complex mechanism of B migration in a magnetic-tunnel-junction trilayer structure—a combined study using XPS and TOF-SIMS

NASA Astrophysics Data System (ADS)

Ying, Ji-Feng; Ji, Rong; Ter Lim, Sze; Tran, Michael N.; Wang, Chen Chen; Ernult, Franck

2016-02-01

The magnetic-tunnel-junction (MTJ) structure is the core of many important devices, such as magnetic recording head and STT-RAM. CoFeB/MgO/CoFeB tri-layer thin-film stack is a widely researched MTJ structure. In this tri-layer, the functional property of the MTJ, i.e. its TMR ratio, is critically dependent on the crystal orientation of the CoFe grains. In order for the desired (1 0 0) out of plane texture to develop in the CoFeB layers, B needs to be engineered to be expelled out of these CoFeB layers, and diffuse or migrate into the adjacent layers. Ta is usually used as a seed layer adjacent to the MTJ structure. In this work, we investigated the important B-migration mechanisms within this MTJ structure through a combined XPS/TOF-SIMS study. Specifically, we tried to elucidate the possible physical/chemical interactions between the B and Ta that could happen with different film stack designs. Previous works have shown that there might be two possible B-migration mechanisms. One mechanism is direct B diffusion into the adjacent Ta layer during annealing. The other B-migration mechanism is through the formation of TaBOx species, in which B could be carried out by the Ta diffusion. In particular, through studying a series of film stacks, we discussed the circumstances under which one of these B-migration mechanisms becomes dominant. Furthermore, we discussed how these B-migration mechanisms facilitated the B expulsion in a common MTJ structure.

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

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.

Collisions of deformable cells lead to collective migration

DOE PAGES

Löber, Jakob; Ziebert, Falko; Aranson, Igor S.

2015-03-17

Collective migration of eukaryotic cells plays a fundamental role in tissue growth, wound healing and immune response. The motion, arising spontaneously or in response to chemical and mechanical stimuli, is also important for understanding life-threatening pathologies, such as cancer and metastasis formation. We present a phase-field model to describe the movement of many self-organized, interacting cells. The model takes into account the main mechanisms of cell motility – acto-myosin dynamics, as well as substrate-mediated and cell-cell adhesion. It predicts that collective cell migration emerges spontaneously as a result of inelastic collisions between neighboring cells: collisions lead to a mutual alignmentmore » of the cell velocities and to the formation of coherently-moving multi-cellular clusters. Small cell-to-cell adhesion, in turn, reduces the propensity for large-scale collective migration, while higher adhesion leads to the formation of moving bands. Our study provides valuable insight into biological processes associated with collective cell motility.« less

Collisions of deformable cells lead to collective migration

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

Löber, Jakob; Ziebert, Falko; Aranson, Igor S.

Collective migration of eukaryotic cells plays a fundamental role in tissue growth, wound healing and immune response. The motion, arising spontaneously or in response to chemical and mechanical stimuli, is also important for understanding life-threatening pathologies, such as cancer and metastasis formation. We present a phase-field model to describe the movement of many self-organized, interacting cells. The model takes into account the main mechanisms of cell motility – acto-myosin dynamics, as well as substrate-mediated and cell-cell adhesion. It predicts that collective cell migration emerges spontaneously as a result of inelastic collisions between neighboring cells: collisions lead to a mutual alignmentmore » of the cell velocities and to the formation of coherently-moving multi-cellular clusters. Small cell-to-cell adhesion, in turn, reduces the propensity for large-scale collective migration, while higher adhesion leads to the formation of moving bands. Our study provides valuable insight into biological processes associated with collective cell motility.« less

Epitaxially grown collagen fibrils reveal diversity in contact guidance behavior among cancer cells.

PubMed

Wang, Juan; Petefish, Joseph W; Hillier, Andrew C; Schneider, Ian C

2015-01-01

Invasion of cancer cells into the surrounding tissue is an important step during cancer progression and is driven by cell migration. Cell migration can be random, but often it is directed by various cues such as aligned fibers composed of extracellular matrix (ECM), a process called contact guidance. During contact guidance, aligned fibers bias migration along the long axis of the fibers. These aligned fibers of ECM are commonly composed of type I collagen, an abundant structural protein around tumors. In this paper, we epitaxially grew several different patterns of organized type I collagen on mica and compared the morphology and contact guidance behavior of two invasive breast cancer cell lines (MDA-MB-231 and MTLn3 cells). Others have shown that these cells randomly migrate in qualitatively different ways. MDA-MB-231 cells exert large traction forces, tightly adhere to the ECM, and migrate with spindle-shaped morphology and thus adopt a mesenchymal mode of migration. MTLn3 cells exert small traction forces, loosely adhere to the ECM, and migrate with a more rounded morphology and thus adopt an amoeboid mode of migration. As the degree of alignment of type I collagen fibrils increases, cells become more elongated and engage in more directed contact guidance. MDA-MB-231 cells perceive the directional signal of highly aligned type I collagen fibrils with high fidelity, elongating to large extents and migrating directionally. Interestingly, behavior in MTLn3 cells differs. While highly aligned type I collagen fibril patterns facilitate spreading and random migration of MTLn3 cells, they do not support elongation or directed migration. Thus, different contact guidance cues bias cell migration differently and the fidelity of contact guidance is cell type dependent, suggesting that ECM alignment is a permissive cue for contact guidance, but requires a cell to have certain properties to interpret that cue.

Mesenchyme Homeobox 2 Enhances Migration of Endothelial Colony Forming Cells Exposed to Intrauterine Diabetes Mellitus.

PubMed

Gohn, Cassandra R; Blue, Emily K; Sheehan, BreAnn M; Varberg, Kaela M; Haneline, Laura S

2017-07-01

Diabetes mellitus (DM) during pregnancy has long-lasting implications for the fetus, including cardiovascular morbidity. Previously, we showed that endothelial colony forming cells (ECFCs) from DM human pregnancies have decreased vasculogenic potential. Here, we evaluate whether the molecular mechanism responsible for this phenotype involves the transcription factor, Mesenchyme Homeobox 2 (MEOX2). In human umbilical vein endothelial cells, MEOX2 upregulates cyclin-dependent kinase inhibitor expression, resulting in increased senescence and decreased proliferation. We hypothesized that dysregulated MEOX2 expression in neonatal ECFCs from DM pregnancies decreases network formation through increased senescence and altered cell cycle progression. Our studies show that nuclear MEOX2 is increased in ECFCs from DM pregnancies. To determine if MEOX2 is sufficient and/or required to induce impaired network formation, MEOX2 was overexpressed and depleted in ECFCs from control and DM pregnancies, respectively. Surprisingly, MEOX2 overexpression in control ECFCs resulted in increased network formation, altered cell cycle progression, and increased senescence. In contrast, MEOX2 knockdown in ECFCs from DM pregnancies led to decreased network formation, while cell cycle progression and senescence were unaffected. Importantly, migration studies demonstrated that MEOX2 overexpression increased migration, while MEOX2 knockdown decreased migration. Taken together, these data suggest that altered migration may be mediating the impaired vasculogenesis of ECFCs from DM pregnancies. While initially believed to be maladaptive, these data suggest that MEOX2 may serve a protective role, enabling increased vessel formation despite exposure to a DM intrauterine environment. J. Cell. Physiol. 232: 1885-1892, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Exopolysaccharide microchannels direct bacterial motility and organize multicellular behavior

DOE PAGES

Berleman, James E.; Zemla, Marcin; Remis, Jonathan P.; ...

2016-05-06

The myxobacteria are a family of soil bacteria that form biofilms of complex architecture, aligned multilayered swarms or fruiting body structures that are simple or branched aggregates containing myxospores. Here, we examined the structural role of matrix exopolysaccharide (EPS) in the organization of these surface-dwelling bacterial cells. Using time-lapse light and fluorescence microscopy, as well as transmission electron microscopy and focused ion beam/scanning electron microscopy (FIB/SEM) electron microscopy, we found that Myxococcus xanthus cell organization in biofilms is dependent on the formation of EPS microchannels. Cells are highly organized within the three-dimensional structure of EPS microchannels that are required formore » cell alignment and advancement on surfaces. Mutants lacking EPS showed a lack of cell orientation and poor colony migration. Purified, cell-free EPS retains a channel-like structure, and can complement EPS - mutant motility defects. In addition, EPS provides the cooperative structure for fruiting body formation in both the simple mounds of M. xanthus and the complex, tree-like structures of Chondromyces crocatus. We furthermore investigated the possibility that EPS impacts community structure as a shared resource facilitating cooperative migration among closely related isolates of M. xanthus.« less

Orbital evolution and accretion of protoplanets tidally interacting with a gas disk. I. Effects of interaction with planetesimals and other protoplanets

NASA Astrophysics Data System (ADS)

Kominami, Junko; Tanaka, Hidekazu; Ida, Shigeru

2005-11-01

We have performed N-body simulations on the stage of protoplanet formation from planetesimals, taking into account so-called "type-I migration," and damping of orbital eccentricities and inclinations, as a result of tidal interaction with a gas disk without gap formation. One of the most serious problems in formation of terrestrial planets and jovian planet cores is that the migration time scale predicted by the linear theory is shorter than the disk lifetime (10 6-10 7 years). In this paper, we investigate retardation of type-I migration of a protoplanet due to a torque from a planetesimal disk in which a gap is opened up by the protoplanet, and torques from other protoplanets which are formed in inner and outer regions. In the first series of runs, we carried out N-body simulations of the planetesimal disk, which ranges from 0.9 to 1.1 AU, with a protoplanet seed in order to clarify how much retardation can be induced by the planetesimal disk and how long such retardation can last. We simulated six cases with different migration speeds. We found that in all of our simulations, a clear gap is not maintained for more than 10 5 years in the planetesimal disk. For very fast migration, a gap cannot be created in the planetesimal disk. For migration slower than some critical speed, a gap does form. However, because of the growth of the surrounding planetesimals, gravitational perturbation of the planetesimals eventually becomes so strong that the planetesimals diffuse into the vicinity of the protoplanets, resulting in destruction of the gap. After the gap is destroyed, close encounters with the planetesimals rather accelerate the protoplanet migration. In this way, the migration cannot be retarded by the torque from the planetesimal disk, regardless of the migration speed. In the second series of runs, we simulated accretion of planetesimals in wide range of semimajor axis, 0.5 to 2-5 AU, starting with equal mass planetesimals without a protoplanet seed. Since formation of comparable-mass multiple protoplanets ("oligarchic growth") is expected, the interactions with other protoplanets have a potential to alter the migration speed. However, inner protoplanets migrate before outer ones are formed, so that the migration and the accretion process of a runaway protoplanet are not affected by the other protoplanets placed inner and outer regions of its orbit. From the results of these two series of simulations, we conclude that the existence of planetesimals and multiple protoplanets do not affect type-I migration and therefore the migration shall proceed as the linear theory has suggested.

Dynamics of neutrophil migration in lymph nodes during infection.

PubMed

Chtanova, Tatyana; Schaeffer, Marie; Han, Seong-Ji; van Dooren, Giel G; Nollmann, Marcelo; Herzmark, Paul; Chan, Shiao Wei; Satija, Harshita; Camfield, Kristin; Aaron, Holly; Striepen, Boris; Robey, Ellen A

2008-09-19

Although the signals that control neutrophil migration from the blood to sites of infection have been well characterized, little is known about their migration patterns within lymph nodes or the strategies that neutrophils use to find their local sites of action. To address these questions, we used two-photon scanning-laser microscopy to examine neutrophil migration in intact lymph nodes during infection with an intracellular parasite, Toxoplasma gondii. We found that neutrophils formed both small, transient and large, persistent swarms via a coordinated migration pattern. We provided evidence that cooperative action of neutrophils and parasite egress from host cells could trigger swarm formation. Neutrophil swarm formation coincided in space and time with the removal of macrophages that line the subcapsular sinus of the lymph node. Our data provide insights into the cellular mechanisms underlying neutrophil swarming and suggest new roles for neutrophils in shaping immune responses.

Dynamics of neutrophil migration in lymph nodes during infection

PubMed Central

Chtanova, Tatyana; Schaeffer, Marie; Han, Seong-Ji; van Dooren, Giel G.; Nollmann, Marcelo; Herzmark, Paul; Chan, Shiao Wei; Satija, Harshita; Camfield, Kristin; Aaron, Holly; Striepen, Boris; Robey, Ellen A.

2008-01-01

Summary While the signals that control neutrophil migration from the blood to sites of infection have been well characterized, little is known about their migration patterns within lymph nodes, or the strategies that neutrophils use to find their local sites of action. To address these questions, we used two-photon scanning laser microscopy (TPSLM) to examine neutrophil migration in intact lymph nodes during infection with an intracellular parasite, Toxoplasma gondii. We find that neutrophils form both small, transient or large, persistent swarms via a strikingly coordinated migration pattern. We provide evidence that cooperative action of neutrophils and parasite egress from host cells can trigger swarm formation. Neutrophil swarm formation coincides in space and time with the removal of macrophages that line the subcapsular sinus of the lymph node. Our data provide insights into the cellular mechanisms underlying neutrophil swarming and suggest new roles for neutrophils in shaping immune responses. PMID:18718768

Migration, Business Formation, and the Informal Economy in Urban Mexico

PubMed Central

Riosmena, Fernando

2013-01-01

Although the informal economy has grown rapidly in several developing nations, and migration and informality may be related to similar types of credit constraints and market failures, previous research has not systematically attempted to identify if migrant households are more likely to start informal and formal businesses alike and if this association varies across local contexts. We examine the relationship between prior U.S. migration and the creation of both formal and informal businesses in urban Mexico using several criteria to indirectly assess sector location. We use data from 56 communities from the Mexican Migration Project to estimate multilevel survival and nonmultilevel competing risk models predicting the likelihood of informal, formal, and no business formation. The recent return migration of the household head is strongly associated with informal business creation, particularly in economically dynamic areas. On the other hand, migrants are only marginally more likely to start formal businesses in highly economically dynamic sending areas. PMID:23721676

Easing the Transition from Paper to Screen: An Evaluatory Framework for CAA Migration

ERIC Educational Resources Information Center

McAlpine, Mhairi

2004-01-01

Computer assisted assessment is becoming more and more common through further and higher education. There is some debate about how easy it will be to migrate current assessment practice to a computer enhanced format and how items which are currently re-used for formative purposes may be adapted to be presented online. This paper proposes an…

Describing Directional Cell Migration with a Characteristic Directionality Time

PubMed Central

Loosley, Alex J.; O’Brien, Xian M.; Reichner, Jonathan S.; Tang, Jay X.

2015-01-01

Many cell types can bias their direction of locomotion by coupling to external cues. Characteristics such as how fast a cell migrates and the directedness of its migration path can be quantified to provide metrics that determine which biochemical and biomechanical factors affect directional cell migration, and by how much. To be useful, these metrics must be reproducible from one experimental setting to another. However, most are not reproducible because their numerical values depend on technical parameters like sampling interval and measurement error. To address the need for a reproducible metric, we analytically derive a metric called directionality time, the minimum observation time required to identify motion as directionally biased. We show that the corresponding fit function is applicable to a variety of ergodic, directionally biased motions. A motion is ergodic when the underlying dynamical properties such as speed or directional bias do not change over time. Measuring the directionality of nonergodic motion is less straightforward but we also show how this class of motion can be analyzed. Simulations are used to show the robustness of directionality time measurements and its decoupling from measurement errors. As a practical example, we demonstrate the measurement of directionality time, step-by-step, on noisy, nonergodic trajectories of chemotactic neutrophils. Because of its inherent generality, directionality time ought to be useful for characterizing a broad range of motions including intracellular transport, cell motility, and animal migration. PMID:25992908

Cell-cell interactions mediate cytoskeleton organization and collective endothelial cell chemotaxis.

PubMed

Shamloo, Amir

2014-09-01

This study investigates the role of cell-cell and cell-ligand interactions in cytoskeleton organization of endothelial cells (ECs) and their directional migration within a microfluidic device. The migration of ECs in response to a biochemical factor was studied. Mathematical analysis of the cell migration pathways and cellular cytoskeleton revealed that directional migration, migration persistence length, migration speed, and cytoskeletal stress fiber alignment can be mediated by the level of cell contacts as well as the presence or absence of a biochemical polarizing factor. It was shown that in the presence of a biochemical polarizing factor, higher cell density and more frequent cell contacts has a reinforcing effect on collective cell chemotaxis. In contrast, in the absence of a polarizing factor, high cell density can decrease or suppress the ability of the cells to migrate. Also, the correlation of actin stress fiber organization and alignment with directional migration of ECs was investigated. It was shown that in the presence of a biochemical polarizing factor, stress fibers within the cytoskeleton of ECs can be significantly aligned parallel to the gradient direction when the cells have higher level of contacts. The results also show that the organization and alignment of actin stress fibers is mediated by cell adhesion junctions during collective cell migration and introduce cell-cell interactions as a key factor during collective cell chemotaxis. © 2014 Wiley Periodicals, Inc.

MiR-592 Promotes Gastric Cancer Proliferation, Migration, and Invasion Through the PI3K/AKT and MAPK/ERK Signaling Pathways by Targeting Spry2.

PubMed

He, Yu; Ge, Yugang; Jiang, Mingkun; Zhou, Jundong; Luo, Dakui; Fan, Hao; Shi, Liang; Lin, Linling; Yang, Li

2018-06-21

Gastric cancer (GC) is one of the most prevalent digestive malignancies. MicroRNAs (miRNAs) are involved in multiple cellular processes, including oncogenesis, and miR-592 itself participates in many malignancies; however, its role in GC remains unknown. In this study, we investigated the expression and molecular mechanisms of miR-592 in GC. Quantitative real-time PCR and immunohistochemistry were performed to determine the expression of miR-592 and its putative targets in human tissues and cell lines. Proliferation, migration, and invasion were evaluated by Cell Counting Kit-8, population doubling time, colony formation, Transwell, and wound-healing assays in transfected GC cells in vitro. A dual-luciferase reporter assay was used to determine whether miR-592 could directly bind its target. A tumorigenesis assay was used to study whether miR-592 affected GC growth in vivo. Proteins involved in signaling pathways and the epithelial-mesenchymal transition (EMT) were detected with western blot. The ectopic expression of miR-592 promoted GC proliferation, migration, and invasion in vitro and facilitated tumorigenesis in vivo. Spry2 was a direct target of miR-592 and Spry2 overexpression partially counteracted the effects of miR-592. miR-592 induced the EMT and promoted its progression in GC via the PI3K/AKT and MAPK/ERK signaling pathways by inhibiting Spry2. Overexpression of miR-592 promotes GC proliferation, migration, and invasion and induces the EMT via the PI3K/AKT and MAPK/ERK signaling pathways by inhibiting Spry2, suggesting a potential therapeutic target for GC. © 2018 The Author(s). Published by S. Karger AG, Basel.

TMPRSS4 regulates levels of integrin α5 in NSCLC through miR-205 activity to promote metastasis.

PubMed

Larzabal, L; de Aberasturi, A L; Redrado, M; Rueda, P; Rodriguez, M J; Bodegas, M E; Montuenga, L M; Calvo, A

2014-02-04

TMPRSS4 is a membrane-anchored protease involved in cell migration and invasion in different cancer types including lung cancer. TMPRSS4 expression is increased in NSCLC and its inhibition through shRNA reduces lung metastasis. However, molecular mechanisms leading to the protumorigenic regulation of TMPRSS4 in lung cancer are unknown. miR-205 was identified as an overexpressed gene upon TMPRSS4 downregulation through microarray analysis. Cell migration and invasion assays and in vivo lung primary tumour and metastasis models were used for functional analysis of miR-205 overexpression in H2170 and H441 cell lines. Luciferase assays were used to identify a new miR-205 direct target in NSCLC. miR-205 overexpression promoted an epithelial phenotype with increased E-cadherin and reduced fibronectin. Furthermore, miR-205 expression caused a G0/G1 cell cycle arrest and inhibition of cell growth, migration, attachment to fibronectin, primary tumour growth and metastasis formation in vivo. Integrin α5 (a proinvasive protein) was identified as a new miR-205 direct target in NSCLC. Integrin α5 downregulation in lung cancer cells resulted in complete abrogation of cell migration, a decreased capacity to adhere to fibronectin and reduced in vivo tumour growth, compared with control cells. TMPRSS4 silencing resulted in a concomitant reduction of integrin α5 levels. We have demonstrated for the first time a new molecular pathway that connects TMPRSS4 and integrin α5 through miR-205 to regulate cancer cell invasion and metastasis. Our results will help designing new therapeutic strategies to inhibit this novel pathway in NSCLC.

Atomic Resolution Structural and Chemical Imaging Revealing the Sequential Migration of Ni, Co, and Mn upon the Battery Cycling of Layered Cathode

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

Yan, Pengfei; Zheng, Jianming; Zhang, Ji-Guang

Layered lithium transition metal oxides (LTMO) are promising candidate cathode materials for next generation high energy density lithium ion battery. The challenge for using this category of cathode is the capacity and voltage fading, which is believed to be associated with the layered structure disordering, a process that is initiated from the surface or solid-electrolyte interface and facilitated by transition metal (TM) reduction and oxygen vacancy formation. However, the atomic level dynamic mechanism of such a layered structure disordering is still not fully clear. In this work, utilizing atomic resolution electron energy loss spectroscopy (EELS), we map, for the firstmore » time at atomic scale, the spatial evolution of Ni, Co and Mn in a cycled LiNi1/3M1/3Co1/3O2 layered cathode. In combination with atomic level structural imaging, we discovered the direct correlation of TM ions migration behavior with lattice disordering, featuring the residing of TM ions in the tetrahedral site and a sequential migration of Ni, Co, and Mn upon the increased lattice disordering of the layered structure. This work highlights that Ni ions, though acting as the dominant redox species in many LTMO, are labile to migrate to cause lattice disordering upon battery cycling; while the Mn ions are more stable as compared with Ni and Co and can act as pillar to stabilize layered structure. Direct visualization of the behavior of TM ions during the battery cycling provides insight for designing of cathode with structural stability and correspondingly a superior performance.« less

Use of Anticlines for Geologic Sequestration of Carbon Dioxide in a Saline Aquifer in Northwestern Taiwan

NASA Astrophysics Data System (ADS)

Lin, Shin-Hsun; Liou, Tai-Sheng

2013-04-01

In this study, migration of CO2 in a deep saline aquifer with anticlines under various injection schemes was numerically simulated using the ECO2N simulator. The hypothetical study site was selected at the Taoyuan Plateau near the second largest coal-fired power plant, Datan power plant (annual CO2 emission of 1.5 Mt/yr), in Northwestern Taiwan. A 15x15 km2 simulation domain, containing two sub-parallel east-northeast Hukou and Pingzhen anticlines, was discretized into unstructured grid with spatial refinement at the injection borehole. Kueichulin sandstone and Chinshui shale in the simulation domain were considered as the storage formation and the cap rock, respectively. It was assumed that no CO2 exists in the aquifer prior to injection, and that the aquifer has a hydrostatic pressure distribution and a constant salinity of 3%. All boundaries were assumed to be "open". Isothermal simulations with 1 Mt/yr injection rate and 20 years of injection period were considered. van Genuchten capillary pressure and Corey relative permeability were assumed for all rock formations. Simulation results indicated that pressure buildup characterized the CO2 migration into three different phases: drainage of brine, formation dry-out, and dissolution and gravity take-over . It was found that the worst leakage scenario occurs if a single injection borehole is placed along the anticline axis. In this case, rock formations near the anticline axis provide a leakage path such that CO2 ultimately leaks out of the upper boundary. On the other hand, CO2 can be safely sequestrated in the storage formation if the injection borehole was placed away from the anticline axis. This is because gas phase CO2 migrates along the counter dipping direction of the anticline as a result of buoyancy. More favorable scenarios were found if a multiple-borehole injection scheme was used. In such cases, not only pressure buildup was significantly mitigated but the amount of precipitated salt was reduced. If a five-borehole scheme was used, for example, pressure buildup and the amount of precipitated salt can be reduced by 20% and 90%, respectively. More interestingly, if injection borehole was placed midway between the two anticlines, buoyancy dominates the migration of CO2 such that most CO2 is accumulated under the apex of anticline. Therefore, it is suggested that a multiple-borehole injection scheme would be a preferable scenario because of the reduced risks of pressure buildup and salt precipitation. Moreover, it would be better to place the injection boreholes away from the anticline axis in order to make good use of all possible trapping mechanisms to permanently sequestrate CO2 in deep rock formations.

Directional Collective Cell Migration Emerges as a Property of Cell Interactions

PubMed Central

Woods, Mae L.; Carmona-Fontaine, Carlos; Barnes, Chris P.; Couzin, Iain D.; Mayor, Roberto; Page, Karen M.

2014-01-01

Collective cell migration is a fundamental process, occurring during embryogenesis and cancer metastasis. Neural crest cells exhibit such coordinated migration, where aberrant motion can lead to fatality or dysfunction of the embryo. Migration involves at least two complementary mechanisms: contact inhibition of locomotion (a repulsive interaction corresponding to a directional change of migration upon contact with a reciprocating cell), and co-attraction (a mutual chemoattraction mechanism). Here, we develop and employ a parameterized discrete element model of neural crest cells, to investigate how these mechanisms contribute to long-range directional migration during development. Motion is characterized using a coherence parameter and the time taken to reach, collectively, a target location. The simulated cell group is shown to switch from a diffusive to a persistent state as the response-rate to co-attraction is increased. Furthermore, the model predicts that when co-attraction is inhibited, neural crest cells can migrate into restrictive regions. Indeed, inhibition of co-attraction in vivo and in vitro leads to cell invasion into restrictive areas, confirming the prediction of the model. This suggests that the interplay between the complementary mechanisms may contribute to guidance of the neural crest. We conclude that directional migration is a system property and does not require action of external chemoattractants. PMID:25181349

Hybrid mechanosensing system to generate the polarity needed for migration in fish keratocytes

PubMed Central

Okimura, Chika; Iwadate, Yoshiaki

2016-01-01

ABSTRACT Crawling cells can generate polarity for migration in response to forces applied from the substratum. Such reaction varies according to cell type: there are both fast- and slow-crawling cells. In response to periodic stretching of the elastic substratum, the intracellular stress fibers in slow-crawling cells, such as fibroblasts, rearrange themselves perpendicular to the direction of stretching, with the result that the shape of the cells extends in that direction; whereas fast-crawling cells, such as neutrophil-like differentiated HL-60 cells and Dictyostelium cells, which have no stress fibers, migrate perpendicular to the stretching direction. Fish epidermal keratocytes are another type of fast-crawling cell. However, they have stress fibers in the cell body, which gives them a typical slow-crawling cell structure. In response to periodic stretching of the elastic substratum, intact keratocytes rearrange their stress fibers perpendicular to the direction of stretching in the same way as fibroblasts and migrate parallel to the stretching direction, while blebbistatin-treated stress fiber-less keratocytes migrate perpendicular to the stretching direction, in the same way as seen in HL-60 cells and Dictyostelium cells. Our results indicate that keratocytes have a hybrid mechanosensing system that comprises elements of both fast- and slow-crawling cells, to generate the polarity needed for migration. PMID:27124267

Periodic direct current does not promote wound closure in an in vitro dynamic model of cell migration.

PubMed

Godbout, Charles; Frenette, Jérôme

2006-01-01

A prevailing paradigm is that electrical fields can promote cell migration and tissue healing. To further validate this paradigm, we tested the hypothesis that periodic direct current (DC) can enhance wound closure using an in vitro dynamic model of cell migration. Layers of primary fibroblasts were wounded and treated with DC under various voltages. Repair area, cell velocity, and directionality as well as lamellipodium area were evaluated at different times. Direct current had no beneficial effect on cell migration. Moreover, prolonged stimulation under the highest voltage led to significant reduction in wound closure and cell velocity. The reduction of membrane protusions in stimulated cells may be associated with the deleterious effect of DC. Contrary to the authors' expectations, they found that periodic DC did not promote wound closure, a finding that emphasizes the need to clarify the complex effects of electrical fields on migrating cells.

Functionalized α-Helical Peptide Hydrogels for Neural Tissue Engineering

PubMed Central

2015-01-01

Trauma to the central and peripheral nervous systems often lead to serious morbidity. Current surgical methods for repairing or replacing such damage have limitations. Tissue engineering offers a potential alternative. Here we show that functionalized α-helical-peptide hydrogels can be used to induce attachment, migration, proliferation and differentiation of murine embryonic neural stem cells (NSCs). Specifically, compared with undecorated gels, those functionalized with Arg-Gly-Asp-Ser (RGDS) peptides increase the proliferative activity of NSCs; promote their directional migration; induce differentiation, with increased expression of microtubule-associated protein-2, and a low expression of glial fibrillary acidic protein; and lead to the formation of larger neurospheres. Electrophysiological measurements from NSCs grown in RGDS-decorated gels indicate developmental progress toward mature neuron-like behavior. Our data indicate that these functional peptide hydrogels may go some way toward overcoming the limitations of current approaches to nerve-tissue repair. PMID:26240838

Preparation of an Arg-Glu-Asp-Val Peptide Density Gradient on Hyaluronic Acid-Coated Poly(ε-caprolactone) Film and Its Influence on the Selective Adhesion and Directional Migration of Endothelial Cells.

PubMed

Yu, Shan; Gao, Ying; Mei, Xu; Ren, Tanchen; Liang, Su; Mao, Zhengwei; Gao, Changyou

2016-11-02

Selective adhesion and migration of endothelial cells (ECs) over smooth muscle cells (SMCs) is very important in the rapid endothelialization of blood-contacting implants to prevent vascular restenosis. In this study, a uniform cell-resistant layer of methacrylate-functionalized hyaluronic acid (HA) was first immobilized on a poly(ε-caprolactone) (PCL) film via polydopamine coupling. Then, a density gradient of thiol-functionalized Arg-Glu-Asp-Val (REDV) peptide was prepared on the HA layer via thiol-ene click chemistry and the continuous injection method. The REDV gradient selectively enhanced EC adhesion and preferential directional migration toward the region of higher REDV density, reaching 86% directionality in the middle of the gradient. The migration rate of ECs was also significantly enhanced twofold compared with that on tissue culture polystyrene (TCPS). In contrast, the gradient significantly weakened the adhesion of SMCs to 25% of that on TCPS but had no obvious impact on the migration rate and directionality. Successful modulation of the selective adhesion and directional migration of ECs over SMCs on biodegradable polymers serves as an important step toward practical applications for guided tissue regeneration.

Do migratory flight paths of raptors follow constant geographical or geomagnetic courses?

USGS Publications Warehouse

Thorup, K.; Fuller, M.; Alerstam, T.; Hake, M.; Kjellen, N.; Strandberg, R.

2006-01-01

We tested whether routes of raptors migrating over areas with homogeneous topography follow constant geomagnetic courses more or less closely than constant geographical courses. We analysed the routes taken over land of 45 individual raptors tracked by satellite-based radiotelemetry: 25 peregrine falcons, Falco peregrinus, on autumn migration between North and South America, and seven honey buzzards, Pernis apivorus, and 13 ospreys, Pandion haliaetus, on autumn migration between Europe and Africa. Overall, migration directions showed a better agreement with constant geographical than constant geomagnetic courses. Tracks deviated significantly from constant geomagnetic courses, but were not significantly different from geographical courses. After we removed movements directed far from the mean direction, which may not be migratory movements, migration directions still showed a better agreement with constant geographical than constant geomagnetic courses, but the directions of honey buzzards and ospreys were not significantly different from constant geomagnetic courses either. That migration routes of raptors followed by satellite telemetry are in closer accordance with constant geographical compass courses than with constant geomagnetic compass courses may indicate that geographical (e.g. based on celestial cues) rather than magnetic compass mechanisms are of dominating importance for the birds' long-distance orientation.

Exoplanetary Atmospheres-Chemistry, Formation Conditions, and Habitability.

PubMed

Madhusudhan, Nikku; Agúndez, Marcelino; Moses, Julianne I; Hu, Yongyun

2016-12-01

Characterizing the atmospheres of extrasolar planets is the new frontier in exoplanetary science. The last two decades of exoplanet discoveries have revealed that exoplanets are very common and extremely diverse in their orbital and bulk properties. We now enter a new era as we begin to investigate the chemical diversity of exoplanets, their atmospheric and interior processes, and their formation conditions. Recent developments in the field have led to unprecedented advancements in our understanding of atmospheric chemistry of exoplanets and the implications for their formation conditions. We review these developments in the present work. We review in detail the theory of atmospheric chemistry in all classes of exoplanets discovered to date, from highly irradiated gas giants, ice giants, and super-Earths, to directly imaged giant planets at large orbital separations. We then review the observational detections of chemical species in exoplanetary atmospheres of these various types using different methods, including transit spectroscopy, Doppler spectroscopy, and direct imaging. In addition to chemical detections, we discuss the advances in determining chemical abundances in these atmospheres and how such abundances are being used to constrain exoplanetary formation conditions and migration mechanisms. Finally, we review recent theoretical work on the atmospheres of habitable exoplanets, followed by a discussion of future outlook of the field.

Exoplanetary Atmospheres—Chemistry, Formation Conditions, and Habitability

NASA Astrophysics Data System (ADS)

Madhusudhan, Nikku; Agúndez, Marcelino; Moses, Julianne I.; Hu, Yongyun

2016-12-01

Characterizing the atmospheres of extrasolar planets is the new frontier in exoplanetary science. The last two decades of exoplanet discoveries have revealed that exoplanets are very common and extremely diverse in their orbital and bulk properties. We now enter a new era as we begin to investigate the chemical diversity of exoplanets, their atmospheric and interior processes, and their formation conditions. Recent developments in the field have led to unprecedented advancements in our understanding of atmospheric chemistry of exoplanets and the implications for their formation conditions. We review these developments in the present work. We review in detail the theory of atmospheric chemistry in all classes of exoplanets discovered to date, from highly irradiated gas giants, ice giants, and super-Earths, to directly imaged giant planets at large orbital separations. We then review the observational detections of chemical species in exoplanetary atmospheres of these various types using different methods, including transit spectroscopy, Doppler spectroscopy, and direct imaging. In addition to chemical detections, we discuss the advances in determining chemical abundances in these atmospheres and how such abundances are being used to constrain exoplanetary formation conditions and migration mechanisms. Finally, we review recent theoretical work on the atmospheres of habitable exoplanets, followed by a discussion of future outlook of the field.

Exoplanetary Atmospheres—Chemistry, Formation Conditions, and Habitability

PubMed Central

Agúndez, Marcelino; Moses, Julianne I; Hu, Yongyun

2016-01-01

Characterizing the atmospheres of extrasolar planets is the new frontier in exoplanetary science. The last two decades of exoplanet discoveries have revealed that exoplanets are very common and extremely diverse in their orbital and bulk properties. We now enter a new era as we begin to investigate the chemical diversity of exoplanets, their atmospheric and interior processes, and their formation conditions. Recent developments in the field have led to unprecedented advancements in our understanding of atmospheric chemistry of exoplanets and the implications for their formation conditions. We review these developments in the present work. We review in detail the theory of atmospheric chemistry in all classes of exoplanets discovered to date, from highly irradiated gas giants, ice giants, and super-Earths, to directly imaged giant planets at large orbital separations. We then review the observational detections of chemical species in exoplanetary atmospheres of these various types using different methods, including transit spectroscopy, Doppler spectroscopy, and direct imaging. In addition to chemical detections, we discuss the advances in determining chemical abundances in these atmospheres and how such abundances are being used to constrain exoplanetary formation conditions and migration mechanisms. Finally, we review recent theoretical work on the atmospheres of habitable exoplanets, followed by a discussion of future outlook of the field. PMID:28057962

Nanotopography guides and directs cell migration in amoeboid and epithelial cells

NASA Astrophysics Data System (ADS)

Lee, Rachel; Das, Satarupa; Hourwitz, Matthew; Sun, Xiaoyu; Parent, Carole; Fourkas, John; Losert, Wolfgang

Cell migration plays a critical role in development, angiogenesis, immune response, wound healing, and cancer metastasis. In many cases, cells also move in the context of a matrix of collagen fibers, and the alignment of these fibers can both affect the migration phenotype and guide cells. Here we show that both fast and slow migrating cells - amoeboid HL-60 and epithelial MCF10A - are affected in similar ways by micro/nanostructures with dimensions similar to those of collagen fibers. Cell alignment enhances the efficiency of migration by increasing directional persistence.

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.

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

Interaction between mDia1 and ROCK in Rho-induced migration and adhesion of human dental pulp cells.

PubMed

Cheng, L; Xu, J; Qian, Y Y; Pan, H Y; Yang, H; Shao, M Y; Cheng, R; Hu, T

2017-01-01

To investigate the effects of mammalian homologue of Drosophila diaphanous-1(mDia1) and Rho-associated coiled-coil-containing protein kinase (ROCK) on the migration and adhesion of dental pulp cells (DPCs). Lysophosphatidic acid (LPA) was used to activate Rho signalling. mDia1 and ROCK were inhibited by short interfering RNA and the specific inhibitor, Y-27632, respectively. The migration of DPCs was assessed using the transwell migration assay and scratch test. Formation of cytoskeleton and focal adhesions(FAs) was observed by confocal laser scanning microscopy. Cell adhesion and spreading assays were performed. Phosphorylation of focal adhesion kinase (FAK) and paxillin was detected by Western blotting, and the bands were analysed using Adobe Photoshop CS5 software. All experiments were performed at least three times, and data were analysed with one-way anova and a post hoc test. LPA-triggered activation of Rho and inhibition of ROCK significantly increased the cell migration rate. Cell migration was inhibited by silencing mDia1. mDia1 silencing and ROCK inhibition suppressed the LPA-induced formation of the cytoskeleton, FA and phosphorylation of FAK and paxillin. Inhibition of ROCK or mDia1 facilitated early cell adhesion and spreading; by contrast, the combined inhibition of ROCK and mDia1 neutralized these effects. mDia1 promoted RhoA-induced migration of DPCs, but ROCK had an opposite effect. Both mDia1 and ROCK participated in cytoskeleton formation and adhesion of DPCs. The interactions between mDia1 and ROCK might influence dental pulp repair by determining the migration and adhesion of DPCs. © 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Toward a Deterministic Model of Planetary Formation. IV. Effects of Type I Migration

NASA Astrophysics Data System (ADS)

Ida, S.; Lin, D. N. C.

