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Sample records for a2 modulates migration

  1. Signature of charge migration in modulations of double ionization

    NASA Astrophysics Data System (ADS)

    Mauger, François; Abanador, Paul M.; Bruner, Adam; Sissay, Adonay; Gaarde, Mette B.; Lopata, Kenneth; Schafer, Kenneth J.

    2018-04-01

    We present a theoretical investigation of charge migration following strong-field ionization in a multielectron system. We study a model homonuclear molecule with two electrons, each restricted to one dimension (1 +1 D ), interacting with a strong, static electric field. We show that in this system charge migration results from the interplay between multiple ionization channels that overlap in space, creating a coherent electron-hole wave packet in the cation. We also find that, in our case, charge migration following the first ionization manifests as a modulation of the subsequent double-ionization signal. We derive a parametrized semiclassical model from the full multielectron system and we discuss the importance of the choice of cation electronic-structure basis for the efficacy of the semiclassical representation. We use the ab initio solution of the full 1 +1 D system as a reference for the qualitative and quantitative results of the parametrized semiclassical model. We discuss the extension of our model to long-wavelength time-dependent fields with full-dimension, many-electron targets.

  2. EphA2 transmembrane domain is uniquely required for keratinocyte migration by regulating ephrin-A1 levels.

    PubMed

    Ventrella, Rosa; Kaplan, Nihal; Hoover, Paul; Perez White, Bethany E; Lavker, Robert M; Getsios, Spiro

    2018-04-26

    EphA2 receptor tyrosine kinase (RTK) is activated by ephrin-A1 ligand, which harbors a GPI-anchor that enhances lipid raft localization. While EphA2 and ephrin-A1 modulate keratinocyte migration and differentiation, the ability of this cell-cell communication complex to localize to different membrane regions in keratinocytes remains unknown. Using a combination of biochemical and imaging approaches, we provide evidence that ephrin-A1 and a ligand-activated form of EphA2 partition outside of lipid raft domains in response to calcium-mediated cell-cell contact stabilization in normal human epidermal keratinocytes (NHEKs). EphA2 transmembrane domain (TMD) swapping with a shorter and molecularly distinct TMD of EphA1 resulted in decreased localization of this RTK at cell-cell junctions and increased expression of ephrin-A1, which is a negative regulator of keratinocyte migration. Accordingly, altered EphA2 membrane distribution at cell-cell contacts limited the ability of keratinocytes to seal linear scratch wounds in vitro in an ephrin-A1-dependent manner. Collectively, these studies highlight a key role for the EphA2 TMD in receptor-ligand membrane distribution at cell-cell contacts that modulates ephrin-A1 levels to allow for efficient keratinocyte migration with relevance for cutaneous wound healing. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Cell intrinsic modulation of Wnt signaling controls neuroblast migration in C. elegans.

    PubMed

    Mentink, Remco A; Middelkoop, Teije C; Rella, Lorenzo; Ji, Ni; Tang, Chung Yin; Betist, Marco C; van Oudenaarden, Alexander; Korswagen, Hendrik C

    2014-10-27

    Members of the Wnt family of secreted signaling proteins are key regulators of cell migration and axon guidance. In the nematode C. elegans, the migration of the QR neuroblast descendants requires multiple Wnt ligands and receptors. We found that the migration of the QR descendants is divided into three sequential phases that are each mediated by a distinct Wnt signaling mechanism. Importantly, the transition from the first to the second phase, which is the main determinant of the final position of the QR descendants along the anteroposterior body axis, is mediated through a cell-autonomous process in which the time-dependent expression of a Wnt receptor turns on the canonical Wnt/β-catenin signaling response that is required to terminate long-range anterior migration. Our results show that, in addition to direct guidance of cell migration by Wnt morphogenic gradients, cell migration can also be controlled indirectly through cell-intrinsic modulation of Wnt signaling responses.

  4. Activation of Adenosine A2A Receptors Inhibits Neutrophil Transuroepithelial Migration

    PubMed Central

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

    2011-01-01

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

  5. Selective Modulation of Integrin-mediated Cell Migration by Distinct ADAM Family MembersV⃞

    PubMed Central

    Huang, Jing; Bridges, Lance C.; White, Judith M.

    2005-01-01

    A disintegrin and a metalloprotease (ADAM) family members have been implicated in many biological processes. Although it is recognized that recombinant ADAM disintegrin domains can interact with integrins, little is known about ADAM-integrin interactions in cellular context. Here, we tested whether ADAMs can selectively regulate integrin-mediated cell migration. ADAMs were expressed in Chinese hamster ovary cells that express defined integrins (α4β1, α5β1, or both), and cell migration on full-length fibronectin or on its α4β1 or α5β1 binding fragments was studied. We found that ADAMs inhibit integrin-mediated cell migration in patterns dictated by the integrin binding profiles of their isolated disintegrin domains. ADAM12 inhibited cell migration mediated by the α4β1 but not the α5β1 integrin. ADAM17 had the reciprocal effect; it inhibited α5β1- but not α4β1-mediated cell migration. ADAM19 and ADAM33 inhibited migration mediated by both α4β1 and α5β1 integrins. A point mutation in the ADAM12 disintegrin loop partially reduced the inhibitory effect of ADAM12 on cell migration on the α4β1 binding fragment of fibronectin, whereas mutations that block metalloprotease activity had no effect. Our results indicate that distinct ADAMs can modulate cell migration mediated by specific integrins in a pattern dictated, at least in part, by their disintegrin domains. PMID:16079176

  6. Intracellular targeting of annexin A2 inhibits tumor cell adhesion, migration, and in vivo grafting.

    PubMed

    Staquicini, Daniela I; Rangel, Roberto; Guzman-Rojas, Liliana; Staquicini, Fernanda I; Dobroff, Andrey S; Tarleton, Christy A; Ozbun, Michelle A; Kolonin, Mikhail G; Gelovani, Juri G; Marchiò, Serena; Sidman, Richard L; Hajjar, Katherine A; Arap, Wadih; Pasqualini, Renata

    2017-06-26

    Cytoskeletal-associated proteins play an active role in coordinating the adhesion and migration machinery in cancer progression. To identify functional protein networks and potential inhibitors, we screened an internalizing phage (iPhage) display library in tumor cells, and selected LGRFYAASG as a cytosol-targeting peptide. By affinity purification and mass spectrometry, intracellular annexin A2 was identified as the corresponding binding protein. Consistently, annexin A2 and a cell-internalizing, penetratin-fused version of the selected peptide (LGRFYAASG-pen) co-localized and specifically accumulated in the cytoplasm at the cell edges and cell-cell contacts. Functionally, tumor cells incubated with LGRFYAASG-pen showed disruption of filamentous actin, focal adhesions and caveolae-mediated membrane trafficking, resulting in impaired cell adhesion and migration in vitro. These effects were paralleled by a decrease in the phosphorylation of both focal adhesion kinase (Fak) and protein kinase B (Akt). Likewise, tumor cells pretreated with LGRFYAASG-pen exhibited an impaired capacity to colonize the lungs in vivo in several mouse models. Together, our findings demonstrate an unrecognized functional link between intracellular annexin A2 and tumor cell adhesion, migration and in vivo grafting. Moreover, this work uncovers a new peptide motif that binds to and inhibits intracellular annexin A2 as a candidate therapeutic lead for potential translation into clinical applications.

  7. KCa3.1 Modulates Neuroblast Migration Along the Rostral Migratory Stream (RMS) In Vivo

    PubMed Central

    Turner, Kathryn L.; Sontheimer, Harald

    2014-01-01

    From the subventricular zone (SVZ), neuronal precursor cells (NPCs), called neuroblasts, migrate through the rostral migratory stream (RMS) to become interneurons in the olfactory bulb (OB). Ion channels regulate neuronal migration during development, yet their role in migration through the adult RMS is unknown. To address this question, we utilized Nestin-CreERT2/R26R-YFP mice to fluorescently label neuroblasts in the adult. Patch-clamp recordings from neuroblasts reveal K+ currents that are sensitive to intracellular Ca2+ levels and blocked by clotrimazole and TRAM-34, inhibitors of intermediate conductance Ca2+-activated K+ (KCa3.1) channels. Immunolabeling and electrophysiology show KCa3.1 expression restricted to neuroblasts in the SVZ and RMS, but absent in OB neurons. Time-lapse confocal microscopy in situ showed inhibiting KCa3.1 prolonged the stationary phase of neuroblasts' saltatory migration, reducing migration speed by over 50%. Both migration and KCa3.1 currents could also be inhibited by blocking Ca2+ influx via transient receptor potential (TRP) channels, which, together with positive immunostaining for transient receptor potential canonical 1 (TRPC1), suggest that TRP channels are an important Ca2+ source modulating KCa3.1 activity. Finally, injecting TRAM-34 into Nestin-CreERT2/R26R-YFP mice significantly reduced the number of neuroblasts that reached the OB, suggesting an important role for KCa3.1 in vivo. These studies describe a previously unrecognized protein in migration of adult NPCs. PMID:23585521

  8. Kinesin-5, a mitotic microtubule-associated motor protein, modulates neuronal migration

    PubMed Central

    Falnikar, Aditi; Tole, Shubha; Baas, Peter W.

    2011-01-01

    Kinesin-5 (also called Eg5 or kif11) is a homotetrameric motor protein that functions by modulating microtubule (MT)–MT interactions. In the case of mitosis, kinesin-5 slows the rate of separation of the half-spindles. In the case of the axon, kinesin-5 limits the frequency of transport of short MTs, and also limits the rate of axonal growth. Here we show that experimental inhibition of kinesin-5 in cultured migratory neurons results in a faster but more randomly moving neuron with a shorter leading process. As is the case with axons of stationary neurons, short MT transport frequency is notably enhanced in the leading process of the migratory neuron when kinesin-5 is inhibited. Conversely, overexpression of kinesin-5, both in culture and in developing cerebral cortex, causes migration to slow and even cease. Regions of anti-parallel MT organization behind the centrosome were shown to be especially rich in kinesin-5, implicating these regions as potential sites where kinesin-5 forces may be especially relevant. We posit that kinesin-5 acts as a “brake” on MT–MT interactions that modulates the advance of the entire MT apparatus. In so doing, kinesin-5 regulates the rate and directionality of neuronal migration and possibly the cessation of migration when the neuron reaches its destination. PMID:21411631

  9. BIGH3 modulates adhesion and migration of hematopoietic stem and progenitor cells

    PubMed Central

    Klamer, Sofieke E; Kuijk, Carlijn GM; Hordijk, Peter L; van der Schoot, C Ellen; von Lindern, Marieke; van Hennik, Paula B; Voermans, Carlijn

    2013-01-01

    Cell adhesion and migration are important determinants of homing and development of hematopoietic stem and progenitor cells (HSPCs) in bone marrow (BM) niches. The extracellular matrix protein transforming growth factor-β (TGF-β) inducible gene H3 (BIGH3) is involved in adhesion and migration, although the effect of BIGH3 is highly cell type-dependent. BIGH3 is abundantly expressed by mesenchymal stromal cells, while its expression in HSPCs is relatively low unless induced by certain BM stressors. Here, we set out to determine how BIGH3 modulates HSPC adhesion and migration. We show that primary HSPCs adhere to BIGH3-coated substrates, which is, in part, integrin-dependent. Overexpression of BIGH3 in HSPCs and HL60 cells reduced the adhesion to the substrate fibronectin in adhesion assays, which was even more profound in electrical cell-substrate impedance sensing (ECIS) assays. Accordingly, the CXCL12 induced migration over fibronectin-coated surface was reduced in BIGH3-expressing HSPCs. The integrin expression profile of HSPCs was not altered upon BIGH3 expression. Although expression of BIGH3 did not alter actin polymerization in response to CXCL12, it inhibited the PMA-induced activation of the small GTPase RAC1 as well as the phosphorylation and activation of extracellular-regulated kinases (ERKs). Reduced activation of ERK and RAC1 may be responsible for the inhibition of cell adhesion and migration by BIGH3 in HSPCs. Induced BIGH3 expression upon BM stress may contribute to the regulation of BM homeostasis. PMID:24152593

  10. Curcumin modulates endothelial permeability and monocyte transendothelial migration by affecting endothelial cell dynamics.

    PubMed

    Monfoulet, Laurent-Emmanuel; Mercier, Sylvie; Bayle, Dominique; Tamaian, Radu; Barber-Chamoux, Nicolas; Morand, Christine; Milenkovic, Dragan

    2017-11-01

    Curcumin is a phenolic compound that exhibits beneficial properties for cardiometabolic health. We previously showed that curcumin reduced the infiltration of immune cells into the vascular wall and prevented atherosclerosis development in mice. This study aimed to investigate the effect of curcumin on monocyte adhesion and transendothelial migration (TEM) and to decipher the underlying mechanisms of these actions. Human umbilical vein endothelial cells (HUVECs) were exposed to curcumin (0.5-1μM) for 3h prior to their activation by Tumor Necrosis Factor alpha (TNF-α). Endothelial permeability, monocyte adhesion and transendothelial migration assays were conducted under static condition and shear stress that mimics blood flow. We further investigated the impact of curcumin on signaling pathways and on the expression of genes using macroarrays. Pre-exposure of endothelial cells to curcumin reduced monocyte adhesion and their transendothelial migration in both static and shear stress conditions. Curcumin also prevented changes in both endothelial permeability and the area of HUVECs when induced by TNF-α. We showed that curcumin modulated the expression of 15 genes involved in the control of cytoskeleton and endothelial junction dynamic. Finally, we showed that curcumin inhibited NF-κB signaling likely through an antagonist interplay with several kinases as suggested by molecular docking analysis. Our findings demonstrate the ability of curcumin to reduce monocyte TEM through a multimodal regulation of the endothelial cell dynamics with a potential benefit on the vascular endothelial function barrier. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Receptor Protein Tyrosine Phosphatase-Receptor Tyrosine Kinase Substrate Screen Identifies EphA2 as a Target for LAR in Cell Migration

    PubMed Central

    Lee, Hojin

    2013-01-01

    Receptor tyrosine kinases (RTKs) exist in equilibrium between tyrosyl-phosphorylated and dephosphorylated states. Despite a detailed understanding of how RTKs become tyrosyl phosphorylated, much less is known about RTK tyrosyl dephosphorylation. Receptor protein tyrosine phosphatases (RPTPs) can play essential roles in the dephosphorylation of RTKs. However, a complete understanding of the involvement of the RPTP subfamily in RTK tyrosyl dephosphorylation has not been established. In this study, we have employed a small interfering RNA (siRNA) screen to identify RPTPs in the human genome that serve as RTK phosphatases. We observed that each RPTP induced a unique fingerprint of tyrosyl phosphorylation among 42 RTKs. We identified EphA2 as a novel LAR substrate. LAR dephosphorylated EphA2 at phosphotyrosyl 930, uncoupling Nck1 from EphA2 and thereby attenuating EphA2-mediated cell migration. These results demonstrate that each RPTP exerts a unique regulatory fingerprint of RTK tyrosyl dephosphorylation and suggest a complex signaling interplay between RTKs and RPTPs. Furthermore, we observed that LAR modulates cell migration through EphA2 site-specific dephosphorylation. PMID:23358419

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

    PubMed Central

    2011-01-01

    of transcription 1 was reduced in LPS-triggered microglia. These transcriptional changes in curcumin-treated LPS-primed microglia also lead to decreased neurotoxicity with reduced apoptosis of 661W photoreceptor cultures. Conclusions Collectively, our results suggest that curcumin is a potent modulator of the microglial transcriptome. Curcumin attenuates microglial migration and triggers a phenotype with anti-inflammatory and neuroprotective properties. Thus, curcumin could be a nutraceutical compound to develop immuno-modulatory and neuroprotective therapies for the treatment of various neurodegenerative disorders. PMID:21958395

  13. Glutaraldehyde pretreatment blocks phospholipase A2 modulation of adrenergic receptors.

    PubMed

    Cohen, R M; McLellan, C; Dauphin, M; Hirata, F

    1985-01-07

    Treatment of rat cerebral cortical membranes with phospholipase A2 affects, in a parallel fashion, beta-, alpha 1- and alpha 2-adrenergic receptor binding, but not the affinity of these receptors for their respective ligands. Pretreatment of membranes with 0.1 percent glutaraldehyde blocks the effects of phospholipase A2 on adrenergic receptor binding. The results support the hypothesis that desensitization or "masking" of adrenergic receptors may involve changes in membrane lipid composition. Furthermore, glutaraldehyde may prove a useful tool in the investigation of the dynamic roles of lipids in receptor function and more specifically, their regulation and coupling to physiological events.

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

    PubMed Central

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

    2013-01-01

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

  15. Macrophages Modulate Migration and Invasion of Human Tongue Squamous Cell Carcinoma

    PubMed Central

    Pirilä, Emma; Väyrynen, Otto; Sundquist, Elias; Päkkilä, Kaisa; Nyberg, Pia; Nurmenniemi, Sini; Pääkkönen, Virve; Pesonen, Paula; Dayan, Dan; Vered, Marilena; Uhlin-Hansen, Lars; Salo, Tuula

    2015-01-01

    Oral tongue squamous cell carcinoma (OTSCC) has a high mortality rate and the incidence is rising worldwide. Despite advances in treatment, the disease lacks specific prognostic markers and treatment modality. The spreading of OTSCC is dependent on the tumor microenvironment and involves tumor-associated macrophages (TAMs). Although the presence of TAMs is associated with poor prognosis in OTSCC, the specific mechanisms underlying this are still unknown. The aim here was to investigate the effect of macrophages (Mfs) on HSC-3 tongue carcinoma cells and NF-kappaB activity. We polarized THP-1 cells to M1 (inflammatory), M2 (TAM-like) and R848 (imidazoquinoline-treated) type Mfs. We then investigated the effect of Mfs on HSC-3 cell migration and NF-kappaB activity, cytokine production and invasion using several different in vitro migration models, a human 3D tissue invasion model, antibody arrays, confocal microscopy, immunohistochemistry and a mouse invasion model. We found that in co-culture studies all types of Mfs fused with HSC-3 cells, a process which was partially due to efferocytosis. HSC-3 cells induced expression of epidermal growth factor and transforming growth factor-beta in co-cultures with M2 Mfs. Direct cell-cell contact between M2 Mfs and HSC-3 cells induced migration and invasion of HSC-3 cells while M1 Mfs reduced HSC-3 cell invasion. M2 Mfs had an excess of NF-kappaB p50 subunit and a lack of p65 subunits both in the presence and absence of HSC-3 cells, indicating dysregulation and pro-tumorigenic NF-kappaB activation. TAM-like cells were abundantly present in close vicinity to carcinoma cells in OTSCC patient samples. We conclude that M2 Mfs/TAMs have an important role in OTSCC regulating adhesion, migration, invasion and cytokine production of carcinoma cells favouring tumor growth. These results demonstrate that OTSCC patients could benefit from therapies targeting TAMs, polarizing TAM-like M2 Mfs to inflammatory macrophages and modulating NF

  16. Transspinal direct current stimulation modulates migration and proliferation of adult newly born spinal cells in mice.

    PubMed

    Samaddar, Sreyashi; Vazquez, Kizzy; Ponkia, Dipen; Toruno, Pedro; Sahbani, Karim; Begum, Sultana; Abouelela, Ahmed; Mekhael, Wagdy; Ahmed, Zaghloul

    2017-02-01

    Direct current electrical fields have been shown to be a major factor in the regulation of cell proliferation, differentiation, migration, and survival, as well as in the maturation of dividing cells during development. During adulthood, spinal cord cells are continuously produced in both animals and humans, and they hold great potential for neural restoration following spinal cord injury. While the effects of direct current electrical fields on adult-born spinal cells cultured ex vivo have recently been reported, the effects of direct current electrical fields on adult-born spinal cells in vivo have not been characterized. Here, we provide convincing findings that a therapeutic form of transspinal direct current stimulation (tsDCS) affects the migration and proliferation of adult-born spinal cells in mice. Specifically, cathodal tsDCS attracted the adult-born spinal cells, while anodal tsDCS repulsed them. In addition, both tsDCS polarities caused a significant increase in cell number. Regarding the potential mechanisms involved, both cathodal and anodal tsDCS caused significant increases in expression of brain-derived neurotrophic factor, while expression of nerve growth factor increased and decreased, respectively. In the spinal cord, both anodal and cathodal tsDCS increased blood flow. Since blood flow and angiogenesis are associated with the proliferation of neural stem cells, increased blood flow may represent a major factor in the modulation of newly born spinal cells by tsDCS. Consequently, we propose that the method and novel findings presented in the current study have the potential to facilitate cellular, molecular, and/or bioengineering strategies to repair injured spinal cords. NEW & NOTEWORTHY Our results indicate that transspinal direct current stimulation (tsDCS) affects the migratory pattern and proliferation of adult newly born spinal cells, a cell population which has been implicated in learning and memory. In addition, our results suggest a

  17. MiR-26b inhibits hepatocellular carcinoma cell proliferation, migration, and invasion by targeting EphA2.

    PubMed

    Li, Hesheng; Sun, Qinglei; Han, Bing; Yu, Xingquan; Hu, Baoguang; Hu, Sanyuan

    2015-01-01

    Deregulated microRNAs (miRNAs) have been shown to play important roles in cancer progression as a result of changes in expression of their target genes. In this study, we investigated the expression of miR-16b in eight hepatocellular carcinoma (HCC) cell lines, revealed the roles of miR-26b on hepatocellular carcinoma (HCC) cell proliferation, migration, and invasion, and confirmed that EphA2 is a direct target of miR-26b. The miR-26b expression was decreased and EphA2 expression was evaluated in HCC cell lines. Luciferase assays revealed that miR-26b inhibited EphA2 expression by targeting the 3'-untranslated region of EphA2 mRNA. Overexpression of miR-26b dramatically inhibited the proliferation, invasion, and migration of HCC cells by targeting EphA2. Moreover, miR-26b down-regulated c-Myc and CyclinD1 expression, which was reversed by overexpressed EphA2. Taken together, our data demonstrated the mechanism of miR-26b contributed to HCC progression and implicated that miR-26b's potential in HCC therapy.

  18. Epithelial cell kinase-B61: an autocrine loop modulating intestinal epithelial migration and barrier function.

    PubMed

    Rosenberg, I M; Göke, M; Kanai, M; Reinecker, H C; Podolsky, D K

    1997-10-01

    Epithelial cell kinase (Eck) is a member of a large family of receptor tyrosine kinases whose functions remain largely unknown. Expression and regulation of Eck and its cognate ligand B61 were analyzed in the human colonic adenocarcinoma cell line Caco-2. Immunocytochemical staining demonstrated coexpression of Eck and B61 in the same cells, suggestive of an autocrine loop. Eck levels were maximal in preconfluent cells. In contrast, B61 levels were barely detectable in preconfluent cells and increased progressively after the cells reached confluence. Caco-2 cells cultured in the presence of added B61 showed a significant reduction in the levels of dipeptidyl peptidase and sucrase-isomaltase mRNA, markers of Caco-2 cell differentiation. Cytokines interleukin-1beta (IL-1beta), basic fibroblast growth factor, IL-2, epidermal growth factor, and transforming growth factor-beta modulated steady-state levels of Eck and B61 mRNA and regulated Eck activation as assessed by tyrosine phosphorylation. Functionally, stimulation of Eck by B61 resulted in increased proliferation, enhanced barrier function, and enhanced restitution of injured epithelial monolayers. These results suggest that the Eck-B61 interaction, a target of regulatory peptides, plays a role in intestinal epithelial cell development, migration, and barrier function, contributing to homeostasis and preservation of continuity of the epithelial barrier.

  19. FixO3 project results, legacy and module migration to EMSO

    NASA Astrophysics Data System (ADS)

    Lampitt, Richard

    2017-04-01

    The fixed point open ocean observatory network (FixO3) project is an international project aimed at integrating in a single network all fixed point open ocean observatories operated by European organisations and to harmonise and coordinate technological, procedural and data management across the stations. The project is running for four years since September 2013 with 29 partners across Europe and a budget of 7M Euros and is now coming to its final phase. In contrast to several past programmes, the opportunity has arisen to ensure that many of the project achievements can migrate into the newly formed European Multidisciplinary Seafloor and water column Observatory (EMSO) research infrastructure. The final phase of the project will focus on developing a strategy to transfer the results in an efficient way to maintain their relevance and maximise their use. In this presentation, we will highlight the significant achievements of FixO3 over the past three years focussing on the modules which will be transferred to EMSO in the coming 9 months. These include: 1. Handbook of best practices for operating fixed point observatories 2. Metadata catalogue 3. Earth Virtual Observatory (EarthVO) for data visualisation and comparison 4. Open Ocean Observatory Yellow Pages (O3YP) 5. Training material for hardware, data and data products used

  20. A space oddity: geographic and specific modulation of migration in Eudyptes penguins.

    PubMed

    Thiebot, Jean-Baptiste; Cherel, Yves; Crawford, Robert J M; Makhado, Azwianewi B; Trathan, Philip N; Pinaud, David; Bost, Charles-André

    2013-01-01

    Post-breeding migration in land-based marine animals is thought to offset seasonal deterioration in foraging or other important environmental conditions at the breeding site. However the inter-breeding distribution of such animals may reflect not only their optimal habitat, but more subtle influences on an individual's migration path, including such factors as the intrinsic influence of each locality's paleoenvironment, thereby influencing animals' wintering distribution. In this study we investigated the influence of the regional marine environment on the migration patterns of a poorly known, but important seabird group. We studied the inter-breeding migration patterns in three species of Eudyptes penguins (E. chrysolophus, E. filholi and E. moseleyi), the main marine prey consumers amongst the World's seabirds. Using ultra-miniaturized logging devices (light-based geolocators) and satellite tags, we tracked 87 migrating individuals originating from 4 sites in the southern Indian Ocean (Marion, Crozet, Kerguelen and Amsterdam Islands) and modelled their wintering habitat using the MADIFA niche modelling technique. For each site, sympatric species followed a similar compass bearing during migration with consistent species-specific latitudinal shifts. Within each species, individuals breeding on different islands showed contrasting migration patterns but similar winter habitat preferences driven by sea-surface temperatures. Our results show that inter-breeding migration patterns in sibling penguin species depend primarily on the site of origin and secondly on the species. Such site-specific migration bearings, together with similar wintering habitat used by parapatrics, support the hypothesis that migration behaviour is affected by the intrinsic characteristics of each site. The paleo-oceanographic conditions (primarily, sea-surface temperatures) when the populations first colonized each of these sites may have been an important determinant of subsequent migration

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

    PubMed

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

    2018-05-01

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

  2. A2A adenosine receptor ligand binding and signalling is allosterically modulated by adenosine deaminase.

    PubMed

    Gracia, Eduard; Pérez-Capote, Kamil; Moreno, Estefanía; Barkešová, Jana; Mallol, Josefa; Lluís, Carme; Franco, Rafael; Cortés, Antoni; Casadó, Vicent; Canela, Enric I

    2011-05-01

    A2ARs (adenosine A2A receptors) are highly enriched in the striatum, which is the main motor control CNS (central nervous system) area. BRET (bioluminescence resonance energy transfer) assays showed that A2AR homomers may act as cell-surface ADA (adenosine deaminase; EC 3.5.4.4)-binding proteins. ADA binding affected the quaternary structure of A2ARs present on the cell surface. ADA binding to adenosine A2ARs increased both agonist and antagonist affinity on ligand binding to striatal membranes where these proteins are co-expressed. ADA also increased receptor-mediated ERK1/2 (extracellular-signal-regulated kinase 1/2) phosphorylation. Collectively, the results of the present study show that ADA, apart from regulating the concentration of extracellular adenosine, may behave as an allosteric modulator that markedly enhances ligand affinity and receptor function. This powerful regulation may have implications for the physiology and pharmacology of neuronal A2ARs.

  3. Kaposi’s Sarcoma-Associated Herpesvirus Interleukin-6 Modulates Endothelial Cell Movement by Upregulating Cellular Genes Involved in Migration

    PubMed Central

    Giffin, Louise; West, John A.