2008-01-01

In a further development of a deterministic planet formation model (Ida & Lin), we consider the effect of type I migration of protoplanetary embryos due to their tidal interaction with their nascent disks. During the early phase of protostellar disks, although embryos rapidly emerge in regions interior to the ice line, uninhibited type I migration leads to their efficient self-clearing. But embryos continue to form from residual planetesimals, repeatedly migrate inward, and provide a main channel of heavy-element accretion onto their host stars. During the advanced stages of disk evolution (a few Myr), the gas surface density declines to values comparable to or smaller than that of the minimum mass nebula model, and type I migration is no longer effective for Mars-mass embryos. Over wide ranges of initial disk surface densities and type I migration efficiencies, the surviving population of embryos interior to the ice line has a total mass of several M⊕. With this reservoir, there is an adequate inventory of residual embryos to subsequently assemble into rocky planets similar to those around the Sun. However, the onset of efficient gas accretion requires the emergence and retention of cores more massive than a few M⊕ prior to the severe depletion of the disk gas. The formation probability of gas giant planets and hence the predicted mass and semimajor axis distributions of extrasolar gas giants are sensitively determined by the strength of type I migration. We suggest that the distributions consistent with observations can be reproduced only if the actual type I migration timescale is at least an order of magnitude longer than that deduced from linear theories.

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.

Quantitative analysis of random migration of cells using time-lapse video microscopy.

PubMed

Jain, Prachi; Worthylake, Rebecca A; Alahari, Suresh K

2012-05-13

Cell migration is a dynamic process, which is important for embryonic development, tissue repair, immune system function, and tumor invasion (1, 2). During directional migration, cells move rapidly in response to an extracellular chemotactic signal, or in response to intrinsic cues (3) provided by the basic motility machinery. Random migration occurs when a cell possesses low intrinsic directionality, allowing the cells to explore their local environment. Cell migration is a complex process, in the initial response cell undergoes polarization and extends protrusions in the direction of migration (2). Traditional methods to measure migration such as the Boyden chamber migration assay is an easy method to measure chemotaxis in vitro, which allows measuring migration as an end point result. However, this approach neither allows measurement of individual migration parameters, nor does it allow to visualization of morphological changes that cell undergoes during migration. Here, we present a method that allows us to monitor migrating cells in real time using video - time lapse microscopy. Since cell migration and invasion are hallmarks of cancer, this method will be applicable in studying cancer cell migration and invasion in vitro. Random migration of platelets has been considered as one of the parameters of platelet function (4), hence this method could also be helpful in studying platelet functions. This assay has the advantage of being rapid, reliable, reproducible, and does not require optimization of cell numbers. In order to maintain physiologically suitable conditions for cells, the microscope is equipped with CO(2) supply and temperature thermostat. Cell movement is monitored by taking pictures using a camera fitted to the microscope at regular intervals. Cell migration can be calculated by measuring average speed and average displacement, which is calculated by Slidebook software.

β1 integrin signaling promotes neuronal migration along vascular scaffolds in the post-stroke brain.

PubMed

Fujioka, Teppei; Kaneko, Naoko; Ajioka, Itsuki; Nakaguchi, Kanako; Omata, Taichi; Ohba, Honoka; Fässler, Reinhard; García-Verdugo, José Manuel; Sekiguchi, Kiyotoshi; Matsukawa, Noriyuki; Sawamoto, Kazunobu

2017-02-01

Cerebral ischemic stroke is a main cause of chronic disability. However, there is currently no effective treatment to promote recovery from stroke-induced neurological symptoms. Recent studies suggest that after stroke, immature neurons, referred to as neuroblasts, generated in a neurogenic niche, the ventricular-subventricular zone, migrate toward the injured area, where they differentiate into mature neurons. Interventions that increase the number of neuroblasts distributed at and around the lesion facilitate neuronal repair in rodent models for ischemic stroke, suggesting that promoting neuroblast migration in the post-stroke brain could improve efficient neuronal regeneration. To move toward the lesion, neuroblasts form chain-like aggregates and migrate along blood vessels, which are thought to increase their migration efficiency. However, the molecular mechanisms regulating these migration processes are largely unknown. Here we studied the role of β1-class integrins, transmembrane receptors for extracellular matrix proteins, in these migrating neuroblasts. We found that the neuroblast chain formation and blood vessel-guided migration critically depend on β1 integrin signaling. β1 integrin facilitated the adhesion of neuroblasts to laminin and the efficient translocation of their soma during migration. Moreover, artificial laminin-containing scaffolds promoted neuroblast chain formation and migration toward the injured area. These data suggest that laminin signaling via β1 integrin supports vasculature-guided neuronal migration to efficiently supply neuroblasts to injured areas. This study also highlights the importance of vascular scaffolds for cell migration in development and regeneration. Copyright © 2017 3-V Biosciences. Published by Elsevier B.V. All rights reserved.

Gap opening by gas accretion and influence on planet populations

NASA Astrophysics Data System (ADS)

Crida, A.; Bitsch, B.; Ndugu, N.; Morbidelli, A.

2017-09-01

Giant planets grow and migrate in protoplanetary disks. Because they accrete gas from their horseshoe region until the latter is depleted, we find that giant planets can open a gap before being lost into their central star by type I migration. A reduced type II migration is then enough and necessary to limit the total amount of migration that a giant planet suffers during its formation.

Quantum chemical and kinetic study of formation of 2-chlorophenoxy radical from 2-chlorophenol: unimolecular decomposition and bimolecular reactions with H, OH, Cl, and O2.

PubMed

Altarawneh, Mohammednoor; Dlugogorski, Bogdan Z; Kennedy, Eric M; Mackie, John C

2008-04-24

This study investigates the kinetic parameters of the formation of the chlorophenoxy radical from the 2-chlorophenol molecule, a key precursor to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCCD/F), in unimolecular and bimolecular reactions in the gas phase. The study develops the reaction potential energy surface for the unimolecular decomposition of 2-chlorophenol. The migration of the phenolic hydrogen to the ortho-C bearing the hydrogen atom produces 2-chlorocyclohexa-2,4-dienone through an activation barrier of 73.6 kcal/mol (0 K). This route holds more importance than the direct fission of Cl or the phenolic H. Reaction rate constants for the bimolecular reactions, 2-chlorophenol + X --> X-H + 2-chlorophenoxy (X = H, OH, Cl, O2) are calculated and compared with the available experimental kinetics for the analogous reactions of X with phenol. OH reaction with 2-chlorophenol produces 2-chlorophenoxy by direct abstraction rather than through addition and subsequent water elimination. The results of the present study will find applications in the construction of detailed kinetic models describing the formation of PCDD/F in the gas phase.

Impacts of rural worker migration on ambient air quality and health in China: From the perspective of upgrading residential energy consumption.

PubMed

Shen, Huizhong; Chen, Yilin; Russell, Armistead G; Hu, Yongtao; Shen, Guofeng; Yu, Haofei; Henneman, Lucas R F; Ru, Muye; Huang, Ye; Zhong, Qirui; Chen, Yuanchen; Li, Yufei; Zou, Yufei; Zeng, Eddy Y; Fan, Ruifang; Tao, Shu

2018-04-01

In China, rural migrant workers (RMWs) are employed in urban workplaces but receive minimal resources and welfare. Their residential energy use mix (REM) and pollutant emission profiles are different from those of traditional urban (URs) and rural residents (RRs). Their migration towards urban areas plays an important role in shaping the magnitudes and spatial patterns of pollutant emissions, ambient PM 2.5 (fine particulate matter with a diameter smaller than 2.5 μm) concentrations, and associated health impacts in both urban and rural areas. Here we evaluate the impacts of RMW migration on REM pollutant emissions, ambient PM 2.5 , and subsequent premature deaths across China. At the national scale, RMW migration benefits ambient air quality because RMWs tend to transition to a cleaner REM upon arrival at urban areas-though not as clean as urban residents'. In 2010, RMW migration led to a decrease of 1.5 μg/m 3 in ambient PM 2.5 exposure concentrations (C ex ) averaged across China and a subsequent decrease of 12,200 (5700 to 16,300, as 90% confidence interval) in premature deaths from exposure to ambient PM 2.5 . Despite the overall health benefit, large-scale cross-province migration increased megacities' PM 2.5 levels by as much as 10 μg/m 3 due to massive RMW inflows. Model simulations show that upgrading within-city RMWs' REMs can effectively offset the RMW-induced PM 2.5 increase in megacities, and that policies that properly navigate migration directions may have potential for balancing the economic growth against ambient air quality deterioration. Our study indicates the urgency of considering air pollution impacts into migration-related policy formation in the context of rapid urbanization in China. Copyright © 2018 Elsevier Ltd. All rights reserved.

Straight as an arrow: humpback whales swim constant course tracks during long-distance migration

PubMed Central

Horton, Travis W.; Holdaway, Richard N.; Zerbini, Alexandre N.; Hauser, Nan; Garrigue, Claire; Andriolo, Artur; Clapham, Phillip J.

2011-01-01

Humpback whale seasonal migrations, spanning greater than 6500 km of open ocean, demonstrate remarkable navigational precision despite following spatially and temporally distinct migration routes. Satellite-monitored radio tag-derived humpback whale migration tracks in both the South Atlantic and South Pacific include constant course segments of greater than 200 km, each spanning several days of continuous movement. The whales studied here maintain these directed movements, often with better than 1° precision, despite the effects of variable sea-surface currents. Such remarkable directional precision is difficult to explain by established models of directional orientation, suggesting that alternative compass mechanisms should be explored. PMID:21508023

Straight as an arrow: humpback whales swim constant course tracks during long-distance migration.

PubMed

Horton, Travis W; Holdaway, Richard N; Zerbini, Alexandre N; Hauser, Nan; Garrigue, Claire; Andriolo, Artur; Clapham, Phillip J

2011-10-23

Humpback whale seasonal migrations, spanning greater than 6500 km of open ocean, demonstrate remarkable navigational precision despite following spatially and temporally distinct migration routes. Satellite-monitored radio tag-derived humpback whale migration tracks in both the South Atlantic and South Pacific include constant course segments of greater than 200 km, each spanning several days of continuous movement. The whales studied here maintain these directed movements, often with better than 1° precision, despite the effects of variable sea-surface currents. Such remarkable directional precision is difficult to explain by established models of directional orientation, suggesting that alternative compass mechanisms should be explored.

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).

DOT1L histone methyltransferase regulates the expression of BCAT1 and is involved in sphere formation and cell migration of breast cancer cell lines.

PubMed

Oktyabri, Dulamsuren; Ishimura, Akihiko; Tange, Shoichiro; Terashima, Minoru; Suzuki, Takeshi

2016-04-01

DOT1L is a histone H3 lysine 79 (H3K79) methyltransferase mainly implicated in leukemia. Here we analyzed the function of DOT1L in breast cancer cells. The expression of DOT1L was up-regulated in malignant breast cancer tissues. Over-expression of DOT1L significantly increased the sphere formation and the cell migration activities of MCF7 breast cancer cell line. In contrast, knockdown of DOT1L reduced the cell migration activity of MDA-MB-231 breast cancer cell line. BCAT1, which encodes a branched-chain amino acid transaminase, was identified as one of the target genes controlled by DOT1L through the regulation of H3K79 methylation. Mechanistic investigation revealed that BCAT1 might be an important regulator responsible for DOT1L-mediated sphere formation and cell migration in breast cancer cells. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

WASP and SCAR are evolutionarily conserved in actin-filled pseudopod-based motility

PubMed Central

2017-01-01

Diverse eukaryotic cells crawl through complex environments using distinct modes of migration. To understand the underlying mechanisms and their evolutionary relationships, we must define each mode and identify its phenotypic and molecular markers. In this study, we focus on a widely dispersed migration mode characterized by dynamic actin-filled pseudopods that we call “α-motility.” Mining genomic data reveals a clear trend: only organisms with both WASP and SCAR/WAVE—activators of branched actin assembly—make actin-filled pseudopods. Although SCAR has been shown to drive pseudopod formation, WASP’s role in this process is controversial. We hypothesize that these genes collectively represent a genetic signature of α-motility because both are used for pseudopod formation. WASP depletion from human neutrophils confirms that both proteins are involved in explosive actin polymerization, pseudopod formation, and cell migration. WASP and WAVE also colocalize to dynamic signaling structures. Moreover, retention of WASP together with SCAR correctly predicts α-motility in disease-causing chytrid fungi, which we show crawl at >30 µm/min with actin-filled pseudopods. By focusing on one migration mode in many eukaryotes, we identify a genetic marker of pseudopod formation, the morphological feature of α-motility, providing evidence for a widely distributed mode of cell crawling with a single evolutionary origin. PMID:28473602

Energetics of defects formation and oxygen migration in pyrochlore compounds from first principles calculations

NASA Astrophysics Data System (ADS)

Li, Yan; Kowalski, Piotr M.

2018-07-01

In order to get better understanding of the selective order-disorder transition in pyrochlore compounds, using ab initio methods we calculated the formation energies of coupled cation anti-site and anion Frenkel pair defects and the energy barriers for the oxygen migration for number of families of A2B2 O7 pyrochlore-type compounds. While these parameters have been previously computed with force field-based methods, the ab initio results provide more reliable values that can be confidently used in subsequent analysis. We found a fairly good correlation between the formation energies of the coupled defects and the stability field of pyrochlores. In line with previous studies, the compounds that crystallize in defect fluorite structure are found to have smaller values of coupled defect formation energies than those crystallizing in the pyrochlore phase, although the correlation is not that sharp as in the case of isolated anion Frenkel pair defect. The investigation of the energy barriers for the oxygen migration shows that it is not a good, sole indicator of the tendency of the order-disorder phase transition in pyrochlores. However, we found that the oxygen migration barrier is reduced in the presence of the cation antisite defect. This points at disordering-induced enhancement of oxygen diffusion in pyrochlore compounds.

MicroRNA-210 Modulates Endothelial Cell Response to Hypoxia and Inhibits the Receptor Tyrosine Kinase Ligand Ephrin-A3*S⃞

PubMed Central

Fasanaro, Pasquale; D'Alessandra, Yuri; Di Stefano, Valeria; Melchionna, Roberta; Romani, Sveva; Pompilio, Giulio; Capogrossi, Maurizio C.; Martelli, Fabio

2008-01-01

MicroRNAs (miRNAs) are small non-protein-coding RNAs that function as negative gene expression regulators. In the present study, we investigated miRNAs role in endothelial cell response to hypoxia. We found that the expression of miR-210 progressively increased upon exposure to hypoxia. miR-210 overexpression in normoxic endothelial cells stimulated the formation of capillary-like structures on Matrigel and vascular endothelial growth factor-driven cell migration. Conversely, miR-210 blockade via anti-miRNA transfection inhibited the formation of capillary-like structures stimulated by hypoxia and decreased cell migration in response to vascular endothelial growth factor. miR-210 overexpression did not affect endothelial cell growth in both normoxia and hypoxia. However, anti-miR-210 transfection inhibited cell growth and induced apoptosis, in both normoxia and hypoxia. We determined that one relevant target of miR-210 in hypoxia was Ephrin-A3 since miR-210 was necessary and sufficient to down-modulate its expression. Moreover, luciferase reporter assays showed that Ephrin-A3 was a direct target of miR-210. Ephrin-A3 modulation by miR-210 had significant functional consequences; indeed, the expression of an Ephrin-A3 allele that is not targeted by miR-210 prevented miR-210-mediated stimulation of both tubulogenesis and chemotaxis. We conclude that miR-210 up-regulation is a crucial element of endothelial cell response to hypoxia, affecting cell survival, migration, and differentiation. PMID:18417479

CROWDING-OUT OF GIANTS BY DWARFS: AN ORIGIN FOR THE LACK OF COMPANION PLANETS IN HOT JUPITER SYSTEMS

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

Ogihara, Masahiro; Inutsuka, Shu-ichiro; Kobayashi, Hiroshi, E-mail: ogihara@nagoya-u.jp

2013-11-20

We investigate the formation of close-in terrestrial planets from planetary embryos under the influence of a hot Jupiter (HJ) using gravitational N-body simulations that include gravitational interactions between the gas disk and the terrestrial planet (e.g., type I migration). Our simulations show that several terrestrial planets efficiently form outside the orbit of the HJ, making a chain of planets, and all of them gravitationally interact directly or indirectly with the HJ through resonance, which leads to inward migration of the HJ. We call this mechanism of induced migration of the HJ ''crowding-out''. The HJ is eventually lost through collision withmore » the central star, and only several terrestrial planets remain. We also find that the efficiency of the crowding-out effect depends on the model parameters; for example, the heavier the disk is, the more efficient the crowding-out is. When planet formation occurs in a massive disk, the HJ can be lost to the central star and is never observed. On the other hand, for a less massive disk, the HJ and terrestrial planets can coexist; however, the companion planets may be below the detection limit of current observations. In both cases, systems with a HJ and terrestrial planets have little chance of detection. Therefore, our model naturally explains the lack of companion planets in HJ systems regardless of the disk mass. In effect, our model provides a theoretical prediction for future observations; additional planets can be discovered just outside the HJ, and their masses should generally be small.« less

Migration, business formation, and the informal economy in urban Mexico.

PubMed

Sheehan, Connor M; Riosmena, Fernando

2013-07-01

Although the informal economy has grown rapidly in several developing nations, and migration and informality may be related to similar types of credit constraints and market failures, previous research has not systematically attempted to identify if migrant households are more likely to start informal and formal businesses alike and if this association varies across local contexts. We examine the relationship between prior US migration and the creation of both formal and informal businesses in urban Mexico using several criteria to indirectly assess sector location. We use data from 56 communities from the Mexican Migration Project to estimate multilevel survival and nonmultilevel competing risk models predicting the likelihood of informal, formal, and no business formation. The recent return migration of the household head is strongly associated with informal business creation, particularly in economically dynamic areas. On the other hand, migrants are only marginally more likely to start formal businesses in highly economically dynamic sending areas. Published by Elsevier Inc.

Acanthamoeba migration in an electric field.

PubMed

Rudell, Jolene Chang; Gao, Jing; Sun, Yuxin; Sun, Yaohui; Chodosh, James; Schwab, Ivan; Zhao, Min

2013-06-21

We investigated the in vitro response of Acanthamoeba trophozoites to electric fields (EFs). Acanthamoeba castellanii were exposed to varying strengths of an EF. During EF exposure, cell migration was monitored using an inverted microscope equipped with a CCD camera and the SimplePCI 5.3 imaging system to capture time-lapse images. The migration of A. castellanii trophozoites was analyzed and quantified with ImageJ software. For analysis of cell migration in a three-dimensional culture system, Acanthamoeba trophozoites were cultured in agar, exposed to an EF, digitally video recorded, and analyzed at various Z focal planes. Acanthamoeba trophozoites move at random in the absence of an EF, but move directionally in response to an EF. Directedness in the absence of an EF is 0.08 ± 0.01, while in 1200 mV/mm EF, directedness is significantly higher at -0.65 ± 0.01 (P < 0.001). We find that the trophozoite migration response is voltage-dependent, with higher directionality with higher voltage application. Acanthamoeba move directionally in a three-dimensional (3D) agar system as well when exposed to an EF. Acanthamoeba trophozoites move directionally in response to an EF in a two-dimensional and 3D culture system. Acanthamoeba trophozoite migration is also voltage-dependent, with increased directionality with increasing voltage. This may provide new treatment modalities for Acanthamoeba keratitis.

Functional consequences of prolactin signalling in endothelial cells: a potential link with angiogenesis in pathophysiology?

PubMed Central

Reuwer, Anne Q; Nowak-Sliwinska, Patrycja; Mans, Laurie A; van der Loos, Chris M; von der Thüsen, Jan H; Twickler, Marcel Th B; Spek, C Arnold; Goffin, Vincent; Griffioen, Arjan W; Borensztajn, Keren S

2012-01-01

Prolactin is best known as the polypeptide anterior pituitary hormone, which regulates the development of the mammary gland. However, it became clear over the last decade that prolactin contributes to a broad range of pathologies, including breast cancer. Prolactin is also involved in angiogenesis via the release of pro-angiogenic factors by leukocytes and epithelial cells. However, whether prolactin also influences endothelial cells, and whether there are functional consequences of prolactin-induced signalling in the perspective of angiogenesis, remains so far elusive. In the present study, we show that prolactin induces phosphorylation of ERK1/2 and STAT5 and induces tube formation of endothelial cells on Matrigel. These effects are blocked by a specific prolactin receptor antagonist, del1-9-G129R-hPRL. Moreover, in an in vivo model of the chorioallantoic membrane of the chicken embryo, prolactin enhances vessel density and the tortuosity of the vasculature and pillar formation, which are hallmarks of intussusceptive angiogenesis. Interestingly, while prolactin has only little effect on endothelial cell proliferation, it markedly stimulates endothelial cell migration. Again, migration was reverted by del1-9-G129R-hPRL, indicating a direct effect of prolactin on its receptor. Immunohistochemistry and spectral imaging revealed that the prolactin receptor is present in the microvasculature of human breast carcinoma tissue. Altogether, these results suggest that prolactin may directly stimulate angiogenesis, which could be one of the mechanisms by which prolactin contributes to breast cancer progression, thereby providing a potential tool for intervention. PMID:22128761

RIT1 controls actin dynamics via complex formation with RAC1/CDC42 and PAK1.

PubMed

Meyer Zum Büschenfelde, Uta; Brandenstein, Laura Isabel; von Elsner, Leonie; Flato, Kristina; Holling, Tess; Zenker, Martin; Rosenberger, Georg; Kutsche, Kerstin

2018-05-01

RIT1 belongs to the RAS family of small GTPases. Germline and somatic RIT1 mutations have been identified in Noonan syndrome (NS) and cancer, respectively. By using heterologous expression systems and purified recombinant proteins, we identified the p21-activated kinase 1 (PAK1) as novel direct effector of RIT1. We found RIT1 also to directly interact with the RHO GTPases CDC42 and RAC1, both of which are crucial regulators of actin dynamics upstream of PAK1. These interactions are independent of the guanine nucleotide bound to RIT1. Disease-causing RIT1 mutations enhance protein-protein interaction between RIT1 and PAK1, CDC42 or RAC1 and uncouple complex formation from serum and growth factors. We show that the RIT1-PAK1 complex regulates cytoskeletal rearrangements as expression of wild-type RIT1 and its mutant forms resulted in dissolution of stress fibers and reduction of mature paxillin-containing focal adhesions in COS7 cells. This effect was prevented by co-expression of RIT1 with dominant-negative CDC42 or RAC1 and kinase-dead PAK1. By using a transwell migration assay, we show that RIT1 wildtype and the disease-associated variants enhance cell motility. Our work demonstrates a new function for RIT1 in controlling actin dynamics via acting in a signaling module containing PAK1 and RAC1/CDC42, and highlights defects in cell adhesion and migration as possible disease mechanism underlying NS.

RIT1 controls actin dynamics via complex formation with RAC1/CDC42 and PAK1

PubMed Central

von Elsner, Leonie; Flato, Kristina; Holling, Tess; Zenker, Martin; Rosenberger, Georg

2018-01-01

RIT1 belongs to the RAS family of small GTPases. Germline and somatic RIT1 mutations have been identified in Noonan syndrome (NS) and cancer, respectively. By using heterologous expression systems and purified recombinant proteins, we identified the p21-activated kinase 1 (PAK1) as novel direct effector of RIT1. We found RIT1 also to directly interact with the RHO GTPases CDC42 and RAC1, both of which are crucial regulators of actin dynamics upstream of PAK1. These interactions are independent of the guanine nucleotide bound to RIT1. Disease-causing RIT1 mutations enhance protein-protein interaction between RIT1 and PAK1, CDC42 or RAC1 and uncouple complex formation from serum and growth factors. We show that the RIT1-PAK1 complex regulates cytoskeletal rearrangements as expression of wild-type RIT1 and its mutant forms resulted in dissolution of stress fibers and reduction of mature paxillin-containing focal adhesions in COS7 cells. This effect was prevented by co-expression of RIT1 with dominant-negative CDC42 or RAC1 and kinase-dead PAK1. By using a transwell migration assay, we show that RIT1 wildtype and the disease-associated variants enhance cell motility. Our work demonstrates a new function for RIT1 in controlling actin dynamics via acting in a signaling module containing PAK1 and RAC1/CDC42, and highlights defects in cell adhesion and migration as possible disease mechanism underlying NS. PMID:29734338

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

Effects of local film properties on the nucleation and growth of tin whiskers and hillocks

NASA Astrophysics Data System (ADS)

Sarobol, Pylin

Whiskers and hillocks grow spontaneously on Pb-free Sn electrodeposited films as a response to thin film stresses. Stress relaxation occurs by atom deposition to specific grain boundaries in the plane of the film, with hillocks being formed when grain boundary migration accompanies growth out of the plane of the film. The implication for whisker formation in electronics is serious: whiskers can grow to be millimeters long, sometimes causing short circuiting between adjacent components and, thereby, posing serious electrical reliability risks. In order to develop more effective whisker mitigation strategies, a predictive physics-based model has been needed. A growth model is developed, based on grain boundary faceting, localized Coble creep, as well as grain boundary sliding for whiskers, and grain boundary sliding with shear induced grain boundary migration for hillocks. In this model of whisker formation, two mechanisms are important: accretion of atoms by Coble creep on grain boundary planes normal to the growth direction inducing a grain boundary shear and grain boundary sliding in the direction of whisker growth. The model accurately captures the importance of the geometry of "surface grains"---shallow grains on film surfaces whose depths are significantly less than their in-plane grain sizes. A critical factor in the analysis is the ratio of the grain boundary sliding coefficient to the in-plane film compressive stress. If the accretion-induced shear stresses are not coupled to grain boundary motion and sliding occurs, a whisker forms. If the shear stress is coupled to grain boundary migration, a hillock forms. Based on this model, long whiskers grow from shallow surface grains with easy grain boundary sliding in the direction of growth. Other observed growth morphologies will be discussed in light of our model. Additional insights into the preferred sites for whisker and hillock growth were developed based on elastic anisotropy, local film microstructure, grain misorientation, and elastic strain energy density (ESED) as the driving force for growth. Local grain orientations and strains measured by synchrotron micro-diffraction in regions containing whiskers or hillocks were compared with elastic finite element analysis simulations, including Sn elastic anisotropy. Whisker and hillock grains were observed to have higher crystallographic misorientations with neighboring grains than generally observed in the microstructure. While elastic simulations predicted higher local out-of-plane elastic strains and ESEDs for whisker and hillock grains, synchrotron measurements of out-of-plane strains of whisker and hillock grains after growth showed relaxation, with correspondingly low ESEDs calculated from measured strains. This suggests that, before whisker or hillock formation, highly misoriented grains with high out-of-plane elastic strains and ESEDs relative to their neighbors determined, at least in part, which grains became whiskers or hillocks. Based on the models and experiments in this thesis, a clearer picture emerges of the necessary and sufficient conditions for tin whisker and hillock formation in thin films.

Regulating the migration of smooth muscle cells by a vertically distributed poly(2-hydroxyethyl methacrylate) gradient on polymer brushes covalently immobilized with RGD peptides.

PubMed

Wu, Sai; Du, Wang; Duan, Yiyuan; Zhang, Deteng; Liu, Yixiao; Wu, Bingbing; Zou, Xiaohui; Ouyang, Hongwei; Gao, Changyou

2018-05-30

The gradient localization of biological cues is of paramount importance to guide directional migration of cells. In this study, poly(2-hydroxyethyl methacrylate-co-glycidyl methacrylate)-block- poly(2-hydroxyethyl methacrylate) (P(HEMA-co-GMA)-b-PHEMA) brushes with a uniform underneath P(HEMA-co-GMA) layer and a gradient thickness of PHEMA blocks were prepared by using surface-initiated atom-transfer radical polymerization and a dynamically controlled polymerization process. The polymer chains were subsequently functionalized with the cell-adhesive arginine-glycine-aspartic acid (RGD) peptides by reaction with the glycidyl groups, and their structures and properties were characterized by X-ray photoelectron spectrometry (XPS), quartz crystal microbalance with dissipation (QCM-D) and air contact angle. Adhesion and migration processes of smooth muscle cells (SMCs) were then studied. Compared with those on the sufficiently exposed RGD surface, the cell adhesion and mobility were well maintained when the RGD peptides were localized at 18.9 nm depth, whereas the adhesion, spreading and migration rate of SMCs were significantly impaired when the RGD peptides were localized at a depth of 38.4 nm. On the RGD depth gradient surface, the SMCs exhibited preferential orientation and enhanced directional migration toward the direction of reduced thickness of the second PHEMA brushes. Half of the cells were oriented within ± 30° to the x-axis direction, and 72% of the cells moved directionally at the optimal conditions. Cell adhesion strength, arrangement of cytoskeleton, and gene and protein expression levels of adhesion-related proteins were studied to corroborate the mechanisms, demonstrating that the cell mobility is regulated by the complex and synergetic intracellular signals resulted from the difference in surface properties. Cell migration is of paramount importance for the processes of tissue repair and regeneration. So far, the gradient localization of biological cues perpendicular to the substrate, which is the usual case for the biological signaling molecules to locate in ECM in vivo, has been scarcely studied, and has not been used to guide the directional migration of cells. In this study, we prepare a depth gradient of RGD peptides along the polymer chains, which is used to guide the directional migration of SMCs after a second hydrophilic bock is prepared in a gradient manner. For the first time the directional migration of SMCs is achieved under the guidance of a depth gradient of RGD ligands. The mechanisms of different cell migration abilities are further discussed based on the results of cell adhesion, cell adhesion force, cytoskeleton alignment and expression of relative proteins and genes. This work paves a new strategy by fabricating a gradient polymer brushes with immobilized bioactive molecules to dominate the directional cell migration, and elucidates the mechanisms underlining the biased migration along RGD depth localization gradients, shedding a light for the design of novel biomaterials to control and guide cell migration and invasion. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Strike-Slip Fault Patterns on Europa: Obliquity or Polar Wander?

NASA Technical Reports Server (NTRS)

Rhoden, Alyssa Rose; Hurford, Terry A.; Manga, Michael

2011-01-01

Variations in diurnal tidal stress due to Europa's eccentric orbit have been considered as the driver of strike-slip motion along pre-existing faults, but obliquity and physical libration have not been taken into account. The first objective of this work is to examine the effects of obliquity on the predicted global pattern of fault slip directions based on a tidal-tectonic formation model. Our second objective is to test the hypothesis that incorporating obliquity can reconcile theory and observations without requiring polar wander, which was previously invoked to explain the mismatch found between the slip directions of 192 faults on Europa and the global pattern predicted using the eccentricity-only model. We compute predictions for individual, observed faults at their current latitude, longitude, and azimuth with four different tidal models: eccentricity only, eccentricity plus obliquity, eccentricity plus physical libration, and a combination of all three effects. We then determine whether longitude migration, presumably due to non-synchronous rotation, is indicated in observed faults by repeating the comparisons with and without obliquity, this time also allowing longitude translation. We find that a tidal model including an obliquity of 1.2?, along with longitude migration, can predict the slip directions of all observed features in the survey. However, all but four faults can be fit with only 1? of obliquity so the value we find may represent the maximum departure from a lower time-averaged obliquity value. Adding physical libration to the obliquity model improves the accuracy of predictions at the current locations of the faults, but fails to predict the slip directions of six faults and requires additional degrees of freedom. The obliquity model with longitude migration is therefore our preferred model. Although the polar wander interpretation cannot be ruled out from these results alone, the obliquity model accounts for all observations with a value consistent with theoretical expectations and cycloid modeling.

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.

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

Connexin 43 expression on peripheral blood eosinophils: role of gap junctions in transendothelial migration.

PubMed

Vliagoftis, Harissios; Ebeling, Cory; Ilarraza, Ramses; Mahmudi-Azer, Salahaddin; Abel, Melanie; Adamko, Darryl; Befus, A Dean; Moqbel, Redwan

2014-01-01

Eosinophils circulate in the blood and are recruited in tissues during allergic inflammation. Gap junctions mediate direct communication between adjacent cells and may represent a new way of communication between immune cells distinct from communication through cytokines and chemokines. We characterized the expression of connexin (Cx)43 by eosinophils isolated from atopic individuals using RT-PCR, Western blotting, and confocal microscopy and studied the biological functions of gap junctions on eosinophils. The formation of functional gap junctions was evaluated measuring dye transfer using flow cytometry. The role of gap junctions on eosinophil transendothelial migration was studied using the inhibitor 18-a-glycyrrhetinic acid. Peripheral blood eosinophils express Cx43 mRNA and protein. Cx43 is localized not only in the cytoplasm but also on the plasma membrane. The membrane impermeable dye BCECF transferred from eosinophils to epithelial or endothelial cells following coculture in a dose and time dependent fashion. The gap junction inhibitors 18-a-glycyrrhetinic acid and octanol did not have a significant effect on dye transfer but reduced dye exit from eosinophils. The gap junction inhibitor 18-a-glycyrrhetinic acid inhibited eosinophil transendothelial migration in a dose dependent manner. Thus, eosinophils from atopic individuals express Cx43 constitutively and Cx43 may play an important role in eosinophil transendothelial migration and function in sites of inflammation.

Real-Time Observation of Iodide Ion Migration in Methylammonium Lead Halide Perovskites.

PubMed

Li, Cheng; Guerrero, Antonio; Zhong, Yu; Gräser, Anna; Luna, Carlos Andres Melo; Köhler, Jürgen; Bisquert, Juan; Hildner, Richard; Huettner, Sven

2017-11-01

Organic-inorganic metal halide perovskites (e.g., CH 3 NH 3 PbI 3- x Cl x ) emerge as a promising optoelectronic material. However, the Shockley-Queisser limit for the power conversion efficiency (PCE) of perovskite-based photovoltaic devices is still not reached. Nonradiative recombination pathways may play a significant role and appear as photoluminescence (PL) inactive (or dark) areas on perovskite films. Although these observations are related to the presence of ions/defects, the underlying fundamental physics and detailed microscopic processes, concerning trap/defect status, ion migration, etc., still remain poorly understood. Here correlated wide-field PL microscopy and impedance spectroscopy are utilized on perovskite films to in situ investigate both the spatial and the temporal evolution of these PL inactive areas under external electric fields. The formation of PL inactive domains is attributed to the migration and accumulation of iodide ions under external fields. Hence, we are able to characterize the kinetic processes and determine the drift velocities of these ions. In addition, it is shown that I 2 vapor directly affects the PL quenching of a perovskite film, which provides evidence that the migration/segregation of iodide ions plays an important role in the PL quenching and consequently limits the PCE of organometal halide-based perovskite photovoltaic devices. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

MicroRNA-140-3p inhibits proliferation, migration and invasion of lung cancer cells by targeting ATP6AP2.

PubMed

Kong, Xiao-Mei; Zhang, Ge-Hong; Huo, Yun-Kui; Zhao, Xiao-Hong; Cao, Da-Wei; Guo, Shu-Fang; Li, Ai-Min; Zhang, Xin-Ri

2015-01-01

MicroRNAs are small noncoding RNA molecules that regulate gene expression at the post-transcriptional level. Compelling evidence reveals that there is a causative link between microRNAs deregulation and lung cancer development and metastasis. The aim of present study was to explore the function of miR-140-3p in the development and metastasis of lung cancer cell. Using real-time PCR, we detected the miR-140-3p expression of lung cancer tissues and its pared non-lung cancer tissue. Then, we evaluated the role of miR-140-3p in cell proliferation, invasion and migration using MTT, colony formation assay, Transwell invasion and Transwell migration assay in lung cancer cell lines. As a result, miR-140-3p expression level was lower in lung cancer tissues compared to adjacent normal lung cancer tissue. After miR-140-3p was upregulated in A549 or H1299 cells, cell proliferation, invasion and migration was notably attenuated. Furthermore, we identified ATP6AP2, which is associated with adenosine triphosphatases (ATPases), was a directly target of miR-140-3p in lung cancer cells. In conclusion, our data suggest miR-140-3p/ATP6AP2 axis might act as a potential therapeutic biomarker for lung cancer.

MicroRNA-140-3p inhibits proliferation, migration and invasion of lung cancer cells by targeting ATP6AP2

PubMed Central

Kong, Xiao-Mei; Zhang, Ge-Hong; Huo, Yun-Kui; Zhao, Xiao-Hong; Cao, Da-Wei; Guo, Shu-Fang; Li, Ai-Min; Zhang, Xin-Ri

2015-01-01

MicroRNAs are small noncoding RNA molecules that regulate gene expression at the post-transcriptional level. Compelling evidence reveals that there is a causative link between microRNAs deregulation and lung cancer development and metastasis. The aim of present study was to explore the function of miR-140-3p in the development and metastasis of lung cancer cell. Using real-time PCR, we detected the miR-140-3p expression of lung cancer tissues and its pared non-lung cancer tissue. Then, we evaluated the role of miR-140-3p in cell proliferation, invasion and migration using MTT, colony formation assay, Transwell invasion and Transwell migration assay in lung cancer cell lines. As a result, miR-140-3p expression level was lower in lung cancer tissues compared to adjacent normal lung cancer tissue. After miR-140-3p was upregulated in A549 or H1299 cells, cell proliferation, invasion and migration was notably attenuated. Furthermore, we identified ATP6AP2, which is associated with adenosine triphosphatases (ATPases), was a directly target of miR-140-3p in lung cancer cells. In conclusion, our data suggest miR-140-3p/ATP6AP2 axis might act as a potential therapeutic biomarker for lung cancer. PMID:26722475

Epidermal growth factor induction of front–rear polarity and migration in keratinocytes is mediated by integrin-linked kinase and ELMO2

PubMed Central

Ho, Ernest; Dagnino, Lina

2012-01-01

Epidermal growth factor (EGF) is a potent chemotactic and mitogenic factor for epidermal keratinocytes, and these properties are central for normal epidermal regeneration after injury. The involvement of mitogen-activated protein kinases as mediators of the proliferative effects of EGF is well established. However, the molecular mechanisms that mediate motogenic responses to this growth factor are not clearly understood. An obligatory step for forward cell migration is the development of front–rear polarity and formation of lamellipodia at the leading edge. We show that stimulation of epidermal keratinocytes with EGF, but not with other growth factors, induces development of front–rear polarity and directional migration through a pathway that requires integrin-linked kinase (ILK), Engulfment and Cell Motility-2 (ELMO2), integrin β1, and Rac1. Furthermore, EGF induction of front–rear polarity and chemotaxis require the tyrosine kinase activity of the EGF receptor and are mediated by complexes containing active RhoG, ELMO2, and ILK. Our findings reveal a novel link between EGF receptor stimulation, ILK-containing complexes, and activation of small Rho GTPases necessary for acquisition of front–rear polarity and forward movement. PMID:22160594

Epidermal growth factor induction of front-rear polarity and migration in keratinocytes is mediated by integrin-linked kinase and ELMO2.

PubMed

Ho, Ernest; Dagnino, Lina

2012-02-01

Epidermal growth factor (EGF) is a potent chemotactic and mitogenic factor for epidermal keratinocytes, and these properties are central for normal epidermal regeneration after injury. The involvement of mitogen-activated protein kinases as mediators of the proliferative effects of EGF is well established. However, the molecular mechanisms that mediate motogenic responses to this growth factor are not clearly understood. An obligatory step for forward cell migration is the development of front-rear polarity and formation of lamellipodia at the leading edge. We show that stimulation of epidermal keratinocytes with EGF, but not with other growth factors, induces development of front-rear polarity and directional migration through a pathway that requires integrin-linked kinase (ILK), Engulfment and Cell Motility-2 (ELMO2), integrin β1, and Rac1. Furthermore, EGF induction of front-rear polarity and chemotaxis require the tyrosine kinase activity of the EGF receptor and are mediated by complexes containing active RhoG, ELMO2, and ILK. Our findings reveal a novel link between EGF receptor stimulation, ILK-containing complexes, and activation of small Rho GTPases necessary for acquisition of front-rear polarity and forward movement.

Higher Education for Palestinian Muslim Female Students in Israel and Jordan: Migration and Identity Formation

ERIC Educational Resources Information Center

Arar, Khalid; Masry-Harzalla, Asmahan; Haj-Yehia, Kussai

2013-01-01

The article investigates the migration of Palestinian Muslim women, citizens of Israel, to the Hebrew University in Jerusalem or to Jordanian universities for academic studies, and the influence of this migration on their norms, behavior and identity. Narrative interviews were conducted with Palestinian Muslim women graduates: eight from the…

Transnational nurse migration: future directions for medical anthropological research.

PubMed

Prescott, Megan; Nichter, Mark

2014-04-01

Transnational nurse migration is a serious global health issue in which inequitably distributed shortages hinder health and development goals. This article selectively reviews the literature on nurse migration that has emerged from nursing, health planning, and the social sciences and offers productive directions for future anthropological research. The literature on global nurse migration has largely focused on push/pull economic logic and the concept of brain drain to understand the causes and effects of nurse migration. These concepts obscure political-economic, historical, and cultural factors that pattern nurse migration and influence the complex effects of nurse migration. Global nurse care chain analysis helps illuminate the numerous nodes in the production and migration of nurses, and management of this transnational process. Examples are provided from the Philippines and India to illustrate ways in which this analysis may be deepened, refined and rendered more critical by anthropological research. Copyright © 2014 Elsevier Ltd. All rights reserved.

Interfacial structures and energetics of the strengthening precipitate phase in creep-resistant Mg-Nd-based alloys.

PubMed

Choudhuri, D; Banerjee, R; Srinivasan, S G

2017-01-17

The extraordinary creep-resistance of Mg-Nd-based alloys can be correlated to the formation of nanoscale-platelets of β 1 -Mg 3 Nd precipitates, that grow along 〈110〉 Mg in bulk hcp-Mg and on dislocation lines. The growth kinetics of β 1 is sluggish even at high temperatures, and presumably occurs via vacancy migration. However, the rationale for the high-temperature stability of precipitate-matrix interfaces and observed growth direction is unknown, and may likely be related to the interfacial structure and excess energy. Therefore, we study two interfaces- {112} β1 /{100} Mg and {111} β1 /{110} Mg - that are commensurate with β 1 /hcp-Mg orientation relationship via first principles calculations. We find that β 1 acquires plate-like morphology to reduce small lattice strain via the formation of energetically favorable {112} β1 /{100} Mg interfaces, and predict that β 1 grows along 〈110〉 Mg on dislocation lines due to the migration of metastable {111} β1 /{110} Mg . Furthermore, electronic charge distribution of the two interfaces studied here indicated that interfacial-energy of coherent precipitates is sensitive to the population of distorted lattice sites, and their spatial extent in the vicinity of interfaces. Our results have implications for alloy design as they suggest that formation of β 1 -like precipitates in the hcp-Mg matrix will require well-bonded coherent interface along precipitate broad-faces, while simultaneously destabilizing other interfaces.

Interfacial structures and energetics of the strengthening precipitate phase in creep-resistant Mg-Nd-based alloys

PubMed Central

Choudhuri, D.; Banerjee, R.; Srinivasan, S. G.

2017-01-01

The extraordinary creep-resistance of Mg-Nd-based alloys can be correlated to the formation of nanoscale-platelets of β1-Mg3Nd precipitates, that grow along 〈110〉Mg in bulk hcp-Mg and on dislocation lines. The growth kinetics of β1 is sluggish even at high temperatures, and presumably occurs via vacancy migration. However, the rationale for the high-temperature stability of precipitate-matrix interfaces and observed growth direction is unknown, and may likely be related to the interfacial structure and excess energy. Therefore, we study two interfaces– {112}β1/{100}Mg and {111}β1/{110}Mg– that are commensurate with β1/hcp-Mg orientation relationship via first principles calculations. We find that β1 acquires plate-like morphology to reduce small lattice strain via the formation of energetically favorable {112}β1/{100}Mg interfaces, and predict that β1 grows along 〈110〉Mg on dislocation lines due to the migration of metastable {111}β1/{110}Mg. Furthermore, electronic charge distribution of the two interfaces studied here indicated that interfacial-energy of coherent precipitates is sensitive to the population of distorted lattice sites, and their spatial extent in the vicinity of interfaces. Our results have implications for alloy design as they suggest that formation of β1-like precipitates in the hcp-Mg matrix will require well-bonded coherent interface along precipitate broad-faces, while simultaneously destabilizing other interfaces. PMID:28094302

A characterization of autumn nocturnal migration detected by weather surveillance radars in the northeastern USA.

PubMed

Farnsworth, Andrew; Van DOREN, Benjamin M; Hochachka, Wesley M; Sheldon, Daniel; Winner, Kevin; Irvine, Jed; Geevarghese, Jeffrey; Kelling, Steve

2016-04-01

Billions of birds migrate at night over North America each year. However, few studies have described the phenology of these movements, such as magnitudes, directions, and speeds, for more than one migration season and at regional scales. In this study, we characterize density, direction, and speed of nocturnally migrating birds using data from 13 weather surveillance radars in the autumns of 2010 and 2011 in the northeastern USA. After screening radar data to remove precipitation, we applied a recently developed algorithm for characterizing velocity profiles with previously developed methods to document bird migration. Many hourly radar scans contained windborne "contamination," and these scans also exhibited generally low overall reflectivities. Hourly scans dominated by birds showed nightly and seasonal patterns that differed markedly from those of low reflectivity scans. Bird migration occurred during many nights, but a smaller number of nights with large movements of birds defined regional nocturnal migration. Densities varied by date, time, and location but peaked in the second and third deciles of night during the autumn period when the most birds were migrating. Migration track (the direction to which birds moved) shifted within nights from south-southwesterly to southwesterly during the seasonal migration peaks; this shift was not consistent with a similar shift in wind direction. Migration speeds varied within nights, although not closely with wind speed. Airspeeds increased during the night; groundspeeds were highest between the second and third deciles of night, when the greatest density of birds was migrating. Airspeeds and groundspeeds increased during the fall season, although groundspeeds fluctuated considerably with prevailing winds. Significant positive correlations characterized relationships among bird densities at southern coastal radar stations and northern inland radar stations. The quantitative descriptions of broadscale nocturnal migration patterns presented here will be essential for biological and conservation applications. These descriptions help to define migration phenology in time and space, fill knowledge gaps in avian annual cycles, and are useful for monitoring long-term population trends of migrants. Furthermore, these descriptions will aid in assessing potential risks to migrants, particularly from structures with which birds collide and artificial lighting that disorients migrants.

Constraining the primordial orbits of the terrestrial planets

NASA Astrophysics Data System (ADS)

Brasser, R.; Walsh, K. J.; Nesvorný, D.

2013-08-01

Evidence in the Solar system suggests that the giant planets underwent an epoch of radial migration that was very rapid, with an e-folding time-scale shorter than 1 Myr. It is probable that the cause of this migration was that the giant planets experienced an orbital instability that caused them to encounter each other, resulting in radial migration. A promising and heavily studied way to accomplish such a fast migration is for Jupiter to have scattered one of the ice giants outwards; this event has been called the `jumping Jupiter' scenario. Several works suggest that this dynamical instability occurred `late', long after all the planets had formed and the solar nebula had dissipated. Assuming that the terrestrial planets had already formed, then their orbits would have been affected by the migration of the giant planets as many powerful resonances would sweep through the terrestrial planet region. This raises two questions. First, what is the expected increase in dynamical excitement of the terrestrial planet orbits caused by late and very fast giant planet migration? And secondly, assuming that the migration occurred late, can we use this migration of the giant planets to obtain information on the primordial orbits of the terrestrial planets? In this work, we attempt to answer both of these questions using numerical simulations. We directly model a large number of terrestrial planet systems and their response to the smooth migration of Jupiter and Saturn, and also two jumping Jupiter simulations. We study the total dynamical excitement of the terrestrial planet system with the angular momentum deficit (AMD) value, including the way it is shared among the planets. We conclude that to reproduce the current AMD with a reasonable probability (˜20 per cent) after late rapid giant planet migration and a favourable jumping Jupiter evolution, the primordial AMD should have been lower than ˜70 per cent of the current value, but higher than 10 per cent. We find that a late giant planet migration scenario that initially had five giant planets rather than four had a higher probability of satisfying the orbital constraints of the terrestrial planets. Assuming late migration, we predict that Mars was initially on an eccentric and inclined orbit while the orbits of Mercury, Venus and Earth were more circular and coplanar. The lower primordial dynamical excitement and the peculiar partitioning between planets impose new constraints for terrestrial planet formation simulations.

Newly designed "pieced" stent in a rabbit model of benign esophageal stricture.

PubMed

Liu, Jin; Shang, Liang; Liu, Ji-Yong; Qin, Cheng-Yong

2015-07-28

To investigate a newly designed stent and its dilatation effect in a rabbit model of benign esophageal stricture. Thirty-four New Zealand white rabbits underwent a corrosive injury in the middle esophagus for esophageal stricture formation. Thirty rabbits with a successful formation of esophageal strictures were randomly allocated into two groups. The control group (n = 15) was implanted with a conventional stent, and the study group (n = 15) was implanted with a detachable "pieced" stent. The study stent (30 mm in length, 10 mm in diameter) was composed of three covered metallic pieces connected by surgical suture lines. The stent was collapsed by pulling the suture lines out of the mesh. Two weeks after stricture formation, endoscopic placement of a conventional stent or the new stent was performed. Endoscopic extraction was carried out four weeks later. The extraction rate, ease of extraction, migration, complications, and survival were evaluated. Stent migration occurred in 3/15 (20%) animals in the control group and 2/15 (13%) animals in the study group; the difference between the two groups was not statistically significant. At the end of four weeks, the remaining stents were successfully extracted with the endoscope in 100% (11/11) of the animals in the study group, and 60% (6/10) of the animals in the control group; this difference was statistically significant (P < 0.05). There was no difference in the mean number of follow-up days between the control and study groups (25.33 vs 25.85). Minor bleeding was reported in five cases in the study group and four in the control group. There were no severe complications directly associated with stent implantation or extraction in either of the two groups. In this experimental protocol of benign esophageal strictures, the novel "pieced" stent demonstrated a superior removal rate with a similar migration rate compared to a conventional stent.

Schwann cells induce cancer cell dispersion and invasion

PubMed Central

Deborde, Sylvie; Lyubchik, Anna; Zhou, Yi; He, Shizhi; McNamara, William F.; Chernichenko, Natalya; Lee, Sei-Young; Barajas, Fernando; Chen, Chun-Hao; Bakst, Richard L.; Vakiani, Efsevia; He, Shuangba; Hall, Alan; Wong, Richard J.

2016-01-01

Nerves enable cancer progression, as cancers have been shown to extend along nerves through the process of perineural invasion, which carries a poor prognosis. Furthermore, the innervation of some cancers promotes growth and metastases. It remains unclear, however, how nerves mechanistically contribute to cancer progression. Here, we demonstrated that Schwann cells promote cancer invasion through direct cancer cell contact. Histological evaluation of murine and human cancer specimens with perineural invasion uncovered a subpopulation of Schwann cells that associates with cancer cells. Coculture of cancer cells with dorsal root ganglion extracts revealed that Schwann cells direct cancer cells to migrate toward nerves and promote invasion in a contact-dependent manner. Upon contact, Schwann cells induced the formation of cancer cell protrusions in their direction and intercalated between the cancer cells, leading to cancer cell dispersion. The formation of these processes was dependent on Schwann cell expression of neural cell adhesion molecule 1 (NCAM1) and ultimately promoted perineural invasion. Moreover, NCAM1-deficient mice showed decreased neural invasion and less paralysis. Such Schwann cell behavior reflects normal Schwann cell programs that are typically activated in nerve repair but are instead exploited by cancer cells to promote perineural invasion and cancer progression. PMID:26999607

Formation and evolution of a drainage network during the Pleistocene through a process of homoclinal shifting initiated by headward erosion.

NASA Astrophysics Data System (ADS)

Castelltort, F. Xavier; Carles Balasch, J.; Cirés, Jordi; Colombo, Ferran

2017-04-01

A homoclinal shifting process in NE of the Ebro basin, NE Iberian Peninsula, reorganized an old flow network into a new one. This process was initiated by the reactivation of a major normal fault (Amer Fault). An anaclinal stream, flowing to the hanging wall block, incised in the fault-line scarp, accessing by headward erosion the less resistant Paleogene units. The result was the formation of a sequence of strike valleys. The first valleys are situated in a more elevated topographical position than the valleys formed later. The last and the most important valley is La Plana de Vic, which is being emptied by differential erosion in front of the resistant base layer. The study of the lateral migration of a drainage basin since its initial stages has allowed the recognition of the layout of a drainage network and its model of evolution. The new drainage network includes three different subsystems. The main subsystem consists of stream courses flowing along the strike valley. While the other two subsystems flow into the main or can flow directly to the basin sink. These are the anaclinal subsystem, which drains the scarp face of the asymmetric valley, and the cataclinal subsystem, which drains the cuesta. The process of homoclinal shifting makes the strike streams migrate laterally and dip in the less resistant unit. This migration implies the reorganization of the other two tributary subsystems. The sequence of reorganizations may be preserved on the resistant bedrock of the cuesta. This allows the reconstruction of the route of the headward erosion of the initial anaclinal stream course through remnants of ancient strike streams flowing into former basin sinks, and its cataclinal tributaries draining the cuesta. In the case study of La Plana de Vic the migration route of the basin sink can be reconstructed from its initial position, Early Pleistocene, until present day. Besides, reorganization of the cataclinal network can also be recognized. During the lateral migration three incisions were made in a large anticlinal structure in the north (Bellmunt Anticline) and one incision was made in a crystalline massif (Montseny) in the south. The last of the incisions into the Bellmunt Anticline captured by headward erosion an older drainage network with headwaters in the axial Pyrenees. The result of the homoclinal shifting process was the capture of older drainage basins and the formation of the current drainage basin of the river Ter.

Effect of azathioprine on Na(+)/H(+) exchanger activity in dendritic cells.

PubMed

Bhandaru, Madhuri; Pasham, Venkanna; Yang, Wenting; Bobbala, Diwakar; Rotte, Anand; Lang, Florian

2012-01-01

Azathioprine is a powerful immunosuppressive drug, which is partially effective by interfering with the maturation and function of dendritic cells (DCs), antigen-presenting cells linking innate and adaptive immunity. DCs are stimulated by bacterial lipopolysaccharides (LPS), which trigger the formation of reactive oxygen species (ROS), paralleled by activation of the Na(+)/H(+) exchanger. The carrier is involved in the regulation of cytosolic pH, cell volume and migration. The present study explored whether azathioprine influences Na(+)/H(+) exchanger activity in DCs. DCs were isolated from murine bone marrow, cytosolic pH (pH(i)) was estimated utilizing 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF-AM) fluorescence, Na(+)/H(+) exchanger activity from the Na(+)-dependent realkalinization following an ammonium pulse, cell volume from forward scatter in FACS analysis, ROS production from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, TNFα release utilizing ELISA, and migration utilizing transwell migration assays. Exposure of DCs to lipopolysaccharide (LPS, 1 μg/ml) led to a transient increase of Na(+)/H(+) exchanger activity, an effect paralleled by ROS formation, increased cell volume, TNFα production and stimulated migration. Azathioprine (10 μM) did not significantly alter the Na(+)/H(+) exchanger activity, cell volume and ROS formation prior to LPS exposure but significantly blunted the LPS-induced stimulation of Na(+)/H(+) exchanger activity, ROS formation, cell swelling, TNFα production and cell migration. In conclusion, azathioprine interferes with the activation of dendritic cell Na(+)/H(+) exchanger by bacterial lipopolysaccharides, an effect likely participating in the anti-inflammatory action of the drug. Copyright © 2012 S. Karger AG, Basel.

40 CFR 146.6 - Area of review.

Code of Federal Regulations, 2014 CFR

2014-07-01

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

40 CFR 146.6 - Area of review.

Code of Federal Regulations, 2013 CFR

2013-07-01

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

40 CFR 146.6 - Area of review.

Code of Federal Regulations, 2011 CFR

2011-07-01

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

Transformation Stasis Phenomenon of Bainite Formation in Low-Carbon, Multicomponent Alloyed Steel

NASA Astrophysics Data System (ADS)

Lan, Liangyun; Kong, Xiangwei

2017-11-01

The transformation stasis phenomenon of bainite formation in low-carbon steel was detected using a high-resolution dilatometer. The phenomenon occurred at different stages for different isothermal temperatures. In combination with microstructural observation, the calculated overall activation energy of transformation and interface migration velocity shed new light on the cause of formation of the stasis phenomenon. The temporary stasis formed at the initial stage of phase transformation for high isothermal temperature was attributed to the drag effect of substitutional atoms, which leads to low-interface migration velocity and large overall activation energy.

Assessment of Perceived Stress Related to Migration and Acculturation in Patients with Psychiatric Disorders (MIGSTR10)-Development, Reliability, and Dimensionality of a Brief Instrument.

PubMed

Müller, Matthias J; Zink, Sabrina; Koch, Eckhardt

2017-09-01

Assessment of stressors related to migration and acculturation in patients with psychiatric disorder and migration background could help improve culturally sensitive concepts of psychiatry and psychotherapy for diagnosis and treatment. The present overview delineates development and psychometric properties of an instrument (MIGSTR10) for assessment of stressors related to migration and acculturation, particularly for application in patients with psychiatric disorders. Ten migration-related stressors were derived from a qualitative content analysis of case histories of patients with psychiatric disorder and migration background and put into a suitable interview and questionnaire format (MIGSTR10; 10 questions, answer format: categorical yes/no, and dimensional 0-10) for self-assessment and observer ratings in several languages. Reliability (interrater agreement, internal consistency) and dimensionality (multi-dimensional scaling, MDS) were investigated in n = 235 patients with migration background and n = 612 indigenous German patients. Interrater agreement (ICC) for MIGSTR10 single items and sum scores (categorical and dimensional) was sufficiently high (≥.58); internal consistency (Cronbach's α) reached medium to high values (.56-.73). MDS revealed a two-dimensional solution with two item clusters (A: communication, migration history, forced marriage, homesickness, discrimination, other stressors; B: family conflicts, loss of status, feelings of shame, guilt feelings). The MIGSTR10 is a rationally developed, straightforward 10-item screening instrument with satisfactory psychometric properties for the assessment of individual and specific stressors related to migration and acculturation.

Texture sensing of cytoskeletal dynamics in cell migration

NASA Astrophysics Data System (ADS)

Das, Satarupa; Lee, Rachel; Hourwitz, Matthew J.; Sun, Xiaoyu; Parent, Carole; Fourkas, John T.; Losert, Wolfgang

Migrating cells can be directed towards a target by gradients in properties such as chemical concentration or mechanical properties of the surrounding microenvironment. In previous studies we have shown that micro/nanotopographical features on scales comparable to those of natural collagen fibers can guide fast migrating amoeboid cells by aligning actin polymerization waves to such nanostructures. We find that actin microfilaments and microtubules are aligned along the nanoridge topographies, modulating overall cell polarity and directional migration in epithelial cells. This work shows that topographic features on a biologically relevant length scale can modulate migration outcomes by affecting the texture sensing property of the cytoskeleton.

Formation and Migration of Trans-Neptunian Objects

NASA Technical Reports Server (NTRS)

Ipatov, S. I.; Oegerle, William (Technical Monitor)

2002-01-01

We consider that trans-Neptunian objects (TNOs) with diameter d greater than 100 kilometers moving now in not very eccentric orbits could be formed directly by the compression of large rarefied dust condensations (with a greater than 30 AU), but not by the accretion of smaller solid planetesimals. Probably, some planetesimals with d approximately 100- 1000 kilometers in the feeding zone of the giant planets and even large main-belt asteroids also could be formed directly by such compression. Some smaller objects (TNOs, planetesimals, asteroids) could be debris of larger objects, and other such objects could be formed directly by compression of condensations. A small portion of planetesimals from the feeding zone of the giant planets that entered into the trans-Neptunian region could left in eccentrical orbits beyond Neptune and became so called "scattered objects". Our computer runs in which gravitational interactions of bodies were taken into account with the use of the spheres method, showed that the embryos of Uranus and Neptune could increase their semimajor axes from less than 10 AU to their present values, moving permanently in orbits with small eccentricities, due to gravitational interactions with the migrating planetesimals. Later on, Thommes et al. considered a similar model using direct numerical integration. The total amount of water delivered to the Earth during the formation of the giant, planets was about the mass of water in the Earth oceans. The end of such bombardment could be caused mainly by the planetesimals that became scattered objects. For the present mass of the trans-Neptunian belt, the collisional lifetime of 1-kilometer TNO is about the age of the Solar system, but only a small portion (less than 1%) of 100-km TNOs could be destroyed during this age. The probability of destruction of a typical TNO (with 30 less than a,less than 50 AU) by scattered objects can be of the same order of magnitude as that by typical TNOs. TNOs could be even more often destroyed during planet formation than during last 4 Gyr. The analysis of the results of the orbital evolution of Jupiter-crossing objects (JCOs) and TNOs showed that, in principle, the trans-Neptunian belt can provide up to 100% of Earth-crossing objects, but, of course, some of them came from the main asteroid belt. Most of the collisions of former JCOs with the Earth were from orbits with aphelia inside Jupiter's orbit and belonged to a small portion of objects which moved in such orbits for a long time. About 1 of 300 JCOs collided with the Sun. The ratio of the total mass of icy planetesimals that migrated from the feeding zone of the giant planets and collided with the planet to the mass of this planet was greater (by a factor of 3 in our runs) for Mars than that for Earth and Venus.

Inhibition of connective tissue growth factor (CTGF/CCN2) in gallbladder cancer cells leads to decreased growth in vitro

PubMed Central

Garcia, Patricia; Leal, Pamela; Ili, Carmen; Brebi, Priscilla; Alvarez, Hector; Roa, Juan C

2013-01-01

Gallbladder cancer (GBC) is an aggressive neoplasm associated with late diagnosis, unsatisfactory treatment and poor prognosis. Previous work showed that connective tissue growth factor (CTGF) expression is increased in this malignancy. This matricellular protein plays an important role in various cellular processes and its involvement in the tumorigenesis of several human cancers has been demonstrated. However, the precise function of CTGF expression in cancer cells is yet to be determined. The aim of this study was to evaluate the CTGF expression in gallbladder cancer cell lines, and its effect on cell viability, colony formation and in vitro cell migration. CTGF expression was evaluated in seven GBC cell lines by Western blot assay. Endogenous CTGF expression was downregulated by lentiviral shRNA directed against CTGF mRNA in G-415 cells, and the effects on cell viability, anchorage-independent growth and migration was assessed by comparing them to scrambled vector-transfected cells. Knockdown of CTGF resulted in significant reduction in cell viability, colony formation and anchorage-independent growth (P < 0.05). An increased p27 expression was observed in G-415 cells with loss of CTGF function. Our results suggest that high expression of this protein in gallbladder cancer may confer a growth advantage for neoplastic cells. PMID:23593935

Genetics Home Reference: 3MC syndrome

MedlinePlus

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

The formation of giant planets in wide orbits by photoevaporation-synchronized migration

NASA Astrophysics Data System (ADS)

Guilera, O. M.; Miller Bertolami, M. M.; Ronco, M. P.

2017-10-01

The discovery of giant planets in wide orbits represents a major challenge for planet formation theory. In the standard core accretion paradigm, planets are expected to form at radial distances ≲20 au in order to form massive cores (with masses ≳10 M⊕) able to trigger the gaseous runaway growth before the dissipation of the disc. This has encouraged authors to find modifications of the standard scenario as well as alternative theories like the formation of planets by gravitational instabilities in the disc to explain the existence of giant planets in wide orbits. However, there is not yet consensus on how these systems are formed. In this Letter, we present a new natural mechanism for the formation of giant planets in wide orbits within the core accretion paradigm. If photoevaporation is considered, after a few Myr of viscous evolution a gap in the gaseous disc is opened. We found that, under particular circumstances planet migration becomes synchronized with the evolution of the gap, which results in an efficient outward planet migration. This mechanism is found to allow the formation of giant planets with masses Mp ≲ 1MJup in wide stable orbits as large as ∼130 au from the central star.

Antibody neutralization of cell-surface gC1qR/HABP1/SF2-p32 prevents lamellipodia formation and tumorigenesis

PubMed Central

Kim, Beom-Chan; Hwang, Hyun-Jung; An, Hyoung-Tae; Lee, Hyun; Park, Jun-Sub; Hong, Jin; Ko, Jesang; Kim, Chungho; Lee, Jae-Seon; Ko, Young-Gyu

2016-01-01

We previously demonstrated that cell-surface gC1qR is a key regulator of lamellipodia formation and cancer metastasis. Here, we screened a monoclonal mouse antibody against gC1qR to prevent cell migration by neutralizing cell-surface gC1qR. The anti-gC1qR antibody prevented growth factor-stimulated lamellipodia formation, cell migration and focal adhesion kinase activation by inactivating receptor tyrosine kinases (RTKs) in various cancer cells such as A549, MDA-MB-231, MCF7 and HeLa cells. The antibody neutralization of cell-surface gC1qR also inhibited angiogenesis because the anti-gC1qR antibody prevented growth factor-stimulated RTK activation, lamellipodia formation, cell migration and tube formation in HUVEC. In addition, we found that A549 tumorigenesis was reduced in a xenograft mouse model by following the administration of the anti-gC1qR antibody. With these data, we can conclude that the antibody neutralization of cell-surface gC1qR could be a good therapeutic strategy for cancer treatment. PMID:27363031

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

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.

Stochastic Modeling of CO2 Migrations and Chemical Reactions in Deep Saline Formations

NASA Astrophysics Data System (ADS)

Ni, C.; Lee, I.; Lin, C.

2013-12-01

Carbon capture and storage (CCS) has been recognized the feasible technology that can significant reduce the anthropogenic CO2 emissions from large point sources. The CO2 injection in geological formations is one of the options to permanently store the captured CO2. Based on this concept a large number of target formations have been identified and intensively investigated with different types of techniques such as the hydrogeophysical experiments or numerical simulations. The numerical simulations of CO2 migrations in saline formations recently gather much attention because a number of models are available for this purpose and there are potential sites existing in many countries. The lower part of Cholan Formation (CF) near Changhua Coastal Industrial Park (CCIP) in west central Taiwan was identified the largest potential site for CO2 sequestration. The top elevations of the KF in this area varies from 1300 to 1700m below the sea level. Laboratory experiment showed that the permeability of CF is 10-14 to 10-12 m2. Over the years the offshore seismic survey and limited onshore borehole logs have provided information for the simulation of CO2 migration in the CF although the original investigations might not focus on the purpose of CO2 sequestration. In this study we modify the TOUGHREACT model to consider the small-scale heterogeneity in target formation and the cap rock of upper CF. A Monte Carlo Simulation (MCS) approach based on the TOUGHREACT model is employed to quantify the effect of small-scale heterogeneity on the CO2 migrations and hydrochemical reactions in the CF. We assume that the small-scale variability of permeability in KF can be described with a known Gaussian distribution. Therefore, the Gaussian type random field generator such as Sequential Gaussian Simulation (SGSIM) in Geostatistical Software Library (GSLIB) can be used to provide the random permeability realizations for the MCS. A variety of statistical parameters such as the variances and correlation lengths in a Gaussian covariance model are varied in the MCS and the uncertainty of the CO2 and other chemical concentrations are evaluated based on 144 random realizations. In this study a constant injection rate of100Mt/year supercritical CO2 is applied in the bottom of CF. The continuous injection time is 20 years and the uncertainty results are evaluated at 100 years. By comparing with the case without small-scale variability simulation results show that the CO2 plume sizes in the horizontal direction increase from tens of meters to hundreds of meters when the variances of small-scale variability are varied from 1.0 to 4.0. The changes of correlation lengths (i.e., from 100m, 200m, to 400m) show small contribution on the size increases of CO2 plumes. Other uncertainties of chemical concentrations show behaviors similar to the CO2 plume patterns.

The data life cycle applied to our own data.

PubMed

Goben, Abigail; Raszewski, Rebecca

2015-01-01

Increased demand for data-driven decision making is driving the need for librarians to be facile with the data life cycle. This case study follows the migration of reference desk statistics from handwritten to digital format. This shift presented two opportunities: first, the availability of a nonsensitive data set to improve the librarians' understanding of data-management and statistical analysis skills, and second, the use of analytics to directly inform staffing decisions and departmental strategic goals. By working through each step of the data life cycle, library faculty explored data gathering, storage, sharing, and analysis questions.

Testing short-range migration of microbial methane as a hydrate formation mechanism: Results from Andaman Sea and Kumano Basin drill sites and global implications

NASA Astrophysics Data System (ADS)

Malinverno, Alberto; Goldberg, David S.

2015-07-01

Methane gas hydrates in marine sediments often concentrate in coarse-grained layers surrounded by fine-grained marine muds that are hydrate-free. Methane in these hydrate deposits is typically microbial, and must have migrated from its source as the coarse-grained sediments contain little or no organic matter. In "long-range" migration, fluid flow through permeable layers transports methane from deeper sources into the gas hydrate stability zone (GHSZ). In "short-range" migration, microbial methane is generated within the GHSZ in fine-grained sediments, where small pore sizes inhibit hydrate formation. Dissolved methane can then diffuse into adjacent sand layers, where pore size does not restrict hydrate formation and hydrates can accumulate. Short-range migration has been used to explain hydrate accumulations in sand layers observed in drill sites on the northern Cascadia margin and in the Gulf of Mexico. Here we test the feasibility of short-range migration in two additional locations, where gas hydrates have been found in coarse-grained volcanic ash layers (Site NGHP-01-17, Andaman Sea, Indian Ocean) and turbidite sand beds (Site IODP-C0002, Kumano forearc basin, Nankai Trough, western Pacific). We apply reaction-transport modeling to calculate dissolved methane concentration and gas hydrate amounts resulting from microbial methane generated within the GHSZ. Model results show that short-range migration of microbial methane can explain the overall amounts of methane hydrate observed at the two sites. Short-range migration has been shown to be feasible in diverse margin environments and is likely to be a widespread methane transport mechanism in gas hydrate systems. It only requires a small amount of organic carbon and sediment sequences consisting of thin coarse-grained layers that can concentrate microbial methane generated within thick fine-grained sediment beds; these conditions are common along continental margins around the globe.

CDYL Deficiency Disrupts Neuronal Migration and Increases Susceptibility to Epilepsy.

PubMed

Qin, Rui; Cao, Shuai; Lyu, Tianjie; Qi, Cai; Zhang, Weiguang; Wang, Yun

2017-01-10

During brain development, the correct migration of newborn neurons is one of the determinants of circuit formation, and neuronal migration defects may lead to neurological and psychiatric disorders. The molecular mechanisms underlying neuronal migration and related disorders are poorly understood. Here, we report that Chromodomain Y-like (CDYL) is critical for neuronal migration in mice. Knocking down CDYL caused neuronal migration defects and disrupted both mobility and multipolar-to-bipolar transition of migrating neurons. We find that CDYL regulates neuronal migration by transcriptionally repressing RhoA. In addition, CDYL deficiency increased the excitability of cortical pyramidal neurons and the susceptibility of mice to convulsant-induced seizures. These results demonstrate that CDYL is a regulator of neuronal migration and shed light on the pathogenesis of seizure-related neurodevelopmental disorders. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Cannabinoids inhibit angiogenic capacities of endothelial cells via release of tissue inhibitor of matrix metalloproteinases-1 from lung cancer cells.

PubMed

Ramer, Robert; Fischer, Sascha; Haustein, Maria; Manda, Katrin; Hinz, Burkhard

2014-09-15

Cannabinoids inhibit tumor neovascularization as part of their tumorregressive action. However, the underlying mechanism is still under debate. In the present study the impact of cannabinoids on potential tumor-to-endothelial cell communication conferring anti-angiogenesis was studied. Cellular behavior of human umbilical vein endothelial cells (HUVEC) associated with angiogenesis was evaluated by Boyden chamber, two-dimensional tube formation and fibrin bead assay, with the latter assessing three-dimensional sprout formation. Viability was quantified by the WST-1 test. Conditioned media (CM) from A549 lung cancer cells treated with cannabidiol, Δ(9)-tetrahydrocannabinol, R(+)-methanandamide or the CB2 agonist JWH-133 elicited decreased migration as well as tube and sprout formation of HUVEC as compared to CM of vehicle-treated cancer cells. Inhibition of sprout formation was further confirmed for cannabinoid-treated A549 cells co-cultured with HUVEC. Using antagonists to cannabinoid-activated receptors the antimigratory action was shown to be mediated via cannabinoid receptors or transient receptor potential vanilloid 1. SiRNA approaches revealed a cannabinoid-induced expression of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) as well as its upstream trigger, the intercellular adhesion molecule-1, to be causally linked to the observed decrease of HUVEC migration. Comparable anti-angiogenic effects were not detected following direct exposure of HUVEC to cannabinoids, but occurred after addition of recombinant TIMP-1 to HUVEC. Finally, antimigratory effects were confirmed for CM of two other cannabinoid-treated lung cancer cell lines (H460 and H358). Collectively, our data suggest a pivotal role of the anti-angiogenic factor TIMP-1 in intercellular tumor-endothelial cell communication resulting in anti-angiogenic features of endothelial cells. Copyright © 2014 Elsevier Inc. All rights reserved.

In-depth understanding of core-shell nanoarchitecture evolution of g-C3N4@C, N co-doped anatase/rutile: Efficient charge separation and enhanced visible-light photocatalytic performance

NASA Astrophysics Data System (ADS)

Mohamed, Mohamad Azuwa; Jaafar, Juhana; M. Zain, M. F.; Minggu, Lorna Jeffery; Kassim, Mohammad B.; Rosmi, Mohamad Saufi; Alias, Nur Hashimah; Mohamad Nor, Nor Azureen; W. Salleh, W. N.; Othman, Mohd Hafiz Dzarfan

2018-04-01

Herein, we demonstrated the simultaneous formation of multi-component heterojunction consisting graphitic carbon nitride (g-C3N4) and C, N co-doped anatase/rutile mixed phase by using facile sol-gel assisted heat treatment. The evolution of core-shell nanostructures heterojunction formation was elucidated by varying the temperature of heat treatment from 300 °C to 600 °C. Homogeneous heterojunction formation between g-C3N4 and anatase/rutile mixed phase was observed in gT400 with C and N doping into TiO2 lattice by O substitution. The core-shell nanoarchitectures between g-C3N4 as shell, and anatase/rutile mixed phase as core with C and N atoms are doped at the interstitial positions of TiO2 lattice was observed in gT500. The result indicated that core-shell nanoarchitectures photocatalyst (gT500) prepared at 500 ◦C exhibited the highest photocatalytic activity in the degradation of methyl orange under visible light irradiation. Meanwhile, the possible mechanisms of charge generation, migration, action species and reaction that probably occur at the gT500 sample were also proposed. The photodegradation results of gT500 correlated completely with the results of the PEC and photoluminescence analysis, which directly evidenced improved charge separation and migration as the crucial parameters governing photocatalysis. It is worthy to note that, the simultaneous formation of multicomponent heterojunction with core-shell structure provided an enormous impact in designing highly active photocatalyst with superior interfacial charge transfer.

Protoplanetary Disks and Planet Formation a Computational Perspective

NASA Astrophysics Data System (ADS)

Backus, Isaac

In this thesis I present my research on the early stages of planet formation. Using advanced computational modeling techniques, I study global gas and gravitational dynamics in proto- planetary disks (PPDs) on length scales from the radius of Jupiter to the size of the solar system. In that environment, I investigate the formation of gas giants and the migration, enhancement, and distribution of small solids--the precursors to planetesimals and gas giant cores. I examine numerical techniques used in planet formation and PPD modeling, especially methods for generating initial conditions (ICs) in these unstable, chaotic systems. Disk simulation outcomes may depend strongly on ICs, which may explain results in the literature. I present the largest suite of high resolution PPD simulations to-date and argue that direct fragmentations of PPDs around M-Dwarfs is a plausible path to rapidly forming gas giants. I implement dust physics to track the migration of centimeter and smaller dust grains in very high resolution PPD simulations. While current dust methods are slow, with strict resolution and/or time-stepping requirements, and have some serious numerical issues, we can still demonstrate that dust does not concentrate at the pressure maxima of spiral arms, an indication that spiral features observed in the dust component are at least as well resolved in the gas. Additionally, coherent spiral arms do not limit dust settling. We suggest a novel mechanism for disk fragmentation at large radii driven by dust accretion from the surrounding nebula. We also investigate self induced dust traps, a mechanism which may help explain the growth of solids beyond meter sizes. We argue that current apparent demonstrations of this mechanism may be due to numerical artifacts and require further investigation.

Migration and invasion induced by linoleic acid are mediated through fascin in MDA-MB-231 breast cancer cells.