    2015-01-01

    ABSTRACT Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of human Kaposi’s sarcoma, a tumor that arises from endothelial cells, as well as two B cell lymphoproliferative diseases, primary effusion lymphoma and multicentric Castleman’s disease. KSHV utilizes a variety of mechanisms to evade host immune responses and promote cellular transformation and growth in order to persist for the life of the host. A viral homolog of human interleukin-6 (hIL-6) named viral interleukin-6 (vIL-6) is encoded by KSHV and expressed in KSHV-associated cancers. Similar to hIL-6, vIL-6 is secreted, but the majority of vIL-6 is retained within the endoplasmic reticulum, where it can initiate functional signaling through part of the interleukin-6 receptor complex. We sought to determine how intracellular vIL-6 modulates the host endothelial cell environment by analyzing vIL-6’s impact on the endothelial cell transcriptome. vIL-6 significantly altered the expression of many cellular genes associated with cell migration. In particular, vIL-6 upregulated the host factor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) at the protein and message levels. CEACAM1 has been implicated in tumor invasion and metastasis and promotes migration and vascular remodeling in endothelial cells. We report that vIL-6 upregulates CEACAM1 by a STAT3-dependent mechanism and that CEACAM1 promotes vIL-6-mediated migration. Furthermore, latent and de novo KSHV infections of endothelial cells also induce CEACAM1 expression. Collectively, our data suggest that vIL-6 modulates endothelial cell migration by upregulating the expression of cellular factors, including CEACAM1. PMID:26646010

  4. In-situ calibration: migrating control system IP module calibration from the bench to the storage ring

    SciTech Connect

    Weber, Jonah M.; Chin, Michael

    2002-04-30

    The Control System for the Advanced Light Source (ALS) at Lawrence Berkeley National Lab (LBNL) uses in-house designed IndustryPack(registered trademark) (IP) modules contained in compact PCI (cPCI) crates with 16-bit analog I/O to control instrumentation. To make the IP modules interchangeable, each module is calibrated for gain and offset compensation. We initially developed a method of verifying and calibrating the IP modules in a lab bench test environment using a PC with LabVIEW. The subsequent discovery that the ADCs have significant drift characteristics over periods of days of installed operation prompted development of an ''in-situ'' calibration process--one in which themore » IP modules can be calibrated without removing them from the cPCI crates in the storage ring. This paper discusses the original LabVIEW PC calibration and the migration to the proposed in-situ EPICS control system calibration.« less

  5. Modulation of human endothelial cell proliferation and migration by fucoidan and heparin.

    PubMed

    Giraux, J L; Matou, S; Bros, A; Tapon-Bretaudière, J; Letourneur, D; Fischer, A M

    1998-12-01

    Fucoidan is a sulfated polysaccharide extracted from brown seaweeds. It has anticoagulant and antithrombotic properties and inhibits, as well as heparin, vascular smooth muscle cell growth. In this study, we investigated, in the presence of serum and human recombinant growth factors, the effects of fucoidan and heparin on the growth and migration of human umbilical vein endothelial cells (HUVEC) in culture. We found that fucoidan stimulated fetal bovine serum-induced HUVEC proliferation, whereas heparin inhibited it. In the presence of fibroblast growth factor-1 (FGF-1), both fucoidan and heparin potentiated HUVEC growth. In contrast, fucoidan and heparin inhibited HUVEC proliferation induced by FGF-2, but did not influence the mitogenic activity of vascular endothelial growth factor (VEGF). In the in vitro migration assay from a denuded area of confluent cells, the two sulfated polysaccharides markedly enhanced the migration of endothelial cells in the presence of FGF-1. Finally, a weak inhibitory effect on cell migration was found only with the two polysaccharides at high concentrations (> or = 100 micro/ml) in presence of serum or combined with FGF-2. All together, the results indicated that heparin and fucoidan can be used as tools to further investigate the cellular mechanisms regulating the proliferation and migration of human vascular cells. Moreover, the data already suggest a potential role of fucoidan as a new therapeutic agent of vegetal origin in the vascular endothelium wound repair.

  6. COUP-TFI mitotically regulates production and migration of dentate granule cells and modulates hippocampal Cxcr4 expression.

    PubMed

    Parisot, Joséphine; Flore, Gemma; Bertacchi, Michele; Studer, Michèle

    2017-06-01

    Development of the dentate gyrus (DG), the primary gateway for hippocampal inputs, spans embryonic and postnatal stages, and involves complex morphogenetic events. We have previously identified the nuclear receptor COUP-TFI as a novel transcriptional regulator in the postnatal organization and function of the hippocampus. Here, we dissect its role in DG morphogenesis by inactivating it in either granule cell progenitors or granule neurons. Loss of COUP-TFI function in progenitors leads to decreased granule cell proliferative activity, precocious differentiation and increased apoptosis, resulting in a severe DG growth defect in adult mice. COUP-TFI-deficient cells express high levels of the chemokine receptor Cxcr4 and migrate abnormally, forming heterotopic clusters of differentiated granule cells along their paths. Conversely, high COUP-TFI expression levels downregulate Cxcr4 expression, whereas increased Cxcr4 expression in wild-type hippocampal cells affects cell migration. Finally, loss of COUP-TFI in postmitotic cells leads to only minor and transient abnormalities, and to normal Cxcr4 expression. Together, our results indicate that COUP-TFI is required predominantly in DG progenitors for modulating expression of the Cxcr4 receptor during granule cell neurogenesis and migration. © 2017. Published by The Company of Biologists Ltd.

  7. Low Doses of Curcuma longa Modulates Cell Migration and Cell-Cell Adhesion.

    PubMed

    de Campos, Paloma Santos; Matte, Bibiana Franzen; Diel, Leonardo Francisco; Jesus, Luciano Henrique; Bernardi, Lisiane; Alves, Alessandro Menna; Rados, Pantelis Varvaki; Lamers, Marcelo Lazzaron

    2017-09-01

    Cell invasion and metastasis are involved in clinical failures in cancer treatment, and both events require the acquisition of a migratory behavior by tumor cells. Curcumin is a promising natural product with anti-proliferative activity, but its effects on cell migration are still unclear. We evaluated the effects of curcumin on the proliferation, apoptosis, migration, and cell-cell adhesion of keratinocyte, oral squamous cell carcinoma (OSCC), and fibroblast cell lines, as well as in a xenograft model of OSCC. Curcumin (2 μM) decreased cell proliferation in cell lines with mesenchymal characteristics, while cell death was detected only at 50 μM. We observed that highly migratory cells showed a decrease on migration speed and directionality when treated with 2 or 5 μM of curcumin (50% and 40%, respectively, p < 0.05). Using spheroids, we observed that curcumin dose dependently decreased cell-cell adhesion, especially on tumor-derived spheroids. Also, in a xenograft model with patient-derived OSCC cells, the administration of curcumin decreased tumor growth and aggressiveness when compared with untreated tumors, indicating the potential antitumor effect in oral cancer. These results suggest that lower doses of curcumin can influence several steps involved in tumorigenesis, including migration properties, suggesting a possible use in cancer therapy. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

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

    PubMed Central

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

    2018-01-01

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

  9. Glia Maturation Factor-γ Regulates Monocyte Migration through Modulation of β1-Integrin*

    PubMed Central

    Aerbajinai, Wulin; Liu, Lunhua; Zhu, Jianqiong; Kumkhaek, Chutima; Chin, Kyung; Rodgers, Griffin P.

    2016-01-01

    Monocyte migration requires the dynamic redistribution of integrins through a regulated endo-exocytosis cycle, but the complex molecular mechanisms underlying this process have not been fully elucidated. Glia maturation factor-γ (GMFG), a novel regulator of the Arp2/3 complex, has been shown to regulate directional migration of neutrophils and T-lymphocytes. In this study, we explored the important role of GMFG in monocyte chemotaxis, adhesion, and β1-integrin turnover. We found that knockdown of GMFG in monocytes resulted in impaired chemotactic migration toward formyl-Met-Leu-Phe (fMLP) and stromal cell-derived factor 1α (SDF-1α) as well as decreased α5β1-integrin-mediated chemoattractant-stimulated adhesion. These GMFG knockdown impaired effects could be reversed by cotransfection of GFP-tagged full-length GMFG. GMFG knockdown cells reduced the cell surface and total protein levels of α5β1-integrin and increased its degradation. Importantly, we demonstrate that GMFG mediates the ubiquitination of β1-integrin through knockdown or overexpression of GMFG. Moreover, GMFG knockdown retarded the efficient recycling of β1-integrin back to the plasma membrane following normal endocytosis of α5β1-integrin, suggesting that the involvement of GMFG in maintaining α5β1-integrin stability may occur in part by preventing ubiquitin-mediated degradation and promoting β1-integrin recycling. Furthermore, we observed that GMFG interacted with syntaxin 4 (STX4) and syntaxin-binding protein 4 (STXBP4); however, only knockdown of STXBP4, but not STX4, reduced monocyte migration and decreased β1-integrin cell surface expression. Knockdown of STXBP4 also substantially inhibited β1-integrin recycling in human monocytes. These results indicate that the effects of GMFG on monocyte migration and adhesion probably occur through preventing ubiquitin-mediated proteasome degradation of α5β1-integrin and facilitating effective β1-integrin recycling back to the plasma membrane

  10. NOR1 promotes hepatocellular carcinoma cell proliferation and migration through modulating the Notch signaling pathway

    SciTech Connect

    You, Kun; Sun, Peisheng; Yue, Zhongyi

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Previous studies have reported that the oxidored-nitro domain containing protein 1 (NOR1) is a novel tumor suppressor in several tumors. Recent evidence suggests that NOR1 is strongly expressed in HCC cells. However, its role and mechanism in HCC are unclear. In the current study, Western blot and qPCR detected strong NOR1 mRNA and protein expression in HepG2 and Hep3B cells. After transfection with NOR1 siRNA or pcDNA3.1-myc-his-NOR1, the proliferation and migration of HepG2 and Hep3B cells were analyzed in vitro. HepG2 or Hep3B cells overexpressing NOR1 showed anmore » increased proliferation and migration, whereas siRNA-mediated silencing of NOR1 showed the opposite effect. Furthermore, NOR1 activated the Notch signaling pathway, indicated by increased levels of Notch1, NICD, Hes1, and Hey1 in protein. Importantly, the Notch inhibitor DAPT downregulated Notch activation and further enhanced siNOR1-induced reduction of cell proliferation and migration in HepG2 and Hep3B cells, whereas DAPT reversed the effect of NOR1 overexpression on cell proliferation and migration. In conclusion, these results indicate that NOR1 may be involved in the progression of HCC and thus may be a potential target for the treatment of liver cancer. - Highlights: • NOR1 expression is up-regulated in HCC cells. • NOR1 promotes the proliferation and migration of HCC cells. • NOR1 promotes the progression of HCC cells by activating Notch pathway.« less

  11. Modulation of eosinophil generation and migration by Mangifera indica L. extract (Vimang).

    PubMed

    Sá-Nunes, Anderson; Rogerio, Alexandre P; Medeiros, Alexandra I; Fabris, Viciany E; Andreu, Gilberto P; Rivera, Dagmar G; Delgado, René; Faccioli, Lúcia H

    2006-09-01

    The effects of Vimang, an aqueous extract of the stem bark of Mangifera indica L. (Anacardiaceae), on cell migration in an experimental model of asthma was investigated. In vivo treatment of Toxocara canis-infected BALB/c mice for 18 days with 50 mg/kg Vimang reduced eosinophil migration into the bronchoalveolar space and peritoneal cavity. Also, eosinophil generation in bone marrow and blood eosinophilia were inhibited in infected mice treated with Vimang. This reduction was associated with inhibition of IL-5 production in serum and eotaxin in lung homogenates. In all these cases the effects of Vimang were more selective than those observed with dexamethasone. Moreover, Vimang treatment is not toxic for the animals, as demonstrated by the normal body weight increase during infection. These data confirm the potent anti-inflammatory effect of Vimang and support its potential use as an alternative therapeutic drug to the treatment of eosinophilic disorders including those caused by nematodes and allergic diseases.

  12. LGL1 modulates proliferation, apoptosis, and migration of human fetal lung fibroblasts.

    PubMed

    Zhang, Hui; Sweezey, Neil B; Kaplan, Feige

    2015-02-15

    Rapid growth and formation of new gas exchange units (alveogenesis) are hallmarks of the perinatal lung. Bronchopulmonary dysplasia (BPD), common in very premature infants, is characterized by premature arrest of alveogenesis. Mesenchymal cells (fibroblasts) regulate both lung branching and alveogenesis through mesenchymal-epithelial interactions. Temporal or spatial deficiency of late-gestation lung 1/cysteine-rich secretory protein LD2 (LGL1/CRISPLD2), expressed in and secreted by lung fibroblasts, can impair both lung branching and alveogenesis (LGL1 denotes late gestation lung 1 protein; LGL1 denotes the human gene; Lgl1 denotes the mouse/rat gene). Absence of Lgl1 is embryonic lethal. Lgl1 levels are dramatically reduced in oxygen toxicity rat models of BPD, and heterozygous Lgl1(+/-) mice exhibit features resembling human BPD. To explore the role of LGL1 in mesenchymal-epithelial interactions in developing lung, we developed a doxycycline (DOX)-inducible RNA-mediated LGL1 knockdown cellular model in human fetal lung fibroblasts (MRC5(LGL1KD)). We assessed the impact of LGL1 on cell proliferation, cell migration, apoptosis, and wound healing. DOX-induced MRC5(LGL1KD) suppressed cell growth and increased apoptosis of annexin V(+) staining cells and caspase 3/7 activity. LGL1-conditioned medium increased migration of fetal rat primary lung epithelial cells and human airway epithelial cells. Impaired healing by MRC5(LGL1KD) cells of a wound model was attenuated by addition of LGL1-conditioned medium. Suppression of LGL1 was associated with dysregulation of extracellular matrix genes (downregulated MMP1, ColXVα1, and ELASTIN) and proapoptosis genes (upregulated BAD, BAK, CASP2, and TNFRSF1B) and inhibition of 44/42MAPK phosphorylation. Our findings define a role for LGL1 in fibroblast expansion and migration, epithelial cell migration, and mesenchymal-epithelial signaling, key processes in fetal lung development. Copyright © 2015 the American Physiological

  13. MicroRNA-155 Modulates Acute Graft-versus-Host Disease by Impacting T Cell Expansion, Migration, and Effector Function.

    PubMed

    Zitzer, Nina C; Snyder, Katiri; Meng, Xiamoei; Taylor, Patricia A; Efebera, Yvonne A; Devine, Steven M; Blazar, Bruce R; Garzon, Ramiro; Ranganathan, Parvathi

    2018-06-15

    MicroRNA-155 (miR-155) is a small noncoding RNA critical for the regulation of inflammation as well as innate and adaptive immune responses. MiR-155 has been shown to be dysregulated in both donor and recipient immune cells during acute graft-versus-host disease (aGVHD). We previously reported that miR-155 is upregulated in donor T cells of mice and humans with aGVHD and that mice receiving miR-155-deficient (miR155 -/- ) splenocytes had markedly reduced aGVHD. However, molecular mechanisms by which miR-155 modulates T cell function in aGVHD have not been fully investigated. We identify that miR-155 expression in both donor CD8 + T cells and conventional CD4 + CD25 - T cells is pivotal for aGVHD pathogenesis. Using murine aGVHD transplant experiments, we show that miR-155 strongly impacts alloreactive T cell expansion through multiple distinct mechanisms, modulating proliferation in CD8 + donor T cells and promoting exhaustion in donor CD4 + T cells in both the spleen and colon. Additionally, miR-155 drives a proinflammatory Th1 phenotype in donor T cells in these two sites, and miR-155 -/- donor T cells are polarized toward an IL-4-producing Th2 phenotype. We further demonstrate that miR-155 expression in donor T cells regulates CCR5 and CXCR4 chemokine-dependent migration. Notably, we show that miR-155 expression is crucial for donor T cell infiltration into multiple target organs. These findings provide further understanding of the role of miR-155 in modulating aGVHD through T cell expansion, effector cytokine production, and migration. Copyright © 2018 by The American Association of Immunologists, Inc.

  14. Drosophila TNF Modulates Tissue Tension in the Embryo to Facilitate Macrophage Invasive Migration.

    PubMed

    Ratheesh, Aparna; Biebl, Julia; Vesela, Jana; Smutny, Michael; Papusheva, Ekaterina; Krens, S F Gabriel; Kaufmann, Walter; Gyoergy, Attila; Casano, Alessandra Maria; Siekhaus, Daria E

    2018-05-07

    Migrating cells penetrate tissue barriers during development, inflammatory responses, and tumor metastasis. We study if migration in vivo in such three-dimensionally confined environments requires changes in the mechanical properties of the surrounding cells using embryonic Drosophila melanogaster hemocytes, also called macrophages, as a model. We find that macrophage invasion into the germband through transient separation of the apposing ectoderm and mesoderm requires cell deformations and reductions in apical tension in the ectoderm. Interestingly, the genetic pathway governing these mechanical shifts acts downstream of the only known tumor necrosis factor superfamily member in Drosophila, Eiger, and its receptor, Grindelwald. Eiger-Grindelwald signaling reduces levels of active Myosin in the germband ectodermal cortex through the localization of a Crumbs complex component, Patj (Pals-1-associated tight junction protein). We therefore elucidate a distinct molecular pathway that controls tissue tension and demonstrate the importance of such regulation for invasive migration in vivo. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Migration of interfacial oxygen ions modulated resistive switching in oxide-based memory devices

    NASA Astrophysics Data System (ADS)

    Chen, C.; Gao, S.; Zeng, F.; Tang, G. S.; Li, S. Z.; Song, C.; Fu, H. D.; Pan, F.

    2013-07-01

    Oxides-based resistive switching memory induced by oxygen ions migration is attractive for future nonvolatile memories. Numerous works had focused their attentions on the sandwiched oxide materials for depressing the characteristic variations, but the comprehensive studies of the dependence of electrodes on the migration behavior of oxygen ions are overshadowed. Here, we investigated the interaction of various metals (Ni, Co, Al, Ti, Zr, and Hf) with oxygen atoms at the metal/Ta2O5 interface under electric stress and explored the effect of top electrode on the characteristic variations of Ta2O5-based memory device. It is demonstrated that chemically inert electrodes (Ni and Co) lead to the scattering switching characteristics and destructive gas bubbles, while the highly chemically active metals (Hf and Zr) formed a thick and dense interfacial intermediate oxide layer at the metal/Ta2O5 interface, which also degraded the resistive switching behavior. The relatively chemically active metals (Al and Ti) can absorb oxygen ions from the Ta2O5 film and avoid forming the problematic interfacial layer, which is benefit to the formation of oxygen vacancies composed conduction filaments in Ta2O5 film thus exhibit the minimum variations of switching characteristics. The clarification of oxygen ions migration behavior at the interface can lead further optimization of resistive switching performance in Ta2O5-based memory device and guide the rule of electrode selection for other oxide-based resistive switching memories.

  16. Navigator-3, a modulator of cell migration, may act as a suppressor of breast cancer progression

    PubMed Central

    Cohen-Dvashi, Hadas; Ben-Chetrit, Nir; Russell, Roslin; Carvalho, Silvia; Lauriola, Mattia; Nisani, Sophia; Mancini, Maicol; Nataraj, Nishanth; Kedmi, Merav; Roth, Lee; Köstler, Wolfgang; Zeisel, Amit; Yitzhaky, Assif; Zylberg, Jacques; Tarcic, Gabi; Eilam, Raya; Wigelman, Yoav; Will, Rainer; Lavi, Sara; Porat, Ziv; Wiemann, Stefan; Ricardo, Sara; Schmitt, Fernando; Caldas, Carlos; Yarden, Yosef

    2015-01-01

    Dissemination of primary tumor cells depends on migratory and invasive attributes. Here, we identify Navigator-3 (NAV3), a gene frequently mutated or deleted in human tumors, as a regulator of epithelial migration and invasion. Following induction by growth factors, NAV3 localizes to the plus ends of microtubules and enhances their polarized growth. Accordingly, NAV3 depletion trimmed microtubule growth, prolonged growth factor signaling, prevented apoptosis and enhanced random cell migration. Mathematical modeling suggested that NAV3-depleted cells acquire an advantage in terms of the way they explore their environment. In animal models, silencing NAV3 increased metastasis, whereas ectopic expression of the wild-type form, unlike expression of two, relatively unstable oncogenic mutants from human tumors, inhibited metastasis. Congruently, analyses of > 2,500 breast and lung cancer patients associated low NAV3 with shorter survival. We propose that NAV3 inhibits breast cancer progression by regulating microtubule dynamics, biasing directionally persistent rather than random migration, and inhibiting locomotion of initiated cells. PMID:25678558

  17. MicroRNA-9 regulates non-small cell lung cancer cell invasion and migration by targeting eukaryotic translation initiation factor 5A2.

    PubMed

    Xu, Guodong; Shao, Guofeng; Pan, Qiaoling; Sun, Lebo; Zheng, Dawei; Li, Minghui; Li, Ni; Shi, Huoshun; Ni, Yiming

    2017-01-01

    MicroRNAs (miRNAs) play a critical role in cancer development and progression. Bioinformatics analyses has identified eukaryotic translation initiation factor 5A2 (eIF5A2) as a target of miR-9. In this study, we attempted to determine whether miR-9 regulates non-small cell lung cancer (NSCLC) cell invasion and migration by targeting eIF5A2 We examined eIF5A2 expression using reverse transcription-quantitative PCR (RT-qPCR) and subsequently transfected A549 and NCI-H1299 NSCLC cells with a miR-9 mimic or miR-9 inhibitor to determine the migration and invasive capability of the cells via wound healing assay and Transwell invasion assay, respectively. E-cadherin and vimentin expression was detected with western blotting. The miR-9 mimic significantly reduced NSCLC cell invasive and metastatic ability, and the miR-9 inhibitor enhanced NSCLC cell migration activity, increasing the number of migrated cells. There was no significant difference between the negative control siRNA and miR-9 mimic groups after knockdown of eIF5A2; western blotting showed that miR-9 regulated E-cadherin and vimentin expression. These data show that miR-9 regulates NSCLC cell invasion and migration through regulating eIF5A2 expression. Taken together, our findings suggest that the mechanism of miR-9-regulated NSCLC cell invasion and migration may be related to epithelial-mesenchymal transition.

  18. Human Rhinovirus Infection of Epithelial Cells Modulates Airway Smooth Muscle Migration.

    PubMed

    Shariff, Sami; Shelfoon, Christopher; Holden, Neil S; Traves, Suzanne L; Wiehler, Shahina; Kooi, Cora; Proud, David; Leigh, Richard

    2017-06-01

    Airway remodeling, a characteristic feature of asthma, begins in early life. Recurrent human rhinovirus (HRV) infections are a potential inciting stimulus for remodeling. One component of airway remodeling is an increase in airway smooth muscle cell (ASMC) mass with a greater proximity of the ASMCs to the airway epithelium. We asked whether human bronchial epithelial cells infected with HRV produced mediators that are chemotactic for ASMCs. ASMC migration was investigated using the modified Boyden Chamber and the xCELLigence Real-Time Cell Analyzer (ACEA Biosciences Inc., San Diego, CA). Multiplex bead analysis was used to measure HRV-induced epithelial chemokine release. The chemotactic effects of CCL5, CXCL8, and CXCL10 were also examined. Supernatants from HRV-infected epithelial cells caused ASMC chemotaxis. Pretreatment of ASMCs with pertussis toxin abrogated chemotaxis, as did treatment with formoterol, forskolin, or 8-bromo-cAMP. CCL5, CXCL8, and CXCL10 were the most up-regulated chemokines produced by HRV-infected airway epithelial cells. When recombinant CCL5, CXCL8, and CXCL10 were used at levels found in epithelial supernatants, they induced ASMC chemotaxis similar to that seen with epithelial cell supernatants. When examined individually, CCL5 was the most effective chemokine in causing ASMC migration, and treatment of supernatant from HRV-infected epithelial cells with anti-CCL5 antibodies significantly attenuated ASMC migration. These findings suggest that HRV-induced CCL5 can induce ASMC chemotaxis and thus may contribute to the pathogenesis of airway remodeling in patients with asthma.

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

    NASA Astrophysics Data System (ADS)

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

    2017-02-01

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

  20. Bioactive Compounds from Posidonia oceanica (L.) Delile Impair Malignant Cell Migration through Autophagy Modulation

    PubMed Central

    Leri, Manuela; Vasarri, Marzia; Peri, Sara; Barletta, Emanuela; Pretti, Carlo; Degl’Innocenti, Donatella

    2018-01-01

    Posidonia oceanica (L.) Delile is a marine plant with interesting biological properties potentially ascribed to the synergistic combination of bioactive compounds. Our previously described extract, obtained from the leaves of P. oceanica, showed the ability to impair HT1080 cell migration by targeting both expression and activity of gelatinases. Commonly, the lack of knowledge about the mechanism of action of phytocomplexes may be an obstacle regarding their therapeutic use and development. The aim of this study was to gain insight into the molecular signaling through which such bioactive compounds impact on malignant cell migration and gelatinolytic activity. The increase in autophagic vacuoles detected by confocal microscopy suggested an enhancement of autophagy in a time and dose dependent manner. This autophagy activation was further confirmed by monitoring pivotal markers of autophagy signaling as well as by evidencing an increase in IGF-1R accumulation on cell membranes. Taken together, our results confirm that the P. oceanica phytocomplex is a promising reservoir of potent and cell safe molecules able to defend against malignancies and other diseases in which gelatinases play a major role in progression. In conclusion, the attractive properties of this phytocomplex may be of industrial interest in regard to the development of novel health-promoting and pharmacological products for the treatment or prevention of several diseases. PMID:29690502

  1. Bioactive Compounds from Posidonia oceanica (L.) Delile Impair Malignant Cell Migration through Autophagy Modulation.

    PubMed

    Leri, Manuela; Ramazzotti, Matteo; Vasarri, Marzia; Peri, Sara; Barletta, Emanuela; Pretti, Carlo; Degl'Innocenti, Donatella

    2018-04-21

    Posidonia oceanica (L.) Delile is a marine plant with interesting biological properties potentially ascribed to the synergistic combination of bioactive compounds. Our previously described extract, obtained from the leaves of P. oceanica , showed the ability to impair HT1080 cell migration by targeting both expression and activity of gelatinases. Commonly, the lack of knowledge about the mechanism of action of phytocomplexes may be an obstacle regarding their therapeutic use and development. The aim of this study was to gain insight into the molecular signaling through which such bioactive compounds impact on malignant cell migration and gelatinolytic activity. The increase in autophagic vacuoles detected by confocal microscopy suggested an enhancement of autophagy in a time and dose dependent manner. This autophagy activation was further confirmed by monitoring pivotal markers of autophagy signaling as well as by evidencing an increase in IGF-1R accumulation on cell membranes. Taken together, our results confirm that the P. oceanica phytocomplex is a promising reservoir of potent and cell safe molecules able to defend against malignancies and other diseases in which gelatinases play a major role in progression. In conclusion, the attractive properties of this phytocomplex may be of industrial interest in regard to the development of novel health-promoting and pharmacological products for the treatment or prevention of several diseases.

  2. Main pathways of action of Brazilian red propolis on the modulation of neutrophils migration in the inflammatory process.

    PubMed

    Bueno-Silva, Bruno; Franchin, Marcelo; Alves, Claudiney de Freitas; Denny, Carina; Colón, David Fernando; Cunha, Thiago Mattar; Alencar, Severino Matias; Napimoga, Marcelo Henrique; Rosalen, Pedro Luiz

    2016-12-01

    Brazilian propolis is popularly used as treatment for different diseases including the ones with inflammatory origin. Brazilian red propolis chemical profile and its anti-inflammatory properties were recently described however, its mechanism of action has not been investigated yet. Elucidate Brazilian red propolis major pathways of action on the modulation of neutrophil migration during the inflammatory process. The ethanolic extract of propolis (EEP) activity was investigated for neutrophil migration into the peritoneal cavity, intravital microscopy (rolling and adhesion of leukocytes), quantification of cytokines TNF-α, IL-1β and chemokines CXCL1/KC, CXCL2/MIP-2, neutrophil chemotaxis induced by CXCL2/MIP-2, calcium influx and CXCR2 expression on neutrophils. EEP at 10mg/kg prevented neutrophil migration into peritoneal cavity (p < 0.05), reduced leukocyte rolling and adhesion on the mesenteric microcirculation (p < 0.05) and inhibited the release TNF-α, IL-1β, CXCL1/KC and CXCL2/MIP-2 (p < 0.05). EEP at 0.01, 0.1 and 1µg/ml reduced the CXCL2/MIP-2-induced neutrophils chemotaxis (p < 0.05) without affect cell viability (p > 0.05).EEP at 1µg/ml decreased the calcium influx induced by CXCL2/MIP-2 (p<0.05). On the other hand, none of EEP concentrations tested altered CXCR2 expression by neutrophils (p>0.05). Brazilian red propolis appears as a promising anti-inflammatory natural product which mechanism seems to be by reducing leukocyte rolling and adhesion; TNF-α, IL-1β, CXCL1/KC and CXCL2/MIP-2 release; CXCL2/MIP-2-induced chemotaxis and calcium influx. Copyright © 2016 Elsevier GmbH. All rights reserved.