PubMed

Gonzalez-Reyes, Christian; Marcial-Medina, Cleofas; Cervantes-Anaya, Nancy; Cortes-Reynosa, Pedro; Salazar, Eduardo Perez

2018-06-01

Epidemiological studies strongly suggest an association between high levels of dietary fat intake and an increased risk of developing breast cancer. Linoleic acid (LA) is an essential omega-6 PUFA and the major fatty acid in occidental diets. In breast cancer cells, LA induces expression of plasminogen activator inhibitor-1, proliferation, migration, and invasion. Fascin is an actin crosslinker globular protein that generates actin bundles made of parallel actin filaments, which mediate formation and stability of microspikes, stress fibers, membrane ruffles, and filopodia. However, the role of fascin in migration and invasion induced by LA in MDA-MB-231 breast cancer cells remains to be studied. We demonstrate here that LA induces an increase of fascin expression in MDA-MB-231 and MCF12A mammary epithelial cells. Particularly, LA induces the formation of filopodia and lamellipodia and the localization of fascin in these actin structures in MDA-MB-231 breast cancer cells. However, LA only induces formation of microspikes and the localization of fascin in these actin structures in mammary non-tumorigenic epithelial cells MCF12A. In addition, LA induces migration, invasion, and matrix metalloproteinase-9 secretion through a fascin-dependent pathway in MDA-MB-231 cells. In summary, our findings demonstrate that fascin is required for migration and invasion induced by LA in MDA-MB-231 breast cancer cells.

Shape and Displacement Fluctuations in Soft Vesicles Filled by Active Particles

PubMed Central

Paoluzzi, Matteo; Di Leonardo, Roberto; Marchetti, M. Cristina; Angelani, Luca

2016-01-01

We investigate numerically the dynamics of shape and displacement fluctuations of two-dimensional flexible vesicles filled with active particles. At low concentration most of the active particles accumulate at the boundary of the vesicle where positive particle number fluctuations are amplified by trapping, leading to the formation of pinched spots of high density, curvature and pressure. At high concentration the active particles cover the vesicle boundary almost uniformly, resulting in fairly homogeneous pressure and curvature, and nearly circular vesicle shape. The change between polarized and spherical shapes is driven by the number of active particles. The center-of-mass of the vesicle performs a persistent random walk with a long time diffusivity that is strongly enhanced for elongated active particles due to orientational correlations in their direction of propulsive motion. In our model shape-shifting induces directional sensing and the cell spontaneously migrate along the polarization direction. PMID:27678166

Grhl3 and Lmo4 play coordinate roles in epidermal migration.

PubMed

Hislop, Nikki R; Caddy, Jacinta; Ting, Stephen B; Auden, Alana; Vasudevan, Sumitha; King, Sarah L; Lindeman, Geoffrey J; Visvader, Jane E; Cunningham, John M; Jane, Stephen M

2008-09-01

In addition to its role in formation of the epidermal barrier, the mammalian transcription factor Grainy head-like 3 (Grhl3) is also essential for neural tube closure and wound repair, processes that are dependent in part on epidermal migration. Here, we demonstrate that the LIM-only domain protein, LMO4 serves as a functional partner of GRHL3 in its established roles, and define a new cooperative role for these factors in another developmental epidermal migration event, eyelid fusion. GRHL3 and LMO4 interact biochemically and genetically, with mutant mice exhibiting fully penetrant exencephaly, thoraco-lumbo-sacral spina bifida, defective skin barrier formation, and a co-incident eyes-open-at-birth (EOB) phenotype, which is not observed in the original individual null lines. The two genes are co-expressed in the surface ectoderm of the migrating eyelid root, and electron microscopy of Grhl3/Lmo4-null eyes reveals a failure in epithelial extension and a lack of peridermal clump formation at the eyelid margins. Accumulation of actin fibers is also absent in the circumference of these eyelids, and ERK1/2 phosphorylation is lost in the epidermis and eyelids of Grhl3(-/-)/Lmo4(-/-) embryos. Keratinocytes from mutant mice fail to "heal" in in vitro scratch assays, consistent with a general epidermal migratory defect that is dependent on ERK activation and actin cable formation.

The FAK–Arp2/3 interaction promotes leading edge advance and haptosensing by coupling nascent adhesions to lamellipodia actin

PubMed Central

Swaminathan, Vinay; Fischer, R. S.; Waterman, Clare M.

2016-01-01

Cell migration is initiated in response to biochemical or physical cues in the environment that promote actin-mediated lamellipodial protrusion followed by the formation of nascent integrin adhesions (NAs) within the protrusion to drive leading edge advance. Although FAK is known to be required for cell migration through effects on focal adhesions, its role in NA formation and lamellipodial dynamics is unclear. Live-cell microscopy of FAK−/− cells with expression of phosphorylation deficient or a FERM-domain mutant deficient in Arp2/3 binding revealed a requirement for FAK in promoting the dense formation, transient stabilization, and timely turnover of NA within lamellipodia to couple actin-driven protrusion to adhesion and advance of the leading edge. Phosphorylation on Y397 of FAK promotes dense NA formation but is dispensable for transient NA stabilization and leading edge advance. In contrast, transient NA stabilization and advance of the cell edge requires FAK–Arp2/3 interaction, which promotes Arp2/3 localization to NA and reduces FAK activity. Haptosensing of extracellular matrix (ECM) concentration during migration requires the interaction between FAK and Arp2/3, whereas FAK phosphorylation modulates mechanosensing of ECM stiffness during spreading. Taken together, our results show that mechanistically separable functions of FAK in NA are required for cells to distinguish distinct properties of their environment during migration. PMID:26842895

Kaempferol Suppresses Transforming Growth Factor-β1-Induced Epithelial-to-Mesenchymal Transition and Migration of A549 Lung Cancer Cells by Inhibiting Akt1-Mediated Phosphorylation of Smad3 at Threonine-179.

PubMed

Jo, Eunji; Park, Seong Ji; Choi, Yu Sun; Jeon, Woo-Kwang; Kim, Byung-Chul

2015-07-01

Kaempferol, a natural dietary flavonoid, is well known to possess chemopreventive and therapeutic anticancer efficacy; however, its antimetastatic effects have not been mechanistically studied so far in any cancer model. This study was aimed to investigate the inhibitory effect and accompanying mechanisms of kaempferol on epithelial-to-mesenchymal transition (EMT) and cell migration induced by transforming growth factor-β1 (TGF-β1). In human A549 non-small lung cancer cells, kaempferol strongly blocked the enhancement of cell migration by TGF-β1-induced EMT through recovering the loss of E-cadherin and suppressing the induction of mesenchymal markers as well as the upregulation of TGF-β1-mediated matrix metalloproteinase-2 activity. Interestingly, kaempferol reversed TGF-β1-mediated Snail induction and E-cadherin repression by weakening Smad3 binding to the Snail promoter without affecting its C-terminus phosphorylation, complex formation with Smad4, and nuclear translocation under TGF-β1 stimulation. Mechanism study revealed that the phosphorylation of Smad3 linker region induced by TGF-β1 was required for the induction of EMT and cell migration, and selective downregulation of the phosphorylation of Smad3 at Thr179 residue (not Ser204, Ser208, and Ser213) in the linker region was responsible for the inhibition by kaempferol of TGF-β1-induced EMT and cell migration. Furthermore, Akt1 was required for TGF-β1-mediated induction of EMT and cell migration and directly phosphorylated Smad3 at Thr179, and kaempferol completely abolished TGF-β1-induced Akt1 phosphorylation. In summary, kaempferol blocks TGF-β1-induced EMT and migration of lung cancer cells by inhibiting Akt1-mediated phosphorylation of Smad3 at Thr179 residue, providing the first evidence of a molecular mechanism for the anticancer effect of kaempferol. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Kaempferol Suppresses Transforming Growth Factor-β1–Induced Epithelial-to-Mesenchymal Transition and Migration of A549 Lung Cancer Cells by Inhibiting Akt1-Mediated Phosphorylation of Smad3 at Threonine-1791

PubMed Central

Jo, Eunji; Park, Seong Ji; Choi, Yu Sun; Jeon, Woo-Kwang; Kim, Byung-Chul

2015-01-01

Kaempferol, a natural dietary flavonoid, is well known to possess chemopreventive and therapeutic anticancer efficacy; however, its antimetastatic effects have not been mechanistically studied so far in any cancer model. This study was aimed to investigate the inhibitory effect and accompanying mechanisms of kaempferol on epithelial-to-mesenchymal transition (EMT) and cell migration induced by transforming growth factor-β1 (TGF-β1). In human A549 non–small lung cancer cells, kaempferol strongly blocked the enhancement of cell migration by TGF-β1–induced EMT through recovering the loss of E-cadherin and suppressing the induction of mesenchymal markers as well as the upregulation of TGF-β1–mediated matrix metalloproteinase-2 activity. Interestingly, kaempferol reversed TGF-β1–mediated Snail induction and E-cadherin repression by weakening Smad3 binding to the Snail promoter without affecting its C-terminus phosphorylation, complex formation with Smad4, and nuclear translocation under TGF-β1 stimulation. Mechanism study revealed that the phosphorylation of Smad3 linker region induced by TGF-β1 was required for the induction of EMT and cell migration, and selective downregulation of the phosphorylation of Smad3 at Thr179 residue (not Ser204, Ser208, and Ser213) in the linker region was responsible for the inhibition by kaempferol of TGF-β1–induced EMT and cell migration. Furthermore, Akt1 was required for TGF-β1–mediated induction of EMT and cell migration and directly phosphorylated Smad3 at Thr179, and kaempferol completely abolished TGF-β1–induced Akt1 phosphorylation. In summary, kaempferol blocks TGF-β1–induced EMT and migration of lung cancer cells by inhibiting Akt1-mediated phosphorylation of Smad3 at Thr179 residue, providing the first evidence of a molecular mechanism for the anticancer effect of kaempferol. PMID:26297431

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

In Vitro, Ex Vivo and In Vivo Techniques to Study Neuronal Migration in the Developing Cerebral Cortex

PubMed Central

Azzarelli, Roberta; Oleari, Roberto; Lettieri, Antonella; Andre', Valentina; Cariboni, Anna

2017-01-01

Neuronal migration is a fundamental biological process that underlies proper brain development and neuronal circuit formation. In the developing cerebral cortex, distinct neuronal populations, producing excitatory, inhibitory and modulatory neurotransmitters, are generated in different germinative areas and migrate along various routes to reach their final positions within the cortex. Different technical approaches and experimental models have been adopted to study the mechanisms regulating neuronal migration in the cortex. In this review, we will discuss the most common in vitro, ex vivo and in vivo techniques to visualize and study cortical neuronal migration. PMID:28448448

Collisions of deformable cells lead to collective migration

NASA Astrophysics Data System (ADS)

Aranson, Igor; Löber, Jakob; Ziebert, Falko

2015-03-01

Collective migration of eukaryotic cells plays a fundamental role in tissue growth, wound healing and immune response. The motion, arising spontaneously or in response to chemical and mechanical stimuli, is also important for understanding life-threatening pathologies, such as cancer and metastasis formation. We present a phase-field model to describe the movement of many self-organized, interacting cells. The model takes into account the main mechanisms of cell motility - actomyosin dynamics, as well as substrate-mediated and cell-cell adhesion. It predicts that collective cell migration emerges spontaneously as a result of inelastic collisions between neighboring cells: collisions lead to a mutual alignment of the cell velocities and to the formation of coherently-moving multi-cellular clusters. Small cell-to-cell adhesion, in turn, reduces the propensity for large-scale collective migration, while higher adhesion leads to the formation of moving bands. Our study provides valuable insight into biological processes associated with collective cell motility. J. L. acknowledges funding from the German Science Foundation (DFG) within the GRK 1558. F. Z. acknowledges funding from the German Science Foundation (DFG) via Project ZI 1232/2-1. I. S. A. was supported by the US Department of Energy (DOE), Office of.

Theoretical investigation of thermodynamic stability and mobility of the oxygen vacancy in ThO 2 –UO 2 solid solutions

DOE PAGES

Liu, B.; Aidhy, D. S.; Zhang, Y.; ...

2014-10-16

The thermodynamic stability and the migration energy barriers of oxygen vacancies in ThO 2 –UO 2 solid solutions are investigated by density functional theory calculations. In pure ThO 2, the formation energy of oxygen vacancy is 7.58 eV and 1.46 eV under O rich and O poor conditions, respectively, while its migration energy barrier is 1.97 eV. The addition of UO 2 into ThO 2 significantly decreases the energetics of formation and migration of the oxygen vacancy. Among the range of UO 2-ThO 2 solid solutions studied in this work, UO 2 exhibits the lowest formation energy (5.99 eV andmore » -0.13 eV under O rich and O poor conditions, respectively) and Th 0.25U0 .75O 2 exhibits the lowest migration energy barrier (~ 1 eV). Moreover, by considering chemical potential, the phase diagram of oxygen vacancy as a function of both temperature and oxygen partial pressure is shown, which could help to gain experimental control over oxygen vacancy concentration.« less

Phloretin Inhibits Platelet-derived Growth Factor-BB-induced Rat Aortic Smooth Muscle Cell Proliferation, Migration, and Neointimal Formation After Carotid Injury.

PubMed

Wang, Dong; Wang, Qingjie; Yan, Gaoliang; Qiao, Yong; Tang, Chengchun

2015-05-01

Abnormal vascular smooth muscle cell proliferation and migration are key factors in many cardiovascular diseases. Here, we investigated the effects of phloretin on platelet-derived growth factor homodimer (PDGF-BB)-induced rat aortic smooth muscle cell (RASMC) proliferation, migration, and neointimal formation after carotid injury. Phloretin significantly inhibited the PDGF-BB-stimulated RASMC proliferation in a concentration-dependent manner (10-100 μM). Also, PDGF-BB-stimulated RASMC migration was inhibited by phloretin at 50 μM. Pretreating RASMC with phloretin dose-dependently inhibited PDGF-BB-induced Akt and p38 mitogen-activated protein kinases activation. Furthermore, phloretin increased p27 and decreased cyclin-dependent kinase 2, CDK4 expression, and p-Rb activation in PDGF-BB-stimulated RASMC in a concentration-dependent manner (10-50 μM). PDGF-BB-induced cell adhesion molecules and matrix metalloproteinase-9 expression were blocked by phloretin at 50 μM. Preincubation with phloretin dose-dependently reduced the intracellular reactive oxygen species production. In vivo study showed that phloretin (20 mg/kg) significantly reduced neointimal formation 14 days after carotid injury in rats. Thus, phloretin may have potential as a treatment against atherosclerosis and restenosis after vascular injury.

Stripes and belly-spots – a review of pigment cell morphogenesis in vertebrates

PubMed Central

Kelsh, Robert N.; Harris, Melissa L.; Colanesi, Sarah; Erickson, Carol A.

2009-01-01

Pigment patterns in the integument have long-attracted attention from both scientists and non-scientists alike since their natural attractiveness combines with their excellence as models for the general problem of pattern formation. Pigment cells are formed from the neural crest and must migrate to reach their final locations. In this review, we focus on our current understanding of mechanisms underlying the control of pigment cell migration and patterning in diverse vertebrates. The model systems discussed here –chick, mouse, and zebrafish – each provide unique insights into the major morphogenetic events driving pigment pattern formation. In birds and mammals, melanoblasts must be specified before they can migrate on the dorsolateral pathway. Transmembrane receptors involved in guiding them onto this route include EphB2 and Ednrb2 in chick, and Kit in mouse. Terminal migration depends, in part, upon extracellular matrix reorganization by ADAMTS20. Invasion of the ectoderm, especially into the feather germ and hair follicles, requires specific signals that are beginning to be characterized. We summarize our current understanding of the mechanisms regulating melanoblast number and organization in the epidermis. We note the apparent differences in pigment pattern formation in poikilothermic vertebrates when compared with birds and mammals. With more pigment cell types, migration pathways are more complex and largely unexplored; nevertheless, a role for Kit signaling in melanophore migration is clear and indicates that at least some patterning mechanisms may be highly conserved. We summarize the multiple factors thought to contribute to zebrafish embryonic pigment pattern formation, highlighting a recent study identifying Sdf1a as one factor crucial for regulation of melanophore positioning. Finally, we discuss the mechanisms generating a second, metamorphic pigment pattern in adult fish, emphasizing recent studies strengthening the evidence that undifferentiated progenitor cells play a major role in generating adult pigment cells. PMID:18977309

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

PubMed Central

Millarte, Valentina; Farhan, Hesso

2012-01-01

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

Determinants of spring migration departure decision in a bat.

PubMed

Dechmann, Dina K N; Wikelski, M; Ellis-Soto, D; Safi, K; O'Mara, M Teague

2017-09-01

Migratory decisions in birds are closely tied to environmental cues and fat stores, but it remains unknown if the same variables trigger bat migration. To learn more about the rare phenomenon of bat migration, we studied departure decisions of female common noctules ( Nyctalus noctula ) in southern Germany. We did not find the fattening period that modulates departure decisions in birds. Female noctules departed after a regular evening foraging session, uniformly heading northeast. As the day of year increased, migratory decisions were based on the interactions among wind speed, wind direction and air pressure. As the migration season progressed, bats were likely to migrate on nights with higher air pressure and faster tail winds in the direction of travel, and also show high probability of migration on low-pressure nights with slow head winds. Common noctules thus monitor complex environmental conditions to find the optimal migration night. © 2017 The Authors.

An Older, Slower Hawaii-Emperor Bend

NASA Astrophysics Data System (ADS)

Sharp, W. D.; Clague, D. A.

2002-12-01

The Hawaii-Emperor Bend is widely interpreted to indicate a profound change in the direction of Pacific Plate motion at about 43 Ma. This interpretation rests on the assumption that the Hawaiian hotspot has remained fixed; however, the fixity of the Hawaiian hotspot has long been challenged on the basis of plate-circuit reconstructions and considerations of mantle dynamics. Moreover, paleomagnetists (e.g., Tarduno and Cottrell, 1997) have suggested that prior to formation of the Bend the Hawaiian hotspot moved southward relative to Earth's spin axis at cm-per-year rates--that is, the Bend may primarily record slowing of the hotspot's own motion. If so, the rate of volcanic migration along the chain--which must be the vector sum of hotspot and Pacific Plate motions--should slow at the Bend. Published interpretations of Hawaii-Emperor seamount ages portray a uniform volcanic migration rate of about 8 cm per year through the Bend; however, many of the ages underlying these interpretations are whole-rock K-Ar and Ar-Ar total fusion ages of uncertain reliability. We report 15 new Ar-Ar plateau ages of milligram quantities of selected feldspars and hornblendes from 6 seamounts that bracket the Bend, extending from 1350 km north of the Bend to 225 km east of the Bend. The dated rocks are post-shield, transitional to alkalic basalts and trachytes that--by analogy with Quaternary Hawaiian volcanoes--erupted between 1 and 2 m.y. after passage of the seamount over the leading edge of the hotspot. Accordingly, north of the Bend, from Suiko seamount (age = 61.3 +/-0.5 Ma, 2σ ) to Koko seamount (50.6 +/-0.2 Ma), volcanism apparently migrated at about 10 cm per year during formation of the southern Emperor Chain. Through the Bend, from Koko seamount via Kimmei (47.3 +/-0.4 Ma), Diakakuji (46.7 +/-0.2 Ma), Abbott (41.5 +/-0.3 Ma) and Colahan (38.8 +/-0.2 Ma) seamounts, migration of volcanism slowed to 5.2 +/-0.6 cm per year--qualitatively consistent with hotspot motion that slowed or stopped near the Bend. Slower migration of volcanism around the Bend accentuates a precipitous drop in eruption rate that accompanied the Bend's inception. Furthermore, the new, older age of Koko seamount indicates that the Bend began to form at about 50 Ma. Therefore, inception of the Bend coincided with--and may have been causally linked to--reorganization of northern Pacific spreading ridges between marine magnetic anomalies 22 and 24, corresponding to 49-53 Ma on the Cande and Kent (1995) geomagnetic polarity time scale. Thus a change in direction of Pacific Plate motion may yet prove to have played a role in forming the Bend, though earlier than previously believed.

The Role of Direct Current Electric Field-Guided Stem Cell Migration in Neural Regeneration.

PubMed

Yao, Li; Li, Yongchao

2016-06-01

Effective directional axonal growth and neural cell migration are crucial in the neural regeneration of the central nervous system (CNS). Endogenous currents have been detected in many developing nervous systems. Experiments have demonstrated that applied direct current (DC) electric fields (EFs) can guide axonal growth in vitro, and attempts have been made to enhance the regrowth of damaged spinal cord axons using DC EFs in in vivo experiments. Recent work has revealed that the migration of stem cells and stem cell-derived neural cells can be guided by DC EFs. These studies have raised the possibility that endogenous and applied DC EFs can be used to direct neural tissue regeneration. Although the mechanism of EF-directed axonal growth and cell migration has not been fully understood, studies have shown that the polarization of cell membrane proteins and the activation of intracellular signaling molecules are involved in the process. The application of EFs is a promising biotechnology for regeneration of the CNS.

Numerical Investigation of Force-Free Magnetophoresis of Nonspherical Microparticles

NASA Astrophysics Data System (ADS)

Zhang, Jie; Wang, Cheng

2017-11-01

Our group recently demonstrated novel force-free magnetophoresis to separate nonspherical particles by shape. In this approach, a uniform magnetic field is used to generate a magnetic torque, which breaks the rotational symmetry of the particles and leads to shape-dependent lateral migration of the particles. We use direct numerical simulations to gain a better understanding of this magnetophoresis mechanism by focusing on ellipsoidal microparticles - a representative type of nonspherical particles encountered in biomedical engineering. We study key effects that influence the rotational and translational behaviors, including particle-wall separation distance, direction and strength of the magnetic field, particle aspect ratio and size. The numerical results show that the lateral migration is negligible in the absence of the magnetic field. When the magnetic field is applied, the particles migrate laterally. The migration direction depends on the direction of external magnetic fields, which controls the symmetry property of the particle rotation. These findings agree well with experiments. Our numerical simulations yield a comprehensive understanding of particle migration mechanism, and provide useful guidelines on design of separating devices for non-spherical micro-particles.

Non-contact method for directing electrotaxis

NASA Astrophysics Data System (ADS)

Ahirwar, Dinesh K.; Nasser, Mohd W.; Jones, Travis H.; Sequin, Emily K.; West, Joseph D.; Henthorne, Timothy L.; Javor, Joshua; Kaushik, Aniruddha M.; Ganju, Ramesh K.; Subramaniam, Vish V.

2015-06-01

We present a method to induce electric fields and drive electrotaxis (galvanotaxis) without the need for electrodes to be in contact with the media containing the cell cultures. We report experimental results using a modification of the transmembrane assay, demonstrating the hindrance of migration of breast cancer cells (SCP2) when an induced a.c. electric field is present in the appropriate direction (i.e. in the direction of migration). Of significance is that migration of these cells is hindered at electric field strengths many orders of magnitude (5 to 6) below those previously reported for d.c. electrotaxis, and even in the presence of a chemokine (SDF-1α) or a growth factor (EGF). Induced a.c. electric fields applied in the direction of migration are also shown to hinder motility of non-transformed human mammary epithelial cells (MCF10A) in the presence of the growth factor EGF. In addition, we also show how our method can be applied to other cell migration assays (scratch assay), and by changing the coil design and holder, that it is also compatible with commercially available multi-well culture plates.

Petrography and stratigraphy of productive beds in the Morgan Formation, Church Buttes Unit No. 19, southwest Wyoming

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

Picard, M.D.

1977-01-01

The combination stratigraphic and structural traps in the Morgan Formation of Pennsylvanian age of Church Buttes, Butcher Knife, and Bruff that produce gas and condensate are directly related to folding of the Church Buttes Arch in SW. Wyoming and NE. Utah. Present knowledge indicates that the Morgan gas and condensate originated in source beds in the lower Morgan formation west of the present Church Buttes Arch and were trapped mainly in porous barrier deposits in the Morgan. Folding of the Church Buttes Arch liberated these accumulations and they migrated updip in their present traps. This work summarizes the sedimentary petrographymore » of the productive beds in the Morgan Formation at the Church Buttes Unit No. 19 (SEC. 8, T 16 N, R 112 W), Uinta County, Wyoming. The stratigraphy is outlined for the whole region and the productive interval at Church Buttes is correlated with other rock units. Nearly all of the rocks studied are dolomite, which is difficult to interpret because of pronounced diagenesis. 33 references.« less

Flight directions of passerine migrants in daylight and darkness: A radar and direct visual study

NASA Technical Reports Server (NTRS)

Gauthreaux, S. A., Jr.

1972-01-01

The application of radar and visual techniques to determine the migratory habits of passerine birds during daylight and darkness is discussed. The effects of wind on the direction of migration are examined. Scatter diagrams of daytime and nocturnal migration track directions correlated with wind direction are presented. It is concluded that migratory birds will fly at altitudes where wind direction and migratory direction are nearly the same. The effects of cloud cover and solar obscuration are considered negligible.

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

Luo, Langli; Su, Mao; Yan, Pengfei

The presence of water vapor, intentional or unavoidable, is crucial to many materials applications, such as steam generator, turbine engine, fuel cell, catalyst, and corrosion 1-6. Phenomenologically, water vapor has been noticed to accelerate oxidation of metals/alloys 7,8, however, the atomistic mechanisms remain elusive. Herein, through direct in situ atomic-scale transmission electron microscopy observation and density functional theory calculation, we reveal that water vapor enhanced oxidation of Ni-Cr alloy is associated with proton dissolution promoted vacancy formation, migration and clustering. Protons derived from water dissociation occupy interstitial position in the oxide lattice, which consequently leads to the lowering of bothmore » vacancy formation energy and the cation diffusion barrier. The atomic scale observations reveal a water vapor derived proton mediated oxide growth mechanism, which provides insights for reckoning many technological processes concerning materials in moist environment at elevated temperatures.« less

Morphogenesis and evolution of vertebrate appendicular muscle

PubMed Central

HAINES, LYNN; CURRIE, PETER D.

2001-01-01

Two different modes are utilised by vertebrate species to generate the appendicular muscle present within fins and limbs. Primitive Chondricthyan or cartilaginous fishes use a primitive mode of muscle formation to generate the muscle of the fins. Direct epithelial myotomal extensions invade the fin and generate the fin muscles while remaining in contact with the myotome. Embryos of amniotes such as chick and mouse use a similar mechanism to that deployed in the bony teleost species, zebrafish. Migratory mesenchymal myoblasts delaminate from fin/limb level somites, migrate to the fin/limb field and differentiate entirely within the context of the fin/limb bud. Migratory fin and limb myoblasts express identical genes suggesting that they possess both morphogenetic and molecular identity. We conclude that the mechanisms controlling tetrapod limb muscle formation arose prior to the Sarcopterygian or tetrapod radiation. PMID:11523824

Formation of Widmanstätten Austenite in Strip Cast Grain-Oriented Silicon Steel

NASA Astrophysics Data System (ADS)

Song, Hong-Yu; Liu, Hai-Tao; Wang, Guo-Dong; Jonas, John J.

2017-04-01

The formation of Widmanstätten austenite was studied in strip cast grain-oriented silicon steel. The microstructure was investigated by optical microscopy and scanning electron microscopy. The orientations of the ferrite, Widmanstätten austenite, and martensite were determined using electron backscatter diffraction. The Widmanstätten austenite exhibits a lath-like shape and nucleates directly on the ferrite grain boundaries. This differs significantly from earlier work on duplex stainless steels. The orientation relationship between the Widmanstätten austenite and the parent ferrite is closer to Kurdjumov-Sachs than to Nishiyama-Wassermann. The ferrite boundaries migrate so as to accommodate the habit planes of the laths, leading to the presence of zigzag boundaries in the as-cast strip. Carbon partitioning into the Widmanstätten austenite and silicon partitioning into the parent ferrite were observed.

High resolution multi-facies realizations of sedimentary reservoir and aquifer analogs

PubMed Central

Bayer, Peter; Comunian, Alessandro; Höyng, Dominik; Mariethoz, Gregoire

2015-01-01

Geological structures are by nature inaccessible to direct observation. This can cause difficulties in applications where a spatially explicit representation of such structures is required, in particular when modelling fluid migration in geological formations. An increasing trend in recent years has been to use analogs to palliate this lack of knowledge, i.e., exploiting the spatial information from sites where the geology is accessible (outcrops, quarry sites) and transferring the observed properties to a study site deemed geologically similar. While this approach is appealing, it is difficult to put in place because of the lack of access to well-documented analog data. In this paper we present comprehensive analog data sets which characterize sedimentary structures from important groundwater hosting formations in Germany and Brazil. Multiple 2-D outcrop faces are described in terms of hydraulic, thermal and chemical properties and interpolated in 3-D using stochastic techniques. These unique data sets can be used by the wider community to implement analog approaches for characterizing reservoir and aquifer formations. PMID:26175910

Experimental Study on Clogging of Fine Particles in Sand Sediments

NASA Astrophysics Data System (ADS)

Hirabayashi, S.

2015-12-01

In the methane hydrate development from the sand sediment beneath the seafloor, it is anticipated that the migrating fine particles may block the pore and consequently reduces the permeability near the production well. Although this phenomenon is known as skin formation, its microscopic mechanism is still unknown. As a part of a Japanese National hydrate research program (MH21, funded by METI), we carried out an experiment on the clogging of fine particles in sand sediments. A transparent core holder was newly developed to directly visualize the behavior of fine particles in the pore of frame sands and formation of skin. It was observed that there seems to be an induction time before the clogging starts to occur. Once clogging occurs, the upstream fine particles cannot move downstream anymore and the skin is formed. It was found that the rate of skin formation is related to the total volume of injected fine particles while the flow velocity has something to do with the length of the induction time.

Spawning of the kissing loach (Leptobotia curta) is limited to periods following the formation of temporary waters.

PubMed

Abe, Tsukasa; Kobayashi, Ichiro; Kon, Masahiro; Sakamoto, Tatsuya

2007-09-01

The kissing loach, an endangered species surviving only in a few Japanese rivers, spawns in the rice-field areas after migration from rivers in early June. To characterize the environmental conditions required for spawning of the kissing loach, spawning was assessed for two years both by direct observation of spawning behavior and by the appearance of eggs, larvae, and juveniles from June to October. All spawning of the kissing loach was limited to within a couple of days after the formation of temporary waters by remarkable rises in water level. Water temperature and daily rainfall fluctuated during the investigation periods, and no clear relationships with spawning were detected. Furthermore, all spawning was observed only in temporary waters with terrestrial grasses. Thus, spawning of the kissing loach is rigidly limited spatio-temporally to after the formation of temporary waters over terrestrial vegetation. Appropriate management of temporary waters will be crucial for the continued existence of this species.

Evaluation of δ2H and δ18O of water in pores extracted by compression method-effects of closed pores and comparison to direct vapor equilibration and laser spectrometry method

NASA Astrophysics Data System (ADS)

Nakata, Kotaro; Hasegawa, Takuma; Oyama, Takahiro; Miyakawa, Kazuya

2018-06-01

Stable isotopes (δ2H and δ18O) of water can help our understanding of origin, mixing and migration of groundwater. In the formation with low permeability, it provides information about migration mechanism of ion such as diffusion and/or advection. Thus it has been realized as very important information to understand the migration of water and ions in it. However, in formation with low permeability it is difficult to obtain the ground water sample as liquid and water in pores needs to be extracted to estimate it. Compressing rock is the most common and widely used method of extracting water in pores. However, changes in δ2H and δ18O may take place during compression because changes in ion concentration have been reported in previous studies. In this study, two natural rocks were compressed, and the changes in the δ2H and δ18O with compression pressure were investigated. Mechanisms for the changes in water isotopes observed during the compression were then discussed. In addition, δ2H and δ18O of water in pores were also evaluated by direct vapor equilibration and laser spectrometry (DVE-LS) and δ2H and δ18O were compared with those obtained by compression. δ2H was found to change during the compression and a part of this change was found to be explained by the effect of water from closed pores extracted by compression. In addition, water isotopes in both open and closed pores were estimated by combining the results of 2 kinds of compression experiments. Water isotopes evaluated by compression that not be affected by water from closed pores showed good agreements with those obtained by DVE-LS indicating compression could show the mixed information of water from open and closed pores, while DVE-LS could show the information only for open pores. Thus, the comparison of water isotopes obtained by compression and DVE-LS could provide the information about water isotopes in closed and open pores.

HIF-2α-induced chemokines stimulate motility of fibroblast-like synoviocytes and chondrocytes into the cartilage-pannus interface in experimental rheumatoid arthritis mouse models.

PubMed

Huh, Yun Hyun; Lee, Gyuseok; Lee, Keun-Bae; Koh, Jeong-Tae; Chun, Jang-Soo; Ryu, Je-Hwang

2015-10-29

Pannus formation and resulting cartilage destruction during rheumatoid arthritis (RA) depends on the migration of synoviocytes to cartilage tissue. Here, we focused on the role of hypoxia-inducible factor (HIF)-2α-induced chemokines by chondrocytes in the regulation of fibroblast-like synoviocyte (FLS) migration into the cartilage-pannus interface and cartilage erosion. Collagen-induced arthritis (CIA), K/BxN serum transfer, and tumor necrosis factor-α transgenic mice were used as experimental RA models. Expression patterns of HIF-2α and chemokines were determined via immunostaining, Western blotting and RT-PCR. FLS motility was evaluated using transwell migration and invasion assays. The specific role of HIF-2α was determined via local deletion of HIF-2α in joint tissues or using conditional knockout (KO) mice. Cartilage destruction, synovitis and pannus formation were assessed via histological analysis. HIF-2α and various chemokines were markedly upregulated in degenerating cartilage and pannus of RA joints. HIF-2α induced chemokine expression by chondrocytes in both primary culture and cartilage tissue. HIF-2α -induced chemokines by chondrocytes regulated the migration and invasion of FLS. Local deletion of HIF-2α in joint tissues inhibited pannus formation adjacent to cartilage tissue and cartilage destruction caused by K/BxN serum transfer. Furthermore, conditional knockout of HIF-2α in cartilage blocked pannus formation in adjacent cartilage but not bone tissue, along with inhibition of cartilage erosion caused by K/BxN serum transfer. Our findings suggest that chemokines induced by IL-1β or HIF-2α in chondrocytes regulate pannus expansion by stimulating FLS migration and invasion, leading to cartilage erosion during RA pathogenesis.

Fingering instabilities in bacterial community phototaxis

NASA Astrophysics Data System (ADS)

Vps, Ritwika; Man Wah Chau, Rosanna; Casey Huang, Kerwyn; Gopinathan, Ajay

Synechocystis sp PCC 6803 is a phototactic cyanobacterium that moves directionally in response to a light source. During phototaxis, these bacterial communities show emergent spatial organisation resulting in the formation of finger-like projections at the propagating front. In this study, we propose an analytical model that elucidates the underlying physical mechanisms which give rise to these spatial patterns. We describe the migrating front during phototaxis as a one-dimensional curve by considering the effects of phototactic bias, diffusion and surface tension. By considering the propagating front as composed of perturbations to a flat solution and using linear stability analysis, we predict a critical bias above which the finger-like projections appear as instabilities. We also predict the wavelengths of the fastest growing mode and the critical mode above which the instabilities disappear. We validate our predictions through comparisons to experimental data obtained by analysing images of phototaxis in Synechocystis communities. Our model also predicts the observed loss of instabilities in taxd1 mutants (cells with inactive TaxD1, an important photoreceptor in finger formation), by considering diffusion in mutually perpendicular directions and a lower, negative bias.

Direct Large-Scale N-Body Simulations of Planetesimal Dynamics

NASA Astrophysics Data System (ADS)

Richardson, Derek C.; Quinn, Thomas; Stadel, Joachim; Lake, George

2000-01-01

We describe a new direct numerical method for simulating planetesimal dynamics in which N˜10 6 or more bodies can be evolved simultaneously in three spatial dimensions over hundreds of dynamical times. This represents several orders of magnitude improvement in resolution over previous studies. The advance is made possible through modification of a stable and tested cosmological code optimized for massively parallel computers. However, owing to the excellent scalability and portability of the code, modest clusters of workstations can treat problems with N˜10 5 particles in a practical fashion. The code features algorithms for detection and resolution of collisions and takes into account the strong central force field and flattened Keplerian disk geometry of planetesimal systems. We demonstrate the range of problems that can be addressed by presenting simulations that illustrate oligarchic growth of protoplanets, planet formation in the presence of giant planet perturbations, the formation of the jovian moons, and orbital migration via planetesimal scattering. We also describe methods under development for increasing the timescale of the simulations by several orders of magnitude.

Roles of endothelial A-type lamins in migration of T cells on and under endothelial layers

NASA Astrophysics Data System (ADS)

Song, Kwang Hoon; Lee, Jaehyun; Park, Hyoungjun; Kim, Hye Mi; Park, Jeehun; Kwon, Keon Woo; Doh, Junsang

2016-03-01

Stiff nuclei in cell-dense microenvironments may serve as distinct biomechanical cues for cell migration, but such a possibility has not been tested experimentally. As a first step addressing this question, we altered nuclear stiffness of endothelial cells (ECs) by reducing the expression of A-type lamins using siRNA, and investigated the migration of T cells on and under EC layers. While most T cells crawling on control EC layers avoided crossing over EC nuclei, a significantly higher fraction of T cells on EC layers with reduced expression of A-type lamins crossed over EC nuclei. This result suggests that stiff EC nuclei underlying T cells may serve as “duro-repulsive” cues to direct T cell migration toward less stiff EC cytoplasm. During subendothelial migration under EC layers with reduced expression of A-type lamins, T cells made prolonged contact and substantially deformed EC nuclei, resulting in reduced speed and directional persistence. This result suggests that EC nuclear stiffness promotes fast and directionally persistent subendothelial migration of T cells by allowing minimum interaction between T cells and EC nuclei.

Inhibition of the proliferation and acceleration of migration of vascular endothelial cells by increased cysteine-rich motor neuron 1

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

Nakashima, Yukiko; Morimoto, Mayuka; Toda, Ken-ichi

2015-07-03

Cysteine-rich motor neuron 1 (CRIM1) is upregulated only in extracellular matrix gels by angiogenic factors such as vascular endothelial growth factor (VEGF). It then plays a critical role in the tube formation of endothelial cells. In the present study, we investigated the effects of increased CRIM1 on other endothelial functions such as proliferation and migration. Knock down of CRIM1 had no effect on VEGF-induced proliferation or migration of human umbilical vein endothelial cells (HUVECs), indicating that basal CRIM1 is not involved in the proliferation or migration of endothelial cells. Stable CRIM1-overexpressing endothelial F-2 cells, termed CR1 and CR2, were constructed,more » because it was difficult to prepare monolayer HUVECs that expressed high levels of CRIM1. Proliferation was reduced and migration was accelerated in both CR1 and CR2 cells, compared with normal F-2 cells. Furthermore, the transient overexpression of CRIM1 resulted in decreased proliferation and increased migration of bovine aortic endothelial cells. In contrast, neither proliferation nor migration of COS-7 cells were changed by the overexpression of CRIM1. These results demonstrate that increased CRIM1 reduces the proliferation and accelerates the migration of endothelial cells. These CRIM1 effects might contribute to tube formation of endothelial cells. CRIM1 induced by angiogenic factors may serve as a regulator in endothelial cells to switch from proliferating cells to morphological differentiation. - Highlights: • CRIM1 was upregulated only in tubular endothelial cells, but not in monolayers. • Increased CRIM1 reduced the proliferation of endothelial cells. • Increased CRIM1 accelerated the migration of endothelial cells. • Increased CRIM1 had no effect on the proliferation or migration of COS-7 cells.« less

On the Nature and Timing of Giant Planet Migration in the Solar System

NASA Astrophysics Data System (ADS)

Agnor, Craig B.

2016-05-01

Giant planet migration is a natural outcome of gravitational scattering and planet formation processes (Fernandez & Ip 1984). There is compelling evidence that the solar system's giant planets experienced large-scale migration involving close approaches between planets as well as smooth radial migration via planetesimal scattering. Aspects of giant planet migration have been invoked to explain many features of the outer solar system including the resonant structure of the Kuiper Belt (e.g., Malhotra 1993, Levison et al. 2008), the eccentricities of Jupiter and Saturn (Tsiganis et al. 2005, Morbidelli et al. 2009), the capture of Jupiter's Trojan companions (Morbidelli et al. 2005) and the capture of irregular planetary satellites (e.g., Nesvorny et al. 2007) to name a few. If this migration epoch occurred after the formation of the inner planets, then it may also explain the so-called lunar Late Heavy Bombardment (Gomes et al. 2005). This scenario necessarily requires coeval terrestrial and migrating giant planets. Recent N-body integrations exploring this issue have shown that giant planet migration may excite the terrestrial system via nodal and apsidal secular resonances (e.g., Brasser et al. 2013), may drive the terrestrial planets to crossing orbits (Kaib & Chambers 2016) or alternatively leave the inner solar system in a state closely resembling the observed one (Roig et al. 2016). The factors accounting for the large range of outcomes remain unclear. Using linear secular models and N-body simulations I am identifying and characterising the principal aspects of giant planet migration that excite the terrestrial planets' orbits. I will present these results and discuss how they inform the nature and timing of giant planet migration in the solar system.

Decreasing mitochondrial fission diminishes vascular smooth muscle cell migration and ameliorates intimal hyperplasia

PubMed Central

Wang, Li; Yu, Tianzheng; Lee, Hakjoo; O'Brien, Dawn K.; Sesaki, Hiromi; Yoon, Yisang

2015-01-01

Aims Vascular smooth muscle cell (VSMC) migration in response to arterial wall injury is a critical process in the development of intimal hyperplasia. Cell migration is an energy-demanding process that is predicted to require mitochondrial function. Mitochondria are morphologically dynamic, undergoing continuous shape change through fission and fusion. However, the role of mitochondrial morphology in VSMC migration is not well understood. The aim of the study is to understand how mitochondrial fission contributes to VSMC migration and provides its in vivo relevance in the mouse model of intimal hyperplasia. Methods and results In primary mouse VSMCs, the chemoattractant PDGF induced mitochondrial shortening through the mitochondrial fission protein dynamin-like protein 1 (DLP1)/Drp1. Perturbation of mitochondrial fission by expressing the dominant-negative mutant DLP1-K38A or by DLP1 silencing greatly decreased PDGF-induced lamellipodia formation and VSMC migration, indicating that mitochondrial fission is an important process in VSMC migration. PDGF induced an augmentation of mitochondrial energetics as well as ROS production, both of which were found to be necessary for VSMC migration. Mechanistically, the inhibition of mitochondrial fission induced an increase of mitochondrial inner membrane proton leak in VSMCs, abrogating the PDGF-induced energetic enhancement and an ROS increase. In an in vivo model of intimal hyperplasia, transgenic mice expressing DLP1-K38A displayed markedly reduced ROS levels and neointima formation in response to femoral artery wire injury. Conclusions Mitochondrial fission is an integral process in cell migration, and controlling mitochondrial fission can limit VSMC migration and the pathological intimal hyperplasia by altering mitochondrial energetics and ROS levels. PMID:25587046

First direct visualization of spillover species emitted from pt nanoparticles.

PubMed

Takakusagi, Satoru; Fukui, Ken-ichi; Tero, Ryugo; Asakura, Kiyotaka; Iwasawa, Yasuhiro

2010-11-02

We studied the methanol adsorption behavior of Pt nanoparticles that were vacuum-deposited on a TiO(2)(110) surface at room temperature by using an ultrahigh vacuum (UHV) scanning tunneling microscope (STM). A large number of bright spots were observed on fivefold-coordinated Ti (Ti(5c)) rows of the TiO(2)(110) surface after exposure of the Pt/TiO(2)(110) to methanol vapor. We assigned the bright spots to methoxy species. These were mobile and were found to hop along the Ti(5c) rows. In situ time-resolved STM observations of the formation and migration of the bright spots on the Pt/TiO(2)(110) were carried out in the presence of methanol. The bright spots were produced at the periphery of the Pt nanoparticles and migrated to the substrate Ti(5c) rows. We discuss the spillover process and behavior of the methoxy species on the Pt/TiO(2)(110).

Bayesian parameter estimation for stochastic models of biological cell migration

NASA Astrophysics Data System (ADS)

Dieterich, Peter; Preuss, Roland

2013-08-01

Cell migration plays an essential role under many physiological and patho-physiological conditions. It is of major importance during embryonic development and wound healing. In contrast, it also generates negative effects during inflammation processes, the transmigration of tumors or the formation of metastases. Thus, a reliable quantification and characterization of cell paths could give insight into the dynamics of these processes. Typically stochastic models are applied where parameters are extracted by fitting models to the so-called mean square displacement of the observed cell group. We show that this approach has several disadvantages and problems. Therefore, we propose a simple procedure directly relying on the positions of the cell's trajectory and the covariance matrix of the positions. It is shown that the covariance is identical with the spatial aging correlation function for the supposed linear Gaussian models of Brownian motion with drift and fractional Brownian motion. The technique is applied and illustrated with simulated data showing a reliable parameter estimation from single cell paths.

First-principles investigation of diffusion and defect properties of Fe and Ni in Cr2O3

NASA Astrophysics Data System (ADS)

Rak, Zs.; Brenner, D. W.

2018-04-01

Diffusion of Fe and Ni and the energetics of Fe- and Ni-related defects in chromium oxide (α-Cr2O3) are investigated using first-principles Density Functional Theory calculations in combination with the climbing-image nudged elastic band method. The orientations of the spin magnetic moments of the migrating ions are taken into account and their effects on migration barriers are examined. Several possible diffusion pathways were explored through interstitial and vacancy mechanisms, and it was found that the principal mode of ion transport in Cr2O3 is via vacancies. Both interstitial- and vacancy-mediated diffusions are anisotropic, with diffusion being faster in the z-direction. The energetics of defect formation indicates that the Ni-related defects are less stable than the Fe-related ones. This is consistent with Ni-diffusion being faster than Fe-diffusion. The results are compared with previous theoretical and experimental data and possible implications in corrosion control are discussed.

Interplay between chemotaxis and contact inhibition of locomotion determines exploratory cell migration

PubMed Central

Lin, Benjamin; Yin, Taofei; Wu, Yi I.; Inoue, Takanari; Levchenko, Andre

2015-01-01

Directed cell migration in native environments is influenced by multiple migratory cues. These cues may include simultaneously occurring attractive soluble growth factor gradients and repulsive effects arising from cell-cell contact, termed contact inhibition of locomotion (CIL). How single cells reconcile potentially conflicting cues remains poorly understood. Here we show that a dynamic crosstalk between epidermal growth factor (EGF) mediated chemotaxis and CIL guide metastatic breast cancer cell motility, whereby cells become progressively insensitive to CIL in a chemotactic input-dependent manner. This balance is determined via integration of protrusion-enhancing signaling from EGF gradients and protrusion-suppressing signaling induced by CIL, mediated in part through EphB. Our results further suggest that EphB and EGF signaling inputs control protrusion formation by converging onto regulation of phosphatidylinositol 3-kinase (PI3K). We propose that this intricate interplay may enhance the spread of loose cell ensembles in pathophysiological conditions such as cancer, and possibly other physiological settings. PMID:25851023

Cdk5 Phosphorylation of ErbB4 is Required for Tangential Migration of Cortical Interneurons

PubMed Central

Rakić, Sonja; Kanatani, Shigeaki; Hunt, David; Faux, Clare; Cariboni, Anna; Chiara, Francesca; Khan, Shabana; Wansbury, Olivia; Howard, Beatrice; Nakajima, Kazunori; Nikolić, Margareta; Parnavelas, John G.

2015-01-01

Interneuron dysfunction in humans is often associated with neurological and psychiatric disorders, such as epilepsy, schizophrenia, and autism. Some of these disorders are believed to emerge during brain formation, at the time of interneuron specification, migration, and synapse formation. Here, using a mouse model and a host of histological and molecular biological techniques, we report that the signaling molecule cyclin-dependent kinase 5 (Cdk5), and its activator p35, control the tangential migration of interneurons toward and within the cerebral cortex by modulating the critical neurodevelopmental signaling pathway, ErbB4/phosphatidylinositol 3-kinase, that has been repeatedly linked to schizophrenia. This finding identifies Cdk5 as a crucial signaling factor in cortical interneuron development in mammals. PMID:24142862

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 Wiley Periodicals, Inc.

Monitoring CO 2 sequestration into deep saline aquifer and associated salt intrusion using coupled multiphase flow modeling and time lapse electrical resistivity tomography

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

Chuan Lu; CHI Zhang; Hai Hanag

2014-04-01

Successful geological storage and sequestration of carbon dioxide (CO2) require efficient monitoring of the migration of CO2 plume during and after large-scale injection in order to verify the containment of the injected CO2 within the target formation and to evaluate potential leakage risk. Field studies have shown that surface and cross-borehole electrical resistivity tomography (ERT) can be a useful tool in imaging and characterizing solute transport in heterogeneous subsurface. In this synthetic study, we have coupled a 3-D multiphase flow model with a parallel 3-D time-lapse ERT inversion code to explore the feasibility of using time-lapse ERT for simultaneously monitoringmore » the migration of CO2 plume in deep saline formation and potential brine intrusion into shallow fresh water aquifer. Direct comparisons of the inverted CO2 plumes resulting from ERT with multiphase flow simulation results indicate the ERT could be used to delineate the migration of CO2 plume. Detailed comparisons on the locations, sizes and shapes of CO2 plume and intruded brine plumes suggest that ERT inversion tends to underestimate the area review of the CO2 plume, but overestimate the thickness and total volume of the CO2 plume. The total volume of intruded brine plumes is overestimated as well. However, all discrepancies remain within reasonable ranges. Our study suggests that time-lapse ERT is a useful monitoring tool in characterizing the movement of injected CO2 into deep saline aquifer and detecting potential brine intrusion under large-scale field injection conditions.« less

Carbon Ion Radiation Inhibits Glioma and Endothelial Cell Migration Induced by Secreted VEGF

PubMed Central

Liu, Yang; Liu, Yuanyuan; Sun, Chao; Gan, Lu; Zhang, Luwei; Mao, Aihong; Du, Yuting; Zhou, Rong; Zhang, Hong

2014-01-01

This study evaluated the effects of carbon ion and X-ray radiation and the tumor microenvironment on the migration of glioma and endothelial cells, a key process in tumorigenesis and angiogenesis during cancer progression. C6 glioma and human microvascular endothelial cells were treated with conditioned medium from cultures of glioma cells irradiated at a range of doses and the migration of both cell types, tube formation by endothelial cells, as well as the expression and secretion of migration-related proteins were evaluated. Exposure to X-ray radiation-conditioned medium induced dose-dependent increases in cell migration and tube formation, which were accompanied by an upregulation of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-2 and -9 expression. However, glioma cells treated with conditioned medium of cells irradiated at a carbon ion dose of 4.0 Gy showed a marked decrease in migratory potential and VEGF secretion relative to non-irradiated cells. The application of recombinant VEGF165 stimulated migration in glioma and endothelial cells, which was associated with increased FAK phosphorylation at Tyr861, suggesting that the suppression of cell migration by carbon ion radiation could be via VEGF-activated FAK signaling. Taken together, these findings indicate that carbon ion may be superior to X-ray radiation for inhibiting tumorigenesis and angiogenesis through modulation of VEGF level in the glioma microenvironment. PMID:24893038

Torques Induced by Scattered Pebble-flow in Protoplanetary Disks

NASA Astrophysics Data System (ADS)

Benítez-Llambay, Pablo; Pessah, Martin E.

2018-03-01

Fast inward migration of planetary cores is a common problem in the current planet formation paradigm. Even though dust is ubiquitous in protoplanetary disks, its dynamical role in the migration history of planetary embryos has not been assessed. In this Letter, we show that the scattered pebble-flow induced by a low-mass planetary embryo leads to an asymmetric dust-density distribution that is able to exert a net torque. By analyzing a large suite of multifluid hydrodynamical simulations addressing the interaction between the disk and a low-mass planet on a fixed circular orbit, and neglecting dust feedback onto the gas, we identify two different regimes, gas- and gravity-dominated, where the scattered pebble-flow results in almost all cases in positive torques. We collect our measurements in a first torque map for dusty disks, which will enable the incorporation of the effect of dust dynamics on migration into population synthesis models. Depending on the dust drift speed, the dust-to-gas mass ratio/distribution, and the embryo mass, the dust-induced torque has the potential to halt inward migration or even induce fast outward migration of planetary cores. We thus anticipate that dust-driven migration could play a dominant role during the formation history of planets. Because dust torques scale with disk metallicity, we propose that dust-driven outward migration may enhance the occurrence of distant giant planets in higher-metallicity systems.

Cell Adhesion-dependent Serine 85 Phosphorylation of Paxillin Modulates Focal Adhesion Formation and Haptotactic Migration via Association with the C-terminal Tail Domain of Talin*

PubMed Central

Kwak, Tae Kyoung; Lee, Mi-Sook; Ryu, Jihye; Choi, Yoon-Ju; Kang, Minkyung; Jeong, Doyoung; Lee, Jung Weon

2012-01-01

Integrin-mediated adhesion to extracellular matrix proteins is dynamically regulated during morphological changes and cell migration. Upon cell adhesion, protein-protein interactions among molecules at focal adhesions (FAs) play major roles in the regulation of cell morphogenesis and migration. Although tyrosine phosphorylation of paxillin is critically involved in adhesion-mediated signaling, the significance of paxillin phosphorylation at Ser-85 and the mechanism by which it regulates cell migration remain unclear. In this study, we examined how Ser-85 phosphorylation of paxillin affects FA formation and cell migration. We found that paxillin phosphorylation at Ser-85 occurred during HeLa cell adhesion to collagen I and was concomitant with tyrosine phosphorylation of both focal adhesion kinase and talin. However, the non-phosphorylatable S85A mutant of paxillin impaired cell spreading, FA turnover, and migration toward collagen I but not toward serum. Furthermore, whereas the (presumably indirect) interaction between paxillin and the C-terminal tail of talin led to dynamic FAs at the cell boundary, S85A paxillin did not bind talin and caused stabilized FAs in the central region of cells. Together, these observations suggest that cell adhesion-dependent Ser-85 phosphorylation of paxillin is important for its interaction with talin and regulation of dynamic FAs and cell migration. PMID:22761432

Modern Processes of Hydrocarbon Migration and Re-Formation of Oil and Gas Fields (Based on the Results of Monitoring and Geochemical Studies)

NASA Astrophysics Data System (ADS)

Plotnikova, Irina; Salakhidinova, Gulmira; Nosova, Fidania; Pronin, Nikita; Ostroukhov, Sergey

2015-04-01

Special geochemical studies of oils allowed to allocate a movable migration component of oils in the industrial oil deposits. In the field the migration component of oils varies in different parts of the field. The largest percentage of the light migration component (gas condensate of the oil) was detected in the central part of the Kama-Kinel troughs system. Monitoring of the composition of water, oil and gas (condensate light oil component) in the sedimentary cover and ni crystalline basement led to the conclusion of modern migration of hydrocarbons in sedimentary cover. This proves the existence of the modern processes of formation and reformation of oil and gas fields. This presentation is dedicated to the problem of definition of geochemical criteria of selection of hydrocarbons deposit reformation zone in the sample wells of Minibaevskaya area of Romashkinskoye field. While carrying out this work we examined 11 samples of oil from the Upper Devonian Pashiysky horizon. Four oil samples were collected from wells reckoned among the "anomalous" zones that were marked out according to the results of geophysical, oil field and geological research. Geochemical studies of oils were conducted in the laboratory of geochemistry of the Kazan (Volga-region) Federal University. The wells where the signs of hydrocarbons influx from the deep zones of the crust were recorded are considered to be "anomalous". A number of scientists connect this fact to the hypothesis about periodic influx of deep hydrocarbons to the oil deposits of Romashkinskoye field. Other researchers believe that the source rocks of the adjacent valleys sedimentary cover generate gases when entering the main zone of gas formation, which then migrate up the section and passing through the previously formed deposits of oil, change and "lighten" their composition. Regardless of the point of view on the source of the hydrocarbons, the study of the process of deposits refilling with light hydrocarbons is an important fundamental task of exceptional practical importance. The reservoir water monitoring has been conducted in five wells that have penetrated the water-saturated, loosely aggregated zones of the South Tatarstan Arch's basement. The long-term testing resulted in the production of reservoir water from the basement. The sedimentary cover in these wells is blocked by the column, which prevents water cross-flowing from the sedimentary cover. The observations have shown that the levels, gas saturation, mineralisation, density, and composition of reservoir waters from the loosely aggregated zones of the basement change with time. The varying characteristics of the water include its component composition, redox potential, and amount of chlorine and some other components and trace elements. Compositional changes in gases of the loosely aggregated zones of the basement, variations in the gas saturation of reservoir waters and of their composition, the decreasing density of oil in the sedimentary cover, - all result from one cause. This cause is the movement of fluids (solutions and gases dissolved in them) through the loosely aggregated zones and faults of the Earth's crust and the sedimentary cover. The fluids mainly move vertically in an upward direction, although their migration through subhorizontal, loosely aggregated zones of the crystalline basement is also possible. Fluid migration still takes place in the Earth's crust of ancient platforms. This phenomenon indicates that some portions of the platforms - primarily, their margins - periodically resume tectonic activities. The fluid dynamic activity of the crust define the processes in the sedimentary cover. It affects the development of the sedimentary basin during the sedimentation period, and the formation of mineral deposits. The monitoring of the present-day movement of fluid systems in the loosely aggregated zones of the basement will permit the more detailed study of the present-day fluid regime in the upper portion of the Earth's crust and the sedimentary cover.

Area 2: Inexpensive Monitoring and Uncertainty Assessment of CO2 Plume Migration using Injection Data

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

Srinivasan, Sanjay

2014-09-30

In-depth understanding of the long-term fate of CO₂ in the subsurface requires study and analysis of the reservoir formation, the overlaying caprock formation, and adjacent faults. Because there is significant uncertainty in predicting the location and extent of geologic heterogeneity that can impact the future migration of CO₂ in the subsurface, there is a need to develop algorithms that can reliably quantify this uncertainty in plume migration. This project is focused on the development of a model selection algorithm that refines an initial suite of subsurface models representing the prior uncertainty to create a posterior set of subsurface models thatmore » reflect injection performance consistent with that observed. Such posterior models can be used to represent uncertainty in the future migration of the CO₂ plume. Because only injection data is required, the method provides a very inexpensive method to map the migration of the plume and the associated uncertainty in migration paths. The model selection method developed as part of this project mainly consists of assessing the connectivity/dynamic characteristics of a large prior ensemble of models, grouping the models on the basis of their expected dynamic response, selecting the subgroup of models that most closely yield dynamic response closest to the observed dynamic data, and finally quantifying the uncertainty in plume migration using the selected subset of models. The main accomplishment of the project is the development of a software module within the SGEMS earth modeling software package that implements the model selection methodology. This software module was subsequently applied to analyze CO₂ plume migration in two field projects – the In Salah CO₂ Injection project in Algeria and CO₂ injection into the Utsira formation in Norway. These applications of the software revealed that the proxies developed in this project for quickly assessing the dynamic characteristics of the reservoir were highly efficient and yielded accurate grouping of reservoir models. The plume migration paths probabilistically assessed by the method were confirmed by field observations and auxiliary data. The report also documents the application of the software to answer practical questions such as the optimum location of monitoring wells to reliably assess the migration of CO₂ plume, the effect of CO₂-rock interactions on plume migration and the ability to detect the plume under those conditions and the effect of a slow, unresolved leak on the predictions of plume migration.« less

Migration of magnetotactic bacteria in porous media.

PubMed

Rismani Yazi, Saeed; Nosrati, Reza; Stevens, Corey A; Vogel, David; Escobedo, Carlos

2018-01-01

Magnetotactic bacteria (MTB) migrate in complex porous sediments where fluid flow is ubiquitous. Here, we demonstrate that magnetotaxis enables MTB to migrate effectively through porous micromodels. Directed MTB can circumvent curved obstacles by traveling along the boundaries and pass flat obstacles by repeatedly switching between forward and backward runs. Magnetotaxis enables directed motion of MTB through heterogeneous porous media, overcoming tortuous flow fields with local velocities as high as 250  μ m s -1 . Our findings bring new insights into the migration behaviour of MTB in their natural habitats and their potential in vivo applications as microbiorobots.

Magnetic Control of Lateral Migration of Ellipsoidal Microparticles in Microscale Flows

NASA Astrophysics Data System (ADS)

Zhou, Ran; Sobecki, Christopher A.; Zhang, Jie; Zhang, Yanzhi; Wang, Cheng

2017-08-01

Precise manipulations of nonspherical microparticles by shape have diverse applications in biology and biomedical engineering. Here, we study lateral migration of ellipsoidal paramagnetic microparticles in low-Reynolds-number flows under uniform magnetic fields. We show that magnetically induced torque alters the rotation dynamics of the particle and results in shape-dependent lateral migration. By adjusting the direction of the magnetic field, we demonstrate versatile control of the symmetric and asymmetric rotation of the particles, thereby controlling the direction of the particle's lateral migration. The particle rotations are experimentally measured, and their symmetry or asymmetry characteristics agree well with the prediction from a simple theory. The lateral migration mechanism is found to be valid for nonmagnetic particles suspended in a ferrofluid. Finally, we demonstrate shape-based sorting of microparticles by exploiting the proposed migration mechanism.

Blood vessel endothelium-directed tumor cell streaming in breast tumors requires the HGF/C-Met signaling pathway

PubMed Central

Leung, E; Xue, A; Wang, Y; Rougerie, P; Sharma, V P; Eddy, R; Cox, D; Condeelis, J

2017-01-01

During metastasis to distant sites, tumor cells migrate to blood vessels. In vivo, breast tumor cells utilize a specialized mode of migration known as streaming, where a linear assembly of tumor cells migrate directionally towards blood vessels on fibronectin-collagen I-containing extracellular matrix (ECM) fibers in response to chemotactic signals. We have successfully reconstructed tumor cell streaming in vitro by co-plating tumors cells, macrophages and endothelial cells on 2.5 μm thick ECM-coated micro-patterned substrates. We found that tumor cells and macrophages, when plated together on the micro-patterned substrates, do not demonstrate sustained directional migration in only one direction (sustained directionality) but show random bi-directional walking. Sustained directionality of tumor cells as seen in vivo was established in vitro when beads coated with human umbilical vein endothelial cells were placed at one end of the micro-patterned ‘ECM fibers' within the assay. We demonstrated that these endothelial cells supply the hepatocyte growth factor (HGF) required for the chemotactic gradient responsible for sustained directionality. Using this in vitro reconstituted streaming system, we found that directional streaming is dependent on, and most effectively blocked, by inhibiting the HGF/C-Met signaling pathway between endothelial cells and tumor cells. Key observations made with the in vitro reconstituted system implicating C-Met signaling were confirmed in vivo in mammary tumors using the in vivo invasion assay and intravital multiphoton imaging of tumor cell streaming. These results establish HGF/C-Met as a central organizing signal in blood vessel-directed tumor cell migration in vivo and highlight a promising role for C-Met inhibitors in blocking tumor cell streaming and metastasis in vivo, and for use in human trials. PMID:27893712

Embryonic cell-cell adhesion: a key player in collective neural crest migration.

PubMed

Barriga, Elias H; Mayor, Roberto

2015-01-01

Cell migration is essential for morphogenesis, adult tissue remodeling, wound healing, and cancer cell migration. Cells can migrate as individuals or groups. When cells migrate in groups, cell-cell interactions are crucial in order to promote the coordinated behavior, essential for collective migration. Interestingly, recent evidence has shown that cell-cell interactions are also important for establishing and maintaining the directionality of these migratory events. We focus on neural crest cells, as they possess extraordinary migratory capabilities that allow them to migrate and colonize tissues all over the embryo. Neural crest cells undergo an epithelial-to-mesenchymal transition at the same time than perform directional collective migration. Cell-cell adhesion has been shown to be an important source of planar cell polarity and cell coordination during collective movement. We also review molecular mechanisms underlying cadherin turnover, showing how the modulation and dynamics of cell-cell adhesions are crucial in order to maintain tissue integrity and collective migration in vivo. We conclude that cell-cell adhesion during embryo development cannot be considered as simple passive resistance to force, but rather participates in signaling events that determine important cell behaviors required for cell migration. © 2015 Elsevier Inc. All rights reserved.

Inflammatory responses and side effects generated by several adjuvant-containing vaccines in turbot.

PubMed

Noia, M; Domínguez, B; Leiro, J; Blanco-Méndez, J; Luzardo-Álvarez, A; Lamas, J

2014-05-01

Several of the adjuvants used in fish vaccines cause adhesions in internal organs when they are injected intraperitoneally. We describe the damage caused by vaccines containing different adjuvants in the turbot Scophthalmus maximus and show that internal adhesions can be greatly reduced by injecting the fish in a specific way. Injection of fish with the needle directed towards the anterior part of the peritoneal cavity induced formation of a single cell-vaccine mass (CVM) that became attached to the parietal peritoneum. However, injection of the fish with the needle pointing in the opposite direction generated many small CVM that became attached to the visceral and parietal peritoneum and in some cases caused internal adhesions. We describe the structural and cellular changes in the adjuvant-induced CVMs. The CVMs mainly comprised neutrophils and macrophages, although most of the former underwent apoptosis, which was particularly evident from day 3 post-injection. The apoptotic cells were phagocytosed by macrophages, which were the dominant cell type from the first days onwards. All of the vaccines induced angiogenesis in the area of contact between the CVM and the mesothelium. Vaccines containing oil-based adjuvants or microspheres induced the formation of granulomas in the CVM; however, no granulomas were observed in the CVM induced by vaccines containing aluminium hydroxide or Matrix-Q(®) as adjuvants. All of the vaccines induced strong migration of cells to the peritoneal cavity. Although some of these cells remained unattached in the peritoneal cavity, most of them formed part of the CVM. We also observed migration of the cells from the peritoneal cavity to lymphoid organs, indicating bidirectional traffic of cells between the inflamed areas and these organs. Copyright © 2014 Elsevier Ltd. All rights reserved.

A novel role of KIF3b in the seminoma cell cycle

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

Shen, Hao-Qing; Xiao, Yu-Xi; She, Zhen-Yu

KIF3b is a protein of the kinesin-2 family which plays an important role in intraflagellar transport. Testis cancer is a common cancer among young men. Its diagnostic rate is increasing and over half of the cases are seminomas. Many aspects of the mechanism and gene expression background of this cancer remain unclear. Using western-blotting and semi-quantitative PCR we found high protein levels of KIF3b enrichment in seminoma tissue despite the mRNA levels remaining equivalent to that of normal testicular tissues. The distribution of KIF3b was mainly in cells with division potential. Wound-healing assays and cell counting kit assays showed thatmore » the knockdown of KIF3b significantly suppressed cell migration ability, viability and number in HeLa cells. Immunofluorescence images during the cell cycle revealed that KIF3b tended to gather at the spindles and was enriched at the central spindle. This indicated that KIF3b may also have direct impacts upon spindle formation and cytokinesis. By counting the numbers of nuclei, spindles and cells, we found that the rates of multipolar division and multi-nucleation were raised in KIF3b-knockdown cells. In this way we demonstrate that KIF3b functions importantly in mitosis and may be essential to seminoma cell division and proliferation as well as being necessary for normal cell division. - Highlights: • A significant upregulation of KIF3b is detected in seminoma. • Knockdown of KIF3b impacts on cell proliferation and migration. • KIF3b may have direct impacts upon spindle formation and cytokinesis.« less

MiR-217 promoted the proliferation and invasion of glioblastoma by repressing YWHAG.

PubMed

Wang, Hongbin; Zhi, Hua; Ma, Dongzhou; Li, Tao

2017-04-01

To study the effects of miR-217 on glioblastoma cell proliferation, migration and invasion and its regulation on YWHAG. QRT-PCR was used to detect the expression of related mRNAs and miRNA in both glioblastoma tissues and cells. Western blot was used to determine the protein expression of related genes. The transfection was performed using lipo2000. MTT assay, colony formation assay, wound healing assay, Transwell assay as well as flow cytometry were employed to determine the viability, proliferation, migration, invasion and mitosis of UG87 MG cell line. Besides, the dual luciferase reporter gene assay was used to determine the direct targeting relationship between miR-217 and YWHAG. Xenograft models were also constructed and the effect of miR-217 on tumor growth was studied in vivo. MiR-217 was up-regulated, whereas YWHAG was down-regulated in glioblastoma tissues and cells. The down-regulation of miR-217 or the up-regulation of YWHAG suppressed the viability, proliferation, migration, invasion and mitosis of U87 MG cells in vitro. In addition, MiR-217 directly targeted 3'UTR of YWHAG and suppressed the expression of YWHAG. Up-regulation of miR-217 could efficiently attenuate the inhibitory effects of YWHAG overexpression on the proliferation and metastasis of U87 MG cells. YWHAG was able to accelerate the phosphorylation of MDM4 and lead to the degradation of P53, which provides a potential mechanism for the tumor-promoting role of miR-217 in glioblastoma cells. By constructing xenograft models, it was also confirmed that miR-217 could promote tumor growth in vivo. MiR-217 could promote the viability, proliferation, migration, invasion and mitosis of glioblastoma cells both in vitro and in vivo. Copyright © 2016 Elsevier Ltd. All rights reserved.

Geological controls on the occurrence of gas hydrate from core, downhole log, and seismic data in the Shenhu area, South China Sea

USGS Publications Warehouse

Xiujuan Wang,; ,; Collett, Timothy S.; Lee, Myung W.; Yang, Shengxiong; Guo, Yiqun; Wu, Shiguo

2014-01-01

Multi-channel seismic reflection data, well logs, and recovered sediment cores have been used in this study to characterize the geologic controls on the occurrence of gas hydrate in the Shenhu area of the South China Sea. The concept of the "gas hydrate petroleum system" has allowed for the systematic analysis of the impact of gas source, geologic controls on gas migration, and the role of the host sediment in the formation and stability of gas hydrates as encountered during the 2007 Guangzhou Marine Geological Survey Gas Hydrate Expedition (GMGS-1) in the Shenhu area. Analysis of seismic and bathymetric data identified seventeen sub-linear, near-parallel submarine canyons in this area. These canyons, formed in the Miocene, migrated in a northeasterly direction, and resulted in the burial and abandonment of canyons partially filled by coarse-grained sediments. Downhole wireline log (DWL) data were acquired from eight drill sites and sediment coring was conducted at five of these sites, which revealed the presence of suitable reservoirs for the occurrence of concentrated gas hydrate accumulations. Gas hydrate-bearing sediment layers were identified from well log and core data at three sites mainly within silt and silt clay sediments. Gas hydrate was also discovered in a sand reservoir at one site as inferred from the analysis of the DWL data. Seismic anomalies attributed to the presence of gas below the base of gas hydrate stability zone, provided direct evidence for the migration of gas into the overlying gas hydrate-bearing sedimentary sections. Geochemical analyses of gas samples collected from cores confirmed that the occurrence of gas hydrate in the Shenhu area is controlled by the presence thermogenic methane gas that has migrated into the gas hydrate stability zone from a more deeply buried source.

BetaPIX and GIT1 regulate HGF-induced lamellipodia formation and WAVE2 transport.

PubMed

Morimura, Shigeru; Suzuki, Katsuo; Takahashi, Kazuhide

2009-05-08

Formation of lamellipodia is the first step during cell migration, and involves actin reassembly at the leading edge of migrating cells through the membrane transport of WAVE2. However, the factors that regulate WAVE2 transport to the cell periphery for initiating lamellipodia formation have not been elucidated. We report here that in human breast cancer MDA-MB-231 cells, the hepatocyte growth factor (HGF) induced the association between the constitutive complex of betaPIX and GIT1 with WAVE2, which was concomitant with the induction of lamellipodia formation and WAVE2 transport. Although depletion of betaPIX by RNA interference abrogated the HGF-induced WAVE2 transport and lamellipodia formation, GIT1 depletion caused HGF-independent WAVE2 transport and lamellipodia formation. Collectively, we suggest that betaPIX releases cells from the GIT1-mediated suppression of HGF-independent responses and recruits GIT1 to WAVE2, thereby facilitating HGF-induced WAVE2 transport and lamellipodia formation.

Nearshore sandbar rotation at single-barred embayed beaches

NASA Astrophysics Data System (ADS)

Blossier, B.; Bryan, K. R.; Daly, C. J.; Winter, C.

2016-04-01

The location of a shore-parallel nearshore sandbar derived from 7 years of video imagery data at the single-barred embayed Tairua Beach (NZ) is investigated to assess the contribution of barline rotation to the overall morphodynamics of sandbars in embayed environments and to characterize the process of rotation in relation to external conditions. Rotation induces cross-shore barline variations at the embayment extremities on the order of magnitude of those induced by alongshore uniform cross-shore migration of the bar. Two semiempirical models have been developed to relate the barline cross-shore migration and rotation to external wave forcing conditions. The rotation model is directly derived from the cross-shore migration model. Therefore, its formulation advocates for a primary role of cross-shore processes in the rotation of sandbars at embayed beaches. The orientation evolves toward an equilibrium angle directly related to the alongshore wave energy gradient due to two different mechanisms. Either the bar extremities migrate in opposite directions with no overall cross-shore bar migration (pivotal rotation) or the rotation relates to an overall migration of the barline which is not uniform along the beach (migration-driven rotation). Migration and rotation characteristic response times are similar, ranging from 10 to 30 days for mild and energetic wave conditions and above 200 days during very calm conditions or when the bar is located far offshore.

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

Estimating and interpreting migration of Amazonian forests using spatially implicit and semi-explicit neutral models.

PubMed

Pos, Edwin; Guevara Andino, Juan Ernesto; Sabatier, Daniel; Molino, Jean-François; Pitman, Nigel; Mogollón, Hugo; Neill, David; Cerón, Carlos; Rivas-Torres, Gonzalo; Di Fiore, Anthony; Thomas, Raquel; Tirado, Milton; Young, Kenneth R; Wang, Ophelia; Sierra, Rodrigo; García-Villacorta, Roosevelt; Zagt, Roderick; Palacios Cuenca, Walter; Aulestia, Milton; Ter Steege, Hans

2017-06-01

With many sophisticated methods available for estimating migration, ecologists face the difficult decision of choosing for their specific line of work. Here we test and compare several methods, performing sanity and robustness tests, applying to large-scale data and discussing the results and interpretation. Five methods were selected to compare for their ability to estimate migration from spatially implicit and semi-explicit simulations based on three large-scale field datasets from South America (Guyana, Suriname, French Guiana and Ecuador). Space was incorporated semi-explicitly by a discrete probability mass function for local recruitment, migration from adjacent plots or from a metacommunity. Most methods were able to accurately estimate migration from spatially implicit simulations. For spatially semi-explicit simulations, estimation was shown to be the additive effect of migration from adjacent plots and the metacommunity. It was only accurate when migration from the metacommunity outweighed that of adjacent plots, discrimination, however, proved to be impossible. We show that migration should be considered more an approximation of the resemblance between communities and the summed regional species pool. Application of migration estimates to simulate field datasets did show reasonably good fits and indicated consistent differences between sets in comparison with earlier studies. We conclude that estimates of migration using these methods are more an approximation of the homogenization among local communities over time rather than a direct measurement of migration and hence have a direct relationship with beta diversity. As betadiversity is the result of many (non)-neutral processes, we have to admit that migration as estimated in a spatial explicit world encompasses not only direct migration but is an ecological aggregate of these processes. The parameter m of neutral models then appears more as an emerging property revealed by neutral theory instead of being an effective mechanistic parameter and spatially implicit models should be rejected as an approximation of forest dynamics.

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

PubMed Central

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

2014-01-01

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

Ancient Martian aeolian processes and palaeomorphology reconstructed from the Stimson formation on the lower slope of Aeolis Mons, Gale crater, Mars

USGS Publications Warehouse

Banham, Steve G.; Gupta, Sanjeev; Rubin, David M.; Watkins, Jessica A.; Sumner, Dawn Y.; Edgett, Kenneth S.; Grotzinger, John P.; Lewis, Kevin W.; Edgar, Lauren; Stack, Kathryn M.; Barnes, Robert; Bell, Jame F. III; Day, Mackenzie D.; Ewing, Ryan C.; Lapotre, Mathieu G.A.; Stein, Nathan T.; Rivera-Hernandez, Frances; Vasavada, Ashwin R.