  3. MicroRNA-424/E2F6 feedback loop modulates cell invasion, migration and EMT in endometrial carcinoma

    PubMed Central

    Lu, Zheng; Nian, Zhou; Jingjing, Zhang; Tao, Luo; Quan, Li

    2017-01-01

    Our previous study explored the roles of microRNA-424 (miR-424) in the development of endometrial carcinoma (EC) and analyzed the miR-424/E2F7 axis in EC cell growth. In this study, we investigated the status of miR-424 in human endometrial cancer tissues, which were collected from a cohort of Zunyi patients. We found that the expression level of miR-424 was associated with clinical tumor stage, cell differentiation, lymph node metastasis and cell migration ability. Cell function experiments demonstrated that miR-424 overexpression suppressed the invasion and migration abilities of endometrial carcinoma cells in vitro. Bioinformatic predictions and dual-luciferase reporter assays suggested E2F6 as a possible target of miR-424. RT-PCR and western blot assays demonstrated that miR-424 transfection reduced the expression level of E2F6, while inhibiting miR-424 with ASO-miR-424 (antisense oligonucleotides of miR-424) increased the expression level of E2F6. Cell function experiments indicated that E2F6 transfection rescued the EC cell phenotype induced by miR-424. In addition, we also found that E2F6 negatively regulated miR-424 expression in EC cells. In summary, our results demonstrated that the miR-424/E2F6 feedback loop modulates cell invasion, migration and EMT in EC and that the miR-424/E2Fs regulation network may serve as a new and potentially important therapeutic target in EC. PMID:29371986

  4. Kindlin-2 Modulates the Survival, Differentiation, and Migration of Induced Pluripotent Cell-Derived Mesenchymal Stromal Cells

    PubMed Central

    Eggenschwiler, Reto; Wichmann, Christian; Buhmann, Raymund; Cantz, Tobias

    2017-01-01

    Kindlin-2 is a multidomain intracellular protein that can be recruited to β-integrin domains to activate signaling, initiate transcriptional programs, and bind to E-cadherin. To explore its involvement in cell fate decisions in mesenchymal cells, we studied the effects of Kindlin-2 modification (overexpression/knockdown) in induced pluripotent cell-derived mesenchymal stromal cells (iPSC-MSCs). Kindlin-2 overexpression resulted in increased proliferation and reduced apoptosis of iPSC-MSCs, as well as inhibition of their differentiation towards osteocytes, adipocytes, and chondrocytes. In contrast, siRNA-mediated Kindlin-2 knockdown induced increased apoptosis and increased differentiation response in iPSC-MSCs. The ability of iPSC-MSCs to adhere to VCAM-1/SDF-1α under shear stress and to migrate in a wound scratch assay was significantly increased after Kindlin-2 overexpression. In contrast, inhibition of mixed lymphocyte reaction (MLR) was generally independent of Kindlin-2 modulation in iPSC-MSCs, except for decreased production of interleukin-2 (IL-2) after Kindlin-2 overexpression in iPS-MSCs. Thus, Kindlin-2 upregulates survival, proliferation, stemness, and migration potential in iPSC-MSCs and may therefore be beneficial in optimizing performance of iPSC-MSC in therapies. PMID:28163724

  5. Sphingosine 1-phosphate and human ether-a'-go-go-related gene potassium channels modulate migration in human anaplastic thyroid cancer cells.

    PubMed

    Asghar, Muhammad Yasir; Viitanen, Tero; Kemppainen, Kati; Törnquist, Kid

    2012-10-01

    Anaplastic thyroid cancer (ATC) is the most aggressive form of human thyroid cancer, lacking any effective treatment. Sphingosine 1-phosphate (S1P) receptors and human ether-a'-go-go-related gene (HERG (KCNH2)) potassium channels are important modulators of cell migration. In this study, we have shown that the S1P(1-3) receptors are expressed in C643 and THJ-16T human ATC cell lines, both at mRNA and protein level. S1P inhibited migration of these cells and of follicular FTC-133 thyroid cancer cells. Using the S1P(1,3) inhibitor VPC-23019, the S1P(2) inhibitor JTE-013, and the S1P(2) receptor siRNA, we showed that the effect was mediated through S1P(2). Treatment of the cells with the Rho inhibitor C3 transferase abolished the effect of S1P on migration. S1P attenuated Rac activity, and inhibiting Rac decreased migration. Sphingosine kinase inhibitor enhanced basal migration of cells, and addition of exogenous S1P inhibited migration. C643 cells expressed a nonconducting HERG protein, and S1P decreased HERG protein expression. The HERG blocker E-4031 decreased migration. Interestingly, downregulating HERG protein with siRNA decreased the basal migration. In experiments using HEK cells overexpressing HERG, we showed that S1P decreased channel protein expression and current and that S1P attenuated migration of the cells. We conclude that S1P attenuates migration of C643 ATC cells by activating S1P(2) and the Rho pathway. The attenuated migration is also, in part, dependent on a S1P-induced decrease of HERG protein.

  6. MicroRNA 203 Modulates Glioma Cell Migration via Robo1/ERK/MMP-9 Signaling

    PubMed Central

    Dontula, Ranadheer; Dinasarapu, Ashok; Chetty, Chandramu; Pannuru, Padmavathi; Herbert, Engelhard; Ozer, Howard

    2013-01-01

    Glioblastoma (GBM) is the most common and malignant primary adult brain cancer. Allelic deletion on chromosome 14q plays an important role in the pathogenesis of GBM, and this site was thought to harbor multiple tumor suppressor genes associated with GBM, a region that also encodes microRNA-203 (miR-203). In this study, we sought to identify the role of miR-203 as a tumor suppressor in the pathogenesis of GBM. We analyzed the miR-203 expression data of GBM patients in 10 normal and 495 tumor tissue samples derived from The Cancer Genome Atlas data set. Quantitative real-time PCR and in situ hybridization in 10 high-grade GBM and 10 low-grade anaplastic astrocytoma tumor samples showed decreased levels of miR-203 expression in anaplastic astrocytoma and GBM tissues and cell lines. Exogenous expression of miR-203 using a plasmid expressing miR-203 precursor (pmiR-203) suppressed glioma cell proliferation, migration, and invasion. We determined that one relevant target of miR-203 was Robo1, given that miR-203 expression decreased mRNA and protein levels as determined by RT-PCR and Western blot analysis. Moreover, cotransfection experiments using a luciferase-based transcription reporter assay have shown direct regulation of Robo1 by miR-203. We also show that Robo1 mediates miR-203 mediated antimigratory functions as up-regulation of Robo1 abrogates miR-203 mediated antimigratory effects. We also show that miR-203 expression suppressed ERK phosphorylation and MMP-9 expression in glioma cells. Furthermore, we demonstrate that miR-203 inhibits migration of the glioma cells by disrupting the Robo1/ERK/MMP-9 signaling axis. Taken together, these studies demonstrate that up-regulation of Robo1 in response to the decrease in miR-203 in glioma cells is responsible for glioma tumor cell migration and invasion. PMID:24167656

  7. Kaposi's Sarcoma-Associated Herpesvirus Interleukin-6 Modulates Endothelial Cell Movement by Upregulating Cellular Genes Involved in Migration.

    PubMed

    Giffin, Louise; West, John A; Damania, Blossom

    2015-12-08

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of human Kaposi's sarcoma, a tumor that arises from endothelial cells, as well as two B cell lymphoproliferative diseases, primary effusion lymphoma and multicentric Castleman's disease. KSHV utilizes a variety of mechanisms to evade host immune responses and promote cellular transformation and growth in order to persist for the life of the host. A viral homolog of human interleukin-6 (hIL-6) named viral interleukin-6 (vIL-6) is encoded by KSHV and expressed in KSHV-associated cancers. Similar to hIL-6, vIL-6 is secreted, but the majority of vIL-6 is retained within the endoplasmic reticulum, where it can initiate functional signaling through part of the interleukin-6 receptor complex. We sought to determine how intracellular vIL-6 modulates the host endothelial cell environment by analyzing vIL-6's impact on the endothelial cell transcriptome. vIL-6 significantly altered the expression of many cellular genes associated with cell migration. In particular, vIL-6 upregulated the host factor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) at the protein and message levels. CEACAM1 has been implicated in tumor invasion and metastasis and promotes migration and vascular remodeling in endothelial cells. We report that vIL-6 upregulates CEACAM1 by a STAT3-dependent mechanism and that CEACAM1 promotes vIL-6-mediated migration. Furthermore, latent and de novo KSHV infections of endothelial cells also induce CEACAM1 expression. Collectively, our data suggest that vIL-6 modulates endothelial cell migration by upregulating the expression of cellular factors, including CEACAM1. Kaposi's sarcoma-associated herpesvirus (KSHV) is linked with the development of three human malignancies, Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma. KSHV expresses many factors that enable the virus to manipulate the host environment in order to persist and induce disease

  8. The A2 Adenosine Receptor: Guanine Nucleotide Modulation of Agonist Binding Is Enhanced by Proteolysis

    PubMed Central

    NANOFF, CHRISTIAN; JACOBSON, KENNETH A.; STILES, GARY L.

    2012-01-01

    only 28% in the Mr 47,000 receptor protein. Our data, therefore, suggest that, unless proteolysis occurs, the A2AR in all tissues studied is tightly associated with the Gs protein and displays minimal guanine nucleotide modulation of agonist binding, which makes the A2AR an atypical stimulatory receptor. PMID:1899902

  9. EphA2 Expression Is a Key Driver of Migration and Invasion and a Poor Prognostic Marker in Colorectal Cancer.

    PubMed

    Dunne, Philip D; Dasgupta, Sonali; Blayney, Jaine K; McArt, Darragh G; Redmond, Keara L; Weir, Jessica-Anne; Bradley, Conor A; Sasazuki, Takehiko; Shirasawa, Senji; Wang, Tingting; Srivastava, Supriya; Ong, Chee Wee; Arthur, Ken; Salto-Tellez, Manuel; Wilson, Richard H; Johnston, Patrick G; Van Schaeybroeck, Sandra

    2016-01-01

    EphA2, a member of the Eph receptor tyrosine kinases family, is an important regulator of tumor initiation, neovascularization, and metastasis in a wide range of epithelial and mesenchymal cancers; however, its role in colorectal cancer recurrence and progression is unclear. EphA2 expression was determined by immunohistochemistry in stage II/III colorectal tumors (N = 338), and findings correlated with clinical outcome. The correlation between EphA2 expression and stem cell markers CD44 and Lgr5 was examined. The role of EphA2 in migration/invasion was assessed using a panel of KRAS wild-type (WT) and mutant (MT) parental and invasive colorectal cancer cell line models. Colorectal tumors displayed significantly higher expression levels of EphA2 compared with matched normal tissue, which positively correlated with high CD44 and Lgr5 expression levels. Moreover, high EphA2 mRNA and protein expression were found to be associated with poor overall survival in stage II/III colorectal cancer tissues, in both univariate and multivariate analyses. Preclinically, we found that EphA2 was highly expressed in KRASMT colorectal cancer cells and that EphA2 levels are regulated by the KRAS-driven MAPK and RalGDS-RalA pathways. Moreover, EphA2 levels were elevated in several invasive daughter cell lines, and downregulation of EphA2 using RNAi or recombinant EFNA1 suppressed migration and invasion of KRASMT colorectal cancer cells. These data show that EpHA2 is a poor prognostic marker in stage II/III colorectal cancer, which may be due to its ability to promote cell migration and invasion, providing support for the further investigation of EphA2 as a novel prognostic biomarker and therapeutic target. ©2015 American Association for Cancer Research.

  10. EphA2 expression is a key driver of migration and invasion and a poor prognostic marker in colorectal cancer

    PubMed Central

    Blayney, Jaine K.; McArt, Darragh G.; Redmond, Keara L.; Weir, Jessica-Anne; Bradley, Conor A.; Sasazuki, Takehiko; Shirasawa, Senji; Wang, Tingting; Srivastava, Supriya; Ong, Chee Wee; Arthur, Ken; Salto-Tellez, Manuel; Wilson, Richard H.

    2015-01-01

    Purpose EphA2, a member of the Eph receptor tyrosine kinases family, is an important regulator of tumour initiation, neo-vascularization and metastasis in a wide range of epithelial and mesenchymal cancers, however its role in colorectal cancer (CRC) recurrence and progression is unclear. Experimental Design EphA2 expression was determined by immunohistochemistry in stage II/III colorectal tumours (N=338), and findings correlated with clinical outcome. The correlation between EphA2 expression and stem cell markers CD44 and Lgr5 was examined. The role of EphA2 in migration/invasion was assessed using a panel of KRAS wild-type (WT) and mutant (MT) parental and invasive CRC cell line models. Results Colorectal tumours displayed significantly higher expression levels of EphA2 compared with matched normal tissue, which positively correlated with high CD44 and Lgr5 expression levels. Moreover, high EphA2 mRNA and protein expression were found to be associated with poor overall survival in stage II/III CRC tissues, in both univariate and multivariate analyses. Pre-clinically, we found that EphA2 was highly expressed in KRASMT CRC cells and that EphA2 levels are regulated by the KRAS-driven MAPK and RalGDS-RalA pathways. Moreover, EphA2 levels were elevated in several invasive daughter cell lines and down-regulation of EphA2 using RNAi or recombinant EFNA1, suppressed migration and invasion of KRASMT CRC cells. Conclusions These data show that EpHA2 is a poor prognostic marker in stage II/III CRC, which may be due to its ability to promote cell migration and invasion, providing support for the further investigation of EphA2 as a novel prognostic biomarker and therapeutic target. PMID:26283684

  11. Vascular Endothelial Growth Factor (VEGF) and Platelet (PF-4) Factor 4 Inputs Modulate Human Microvascular Endothelial Signaling in a Three-Dimensional Matrix Migration Context*

    PubMed Central

    Hang, Ta-Chun; Tedford, Nathan C.; Reddy, Raven J.; Rimchala, Tharathorn; Wells, Alan; White, Forest M.; Kamm, Roger D.; Lauffenburger, Douglas A.

    2013-01-01

    The process of angiogenesis is under complex regulation in adult organisms, particularly as it often occurs in an inflammatory post-wound environment. As such, there are many impacting factors that will regulate the generation of new blood vessels which include not only pro-angiogenic growth factors such as vascular endothelial growth factor, but also angiostatic factors. During initial postwound hemostasis, a large initial bolus of platelet factor 4 is released into localized areas of damage before progression of wound healing toward tissue homeostasis. Because of its early presence and high concentration, the angiostatic chemokine platelet factor 4, which can induce endothelial anoikis, can strongly affect angiogenesis. In our work, we explored signaling crosstalk interactions between vascular endothelial growth factor and platelet factor 4 using phosphotyrosine-enriched mass spectrometry methods on human dermal microvascular endothelial cells cultured under conditions facilitating migratory sprouting into collagen gel matrices. We developed new methods to enable mass spectrometry-based phosphorylation analysis of primary cells cultured on collagen gels, and quantified signaling pathways over the first 48 h of treatment with vascular endothelial growth factor in the presence or absence of platelet factor 4. By observing early and late signaling dynamics in tandem with correlation network modeling, we found that platelet factor 4 has significant crosstalk with vascular endothelial growth factor by modulating cell migration and polarization pathways, centered around P38α MAPK, Src family kinases Fyn and Lyn, along with FAK. Interestingly, we found EphA2 correlational topology to strongly involve key migration-related signaling nodes after introduction of platelet factor 4, indicating an influence of the angiostatic factor on this ambiguous but generally angiogenic signal in this complex environment. PMID:24023389

  12. An oyster species-specific miRNA scaffold42648_5080 modulates haemocyte migration by targeting integrin pathway.

    PubMed

    Chen, Hao; Wang, Hao; Jiang, Shuai; Xu, Jiachao; Wang, Lingling; Qiu, Limei; Song, Linsheng

    2016-10-01

    miRNAs are important gene regulators at post-transcriptional level and can modulate diverse biological processes, including immune response. Dozens of species-specific miRNAs have been identified in oyster Crassostrea gigas while their functions remain largely unknown. In the present study, an oyster species-specific miRNA scaffold42648_5080 was found responsive to LPS stimulation and might target a total of 31 oyster genes possibly involved in cell communication, cellular localization and cellular response to stimulus. Besides, in gain-of-function assay of scaffold42648_5080 in vivo, the phagocytosis (30.90% in miRNA group verse 23.20% in miRNA control group), apoptosis (3.10% in miRNA group verse 5.30% in miRNA control group) and migration rate (13.88% in miRNA group verse 21.03% in miRNA control group) of oyster haemocytes were found significantly altered after the injection of scaffold42648_5080 mimics. Among the target genes, integrin-linked kinase (CgILK) was considered crucial in cell migration and its interaction with scaffold42648_5080 was then verified both in vitro and in vivo. Consequently, a significant decrease of relative luciferase ratio was observed in CgILK 3'-UTR luciferase reporter assay after transfection of scaffold42648_5080 mimics (0.70-fold of that in blank group, p < 0.01). Meanwhile, when scaffold42648_5080 was overexpressed in vivo (5.41-fold of miRNA control group, p < 0.01), the expression of CgILK declined significantly to 0.25-fold of miRNA control group (p < 0.01). Comparatively, a significant decrease of the haemocyte migration rate (19.76% verse 34.82% in siEGFP control group, p < 0.01) was observed after knock-down of CgILK in vivo. The present study, as far as we know, for the first time revealed the immunomodulation role of an oyster species-specific miRNA, which might provide new insights into miRNA-mediated adaptation mechanism of oysters. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Rac1 and Cdc42 Differentially Modulate Cigarette Smoke–Induced Airway Cell Migration through p120-Catenin–Dependent and –Independent Pathways

    PubMed Central

    Zhang, Lili; Gallup, Marianne; Zlock, Lorna; Finkbeiner, Walter E.; McNamara, Nancy A.

    2014-01-01

    The adherens junction protein p120-catenin (p120ctn) shuttles between E-cadherin–bound and cytoplasmic pools to regulate E-cadherin/catenin complex stability and cell migration, respectively. When released from the adherens junction, p120ctn promotes cell migration through modulation of the Rho GTPases Rac1, Cdc42, and RhoA. Accordingly, the down-regulation and cytoplasmic mislocalization of p120ctn has been reported in all subtypes of lung cancers and is associated with grave prognosis. Previously, we reported that cigarette smoke induced cytoplasmic translocation of p120ctn and cell migration, but the underlying mechanism was unclear. Using primary human bronchial epithelial cells exposed to smoke-concentrated medium (Smk), we observed the translocation of Rac1 and Cdc42, but not RhoA, to the leading edge of polarized and migrating human bronchial epithelial cells. Rac1 and Cdc42 were robustly activated by smoke, whereas RhoA was inhibited. Accordingly, siRNA knockdown of Rac1 or Cdc42 completely abolished Smk-induced cell migration, whereas knockdown of RhoA had no effect. p120ctn/Rac1 double knockdown completely abolished Smk-induced cell migration, whereas p120ctn/Cdc42 double knockdown did not. These data suggested that Rac1 and Cdc42 coactivation was essential to smoke-promoted cell migration in the presence of p120ctn, whereas migration proceeded via Rac1 alone in the absence of p120ctn. Thus, Rac1 may provide an omnipotent therapeutic target in reversing cell migration during the early (intact p120ctn) and late (loss of p120ctn) stages of lung carcinogenesis. PMID:23562274

  14. HDAC 1 and 6 modulate cell invasion and migration in clear cell renal cell carcinoma.

    PubMed

    Ramakrishnan, Swathi; Ku, ShengYu; Ciamporcero, Eric; Miles, Kiersten Marie; Attwood, Kris; Chintala, Sreenivasulu; Shen, Li; Ellis, Leigh; Sotomayor, Paula; Swetzig, Wendy; Huang, Ray; Conroy, Dylan; Orillion, Ashley; Das, Gokul; Pili, Roberto

    2016-08-09

    Class I histone deacetylases (HDACs) have been reported to be overexpressed in clear cell renal cell carcinoma (ccRCC), whereas the expression of class II HDACs is unknown. Four isogenic cell lines C2/C2VHL and 786-O/786-OVHL with differential VHL expression are used in our studies. Cobalt chloride is used to mimic hypoxia in vitro. HIF-2α knockdowns in C2 and 786-O cells is used to evaluate the effect on HDAC 1 expression and activity. Invasion and migration assays are used to investigate the role of HDAC 1 and HDAC 6 expression in ccRCC cells. Comparisons are made between experimental groups using the paired T-test, the two-sample Student's T-test or one-way ANOVA, as appropriate. ccRCC and the TCGA dataset are used to observe the clinical correlation between HDAC 1 and HDAC 6 overexpression and overall and progression free survival. Our analysis of tumor and matched non-tumor tissues from radical nephrectomies showed overexpression of class I and II HDACs (HDAC6 only in a subset of patients). In vitro, both HDAC1 and HDAC6 over-expression increased cell invasion and motility, respectively, in ccRCC cells. HDAC1 regulated invasiveness by increasing matrix metalloproteinase (MMP) expression. Furthermore, hypoxia stimulation in VHL-reconstituted cell lines increased HIF isoforms and HDAC1 expression. Presence of hypoxia response elements in the HDAC1 promoter along with chromatin immunoprecipitation data suggests that HIF-2α is a transcriptional regulator of HDAC1 gene. Conversely, HDAC6 and estrogen receptor alpha (ERα) were co-localized in cytoplasm of ccRCC cells and HDAC6 enhanced cell motility by decreasing acetylated α-tubulin expression, and this biological effect was attenuated by either biochemical or pharmacological inhibition. Finally, analysis of human ccRCC specimens revealed positive correlation between HIF isoforms and HDAC. HDAC1 mRNA upregulation was associated with worse overall survival in the TCGA dataset. Taking together, these results

  15. Stereotypes of Aging. Module A-2. Block A. Basic Knowledge of the Aging Process.

    ERIC Educational Resources Information Center

    Harvey, Dexter; Cap, Orest

    This instructional module on stereotypes of aging is one in a block of 10 modules designed to provide the human services worker who works with older adults with basic information regarding the aging process. An introduction provides an overview of the module content. A listing of general objectives follows. Three sections present informative…

  16. Two proteins modulating transendothelial migration of leukocytes recognize novel carboxylated glycans on endothelial cells.

    PubMed

    Srikrishna, G; Panneerselvam, K; Westphal, V; Abraham, V; Varki, A; Freeze, H H

    2001-04-01

    We recently showed that a class of novel carboxylated N:-glycans was constitutively expressed on endothelial cells. Activated, but not resting, neutrophils expressed binding sites for the novel glycans. We also showed that a mAb against these novel glycans (mAbGB3.1) inhibited leukocyte extravasation in a murine model of peritoneal inflammation. To identify molecules that mediated these interactions, we isolated binding proteins from bovine lung by their differential affinity for carboxylated or neutralized glycans. Two leukocyte calcium-binding proteins that bound in a carboxylate-dependent manner were identified as S100A8 and annexin I. An intact N terminus of annexin I and heteromeric assembly of S100A8 with S100A9 (another member of the S100 family) appeared necessary for this interaction. A mAb to S100A9 blocked neutrophil binding to immobilized carboxylated glycans. Purified human S100A8/A9 complex and recombinant human annexin I showed carboxylate-dependent binding to immobilized bovine lung carboxylated glycans and recognized a subset of mannose-labeled endothelial glycoproteins immunoprecipitated by mAbGB3.1. Saturable binding of S100A8/A9 complex to endothelial cells was also blocked by mAbGB3.1. These results suggest that the carboxylated glycans play important roles in leukocyte trafficking by interacting with proteins known to modulate extravasation.

  17. Purinergic A2b Receptor Activation by Extracellular Cues Affects Positioning of the Centrosome and Nucleus and Causes Reduced Cell Migration.

    PubMed

    Ou, Young; Chan, Gordon; Zuo, Jeremy; Rattner, Jerome B; van der Hoorn, Frans A

    2016-07-15

    The tight, relative positioning of the nucleus and centrosome in mammalian cells is important for the regulation of cell migration. Under pathophysiological conditions, the purinergic A2b receptor can regulate cell motility, but the underlying mechanism remains unknown. Expression of A2b, normally low, is increased in tissues experiencing adverse physiological conditions, including hypoxia and inflammation. ATP is released from such cells. We investigated whether extracellular cues can regulate centrosome-nucleus positioning and cell migration. We discovered that hypoxia as well as extracellular ATP cause a reversible increase in the distance between the centrosome and nucleus and reduced cell motility. We uncovered the underlying pathway: both treatments act through the A2b receptor and specifically activate the Epac1/RapGef3 pathway. We show that cells lacking A2b do not respond in this manner to hypoxia or ATP but transfection of A2b restores this response, that Epac1 is critically involved, and that Rap1B is important for the relative positioning of the centrosome and nucleus. Our results represent, to our knowledge, the first report demonstrating that pathophysiological conditions can impact the distance between the centrosome and nucleus. Furthermore, we identify the A2b receptor as a central player in this process. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Purinergic A2b Receptor Activation by Extracellular Cues Affects Positioning of the Centrosome and Nucleus and Causes Reduced Cell Migration*

    PubMed Central

    Ou, Young; Chan, Gordon; Zuo, Jeremy; Rattner, Jerome B.; van der Hoorn, Frans A.

    2016-01-01

    The tight, relative positioning of the nucleus and centrosome in mammalian cells is important for the regulation of cell migration. Under pathophysiological conditions, the purinergic A2b receptor can regulate cell motility, but the underlying mechanism remains unknown. Expression of A2b, normally low, is increased in tissues experiencing adverse physiological conditions, including hypoxia and inflammation. ATP is released from such cells. We investigated whether extracellular cues can regulate centrosome-nucleus positioning and cell migration. We discovered that hypoxia as well as extracellular ATP cause a reversible increase in the distance between the centrosome and nucleus and reduced cell motility. We uncovered the underlying pathway: both treatments act through the A2b receptor and specifically activate the Epac1/RapGef3 pathway. We show that cells lacking A2b do not respond in this manner to hypoxia or ATP but transfection of A2b restores this response, that Epac1 is critically involved, and that Rap1B is important for the relative positioning of the centrosome and nucleus. Our results represent, to our knowledge, the first report demonstrating that pathophysiological conditions can impact the distance between the centrosome and nucleus. Furthermore, we identify the A2b receptor as a central player in this process. PMID:27226580

  19. Quaternary-Linked Changes in Structure and Dynamics That Modulate O2 Migration within Hemoglobin's Gas Diffusion Tunnels.

    PubMed

    Shadrina, Maria S; Peslherbe, Gilles H; English, Ann M

    2015-09-01

    Atomistic molecular dynamics simulations of diffusion of O2 from the hemes to the external solvent in the α- and β-subunits of the human hemoglobin (HbA) tetramer reveal transient gas tunnels that are not seen in crystal structures. We find here that the tunnel topology, which encompasses the reported experimental Xe binding cavities, is identical in HbA's T, R, and R2 quaternary states. However, the O2 population in the cavities and the preferred O2 escape portals vary significantly with quaternary structure. For example, most O2 molecules escape from the T β-subunit via the cavity at the center of the tetramer, but direct exit from the distal heme pocket dominates in the R2 β-subunit. To understand what triggers the quaternary-linked redistribution of O2 within its tunnels, we examined how the simulated tertiary structure and dynamics of each subunit differs among T, R, and R2 and report that minor adjustments in α-chain dynamics and β-heme position modulate O2 distribution and escape in HbA. Coupled to the β-heme position, residue βF71 undergoes quaternary-linked conformations that strongly regulate O2 migration between the β-subunit and HbA's central cavity. Remarkably, the distal histidine (HisE7) remains in a closed conformation near the α- and β-hemes in all states, but this does not prevent an average of 23, 31, and 46% of O2 escapes from the distal heme pockets of T, R, and R2, respectively, via several distal portals, with the balance of escapes occurring via the interior tunnels. Furthermore, preventing or restricting the access of O2 to selected cavities by mutating HisE7 and other heme pocket residues to tryptophan reveals how O2 migration adjusts to the bulky indole ring and sheds light on the experimental ligand binding kinetics of these variants. Overall, our simulations underscore the high gas porosity of HbA in its T, R, and R2 quaternary states and provide new mechanistic insights into why undergoing transitions among these states

  20. The lutheran/basal cell adhesion molecule promotes tumor cell migration by modulating integrin-mediated cell attachment to laminin-511 protein.