2018-01-01

Reconstruction of the palaeoenvironmental context of Martian sedimentary rocks is central to studies of ancient Martian habitability and regional palaeoclimate history. This paper reports the analysis of a distinct aeolian deposit preserved in Gale crater, Mars, and evaluates its palaeomorphology, the processes responsible for its deposition, and its implications for Gale crater geological history and regional palaeoclimate. Whilst exploring the sedimentary succession cropping out on the northern flank of Aeolis Mons, Gale crater, the Mars Science Laboratory rover Curiosity encountered a decametre‐thick sandstone succession, named the Stimson formation, unconformably overlying lacustrine deposits of the Murray formation. The sandstone contains sand grains characterized by high roundness and sphericity, and cross‐bedding on the order of 1 m in thickness, separated by sub‐horizontal bounding surfaces traceable for tens of metres across outcrops. The cross‐beds are composed of uniform thickness cross‐laminations interpreted as wind‐ripple strata. Cross‐sets are separated by sub‐horizontal bounding surfaces traceable for tens of metres across outcrops that are interpreted as dune migration surfaces. Grain characteristics and presence of wind‐ripple strata indicate deposition of the Stimson formation by aeolian processes. The absence of features characteristic of damp or wet aeolian sediment accumulation indicate deposition in a dry aeolian system. Reconstruction of the palaeogeomorphology suggests that the Stimson dune field was composed largely of simple sinuous crescentic dunes with a height of ca10 m, and wavelengths of ca 150 m, with local development of complex dunes. Analysis of cross‐strata dip‐azimuths indicates that the general dune migration direction and hence net sediment transport was towards the north‐east. The juxtaposition of a dry aeolian system unconformably above the lacustrine Murray formation represents starkly contrasting palaeoenvironmental and palaeoclimatic conditions. Stratigraphic relationships indicate that this transition records a significant break in time, with the Stimson formation being deposited after the Murray formation and stratigraphically higher Mount Sharp group rocks had been buried, lithified and subsequently eroded.

Interleukin-17A and vascular remodelling in severe asthma; lack of evidence for a direct role.

PubMed

Panariti, A; Baglole, C J; Sanchez, V; Eidelman, D H; Hussain, S; Olivenstein, R; Martin, J G; Hamid, Q

2018-04-01

Bronchial vascular remodelling may contribute to the severity of airway narrowing through mucosal congestion. Interleukin (IL)-17A is associated with the most severe asthmatic phenotype but whether it might contribute to vascular remodelling is uncertain. To assess vascular remodelling in severe asthma and whether IL-17A directly or indirectly may cause endothelial cell activation and angiogenesis. Bronchial vascularization was quantified in asthmatic subjects, COPD and healthy subjects together with the number of IL-17A + cells as well as the concentration of angiogenic factors in the sputum. The effect of IL-17A on in vitro angiogenesis, cell migration and endothelial permeability was assessed directly on primary human lung microvascular endothelial cells (HMVEC-L) or indirectly with conditioned medium derived from normal bronchial epithelial cells (NHBEC), fibroblasts (NHBF) and airway smooth muscle cells (ASMC) after IL-17A stimulation. Severe asthmatics have increased vascularity compared to the other groups, which correlates positively with the concentrations of angiogenic factors in sputum. Interestingly, we demonstrated that increased bronchial vascularity correlates positively with the number of subepithelial IL-17A + cells. However IL-17A had no direct effect on HMVEC-L function but it enhanced endothelial tube formation and cell migration through the production of angiogenic factors by NHBE and ASMC. Our results shed light on the role of IL-17A in vascular remodelling, most likely through stimulating the synthesis of other angiogenic factors. Knowledge of these pathways may aid in the identification of new therapeutic targets. © 2018 John Wiley & Sons Ltd.

Geochemical study of the organic matter from Querecual formation, Anzoategui State, Venezuela

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

Garban, G.; Lopez, L.; Lo Monaco, S.

1996-08-01

Kerogen and bitumen fractions extracted from twenty-one limestone samples from kind section of Querecual formation (Querecual River, Anzoategui State, Venezuela) were analyzed for their content of Co, Cr, Fe, Mn, Mo, Ni, S, Sr, V and Zn. S and trace-metals content from the kerogen fraction were used to obtain information about paleoenvironmental sedimentation conditions of the Querecual formation. Based on these data, and especially on the V and S content variations plus V/Ni, VIV+Ni and Mo/Mo+Cr ratios, we confirm an ancient-reducer condition on this region according with a sulfur-reducer environment. Trace-metals content variations from the bitumen fraction along the studymore » section were used as possible primary migration indicators. V and Ni were the only elements showing a clear tendency to be used as primary migration indicators. The observed tendency allows us to postulate a vertical migration of the bitumen, from center to the extremes of the section.« less

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

Basolateral junctions are sufficient to suppress epithelial invasion during Drosophila oogenesis.

PubMed

Szafranski, Przemyslaw; Goode, Scott

2007-02-01

Epithelial junctions play crucial roles during metazoan evolution and development by facilitating tissue formation, maintenance, and function. Little is known about the role of distinct types of junctions in controlling epithelial transformations leading to invasion of neighboring tissues. Discovering the key junction complexes that control these processes and how they function may also provide mechanistic insight into carcinoma cell invasion. Here, using the Drosophila ovary as a model, we show that four proteins of the basolateral junction (BLJ), Fasciclin-2, Neuroglian, Discs-large, and Lethal-giant-larvae, but not proteins of other epithelial junctions, directly suppress epithelial tumorigenesis and invasion. Remarkably, the expression pattern of Fasciclin-2 predicts which cells will invade. We compared the apicobasal polarity of BLJ tumor cells to border cells (BCs), an epithelium-derived cluster that normally migrates during mid-oogenesis. Both tumor cells and BCs differentiate a lateralized membrane pattern that is necessary but not sufficient for invasion. Independent of lateralization, derepression of motility pathways is also necessary, as indicated by a strong linear correlation between faster BC migration and an increased incidence of tumor invasion. However, without membrane lateralization, derepression of motility pathways is also not sufficient for invasion. Our results demonstrate that spatiotemporal patterns of basolateral junction activity directly suppress epithelial invasion by organizing the cooperative activity of distinct polarity and motility pathways.

Growth optimization toward low angle incidence microchannel epitaxy of GaN using ammonia-based metal-organic molecular beam epitaxy

NASA Astrophysics Data System (ADS)

Lin, Chia-Hung; Abe, Ryota; Uchiyama, Shota; Maruyama, Takahiro; Naritsuka, Shigeya

2012-08-01

Growth optimization toward low angle incidence microchannel epitaxy (LAIMCE) of GaN was accomplished using ammonia-based metal-organic molecular beam epitaxy (NH3-based MOMBE). Firstly, the [NH3]/[trimethylgallium (TMG)] ratio (R) dependence of selective GaN growth was studied. The growth temperature was set at 860 °C while R was varied from 5 to 200 with precursors being supplied parallel to the openings cut in the SiO2 mask. The selectivity of the growth was superior for all R, because TMG and NH3 preferably decompose on the GaN film. The formation of {112¯0}GaN or {112¯2}GaN sidewalls and (0001)GaN surface were observed by the change in R. The intersurface diffusion of Ga adatoms was also changed by a change in R. Ga adatoms migrate from the sidewalls to the top at R lower than 50, whereas the migration weakened with R greater than 100. Secondly, LAIMCE was optimized by changing the growth temperature. Consequently, 6 μm wide lateral overgrowth in the direction of precursor incidence was achieved with no pit after etching by H3PO4, which was six times wider than that in the opposite direction.

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.

Unexpected role of the copper transporter ATP7A in PDGF-induced vascular smooth muscle cell migration.

PubMed

Ashino, Takashi; Sudhahar, Varadarajan; Urao, Norifumi; Oshikawa, Jin; Chen, Gin-Fu; Wang, Huan; Huo, Yuqing; Finney, Lydia; Vogt, Stefan; McKinney, Ronald D; Maryon, Edward B; Kaplan, Jack H; Ushio-Fukai, Masuko; Fukai, Tohru

2010-09-17

Copper, an essential nutrient, has been implicated in vascular remodeling and atherosclerosis with unknown mechanism. Bioavailability of intracellular copper is regulated not only by the copper importer CTR1 (copper transporter 1) but also by the copper exporter ATP7A (Menkes ATPase), whose function is achieved through copper-dependent translocation from trans-Golgi network (TGN). Platelet-derived growth factor (PDGF) promotes vascular smooth muscle cell (VSMC) migration, a key component of neointimal formation. To determine the role of copper transporter ATP7A in PDGF-induced VSMC migration. Depletion of ATP7A inhibited VSMC migration in response to PDGF or wound scratch in a CTR1/copper-dependent manner. PDGF stimulation promoted ATP7A translocation from the TGN to lipid rafts, which localized at the leading edge, where it colocalized with PDGF receptor and Rac1, in migrating VSMCs. Mechanistically, ATP7A small interfering RNA or CTR small interfering RNA prevented PDGF-induced Rac1 translocation to the leading edge, thereby inhibiting lamellipodia formation. In addition, ATP7A depletion prevented a PDGF-induced decrease in copper level and secretory copper enzyme precursor prolysyl oxidase (Pro-LOX) in lipid raft fraction, as well as PDGF-induced increase in LOX activity. In vivo, ATP7A expression was markedly increased and copper accumulation was observed by synchrotron-based x-ray fluorescence microscopy at neointimal VSMCs in wire injury model. These findings suggest that ATP7A plays an important role in copper-dependent PDGF-stimulated VSMC migration via recruiting Rac1 to lipid rafts at the leading edge, as well as regulating LOX activity. This may contribute to neointimal formation after vascular injury. Our findings provide insight into ATP7A as a novel therapeutic target for vascular remodeling and atherosclerosis.

Mechano-growth factor protects against mechanical overload induced damage and promotes migration of growth plate chondrocytes through RhoA/YAP pathway.

PubMed

Jing, Xingzhi; Ye, Yaping; Bao, Yuan; Zhang, Jinming; Huang, Junming; Wang, Rui; Guo, Jiachao; Guo, Fengjing

2018-05-15

Epiphyseal growth plate is highly dynamic tissue which is controlled by a variety of endocrine, paracrine hormones, and by complex local signaling loops and mechanical loading. Mechano growth factor (MGF), the splice variant of the IGF-I gene, has been discovered to play important roles in tissue growth and repair. However, the effect of MGF on the growth plate remains unclear. In the present study, we found that MGF mRNA expression of growth plate chondrocytes was upregulated in response to mechanical stimuli. Treatment of MGF had no effect on growth plate chondrocytes proliferation and differentiation. But it could inhibit growth plate chondrocytes apoptosis and inflammation under mechanical overload. Moreover, both wound healing and transwell assay indicated that MGF could significantly enhance growth plate chondrocytes migration which was accompanied with YAP activation and nucleus translocation. Knockdown of YAP with YAP siRNA suppressed migration induced by MGF, indicating the essential role of YAP in MGF promoting growth plate chondrocytes migration. Furthermore, MGF promoted YAP activation through RhoA GTPase mediated cytoskeleton reorganization, RhoA inhibition using C3 toxin abrogated MGF induced YAP activation. Importantly, we found that MGF promoted focal adhesion(FA) formation and knockdown of YAP with YAP siRNA partially suppressed the activation of FA kinase, implying that YAP is associated with FA formation. In conclusion, MGF is an autocrine growth factor which is regulated by mechanical stimuli. MGF could not only protect growth plate chondrocytes against damage by mechanical overload, but also promote migration through activation of RhoA/YAP signaling axis. Most importantly, our findings indicate that MGF promote cell migration through YAP mediated FA formation to determine the FA-cytoskeleton remodeling. Copyright © 2018. Published by Elsevier Inc.

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

Effects of saline-wastewater injection on water quality in the Altamont-Bluebell oil and gas field, Duchesne County, Utah, 1990-2005

USGS Publications Warehouse

Steiger, Judy I.

2007-01-01

The Altamont-Bluebell oil and gas field in the Uinta Basin in northeastern Utah has been an important oil and natural gas production area since the 1950s. Saline water is produced along with oil during the oil-well drilling and pumping process. The saline wastewater is disposed of by injection into wells completed in the Duchesne River Formation, Uinta Formation, and other underlying formations. There are concerns that the injected saline wastewater could migrate into the upper part of the Duchesne River and Uinta Formations and surficial deposits that are used for drinking-water supply and degrade the quality of the drinking water. The U.S. Geological Survey, in cooperation with the Utah Department of Natural Resources, Division of Oil, Gas, and Mining, began a program in 1990 to monitor water quality in five wells in the Altamont-Bluebell oil and gas field. By 1996, water-quality samples had been collected from 20 wells. Ten of the 20 wells were sampled yearly during 1996-2005 and analyzed for bromide, chloride, and stable isotopes. Comparison of major chemical constituents, bromide-to-chloride ratios, trend analysis, and isotope ratios were used to assess if saline wastewater is migrating into parts of the formation that are developed for drinking-water supplies. Results of four different analyses all indicate that saline wastewater injected into the lower part of the Duchesne River and Uinta Formations and underlying formations is not migrating upward into the upper parts of the formations that are used for drinking-water supplies.

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

USGS Publications Warehouse

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

2001-01-01

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

Extracellular matrix-specific Caveolin-1 phosphorylation on tyrosine 14 is linked to augmented melanoma metastasis but not tumorigenesis

PubMed Central

Ortiz, Rina; Díaz, Jorge; Díaz, Natalia; Lobos-Gonzalez, Lorena; Cárdenas, Areli; Contreras, Pamela; Díaz, María Inés; Otte, Ellen; Cooper-White, Justin; Torres, Vicente; Leyton, Lisette; Quest, Andrew F.G.

2016-01-01

Caveolin-1 (CAV1) is a scaffolding protein that plays a dual role in cancer. In advanced stages of this disease, CAV1 expression in tumor cells is associated with enhanced metastatic potential, while, at earlier stages, CAV1 functions as a tumor suppressor. We recently implicated CAV1 phosphorylation on tyrosine 14 (Y14) in CAV1-enhanced cell migration. However, the contribution of this modification to the dual role of CAV1 in cancer remained unexplored. Here, we used in vitro [2D and transendothelial cell migration (TEM), invasion] and in vivo (metastasis) assays, as well as genetic and biochemical approaches to address this question in B16F10 murine melanoma cells. CAV1 promoted directional migration on fibronectin or laminin, two abundant lung extracellular matrix (ECM) components, which correlated with enhanced Y14 phosphorylation during spreading. Moreover, CAV1-driven migration, invasion, TEM and metastasis were ablated by expression of the phosphorylation null CAV1(Y14F), but not the phosphorylation mimicking CAV1(Y14E) mutation. Finally, CAV1-enhanced focal adhesion dynamics and surface expression of beta1 integrin were required for CAV1-driven TEM. Importantly, CAV1 function as a tumor suppressor in tumor formation assays was not altered by the Y14F mutation. In conclusion, our results provide critical insight to the mechanisms of CAV1 action during cancer development. Specific ECM-integrin interactions and Y14 phosphorylation are required for CAV1-enhanced melanoma cell migration, invasion and metastasis to the lung. Because Y14F mutation diminishes metastasis without inhibiting the tumor suppressor function of CAV1, Y14 phosphorylation emerges as an attractive therapeutic target to prevent metastasis without altering beneficial traits of CAV1. PMID:27259249

Caenorhabditis elegans anillin (ani-1) regulates neuroblast cytokinesis and epidermal morphogenesis during embryonic development.

PubMed

Fotopoulos, N; Wernike, D; Chen, Y; Makil, N; Marte, A; Piekny, A

2013-11-01

The formation of tissues is essential for metazoan development. During Caenorhabditis elegans embryogenesis, ventral epidermal cells migrate to encase the ventral surface of the embryo in a layer of epidermis by a process known as ventral enclosure. This process is regulated by guidance cues secreted by the underlying neuroblasts. However, since the cues and their receptors are differentially expressed in multiple cell types, the role of the neuroblasts in ventral enclosure is not fully understood. Furthermore, although F-actin is required for epidermal cell migration, it is not known if nonmuscle myosin is also required. Anillin (ANI-1) is an actin and myosin-binding protein that coordinates actin-myosin contractility in the early embryo. Here, we show that ANI-1 localizes to the cleavage furrows of dividing neuroblasts during mid-embryogenesis and is required for their division. Embryos depleted of ani-1 display a range of ventral enclosure phenotypes, where ventral epidermal cells migrate with similar speeds to control embryos, but contralateral neighbors often fail to meet and are misaligned. The ventral enclosure phenotypes in ani-1 RNAi embryos suggest that the position or shape of neuroblasts is important for directing ventral epidermal cell migration, although does not rule out an autonomous requirement for ani-1 in the epidermal cells. Furthermore, we show that rho-1 and other regulators of nonmuscle myosin activity are required for ventral epidermal cell migration. Interestingly, altering nonmuscle myosin contractility alleviates or strengthens ani-1's ventral enclosure phenotypes. Our findings suggest that ventral enclosure is a complex process that likely relies on inputs from multiple tissues. © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

An in silico agent-based model demonstrates Reelin function in directing lamination of neurons during cortical development.

PubMed

Caffrey, James R; Hughes, Barry D; Britto, Joanne M; Landman, Kerry A

2014-01-01

The characteristic six-layered appearance of the neocortex arises from the correct positioning of pyramidal neurons during development and alterations in this process can cause intellectual disabilities and developmental delay. Malformations in cortical development arise when neurons either fail to migrate properly from the germinal zones or fail to cease migration in the correct laminar position within the cortical plate. The Reelin signalling pathway is vital for correct neuronal positioning as loss of Reelin leads to a partially inverted cortex. The precise biological function of Reelin remains controversial and debate surrounds its role as a chemoattractant or stop signal for migrating neurons. To investigate this further we developed an in silico agent-based model of cortical layer formation. Using this model we tested four biologically plausible hypotheses for neuron motility and four biologically plausible hypotheses for the loss of neuron motility (conversion from migration). A matrix of 16 combinations of motility and conversion rules was applied against the known structure of mouse cortical layers in the wild-type cortex, the Reelin-null mutant, the Dab1-null mutant and a conditional Dab1 mutant. Using this approach, many combinations of motility and conversion mechanisms can be rejected. For example, the model does not support Reelin acting as a repelling or as a stopping signal. In contrast, the study lends very strong support to the notion that the glycoprotein Reelin acts as a chemoattractant for neurons. Furthermore, the most viable proposition for the conversion mechanism is one in which conversion is affected by a motile neuron sensing in the near vicinity neurons that have already converted. Therefore, this model helps elucidate the function of Reelin during neuronal migration and cortical development.

Suppressed Sr segregation and performance of directly assembled La0.6Sr0.4Co0.2Fe0.8O3-δ oxygen electrode on Y2O3-ZrO2 electrolyte of solid oxide electrolysis cells

NASA Astrophysics Data System (ADS)

Ai, Na; He, Shuai; Li, Na; Zhang, Qi; Rickard, William D. A.; Chen, Kongfa; Zhang, Teng; Jiang, San Ping

2018-04-01

Active and stable oxygen electrode is probably the most important in the development of solid oxide electrolysis cells (SOECs) technologies. Herein, we report the successful development of mixed ionic and electronic conducting (MIEC) La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) perovskite oxides directly assembled on barrier-layer-free yttria-stabilized zirconia (YSZ) electrolyte as highly active and stable oxygen electrodes of SOECs. Electrolysis polarization effectively induces the formation of electrode/electrolyte interface, similar to that observed under solid oxide fuel cell (SOFC) operation conditions. However, in contrast to the significant performance decay under SOFC operation conditions, the cell with directly assembled LSCF oxygen electrodes shows excellent stability, tested for 300 h at 0.5 A cm-2 and 750 °C under SOEC operation conditions. Detailed microstructure and phase analysis reveal that Sr segregation is inevitable for LSCF electrode, but anodic polarization substantially suppresses Sr segregation and migration to the electrode/electrolyte interface, leading to the formation of stable and efficient electrode/electrolyte interface for water and CO2 electrolysis under SOECs operation conditions. The present study demonstrates the feasibility of using directly assembled MIEC cobaltite based oxygen electrodes on barrier-layer-free YSZ electrolyte of SOECs.

Sensing of substratum rigidity and directional migration by fast-crawling cells

NASA Astrophysics Data System (ADS)

Okimura, Chika; Sakumura, Yuichi; Shimabukuro, Katsuya; Iwadate, Yoshiaki

2018-05-01

Living cells sense the mechanical properties of their surrounding environment and respond accordingly. Crawling cells detect the rigidity of their substratum and migrate in certain directions. They can be classified into two categories: slow-moving and fast-moving cell types. Slow-moving cell types, such as fibroblasts, smooth muscle cells, mesenchymal stem cells, etc., move toward rigid areas on the substratum in response to a rigidity gradient. However, there is not much information on rigidity sensing in fast-moving cell types whose size is ˜10 μ m and migration velocity is ˜10 μ m /min . In this study, we used both isotropic substrata with different rigidities and an anisotropic substratum that is rigid on the x axis but soft on the y axis to demonstrate rigidity sensing by fast-moving Dictyostelium cells and neutrophil-like differentiated HL-60 cells. Dictyostelium cells exerted larger traction forces on a more rigid isotropic substratum. Dictyostelium cells and HL-60 cells migrated in the "soft" direction on the anisotropic substratum, although myosin II-null Dictyostelium cells migrated in random directions, indicating that rigidity sensing of fast-moving cell types differs from that of slow types and is induced by a myosin II-related process.

Sensing of substratum rigidity and directional migration by fast-crawling cells.

PubMed

Okimura, Chika; Sakumura, Yuichi; Shimabukuro, Katsuya; Iwadate, Yoshiaki

2018-05-01

Living cells sense the mechanical properties of their surrounding environment and respond accordingly. Crawling cells detect the rigidity of their substratum and migrate in certain directions. They can be classified into two categories: slow-moving and fast-moving cell types. Slow-moving cell types, such as fibroblasts, smooth muscle cells, mesenchymal stem cells, etc., move toward rigid areas on the substratum in response to a rigidity gradient. However, there is not much information on rigidity sensing in fast-moving cell types whose size is ∼10 μm and migration velocity is ∼10 μm/min. In this study, we used both isotropic substrata with different rigidities and an anisotropic substratum that is rigid on the x axis but soft on the y axis to demonstrate rigidity sensing by fast-moving Dictyostelium cells and neutrophil-like differentiated HL-60 cells. Dictyostelium cells exerted larger traction forces on a more rigid isotropic substratum. Dictyostelium cells and HL-60 cells migrated in the "soft" direction on the anisotropic substratum, although myosin II-null Dictyostelium cells migrated in random directions, indicating that rigidity sensing of fast-moving cell types differs from that of slow types and is induced by a myosin II-related process.

A galvanotaxis assay for analysis of neural precursor cell migration kinetics in an externally applied direct current electric field.

PubMed

Babona-Pilipos, Robart; Popovic, Milos R; Morshead, Cindi M

2012-10-13

The discovery of neural stem and progenitor cells (collectively termed neural precursor cells) (NPCs) in the adult mammalian brain has led to a body of research aimed at utilizing the multipotent and proliferative properties of these cells for the development of neuroregenerative strategies. A critical step for the success of such strategies is the mobilization of NPCs toward a lesion site following exogenous transplantation or to enhance the response of the endogenous precursors that are found in the periventricular region of the CNS. Accordingly, it is essential to understand the mechanisms that promote, guide, and enhance NPC migration. Our work focuses on the utilization of direct current electric fields (dcEFs) to promote and direct NPC migration - a phenomenon known as galvanotaxis. Endogenous physiological electric fields function as critical cues for cell migration during normal development and wound repair. Pharmacological disruption of the trans-neural tube potential in axolotl embryos causes severe developmental malformations(1). In the context of wound healing, the rate of repair of wounded cornea is directly correlated with the magnitude of the epithelial wound potential that arises after injury, as shown by pharmacological enhancement or disruption of this dcEF(2-3). We have demonstrated that adult subependymal NPCs undergo rapid and directed cathodal migration in vitro when exposed to an externally applied dcEF. In this protocol we describe our lab's techniques for creating a simple and effective galvanotaxis assay for high-resolution, long-term observation of directed cell body translocation (migration) on a single-cell level. This assay would be suitable for investigating the mechanisms that regulate dcEF transduction into cellular motility through the use of transgenic or knockout mice, short interfering RNA, or specific receptor agonists/antagonists.

Migration & Extra-solar Terrestrial Planets: Watering the Planets

NASA Astrophysics Data System (ADS)

Carter-Bond, Jade C.; O'Brien, David P.; Raymond, Sean N.

2014-04-01

A diverse range of terrestrial planet compositions is believed to exist within known extrasolar planetary systems, ranging from those that are relatively Earth-like to those that are highly unusual, dominated by species such as refractory elements (Al and Ca) or C (as pure C, TiC and SiC)(Bond et al. 2010b). However, all prior simulations have ignored the impact that giant planet migration during planetary accretion may have on the final terrestrial planetary composition. Here, we combined chemical equilibrium models of the disk around five known planetary host stars (Solar, HD4203, HD19994, HD213240 and Gl777) with dynamical models of terrestrial planet formation incorporating various degrees of giant planet migration. Giant planet migration is found to drastically impact terrestrial planet composition by 1) increasing the amount of Mg-silicate species present in the final body; and 2) dramatically increasing the efficiency and amount of water delivered to the terrestrial bodies during their formation process.

Lignans from the stems and leaves of Brandisia hancei and their effects on VEGF-induced vascular permeability and migration of HRECs and DLAV formation in zebrafish.

PubMed

Lee, Ik-Soo; Kim, Young Sook; Jung, Seung-Hyun; Yu, Song Yi; Kim, Joo-Hwan; Sun, Hang; Kim, Jin Sook

2015-01-01

In our continuing search for novel antiangiogenic agents, a new lignan glycoside, (7R,8R)-1-(4-O-β-d-glucopyranosyl-3-methoxyphenyl)-2-{2-methoxy-4-[1-(E)-propene-3-ol]-phenoxyl}-propane-1,3-diol (1), along with three known lignans (2-4), were isolated from the 80% EtOH extract of Brandisia hancei stems and leaves. These isolates (1-4) were subjected to an in vitro bioassay to evaluate their effects on vascular endothelial growth factor (VEGF)-induced vascular permeability and migration of human retinal endothelial cells (HRECs). Of the compounds tested, compound 1 resulted in the greatest reduction in VEGF-induced vascular permeability by about 31.5% at 10 μM compared to the VEGF-treated control. In the migration assay, compounds 1 and 2 significantly decreased VEGF-induced HREC migration. Furthermore, zebrafish embryos treated with compounds 1 and 2 showed mild reductions of dorsal longitudinal anastomotic vessel (DLAV) formation.

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

Planetary system formation: Effects of planet-disk tidal interaction

NASA Astrophysics Data System (ADS)

Bryden, Geoffrey

The standard theory of planet formation begins with the coagulation of solid planetesimals (Safronov 1969, Wetherill & Stewart 1989) followed by the accretion of disk gas once the solid core reaches a critical mass >~10M⊕ (Perri & Cameron 1974, Mizuno 1980, Bodenheimer & Pollack 1986). The classic picture of planet formation, in which each planet's position in the nebula remain fixed, is challenged by the observed distribution of extra-solar planets (e.g. Mayor & Queloz 1995, Butler et al. 1999). The majority of these planets are on short-period orbits ( P<~10 days) very close to their central stars ( ap<~0.1 AU), suggesting that orbital migration plays an important role in the formation of planetary systems. The intent of this thesis is to explore the inclusion of protoplanetary tidal forces into the classical theory of planetary system formation. Protoplanetary interaction with the surrounding gaseous nebulae directly determines giant planets' semi-major axes, masses, gas/solid ratio, and relative spacing. In essence, the process of gap formation determines the primary observational characteristics of both individual planets and their composite systems. Detailed simulations of gap formation produce a range of planetary masses consistent with the observed distribution. Fully self-interacting models of planetary system formation can be used to create a wide variety of planetary systems, ranging from the solar system to Upsilon Andromeda (Butler et al. 1999).

Grip and slip of L1-CAM on adhesive substrates direct growth cone haptotaxis

PubMed Central

Abe, Kouki; Katsuno, Hiroko; Toriyama, Michinori; Baba, Kentarou; Mori, Tomoyuki; Hakoshima, Toshio; Kanemura, Yonehiro; Watanabe, Rikiya; Inagaki, Naoyuki

2018-01-01

Chemical cues presented on the adhesive substrate direct cell migration, a process termed haptotaxis. To migrate, cells must generate traction forces upon the substrate. However, how cells probe substrate-bound cues and generate directional forces for migration remains unclear. Here, we show that the cell adhesion molecule (CAM) L1-CAM is involved in laminin-induced haptotaxis of axonal growth cones. L1-CAM underwent grip and slip on the substrate. The ratio of the grip state was higher on laminin than on the control substrate polylysine; this was accompanied by an increase in the traction force upon laminin. Our data suggest that the directional force for laminin-induced growth cone haptotaxis is generated by the grip and slip of L1-CAM on the substrates, which occur asymmetrically under the growth cone. This mechanism is distinct from the conventional cell signaling models for directional cell migration. We further show that this mechanism is disrupted in a human patient with L1-CAM syndrome, suffering corpus callosum agenesis and corticospinal tract hypoplasia. PMID:29483251

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.

Comments in reply: new directions in migration research.

PubMed

Shaw, R P

1986-01-01

The author comments on a review of his recent book NEW DIRECTIONS IN MIGRATION RESEARCH and reflects on theory and model specification, problems of estimation and statistical inference, realities of temporal and spatial heterogeneity, choices of explanatory variables, and the importance of broader political issues in migration studies. A core hypothesis is that market forces have declined as influences on internal migration in Canada over the last 30 years. Theoretical underpinnings include declining relevance of wage considerations in the decision to migrate on the assumption that marginal utility of money diminishes and marginal utility of leisure increases as society becomes wealthier. The author perceives the human capital model to have limitations and is especially troubled by the "as if" clause--that all migrants behave "as if" they calculate benefits and risks with equal rigor. The author has "shadowed" and not quantified the costs involved. He implies that normative frameworks for future migration research and planning should be established.

Visualization of migration of human cortical neurons generated from induced pluripotent stem cells.

PubMed

Bamba, Yohei; Kanemura, Yonehiro; Okano, Hideyuki; Yamasaki, Mami

2017-09-01

Neuronal migration is considered a key process in human brain development. However, direct observation of migrating human cortical neurons in the fetal brain is accompanied by ethical concerns and is a major obstacle in investigating human cortical neuronal migration. We established a novel system that enables direct visualization of migrating cortical neurons generated from human induced pluripotent stem cells (hiPSCs). We observed the migration of cortical neurons generated from hiPSCs derived from a control and from a patient with lissencephaly. Our system needs no viable brain tissue, which is usually used in slice culture. Migratory behavior of human cortical neuron can be observed more easily and more vividly by its fluorescence and glial scaffold than that by earlier methods. Our in vitro experimental system provides a new platform for investigating development of the human central nervous system and brain malformation. Copyright © 2017 Elsevier B.V. All rights reserved.

Direct observations of American eels migrating across the continental shelf to the Sargasso Sea

PubMed Central

Béguer-Pon, Mélanie; Castonguay, Martin; Shan, Shiliang; Benchetrit, José; Dodson, Julian J.

2015-01-01

Since inferring spawning areas from larval distributions in the Sargasso Sea a century ago, the oceanic migration of adult American eels has remained a mystery. No adult eel has ever been observed migrating in the open ocean or in the spawning area. Here, we track movements of maturing eels equipped with pop-up satellite archival tags from the Scotian Shelf (Canada) into the open ocean, with one individual migrating 2,400 km to the northern limit of the spawning site in the Sargasso Sea. The reconstructed routes suggest a migration in two phases: one over the continental shelf and along its edge in shallow waters; the second in deeper waters straight south towards the spawning area. This study is the first direct evidence of adult Anguilla migrating to the Sargasso Sea and represents an important step forward in the understanding of routes and migratory cues. PMID:26505325

Electric Signals Regulate the Directional Migration of Oligodendrocyte Progenitor Cells (OPCs) via β1 Integrin.

PubMed

Zhu, Bangfu; Nicholls, Matthew; Gu, Yu; Zhang, Gaofeng; Zhao, Chao; Franklin, Robin J M; Song, Bing

2016-11-22

The guided migration of neural cells is essential for repair in the central nervous system (CNS). Oligodendrocyte progenitor cells (OPCs) will normally migrate towards an injury site to re-sheath demyelinated axons; however the mechanisms underlying this process are not well understood. Endogenous electric fields (EFs) are known to influence cell migration in vivo, and have been utilised in this study to direct the migration of OPCs isolated from neonatal Sprague-Dawley rats. The OPCs were exposed to physiological levels of electrical stimulation, and displayed a marked electrotactic response that was dependent on β1 integrin, one of the key subunits of integrin receptors. We also observed that F-actin, an important component of the cytoskeleton, was re-distributed towards the leading edge of the migrating cells, and that this asymmetric rearrangement was associated with β1 integrin function.

The effects of small interfering RNA–targeting tissue factor on an in vitro model of neovascularization

PubMed Central

Peng, Wenyan; Yu, Ying; Li, Tiejun; Zhu, Yuanyuan

2013-01-01

Purpose Tissue factor (TF) plays an important role in neovascularization (NV). This study aimed to determine whether small interfering RNA–targeting TF (TF-siRNA) could knock down TF expression and inhibit cell proliferation, cell migration, and tube formation in an in vitro model of NV. Methods Lipopolysaccharide (LPS) was used to stimulate human umbilical vein endothelial cell (HUVEC) lines to express TF and mimic certain phenotypes of NV in vitro. HUVECs were transfected with TF-siRNAs and control siRNAs using LipofectamineTM 2000. The inhibitory effect of the siRNAs on the expression of TF mRNA and protein was evaluated by quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) and western blot analysis. The effects on the cell viability, migration, and tube formation of siRNA-treated cells were examined by MTT assay, wound-healing assay, and Matrigel-induced capillary tube formation. Results Lipopolysaccharide treatment increased the expression of TF. TF-siRNAs effectively knocked down TF expression, with the most efficient TF-siRNA reducing 78.9% of TF expression. TF protein was also notably curtailed by TF-siRNA. The MTT and wound-healing assays showed that the TF-siRNA substantially inhibited the proliferation and migration of HUVECs. Tube formation was decreased by 47.4% and 59.4% in cells treated with the TF-siRNA and vascular endothelial growth factor–siRNA, respectively, compared with the blank control. Conclusions TF-siRNA can knockdown TF expression and inhibit cell proliferation, migration, and tube formation in vitro. TF-siRNA may provide a novel therapeutic candidate for NV-related diseases. PMID:23805036

Silicone Migration From Baked-on Silicone Layers. Particle Characterization in Placebo and Protein Solutions.

PubMed

Funke, Stefanie; Matilainen, Julia; Nalenz, Heiko; Bechtold-Peters, Karoline; Mahler, Hanns-Christian; Friess, Wolfgang

2016-12-01

A significant number of therapeutic proteins are marketed as pre-filled syringes or other drug/device combination products and have been safely used in these formats for years. Silicone oil, which is used as lubricant, can migrate into the drug product and may interact with therapeutic proteins. In this study, particles in the size range of 0.2-5 μm and ≥1 μm as determined by resonant mass measurement and micro-flow imaging/light obscuration, respectively, resulted from silicone sloughing off the container barrel after agitation. The degree of droplet formation correlated well with the applied baked-on silicone levels of 13 μg and 94 μg per cartridge. Silicone migration was comparable in placebo, 2 mg/mL and 33 mg/mL IgG1 formulations containing 0.04% (w/v) polysorbate 20. Headspace substantially increased the formation of silicone droplets during agitation. The highest particle concentrations reached, however, were still very low compared to numbers described for spray-on siliconized containers. When applying adequate baked-on silicone levels below 100 μg, bake-on siliconization efficiently limits silicone migration into the drug product without compromising device functionality. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

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

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.

Chemometric differentiation of crude oil families in the San Joaquin Basin, California

USGS Publications Warehouse

Peters, Kenneth E.; Coutrot, Delphine; Nouvelle, Xavier; Ramos, L. Scott; Rohrback, Brian G.; Magoon, Leslie B.; Zumberge, John E.

2013-01-01

Chemometric analyses of geochemical data for 165 crude oil samples from the San Joaquin Basin identify genetically distinct oil families and their inferred source rocks and provide insight into migration pathways, reservoir compartments, and filling histories. In the first part of the study, 17 source-related biomarker and stable carbon-isotope ratios were evaluated using a chemometric decision tree (CDT) to identify families. In the second part, ascendant hierarchical clustering was applied to terpane mass chromatograms for the samples to compare with the CDT results. The results from the two methods are remarkably similar despite differing data input and assumptions. Recognized source rocks for the oil families include the (1) Eocene Kreyenhagen Formation, (2) Eocene Tumey Formation, (3–4) upper and lower parts of the Miocene Monterey Formation (Buttonwillow depocenter), and (5–6) upper and lower parts of the Miocene Monterey Formation (Tejon depocenter). Ascendant hierarchical clustering identifies 22 oil families in the basin as corroborated by independent data, such as carbon-isotope ratios, sample location, reservoir unit, and thermal maturity maps from a three-dimensional basin and petroleum system model. Five families originated from the Eocene Kreyenhagen Formation source rock, and three families came from the overlying Eocene Tumey Formation. Fourteen families migrated from the upper and lower parts of the Miocene Monterey Formation source rocks within the Buttonwillow and Tejon depocenters north and south of the Bakersfield arch. The Eocene and Miocene families show little cross-stratigraphic migration because of seals within and between the source rocks. The data do not exclude the possibility that some families described as originating from the Monterey Formation actually came from source rock in the Temblor Formation.

Polar Cap Formation on Ganymede

NASA Technical Reports Server (NTRS)

Pilcher, C. B.; Shaya, E. J.

1985-01-01

Since thermal migration is not an effective mechanism for water transport in the polar regions at the Galilean satellites, some other process must be responsible for the formation of Ganymede's polar caps. It is proposed that Ganymede's polar caps are the optical manifestation of a process that began with the distribution of an ice sheet over the surface of Ganymede. The combined processes of impact gardening and thermal migration led, in regions at latitudes less than 40 to 45 deg., to the burial of some fraction of this ice, the migration of some to the polar caps margins, and a depletion of free ice in the optical surface. At higher latitudes, no process was effective in removing ice from the optical surface, so the remanants of the sheet are visible today.

[Study of migration and distribution of bone marrow cells transplanted animals with B16 melanoma ].

PubMed

Poveshchenko, A F; Solovieva, A O; Zubareva, K E; Strunkin, D N; Gricyk, O B; Poveshchenko, O V; Shurlygina, A V; Konenkov, V I

2017-01-01

Purpose. Reveal features migration and distribution of syngeneic bone marrow cells (BMC) and subpopulations (MSC) after transplantation into the recipient carrier B16 melanoma bodies. Methods. We used mouse male and female C57BL/6 mice. Induction of Tumor Growth: B16 melanoma cells implanted subcutaneously into right hind paw of female C57BL/6 mice at a dose of 2.5 x 105 cells / mouse. migration study in vivo distribution and BMC and MSC was performed using genetic markers - Y-chromosome specific sequence line male C57Bl/6 syngeneic intravenous transplantation in females using the polymerase chain reaction (PCR) in real time on Authorized Termal Cycler - Light Cycler 480 II / 96 (Roche). Introduction suspension of unseparated bone marrow cells, mesenchymal stem cells from donor to recipient male mice (syngeneic recipient female C57BL/6), followed by isolation of recipients of organs was performed at regular intervals, then of organ recipients isolated DNA. Results. It was shown that bone marrow cells positive for Y-chromosome in migrate lymphoid (lymph nodes, spleen, bone marrow) or in non-lymphoid organs (liver, heart, brain, skin) syngeneic recipients. In addition to the migration of cells from the bone marrow to other organs, there is a way back migration of cells from the circulation to the bone marrow. B16 melanoma stimulates the migration of transplanted MSCs and BMC in bone marrow. It is found that tumor growth enhanced migration of transplanted bone marrow cells, including populations of MSCs in the bone marrow. In the early stages of tumor formation MSC migration activity higher than the BMC. In the later stages of tumor formation undivided population of bone marrow cells migrate to the intense swelling compared with a population of MSCs. Conclusion. The possibility of using bone marrow MSCs for targeted therapy of tumor diseases, because migration of MSCs in tumor tissue can be used to effectively deliver anticancer drugs.

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. PMID:19816580

Optimal strategies for insects migrating in the flight boundary layer: mechanisms and consequences.

PubMed

Srygley, Robert B; Dudley, Robert

2008-07-01

Directed aerial displacement requires that a volant organism's airspeed exceeds ambient wind speed. For biologically relevant altitudes, wind speed increases exponentially with increased height above the ground. Thus, dispersal of most insects is influenced by atmospheric conditions. However, insects that fly close to the Earth's surface displace within the flight boundary layer where insect airspeeds are relatively high. Over the past 17 years, we have studied boundary-layer insects by following individuals as they migrate across the Caribbean Sea and the Panama Canal. Although most migrants evade either drought or cold, nymphalid and pierid butterflies migrate across Panama near the onset of the rainy season. Dragonflies of the genus Pantala migrate in October concurrently with frontal weather systems. Migrating the furthest and thereby being the most difficult to study, the diurnal moth Urania fulgens migrates between Central and South America. Migratory butterflies and dragonflies are capable of directed movement towards a preferred compass direction in variable winds, whereas the moths drift with winds over water. Butterflies orient using both global and local cues. Consistent with optimal migration theory, butterflies and dragonflies adjust their flight speeds in ways that maximize migratory distance traveled per unit fuel, whereas the moths do not. Moreover, only butterflies adjust their flight speed in relation to endogenous fat reserves. It is likely that these insects use optic flow to gauge their speed and drift, and thus must migrate where sufficient detail in the Earth's surface is visible to them. The abilities of butterflies and dragonflies to adjust their airspeed over water indicate sophisticated control and guidance systems pertaining to migration.

Effects of direct current electric fields on lung cancer cell electrotaxis in a PMMA-based microfluidic device.

PubMed

Li, Yaping; Xu, Tao; Chen, Xiaomei; Lin, Shin; Cho, Michael; Sun, Dong; Yang, Mengsu

2017-03-01

Tumor metastasis is the primary cause of cancer death. Numerous studies have demonstrated the electrotactic responses of various cancer cell types, and suggested its potential implications in metastasis. In this study, we used a microfluidic device to emulate endogenous direct current electric field (dcEF) environment, and studied the electrotactic migration of non-small cell lung cancer cell lines (H460, HCC827, H1299, and H1975) and the underlying mechanisms. These cell lines exhibited greatly different response in applied dcEFs (2-6 V/cm). While H460 cells (large cell carcinoma) showed slight migration toward cathode, H1299 cells (large cell carcinoma) showed increased motility and dcEF-dependent anodal migration with cell reorientation. H1975 cells (adenocarcinoma) showed dcEF-dependent cathodal migration with increased motility, and HCC827 cells (adenocarcinoma) responded positively in migration speed and reorientation but minimally in migrating directions to dcEF. Activation of MAPK and PI3K signaling pathways was found to be associated with the realignment and directed migration of lung cancer cells. In addition, both Ca 2+ influx through activated stretch-activated calcium channels (SACCs) (but not voltage-gated calcium channels, VGCCs) and Ca 2+ release from intracellular storage were involved in lung cancer cell electrotactic responses. The results demonstrated that the microfluidic device provided a stable and controllable microenvironment for cell electrotaxis study, and revealed that the electrotactic responses of lung cancer cells were heterogeneous and cell-type dependent, and multiple signals contributed to lung cancer cells electrotaxis.

Radiation resistance of oxide dispersion strengthened alloys: Perspectives from in situ observations and rate theory calculations

DOE PAGES

Liu, Xiang; Miao, Yinbin; Li, Meimei; ...

2018-04-15

Here, in situ ion irradiation and rate theory calculations were employed to directly compare the radiation resistance of an oxide dispersion strengthened alloy with that of a conventional ferritic/martensitic alloy. Compared to the rapid buildup of dislocation loops, loop growth, and formation of network dislocations in the conventional ferritic/martensitic alloy, the superior radiation resistance of the oxide dispersion strengthened alloy is manifested by its stable dislocation structure under the same irradiation conditions. Thus, the results are consistent with rate theory calculations, which show that high-density nanoparticles can significantly reduce freely migrating defects and suppress the buildup of clustered defects.

Radiation resistance of oxide dispersion strengthened alloys: Perspectives from in situ observations and rate theory calculations

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

Liu, Xiang; Miao, Yinbin; Li, Meimei

Here, in situ ion irradiation and rate theory calculations were employed to directly compare the radiation resistance of an oxide dispersion strengthened alloy with that of a conventional ferritic/martensitic alloy. Compared to the rapid buildup of dislocation loops, loop growth, and formation of network dislocations in the conventional ferritic/martensitic alloy, the superior radiation resistance of the oxide dispersion strengthened alloy is manifested by its stable dislocation structure under the same irradiation conditions. Thus, the results are consistent with rate theory calculations, which show that high-density nanoparticles can significantly reduce freely migrating defects and suppress the buildup of clustered defects.

Inhibition of connective tissue growth factor (CTGF/CCN2) in gallbladder cancer cells leads to decreased growth in vitro.

PubMed

Garcia, Patricia; Leal, Pamela; Ili, Carmen; Brebi, Priscilla; Alvarez, Hector; Roa, Juan C

2013-06-01

Gallbladder cancer (GBC) is an aggressive neoplasm associated with late diagnosis, unsatisfactory treatment and poor prognosis. Previous work showed that connective tissue growth factor (CTGF) expression is increased in this malignancy. This matricellular protein plays an important role in various cellular processes and its involvement in the tumorigenesis of several human cancers has been demonstrated. However, the precise function of CTGF expression in cancer cells is yet to be determined. The aim of this study was to evaluate the CTGF expression in gallbladder cancer cell lines, and its effect on cell viability, colony formation and in vitro cell migration. CTGF expression was evaluated in seven GBC cell lines by Western blot assay. Endogenous CTGF expression was downregulated by lentiviral shRNA directed against CTGF mRNA in G-415 cells, and the effects on cell viability, anchorage-independent growth and migration was assessed by comparing them to scrambled vector-transfected cells. Knockdown of CTGF resulted in significant reduction in cell viability, colony formation and anchorage-independent growth (P < 0.05). An increased p27 expression was observed in G-415 cells with loss of CTGF function. Our results suggest that high expression of this protein in gallbladder cancer may confer a growth advantage for neoplastic cells. © 2013 The Authors. International Journal of Experimental Pathology © 2013 International Journal of Experimental Pathology.

CDC-42 Orients Cell Migration during Epithelial Intercalation in the Caenorhabditis elegans Epidermis.

PubMed

Walck-Shannon, Elise; Lucas, Bethany; Chin-Sang, Ian; Reiner, David; Kumfer, Kraig; Cochran, Hunter; Bothfeld, William; Hardin, Jeff

2016-11-01

Cell intercalation is a highly directed cell rearrangement that is essential for animal morphogenesis. As such, intercalation requires orchestration of cell polarity across the plane of the tissue. CDC-42 is a Rho family GTPase with key functions in cell polarity, yet its role during epithelial intercalation has not been established because its roles early in embryogenesis have historically made it difficult to study. To circumvent these early requirements, in this paper we use tissue-specific and conditional loss-of-function approaches to identify a role for CDC-42 during intercalation of the Caenorhabditis elegans dorsal embryonic epidermis. CDC-42 activity is enriched in the medial tips of intercalating cells, which extend as cells migrate past one another. Moreover, CDC-42 is involved in both the efficient formation and orientation of cell tips during cell rearrangement. Using conditional loss-of-function we also show that the PAR complex functions in tip formation and orientation. Additionally, we find that the sole C. elegans Eph receptor, VAB-1, functions during this process in an Ephrin-independent manner. Using epistasis analysis, we find that vab-1 lies in the same genetic pathway as cdc-42 and is responsible for polarizing CDC-42 activity to the medial tip. Together, these data establish a previously uncharacterized role for polarized CDC-42, in conjunction with PAR-6, PAR-3 and an Eph receptor, during epithelial intercalation.

CDC-42 Orients Cell Migration during Epithelial Intercalation in the Caenorhabditis elegans Epidermis

PubMed Central

Lucas, Bethany; Chin-Sang, Ian; Reiner, David; Kumfer, Kraig

2016-01-01

Cell intercalation is a highly directed cell rearrangement that is essential for animal morphogenesis. As such, intercalation requires orchestration of cell polarity across the plane of the tissue. CDC-42 is a Rho family GTPase with key functions in cell polarity, yet its role during epithelial intercalation has not been established because its roles early in embryogenesis have historically made it difficult to study. To circumvent these early requirements, in this paper we use tissue-specific and conditional loss-of-function approaches to identify a role for CDC-42 during intercalation of the Caenorhabditis elegans dorsal embryonic epidermis. CDC-42 activity is enriched in the medial tips of intercalating cells, which extend as cells migrate past one another. Moreover, CDC-42 is involved in both the efficient formation and orientation of cell tips during cell rearrangement. Using conditional loss-of-function we also show that the PAR complex functions in tip formation and orientation. Additionally, we find that the sole C. elegans Eph receptor, VAB-1, functions during this process in an Ephrin-independent manner. Using epistasis analysis, we find that vab-1 lies in the same genetic pathway as cdc-42 and is responsible for polarizing CDC-42 activity to the medial tip. Together, these data establish a previously uncharacterized role for polarized CDC-42, in conjunction with PAR-6, PAR-3 and an Eph receptor, during epithelial intercalation. PMID:27861585

Turning points in international labor migration: a case study of Thailand.

PubMed

Vasuprasat, P

1994-01-01

"This article describes the dynamics of the structural transformation of the Thai economy, labor migration and direct foreign investment and proposes an econometric model to explain the migration phenomenon. Though migration shifts have been significantly influenced by political factors such as the Gulf crisis and tensions with Saudi Arabia, economic factors such as the Thai government's liberalization of markets and the expansion of trade and direct foreign investment have contributed to changes in labor market needs. The economic conditions of a shift from net exporter to net importer for labor are posited in the model. The empirical results reveal a turning point in labor migration from Thailand and also confirm the contribution of commodity export in place of labor export in creating employment and income." excerpt

An insight on acyl migration in solvent-free ethanolysis of model triglycerides using Novozym 435.

PubMed

Sánchez, Daniel Alberto; Tonetto, Gabriela Marta; Ferreira, María Luján

2016-02-20

In this work, the ethanolysis of triglycerides catalyzed by immobilized lipase was studied, focusing on the secondary reaction of acyl migration. The catalytic tests were performed in a solvent-free reaction medium using Novozym 435 as biocatalyst. The selected experimental variables were biocatalyst loading (5-20mg), reaction time (30-90min), and chain length of the fatty acids in triglycerides with and without unsaturation (short (triacetin), medium (tricaprylin) and long (tripalmitin/triolein)). The formation of 2-monoglyceride by ethanolysis of triglycerides was favored by long reaction times and large biocatalyst loading with saturated short- to medium-chain triglycerides. In the case of long-chain triglycerides, the formation of this monoglyceride was widely limited by acyl migration. In turn, acyl migration increased the yield of ethyl esters and minimized the content of monoglycerides and diglycerides. Thus, the enzymatic synthesis of biodiesel was favored by long-chain triglycerides (which favor the acyl migration), long reaction times and large biocatalyst loading. The conversion of acylglycerides made from long-chain fatty acids with unsaturation was relatively low due to limitations in their access to the active site of the lipase. Copyright © 2016 Elsevier B.V. All rights reserved.

RELIABILITY AND APPLICABILITY OF DSTS AND BOTTOMHOLE PRESSURE MEASUREMENTS IN TEXAS GULF TERTIARY FORMATIONS

EPA Science Inventory

Pressure data gathered from drillstem tests (DSTs) and bottomhole pressure measurements provide critical information toward formation and can be used for an assessment of prevailing pressure regimes and their influence on the migration potential of formation fluids. Reliability o...

Physical mechanisms for chemotactic pattern formation by bacteria.

PubMed Central

Brenner, M P; Levitov, L S; Budrene, E O

1998-01-01

This paper formulates a theory for chemotactic pattern formation by the bacteria Escherichia coli in the presence of excreted attractant. In a chemotactically neutral background, through chemoattractant signaling, the bacteria organize into swarm rings and aggregates. The analysis invokes only those physical processes that are both justifiable by known biochemistry and necessary and sufficient for swarm ring migration and aggregate formation. Swarm rings migrate in the absence of an external chemoattractant gradient. The ring motion is caused by the depletion of a substrate that is necessary to produce attractant. Several scaling laws are proposed and are demonstrated to be consistent with experimental data. Aggregate formation corresponds to finite time singularities in which the bacterial density diverges at a point. Instabilities of swarm rings leading to aggregate formation occur via a mechanism similar to aggregate formation itself: when the mass density of the swarm ring exceeds a threshold, the ring collapses cylindrically and then destabilizes into aggregates. This sequence of events is demonstrated both in the theoretical model and in the experiments. PMID:9545032

Veins in Silicates of IIE Iron Mont Dieu II: Melt Migration Caused by Impact?

NASA Astrophysics Data System (ADS)

Van Roosbroek, N.; Debaille, V.; Pittarello, L.; Hecht, L.; Claeys, Ph.

2014-09-01

Mont Dieu II is a ~450kg meteorite classified as IIE iron. The primitive silicate inclusions can be linked to the H-chondrites. Thick metal veins with angular clasts crosscut these inclusions and could point to an impact-melt migration formation.

Atomic-Scale Observations of (010) LiFePO4 Surfaces Before and After Chemical Delithiation.

PubMed

Kobayashi, Shunsuke; Fisher, Craig A J; Kato, Takeharu; Ukyo, Yoshio; Hirayama, Tsukasa; Ikuhara, Yuichi

2016-09-14

The ability to view directly the surface structures of battery materials with atomic resolution promises to dramatically improve our understanding of lithium (de)intercalation and related processes. Here we report the use of state-of-the-art scanning transmission electron microscopy techniques to probe the (010) surface of commercially important material LiFePO4 and compare the results with theoretical models. The surface structure is noticeably different depending on whether Li ions are present in the topmost surface layer or not. Li ions are also found to migrate back to surface regions from within the crystal relatively quickly after partial delithiation, demonstrating the facile nature of Li transport in the [010] direction. The results are consistent with phase transformation models involving metastable phase formation and relaxation, providing atomic-level insights into these fundamental processes.

Carrier-envelope phase dependence of the directional fragmentation and hydrogen migration in toluene in few-cycle laser fields.

PubMed

Li, Hui; Kling, Nora G; Förg, Benjamin; Stierle, Johannes; Kessel, Alexander; Trushin, Sergei A; Kling, Matthias F; Kaziannis, Spyros

2016-07-01

The dissociative ionization of toluene initiated by a few-cycle laser pulse as a function of the carrier envelope phase (CEP) is investigated using single-shot velocity map imaging. Several ionic fragments, CH3 (+), H2 (+), and H3 (+), originating from multiply charged toluene ions present a CEP-dependent directional emission. The formation of H2 (+) and H3 (+) involves breaking C-H bonds and forming new bonds between the hydrogen atoms within the transient structure of the multiply charged precursor. We observe appreciable intensity-dependent CEP-offsets. The experimental data are interpreted with a mechanism that involves laser-induced coupling of vibrational states, which has been found to play a role in the CEP-control of molecular processes in hydrocarbon molecules, and appears to be of general importance for such complex molecules.

Characterization and disinfection by-product formation potential of natural organic matter in surface and ground waters from Northern Florida

USGS Publications Warehouse

Rostad, C.E.; Leenheer, J.A.; Katz, B.; Martin, B.S.; Noyes, T.I.

2000-01-01

Streamwaters in northern Florida have large concentrations of natural organic matter (NOM), and commonly flow directly into the ground water system through karst features, such as sinkholes. In this study NOM from northern Florida stream and ground waters was fractionated, the fractions characterized by infrared (IR) and nuclear magnetic resonance (NMR), and then chlorinated to investigate their disinfection by-product (DBP) formation potential (FP). As the NOM character changed (as quantified by changes in NOM distribution in various fractions, such as hydrophilic acids or hydrophobic neutrals) due to migration through the aquifer, the total organic halide (TOX)-FP and trihalomethane (THM)-FP yield of each of these fractions varied also. In surface waters, the greatest DBP yields were produced by the colloid fraction. In ground waters, DBP yield of the hydrophobic acid fraction (the greatest in terms of mass) decreased during infiltration.

Actomyosin-dependent formation of the mechanosensitive talin–vinculin complex reinforces actin anchoring

PubMed Central

Ciobanasu, Corina; Faivre, Bruno; Le Clainche, Christophe

2014-01-01

The force generated by the actomyosin cytoskeleton controls focal adhesion dynamics during cell migration. This process is thought to involve the mechanical unfolding of talin to expose cryptic vinculin-binding sites. However, the ability of the actomyosin cytoskeleton to directly control the formation of a talin–vinculin complex and the resulting activity of the complex are not known. Here we develop a microscopy assay with pure proteins in which the self-assembly of actomyosin cables controls the association of vinculin to a talin-micropatterned surface in a reversible manner. Quantifications indicate that talin refolding is limited by vinculin dissociation and modulated by the actomyosin network stability. Finally, we show that the activation of vinculin by stretched talin induces a positive feedback that reinforces the actin–talin–vinculin association. This in vitro reconstitution reveals the mechanism by which a key molecular switch senses and controls the connection between adhesion complexes and the actomyosin cytoskeleton. PMID:24452080

Atomic origins of water-vapour-promoted alloy oxidation

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

Luo, Langli; Su, Mao; Yan, Pengfei

The presence of water vapor, intentional or unavoidable, is crucial to many materials applications, such as steam generator, turbine engine, fuel cell, catalyst, and corrosion 1-6. Phenomenologically, water vapor has been noticed to accelerate oxidation of metals/alloys 7,8, however, the atomistic mechanisms remain elusive. Herein, through direct in situ atomic-scale transmission electron microscopy observation and density functional theory calculation, we reveal that water vapor enhanced oxidation of Ni-Cr alloy is associated with proton dissolution promoted vacancy formation, migration and clustering. Protons derived from water dissociation occupy interstitial position in the oxide lattice, which consequently leads to the lowering of bothmore » vacancy formation energy and the cation diffusion barrier. The atomic scale observations reveal a water vapor derived proton mediated oxide growth mechanism, which provides insights for reckoning many technological processes concerning materials in moist environment at elevated temperatures.« less

Hydraulic fracture height limits and fault interactions in tight oil and gas formations

NASA Astrophysics Data System (ADS)

Flewelling, Samuel A.; Tymchak, Matthew P.; Warpinski, Norm

2013-07-01

widespread use of hydraulic fracturing (HF) has raised concerns about potential upward migration of HF fluid and brine via induced fractures and faults. We developed a relationship that predicts maximum fracture height as a function of HF fluid volume. These predictions generally bound the vertical extent of microseismicity from over 12,000 HF stimulations across North America. All microseismic events were less than 600 m above well perforations, although most were much closer. Areas of shear displacement (including faults) estimated from microseismic data were comparatively small (radii on the order of 10 m or less). These findings suggest that fracture heights are limited by HF fluid volume regardless of whether the fluid interacts with faults. Direct hydraulic communication between tight formations and shallow groundwater via induced fractures and faults is not a realistic expectation based on the limitations on fracture height growth and potential fault slip.

The search for a source rock for the giant Tar Sand triangle accumulation, southeastern Utah

USGS Publications Warehouse

Huntoon, J.E.; Hansley, P.L.; Naeser, N.D.

1999-01-01

A large proportion (about 36%) of the world's oil resource is contained in accumulations of heavy oil or tar. In these large deposits of degraded oil, the oil in place represents only a fraction of what was present at the time of accumulation. In many of these deposits, the source of the oil is unknown, and the oil is thought to have migrated over long distances to the reservoirs. The Tar Sand triangle in southeastern Utah contains the largest tar sand accumulation in the United States, with 6.3 billion bbl of heavy oil estimated to be in place. The deposit is thought to have originally contained 13-16 billion bbl prior to the biodegradation, water washing, and erosion that have taken place since the middle - late Tertiary. The source of the oil is unknown. The tar is primarily contained within the Lower Permian White Rim Sandstone, but extends into permeable parts of overlying and underlying beds. Oil is interpreted to have migrated into the White Rim sometime during the Tertiary when the formation was at a depth of approximately 3500 m. This conclusion is based on integration of fluid inclusion analysis, time-temperature reconstruction, and apatite fission-track modeling for the White Rim Sandstone. Homogenization temperatures cluster around 85-90??C for primary fluid inclusions in authigenic, nonferroan dolomite in the White Rim. The fluid inclusions are associated with fluorescent oil-bearing inclusions, indicating that dolomite precipitation was coeval with oil migration. Burial reconstruction suggests that the White Rim Sandstone reached its maximum burial depth from 60 to 24 Ma, and that maximum burial was followed by unroofing from 24 to 0 Ma. Time-temperature modeling indicates that the formation experienced temperatures of 85-90??C from about 35 to 40 Ma during maximum burial. Maximum formation temperatures of about 105-110??C were reached at about 24 Ma, just prior to unroofing. Thermal modeling is used to examine the history of potential source rocks for the White Rim oil. The most attractive potential sources for White Rim oil include beds within one or more of the following formations: the Proterozoic Chuar Group, which is present in the subsurface southwest of the Tar Sand triangle; the Mississippian Delle Phosphatic Member of the Deseret Limestone and equivalent formations, the Permian Kaibab Limestone, the Sinbad Limestone Member of the Triassic Moenkopi Formation, and the Jurassic Arapien Shale, Twin Creek Limestone, and Carmel Formation, which are present west of the Tar Sand triangle; the Pennsylvanian Paradox Formation in the Paradox basin east of the Tar Sand triangle; and the Permian Park City Formation northwest of the Tar Sand triangle. Each formation has a high total organic carbon content and is distributed over a wide enough geographic area to have provided a huge volume of oil. Source beds in all of the formations reached thermal maturity at times prior to or during the time that migration into the White Rim is interpreted to have occurred. Based on all available data, the most likely source for the Tar Sand triangle appears to be the Mississippian Delle Phosphatic Member of the Deseret Limestone. Secondary migration out of the Delle is interpreted to have occurred during the Cretaceous, during Sevier thrusting. Subsequent tertiary migration into the Tar Sand triangle reservoir is interpreted to have occurred later, during middle Tertiary Laramide deformation.

Migration Systems in Europe: Evidence From Harmonized Flow Data

PubMed Central

Kim, Keuntae; Raymer, James

2014-01-01

Empirical tests of migration systems theory require consistent and complete data on international migration flows. Publicly available data, however, represent an inconsistent and incomplete set of measurements obtained from a variety of national data collection systems. We overcome these obstacles by standardizing the available migration reports of sending and receiving countries in the European Union and Norway each year from 2003–2007 and by estimating the remaining missing flows. The resulting harmonized estimates are then used to test migration systems theory. First, locating thresholds in the size of flows over time, we identify three migration systems within the European Union and Norway. Second, examining the key determinants of flows with respect to the predictions of migration systems theory, our results highlight the importance of shared experiences of nation-state formation, geography, and accession status in the European Union. Our findings lend support to migration systems theory and demonstrate that knowledge of migration systems may improve the accuracy of migration forecasts toward managing the impacts of migration as a source of social change in Europe. PMID:22791267

A model for migration and accumulation of hydrocarbons in the Thamama and Arab reservoirs in Abu Dhabi, U.A.E.

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

Hawas, M.F.; Takezaki, H.

1995-08-01

The distribution of hydrocarbons in the Lower Cretaceous Thamama Group and Upper Jurassic Arab Formation in Abu Dhabi is influenced by the development of the intervening Hith anhydrites. The geochemical analysis of Thamama and Arab hydrocarbons indicate that they were generated from a common source rock: the Upper Jurassic Diyab Formation. Studies carried out on the Miocene sabkha anhydrites in the coastal flat west of Abu Dhabi supported a model for vertical migration through the Hith anhydrites under certain conditions. The established model implies that the Diyab oil and gas had migrated essentially vertically and individually which means that themore » oil migrated prior to the gas and their distribution is controlled by the differential sealing potential of the anhydrites at each migration phase: a Hith anhydrite bed of more than 30 feet (ft.) thick was a perfect seal for hydrocarbon migration into the Arab reservoirs. In this case, oils could not break through to the overlying Thamama group. But where the anhydride bed thicknesses dropped below 30 ft. thick, this permitted oil migration through to the overlying Thamama reservoirs during the oil generation phase in the Turonian time. At a later stage, with additional depth of burial and progressive diagenesis anhydrite beds as thin as 8 ft. thick became effective seals. These controlled the distribution of the gas during the gas generation phase in the Eocene time.« less

The Exoplanet Migration Timescale from K2 Young Clusters

NASA Astrophysics Data System (ADS)

Rizzuto, Aaron

A significant fraction of exoplanets orbit within 0.1 AU of their host star, with periods of <20 days. The discovery of these close-in planets has defied conventional models of planet formation and evolution based on our own solar system. It is widely accepted that these close-in planets did not form in such close proximity to their host stars (both rocky planets and hot Jupiters), but rather that dynamical or interactive processes caused them to migrate inwards from larger orbital semimajor axes and periods. There are multiple planet migration scenarios proposed in the literature, though it is unclear how much of the known planet population is attributable to each mechanism. Planetary migration models can be loosely divided into two categories: disk-driven migration and dynamical migration. Disk migration occurs over the lifetime of the protoplanetary disk (<5 Myr), while migration involving dynamical multi-body interactions operates on timescales of 100 Myr to 1Gyr, a lengthier process than disk migration. The K2 mission has measured planet formation timescales and migration pathways by sampling groups of stars at key ages. Over the past 10 campaigns, multiple groups of young stars have been observed by K2, ranging from the 10 Myr Upper Scorpius OB association, through the <120 Myr Pleiades cluster, to the ,600-800 Myr Hyades and Praesepe clusters. Upcoming data from more recent campaigns include the 2Myr Taurus region and significantly more Upper Scorpius members in C13 and 15. The frequency, orbital properties, and compositions of the exoplanet population in these samples of different age, with careful treatment of detection completeness, distinguish these scenarios of exoplanet migration as their host stars are settling onto the main sequence. We have pioneered efforts to identify transiting exoplanets in the K2 data for young clusters and moving groups, and have developed a new, highly complete, detrending algorithm for rotational induced variability that is 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.

Adult subependymal neural precursors, but not differentiated cells, undergo rapid cathodal migration in the presence of direct current electric fields.

PubMed

Babona-Pilipos, Robart; Droujinine, Ilia A; Popovic, Milos R; Morshead, Cindi M

2011-01-01

The existence of neural stem and progenitor cells (together termed neural precursor cells) in the adult mammalian brain has sparked great interest in utilizing these cells for regenerative medicine strategies. Endogenous neural precursors within the adult forebrain subependyma can be activated following injury, resulting in their proliferation and migration toward lesion sites where they differentiate into neural cells. The administration of growth factors and immunomodulatory agents following injury augments this activation and has been shown to result in behavioural functional recovery following stroke. With the goal of enhancing neural precursor migration to facilitate the repair process we report that externally applied direct current electric fields induce rapid and directed cathodal migration of pure populations of undifferentiated adult subependyma-derived neural precursors. Using time-lapse imaging microscopy in vitro we performed an extensive single-cell kinematic analysis demonstrating that this galvanotactic phenomenon is a feature of undifferentiated precursors, and not differentiated phenotypes. Moreover, we have shown that the migratory response of the neural precursors is a direct effect of the electric field and not due to chemotactic gradients. We also identified that epidermal growth factor receptor (EGFR) signaling plays a role in the galvanotactic response as blocking EGFR significantly attenuates the migratory behaviour. These findings suggest direct current electric fields may be implemented in endogenous repair paradigms to promote migration and tissue repair following neurotrauma.

Growth and evolution of satellites in a Jovian massive disc

NASA Astrophysics Data System (ADS)

Moraes, R. A.; Kley, W.; Vieira Neto, E.

2018-03-01

The formation of satellite systems in circum-planetary discs is considered to be similar to the formation of rocky planets in a proto-planetary disc, especially super-Earths. Thus, it is possible to use systems with large satellites to test formation theories that are also applicable to extrasolar planets. Furthermore, a better understanding of the origin of satellites might yield important information about the environment near the growing planet during the last stages of planet formation. In this work, we investigate the formation and migration of the Jovian satellites through N-body simulations. We simulated a massive, static, low-viscosity, circum-planetary disc in agreement with the minimum mass sub-nebula model prescriptions for its total mass. In hydrodynamic simulations, we found no signs of gaps, therefore type II migration is not expected. Hence, we used analytic prescriptions for type I migration, eccentricity and inclination damping, and performed N-body simulations with damping forces added. Detailed parameter studies showed that the number of final satellites is strong influenced by the initial distribution of embryos, the disc temperature, and the initial gas density profile. For steeper initial density profiles, it is possible to form systems with multiple satellites in resonance while a flatter profile favours the formation of satellites close to the region of the Galilean satellites. We show that the formation of massive satellites such as Ganymede and Callisto can be achieved for hotter discs with an aspect ratio of H/r ˜ 0.15 for which the ice line was located around 30RJ.

miR-125b suppresses the proliferation and migration of osteosarcoma cells through down-regulation of STAT3

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

Liu, Li-hong; Li, Hui; Li, Jin-ping

2011-12-09

Highlights: Black-Right-Pointing-Pointer miR-125b is frequently down-regulated in osteosarcoma samples and human osteosarcoma cell lines. Black-Right-Pointing-Pointer Ectopic restoration of miR-125b suppresses cell proliferation and migration in vitro. Black-Right-Pointing-Pointer STAT3 is the direct and functional downstream target of miR-125b. Black-Right-Pointing-Pointer STAT3 can bind to the promoter region of miR-125b and serves as a transactivator. -- Abstract: There is accumulating evidence that microRNAs are involved in multiple processes in development and tumor progression. Abnormally expressed miR-125b was found to play a fundamental role in several types of cancer; however, whether miR-125b participates in regulating the initiation and progress of osteosarcoma still remains unclear.more » Here we demonstrate that miR-125b is frequently down-regulated in osteosarcoma samples and human osteosarcoma cell lines. The ectopic restoration of miR-125b expression in human osteosarcoma cells suppresses proliferation and migration in vitro and inhibits tumor formation in vivo. We further identified signal transducer and activator of transcription 3 (STAT3) as the direct and functional downstream target of miR-125b. Interestingly, we discovered that the expression of miR-125b is regulated by STAT3 at the level of transcription. STAT3 binds to the promoter region of miR-125b in vitro and serves as a transactivator. Taken together, our findings point to an important role in the molecular etiology of osteosarcoma and suggest that miR-125b is a potential target in the treatment of osteosarcoma.« less

PEG-protein interaction induced contraction of NalD chains.

PubMed

Yu, Jiyan; Chen, Weizhong; Wu, Chi; Chen, Hao

2014-01-01

In a recent attempt to crystallize a regulator of MexAB-OprM multi-drug efflux systems in Pseudomonas aeruginosa (NalD), we found that adding polyethylene glycol (PEG3350, Mw = 3,350 g/mol) into the protein solution increases the speed of NalD migration in gel electrophoresis, signaling a smaller hydrodynamic size. At first we conjectured that NalD was degraded unexpectedly by PEG; however, we found that there was no change in its molar mass by MALDI-TOF characterization. Moreover, we found that adding polyacrylic acid (PAA) into the solution mixture returned the NalD migration to its normal speed. Furthermore, our analytic ultracentrifugation and dynamic laser light scattering results directly reveal that NalD interacts with PEG so that individual NalD chains gradually shrink as more PEG chains are added in the range of 10-50 mg/mL. Size exclusion chromatography also confirms that the NalD chain shrinks in the presence of PEG. A combination of these results indicates that PEG3350 chains can complex with NalD to induce an intra-protein chain contraction, presumably via the formation of hydrogen bond between -C-O-C- on PEG and -COOH on NalD, resulting in a smaller hydrodynamic size (faster migration) and a higher apparent molar mass. Note that because the presence of PEG affects osmotic pressure, it is considered to be a precipitator of protein crystallization. Our current finding reveals that the interaction of PEG/protein may play a significant role in protein crystallization. The complexation potentially makes the protein chain segments less flexible, and consequently makes crystallization easier. Hopefully, our current results will stimulate further studies in this direction.

PEG-Protein Interaction Induced Contraction of NalD Chains

PubMed Central

Yu, Jiyan; Chen, Weizhong; Wu, Chi; Chen, Hao

2014-01-01

In a recent attempt to crystallize a regulator of MexAB-OprM multi-drug efflux systems in Pseudomonas aeruginosa (NalD), we found that adding polyethylene glycol (PEG3350, Mw = 3,350 g/mol) into the protein solution increases the speed of NalD migration in gel electrophoresis, signaling a smaller hydrodynamic size. At first we conjectured that NalD was degraded unexpectedly by PEG; however, we found that there was no change in its molar mass by MALDI-TOF characterization. Moreover, we found that adding polyacrylic acid (PAA) into the solution mixture returned the NalD migration to its normal speed. Furthermore, our analytic ultracentrifugation and dynamic laser light scattering results directly reveal that NalD interacts with PEG so that individual NalD chains gradually shrink as more PEG chains are added in the range of 10–50 mg/mL. Size exclusion chromatography also confirms that the NalD chain shrinks in the presence of PEG. A combination of these results indicates that PEG3350 chains can complex with NalD to induce an intra-protein chain contraction, presumably via the formation of hydrogen bond between –C-O-C– on PEG and –COOH on NalD, resulting in a smaller hydrodynamic size (faster migration) and a higher apparent molar mass. Note that because the presence of PEG affects osmotic pressure, it is considered to be a precipitator of protein crystallization. Our current finding reveals that the interaction of PEG/protein may play a significant role in protein crystallization. The complexation potentially makes the protein chain segments less flexible, and consequently makes crystallization easier. Hopefully, our current results will stimulate further studies in this direction. PMID:24810951

Use of palm mid-fraction in dark chocolate as base filling centre at different storage temperatures.

PubMed

Jinap, S; Ali, A A; Man, Y B; Suria, A M

2000-11-01

Dark chocolates filled with palm mid-fraction (PMF) were stored at different temperatures to evaluate the physical and chemical changes. Storage at low temperature (18 degrees C) reduces the PMF migration to negligible extent. Higher storage temperatures (30 and 35 degrees C) increased the PMF migration from the filling centre into the chocolate coating. As a consequence of fat migration, fatty acid composition, triglyceride composition, hardness, solid fat content, melting point and polymorphic structure changed, leading to bloom formation, which started by fat migration and was influenced by recrystallization tendency within the chocolate coating.

Micro-scale and meso-scale architectural cues cooperate and compete to direct aligned tissue formation

PubMed Central

Gilchrist, Christopher L.; Ruch, David S.; Little, Dianne; Guilak, Farshid

2014-01-01

Tissue and biomaterial microenvironments provide architectural cues that direct important cell behaviors including cell shape, alignment, migration, and resulting tissue formation. These architectural features may be presented to cells across multiple length scales, from nanometers to millimeters in size. In this study, we examined how architectural cues at two distinctly different length scales, “micro-scale” cues on the order of ~1–2 μm, and “meso-scale” cues several orders of magnitude larger (>100 μm), interact to direct aligned neo-tissue formation. Utilizing a micro-photopatterning (μPP) model system to precisely arrange cell-adhesive patterns, we examined the effects of substrate architecture at these length scales on human mesenchymal stem cell (hMSC) organization, gene expression, and fibrillar collagen deposition. Both micro- and meso-scale architectures directed cell alignment and resulting tissue organization, and when combined, meso cues could enhance or compete against micro-scale cues. As meso boundary aspect ratios were increased, meso-scale cues overrode micro-scale cues and controlled tissue alignment, with a characteristic critical width (~500 μm) similar to boundary dimensions that exist in vivo in highly aligned tissues. Meso-scale cues acted via both lateral confinement (in a cell-density-dependent manner) and by permitting end-to-end cell arrangements that yielded greater fibrillar collagen deposition. Despite large differences in fibrillar collagen content and organization between μPP architectural conditions, these changes did not correspond with changes in gene expression of key matrix or tendon-related genes. These findings highlight the complex interplay between geometric cues at multiple length scales and may have implications for tissue engineering strategies, where scaffold designs that incorporate cues at multiple length scales could improve neo-tissue organization and resulting functional outcomes. PMID:25263687

New hydrologic model of fluid migration in deep porous media

NASA Astrophysics Data System (ADS)

Dmitrievsky, A.; Balanyuk, I.

2009-04-01

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

Numerical modeling of experimental observations on gas formation and multi-phase flow of carbon dioxide in subsurface formations

NASA Astrophysics Data System (ADS)

Pawar, R.; Dash, Z.; Sakaki, T.; Plampin, M. R.; Lassen, R. N.; Illangasekare, T. H.; Zyvoloski, G.