    PubMed

    Kikkawa, Yamato; Ogawa, Takaho; Sudo, Ryo; Yamada, Yuji; Katagiri, Fumihiko; Hozumi, Kentaro; Nomizu, Motoyoshi; Miner, Jeffrey H

    2013-10-25

    Cell-matrix interactions are critical for tumor cell migration. Lutheran (Lu), also known as basal cell adhesion molecule (B-CAM), competes with integrins for binding to laminin α5, a subunit of LM-511, a major component of basement membranes. Here we show that the preferential binding of Lu/B-CAM to laminin α5 promotes tumor cell migration. The attachment of Lu/B-CAM transfectants to LM-511 was slightly weaker than that of control cells, and this was because Lu/B-CAM disturbed integrin binding to laminin α5. Lu/B-CAM induced a spindle cell shape with pseudopods and promoted cell migration on LM-511. In addition, blocking with an anti-Lu/B-CAM antibody led to a flat cell shape and inhibited migration on LM-511, similar to the effects of an activating integrin β1 antibody. We conclude that tumor cell migration on LM-511 requires that Lu/B-CAM competitively modulates cell attachment through integrins. We suggest that this competitive interaction is involved in a balance between static and migratory cell behaviors.

  1. Hsp90 is an essential regulator of EphA2 receptor stability and signaling: Implications for cancer cell migration and metastasis

    PubMed Central

    Annamalai, Balasubramaniam; Liu, Xueguang; Gopal, Udhayakumar; Isaacs, Jennifer

    2011-01-01

    A subset of Eph receptors and their corresponding ligands are commonly expressed in tumor cells, where they mediate biological processes such as cell migration and adhesion, while their expression in endothelial cells promotes angiogenesis. In particular, the tumor-specific upregulation of EphA2 confers properties of increased cellular motility, invasiveness, tumor angiogenesis, and tumor progression, and its overexpression correlates with poor prognosis in several cancer types. The cellular chaperone Hsp90 also plays a significant role in regulating cell migration and angiogenesis, although the full repertoire of motility driving proteins dependent upon Hsp90 function remain poorly defined. We explored the hypothesis that Hsp90 may regulate the activity of EphA2 and examined the potential relationship between EphA2 receptor signaling and chaperone function. We demonstrate that geldanamycin (GA), an Hsp90 antagonist, dramatically destabilizes newly synthesized EphA2 protein and diminishes receptor levels in a proteasome-dependent pathway. In addition, GA treatment impairs EphA2 signaling, as evidenced by a decrease in ligand-dependent receptor phosphorylation and subsequent cell rounding. Therefore, Hsp90 exerts a dual role in regulating the stability of nascent EphA2 protein, and maintaining the signaling capacity of the mature receptor. Our findings also suggest that the GA-dependent mitigation of EphA2 signaling in receptor-overexpressing cancer cells may be sufficient to recapitulate the anti-motility effects of this drug. Finally, the identification of a pharmacologic approach to suppress EphA2 expression and signaling highlights the attractive possibility that Hsp90 inhibitors may have clinical utility in antagonizing EphA2-dependent tumorigenic progression. PMID:19567782

  2. Thermodynamics and structural analysis of positive allosteric modulation of the ionotropic glutamate receptor GluA2.

    PubMed

    Krintel, Christian; Frydenvang, Karla; Olsen, Lars; Kristensen, Maria T; de Barrios, Oriol; Naur, Peter; Francotte, Pierre; Pirotte, Bernard; Gajhede, Michael; Kastrup, Jette S

    2012-01-01

    Positive allosteric modulators of the ionotropic glutamate receptor-2 (GluA2) are promising compounds for the treatment of cognitive disorders, e.g. Alzheimer's disease. These modulators bind within the dimer interface of the LBD (ligand-binding domain) and stabilize the agonist-bound conformation slowing receptor desensitization and/or deactivation. In the present study, we employ isothermal titration calorimetry to determine binding affinities and thermodynamic details of binding of modulators of GluA2. A mutant of the LBD of GluA2 (LBD-L483Y-N754S) that forms a stable dimer in solution was used. The potent GluA2 modulator BPAM-97 was used as a reference compound. Evidence that BPAM-97 binds in the same pocket as the well-known GluA2 modulator cyclothiazide was obtained from X-ray structures. The LBD-L483Y-N754S:BPAM-97 complex has a Kd of 5.6 μM (ΔH=-4.9 kcal/mol, -TΔS=-2.3 kcal/mol; where 1 kcal≈4.187 kJ). BPAM-97 was used in a displacement assay to determine a Kd of 0.46 mM (ΔH=-1.2 kcal/mol, -TΔS=-3.3 kcal/mol) for the LBD-L483Y-N754S:IDRA-21 complex. The major structural factors increasing the potency of BPAM-97 over IDRA-21 are the increased van der Waals contacts to, primarily, Met496 in GluA2 imposed by the ethyl substituent of BPAM-97. These results add important information on binding affinities and thermodynamic details, and provide a new tool in the development of drugs against cognitive disorders.

  3. Hepatic Hemodynamics and Portal Flow Modulation: The A2ALL Experience.

    PubMed

    Emond, Jean C; Goodrich, Nathan P; Pomposelli, James J; Baker, Talia B; Humar, Abhinav; Grant, David R; Abt, Peter; Friese, Chris E; Fisher, Robert A; Kam, Igal; Sherker, Averell H; Gillespie, Brenda W; Merion, Robert M

    2017-10-01

    A principal aim of the Adult-to-Adult Living Donor Liver Transplantation Cohort Study was to study hepatic blood flow and effect of portal flow modulation on graft outcomes in the setting of increasing use of smaller and left lobe grafts. Recipients of 274 living donor liver transplant were enrolled in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study, including 233 (85.0%) right lobes, 40 (14.6%) left lobes, and 1 (0.5%) left lateral section. Hepatic hemodynamics were recorded after reperfusion. A total of 57 portal flow modulations were performed on 52 subjects. Modulation lowered portal pressure in 68% of subjects with inconsistent effects on hepatic arterial and portal flow. A higher rate of graft dysfunction was observed in modulated vs. unmodulated subjects (31% vs. 18%; P = 0.03); however, graft survival in modulated subjects was not different from unmodulated subjects at 3 years. These results suggest the need for a study using a prespecified portal flow modulation protocol with defined indications to better define the effects of these interventions.

  4. EphA2 silencing promotes growth, migration, and metastasis in salivary adenoid cystic carcinoma: in vitro and in vivo study.

    PubMed

    Wang, Meng; Zhao, Xiao-Ping; Xu, Zhi; Yan, Ting-Lin; Song, Yong; Song, Kai; Huang, Chun-Ming; Wang, Lin; Zhou, Xiao-Cheng; Jiang, Er-Hui; Shao, Zhe; Shang, Zheng-Jun

    2016-01-01

    EphA2 is associated with tumor growth and distant metastasis in numerous human tumors. Considering the controversial effects of EphA2 in different tumors and the lack of reports in salivary adenoid cystic carcinoma (SACC), we evaluated the effects of EphA2 inhibition by short hairpin RNA on SACC through in vivo and in vitro researches for the first time. Real-time reverse transcriptase-PCR and western blot analysis were conducted to verify the interference effect on SACC cells. Using Cell Counting Kit-8, wound healing, Transwell and Matrigel adhesion assays, we confirm that inhibition of EphA2 promotes the migration, invasion and adhesion ability of SACC cells. In vivo research, we prove that silencing of EphA2 significantly accelerates tumor growth and lung metastasis ability by establishing xenograft models in mice, including subcutaneous inoculation and tail vein injection. In addition, immunostaining of EphA2, E-cadherin and Slug from 40 specimens and in vitro simulation of perineural invasion (PNI) assay imply that suppression of EphA2 partially contribute to epithelial-mesenchymal transition and enhancement of PNI in SACC. In conclusion, all the data suggest that EphA2 may act as a tumor suppressor in SACC progression.

  5. EphA2 silencing promotes growth, migration, and metastasis in salivary adenoid cystic carcinoma: in vitro and in vivo study

    PubMed Central

    Wang, Meng; Zhao, Xiao-Ping; Xu, Zhi; Yan, Ting-Lin; Song, Yong; Song, Kai; Huang, Chun-Ming; Wang, Lin; Zhou, Xiao-Cheng; Jiang, Er-Hui; Shao, Zhe; Shang, Zheng-Jun

    2016-01-01

    EphA2 is associated with tumor growth and distant metastasis in numerous human tumors. Considering the controversial effects of EphA2 in different tumors and the lack of reports in salivary adenoid cystic carcinoma (SACC), we evaluated the effects of EphA2 inhibition by short hairpin RNA on SACC through in vivo and in vitro researches for the first time. Real-time reverse transcriptase-PCR and western blot analysis were conducted to verify the interference effect on SACC cells. Using Cell Counting Kit-8, wound healing, Transwell and Matrigel adhesion assays, we confirm that inhibition of EphA2 promotes the migration, invasion and adhesion ability of SACC cells. In vivo research, we prove that silencing of EphA2 significantly accelerates tumor growth and lung metastasis ability by establishing xenograft models in mice, including subcutaneous inoculation and tail vein injection. In addition, immunostaining of EphA2, E-cadherin and Slug from 40 specimens and in vitro simulation of perineural invasion (PNI) assay imply that suppression of EphA2 partially contribute to epithelial-mesenchymal transition and enhancement of PNI in SACC. In conclusion, all the data suggest that EphA2 may act as a tumor suppressor in SACC progression. PMID:27186278

  6. Age-Associated Defects in EphA2 Signaling Impair the Migration of Human Cardiac Progenitor Cells

    PubMed Central

    Goichberg, Polina; Kannappan, Ramaswamy; Cimini, Maria; Bai, Yingnan; Sanada, Fumihiro; Sorrentino, Andrea; Signore, Sergio; Kajstura, Jan; Rota, Marcello; Anversa, Piero; Leri, Annarosa

    2014-01-01

    Background Aging negatively impacts on the function of resident human cardiac progenitor cells (hCPCs). Effective regeneration of the injured heart requires mobilization of hCPCs to the sites of damage. In the young heart, signaling by the guidance receptor EphA2 in response to the ephrin A1 ligand promotes hCPC motility and improves cardiac recovery after infarction. Methods and Results We report that old hCPCs are characterized by cell-autonomous inhibition of their migratory ability ex vivo and impaired translocation in vivo in the damaged heart. EphA2 expression was not decreased in old hCPCs; however, the elevated level of reactive oxygen species in aged cells induced post-translational modifications of the EphA2 protein. EphA2 oxidation interfered with ephrin A1-stimulated receptor auto-phosphorylation, activation of Src family kinases, and caveolin-1-mediated internalization of the receptor. Cellular aging altered the EphA2 endocytic route, affecting the maturation of EphA2-containing endosomes and causing premature signal termination. Over-expression of functionally intact EphA2 in old hCPCs corrected the defects in endocytosis and downstream signaling, enhancing cell motility. Based on the ability of phenotypically young hCPCs to respond efficiently to ephrin A1, we developed a novel methodology for the prospective isolation of live hCPCs with preserved migratory capacity and growth reserve. Conclusions Our data demonstrate that the ephrin A1/EphA2 pathway may serve as a target to facilitate trafficking of hCPCs in the senescent myocardium. Importantly, EphA2 receptor function can be implemented for the selection of hCPCs with high therapeutic potential, a clinically relevant strategy that does not require genetic manipulation of stem cells. PMID:24141256

  7. Resveratrol modulates MED28 (Magicin/EG-1) expression and inhibits epidermal growth factor (EGF)-induced migration in MDA-MB-231 human breast cancer cells.

    PubMed

    Lee, Ming-Fen; Pan, Min-Hsiung; Chiou, Yi-Siou; Cheng, An-Chin; Huang, Han

    2011-11-09

    Resveratrol and pterostilbene exhibit diverse biological activities. MED28, a subunit of the mammalian Mediator complex for transcription, was also identified as magicin, an actin cytoskeleton Grb2-associated protein, and as endothelial-derived gene (EG-1). Several tumors exhibit aberrant MED28 expression, whereas the underlying mechanism is unclear. Triple-negative breast cancers, often expressing epidermal growth factor (EGF) receptor (EGFR), are associated with metastasis and poor survival. The objective of this study is to compare the effect of resveratrol and pterostilbene and to investigate the role of MED28 in EGFR-overexpressing MDA-MB-231 breast cancer cells. Pretreatment of resveratrol, but not pterostlbene, suppressed EGF-mediated migration and expression of MED28 and matrix metalloproteinase (MMP)-9 in MDA-MB-231 cells. Moreover, overexpression of MED28 increased migration, and the addition of EGF further enhanced migration. Our data indicate that resveratrol modulates the effect of MED28 on cellular migration, presumably through the EGFR/phosphatidylinositol 3-kinase (PI3K) signaling pathway, in breast cancer cells.

  8. Ganglioside GM2 mediates migration of tumor cells by interacting with integrin and modulating the downstream signaling pathway.

    PubMed

    Kundu, Manjari; Mahata, Barun; Banerjee, Avisek; Chakraborty, Sohini; Debnath, Shibjyoti; Ray, Sougata Sinha; Ghosh, Zhumur; Biswas, Kaushik

    2016-07-01

    The definitive role of ganglioside GM2 in mediating tumor-induced growth and progression is still unknown. Here we report a novel role of ganglioside GM2 in mediating tumor cell migration and uncovered its mechanism. Data shows differential expression levels of GM2-synthase as well as GM2 in different human cancer cells. siRNA mediated knockdown of GM2-synthase in CCF52, A549 and SK-RC-26B cells resulted in significant inhibition of tumor cell migration as well as invasion in vitro without affecting cellular proliferation. Over-expression of GM2-synthase in low-GM2 expressing SK-RC-45 cells resulted in a consequent increase in migration thus confirming the potential role GM2 and its downstream partners play in tumor cell migration and motility. Further, treatment of SK-RC-45 cells with exogenous GM2 resulted in a dramatic increase in migratory and invasive capacity with no change in proliferative capacity, thereby confirming the role of GM2 in tumorigenesis specifically by mediating tumor migration and invasion. Gene expression profiling of GM2-synthase silenced cells revealed altered expression of several genes involved in cell migration primarily those controlling the integrin mediated signaling. GM2-synthase knockdown resulted in decreased phosphorylation of FAK, Src as well as Erk, while over-expression and/or exogenous GM2 treatment caused increased FAK and Erk phosphorylation respectively. Again, GM2 mediated invasion and Erk phosphorylation is blocked in integrin knockdown SK-RC-45 cells, thus confirming that GM2 mediated migration and phosphorylation of Erk is integrin dependent. Finally, confocal microscopy suggested co-localization while co-immunoprecipitation and surface plasmon resonance (SPR) confirmed direct interaction of membrane bound ganglioside, GM2 with the integrin receptor. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Identification of novel modulators for ionotropic glutamate receptor, iGluA2 by in-silico screening

    PubMed Central

    2013-01-01

    Background Ionotropic glutamate receptors (iGluAs, IUPHAR nomenclature) are the major excitatory amino acid neurotransmitter receptors in the mammalian central nervous system (CNS). iGluAs are potential therapeutic drug targets for various neurological disorders including ischemia, epilepsy, Parkinson’s and Alzheimer’s diseases. The known iGluA modulators, cyclothiazide (CTZ), IDRA-21, and other benzothiadiazide derivatives (ALTZ, HCTZ, and CLTZ) bind to the ligand-binding domain of flip-form of iGluA2 at the dimer interface, thereby increasing steady-state activation by reducing desensitization. Methods To discover new modulator compounds, we performed virtual screening for the ligand binding domain (LBD) of iGluA2 against NCI Diversity Set III library containing 1597 compounds, and subsequently performed binding-energy analysis for selected compounds. The crystal structure of rat iGluA2 S1S2J (PDB ID: 3IJO) was used for docking studies. Results and conclusion From this study, we obtained four compounds: (1) 10-2(methoxyethyl)-3-phenylbenzo[g]pteridine-2,4-dione, (2) 2-benzo[e]benzotriazol-2-yl-aniline, (3) 9-nitro-6H-indolo-(2,3,-b)quinoxaline, and (4) 1-hydroxy-n-(3-nitrophenyl)-2-napthamide. The binding mode of these four compounds is very similar to that of abovementioned established modulators: two molecules of each compound independently bind to the protein symmetrically at the dimer interface; occupy the subsites B, C, B’ and C’; potentially interact with Ser518 and Ser775. Binding energy analysis shows that all the four hits are comparable to the drug molecule, CTZ, and hence, we propose that the discovered hits may be potential molecules to develop new chemical libraries for modulating the flip form of iGluA2 function. PMID:23855825

  10. Identification of novel modulators for ionotropic glutamate receptor, iGluA2 by in-silico screening.

    PubMed

    Padmanabhan, Balasundaram

    2013-07-15

    Ionotropic glutamate receptors (iGluAs, IUPHAR nomenclature) are the major excitatory amino acid neurotransmitter receptors in the mammalian central nervous system (CNS). iGluAs are potential therapeutic drug targets for various neurological disorders including ischemia, epilepsy, Parkinson's and Alzheimer's diseases. The known iGluA modulators, cyclothiazide (CTZ), IDRA-21, and other benzothiadiazide derivatives (ALTZ, HCTZ, and CLTZ) bind to the ligand-binding domain of flip-form of iGluA2 at the dimer interface, thereby increasing steady-state activation by reducing desensitization. To discover new modulator compounds, we performed virtual screening for the ligand binding domain (LBD) of iGluA2 against NCI Diversity Set III library containing 1597 compounds, and subsequently performed binding-energy analysis for selected compounds. The crystal structure of rat iGluA2 S1S2J (PDB ID: 3IJO) was used for docking studies. From this study, we obtained four compounds: (1) 10-2(methoxyethyl)-3-phenylbenzo[g]pteridine-2,4-dione, (2) 2-benzo[e]benzotriazol-2-yl-aniline, (3) 9-nitro-6H-indolo-(2,3,-b)quinoxaline, and (4) 1-hydroxy-n-(3-nitrophenyl)-2-napthamide. The binding mode of these four compounds is very similar to that of abovementioned established modulators: two molecules of each compound independently bind to the protein symmetrically at the dimer interface; occupy the subsites B, C, B' and C'; potentially interact with Ser518 and Ser775. Binding energy analysis shows that all the four hits are comparable to the drug molecule, CTZ, and hence, we propose that the discovered hits may be potential molecules to develop new chemical libraries for modulating the flip form of iGluA2 function.

  11. A Small Molecule Agonist of EphA2 Receptor Tyrosine Kinase Inhibits Tumor Cell Migration In Vitro and Prostate Cancer Metastasis In Vivo

    PubMed Central

    Guo, Hong; Miao, Hui; Tochtrop, Gregory P.; Hsieh, Jer-Tsong; Page, Phillip; Liu, Lili; Lindner, Daniel J.; Acharya, Chayan; MacKerell, Alexander D.; Ficker, Eckhard; Song, Jianxing; Wang, Bingcheng

    2012-01-01

    During tumor progression, EphA2 receptor can gain ligand-independent pro-oncogenic functions due to Akt activation and reduced ephrin-A ligand engagement. The effects can be reversed by ligand stimulation, which triggers the intrinsic tumor suppressive signaling pathways of EphA2 including inhibition of PI3/Akt and Ras/ERK pathways. These observations argue for development of small molecule agonists for EphA2 as potential tumor intervention agents. Through virtual screening and cell-based assays, we report here the identification and characterization of doxazosin as a novel small molecule agonist for EphA2 and EphA4, but not for other Eph receptors tested. NMR studies revealed extensive contacts of doxazosin with EphA2/A4, recapitulating both hydrophobic and electrostatic interactions recently found in the EphA2/ephrin-A1 complex. Clinically used as an α1-adrenoreceptor antagonist (Cardura®) for treating hypertension and benign prostate hyperplasia, doxazosin activated EphA2 independent of α1-adrenoreceptor. Similar to ephrin-A1, doxazosin inhibited Akt and ERK kinase activities in an EphA2-dependent manner. Treatment with doxazosin triggered EphA2 receptor internalization, and suppressed haptotactic and chemotactic migration of prostate cancer, breast cancer, and glioma cells. Moreover, in an orthotopic xenograft model, doxazosin reduced distal metastasis of human prostate cancer cells and prolonged survival in recipient mice. To our knowledge, doxazosin is the first small molecule agonist of a receptor tyrosine kinase that is capable of inhibiting malignant behaviors in vitro and in vivo. PMID:22916121

  12. Oxygen-induced cell migration and on-line monitoring biomarkers modulation of cervical cancers on a microfluidic system

    PubMed Central

    Lin, Xuexia; Chen, Qiushui; Liu, Wu; Zhang, Jie; Wang, Shiqi; Lin, Zhixiong; Lin, Jin-Ming

    2015-01-01

    In this work, we report an integrated microfluidic device for cell co-culture under different concentrations of oxygen, in which the secreted protein VEGF165 was on-line qualitatively and semi-quantitatively analyzed by functional nucleic acid, hemin, ABTS and peroxide system. This microfluidic platform allowed investigation of various oxygen and distances effect on cell-to-cell communication. Besides, the microfluidic device was used for real-time analysis of VEGF165 protein by aptamer-functionalized microchannels. Under 5% O2 condition, we found that the migration of CaSki cells was faster than the migration of human umbilical vein endothelial cells. However, the migration of CaSki cells was slower than the migration of HUVECs under 15% O2 condition. Moreover, the shorter intercellular distances, the quicker cells migration. Furthermore, HIF-1α and VEGF165 genes, ROS were analyzed, and the results would provide new perspectives for the diagnosis and medical treatment of cervical cancer. PMID:25905434

  13. Naringin suppress chondrosarcoma migration through inhibition vascular adhesion molecule-1 expression by modulating miR-126.

    PubMed

    Tan, Tzu-Wei; Chou, Ying-Erh; Yang, Wei-Hung; Hsu, Chin-Jung; Fong, Yi-Chin; Tang, Chih-Hsin

    2014-09-01

    Chondrosarcoma, a primary malignant bone cancer, has a potent capacity to invade locally and cause distant metastasis, especially to the lungs. Patients diagnosed with it have poor prognosis. Naringin, polymethoxylated flavonoid commonly found in citrus fruits, has anti-oxidant, anti-inflammatory and anti-tumor activity; whether naringin regulates migration of chondrosarcoma is largely unknown. Here we report that naringin does not expedite apoptosis in human chondrosarcoma. By contrast, at noncytotoxic concentrations, naringin suppressed migration and invasion of chondrosarcoma cells. Vascular cell adhesion molecule-1 (VCAM-1) of the immunoglobulin superfamily is linked with metastasis; we found incubation of chondrosarcoma cells with naringin reducing mRNA transcription for, and cell surface expression of, VCAM-1. We also observed that naringin enhancing miR-126 expression, and miR-126 inhibitor reversed the naringin-inhibited cell motility and VCAM-1 expression. Therefore, naringin inhibits migration and invasion of human chondrosarcoma via down-regulation of VCAM-1 by increasing miR-126. Thus, naringin may be a novel anti-migration agent for the treatment of migration in chondrosarcoma. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Fibronectin Modulates Cell Adhesion and Signaling to Promote Single Cell Migration of Highly Invasive Oral Squamous Cell Carcinoma

    PubMed Central

    Ramos, Grasieli de Oliveira; Bernardi, Lisiane; Lauxen, Isabel; Sant’Ana Filho, Manoel; Horwitz, Alan Rick; Lamers, Marcelo Lazzaron

    2016-01-01

    Cell migration is regulated by adhesion to the extracellular matrix (ECM) through integrins and activation of small RhoGTPases, such as RhoA and Rac1, resulting in changes to actomyosin organization. During invasion, epithelial-derived tumor cells switch from laminin-enriched basal membrane to collagen and fibronectin-enriched connective tissue. How this switch affects the tumor migration is still unclear. We tested the hypothesis that ECM dictates the invasiveness of Oral Squamous Cell Carcinoma (OSCC). We analyzed the migratory properties of two OSCC lines, a low invasive cell line with high e-cadherin levels (Linv/HE-cad) or a highly invasive cell line with low e-cadherin levels (Hinv/LE-cad), plated on different ECM components. Compared to laminin, fibronectin induced non-directional collective migration and decreased RhoA activity in Linv/HE-cad OSCC. For Hinv/LE-cad OSCC, fibronectin increased Rac1 activity and induced smaller adhesions, resulting in a fast single cell migration in both 2D and 3D environments. Consistent with these observations, human OSCC biopsies exhibited similar changes in cell-ECM adhesion distribution at the invasive front of the tumor, where cells encounter fibronectin. Our results indicate that ECM composition might induce a switch from collective to single cell migration according to tumor invasiveness due to changes in cell-ECM adhesion and the resulting signaling pathways that alter actomyosin organization. PMID:26978651

  15. A2BR adenosine receptor modulates sweet taste in circumvallate taste buds.

    PubMed

    Kataoka, Shinji; Baquero, Arian; Yang, Dan; Shultz, Nicole; Vandenbeuch, Aurelie; Ravid, Katya; Kinnamon, Sue C; Finger, Thomas E

    2012-01-01

    In response to taste stimulation, taste buds release ATP, which activates ionotropic ATP receptors (P2X2/P2X3) on taste nerves as well as metabotropic (P2Y) purinergic receptors on taste bud cells. The action of the extracellular ATP is terminated by ectonucleotidases, ultimately generating adenosine, which itself can activate one or more G-protein coupled adenosine receptors: A1, A2A, A2B, and A3. Here we investigated the expression of adenosine receptors in mouse taste buds at both the nucleotide and protein expression levels. Of the adenosine receptors, only A2B receptor (A2BR) is expressed specifically in taste epithelia. Further, A2BR is expressed abundantly only in a subset of taste bud cells of posterior (circumvallate, foliate), but not anterior (fungiform, palate) taste fields in mice. Analysis of double-labeled tissue indicates that A2BR occurs on Type II taste bud cells that also express Gα14, which is present only in sweet-sensitive taste cells of the foliate and circumvallate papillae. Glossopharyngeal nerve recordings from A2BR knockout mice show significantly reduced responses to both sucrose and synthetic sweeteners, but normal responses to tastants representing other qualities. Thus, our study identified a novel regulator of sweet taste, the A2BR, which functions to potentiate sweet responses in posterior lingual taste fields.

  16. A2BR Adenosine Receptor Modulates Sweet Taste in Circumvallate Taste Buds

    PubMed Central

    Yang, Dan; Shultz, Nicole; Vandenbeuch, Aurelie; Ravid, Katya; Kinnamon, Sue C.; Finger, Thomas E.

    2012-01-01

    In response to taste stimulation, taste buds release ATP, which activates ionotropic ATP receptors (P2X2/P2X3) on taste nerves as well as metabotropic (P2Y) purinergic receptors on taste bud cells. The action of the extracellular ATP is terminated by ectonucleotidases, ultimately generating adenosine, which itself can activate one or more G-protein coupled adenosine receptors: A1, A2A, A2B, and A3. Here we investigated the expression of adenosine receptors in mouse taste buds at both the nucleotide and protein expression levels. Of the adenosine receptors, only A2B receptor (A2BR) is expressed specifically in taste epithelia. Further, A2BR is expressed abundantly only in a subset of taste bud cells of posterior (circumvallate, foliate), but not anterior (fungiform, palate) taste fields in mice. Analysis of double-labeled tissue indicates that A2BR occurs on Type II taste bud cells that also express Gα14, which is present only in sweet-sensitive taste cells of the foliate and circumvallate papillae. Glossopharyngeal nerve recordings from A2BR knockout mice show significantly reduced responses to both sucrose and synthetic sweeteners, but normal responses to tastants representing other qualities. Thus, our study identified a novel regulator of sweet taste, the A2BR, which functions to potentiate sweet responses in posterior lingual taste fields. PMID:22253866

  17. Annexin A2 Modulates Radiation-Sensitive Transcriptional Programming and Cell Fate

    SciTech Connect

    Waters, Katrina M.; Stenoien, David L.; Sowa, Marianne B.