2011-12-01

One of the concerns related to geologic CO2 sequestration is potential leakage of CO2 and its subsequent migration to shallow groundwater resources leading to geochemical impacts. Developing approaches to monitor CO2 migration in shallow aquifer and mitigate leakage impacts will require improving our understanding of gas phase formation and multi-phase flow subsequent to CO2 leakage in shallow aquifers. We are utilizing an integrated approach combining laboratory experiments and numerical simulations to characterize the multi-phase flow of CO2 in shallow aquifers. The laboratory experiments involve a series of highly controlled experiments in which CO2 dissolved water is injected in homogeneous and heterogeneous soil columns and tanks. The experimental results are used to study the effects of soil properties, temperature, pressure gradients and heterogeneities on gas formation and migration. We utilize the Finite Element Heat and Mass (FEHM) simulator (Zyvoloski et al, 2010) to numerically model the experimental results. The numerical models capture the physics of CO2 exsolution, multi-phase fluid flow as well as sand heterogeneity. Experimental observations of pressure, temperature and gas saturations are used to develop and constrain conceptual models for CO2 gas-phase formation and multi-phase CO2 flow in porous media. This talk will provide details of development of conceptual models based on experimental observation, development of numerical models for laboratory experiments and modelling results.

Burn Eschar Stimulates Fibroblast and Adipose Mesenchymal Stromal Cell Proliferation and Migration but Inhibits Endothelial Cell Sprouting

PubMed Central

Monsuur, Hanneke N.; van den Broek, Lenie J.; Jhingoerie, Renushka L.; Vloemans, Adrianus F. P. M.

2017-01-01

The majority of full-thickness burn wounds heal with hypertrophic scar formation. Burn eschar most probably influences early burn wound healing, since granulation tissue only forms after escharotomy. In order to investigate the effect of burn eschar on delayed granulation tissue formation, burn wound extract (BWE) was isolated from the interface between non-viable eschar and viable tissue. The influence of BWE on the activity of endothelial cells derived from dermis and adipose tissue, dermal fibroblasts and adipose tissue-derived mesenchymal stromal cells (ASC) was determined. It was found that BWE stimulated endothelial cell inflammatory cytokine (CXCL8, IL-6 and CCL2) secretion and migration. However, BWE had no effect on endothelial cell proliferation or angiogenic sprouting. Indeed, BWE inhibited basic Fibroblast Growth Factor (bFGF) induced endothelial cell proliferation and sprouting. In contrast, BWE stimulated fibroblast and ASC proliferation and migration. No difference was observed between cells isolated from dermis or adipose tissue. The inhibitory effect of BWE on bFGF-induced endothelial proliferation and sprouting would explain why excessive granulation tissue formation is prevented in full-thickness burn wounds as long as the eschar is still present. Identifying the eschar factors responsible for this might give indications for therapeutic targets aimed at reducing hypertrophic scar formation which is initiated by excessive granulation tissue formation once eschar is removed. PMID:28820426

Planet Formation in Disks with Inclined Binary Companions: Can Primordial Spin-Orbit Misalignment be Produced?

NASA Astrophysics Data System (ADS)

Zanazzi, J. J.; Lai, Dong

2018-04-01

Many hot Jupiter (HJ) systems have been observed to have their stellar spin axis misaligned with the planet's orbital angular momentum axis. The origin of this spin-orbit misalignment and the formation mechanism of HJs remain poorly understood. A number of recent works have suggested that gravitational interactions between host stars, protoplanetary disks, and inclined binary companions may tilt the stellar spin axis with respect to the disk's angular angular momentum axis, producing planetary systems with misaligned orbits. These previous works considered idealized disk evolution models and neglected the gravitational influence of newly formed planets. In this paper, we explore how disk photoevaporation and planet formation and migration affect the inclination evolution of planet-star-disk-binary systems. We take into account planet-disk interactions and the gravitational spin-orbit coupling between the host star and the planet. We find that the rapid depletion of the inner disk via photoevaporation reduces the excitation of stellar obliquities. Depending on the formation and migration history of HJs, the spin-orbit coupling between the star and the planet may reduces and even completely suppress the excitation of stellar obliquities. Our work constrains the formation/migration history of HJs. On the other hand, planetary systems with "cold" Jupiters or close-in super-earths may experience excitation of stellar obliquities in the presence of distant inclined companions.

Planet formation in discs with inclined binary companions: can primordial spin-orbit misalignment be produced?

NASA Astrophysics Data System (ADS)

Zanazzi, J. J.; Lai, Dong

2018-07-01

Many hot Jupiter (HJ) systems have been observed to have their stellar spin axis misaligned with the planet's orbital angular momentum axis. The origin of this spin-orbit misalignment and the formation mechanism of HJs remain poorly understood. A number of recent works have suggested that gravitational interactions between host stars, protoplanetary discs, and inclined binary companions may tilt the stellar spin axis with respect to the disc's angular angular momentum axis, producing planetary systems with misaligned orbits. These previous works considered idealized disc evolution models and neglected the gravitational influence of newly formed planets. In this paper, we explore how disc photoevaporation and planet formation and migration affect the inclination evolution of planet-star-disc-binary systems. We take into account planet-disc interactions and the gravitational spin-orbit coupling between the host star and the planet. We find that the rapid depletion of the inner disc via photoevaporation reduces the excitation of stellar obliquities. Depending on the formation and migration history of HJs, the spin-orbit coupling between the star and the planet may reduces and even completely suppress the excitation of stellar obliquities. Our work constrains the formation/migration history of HJs. On the other hand, planetary systems with `cold' Jupiters or close-in super-earths may experience excitation of stellar obliquities in the presence of distant inclined companions.

PDGF-A suppresses contact inhibition during directional collective cell migration.

PubMed

Nagel, Martina; Winklbauer, Rudolf

2018-06-08

The leading edge mesendoderm (LEM) of the Xenopus gastrula moves as an aggregate by collective migration. However, LEM cells on fibronectin in vitro show contact inhibition of locomotion by quickly retracting lamellipodia upon mutual contact. We found that a fibronectin-integrin-syndecan module acts between p21-activated kinase-1 upstream and ephrinB1 downstream to promote the contact-induced collapse of lamellipodia. To function in this module, fibronectin has to be present as puncta on the surface of LEM cells. To overcome contact inhibition in LEM cell aggregates, PDGF-A deposited in the endogenous substratum of LEM migration blocks the fibronectin-integrin-syndecan module at the integrin level. This stabilizes lamellipodia preferentially in the direction of normal LEM movement and supports cell orientation and the directional migration of the coherent LEM cell mass. © 2018. Published by The Company of Biologists Ltd.

Comparative Effects of Platelet-Rich Plasma, Platelet Lysate, and Fetal Calf Serum on Mesenchymal Stem Cells.

PubMed

Lykov, A P; Bondarenko, N A; Surovtseva, M A; Kim, I I; Poveshchenko, O V; Pokushalov, E A; Konenkov, V I

2017-10-01

We studied the effects of human platelet-rich plasma and platelet lysate on proliferation, migration, and colony-forming properties of rat mesenchymal stem cells. Platelet-rich plasma and platelet lysate stimulated the proliferation, migration, and colony formation of mesenchymal stem cells. A real-time study showed that platelet-rich plasma produces the most potent stimulatory effect, while both platelet-rich plasma and platelet lysate stimulated migration of cells.

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

State policies and internal migration in Asia.

PubMed

Oberai, A S

1981-01-01

The objective of this discussion is to identify policies and programs in Asia that are explicitly or implicitly designed to influence migration, to investigate why they were adopted and how far they have actually been implemented, and to assess their direct and indirect consequences. For study purposes, policies and programs are classified according to whether they prohibit or reverse migration, redirect or channel migration to specific rural or urban locations, reduce the total volume of migration, or encourage or discourage urban in-migration. Discussion of each type of policy is accompanied by a description of its rationale and implementation mechanism, examples of countries in Asia that have recourse to it, and its intended or actual effect on migration. Several countries in Asia have taken direct measures to reverse the flow of migration and to stop or discourage migration to urban areas. These measures have included administrative and legal controls, police registration, and direct "rustication" programs to remove urban inhabitants to the countryside. The availability of public land has prompted many Asian countries to adopt schemes that have been labeled resettlement, transmigration, colonization, or land development. These schemes have been designed to realize 1 or more of the following objectives: to provide land and income to the landless; increase agricultural production; correct spatial imbalances in the distribution of population; or exploit frontier lands for reasons of national security. 1 of the basic goals of decentralized industrialization and regional development policies has been the reduction of interregional disparities and the redirection of migrations from large metropolitan areas to smaller and medium sized towns. To encourage industry to move to small urban locations initial infrastructure investments, tax benefits, and other incentives have been offered. Policies to reduce the overall volume of migration have frequently included rural development programs, the primary purpose of which is to retain potential migrants in the rural areas, and preferential policies for natives with a view toward discouraging interregional migration. The explicit goal of rural development strategies is often to slow rural-urban migration. Slowly the attitude towards migrant squatters and slum dwellers is changing from punitive to more tolerant. Several measures have been taken to accommodate migrants in urban areas and to promote their welfare.

Differential regulation of microtubule severing by APC underlies distinct patterns of projection neuron and interneuron migration

PubMed Central

Eom, Tae-Yeon; Stanco, Amelia; Guo, Jiami; Wilkins, Gary; Deslauriers, Danielle; Yan, Jessica; Monckton, Chase; Blair, Josh; Oon, Eesim; Perez, Abby; Salas, Eduardo; Oh, Adrianna; Ghukasyan, Vladimir; Snider, William D.; Rubenstein, John L. R.; Anton, E. S.

2014-01-01

Coordinated migration of distinct classes of neurons to appropriate positions leads to the formation of functional neuronal circuitry in the cerebral cortex. Two major classes of cortical neurons, interneurons and projection neurons, utilize distinctly different modes (radial vs. tangential) and routes of migration to arrive at their final positions in the cerebral cortex. Here, we show that adenomatous polyposis coli (APC) modulates microtubule (MT) severing in interneurons to facilitate tangential mode of interneuron migration, but not the glial-guided, radial migration of projection neurons. APC regulates the stability and activity of the MT severing protein p60-katanin in interneurons to promote the rapid remodeling of neuronal processes necessary for interneuron migration. These findings reveal how severing and restructuring of MTs facilitate distinct modes of neuronal migration necessary for laminar organization of neurons in the developing cerebral cortex. PMID:25535916

Reverse time migration in tilted transversely isotropic media

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

Zhang, Linbing; Rector III, James W.; Hoversten, G. Michael

2004-07-01

This paper presents a reverse time migration (RTM) method for the migration of shot records in tilted transversely isotropic (TTI) media. It is based on the tilted TI acoustic wave equation that was derived from the dispersion relation. The RTM is a full depth migration allowing for velocity to vary laterally as well as vertically and has no dip limitations. The wave equation is solved by a tenth-order finite difference scheme. Using 2D numerical models, we demonstrate that ignoring the tilt angle will introduce both lateral and vertical shifts in imaging. The shifts can be larger than 0.5 wavelength inmore » the vertical direction and 1.5 wavelength in the lateral direction.« less

The activation of directional stem cell motility by green light-emitting diode irradiation.

PubMed

Ong, Wei-Kee; Chen, How-Foo; Tsai, Cheng-Ting; Fu, Yun-Ju; Wong, Yi-Shan; Yen, Da-Jen; Chang, Tzu-Hao; Huang, Hsien-Da; Lee, Oscar Kuang-Sheng; Chien, Shu; Ho, Jennifer Hui-Chun

2013-03-01

Light-emitting diode (LED) irradiation is potentially a photostimulator to manipulate cell behavior by opsin-triggered phototransduction and thermal energy supply in living cells. Directional stem cell motility is critical for the efficiency and specificity of stem cells in tissue repair. We explored that green LED (530 nm) irradiation directed the human orbital fat stem cells (OFSCs) to migrate away from the LED light source through activation of extracellular signal-regulated kinases (ERK)/MAP kinase/p38 signaling pathway. ERK inhibitor selectively abrogated light-driven OFSC migration. Phosphorylation of these kinases as well as green LED irradiation-induced cell migration was facilitated by increasing adenosine triphosphate (ATP) production in OFSCs after green LED exposure, and which was thermal stress-independent mechanism. OFSCs, which are multi-potent mesenchymal stem cells isolated from human orbital fat tissue, constitutionally express three opsins, i.e. retinal pigment epithelium-derived rhodopsin homolog (RRH), encephalopsin (OPN3) and short-wave-sensitive opsin 1 (OPN1SW). However, only two non-visual opsins, i.e. RRH and OPN3, served as photoreceptors response to green LED irradiation-induced OFSC migration. In conclusion, stem cells are sensitive to green LED irradiation-induced directional cell migration through activation of ERK signaling pathway via a wavelength-dependent phototransduction. Copyright © 2012 Elsevier Ltd. All rights reserved.

Low-intensity pulsed ultrasound promotes spinal fusion and enhances migration and proliferation of MG63s through sonic hedgehog signaling pathway.

PubMed

Zhou, Xiao-Yi; Xu, Xi-Ming; Wu, Sui-Yi; Zhang, Zi-Cheng; Wang, Fei; Yang, Yi-Lin; Li, Ming; Wei, Xian-Zhao

2018-05-01

Low-intensity pulsed ultrasound (LIPUS) has been found to accelerate the healing process of spinal fusion via a process closely related to osteoblast differentiation and migration. Sonic hedgehog (Shh) signaling plays an important role in development and homeostasis, including a critical function in bone formation. However, its role in spinal fusion during LIPUS treatment is still unknown. This study showed that LIPUS treatment after spinal fusion surgery increased bone formation. The increased bone mass under LIPUS treatment appeared to result from the increased migration and proliferation of osteoblasts, resulting from upregulation of the Shh signaling pathway. In contrast, inhibition of Shh reduced the migratory and proliferative ability of osteoblast-like MG63 cells and blocked the efficacy of LIPUS treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

New directions for migration policy in Europe.

PubMed Central

Laczko, Frank

2002-01-01

There is a growing debate about the future direction of migration policy in Europe. After nearly 30 years of pursuing restrictive immigration and asylum policies, many European Union (EU) governments are beginning to re-assess their migration policies and to call for a new approach. For the first time in many years, several EU governments have begun to talk again about the benefits of labour migration and, even more significantly, have even begun to take action to recruit more migrants, especially skilled workers. This paper looks at the background to current calls for a new approach to migration in Europe and public reaction to these new initiatives. It first describes recent trends in migration in Europe and then briefly considers the demographic case for more migration. This is followed by a brief outline of some of the measures being considered by European governments to promote selective labour migration. The remainder of the paper is devoted to a discussion of some of the implications of this change in policy, focusing on two main issues: the likely consequences for sending countries, and the implications for the fight against the smuggling and trafficking of people. PMID:12028795

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

Lamellipodia and Membrane Blebs Drive Efficient Electrotactic Migration of Rat Walker Carcinosarcoma Cells WC 256

PubMed Central

Sroka, Jolanta; Krecioch, Izabela; Zimolag, Eliza; Lasota, Slawomir; Rak, Monika; Kedracka-Krok, Sylwia; Borowicz, Pawel; Gajek, Marta; Madeja, Zbigniew

2016-01-01

The endogenous electric field (EF) may provide an important signal for directional cell migration during wound healing, embryonic development and cancer metastasis but the mechanism of cell electrotaxis is poorly understood. Additionally, there is no research addressing the question on the difference in electrotactic motility of cells representing various strategies of cell movement—specifically blebbing vs. lamellipodial migration. In the current study we constructed a unique experimental model which allowed for the investigation of electrotactic movement of cells of the same origin but representing different modes of cell migration: weakly adherent, spontaneously blebbing (BC) and lamellipodia forming (LC) WC256 cells. We report that both BC and LC sublines show robust cathodal migration in a physiological EF (1–3 V/cm). The directionality of cell movement was completely reversible upon reversing the field polarity. However, the full reversal of cell direction after the change of EF polarity was much faster in the case of BC (10 minutes) than LC cells (30 minutes). We also investigated the distinct requirements for Rac, Cdc42 and Rho pathways and intracellular Ca2+ in electrotaxis of WC256 sublines forming different types of cell protrusions. It was found that Rac1 is required for directional movement of LC to a much greater extent than for BC, but Cdc42 and RhoA are more crucial for BC than for LC cells. The inhibition of ROCK did not affect electrotaxis of LC in contrast to BC cells. The results also showed that intracellular Ca2+ is essential only for the electrotactic reaction of BC cells. Moreover, inhibition of MLCK and myosin II did not affect the electrotaxis of LC in contrast to BC cells. In conclusion, our results revealed that both lamellipodia and membrane blebs can efficiently drive electrotactic migration of WC 256 carcinosarcoma cells, however directional migration is mediated by different signalling pathways. PMID:26863616

Lamellipodia and Membrane Blebs Drive Efficient Electrotactic Migration of Rat Walker Carcinosarcoma Cells WC 256.

PubMed

Sroka, Jolanta; Krecioch, Izabela; Zimolag, Eliza; Lasota, Slawomir; Rak, Monika; Kedracka-Krok, Sylwia; Borowicz, Pawel; Gajek, Marta; Madeja, Zbigniew

2016-01-01

The endogenous electric field (EF) may provide an important signal for directional cell migration during wound healing, embryonic development and cancer metastasis but the mechanism of cell electrotaxis is poorly understood. Additionally, there is no research addressing the question on the difference in electrotactic motility of cells representing various strategies of cell movement-specifically blebbing vs. lamellipodial migration. In the current study we constructed a unique experimental model which allowed for the investigation of electrotactic movement of cells of the same origin but representing different modes of cell migration: weakly adherent, spontaneously blebbing (BC) and lamellipodia forming (LC) WC256 cells. We report that both BC and LC sublines show robust cathodal migration in a physiological EF (1-3 V/cm). The directionality of cell movement was completely reversible upon reversing the field polarity. However, the full reversal of cell direction after the change of EF polarity was much faster in the case of BC (10 minutes) than LC cells (30 minutes). We also investigated the distinct requirements for Rac, Cdc42 and Rho pathways and intracellular Ca2+ in electrotaxis of WC256 sublines forming different types of cell protrusions. It was found that Rac1 is required for directional movement of LC to a much greater extent than for BC, but Cdc42 and RhoA are more crucial for BC than for LC cells. The inhibition of ROCK did not affect electrotaxis of LC in contrast to BC cells. The results also showed that intracellular Ca2+ is essential only for the electrotactic reaction of BC cells. Moreover, inhibition of MLCK and myosin II did not affect the electrotaxis of LC in contrast to BC cells. In conclusion, our results revealed that both lamellipodia and membrane blebs can efficiently drive electrotactic migration of WC 256 carcinosarcoma cells, however directional migration is mediated by different signalling pathways.

Crossing the ultimate ecological barrier: Evidence for an 11,000-km-long non-stop flight from Alaska to New Zealand and Eastern Australia by Bar-tailed Godwits

USGS Publications Warehouse

Gill, Robert E.; Piersma, Theunis; Hufford, Gary; Servranckx, R.; Riegen, Adrian C.

2005-01-01

Populations of the Bar-tailed Godwit (Limosa lapponica; Scolopacidae) embark on some of the longest migrations known among birds. The baueri race breeds in westernAlaska and spends the nonbreeding season a hemisphere away inNew Zealand and eastern Australia; the menzbieri race breeds in Siberia and migrates to western and northern Australia. Although the Siberian birds are known to follow the coast of Asia during both migrations, the southern pathway followed by the Alaskabreeders has remained unknown. Two questions have particularecological importance: (1) do Alaska godwits migrate directly across the Pacific, a distance of 11 000 km? and (2) are they capable of doing this in a single flight without stopping to rest or refuel? We explored six lines of evidence to answer these questions. The distribution of resightings of marked birds of the baueri and menzbieri races was significantly different between northward and southward flights with virtually no marked baueri resighted along the Asian mainland during southward migration. The timing of southward migration of the two races further indicates the absence of a coastal Asia route by baueri with peak passage of godwits in general occurring there a month prior to the departure of most birds from Alaska. The use of a direct route across the Pacific is also supported by significantly more records of godwits reported from within a direct migration corridor than elsewhere in Oceania, and during the September to November period than at other times of the year. The annual but rare occurrence of Hudsonian Godwits (L. haemastica) in New Zealand and the absence of their records along the Asian mainland also support a direct flight and are best explained by Hudsonian Godwits accompanying Bar-tailed Godwits from known communal staging areas in Alaska. Flight simulation models, extreme fat loads, and the apparent evolution of a wind-selected migration from Alaska further support a direct, nonstop flight.

Computational modelling of cell chain migration reveals mechanisms that sustain follow-the-leader behaviour

PubMed Central

Wynn, Michelle L.; Kulesa, Paul M.; Schnell, Santiago

2012-01-01

Follow-the-leader chain migration is a striking cell migratory behaviour observed during vertebrate development, adult neurogenesis and cancer metastasis. Although cell–cell contact and extracellular matrix (ECM) cues have been proposed to promote this phenomenon, mechanisms that underlie chain migration persistence remain unclear. Here, we developed a quantitative agent-based modelling framework to test mechanistic hypotheses of chain migration persistence. We defined chain migration and its persistence based on evidence from the highly migratory neural crest model system, where cells within a chain extend and retract filopodia in short-lived cell contacts and move together as a collective. In our agent-based simulations, we began with a set of agents arranged as a chain and systematically probed the influence of model parameters to identify factors critical to the maintenance of the chain migration pattern. We discovered that chain migration persistence requires a high degree of directional bias in both lead and follower cells towards the target. Chain migration persistence was also promoted when lead cells maintained cell contact with followers, but not vice-versa. Finally, providing a path of least resistance in the ECM was not sufficient alone to drive chain persistence. Our results indicate that chain migration persistence depends on the interplay of directional cell movement and biased cell–cell contact. PMID:22219399

Deep low-frequency earthquake activities during the failed magmatic eruptions of Mts. Iwate and Fuji, Japan

NASA Astrophysics Data System (ADS)

Nakamichi, H.; Hamaguchi, H.; Ukawa, M.; Tanaka, S.; Ueki, S.; Nishimura, T.

2008-12-01

I review deep low-frequency earthquake (DLF) activities during the failed magmatic eruptions of Mts. Iwate and Fuji, Japan. Volcanic unrests at Mts. Iwate and Fuji were observed in 1998-1999 and 2000-2001, respectively. Several hundred DLFs occurred during the unrest at Mt. Iwate; the number of DLFs in a normal year is less than or equal to 10. The DLF activity at Mt. Fuji increased sharply during the period from September 2000 to May 2001. The frequency of DLFs at Mt. Fuji during the DLF swarm was 20 times higher than that during normal activity. The DLFs of Mts. Iwate and Fuji show non-DC source mechanisms and suggest fluid motion at the focal regions. The DLF hypocenters of Mt. Fuji defined an ellipsoid with a diameter of 5 km; their focal depths are 11-16 km. The ellipsoid was centered 3 km northeast of the summit, and its major axis was directed in the northwest-southeast direction. The center of the ellipsoid gradually migrated upward, and 2-3 km in the northwest direction during 1998-2001. The migration of the DLFs reflects the volcanic fluid migration associated with a northwest-southeast-oriented dike beneath Mt. Fuji. The DLFs of Mt. Iwate were located at intermediate depths (5-12 km) beneath the summit and at deep depths (31-37 km) in the regions located 10 km south and 10 km northeast of the summit. In April 1998, the frequency of DLFs increased five days before an increase in the occurrence of shallow volcanic earthquakes at Mt. Iwate. Hypocenter migration of the DLFs at intermediate depths was observed from April 1998 to September 1998. New fumarole activity in the western region of Mt. Iwate commenced in 1999. These observations indicate that DLFs at Mts. Fuji and Iwate have common features in their activities and source mechanisms. But, shallow volcanic activities at these two volcanoes were much different: strong shallow seismic activity and volcano inflations as well as a new formation of fumarolic area were observed at Mt. Iwate, while such shallow activities were not detected at Mt. Fuji. Although it is still unknown what mechanisms control their magma supply systems, we may say that activation of DLF beneath active volcanoes does not always accompany magma intrusions in the shallow volcano edifice.

Direct Measurement of Intracellular Pressure

PubMed Central

Petrie, Ryan J.; Koo, Hyun

2014-01-01

A method to directly measure the intracellular pressure of adherent, migrating cells is described in the Basic Protocol. This approach is based on the servo-null method where a microelectrode is introduced into the cell to directly measure the physical pressure of the cytoplasm. We also describe the initial calibration of the microelectrode as well as the application of the method to cells migrating inside three-dimensional (3D) extracellular matrix (ECM). PMID:24894836

Turbulence investigation and reproduction for assisting downstream migrating juvenile salmonids, Part II of II: Effects of induced turbulence on behavior of juvenile salmon, 2001-2005 final report

USGS Publications Warehouse

Perry, R.; Farley , M.; Hansen, G.; Morse , J.; Rondorf, D.

2005-01-01

Passage through dams is a major source of mortality of anadromous juvenile salmonids because some populations must negotiate up to eight dams in Columbia and Snake rivers. Dams cause direct mortality when fish pass through turbines, but dams may also cause indirect mortality by altering migration conditions in rivers. Forebays immediately upstream of dams have decreased the water velocity of rivers and may contribute substantially to the total migration delay of juvenile salmonids. Recently, Coutant (2001a) suggested that in addition to low water velocities, lack of natural turbulence may contribute to migration delay by causing fish to lose directional cues. Coutant (2001a) further hypothesized that restoring turbulence in dam forebays may reduce migration delay by providing directional cues that allow fish to find passage routes more quickly (Coutant 2001a). Although field experiments have yielded proof of the concept of using induced turbulence to guide fish to safe passage routes, little is known about mechanisms actually causing behavioral changes. To test hypotheses about how turbulence influences movement and behavior of migrating juvenile salmonids, we conducted two types of controlled experiments at Cowlitz Falls Dam, Washington. A common measure of migration delay is the elapsed time between arrival at, and passage through, a dam. Therefore, for the first set of experiments, we tested the effect of induced turbulence on the elapsed time needed for fish to traverse through a raceway and pass over a weir at its downstream end (time trial experiment). If turbulence helps guide fish to passage routes, then fish should pass through the raceway quicker in the presence of appropriately scaled and directed turbulent cues. Second, little is known about how the physical properties of water movement provide directional cues to migrating juvenile salmonids. To examine the feasibility of guiding fish with turbulence, we tested whether directed turbulence could guide fish into one of two channels in the raceway, and subsequently cause them to pass disproportionately over the weir where turbulent cues were aimed (guidance experiment). Last, we measured and mapped water velocity and turbulence during the experiments to understand water movement patterns and the spatial distribution of turbulence in the raceways.

Wind selection and drift compensation optimize migratory pathways in a high-flying moth.

PubMed

Chapman, Jason W; Reynolds, Don R; Mouritsen, Henrik; Hill, Jane K; Riley, Joe R; Sivell, Duncan; Smith, Alan D; Woiwod, Ian P

2008-04-08

Numerous insect species undertake regular seasonal migrations in order to exploit temporary breeding habitats [1]. These migrations are often achieved by high-altitude windborne movement at night [2-6], facilitating rapid long-distance transport, but seemingly at the cost of frequent displacement in highly disadvantageous directions (the so-called "pied piper" phenomenon [7]). This has lead to uncertainty about the mechanisms migrant insects use to control their migratory directions [8, 9]. Here we show that, far from being at the mercy of the wind, nocturnal moths have unexpectedly complex behavioral mechanisms that guide their migratory flight paths in seasonally-favorable directions. Using entomological radar, we demonstrate that free-flying individuals of the migratory noctuid moth Autographa gamma actively select fast, high-altitude airstreams moving in a direction that is highly beneficial for their autumn migration. They also exhibit common orientation close to the downwind direction, thus maximizing the rectilinear distance traveled. Most unexpectedly, we find that when winds are not closely aligned with the moth's preferred heading (toward the SSW), they compensate for cross-wind drift, thus increasing the probability of reaching their overwintering range. We conclude that nocturnally migrating moths use a compass and an inherited preferred direction to optimize their migratory track.

Uncovering patterns of spring migration in the monarch butterfly using stable isotopes and demographic models

NASA Astrophysics Data System (ADS)

Norris, R.; Miller, N.; Wassenaar, L.; Hobson, K.

2010-12-01

Each spring, millions of monarch butterflies (Danaus plexippus) migrate up to 3000 km from central Mexico to re-colonize eastern North America. However, despite centuries of research, the patterns of re-colonization are not well understood. We combined stable-hydrogen (δD) and -carbon (δ13C) isotope measurements with demographic models to test (1) whether individuals sampled in the northern part of the breeding range in the Great Lakes originate directly from Mexico or are second generation individuals born in the southern US and (2) to estimate whether populations on the eastern seaboard migrate longitudinally over the Appalachians or originate directly from the Gulf Coast. In the Great Lakes, we found that the majority of individuals were second-generation monarchs born in the Gulf Coast and Central regions of the US. However, 25% individuals originated directly from Mexico and we estimated that these individuals produced the majority of offspring born in the Great Lakes region during June. On the eastern seaboard, we found the majority of monarchs (88%) originated in the mid-west and Great Lakes regions, providing the first direct evidence that second generation monarchs born in June complete a (trans-) longitudinal migration across the Appalachian mountains. The remaining individuals (12%) originated from parents that migrated directly from the Gulf coast during early spring. Our results demonstrate how stable isotopes, when combined with ecological data, can provide insights into patterns of connectivity in migratory insects that have been impossible to test using conventional techniques. The migration patterns presented here have important implications for predicting future changes in population size and for developing effective conservation plans for this species.

The origin of collapse features appearing in a migrating parabolic dune along the southern coast of Lake Michigan

NASA Astrophysics Data System (ADS)

Argyilan, Erin P.; Avis, Peter G.; Krekeler, Mark P. S.; Morris, Charles C.

2015-12-01

Dune decomposition chimneys are collapse features formed when migrating dunes encroach on a forest and buried trees subsequently decay, leaving a temporarily stable open hole. The recent appearance of holes on the stoss slope of Mount Baldy at the Indiana Dunes National Lakeshore provided an opportunity for study of such features. Mount Baldy is a large parabolic dune that is rapidly migrating onshore over a late Holocene landscape with stabilized relict parabolic dunes that supported oak (Quercus spp.) trees visible on the 1939 aerial photo. Individual holes were mapped to locations on the dune surface that would directly overlie the arm of a buried relict parabolic dune. Analyses of buried trees and surrounding sediment indicated that saprotrophic wood decay fungi continue to actively decompose trees after burial and biomineralization of a calcium-carbonate-rich cement occurs at the contact between organic material and sands. Scanning electron microscopy of the cement showed neoformed authigenic minerals and organic structures consistent in morphology with fungal hyphae. We propose that, within the dune, portions of the decayed trees progressively collapse and infill, and open holes are temporarily stabilized by the calcium-carbonate-rich cement. Further, holes can exist undetected at the surface, covered by a thin veneer of sand. Migrating dune systems are observed in many coastal and inland areas. Ongoing work must address the relative contributions of individual environmental factors on the formation of dune decomposition chimneys, including the biomineralization of cement, sand mineralogy, rate of dune movement, tree species, climate, and the composition of fungal communities.

Migration of scientists and the International Centre for Theoretical Physics -- a Personal and Professional Perspective

NASA Astrophysics Data System (ADS)

Sreenivasan, Katepalli R.

2011-03-01

Scientists migrate for a variety of reasons: political problems with their governments, lack of professional opportunities in their countries, the lure of better lives, financial security for them and their families, better education for their off-springs, and so forth. Migration usually occurs from poor and oppressed countries--the two categories are not one and the same--to the rich and the open. It has created, over time, a dilemma for the poor countries: in the midst of all their other problems, how to justify spending on higher education and research when that investment often results in the most enterprising of its citizens to leave their countries behind? (When migration has reversed direction occasionally, it is because of certain necessities of the scientists to be back in their countries or for opportunities that some individuals see for wielding greater scientific power.) The ideal of keeping the best scientists in their own countries, still ensuring that they remain scientifically productive and inspiring to the youth, is what provided the motivation for the creation of the International Centre for Theoretical Physics in Trieste, Italy, where I served as Director for some seven years. In this talk, I will present the story behind the formation of the Centre in 1964, explain its rationale, and analyze its evolution over time to accommodate the changing scene in world; I will discuss how some things have remained the same even as more of them have changed over time. Finally, I will remark on the broad needs of developing countries even though such needs are often very specific to a country.

Memory, not just perception, plays an important role in terrestrial mammalian migration

PubMed Central

Mueller, Thomas

2017-01-01

One of the key questions regarding the underlying mechanisms of mammalian land migrations is how animals select where to go. Most studies assume perception of resources as the navigational mechanism. The possible role of memory that would allow forecasting conditions at distant locations and times based on information about environmental conditions from previous years has been little studied. We study migrating zebra in Botswana using an individual-based simulation model, where perceptually guided individuals use currently sensed resources at different perceptual ranges, while memory-guided individuals use long-term averages of past resources to forecast future conditions. We compare simulated individuals guided by perception or memory on resource landscapes of remotely sensed vegetation data to trajectories of GPS-tagged zebras. Our results show that memory provides a clear signal that best directs migrants to their destination compared to perception at even the largest perceptual ranges. Zebras modelled with memory arrived two to four times, or up to 100 km, closer to the migration destination than those using perception. We suggest that memory in addition to perception is important for directing ungulate migration. Furthermore, our findings are important for the conservation of migratory mammals, as memory informing direction suggests migration routes could be relatively inflexible. PMID:28539516

Memory, not just perception, plays an important role in terrestrial mammalian migration.

PubMed

Bracis, Chloe; Mueller, Thomas

2017-05-31

One of the key questions regarding the underlying mechanisms of mammalian land migrations is how animals select where to go. Most studies assume perception of resources as the navigational mechanism. The possible role of memory that would allow forecasting conditions at distant locations and times based on information about environmental conditions from previous years has been little studied. We study migrating zebra in Botswana using an individual-based simulation model, where perceptually guided individuals use currently sensed resources at different perceptual ranges, while memory-guided individuals use long-term averages of past resources to forecast future conditions. We compare simulated individuals guided by perception or memory on resource landscapes of remotely sensed vegetation data to trajectories of GPS-tagged zebras. Our results show that memory provides a clear signal that best directs migrants to their destination compared to perception at even the largest perceptual ranges. Zebras modelled with memory arrived two to four times, or up to 100 km, closer to the migration destination than those using perception. We suggest that memory in addition to perception is important for directing ungulate migration. Furthermore, our findings are important for the conservation of migratory mammals, as memory informing direction suggests migration routes could be relatively inflexible. © 2017 The Author(s).

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

Interstitial flow influences direction of tumor cell migration through competing mechanisms

PubMed Central

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

2011-01-01

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

mDia1 and WAVE2 proteins interact directly with IRSp53 in filopodia and are involved in filopodium formation.

PubMed

Goh, Wah Ing; Lim, Kim Buay; Sudhaharan, Thankiah; Sem, Kai Ping; Bu, Wenyu; Chou, Ai Mei; Ahmed, Sohail

2012-02-10

Filopodia are dynamic actin-rich cell surface protrusions involved in cell migration, axon guidance, and wound healing. The RhoGTPase Cdc42 generates filopodia via IRSp53, a multidomain protein that links the processes of plasma membrane deformation and actin dynamics required for their formation in mammalian cells. The Src homology 3 domain of IRSp53 binds to the actin regulators Mena, Eps8, WAVE1, WAVE2, mDia1, and mDia2. We show that mDia1 and WAVE2 synergize with IRSp53 to form filopodia. IRSp53 also interacts directly with these two proteins within filopodia, as observed in acceptor photobleaching FRET studies. Measurement of filopodium formation by time-lapse imaging of live cells also revealed that depleting neuronal cells of either mDia1 or WAVE2 protein decreases the ability of IRSp53 to induce filopodia. In contrast, IRSp53 does not appear to partner WAVE1 or mDia2 to give rise to these structures. In addition, although all three isoforms of mDia are capable of inducing filopodia, IRSp53 requires only mDia1 to do so. These findings suggest that mDia1 and WAVE2 are important Src homology 3 domain partners of IRSp53 in forming filopodia.

mDia1 and WAVE2 Proteins Interact Directly with IRSp53 in Filopodia and Are Involved in Filopodium Formation

PubMed Central

Goh, Wah Ing; Lim, Kim Buay; Sudhaharan, Thankiah; Sem, Kai Ping; Bu, Wenyu; Chou, Ai Mei; Ahmed, Sohail

2012-01-01

Filopodia are dynamic actin-rich cell surface protrusions involved in cell migration, axon guidance, and wound healing. The RhoGTPase Cdc42 generates filopodia via IRSp53, a multidomain protein that links the processes of plasma membrane deformation and actin dynamics required for their formation in mammalian cells. The Src homology 3 domain of IRSp53 binds to the actin regulators Mena, Eps8, WAVE1, WAVE2, mDia1, and mDia2. We show that mDia1 and WAVE2 synergize with IRSp53 to form filopodia. IRSp53 also interacts directly with these two proteins within filopodia, as observed in acceptor photobleaching FRET studies. Measurement of filopodium formation by time-lapse imaging of live cells also revealed that depleting neuronal cells of either mDia1 or WAVE2 protein decreases the ability of IRSp53 to induce filopodia. In contrast, IRSp53 does not appear to partner WAVE1 or mDia2 to give rise to these structures. In addition, although all three isoforms of mDia are capable of inducing filopodia, IRSp53 requires only mDia1 to do so. These findings suggest that mDia1 and WAVE2 are important Src homology 3 domain partners of IRSp53 in forming filopodia. PMID:22179776

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

NASA Astrophysics Data System (ADS)

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

2012-12-01

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

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

The impact of outmigration of men on fertility and marriage in the migrant-sending states of Mexico, 1995–2000

PubMed Central

White, Kari; Potter, Joseph E.

2015-01-01

Using the 2000 Mexican Census, we examined whether the level of migration was associated with total fertility and the proportion of women married in 314 municipalities from seven traditional sending states. Across these municipalities, we observe lower fertility in higher-migration areas. Municipalities in the quartile with the highest levels of migration have total fertility more than half a child lower than municipalities in the lowest migration quartile. However, there are no differences in marital fertility by level of migration, indicating that lower proportions of women married account for lower total fertility in high-migration municipalities. In municipal-level regression models, lower sex ratios are associated with a lower proportion of women married, while there is an inverse association between education and marriage. The level of migration also has an independent association with marriage, suggesting that there may be changing ideas surrounding family formation in high-migration areas. PMID:23009347