    2013-01-01

    There is considerable public interest in the health effects of low doses of radiation (LDR) that fall below the doses that can be plausibly investigated in epidemiological studies. At these low doses, experimental models can detect perturbations in signaling pathways and use this information to define functional consequences of LDR exposures prospectively. In this study, we show increased nuclear annexin A2 (AnxA2) levels in human skin organotypic culture and murine progenitor cell model systems following exposure to X-radiation (10-200 cGy). LDR (2-20 cGy) inhibits cell transformation responses following epidermal growth factor (EGF) or 12-O-tetradecanoylphorbol-13-acetate (TPA) exposures, indicating LDR may havemore » a protective component mediated in part by nuclear localization of AnxA2. Oncogenic protein kinase C epsilon (PKC) levels are increased in nuclear extracts from AnxA2 silenced [shRNA] cells, suggesting that AnxA2 may contribute to PKC nuclear export, perhaps reducing oncogenic potential. Coordinately, silencing AnxA2 results in a sensitive phenotype and cells grow constitutively in soft agar. Using global microarray analysis, we show that silencing AnxA2 fundamentally alters transcriptional programming, changing the radioresponsive transcriptome and revealing biological processes that are induced in the absence of AnxA2. These observations suggest that AnxA2 plays a fundamental role in the sensitivity of cellular and tissue response to ionizing radiation, and deficiency of AnxA2 could result in a permissive environment for radiation-induced health effects.« less

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

    ERIC Educational Resources Information Center

    Mukai, Gary; Brunette, Rachel

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

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

    PubMed

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

    2017-07-01

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

  20. Adenosine A2B receptor modulates intestinal barrier function under hypoxic and ischemia/reperfusion conditions.

    PubMed

    Yang, Yang; Qiu, Yuan; Wang, Wensheng; Xiao, Weidong; Liang, Hongyin; Zhang, Chaojun; Yang, Hanwenbo; Teitelbaum, Daniel H; Sun, Li-Hua; Yang, Hua

    2014-01-01

    Intestinal barrier function failure from ischemia/reperfusion (I/R) and acute hypoxia has been implicated as a critical determinant in the predisposition to intestinal inflammation and a number of inflammatory disorders. Here, we identified the role of Adenosine A2B receptor (A2BAR) in the regulation of intestinal barrier function under I/R and acute hypoxic conditions. C57BL/6J mice were used, and were randomized into three groups: Sham, I/R, IR+PSB1115 (a specific A2BAR antagonist) groups. After surgery, the small bowel was harvested for immunohistochemical staining, RNA and protein content, and intestinal permeability analyses. Using an epithelial cell culture model, we investigated the influence of hypoxia on the epithelial function, and the role of A2BAR in the expressions of tight junction and epithelial permeability. The expressions of Claudin-1, occludin and ZO-1 were detected by RT-PCR and Western-Blot. Epithelial barrier function was assessed with transepithelial resistance (TER). The A2BAR antagonist, PSB1115, significantly increased tight junction protein expression after intestinal I/R or acute hypoxia conditions. PSB1115 also attenuated the disrupted distribution of TJ proteins. Furthermore, inhibition of A2BAR attenuated the decrease in TER induced by I/R or acute hypoxic conditions, and maintained intestinal barrier function. Antagonism of A2BAR activity improves intestinal epithelial structure and barrier function in a mouse model of intestinal I/R and a cell model of acute hypoxia. These findings support a potentially destructive role for A2BAR under intestinal I/R and acute hypoxic conditions.

  1. EphB6 promotes anoikis by modulating EphA2 signaling.

    PubMed

    Akada, Mai; Harada, Kohei; Negishi, Manabu; Katoh, Hironori

    2014-12-01

    Anoikis is a specific type of apoptosis induced by detachment of epithelial cells from extracellular matrix, and acquiring resistance to anoikis is an important step that enables cancer cells to metastasize. EphA2, which is overexpressed in a variety of human cancers, is phosphorylated by Akt on serine 897 and mediates ligand ephrin-independent promotion of anoikis resistance through the RhoG activator Ephexin4. EphB6 is frequently silenced in invasive and metastatic cancers; however, its role in cancer progression is poorly understood. Here we show that EphB6 interacts with EphA2 and suppresses EphA2-mediated promotion of anoikis resistance in MCF7 breast cancer cells. On the other hand, knockdown of EphB6 promotes anoikis resistance. We further show that expression of EphB6 decreases serine 897 phosphorylation of EphA2 and suppresses EphA2-Ephexin4 interaction and the RhoG activation. These findings implicate EphB6 as a negative regulator of EphA2 oncogenic signaling. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. The A2a adenosine receptor modulates the reinforcement efficacy and neurotoxicity of MDMA.

    PubMed

    Ruiz-Medina, Jessica; Ledent, Catherine; Carretón, Olga; Valverde, Olga

    2011-04-01

    Adenosine is an endogenous purine nucleoside that plays a neuromodulatory role in the central nervous system. A2a adenosine receptors have been involved in reward-related processes, inflammatory phenomena and neurotoxicity reactions. In the present study, we investigated the role of A2a adenosine receptors on the acute pharmacological effects, reinforcement and neuroinflammation induced by MDMA administration. First, the acute effects of MDMA on body temperature, locomotor activity and anxiety-like responses were measured in A2a knockout mice and wild-type littermates. Second, MDMA reinforcing properties were evaluated using the intravenous self-administration paradigm. Finally, we assessed striatal astrogliosis and microgliosis as markers of MDMA neurotoxicity. Our results showed that acute MDMA produced a biphasic effect on body temperature and increased locomotor activity and anxiogenic-like responses in both genotypes. However, MDMA reinforcing properties were dramatically affected by the lack of A2a adenosine receptors. Thus, wild-type mice maintained MDMA self-administration under a fixed ratio 1 reinforcement schedule, whereas the operant response appeared completely abolished in A2a knockout mice. In addition, the MDMA neurotoxic regime produced an enhanced inflammatory response in striatum of wild-type mice, revealed by a significant increase in glial expression, whereas such activation was attenuated in mutant mice. This is the first report indicating that A2a adenosine receptors play a key role in reinforcement and neuroinflammation induced by the widely used psychostimulant.

  3. Inhibition of sirtuins 1 and 2 impairs cell survival and migration and modulates the expression of P-glycoprotein and MRP3 in hepatocellular carcinoma cell lines.

    PubMed

    Ceballos, María Paula; Decándido, Giulia; Quiroga, Ariel Darío; Comanzo, Carla Gabriela; Livore, Verónica Inés; Lorenzetti, Florencia; Lambertucci, Flavia; Chazarreta-Cifre, Lorena; Banchio, Claudia; Alvarez, María de Luján; Mottino, Aldo Domingo; Carrillo, María Cristina

    2018-06-01

    Sirtuins (SIRTs) 1 and 2 deacetylases are overexpressed in hepatocellular carcinoma (HCC) and are associated with tumoral progression and multidrug resistance (MDR). In this study we analyzed whether SIRTs 1 and 2 activities blockage was able to affect cellular survival and migration and to modulate p53 and FoxO1 acetylation in HepG2 and Huh7 cells. Moreover, we analyzed ABC transporters P-glycoprotein (P-gp) and multidrug resistance-associated protein 3 (MRP3) expression. We used cambinol and EX-527 as SIRTs inhibitors. Both drugs reduced cellular viability, number of colonies and cellular migration and augmented apoptosis. In 3D cultures, SIRTs inhibitors diminished spheroid growth and viability. 3D culture was less sensitive to drugs than 2D culture. The levels of acetylated p53 and FoxO1 increased after treatments. Drugs induced a decrease in ABC transporters mRNA and protein levels in HepG2 cells; however, only EX-527 was able to reduce MRP3 mRNA and protein levels in Huh7 cells. This is the first work demonstrating the regulation of MRP3 by SIRTs. In conclusion, both drugs decreased HCC cells survival and migration, suggesting SIRTs 1 and 2 activities blockage could be beneficial during HCC therapy. Downregulation of the expression of P-gp and MRP3 supports the potential application of SIRTs 1 and 2 inhibitions in combination with conventional chemotherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Long Non-Coding RNA MALAT1 Interacts With miR-204 to Modulate Human Hilar Cholangiocarcinoma Proliferation, Migration, and Invasion by Targeting CXCR4.

    PubMed

    Tan, Xinyu; Huang, Zhiguo; Li, Xiaogang

    2017-11-01

    Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is involved in the development and progression of many types of tumors. An aberrant expression of MALAT1 was observed in many kinds of cancers. However, the exact effects and molecular mechanisms of MALAT1 in human hilar cholangiocarcinoma (HCCA) progression are still unknown. Here, we investigated the role of MALAT1 in human HCCA cell lines and clinical tumor samples in order to determine the function of this lncRNA. In our research, lncRNA-MALAT1 was specifically upregulated in HCCA tissues and cell lines, and was associated with pathological T stage, a larger tumor size, and perineural invasion. Knockdown of MALAT1 inhibited the proliferation, migration, and invasion of human HCCA cell. In addition, chemokine receptor-4 (CXCR4) was involved in MALAT1 induced human HCCA growth, migration, and invasion. By using online tools and a series of mechanistic analysis, we also demonstrated that miR-204-dependent CXCR4 regulation was required in MALAT1 modulating HCCA cell growth, migration and invasion. Taken together, our data indicated that MALAT1 might play an oncogenic role in HCCA through miR-204-dependent CXCR4 regulation, and could be regarded as a therapeutic target in HCCA. J. Cell. Biochem. 118: 3643-3653, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. A novel 3D bone-mimetic scaffold composed of collagen/MTA/MWCNT modulates cell migration and osteogenesis.

    PubMed

    Valverde, Thalita M; Castro, Elisandra G; Cardoso, Maíssa H S; Martins-Júnior, Paulo A; Souza, Lívia M O; Silva, Patrícia P; Ladeira, Luiz O; Kitten, Gregory T

    2016-10-01

    This study characterized a three-dimensional (3D) biocomposite scaffolds produced using type I collagen, mineral trioxide aggregate (MTA) and multi-walled carbon nanotubes (MWCNT) to be used in bone tissue regeneration. The scaffolds were analyzed via scanning (SEM) and transmission (TEM) electron microscopy, as well as the viability and migration of osteoblasts and mineralization of the scaffolds. SEM and TEM analyses showed that MTA and MWCNT were distributed as both large agglomerates entrapped within the collagen network and as smaller accumulations or individual molecules dispersed throughout the scaffold. Ultrastructural analysis revealed that osteoblastic MC3T3-E1 cells grown in the biocomposite endocytosed MWCNT, which were localized in the cytoplasm and in vesicles. Analysis of cells grown in the 3D scaffolds demonstrated that >95% of the cells remained viable in all tested combinations and concentrations of the biocomposite. MC3T3-E1 osteoblasts migrated into scaffolds formed with concentrations of type I collagen between 1.75 and 3.0mg/mL. Cells displayed increased migration into scaffolds formed with collagen and a range of low to high concentrations of MTA. In contrast, the presence of MWCNT in the biocomposite had a slight negative effect on migration. Collagen gels containing specific concentrations of MTA, or MWCNT, or combinations of MTA/MWCNT, caused an increase in mineralization of scaffolds. Scaffolds composed of defined concentrations of type I collagen, MTA and MWCNT are biocompatible, promote migration and mineralization of osteoblasts, and hence may be useful as bone tissue mimetics. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Purinoceptor modulation of noradrenaline release in rat tail artery: tonic modulation mediated by inhibitory P2Y- and facilitatory A2A-purinoceptors.

    PubMed Central

    Gonçalves, J.; Queiroz, G.

    1996-01-01

    1. The effects of analogues of adenosine and ATP on noradrenaline release elicited by electrical stimulation (5 Hz, 2700 pulses) were studied in superfused preparations of rat tail artery. The effects of purinoceptor antagonists, of adenosine deaminase and of adenosine uptake blockade were also examined. Noradrenaline was measured by h.p.l.c. electrochemical detection. 2. The A1-adenosine receptor agonist, N6-cyclopentyladenosine (CPA; 0.1-100 nM) reduced, whereas the A2A-receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680; 3-30 nM) increased evoked noradrenaline overflow. These effects were antagonized by the A1-adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 20 nM) and the A2-adenosine receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX; 100 nM), respectively. The P2Y-purinoceptor agonist, 2-methylthio-ATP (1-100 microM) reduced noradrenaline overflow, an effect prevented by the P2-purinoceptor antagonist, cibacron blue 3GA (100 microM) and suramin (100 microM). 3. Adenosine deaminase (2 u ml-1), DMPX (100 nM) and inhibition of adenosine uptake with S-(p-nitrobenzyl)-6-thioinosine (NBTI; 50 nM) decreased evoked noradrenaline overflow. DPCPX alone did not change noradrenaline overflow but prevented the inhibition caused by NBTI. The P2Y-purinoceptor antagonist, cibacron blue 3GA (100 microM) increased evoked noradrenaline overflow as did suramin, a non-selective P2-antagonist. 4. It is concluded that, in rat tail artery, inhibitory (A1 and P2Y) and facilitatory (A2A) purinoceptors are present and modulate noradrenaline release evoked by electrical stimulation. Endogenous purines tonically modulate noradrenaline release through activation of inhibitory P2Y and facilitatory A2A purinoceptors, whereas a tonic activation of inhibitory A1 purinoceptors seems to be prevented by adenosine uptake. PMID:8825357

  7. MiR-137 inhibited cell proliferation and migration of vascular smooth muscle cells via targeting IGFBP-5 and modulating the mTOR/STAT3 signaling

    PubMed Central

    Li, Kai; Huang, Wei; Zhang, Xiaoqing

    2017-01-01

    Abnormal proliferation of vascular smooth muscle cells (VSMCs) contributes to the development of cardiovascular diseases. Studies have shown the great impact of microRNAs (miRNAs) on the cell proliferation of VSMCs. This study examined the effects of miR-137 on the cell proliferation and migration of VSMCs and also explored the underlying molecular mechanisms. The mRNA and protein expression levels were determined by qRT-PCR and western blot assays, respectively. The CCK-8 assay, wound healing assay and transwell migration assay were performed to measure cell proliferation and migration of VSMCs. The miR-137-targeted 3’untranslated region of insulin-like growth factor-binding protein-5 (IGFBP-5) was confirmed by luciferase reporter assay. Platelet-derived growth factor-bb (PDGF-bb) treatment enhanced cell proliferation and suppressed the expression of miR-137 in VSMCs. The gain-of-function and loss-of-function assays showed that overexpression of miR-137 suppressed the cell proliferation and migration, and also inhibited the expression of matrix genes of VSMCs; down-regulation of miR-137 had the opposite effects on VSMCs. Bioinformatics analysis and luciferase report assay results showed that IGFBP-5 was a direct target of miR-137, and miR-137 overexpression suppressed the IGFBP-5 expression and down-regulation of miR-137 increased the IGFBP-5 expression in VSMCs. PDGF-bb treatment also increased the IGFBP-5 mRNA expression. In addition, enforced expression of IGFBP-5 reversed the inhibitory effects of miR-137 on cell proliferation and migration of VSMCs. More importantly, overexpression of miR-137 also suppressed the activity of mTOR/STAT3 signaling in VSMCs. Taken together, the results suggest that miR-137 may suppress cell proliferation and migration of VSMCs via targeting IGFBP-5 and modulating mTOR/STAT3 signaling pathway. PMID:29016699

  8. Phosphorylation of rat liver heterogeneous nuclear ribonucleoproteins A2 and C can be modulated by calmodulin.

    PubMed Central

    Bosser, R; Faura, M; Serratosa, J; Renau-Piqueras, J; Pruschy, M; Bachs, O

    1995-01-01

    It was previously reported that the phosphorylation of three proteins of 36, 40 to 42, and 50 kDa by casein kinase 2 is inhibited by calmodulin in nuclear extracts from rat liver cells (R. Bosser, R. Aligué, D. Guerini, N. Agell, E. Carafoli, and O. Bachs, J. Biol. Chem. 268:15477-15483, 1993). By immunoblotting, peptide mapping, and endogenous phosphorylation experiments, the 36- and 40- to 42-kDa proteins have been identified as the A2 and C proteins, respectively, of the heterogeneous nuclear ribonucleoprotein particles. To better understand the mechanism by which calmodulin inhibits the phosphorylation of these proteins, they were purified by using single-stranded DNA chromatography, and the effect of calmodulin on their phosphorylation by casein kinase 2 was analyzed. Results revealed that whereas calmodulin inhibited the phosphorylation of purified A2 and C proteins in a Ca(2+)-dependent manner, it did not affect the casein kinase 2 phosphorylation of a different protein substrate, i.e., beta-casein. These results indicate that the effect of calmodulin was not on casein kinase 2 activity but on specific protein substrates. The finding that the A2 and C proteins can bind to a calmodulin-Sepharose column in a Ca(2+)-dependent manner suggests that this association could prevent the phosphorylation of the proteins by casein kinase 2. Immunoelectron microscopy studies have revealed that such interactions could also occur in vivo, since calmodulin and A2 and C proteins colocalize on the ribonucleoprotein particles in rat liver cell nuclei. PMID:7823935

  9. Membrane omega-3 fatty acids modulate the oligomerisation kinetics of adenosine A2A and dopamine D2 receptors

    NASA Astrophysics Data System (ADS)

    Guixà-González, Ramon; Javanainen, Matti; Gómez-Soler, Maricel; Cordobilla, Begoña; Domingo, Joan Carles; Sanz, Ferran; Pastor, Manuel; Ciruela, Francisco; Martinez-Seara, Hector; Selent, Jana

    2016-01-01

    Membrane levels of docosahexaenoic acid (DHA), an essential omega-3 polyunsaturated fatty acid (ω-3 PUFA), are decreased in common neuropsychiatric disorders. DHA modulates key cell membrane properties like fluidity, thereby affecting the behaviour of transmembrane proteins like G protein-coupled receptors (GPCRs). These receptors, which have special relevance for major neuropsychiatric disorders have recently been shown to form dimers or higher order oligomers, and evidence suggests that DHA levels affect GPCR function by modulating oligomerisation. In this study, we assessed the effect of membrane DHA content on the formation of a class of protein complexes with particular relevance for brain disease: adenosine A2A and dopamine D2 receptor oligomers. Using extensive multiscale computer modelling, we find a marked propensity of DHA for interaction with both A2A and D2 receptors, which leads to an increased rate of receptor oligomerisation. Bioluminescence resonance energy transfer (BRET) experiments performed on living cells suggest that this DHA effect on the oligomerisation of A2A and D2 receptors is purely kinetic. This work reveals for the first time that membrane ω-3 PUFAs play a key role in GPCR oligomerisation kinetics, which may have important implications for neuropsychiatric conditions like schizophrenia or Parkinson’s disease.

  10. Enthalpy-Entropy Compensation in the Binding of Modulators at Ionotropic Glutamate Receptor GluA2.

    PubMed

    Krintel, Christian; Francotte, Pierre; Pickering, Darryl S; Juknaitė, Lina; Pøhlsgaard, Jacob; Olsen, Lars; Frydenvang, Karla; Goffin, Eric; Pirotte, Bernard; Kastrup, Jette S

    2016-06-07

    The 1,2,4-benzothiadiazine 1,1-dioxide type of positive allosteric modulators of the ionotropic glutamate receptor A2 (GluA2) are promising lead compounds for the treatment of cognitive disorders, e.g., Alzheimer's disease. The modulators bind in a cleft formed by the interface of two neighboring ligand binding domains and act by stabilizing the agonist-bound open-channel conformation. The driving forces behind the binding of these modulators can be significantly altered with only minor substitutions to the parent molecules. In this study, we show that changing the 7-fluorine substituent of modulators BPAM97 (2) and BPAM344 (3) into a hydroxyl group (BPAM557 (4) and BPAM521 (5), respectively), leads to a more favorable binding enthalpy (ΔH, kcal/mol) from -4.9 (2) and -7.5 (3) to -6.2 (4) and -14.5 (5), but also a less favorable binding entropy (-TΔS, kcal/mol) from -2.3 (2) and -1.3 (3) to -0.5 (4) and 4.8 (5). Thus, the dissociation constants (Kd, μM) of 4 (11.2) and 5 (0.16) are similar to those of 2 (5.6) and 3 (0.35). Functionally, 4 and 5 potentiated responses of 10 μM L-glutamate at homomeric rat GluA2(Q)i receptors with EC50 values of 67.3 and 2.45 μM, respectively. The binding mode of 5 was examined with x-ray crystallography, showing that the only change compared to that of earlier compounds was the orientation of Ser-497 pointing toward the hydroxyl group of 5. The favorable enthalpy can be explained by the formation of a hydrogen bond from the side-chain hydroxyl group of Ser-497 to the hydroxyl group of 5, whereas the unfavorable entropy might be due to desolvation effects combined with a conformational restriction of Ser-497 and 5. In summary, this study shows a remarkable example of enthalpy-entropy compensation in drug development accompanied with a likely explanation of the underlying structural mechanism. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  11. Macrophage A2A Adenosinergic Receptor Modulates Oxygen-Induced Augmentation of Murine Lung Injury

    PubMed Central

    D’Alessio, Franco R.; Eto, Yoshiki; Chau, Eric; Avalos, Claudia; Waickman, Adam T.; Garibaldi, Brian T.; Mock, Jason R.; Files, Daniel C.; Sidhaye, Venkataramana; Polotsky, Vsevolod Y.; Powell, Jonathan; Horton, Maureen; King, Landon S.

    2013-01-01

    Acute respiratory distress syndrome (ARDS) causes significant morbidity and mortality. Exacerbating factors increasing the risk of ARDS remain unknown. Supplemental oxygen is often necessary in both mild and severe lung disease. The potential effects of supplemental oxygen may include augmentation of lung inflammation by inhibiting anti-inflammatory pathways in alveolar macrophages. We sought to determine oxygen-derived effects on the anti-inflammatory A2A adenosinergic (ADORA2A) receptor in macrophages, and the role of the ADORA2A receptor in lung injury. Wild-type (WT) and ADORA2A−/− mice received intratracheal lipopolysaccharide (IT LPS), followed 12 hours later by continuous exposure to 21% oxygen (control mice) or 60% oxygen for 1 to 3 days. We measured the phenotypic endpoints of lung injury and the alveolar macrophage inflammatory state. We tested an ADORA2A-specific agonist, CGS-21680 hydrochloride, in LPS plus oxygen-exposed WT and ADORA2A−/− mice. We determined the specific effects of myeloid ADORA2A, using chimera experiments. Compared with WT mice, ADORA2A−/− mice exposed to IT LPS and 60% oxygen demonstrated significantly more histologic lung injury, alveolar neutrophils, and protein. Macrophages from ADORA2A−/− mice exposed to LPS plus oxygen expressed higher concentrations of proinflammatory cytokines and cosignaling molecules. CGS-21680 prevented the oxygen-induced augmentation of lung injury after LPS only in WT mice. Chimera experiments demonstrated that the transfer of WT but not ADORA2A−/− bone marrow cells into irradiated ADORA2A−/− mice reduced lung injury after LPS plus oxygen, demonstrating myeloid ADORA2A protection. ADORA2A is protective against lung injury after LPS and oxygen. Oxygen after LPS increases macrophage activation to augment lung injury by inhibiting the ADORA2A pathway. PMID:23349051

  12. Benzodiazepines modulate the A2 adenosine binding sites on 108CC15 neuroblastoma X glioma hybrid cells.

    PubMed Central

    Snell, C. R.; Snell, P. H.

    1984-01-01

    We have demonstrated high affinity diazepam binding sites of the Ro5-4864 benzodiazepine receptor subtype on 108CC15 neuroblastoma X glioma hybrid cells. These cells were previously shown to have purinoceptors of the A2 adenosine subtype and we have now found that [3H]-adenosine can be displaced from this binding site by the benzodiazepines and related compounds that can also bind to the Ro5-4864 site. Diazepam was found to have no intrinsic activity at the A2-receptor as measured by the stimulation of adenosine 3':5'-cyclic monophosphate (cyclic AMP) production in this cell line. At concentrations sufficient to compete for the A2-receptor, diazepam was shown to facilitate, by approximately 2 fold, the stimulation of cyclic AMP by adenosine. These effects are not due to inhibition of adenosine uptake or phosphodiesterase activity, but are probably a consequence of modulation of the coupling of the A2-receptor to cyclic AMP production in this hybrid cell line. PMID:6150742

  13. Expression of membrane progesterone receptors (mPRs) in rat peripheral glial cell membranes and their potential role in the modulation of cell migration and protein expression.

    PubMed

    Castelnovo, Luca F; Magnaghi, Valerio; Thomas, Peter

    2017-09-28

    The role played by progestogens in modulating Schwann cell pathophysiology is well established. Progestogens exert their effects in these cells through both classical genomic and non-genomic mechanisms, the latter mediated by the GABA-A receptor. However, there is evidence that other receptors may be involved. Membrane progesterone receptors (mPRs) are novel 7-transmembrane receptors coupled to G proteins that have been characterized in different tissues and cells, including the central nervous system (CNS). The mPRs were shown to mediate some of progestogens' neuroprotective effects in the CNS, and to be upregulated in glial cells after traumatic brain injury. Based on this evidence, this paper investigated the possible involvement of mPRs in mediating progestogen actions in S42 Schwann cells. All five mPR isoforms and progesterone receptor membrane component 1 (PGRMC1) were detected in Schwann cells, and were present on the cell membrane. Progesterone and the mPR-specific agonist, Org-OD-02-0 (02) bound to these membranes, indicating the presence of functional mPRs. The mPR agonist 02 rapidly increased cell migration in an in vitro assay, suggesting a putative role of mPRs in the nerve regeneration process. Treatment with pertussis toxin and 8-Br-cAMP blocked 02-induced cell migration, suggesting this progestogen action is mediated by activation of an inhibitory G protein, leading to a decrease in intracellular cAMP levels. In contrast, long-term mPR activation led to increased expression levels of myelin associated glycoprotein (MAG). Taken together, these findings show that mPRs are present and active in Schwann cells and have a role in modulating their physiological processes. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Structural modulation of brain development by oxygen: evidence on adolescents migrating from high altitude to sea level environment.

    PubMed

    Zhang, Jiaxing; Zhang, Haiyan; Chen, Ji; Fan, Ming; Gong, Qiyong

    2013-01-01

    The present study aimed to investigate structural modulation of brain by high level of oxygen during its peak period of development. Voxel-based morphometry analysis of gray matter (GM) and white matter (WM) volumes and Tract-Based Spatial Statistics analysis of WM fractional anisotropy (FA) and mean diffusion (MD) based on MRI images were carried out on 21 Tibetan adolencents (15-18 years), who were born and raised in Qinghai-Tibetan Plateau (2900-4700 m) and have lived at sea level (SL) in the last 4 years. The control group consisted of matched Tibetan adolescents born and raised at high altitude all the time. SL immigrants had increased GM volume in the left insula, left inferior parietal gyrus, and right superior parietal gyrus and decreased GM in the left precentral cortex and multiple sites in cerebellar cortex (left lobule 8, bilateral lobule 6 and crus 1/2). Decreased WM volume was found in the right superior frontal gyrus in SL immigrants. SL immigrants had higher FA and lower MD at multiple sites of WM tracts. Moreover, we detected changes in ventilation and circulation. GM volume in cerebellum lobule 8 positively correlated with diastolic pressure, while GM volume in insula positively correlated vital capacity and hypoxic ventilatory response. Our finding indicate that the structural modulations of GM by high level of oxygen during its peak period of development are related to respiratory and circulatory regulations, while the modulation in WM mainly exhibits an enhancement in myelin maturation.

  15. A novel synthetic oleanane triterpenoid suppresses adhesion, migration and invasion of highly metastatic melanoma cells by modulating gelatinase signaling axis

    PubMed Central

    Sinha, Dona; Dutta, Kaustav; Ganguly, Kirat K.; Biswas, Jaydip; Bishayee, Anupam

    2014-01-01

    Background A methyl derivative natural triterpenoid amooranin (methyl-25-hydroxy-3-oxoolean-12-en-28-oate, AMR-Me) has been found to possess antiproliferative, proapoptotic and anti-inflammatory effects against established tumor cells. Large-scale synthesis of pure AMR-Me has eliminated the need of the natural phytochemical for further development of AMR-Me as an anticancer drug. Metastatic melanoma is a fatal form of cutaneous malignancy with poor prognosis and limited therapeutic options. It was hypothesized that antitumor pharmacological effect of AMR-Me could be linked to AMR-Me-mediated suppression of the metastatic potential of B16F10 murine melanoma. Methods AMR-Me was assessed for its antimetastatic efficacy by cell adhesion, migration and invasion assays in B16F10 cells. The signaling crosstalk was explored by gelatin zymography, Western blot, ELISA and immunocytochemistry. Results The results elicited that AMR-Me was successful in restricting the adhesion, migration and invasion of highly metastatic cells. The antimetastatic potential of this compound may be attributed to the reduced expression of membrane type 1 metalloproteinase (MT1-MMP) and matrix metalloproteinases (MMP-2 and MMP-9). AMR-Me was found to downregulate vascular endothelial growth factor (VEGF)/prosphorylated forms of focal adhesion kinase (pFAK397)/Jun N-terminus kinase (pJNK)/extracellular signal-regulated kinase (pERK). This, in turn, inhibited transcription factor nuclear factor-κB (NF-κB) and transactivation of MMPs. Moreover the activation of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) might have influenced the downmodulation of MT1-MMP, MMP-2 and MMP-9. Conclusion AMR-Me suppresses the activity of MT1-MMP, MMP-2 and MMP-9 by downregulation of VEGF/pFAK397/pJNK/pERK/NF-κB and activation of TIMP-1 and TIMP-2 in metastatic melanoma cell line, B16F10. General significance AMR-Me has the potential as an effective anticancer drug for metastatic melanoma which is a

  16. Three-dimensional matrix fiber alignment modulates cell migration and MT1-MMP utility by spatially and temporally directing protrusions

    NASA Astrophysics Data System (ADS)

    Fraley, Stephanie I.; Wu, Pei-Hsun; He, Lijuan; Feng, Yunfeng; Krisnamurthy, Ranjini; Longmore, Gregory D.; Wirtz, Denis

    2015-10-01

    Multiple attributes of the three-dimensional (3D) extracellular matrix (ECM) have been independently implicated as regulators of cell motility, including pore size, crosslink density, structural organization, and stiffness. However, these parameters cannot be independently varied within a complex 3D ECM protein network. We present an integrated, quantitative study of these parameters across a broad range of complex matrix configurations using self-assembling 3D collagen and show how each parameter relates to the others and to cell motility. Increasing collagen density resulted in a decrease and then an increase in both pore size and fiber alignment, which both correlated significantly with cell motility but not bulk matrix stiffness within the range tested. However, using the crosslinking enzyme Transglutaminase II to alter microstructure independently of density revealed that motility is most significantly predicted by fiber alignment. Cellular protrusion rate, protrusion orientation, speed of migration, and invasion distance showed coupled biphasic responses to increasing collagen density not predicted by 2D models or by stiffness, but instead by fiber alignment. The requirement of matrix metalloproteinase (MMP) activity was also observed to depend on microstructure, and a threshold of MMP utility was identified. Our results suggest that fiber topography guides protrusions and thereby MMP activity and motility.

  17. Emodin Suppresses Migration and Invasion through the Modulation of CXCR4 Expression in an Orthotopic Model of Human Hepatocellular Carcinoma

    PubMed Central

    Ong, Tina H.; Subramaniam, Aruljothi; Siveen, Kodappully Sivaraman; Perumal, Ekambaram; Samy, Ramar Perumal; Bist, Pradeep; Lim, Lina H. K.; Kumar, Alan Prem; Hui, Kam M.; Sethi, Gautam

    2013-01-01

    Accumulating evidence(s) indicate that CXCL12-CXCR4 signaling cascade plays an important role in the process of invasion and metastasis that accounts for more than 80% of deaths in hepatocellular carcinoma (HCC) patients. Thus, identification of novel agents that can downregulate CXCR4 expression and its associated functions have a great potential in the treatment of metastatic HCC. In the present report, we investigated an anthraquinone derivative, emodin for its ability to affect CXCR4 expression as well as function in HCC cells. We observed that emodin downregulated the expression of CXCR4 in a dose-and time-dependent manner in HCC cells. Treatment with pharmacological proteasome and lysosomal inhibitors did not have substantial effect on emodin-induced decrease in CXCR4 expression. When investigated for the molecular mechanism(s), it was observed that the suppression of CXCR4 expression was due to downregulation of mRNA expression, inhibition of NF-κB activation, and abrogation of chromatin immunoprecipitation activity. Inhibition of CXCR4 expression by emodin further correlated with the suppression of CXCL12-induced migration and invasion in HCC cell lines. In addition, emodin treatment significantly suppressed metastasis to the lungs in an orthotopic HCC mice model and CXCR4 expression in tumor tissues. Overall, our results show that emodin exerts its anti-metastatic effect through the downregulation of CXCR4 expression and thus has the potential for the treatment of HCC. PMID:23472074

  18. Antioxidative Dietary Compounds Modulate Gene Expression Associated with Apoptosis, DNA Repair, Inhibition of Cell Proliferation and Migration

    PubMed Central

    Wang, Likui; Gao, Shijuan; Jiang, Wei; Luo, Cheng; Xu, Maonian; Bohlin, Lars; Rosendahl, Markus; Huang, Wenlin

    2014-01-01

    Many dietary compounds are known to have health benefits owing to their antioxidative and anti-inflammatory properties. To determine the molecular mechanism of these food-derived compounds, we analyzed their effect on various genes related to cell apoptosis, DNA damage and repair, oxidation and inflammation using in vitro cell culture assays. This review further tests the hypothesis proposed previously that downstream products of COX-2 (cyclooxygenase-2) called electrophilic oxo-derivatives induce antioxidant responsive elements (ARE), which leads to cell proliferation under antioxidative conditions. Our findings support this hypothesis and show that cell proliferation was inhibited when COX-2 was down-regulated by polyphenols and polysaccharides. Flattened macrophage morphology was also observed following the induction of cytokine production by polysaccharides extracted from viili, a traditional Nordic fermented dairy product. Coix lacryma-jobi (coix) polysaccharides were found to reduce mitochondrial membrane potential and induce caspase-3- and 9-mediated apoptosis. In contrast, polyphenols from blueberries were involved in the ultraviolet-activated p53/Gadd45/MDM2 DNA repair system by restoring the cell membrane potential. Inhibition of hypoxia-inducible factor-1 by saponin extracts of ginsenoside (Ginsen) and Gynostemma and inhibition of S100A4 by coix polysaccharides inhibited cancer cell migration and invasion. These observations suggest that antioxidants and changes in cell membrane potential are the major driving forces that transfer signals through the cell membrane into the cytosol and nucleus, triggering gene expression, changes in cell proliferation and the induction of apoptosis or DNA repair. PMID:25226533

  19. BPAG1a and b associate with EB1 and EB3 and modulate vesicular transport, Golgi apparatus structure, and cell migration in C2.7 myoblasts.

    PubMed

    Poliakova, Kseniia; Adebola, Adijat; Leung, Conrad L; Favre, Bertrand; Liem, Ronald K H; Schepens, Isabelle; Borradori, Luca

    2014-01-01

    BPAG1a and BPAG1b (BPAG1a/b) constitute two major isoforms encoded by the dystonin (Dst) gene and show homology with MACF1a and MACF1b. These proteins are members of the plakin family, giant multi-modular proteins able to connect the intermediate filament, microtubule and microfilament cytoskeletal networks with each other and to distinct cell membrane sites. They also serve as scaffolds for signaling proteins that modulate cytoskeletal dynamics. To gain better insights into the functions of BPAG1a/b, we further characterized their C-terminal region important for their interaction with microtubules and assessed the role of these isoforms in the cytoskeletal organization of C2.7 myoblast cells. Our results show that alternative splicing does not only occur at the 5' end of Dst and Macf1 pre-mRNAs, as previously reported, but also at their 3' end, resulting in expression of additional four mRNA variants of BPAG1 and MACF1. These isoform-specific C-tails were able to bundle microtubules and bound to both EB1 and EB3, two microtubule plus end proteins. In the C2.7 cell line, knockdown of BPAG1a/b had no major effect on the organization of the microtubule and microfilament networks, but negatively affected endocytosis and maintenance of the Golgi apparatus structure, which became dispersed. Finally, knockdown of BPAG1a/b caused a specific decrease in the directness of cell migration, but did not impair initial cell adhesion. These data provide novel insights into the complexity of alternative splicing of Dst pre-mRNAs and into the role of BPAG1a/b in vesicular transport, Golgi apparatus structure as well as in migration in C2.7 myoblasts.

  20. BPAG1a and b Associate with EB1 and EB3 and Modulate Vesicular Transport, Golgi Apparatus Structure, and Cell Migration in C2.7 Myoblasts

    PubMed Central

    Poliakova, Kseniia; Adebola, Adijat; Leung, Conrad L.; Favre, Bertrand; Liem, Ronald K. H.; Schepens, Isabelle; Borradori, Luca

    2014-01-01

    BPAG1a and BPAG1b (BPAG1a/b) constitute two major isoforms encoded by the dystonin (Dst) gene and show homology with MACF1a and MACF1b. These proteins are members of the plakin family, giant multi-modular proteins able to connect the intermediate filament, microtubule and microfilament cytoskeletal networks with each other and to distinct cell membrane sites. They also serve as scaffolds for signaling proteins that modulate cytoskeletal dynamics. To gain better insights into the functions of BPAG1a/b, we further characterized their C-terminal region important for their interaction with microtubules and assessed the role of these isoforms in the cytoskeletal organization of C2.7 myoblast cells. Our results show that alternative splicing does not only occur at the 5′ end of Dst and Macf1 pre-mRNAs, as previously reported, but also at their 3′ end, resulting in expression of additional four mRNA variants of BPAG1 and MACF1. These isoform-specific C-tails were able to bundle microtubules and bound to both EB1 and EB3, two microtubule plus end proteins. In the C2.7 cell line, knockdown of BPAG1a/b had no major effect on the organization of the microtubule and microfilament networks, but negatively affected endocytosis and maintenance of the Golgi apparatus structure, which became dispersed. Finally, knockdown of BPAG1a/b caused a specific decrease in the directness of cell migration, but did not impair initial cell adhesion. These data provide novel insights into the complexity of alternative splicing of Dst pre-mRNAs and into the role of BPAG1a/b in vesicular transport, Golgi apparatus structure as well as in migration in C2.7 myoblasts. PMID:25244344

  1. Pressure Modulation of the Enzymatic Activity of Phospholipase A2, A Putative Membrane-Associated Pressure Sensor.

    PubMed

    Suladze, Saba; Cinar, Suleyman; Sperlich, Benjamin; Winter, Roland

    2015-10-07

    Phospholipases A2 (PLA2) catalyze the hydrolysis reaction of sn-2 fatty acids of membrane phospholipids and are also involved in receptor signaling and transcriptional pathways. Here, we used pressure modulation of the PLA2 activity and of the membrane's physical-chemical properties to reveal new mechanistic information about the membrane association and subsequent enzymatic reaction of PLA2. Although the effect of high hydrostatic pressure (HHP) on aqueous soluble and integral membrane proteins has been investigated to some extent, its effect on enzymatic reactions operating at the water/lipid interface has not been explored, yet. This study focuses on the effect of HHP on the structure, membrane binding and enzymatic activity of membrane-associated bee venom PLA2, covering a pressure range up to 2 kbar. To this end, high-pressure Fourier-transform infrared and high-pressure stopped-flow fluorescence spectroscopies were applied. The results show that PLA2 binding to model biomembranes is not significantly affected by pressure and occurs in at least two kinetically distinct steps. Followed by fast initial membrane association, structural reorganization of α-helical segments of PLA2 takes place at the lipid water interface. FRET-based activity measurements reveal that pressure has a marked inhibitory effect on the lipid hydrolysis rate, which decreases by 75% upon compression up to 2 kbar. Lipid hydrolysis under extreme environmental conditions, such as those encountered in the deep sea where pressures up to the kbar-level are encountered, is hence markedly affected by HHP, rendering PLA2, next to being a primary osmosensor, a good candidate for a sensitive pressure sensor in vivo.

  2. Spatiotemporal brain dynamics of emotional face processing modulations induced by the serotonin 1A/2A receptor agonist psilocybin.

    PubMed

    Bernasconi, Fosco; Schmidt, André; Pokorny, Thomas; Kometer, Michael; Seifritz, Erich; Vollenweider, Franz X

    2014-12-01

    Emotional face processing is critically modulated by the serotonergic system. For instance, emotional face processing is impaired by acute psilocybin administration, a serotonin (5-HT) 1A and 2A receptor agonist. However, the spatiotemporal brain mechanisms underlying these modulations are poorly understood. Here, we investigated the spatiotemporal brain dynamics underlying psilocybin-induced modulations during emotional face processing. Electrical neuroimaging analyses were applied to visual evoked potentials in response to emotional faces, following psilocybin and placebo administration. Our results indicate a first time period of strength (i.e., Global Field Power) modulation over the 168-189 ms poststimulus interval, induced by psilocybin. A second time period of strength modulation was identified over the 211-242 ms poststimulus interval. Source estimations over these 2 time periods further revealed decreased activity in response to both neutral and fearful faces within limbic areas, including amygdala and parahippocampal gyrus, and the right temporal cortex over the 168-189 ms interval, and reduced activity in response to happy faces within limbic and right temporo-occipital brain areas over the 211-242 ms interval. Our results indicate a selective and temporally dissociable effect of psilocybin on the neuronal correlates of emotional face processing, consistent with a modulation of the top-down control. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Structural and Functional Analysis of Two New Positive Allosteric Modulators of GluA2 Desensitization and Deactivation

    PubMed Central

    Timm, David E.; Benveniste, Morris; Weeks, Autumn M.; Nisenbaum, Eric S.

    2011-01-01

    At the dimer interface of the extracellular ligand-binding domain of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors a hydrophilic pocket is formed that is known to interact with two classes of positive allosteric modulators, represented by cyclothiazide and the ampakine 2H,3H,6aH-pyrrolidino(2,1–3′,2′)1,3-oxazino(6′,5′-5,4)benzo(e)1,4-dioxan-10-one (CX614). Here, we present structural and functional data on two new positive allosteric modulators of AMPA receptors, phenyl-1,4-bis-alkylsulfonamide (CMPDA) and phenyl-1,4-bis-carboxythiophene (CMPDB). Crystallographic data show that these compounds bind within the modulator-binding pocket and that substituents of each compound overlap with distinct moieties of cyclothiazide and CX614. The goals of the present study were to determine 1) the degree of modulation by CMPDA and CMPDB of AMPA receptor deactivation and desensitization; 2) whether these compounds are splice isoform-selective; and 3) whether predictions of mechanism of action could be inferred by comparing molecular interactions between the ligand-binding domain and each compound with those of cyclothiazide and CX614. CMPDB was found to be more isoform-selective than would be predicted from initial binding assays. It is noteworthy that these new compounds are both more potent and more effective and may be more clinically relevant than the AMPA receptor modulators described previously. PMID:21543522

  4. Earth Observing System/Advanced Microwave Sounding Unit-A (EOS/AMSU-A): Reliability prediction report for module A1 (channels 3 through 15) and module A2 (channels 1 and 2)

    NASA Technical Reports Server (NTRS)

    Geimer, W.

    1995-01-01

    This report documents the final reliability prediction performed on the Earth Observing System/Advanced Microwave Sounding Unit-A (EOS/AMSU-A). The A1 Module contains Channels 3 through 15, and is referred to herein as 'EOS/AMSU-A1'. The A2 Module contains Channels 1 and 2, and is referred herein as 'EOS/AMSU-A2'. The 'specified' figures were obtained from Aerojet Reports 8897-1 and 9116-1. The predicted reliability figure for the EOS/AMSU-A1 meets the specified value and provides a Mean Time Between Failures (MTBF) of 74,390 hours. The predicted reliability figure for the EOS/AMSU-A2 meets the specified value and provides a MTBF of 193,110 hours.

  5. The Alzheimer Disease Protective Mutation A2T Modulates Kinetic and Thermodynamic Properties of Amyloid-β (Aβ) Aggregation*

    PubMed Central

    Benilova, Iryna; Gallardo, Rodrigo; Ungureanu, Andreea-Alexandra; Castillo Cano, Virginia; Snellinx, An; Ramakers, Meine; Bartic, Carmen; Rousseau, Frederic; Schymkowitz, Joost; De Strooper, Bart

    2014-01-01

    Missense mutations in alanine 673 of the amyloid precursor protein (APP), which corresponds to the second alanine of the amyloid β (Aβ) sequence, have dramatic impact on the risk for Alzheimer disease; A2V is causative, and A2T is protective. Assuming a crucial role of amyloid-Aβ in neurodegeneration, we hypothesized that both A2V and A2T mutations cause distinct changes in Aβ properties that may at least partially explain these completely different phenotypes. Using human APP-overexpressing primary neurons, we observed significantly decreased Aβ production in the A2T mutant along with an enhanced Aβ generation in the A2V mutant confirming earlier data from non-neuronal cell lines. More importantly, thioflavin T fluorescence assays revealed that the mutations, while having little effect on Aβ42 peptide aggregation, dramatically change the properties of the Aβ40 pool with A2V accelerating and A2T delaying aggregation of the Aβ peptides. In line with the kinetic data, Aβ A2T demonstrated an increase in the solubility at equilibrium, an effect that was also observed in all mixtures of the A2T mutant with the wild type Aβ40. We propose that in addition to the reduced β-secretase cleavage of APP, the impaired propensity to aggregate may be part of the protective effect conferred by A2T substitution. The interpretation of the protective effect of this mutation is thus much more complicated than proposed previously. PMID:25253695

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

    PubMed

    Meng, Xian-Guo; Yue, Shou-Wei

    2014-01-01

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

  7. 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

  8. Self-pulsing in a 2 km single-mode fiber with the seed source broadened via WNS phase modulation

    NASA Astrophysics Data System (ADS)

    Zha, Congwen; Sun, Yinhong; Wang, Yanshan; Li, Tenglong; Peng, Wanjing; Ma, Yi; Zhang, Kai

    2018-03-01

    The seed source with spectral linewidth broadening via phase modulation is potential to achieve the higher output power with effective SBS suppression. However, self-pulsing from the amplifier output is harmful. In this work, we study the self-pulsing characteristics in a long single-mode fiber with lower self-pulsing threshold instead of the high power amplifier. We provide a powerful experimental support for the self-pulsing mechanism in high-power narrow-linewidth fiber lasers, which is important for further output power scaling.

  9. A2A-D2 receptor-receptor interaction modulates gliotransmitter release from striatal astrocyte processes.

    PubMed

    Cervetto, Chiara; Venturini, Arianna; Passalacqua, Mario; Guidolin, Diego; Genedani, Susanna; Fuxe, Kjell; Borroto-Esquela, Dasiel O; Cortelli, Pietro; Woods, Amina; Maura, Guido; Marcoli, Manuela; Agnati, Luigi F

    2017-01-01

    Evidence for striatal A2A-D2 heterodimers has led to a new perspective on molecular mechanisms involved in schizophrenia and Parkinson's disease. Despite the increasing recognition of astrocytes' participation in neuropsychiatric disease vulnerability, involvement of striatal astrocytes in A2A and D2 receptor signal transmission has never been explored. Here, we investigated the presence of D2 and A2A receptors in isolated astrocyte processes prepared from adult rat striatum by confocal imaging; the effects of receptor activation were measured on the 4-aminopyridine-evoked release of glutamate from the processes. Confocal analysis showed that A2A and D2 receptors were co-expressed on the same astrocyte processes. Evidence for A2A-D2 receptor-receptor interactions was obtained by measuring the release of the gliotransmitter glutamate: D2 receptors inhibited the glutamate release, while activation of A2A receptors, per se ineffective, abolished the effect of D2 receptor activation. The synthetic D2 peptide VLRRRRKRVN corresponding to the receptor region involved in electrostatic interaction underlying A2A-D2 heteromerization abolished the ability of the A2A receptor to antagonize the D2 receptor-mediated effect. Together, the findings are consistent with heteromerization of native striatal astrocytic A2A-D2 receptors that via allosteric receptor-receptor interactions could play a role in the control of striatal glutamatergic transmission. These new findings suggest possible new pathogenic mechanisms and/or therapeutic approaches to neuropsychiatric disorders. © 2016 International Society for Neurochemistry.

  10. Cell Migration

    PubMed Central

    Trepat, Xavier; Chen, Zaozao; Jacobson, Ken

    2015-01-01

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

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

    PubMed

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

    2016-01-01

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

  12. SK3/TRPC1/Orai1 complex regulates SOCE-dependent colon cancer cell migration: a novel opportunity to modulate anti-EGFR mAb action by the alkyl-lipid Ohmline

    PubMed Central

    Guéguinou, Maxime; Harnois, Thomas; Crottes, David; Uguen, Arnaud; Deliot, Nadine; Gambade, Audrey; Chantôme, Aurélie; Haelters, Jean Pierre; Jaffrès, Paul Alain; Jourdan, Marie Lise; Weber, Günther; Soriani, Olivier; Bougnoux, Philippe; Mignen, Olivier; Bourmeyster, Nicolas; Constantin, Bruno; Lecomte, Thierry

    2016-01-01

    Background Barely 10-20% of patients with metastatic colorectal cancer (mCRC) receive a clinical benefit from the use of anti-EGFR monoclonal antibodies (mAbs). We hypothesized that this could depends on their efficiency to reduce Store Operated Calcium Entry (SOCE) that are known to enhance cancer cells. Results In the present study, we demonstrate that SOCE promotes migration of colon cancer cell following the formation of a lipid raft ion channel complex composed of TRPC1/Orai1 and SK3 channels. Formation of this complex is stimulated by the phosphorylation of the reticular protein STIM1 by EGF and activation of the Akt pathway. Our data show that, in a positive feedback loop SOCE activates both Akt pathway and SK3 channel activity which lead to SOCE amplification. This amplification occurs through the activation of Rac1/Calpain mediated by Akt. We also show that Anti-EGFR mAbs can modulate SOCE and cancer cell migration through the Akt pathway. Interestingly, the alkyl-lipid Ohmline, which we previously showed to be an inhibitor of SK3 channel, can dissociated the lipid raft ion channel complex through decreased phosphorylation of Akt and modulation of mAbs action. Conclusions This study demonstrates that the inhibition of the SOCE-dependent colon cancer cell migration trough SK3/TRPC1/Orai1 channel complex by the alkyl-lipid Ohmline may be a novel strategy to modulate Anti-EGFR mAb action in mCRC. PMID:27102434

  13. CD147 regulates cancer migration via direct interaction with Annexin A2 and DOCK3-β-catenin-WAVE2 signaling.

    PubMed

    Cui, Hong-Yong; Wang, Shi-Jie; Miao, Ji-Yu; Fu, Zhi-Guang; Feng, Fei; Wu, Jiao; Yang, Xiang-Min; Chen, Zhi-Nan; Jiang, Jian-Li

    2016-02-02

    The acquisition of inappropriate migratory feature is crucial for tumor metastasis. It has been suggested that CD147 and Annexin A2 are involved in regulating tumor cell movement, while the regulatory mechanisms are far from clear. In this study, we demonstrated that CD147 physically interacted with the N-terminal domain of Annexin A2 and decreased Annexin A2 phosphorylation on tyrosine 23. In vitro kinase assay showed that the I domain of CD147 was indispensable for CD147-mediated downregulation of Annexin A2 phosphorylation by Src. Furthermore, we determined that p-Annexin A2 promoted the expression of dedicator of cytokinesis 3 (DOCK3) and DOCK3 blocked β-catenin nuclear translocation, resulting in inhibition of β-catenin signaling. In addition, DOCK3 inhibited lamellipodium dynamics and tumor cell movement. Also, we found that β-catenin signaling increased WAVE2 expression. Therefore, DOCK3 was characterized as a negative regulator of WAVE2 expression via inhibiting β-catenin signaling. Our study provides the first evidence that CD147 promotes tumor cell movement and metastasis via direct interaction with Annexin A2 and DOCK3-β-catenin-WAVE2 signaling axis.

  14. CD147 regulates cancer migration via direct interaction with Annexin A2 and DOCK3-β-catenin-WAVE2 signaling

    PubMed Central

    Feng, Fei; Wu, Jiao; Yang, Xiang-Min; Chen, Zhi-Nan; Jiang, Jian-Li

    2016-01-01

    The acquisition of inappropriate migratory feature is crucial for tumor metastasis. It has been suggested that CD147 and Annexin A2 are involved in regulating tumor cell movement, while the regulatory mechanisms are far from clear. In this study, we demonstrated that CD147 physically interacted with the N-terminal domain of Annexin A2 and decreased Annexin A2 phosphorylation on tyrosine 23. In vitro kinase assay showed that the I domain of CD147 was indispensable for CD147-mediated downregulation of Annexin A2 phosphorylation by Src. Furthermore, we determined that p-Annexin A2 promoted the expression of dedicator of cytokinesis 3 (DOCK3) and DOCK3 blocked β-catenin nuclear translocation, resulting in inhibition of β-catenin signaling. In addition, DOCK3 inhibited lamellipodium dynamics and tumor cell movement. Also, we found that β-catenin signaling increased WAVE2 expression. Therefore, DOCK3 was characterized as a negative regulator of WAVE2 expression via inhibiting β-catenin signaling. Our study provides the first evidence that CD147 promotes tumor cell movement and metastasis via direct interaction with Annexin A2 and DOCK3-β-catenin-WAVE2 signaling axis. PMID:26716413

  15. Impact of recurrent hypoglycemic stress on hindbrain A2 nerve cell energy metabolism and catecholamine biosynthesis: modulation by estradiol.

    PubMed

    Tamrakar, Pratistha; Briski, Karen P

    2017-01-01

    It is unclear if habituation of hindbrain A2 metabolo‑sensory neurons to recurrent insulin-induced hypoglycemia (RIIH) correlates with estradiol-dependent adjustments in energy metabolism that favor positive energy balance. Laser-microdissected A2 cells from estradiolor oil-implanted ovariectomized female rats were analyzed by Western blot to assess effects of three prior daily insulin injections on basal and hypoglycemic patterns of catecholamine biosynthetic enzyme dopamine-beta-hydroxylase (DβH) and rate-limiting energy pathway enzyme protein expression. Precedent hypoglycemia respectively decreased or increased baseline DβH expression in estradiol- (E) vs. oil (O)-treated rats; this protein profile was further suppressed or augmented in those animals at 2 hr after re-induction of hypoglycemia. These data suggest that estradiol may curtail A2 noradrenergic‑controlled functions both in the midst of and between hypoglycemic bouts. Results also show that prior hypoglycemia exposure upregulated A2 neuron glycolytic enzyme protein levels when E was present, and exerted differential effects on basal and hypoglycemia-associated respiratory chain and fatty acid synthetic pathway enzyme expression. E may thus accordingly amplify glycolysis-derived metabolites/energy, coupled with reduced reliance on oxidative phosphorylation, and activate the fatty acid synthetic pathway during RIIH. E may also be of benefit by preventing maladaptive reductions in A2 neuron Krebs cycle/electron transport enzyme expression during re-exposure to hypoglycemia. Augmentation of negative energy balance during this recurring metabolic stress in the absence of E is a likely impetus for augmented vs. decreased A2 signaling of energy imbalance by DβH in O vs. E rats during RIIH.

  16. Adenosine A2A receptors modulate the dopamine D2 receptor-mediated inhibition of synaptic transmission in the mouse prefrontal cortex.

    PubMed

    Real, Joana I; Simões, Ana Patrícia; Cunha, Rodrigo A; Ferreira, Samira G; Rial, Daniel

    2018-05-01

    Prefrontal cortex (PFC) circuits are modulated by dopamine acting on D 1 - and D 2 -like receptors, which are pharmacologically exploited to manage neuropsychiatric conditions. Adenosine A 2A receptors (A 2 A R) also control PFC-related responses and A 2 A R antagonists are potential anti-psychotic drugs. As tight antagonistic A 2 A R-D 2 R and synergistic A 2 A R-D 1 R interactions occur in other brain regions, we now investigated the crosstalk between A 2 A R and D 1 /D 2 R controlling synaptic transmission between layers II/III and V in mouse PFC coronal slices. Dopamine decreased synaptic transmission, a presynaptic effect based on the parallel increase in paired-pulse responses. Dopamine inhibition was prevented by the D 2 R-like antagonist sulpiride but not by the D 1 R antagonist SCH23390 and was mimicked by the D 2 R agonist sumanirole, but not by the agonists of either D 4 R (A-412997) or D 3 R (PD128907). Dopamine inhibition was prevented by the A 2 A R antagonist, SCH58261, and attenuated in A 2 A R knockout mice. Accordingly, triple-labelling immunocytochemistry experiments revealed the co-localization of A 2 A R and D 2 R immunoreactivity in glutamatergic (vGluT1-positive) nerve terminals of the PFC. This reported positive A 2 A R-D 2 R interaction controlling PFC synaptic transmission provides a mechanistic justification for the anti-psychotic potential of A 2 A R antagonists. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  17. The neuronal Ca(2+) -binding protein 2 (NECAB2) interacts with the adenosine A(2A) receptor and modulates the cell surface expression and function of the receptor.

    PubMed

    Canela, Laia; Luján, Rafael; Lluís, Carme; Burgueño, Javier; Mallol, Josefa; Canela, Enric I; Franco, Rafael; Ciruela, Francisco

    2007-09-01

    Heptaspanning membrane also known as G protein-coupled receptors (GPCR) do interact with a variety of intracellular proteins whose function is regulate receptor traffic and/or signaling. Using a yeast two-hybrid screen, NECAB2, a neuronal calcium binding protein, was identified as a binding partner for the adenosine A(2A) receptor (A(2A)R) interacting with its C-terminal domain. Co-localization, co-immunoprecipitation and pull-down experiments showed a close and specific interaction between A(2A)R and NECAB2 in both transfected HEK-293 cells and also in rat striatum. Immunoelectron microscopy detection of NECAB2 and A(2A)R in the rat striatopallidal structures indicated that both proteins are co-distributed in the same glutamatergic nerve terminals. The interaction of NECAB2 with A(2A)R modulated the cell surface expression, the ligand-dependent internalization and the receptor-mediated activation of the MAPK pathway. Overall, these results show that A(2A)R interacts with NECAB2 in striatal neurones co-expressing the two proteins and that the interaction is relevant for A(2A)R function.

  18. A 2D Micromodel Study of Fines Migration and Clogging Behavior in Porous Media: Implications of Fines on Methane Extraction from Hydrate-Bearing Sediments

    NASA Astrophysics Data System (ADS)

    Cao, S. C.; Jang, J.; Waite, W. F.; Jafari, M.; Jung, J.

    2017-12-01

    Fine-grained sediment, or "fines," exist nearly ubiquitously in natural sediment, even in the predominantly coarse-grained sediments that host gas hydrates. Fines within these sandy sediments can play a crucial role during gas hydrate production activities. During methane extraction, several processes can alter the mobility and clogging potential of fines: 1) fluid flow as the formation is depressurized to release methane from hydrate; 2) pore-fluid chemistry shifts as pore-fluid brine freshens due to pure water released from dissociating hydrate; 3) the presence of a moving gas/water interface as gas evolves from dissociating hydrate and moves through the reservoir toward the production well. To evaluate fines migration and clogging behavior changes resulting from methane gas production and pore-water freshening during hydrate dissociation, 2D micromodel experiments have been conducted on a selection of pure fines, pore-fluids, and micromodel pore-throat sizes. Additionally, tests have been run with and without an invading gas phase (CO2) to test the significance of a moving meniscus on fines mobility and clogging. The endmember fine particles chosen for this research include silica silt, mica, calcium carbonate, diatoms, kaolinite, illite, and bentonite (primarily made of montmorillonite). The pore fluids include deionized water, sodium chloride brine (2M concentration), and kerosene. The microfluidic pore models, used as porous media analogs, were fabricated with pore-throat widths of 40, 60, and 100 µm. Results from this research show that in addition to the expected dependence of clogging on the ratio of particle-to-pore-throat size, pore-fluid chemistry is also a significant factor because the interaction between a particular type of fine and pore fluid influences that fine's capacity to cluster, clump together and effectively increase its particle "size" relative to the pore-throat width. The presence of a moving gas/fluid meniscus increases the clogging

  19. Modulation of mitochondrial function and morphology by interaction of Omi/HtrA2 with the mitochondrial fusion factor OPA1

    SciTech Connect

    Kieper, Nicole; Holmstroem, Kira M.; Ciceri, Dalila

    2010-04-15

    Loss of Omi/HtrA2 function leads to nerve cell loss in mouse models and has been linked to neurodegeneration in Parkinson's and Huntington's disease. Omi/HtrA2 is a serine protease released as a pro-apoptotic factor from the mitochondrial intermembrane space into the cytosol. Under physiological conditions, Omi/HtrA2 is thought to be involved in protection against cellular stress, but the cytological and molecular mechanisms are not clear. Omi/HtrA2 deficiency caused an accumulation of reactive oxygen species and reduced mitochondrial membrane potential. In Omi/HtrA2 knockout mouse embryonic fibroblasts, as well as in Omi/HtrA2 silenced human HeLa cells and Drosophila S2R+ cells, we found elongatedmore » mitochondria by live cell imaging. Electron microscopy confirmed the mitochondrial morphology alterations and showed abnormal cristae structure. Examining the levels of proteins involved in mitochondrial fusion, we found a selective up-regulation of more soluble OPA1 protein. Complementation of knockout cells with wild-type Omi/HtrA2 but not with the protease mutant [S306A]Omi/HtrA2 reversed the mitochondrial elongation phenotype and OPA1 alterations. Finally, co-immunoprecipitation showed direct interaction of Omi/HtrA2 with endogenous OPA1. Thus, we show for the first time a direct effect of loss of Omi/HtrA2 on mitochondrial morphology and demonstrate a novel role of this mitochondrial serine protease in the modulation of OPA1. Our results underscore a critical role of impaired mitochondrial dynamics in neurodegenerative disorders.« less

  20. Annexin 1 Modulates Monocyte-Endothelial Cell Interaction In Vitro and Cell Migration In Vivo in the Human SCID Mouse Transplantation Model1

    PubMed Central

    Perretti, Mauro; Ingegnoli, Francesca; Wheller, Samantha K.; Blades, Mark C.; Solito, Egle; Pitzalis, Costantino

    2015-01-01

    The effect of the glucocorticoid inducible protein annexin 1 (ANXA1) on the process of monocytic cell migration was studied using transfected U937 cells expressing variable protein levels. An antisense (AS) (36.4AS; ~50% less ANXA1) and a sense (S) clone (15S; overexpressing the bioactive 24-kDa fragment) together with the empty plasmid CMV clone were obtained and compared with wild-type U937 cells in various models of cell migration in vitro and in vivo. 15S-transfected U937 cells displayed a reduced (50%) degree of trans-endothelial migration in response to stromal cell-derived factor-1α (CXC chemokine ligand 12 (CXCL12)). In addition, the inhibitory role of endogenous ANXA1 on U937 cell migration in vitro was confirmed by the potentiating effect of a neutralizing anti-ANXA1 serum. Importantly, overexpression of ANXA1 in clone 15S inhibited the extent of cell migration into rheumatoid synovial grafts transplanted into SCID mice. ANXA1 inhibitory effects were not due to modifications in adhesion molecule or CXCL12 receptor (CXCR4) expression as shown by the similar amounts of surface molecules found in transfected and wild-type U937 cells. Likewise, an equal chemotactic response to CXCL12 in vitro excluded an intrinsic defect in cell motility in clones 15S and 36.4AS. These data strongly support the notion that ANXA1 critically interferes with a leukocyte endothelial step essential for U937 cell, and possibly monocyte, transmigration both in vitro and in vivo. PMID:12165536

  1. Involvement of adenosine A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of cocaine and methamphetamine in rats.

    PubMed

    Justinova, Zuzana; Ferre, Sergi; Segal, Pavan N; Antoniou, Katerina; Solinas, Marcello; Pappas, Lara A; Highkin, Jena L; Hockemeyer, Jorg; Munzar, Patrik; Goldberg, Steven R

    2003-12-01

    Adenosine, by acting on adenosine A1 and A2A receptors, is known to antagonistically modulate dopaminergic neurotransmission. We have recently reported that nonselective adenosine receptor antagonists (caffeine and 3,7-dimethyl-1-propargylxanthine) can partially substitute for the discriminative-stimulus effects of methamphetamine. In the present study, by using more selective compounds, we investigated the involvement of A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of both cocaine and methamphetamine. The effects of the A1 receptor agonist N6-cyclopentyladenosine (CPA; 0.01-0.1 mg/kg) and antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT; 1.3-23.7 mg/kg) and the A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680; 0.03-0.18 mg/kg) and antagonist 3-(3-hydroxypropyl)-8-(3-methoxystyryl)-7-methyl-1-propargylxanthin phosphate disodium salt (MSX-3; 1-56 mg/kg) were evaluated in rats trained to discriminate either 1 mg/kg methamphetamine or 10 mg/kg cocaine from saline under a fixed-ratio 10 schedule of food presentation. The A1 and A2A receptor antagonists (CPT and MSX-3) both produced high levels of drug-lever selection when substituted for either methamphetamine or cocaine and significantly shifted dose-response curves of both psychostimulants to the left. Unexpectedly, the A2A receptor agonist CGS 21680 also produced drug-appropriate responding (although at lower levels) when substituted for the cocaine-training stimulus, and both CGS 21680 and the A1 receptor agonist CPA significantly shifted the cocaine dose-response curve to the left. In contrast, both agonists did not produce significant levels of drug-lever selection when substituted for the methamphetamine-training stimulus and failed to shift the methamphetamine dose-response curve. Therefore, adenosine A1 and A2A receptors appear to play important but differential roles in the modulation of the

  2. Genetic variation in SLC7A2 interacts with calcium and magnesium intakes in modulating the risk of colorectal polyps.

    PubMed

    Sun, Pin; Zhu, Xiangzhu; Shrubsole, Martha J; Ness, Reid M; Hibler, Elizabeth A; Cai, Qiuyin; Long, Jirong; Chen, Zhi; Li, Guoliang; Hou, Lifang; Smalley, Walter E; Edwards, Todd L; Giovannucci, Edward; Zheng, Wei; Dai, Qi

    2017-09-01

    Solute carrier family 7, member 2 (SLC7A2) gene encodes a protein called cationic amino acid transporter 2, which mediates the transport of arginine, lysine and ornithine. l-Arginine is necessary for cancer development and progression, including an important role in colorectal cancer pathogenesis. Furthermore, previous studies found that both calcium and magnesium inhibit the transport of arginine. Thus, calcium, magnesium or calcium:magnesium intake ratio may interact with polymorphisms in the SLC7A2 gene in association with colorectal cancer. We conducted a two-phase case-control study within the Tennessee Colorectal Polyps Study. In the first phase, 23 tagging single-nucleotide polymorphisms in the SLC7A2 gene were included for 725 colorectal adenoma cases and 755 controls. In the second phase conducted in an independent set of 607 cases and 2113 controls, we replicated the significant findings in the first phase. We observed that rs2720574 significantly interacted with calcium:magnesium intake ratio in association with odds of adenoma, particularly multiple/advanced adenoma. In the combined analysis, among those with a calcium:magnesium intake ratio below 2.78, individuals who carried GC/CC genotypes demonstrated higher odds of adenoma [OR (95% CI):1.36 (1.11-1.68)] and multiple/advanced adenoma [OR (95% CI): 1.68 (1.28, 2.20)] than those who carried the GG genotype. The P values for interactions between calcium:magnesium intake ratio and rs2720574 were .002 for all adenomas and <.001 for multiple/advanced adenoma. Among those with the GG genotype, a high calcium:magnesium ratio was associated with increased odds of colorectal adenoma [OR (95% CI): 1.73 (1.27-2.36)] and advanced/multiple adenomas [1.62 (1.05-2.50)], whereas among those with the GC/CC genotypes, high calcium:magnesium ratio was related to reduced odds of colorectal adenoma [0.64 (0.42-0.99)] and advanced/multiple adenomas [0.55 (0.31-1.00)]. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. EphA2 modulates radiosensitive of hepatocellular carcinoma cells via p38/mitogen-activated protein kinase-mediated signal pathways.

    PubMed

    Jin, Qiao; Li, Xiangjun; Cao, Peiguo

    2015-10-01

    This experiment was conducted to investigate the role of EPH receptor A2 (EphA2) in the modulation of radiosensitivity of hepatic cellular cancer (HCC) cells and to determine whether p38/mitogen-activated protein kinase (p38MAPK) signaling mediated EphA2 function in this respect. The protein expressions of EphA2 and phosphorylated p38MAPK were tested in HCC and normal hepatic tissues. In HCC 97H cells, EphA2 was overexpressed and knocked out by transfection with EphA2 expression vector and EphA2-ShRNA, respectively, prior to cell exposure to low-dose irradiation. Significantly upregulated EphA2 and phosphorylated p38MAPK were observed in HCC tissues, compared with those in normal hepatic tissues. Low-dose irradiation (1 Gy) only caused minor damage to HCC 97H cells, as assessed by alterations in cell viability, apoptosis rate, and cell healing capacity (p = 0.072, p = 0.078, and p = 0.069 respectively). However, EphA2 knock-out in HCC 97H cells induced significant reduction in cell viability and cell healing capacity after these cells were subjected to low-dose irradiation. Apoptosis rate underwent dramatic increase (p < 0.01). By contrast, EphA2 overexpression in HCC 97H cells reversed these effects and enhanced cell colony formation rate, thus displaying remarkable attenuation of radiosensitivity of HCC 97H cells. Further, SB203580, a specific inhibitor of p38MAPK, was added to HCC 97H cells over-expressing EphA2. The effect of EphA2 overexpression on the radiosensitivity of HCC 97H cells was abrogated. Thus, the present study indicates that EphA2 have the ability to negatively regulate the radiosensitivity of HCC 97H cells, which mainly depends on 38MAPK-mediated signal pathways. Copyright © 2015. Published by Elsevier Taiwan.

  4. Bidirectional signalling between EphA2 and ephrinA1 increases tubular cell attachment, laminin secretion and modulates erythropoietin expression after renal hypoxic injury.

    PubMed

    Rodriguez, Stéphane; Rudloff, Stefan; Koenig, Katrin Franziska; Karthik, Swapna; Hoogewijs, David; Huynh-Do, Uyen

    2016-08-01

    Acute kidney injury (AKI) is common in hospitalized patients and has a poor prognosis, the severity of AKI being linked to progression to chronic kidney disease. This stresses the need to search for protective mechanisms during the acute phase. We investigated kidney repair after hypoxic injury using a rat model of renal artery branch ligation, which led to an oxygen gradient vertical to the corticomedullary axis. Three distinct zones were observed: tubular necrosis, infarction border zone and preserved normal tissue. EphA2 is a receptor tyrosine kinase with pivotal roles in cell architecture, migration and survival, upon juxtacrine contact with its membrane-bound ligand EphrinA1. Following hypoxia, EphA2 was up-regulated in cortical and medullary tubular cells, while EphrinA1 was up-regulated in interstitial cells adjacent to peritubular capillaries. Moreover, erythropoietin (EPO) messenger RNA (mRNA) was strongly expressed in the border zone of infarcted kidney within the first 6 h. To gain more insight into the biological impact of EphA2 and EphrinA1 up-regulation, we activated the signalling pathways in vitro using recombinant EphrinA1/Fc or EphA2/Fc proteins. Stimulation of EphA2 forward signalling in the proximal tubular cell line HK2 increased cell attachment and laminin secretion at the baso-lateral side. Conversely, activation of reverse signalling through EphrinA1 expressed by Hep3B cells promoted EPO production at both the transcriptional and protein level. Strikingly, in co-culture experiments, juxtacrine contact between EphA2 expressing MDCK and EphrinA1 expressing Hep3B was sufficient to induce a significant up-regulation of EPO mRNA production in the latter cells, even in the absence of hypoxic conditions. The synergistic effects of EphA2 and hypoxia led to a 15-20-fold increase of EPO expression. Collectively, our results suggest an important role of EphA2/EphrinA1 signalling in kidney repair after hypoxic injury through stimulation of (i) tubular

  5. Laminin-5γ-2 (LAMC2) Is Highly Expressed in Anaplastic Thyroid Carcinoma and Is Associated With Tumor Progression, Migration, and Invasion by Modulating Signaling of EGFR

    PubMed Central

    Kanojia, Deepika; Okamoto, Ryoko; Jain, Saket; Madan, Vikas; Chien, Wenwen; Sampath, Abhishek; Ding, Ling-Wen; Xuan, Meng; Said, Jonathan W.; Doan, Ngan B.; Liu, Li-Zhen; Yang, Henry; Gery, Sigal; Braunstein, Glenn D.; Koeffler, H. Phillip

    2014-01-01

    Context: Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy having no effective treatment. Laminin subunit-γ-2 (LAMC2) is an epithelial basement membrane protein involved in cell migration and tumor invasion and might represent an ideal target for the development of novel therapeutic approaches for ATC. Objective: The objective of the investigation was to study the role of LAMC2 in ATC tumorigenesis. Design: LAMC2 expression was evaluated by RT-PCR, Western blotting, and immunohistochemistry in tumor specimens, adjacent noncancerous tissues, and cell lines. The short hairpin RNA (shRNA) approach was used to investigate the effect of LAMC2 knockdown on the tumorigenesis of ATC. Results: LAMC2 was highly expressed in ATC samples and cell lines compared with normal thyroid tissues. Silencing LAMC2 by shRNA in ATC cells moderately inhibited cell growth in liquid culture and dramatically decreased growth in soft agar and in xenografts growing in immunodeficient mice. Silencing LAMC2 caused cell cycle arrest and significantly suppressed the migration, invasion, and wound healing of ATC cells. Rescue experiments by overexpressing LAMC2 in LAMC2 knockdown cells reversed the inhibitory effects as shown by increased cell proliferation and colony formation. Microarray data demonstrated that LAMC2 shRNA significantly altered the expression of genes associated with migration, invasion, proliferation, and survival. Immunoprecipitation studies showed that LAMC2 bound to epidermal growth factor receptor (EGFR) in the ATC cells. Silencing LAMC2 partially blocked epidermal growth factor-mediated activation of EGFR and its downstream pathway. Interestingly, cetuximab (an EGFR blocking antibody) or EGFR small interfering RNA additively enhanced the antiproliferative activity of the LAMC2 knockdown ATC cells compared with the control cells. Conclusions: To our knowledge, this is the first report investigating the effect of LAMC2 on cell growth, cell cycle, migration

  6. CD98hc (SLC3A2) Loss Protects Against Ras-Driven Tumorigenesis by Modulating Integrin-Mediated Mechanotransduction

    PubMed Central

    Estrach, Soline; Lee, Sin-Ae; Boulter, Etienne; Pisano, Sabrina; Errante, Aurélia; Tissot, Floriane S.; Cailleteau, Laurence; Pons, Catherine; Ginsberg, Mark H.; Féral, Chloé C.

    2016-01-01

    CD98hc (SLC3A2) is the heavy chain component of the dimeric transmembrane glycoprotein CD98, which comprises the large neutral amino acid transporter LAT1 (SLC7A5) in cells. Overexpression of CD98hc occurs widely in cancer cells, and is associated with poor prognosis clinically, but its exact contributions to tumorigenesis are uncertain. In this study, we showed that that genetic deficiency of CD98hc protects against Ras-driven skin carcinogenesis. Deleting CD98hc after tumor induction was also sufficient to cause regression of existing tumors. Investigations into the basis for these effects defined two new functions of CD98hc that contribute to epithelial cancer beyond an intrinsic effect on CD98hc on tumor cell proliferation. First, CD98hc increased the stiffness of the tumor microenvironment. Second, CD98hc amplified the capacity of cells to respond to matrix rigidity, an essential factor in tumor development. Mechanistically, CD98hc mediated this stiffness-sensing by increasing Rho kinase (ROCK) activity, resulting in increased transcription mediated by YAP/TAZ, a nuclear relay for mechanical signals. Our results suggest that CD98hc contributes to carcinogenesis by amplifying a positive feedback loop which increases both extracellular matrix stiffness and resulting cellular responses. This work supports a rationale to explore the use of CD98hc inhibitors as cancer therapeutics, PMID:25267066

  7. Rubus idaeus extract suppresses migration and invasion of human oral cancer by inhibiting MMP-2 through modulation of the Erk1/2 signaling pathway.

    PubMed

    Huang, Yi-Wen; Chuang, Chun-Yi; Hsieh, Yih-Shou; Chen, Pei-Ni; Yang, Shun-Fa; Shih-Hsuan-Lin; Chen, Yang-Yu; Lin, Chiao-Wen; Chang, Yu-Chao

    2017-03-01

    Raspberries (Rubus idaeus L.) have been extensively studies worldwide because of their beneficial effects on health. Recently reports indicate that crude extracts of Rubus idaeus (RIE) have antioxidant and anticancer ability. The aim of this study was to evaluate the mechanism of its antimetastatic ability in oral cancer cells. In this study, SCC-9 and SAS oral cancer cells were subjected to a treatment with RIE and then analyzed the effect of RIE on migration and invasion. The addition of RIE inhibited the migration and invasion ability of oral cancer cells. Real time PCR, western blot and zymography analysis demonstrated that mRNA, protein expression and enzyme activity of matrix metalloproteinases-2 (MMP-2) were down-regulated by RIE. Moreover, the phosphorylation of Focal adhesion kinase (FAK), src, and extracellular signal-regulated kinase (ERK) were inhibited after RIE treatment. In conclusion, these results demonstrated that RIE exerted an inhibitory effect of migration and invasion in oral cancer cells and alter metastasis by suppression of MMP-2 expression through FAK/Scr/ERK signaling pathway. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1037-1046, 2017. © 2016 Wiley Periodicals, Inc.

  8. Rubus idaeus Inhibits Migration and Invasion of Human Nasopharyngeal Carcinoma Cells by Suppression of MMP-2 through Modulation of the ERK1/2 Pathway.

    PubMed

    Hsin, Chung-Han; Huang, Cheng-Chen; Chen, Pei-Ni; Hsieh, Yih-Shou; Yang, Shun-Fa; Ho, Yu-Ting; Lin, Chiao-Wen

    2017-01-01

    Nasopharyngeal carcinoma (NPC) is characterized by a high incidence of metastasis in the neck lymph nodes, resulting in a poor prognosis and posing challenges for treatment. In this study, we investigated the in vitro antimetastatic properties of Rubus idaeus extract (RIE) on human nasopharyngeal carcinoma cells. HONE-1, NPC-39 and NPC-BM cells were subjected to RIE treatment, and effects on the migration and invasion of tumor cells were analyzed. The results showed that RIE suppressed the migration and invasion of NPC cells. Gelatin zymography assay, Western blotting and real-time PCR showed that matrix metalloproteinases-2 (MMP-2) enzyme activity, protein expression and mRNA levels were down-regulated by RIE treatment. To identify the signaling pathway, mitogen-activated protein kinase proteins were examined, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of RIE. In summary, our data showed that RIE inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by down-regulating the ERK1/2 signaling pathway, suggesting that Rubus idaeus may serve as chemotherapeutic and chemopreventive agent for NPC.

  9. Leupaxin stimulates adhesion and migration of prostate cancer cells through modulation of the phosphorylation status of the actin-binding protein caldesmon

    PubMed Central

    Schmidt, Thomas; Bremmer, Felix; Burfeind, Peter; Kaulfuß, Silke

    2015-01-01

    The focal adhesion protein leupaxin (LPXN) is overexpressed in a subset of prostate cancers (PCa) and is involved in the progression of PCa. In the present study, we analyzed the LPXN-mediated adhesive and cytoskeletal changes during PCa progression. We identified an interaction between the actin-binding protein caldesmon (CaD) and LPXN and this interaction is increased during PCa cell migration. Furthermore, knockdown of LPXN did not affect CaD expression but reduced CaD phosphorylation. This is known to destabilize the affinity of CaD to F-actin, leading to dynamic cell structures that enable cell motility. Thus, downregulation of CaD increased migration and invasion of PCa cells. To identify the kinase responsible for the LPXN-mediated phosphorylation of CaD, we used data from an antibody array, which showed decreased expression of TGF-beta-activated kinase 1 (TAK1) after LPXN knockdown in PC-3 PCa cells. Subsequent analyses of the downstream kinases revealed the extracellular signal-regulated kinase (ERK) as an interaction partner of LPXN that facilitates CaD phosphorylation during LPXN-mediated PCa cell migration. In conclusion, we demonstrate that LPXN directly influences cytoskeletal dynamics via interaction with the actin-binding protein CaD and regulates CaD phosphorylation by recruiting ERK to highly dynamic structures within PCa cells. PMID:26079947

  10. Secreted phospholipase A2 inhibitor modulates fatty acid composition and reduces obesity-induced inflammation in Beagle dogs.

    PubMed

    Xu, J; Bourgeois, H; Vandermeulen, E; Vlaeminck, B; Meyer, E; Demeyere, K; Hesta, M

    2015-05-01

    Secreted phospholipase A2 inhibitor (sPLA2i) has been reported to have an anti-inflammatory function by blocking the production of inflammatory mediators. Obesity is characterized by low-grade inflammation and oxidative stress. The aim of this study was to investigate the effects of dietary supplementation of sPLA2i on inflammation, oxidative stress and serum fatty acid profile in dogs. Seven obese and seven lean Beagle dogs were used in a 28-day double blind cross-over design. Dogs were fed a control diet without supplemental sPLA2i or an sPLA2i supplemented diet. The sPLA2i diet decreased plasma fibrinogen levels and increased the protein:fibrinogen ratio in obese dogs to levels similar to those of lean dogs fed the same diet. Obese dogs had a higher plasma concentration of the lipophilic vitamin A with potential antioxidative capacity and a lower ratio of retinol binding protein 4:vitamin A compared to lean dogs, independent of the diets. A higher proportion of myristic acid (C14:0) and a lower proportion of linoleic acid (C18:2n-6) were observed in the dogs fed with the sPLA2i diet compared to dogs fed with the control diet. Furthermore, a higher ratio of n-6 to n-3, a lower proportion of n-3 polyunsaturated fatty acids and lower omega-3 index were observed in obese compared to lean dogs. The results indicate that obese dogs are characterized by a more 'proinflammatory' serum fatty acid profile and that diet inclusion of sPLA2i may reduce inflammation and alter fatty acid profile. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. A critical role of striatal A2A R-mGlu5 R interactions in modulating the psychomotor and drug-seeking effects of methamphetamine.

    PubMed

    Wright, Sherie R; Zanos, Panos; Georgiou, Polymnia; Yoo, Ji-Hoon; Ledent, Catherine; Hourani, Susanna M; Kitchen, Ian; Winsky-Sommerer, Raphaelle; Bailey, Alexis

    2016-07-01

    Addiction to psychostimulants is a major public health problem with no available treatment. Adenosine A2A receptors (A2A R) co-localize with metabotropic glutamate 5 receptors (mGlu5 R) in the striatum and functionally interact to modulate behaviours induced by addictive substances, such as alcohol. Using genetic and pharmacological antagonism of A2A R in mice, we investigated whether A2A R-mGlu5 R interaction can regulate the locomotor, stereotypic and drug-seeking effect of methamphetamine and cocaine, two drugs that exhibit distinct mechanism of action. Genetic deletion of A2A R, as well as combined administration of sub-threshold doses of the selective A2A R antagonist (SCH 58261, 0.01 mg/kg, i.p.) with the mGlu5 R antagonist, 3-((2-methyl-4-thiazolyl)ethynyl)pyridine (0.01 mg/kg, i.p.), prevented methamphetamine- but not cocaine-induced hyperactivity and stereotypic rearing behaviour. This drug combination also prevented methamphetamine-rewarding effects in a conditioned-place preference paradigm. Moreover, mGlu5 R binding was reduced in the nucleus accumbens core of A2A R knockout (KO) mice supporting an interaction between these receptors in a brain region crucial in mediating addiction processes. Chronic methamphetamine, but not cocaine administration, resulted in a significant increase in striatal mGlu5 R binding in wild-type mice, which was absent in the A2A R KO mice. These data are in support of a critical role of striatal A2A R-mGlu5 R functional interaction in mediating the ambulatory, stereotypic and reinforcing effects of methamphetamine but not cocaine-induced hyperlocomotion or stereotypy. The present study highlights a distinct and selective mechanistic role for this receptor interaction in regulating methamphetamine-induced behaviours and suggests that combined antagonism of A2A R and mGlu5 R may represent a novel therapy for methamphetamine addiction. © 2015 Society for the Study of Addiction.

  12. Myelin Proteolipid Protein Complexes with αv Integrin and AMPA Receptors In Vivo and Regulates AMPA-Dependent Oligodendrocyte Progenitor Cell Migration through the Modulation of Cell-Surface GluR2 Expression

    PubMed Central

    Harlow, Danielle E.; Saul, Katherine E.; Komuro, Hitoshi

    2015-01-01

    In previous studies, stimulation of ionotropic AMPA/kainate glutamate receptors on cultured oligodendrocyte cells induced the formation of a signaling complex that includes the AMPA receptor, integrins, calcium-binding proteins, and, surprisingly, the myelin proteolipid protein (PLP). AMPA stimulation of cultured oligodendrocyte progenitor cells (OPCs) also caused an increase in OPC migration. The current studies focused primarily on the formation of the PLP–αv integrin–AMPA receptor complex in vivo and whether complex formation impacts OPC migration in the brain. We found that in wild-type cerebellum, PLP associates with αv integrin and the calcium-impermeable GluR2 subunit of the AMPA receptor, but in mice lacking PLP, αv integrin did not associate with GluR2. Live imaging studies of OPC migration in ex vivo cerebellar slices demonstrated altered OPC migratory responses to neurotransmitter stimulation in the absence of PLP and GluR2 or when αv integrin levels were reduced. Chemotaxis assays of purified OPCs revealed that AMPA stimulation was neither attractive nor repulsive but clearly increased the migration rate of wild-type but not PLP null OPCs. AMPA receptor stimulation of wild-type OPCs caused decreased cell-surface expression of the GluR2 AMPA receptor subunit and increased intracellular Ca2+ signaling, whereas PLP null OPCs did not reduce GluR2 at the cell surface or increase Ca2+ signaling in response to AMPA treatment. Together, these studies demonstrate that PLP is critical for OPC responses to glutamate signaling and has important implications for OPC responses when levels of glutamate are high in the extracellular space, such as following demyelination. SIGNIFICANCE STATEMENT After demyelination, such as occurs in multiple sclerosis, remyelination of axons is often incomplete, leading to loss of neuronal function and clinical disability. Remyelination may fail because oligodendrocyte precursor cells (OPCs) do not completely migrate into

  13. Curve Modulation and Apex Migration Using Shilla Growth Guidance Rods for Early-onset Scoliosis at 5-Year Follow-up.

    PubMed

    Wilkinson, John T; Songy, Chad E; Bumpass, David B; McCullough, Francis L; McCarthy, Richard E

    2017-04-03

    The Shilla procedure was designed to correct and control early-onset spinal deformity while harnessing a child's remaining spinal growth. It allows for controlled axial skeletal growth within the construct, avoiding the need for frequent surgeries to lengthen implants. We hypothesized that curve characteristics evolve over time after initial apex fusion and placement of the Shilla implants. The purpose of this study was to identify trends in curve evolution after Shilla implantation and understand how these changes influence ultimate outcome. A single-center, retrospective review of all patients with Shilla implants in place for ≥5 years yielded 21 patients. Charts and radiographs were reviewed to compare coronal curve characteristics preoperatively, postoperatively, and at last follow-up to note changes in the apex of the primary curve. Also noted were the development of adjacent compensatory curves, the overall vertical spinal growth, and the need for definitive spinal fusion once skeletal maturity was reached. Of the 21 patients, the curve apex migrated caudally in 12 patients (57%) and cephalad in 1 patient (5%), with a mean migration of 2.7 vertebral levels. Two patients (10%) developed new, significant compensatory curves (1 caudal and 1 cephalad). All patients demonstrated spinal growth in T1-S1 length following index surgery (mean, 45 mm). At skeletal maturity, 10 patients underwent definitive posterior spinal fusion and instrumentation, and 3 underwent implant removal alone. This study constitutes the longest follow-up of Shilla patients evaluating curve and implant behavior. Results of this review suggest that the apex of the fused primary curve shifts in approximately 62% of patients, with nearly all of these (92%) involving a distal migration. Compensatory curves did develop after Shilla placement as well. Overall, these findings represent adding-on distal to the apex after Shilla instrumentation rather than a crankshaft phenomenon about the apex. A

  14. The Long Non-Coding RNA XIST Interacted with MiR-124 to Modulate Bladder Cancer Growth, Invasion and Migration by Targeting Androgen Receptor (AR).

    PubMed

    Xiong, Yaoyao; Wang, Long; Li, Yuan; Chen, Minfeng; He, Wei; Qi, Lin

    2017-01-01

    Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in the progression of several tumors. The interaction between lncRNA and miRNA or miRNA's target genes is reported to play crucial roles in malignancy. In addition, Androgen receptor (AR) is considered to be involved in bladder cancer progression. In this study, we investigated the role of XIST in human bladder cancer and its interaction with miR-124 and AR. XIST and AR expression was detected in bladder tumor samples and cell lines. Effects of XIST and AR on bladder cancer cells growth, invasion and migration were analyzed. Bioinformatic analysis and luciferase assays were used to identify the interaction among XIST, AR and miR-124. The correlations of miR-124 with XIST and AR in bladder cancer samples were statistically analyzed. XIST and AR were upregulated in bladder cancer tissues and positively correlated. Higher XIST and AR expression were related to poorer TNM stage of bladder cancer. XIST knockdown reduced bladder cancer cells' proliferation, invasion and migration. While this inhibitory effect could be partially restored by AR overexpression. XIST inhibited miR-124 expression by directly targeting. Moreover, miR-124 could bind to the 3'UTR of AR to regulate its expression. MiR-124 inhibition partially restored the XIST knockdown-induced reduction of AR, c-myc, p27, MMP13 and MMP9 expression. In bladder cancer tissues, miR-124 level was inversely correlated with the expression of XIST and AR, respectively. These findings indicated that XIST might be an oncogenic lncRNA that promoted the bladder cancer growth, invasion and migration via miR-124 dependent AR regulation. © 2017 The Author(s). Published by S. Karger AG, Basel.

  15. Capns1, a new binding partner of RasGAP-SH3 domain in K-Ras(V12) oncogenic cells: modulation of cell survival and migration.

    PubMed

    Pamonsinlapatham, Perayot; Gril, Brunilde; Dufour, Sylvie; Hadj-Slimane, Réda; Gigoux, Véronique; Pethe, Stéphanie; L'hoste, Sébastien; Camonis, Jacques; Garbay, Christiane; Raynaud, Françoise; Vidal, Michel

    2008-11-01

    Ras GTPase-activating protein (RasGAP) is hypothesized to be an effector of oncogenic Ras stimulating numerous downstream cellular signaling cascades involved in survival, proliferation and motility. In this study, we identified calpain small subunit-1 (Capns1) as a new RasGAP-SH3 domain binding partner, using yeast two-hybrid screening. The interaction was confirmed by co-immunoprecipitation assay and was found specific to cells expressing oncogenic K-Ras. We used confocal microscopy to analyze our stably transfected cell model producing mutant Ras (PC3Ras(V12)). Staining for RasGAP-SH3/Capns1 co-localization was two-fold stronger in the protrusions of Ras(V12) cells than in PC3 cells. RasGAP or Capns1 knockdown in PC3Ras(V12) cells induced a two- to three-fold increase in apoptosis. Capns1 gene silencing reduced the speed and increased the persistence of movement in PC3Ras(V12) cells. In contrast, RasGAP knockdown in PC3Ras(V12) cells increased cell migration. Knockdown of both proteins altered the speed and directionality of cell motility. Our findings suggest that RasGAP and Capns1 interaction in oncogenic Ras cells is involved in regulating migration and cell survival.

  16. Di-Ethylhexylphthalate (DEHP) Modulates Cell Invasion, Migration and Anchorage Independent Growth through Targeting S100P in LN-229 Glioblastoma Cells

    PubMed Central

    Sims, Jennifer Nicole; Graham, Barbara; Pacurari, Maricica; Leggett, Sophia S.; Tchounwou, Paul B.; Ndebele, Kenneth

    2014-01-01

    Glioblastoma multiforme (GBM) is the most aggressive brain cancer with a median survival of 1–2 years. The treatment of GBM includes surgical resection, radiation and chemotherapy, which minimally extends survival. This poor prognosis necessitates the identification of novel molecular targets associated with glioblastoma. S100P is associated with drug resistance, metastasis, and poor clinical outcomes in many malignancies. The functional role of S100P in glioblastoma has not been fully investigated. In this study, we examined the role of S100P mediating the effects of the environmental contaminant, DEHP, in glioblastoma cells (LN-229) by assessing cell proliferation, apoptosis, anchorage independent growth, cell migration and invasion following DEHP exposure. Silencing S100P and DEHP treatment inhibited LN-229 glioblastoma cell proliferation and induced apoptosis. Anchorage independent growth study revealed significantly decreased colony formation in shS100P cells. We also observed reduced cell migration in cells treated with DEHP following S100P knockdown. Similar results were observed in spheroid formation and expansion. This study is the first to demonstrate the effects of DEHP on glioblastoma cells, and implicates S100P as a potential therapeutic target that may be useful as a drug response biomarker. PMID:24821384

  17. Soluble Factors from Biofilms of Wound Pathogens Modulate Human Bone Marrow-derived Stromal Cell Differentiation, Migration, Angiogenesis, and Cytokine Secretion

    DTIC Science & Technology

    2015-03-28

    Becerra, Christopher R Rathbone and Joseph C Wenke Abstract Background: Chronic, non- healing wounds are often characterized by the persistence of bacteria...within biofilms - aggregations of cells encased within a self -produced polysaccharide matrix. Biofilm bacteria exhibit unique characteristics from...modulation of host-immune responses by secreting factors that promote wound healing . While these characteristics make MSCs an attractive therapeutic

  18. Oxygen-ion-migration-modulated bipolar resistive switching and complementary resistive switching in tungsten/indium tin oxide/gold memory device

    NASA Astrophysics Data System (ADS)

    Wu, Xinghui; Zhang, Qiuhui; Cui, Nana; Xu, Weiwei; Wang, Kefu; Jiang, Wei; Xu, Qixing

    2018-06-01

    In this paper, we report our investigation of room-temperature-fabricated tungsten/indium tin oxide/gold (W/ITO/Au) resistive random access memory (RRAM), which exhibits asymmetric bipolar resistive switching (BRS) behavior. The device displays good write/erase endurance and data retention properties. The device shows complementary resistive switching (CRS) characteristics after controlling the compliance current. A WO x layer electrically formed at the W/ITO in the forming process. Mobile oxygen ions within ITO migrate toward the electrode/ITO interface and produce a semiconductor-like layer that acts as a free-carrier barrier. The CRS characteristic here can be elucidated in light of the evolution of an asymmetric free-carrier blocking layer at the electrode/ITO interface.

  19. microRNA-145 modulates epithelial-mesenchymal transition and suppresses proliferation, migration and invasion by targeting SIP1 in human cervical cancer cells.

    PubMed

    Sathyanarayanan, Anusha; Chandrasekaran, Karthik Subramanian; Karunagaran, Devarajan

    2017-04-01

    Previously, it has been reported that microRNA-145 (miR-145) is lowly expressed in human cervical cancers and that its putative tumour suppressive role may be attributed to epithelial-mesenchymal transition (EMT) regulation. Here, we aimed to assess whether miR-145 may affect EMT-associated markers/genes and suppress cervical cancer growth and motility, and to provide a mechanistic basis for these phenomena. The identification of the SMAD-interacting protein 1 (SIP1) mRNA as putative miR-145 target was investigated using a 3' untranslated region (3'UTR) luciferase assay and Western blotting, respectively. The functional effects of exogenous miR-145 expression, miR-145 suppression or siRNA-mediated SIP1 expression down-regulation in cervical cancer-derived C33A and SiHa cells were analysed using Western blotting, BrdU incorporation (proliferation), transwell migration and invasion assays. In addition, the expression levels of miR-145 and SIP1 were determined in primary human cervical cancer and non-cancer tissue samples using qRT-PCR. We found that miR-145 binds to the wild-type 3'UTR of SIP1, but not to its mutant counterpart, and that, through this binding, miR-145 can effectively down-regulate SIP1 expression. In addition, we found that exogenous miR-145 expression or siRNA-mediated down-regulation of SIP1 expression attenuates the proliferation, migration and invasion of C33A and SiHa cells and alters the expression of the EMT-associated markers CDH1, VIM and SNAI1, whereas inhibition of endogenous miR-145 expression elicited the opposite effects. The expression of miR-145 in cervical cancer tissue samples was found to be low, while that of SIP1 was found to be high compared to non-cancerous cervical tissues. An inverse expression correlation between the two was substantiated through the anlaysis of data deposited in the TCGA database. Our data indicate that low miR-145 expression levels in conjunction with elevated SIP1 expression levels may contribute to

  20. MeCP2 overexpression inhibits proliferation, migration and invasion of C6 glioma by modulating ERK signaling and gene expression.

    PubMed

    Sharma, Kedarlal; Singh, Juhi; Frost, Emma E; Pillai, Prakash P

    2018-05-01

    MethylCpG binding protein-2 (MeCP2) is an epigenetic regulator and essential for brain development. MeCP2 mutations are associated with a spectrum of neuro-developmental disorders that vary depending on the patient gender, most notably Rett Syndrome. MeCP2 is essential for normal neuronal maturation, and glial cell function in the brain. Besides, its role in neurodevelopmental disorders, MeCP2 is involved in many cancers such as breast, colorectal, lung, liver, and prostate cancer. Glioma is the most lethal form of brain cancer. Studies have shown that dysfunctional epigenetic regulation plays a crucial role in glioma progression. Further, previous studies have suggested a role for MeCP2 in glioma pathogenesis. In this study, we show that MeCP2 may play a critical role in the suppression of glioma progression. Stable overexpression of MeCP2in C6 glioma cells inhibits proliferation, migration, invasion, and adhesion. Moreover, MeCP2 overexpression inhibits pERKand BDNF expression while inducing GFAP expression in C6 glioma. These findings suggest that MeCP2 may play a crucial role in suppression of glioma progression. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. CXCR4 and CXCL12 are inversely expressed in colorectal cancer cells and modulate cancer cell migration, invasion and MMP-9 activation

    SciTech Connect

    Brand, Stephan; Dambacher, Julia; Beigel, Florian

    2005-10-15

    Colorectal cancer (CRC) is characterized by a distinct metastatic pattern resembling chemokine-induced leukocyte trafficking. This prompted us to investigate expression, signal transduction and specific functions of the chemokine receptor CXCR4 in CRC cells and metastases. Using RT-PCR analysis and Western blotting, we demonstrated CXCR4 and CXCL12 expression in CRC and CRC metastases. Cell differentiation increases CXCL12 mRNA levels. Moreover, CXCR4 and its ligand are inversely expressed in CRC cell lines with high CXCR4 and low or not detectable CXCL12 expression. CXCL12 activates ERK-1/2, SAPK/JNK kinases, Akt and matrix metalloproteinase-9. These CXCL12-induced signals mediate reorganization of the actin cytoskeleton resulting inmore » increased cancer cell migration and invasion. Moreover, CXCL12 increases vascular endothelial growth factor (VEGF) expression and cell proliferation but has no effect on CRC apoptosis. Therefore, the CXCL12/CXCR4 system is an important mediator of invasion and metastasis of CXCR4 expressing CRC cells.« less

  2. Increased migration of uncemented acetabular cups in female total hip arthroplasty patients with low systemic bone mineral density. A 2-year RSA and 8-year radiographic follow-up study of 34 patients.

    PubMed

    Finnilä, Sami; Moritz, Niko; SvedströM, Erkki; Alm, Jessica J; Aro, Hannu T

    2016-02-01

    Low bone mineral density (BMD) may jeopardize the initial component stability and delay osseointegration of uncemented acetabular cups in total hip arthroplasty (THA). We measured the migration of uncemented cups in women with low or normal BMD. We used radiostereometric analysis (RSA) to measure the migration of hydroxyapatite-coated titanium alloy cups with alumina-on-alumina bearings in THA of 34 female patients with a median age of 64 (41-78) years. 10 patients had normal BMD and 24 patients had low systemic BMD (T-score ≤ -1) based on dual-energy X-ray absorptiometry (DXA). Cup migration was followed with RSA for 2 years. Radiographic follow-up was done at a median of 8 (2-10) years. Patients with normal BMD did not show a statistically significant cup migration after the settling period of 3 months, while patients with low BMD had a continuous proximal migration between 3 and 12 months (p = 0.03). These differences in cup migration persisted at 24 months. Based on the perceived risk of cup revision, 14 of the 24 cases were "at risk" (proximal translation of 0.2 to 1.0 mm) in the low-BMD group and 2 of the 10 cases were "at risk" in the normal-BMD group (odds ratio (OR) = 8.0, 95% CI: 1.3-48). The radiographic follow-up showed no radiolucent lines or osteolysis. 2 cups have been revised for fractures of the ceramic bearings, but none for loosening. Low BMD contributed to cup migration beyond the settling period of 3 months, but the migrating cups appeared to osseointegrate eventually.

  3. Phase modulation in dipolar-coupled A 2 spin systems: effect of maximum state mixing in 1H NMR in vivo

    NASA Astrophysics Data System (ADS)

    Schröder, Leif; Schmitz, Christian; Bachert, Peter

    2004-12-01

    Coupling constants of nuclear spin systems can be determined from phase modulation of multiplet resonances. Strongly coupled systems such as citrate in prostatic tissue exhibit a more complex modulation than AX connectivities, because of substantial mixing of quantum states. An extreme limit is the coupling of n isochronous spins (A n system). It is observable only for directly connected spins like the methylene protons of creatine and phosphocreatine which experience residual dipolar coupling in intact muscle tissue in vivo. We will demonstrate that phase modulation of this "pseudo-strong" system is quite simple compared to those of AB systems. Theory predicts that the spin-echo experiment yields conditions as in the case of weak interactions, in particular, the phase modulation depends linearly on the line splitting and the echo time.

  4. The conformational flexibility of the carboxy terminal residues 105–114 is a key modulator of the catalytic activity and stability of Macrophage Migration Inhibitory Factor (MIF)†

    PubMed Central

    El-Turk, Farah; Cascella, Michele; Ouertatani-Sakouhi, Hajer; Narayanan, Raghavendran Lakshmi; Leng, Lin; Bucala, Richard; Hweckstetter, Markus; Rothlisberger, Ursula; Lashuel, Hilal A.

    2013-01-01

    Macrophage migration inhibitory factor (MIF) is a multifunctional protein and a major mediator of innate immunity. Although X-ray crystallography revealed that MIF exists as a homotrimer, its oligomerization state in vivo as well as the factors governing its oligomerization and stability remain poorly understood. The C-terminal region of MIF is highly conserved and participates in several intramolecular interactions that suggest a role in modulating the stability and biochemical activity of MIF. To determine the importance of these interactions, point mutations (A48P, L46A), insertions (P107) at the monomer-monomer interfaces, and C-terminal deletion (Δ110-114NSTFA and Δ105–114NVGWNNSTFA) variants were designed and their structural properties, thermodynamic stability, oligomerization state, catalytic activity and receptor binding were characterized using a battery of biophysical methods. The C-terminal deletion mutants ΔC5 huMIF1-109 and ΔC10 huMIF1-104 were enzymatically inactive and thermodynamically less stable than wild type MIF. Analytical ultracentrifugation studies demonstrate that both C-terminal mutants sediment as trimers and exhibit similar binding to CD74 as the wild type protein. Disrupting the conformation of the C-terminal region 105–114 and increasing its conformational flexibility through the insertion of a proline residue at position 107 was sufficient to reproduce the structural, biochemical and thermodynamic properties of the deletion mutants. P107 MIF forms an enzymatically inactive trimer and exhibits reduced thermodynamic stability relative to the wild type protein. To provide a rationale for the changes induced by these mutations at the molecular level, we also performed molecular dynamics simulations on these mutants in comparison to the wild type MIF. Together, our studies demonstrate that inter-subunit interactions involving the C-terminal region 105–114, including a salt-bridge interaction between Arg73 of one monomer and the

  5. A small peptide promotes EphA2 kinase-dependent signaling by stabilizing EphA2 dimers.

    PubMed

    Singh, Deo R; Pasquale, Elena B; Hristova, Kalina

    2016-09-01

    The EphA2 receptor tyrosine kinase is known to promote cancer cell malignancy in the absence of activation by ephrin ligands. This behavior depends on high EphA2 phosphorylation on Ser897 and low tyrosine phosphorylation, resulting in increased cell migration and invasiveness. We have previously shown that EphA2 forms dimers in the absence of ephrin ligand binding, and that dimerization of unliganded EphA2 can decrease EphA2 Ser897 phosphorylation. We have also identified a small peptide called YSA, which binds EphA2 and competes with the naturally occurring ephrin ligands. Here, we investigate the effect of YSA on EphA2 dimer stability and EphA2 function using quantitative FRET techniques, Western blotting, and cell motility assays. We find that the YSA peptide stabilizes the EphA2 dimer, increases EphA2 Tyr phosphorylation, and decreases both Ser897 phosphorylation and cell migration. The experiments demonstrate that the small peptide ligand YSA reduces EphA2 Ser897 pro-tumorigenic signaling by stabilizing the EphA2 dimer. This work is a proof-of-principle demonstration that EphA2 homointeractions in the plasma membrane can be pharmacologically modulated to decrease the pro-tumorigenic signaling of the receptor. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. 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.

  7. The molecular mechanism of flop-selectivity and subsite recognition for an AMPA receptor allosteric modulator: Structures of GluA2 and GluA3 complexed with PEPA

    PubMed Central

    Ahmed, Ahmed H.; Ptak, Christopher P.; Oswald, Robert E.

    2011-01-01

    Glutamate receptors are important potential drug targets for cognitive enhancement and the treatment of schizophrenia in part because they are the most prevalent excitatory neurotransmitter receptors in the vertebrate central nervous system. One approach to the application of therapeutic agents to the AMPA subtype of glutamate receptors is the use of allosteric modulators, which promote dimerization by binding to a dimer interface thereby reducing desensitization and deactivation. AMPA receptors exist in two alternatively spliced variants (flip and flop) that differ in desensitization and receptor activation profiles. Most of the structural information on modulators of the AMPA receptor target the flip subtype. We report here the crystal structure of the flop-selective allosteric modulator, PEPA, bound to the binding domains of the GluA2 and GluA3 flop isoforms of AMPA receptors. Specific hydrogen bonding patterns can explain the preference for the flop isoform. This includes a bidentate hydrogen bonding pattern between PEPA and N754 of the flop isoforms of GluA2 and GluA3 (the corresponding position in the flip isoform is S754). Comparison with other allosteric modulators provides a framework for the development of new allosteric modulators with preferences for either the flip or flop isoforms. In addition to interactions with N/S754, specific interactions of the sulfonamide with conserved residues in the binding site are characteristics of a number of allosteric modulators. These, in combination, with variable interactions with five subsites on the binding surface lead to different stoichiometries, orientations within the binding pockets, and functional outcomes. PMID:20199107

  8. Calcium modulates calmodulin/α-actinin 1 interaction with and agonist-dependent internalization of the adenosine A2A receptor.

    PubMed

    Piirainen, Henni; Taura, Jaume; Kursula, Petri; Ciruela, Francisco; Jaakola, Veli-Pekka

    2017-04-01

    Adenosine receptors are G protein-coupled receptors that sense extracellular adenosine to transmit intracellular signals. One of the four adenosine receptor subtypes, the adenosine A 2A receptor (A 2A R), has an exceptionally long intracellular C terminus (A 2A R-ct) that mediates interactions with a large array of proteins, including calmodulin and α-actinin. Here, we aimed to ascertain the α-actinin 1/calmodulin interplay whilst binding to A 2A R and the role of Ca 2+ in this process. First, we studied the A 2A R-α-actinin 1 interaction by means of native polyacrylamide gel electrophoresis, isothermal titration calorimetry, and surface plasmon resonance, using purified recombinant proteins. α-Actinin 1 binds the A 2A R-ct through its distal calmodulin-like domain in a Ca 2+ -independent manner with a dissociation constant of 5-12μM, thus showing an ~100 times lower affinity compared to the A 2A R-calmodulin/Ca 2+ complex. Importantly, calmodulin displaced α-actinin 1 from the A 2A R-ct in a Ca 2+ -dependent fashion, disrupting the A 2A R-α-actinin 1 complex. Finally, we assessed the impact of Ca 2+ on A 2A R internalization in living cells, a function operated by the A 2A R-α-actinin 1 complex. Interestingly, while Ca 2+ influx did not affect constitutive A 2A R endocytosis, it abolished agonist-dependent internalization. In addition, we demonstrated that the A 2A R/α-actinin interaction plays a pivotal role in receptor internalization and function. Overall, our results suggest that the interplay of A 2A R with calmodulin and α-actinin 1 is fine-tuned by Ca 2+ , a fact that might power agonist-mediated receptor internalization and function. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Modulation of C-reactive protein and plasma omega-6 fatty acid levels by phospholipase A2 gene polymorphisms following a 6-week supplementation with fish oil.

    PubMed

    Tremblay, B L; Rudkowska, I; Couture, P; Lemieux, S; Julien, P; Vohl, M C

    2015-12-01

    This clinical trial investigated the impact of a six-week supplementation with fish oil and single nucleotide polymorphisms (SNPs) in PLA2G4A and PLA2G6 genes on total omega-6 fatty acid (n-6 FA) levels in plasma phospholipids (PL) and plasma C-reactive protein (CRP) levels in 191 subjects. Interaction effects between SNPs and supplementation modulated total n-6 FAs and CRP levels in both men and women. Associations between SNPs and total n-6 FA levels and between SNPs and CRP levels were identified in men, independently of supplementation. Supplementation decreased total n-6 FAs without affecting plasma CRP levels. Changes in CRP levels correlated positively with changes in total n-6 FAs in men (r=0.25 p=0.01), but not in women. In conclusion, total n-6 FA levels in plasma PL and plasma CRP levels are modulated by SNPs within PLA2G4A and PLA2G6 genes alone or in combination with fish oil supplementation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Spatially modulated ephrinA1:EphA2 signaling increases local contractility and global focal adhesion dynamics to promote cell motility.

    PubMed

    Chen, Zhongwen; Oh, Dongmyung; Biswas, Kabir H; Yu, Cheng-Han; Zaidel-Bar, Ronen; Groves, Jay T

    2018-06-19

    Recent studies have revealed pronounced effects of the spatial distribution of EphA2 receptors on cellular response to receptor activation. However, little is known about molecular mechanisms underlying this spatial sensitivity, in part due to lack of experimental systems. Here, we introduce a hybrid live-cell patterned supported lipid bilayer experimental platform in which the sites of EphA2 activation and integrin adhesion are spatially controlled. Using a series of live-cell imaging and single-molecule tracking experiments, we map the transmission of signals from ephrinA1:EphA2 complexes. Results show that ligand-dependent EphA2 activation induces localized myosin-dependent contractions while simultaneously increasing focal adhesion dynamics throughout the cell. Mechanistically, Src kinase is activated at sites of ephrinA1:EphA2 clustering and subsequently diffuses on the membrane to focal adhesions, where it up-regulates FAK and paxillin tyrosine phosphorylation. EphrinA1:EphA2 signaling triggers multiple cellular responses with differing spatial dependencies to enable a directed migratory response to spatially resolved contact with ephrinA1 ligands.

  11. In vivo dosimetry with optically stimulated luminescent dosimeters for conformal and intensity-modulated radiation therapy: A 2-year multicenter cohort study.

    PubMed

    Riegel, Adam C; Chen, Yu; Kapur, Ajay; Apicello, Laura; Kuruvilla, Abraham; Rea, Anthony J; Jamshidi, Abolghassem; Potters, Louis

    Optically stimulated luminescent dosimeters (OSLDs) are utilized for in vivo dosimetry (IVD) of modern radiation therapy techniques such as intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). Dosimetric precision achieved with conventional techniques may not be attainable. In this work, we measured accuracy and precision for a large sample of clinical OSLD-based IVD measurements. Weekly IVD measurements were collected from 4 linear accelerators for 2 years and were expressed as percent differences from planned doses. After outlier analysis, 10,224 measurements were grouped in the following way: overall, modality (photons, electrons), treatment technique (3-dimensional [3D] conformal, field-in-field intensity modulation, inverse-planned IMRT, and VMAT), placement location (gantry angle, cardinality, and central axis positioning), and anatomical site (prostate, breast, head and neck, pelvis, lung, rectum and anus, brain, abdomen, esophagus, and bladder). Distributions were modeled via a Gaussian function. Fitting was performed with least squares, and goodness-of-fit was assessed with the coefficient of determination. Model means (μ) and standard deviations (σ) were calculated. Sample means and variances were compared for statistical significance by analysis of variance and the Levene tests (α = 0.05). Overall, μ ± σ was 0.3 ± 10.3%. Precision for electron measurements (6.9%) was significantly better than for photons (10.5%). Precision varied significantly among treatment techniques (P < .0001) with field-in-field lowest (σ = 7.2%) and IMRT and VMAT highest (σ = 11.9% and 13.4%, respectively). Treatment site models with goodness-of-fit greater than 0.90 (6 of 10) yielded accuracy within ±3%, except for head and neck (μ = -3.7%). Precision varied with treatment site (range, 7.3%-13.0%), with breast and head and neck yielding the best and worst precision, respectively. Placement on the central axis of cardinal gantry

  12. Population, migration and urbanization.

    PubMed

    1982-06-01

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

  13. [Circular migration in Indonesia].

    PubMed

    Mantra, I B

    1979-12-01

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

  14. Migration and Adult Education

    ERIC Educational Resources Information Center

    Gois, William

    2007-01-01

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

  15. More Myths of Migration.

    ERIC Educational Resources Information Center

    Basch, Linda; Lerner, Gail

    1986-01-01

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

  16. Chandra Contaminant Migration Model

    NASA Technical Reports Server (NTRS)

    Swartz, Douglas A.; O'Dell, Steve L.

    2014-01-01

    High volatility cleans OBFs and low volatility produces a high build-up at OBF centers; only a narrow (factor of 2 or less) volatility range produces the observed spatial pattern. Simulations predict less accumulation above outer S-array CCDs; this may explain, in part, gratings/imaging C/MnL discrepancies. Simulations produce a change in center accumulation due solely to DH heater ON/OFF temperature change; but a 2nd contaminant and perhaps a change in source rate is also required. Emissivity E may depend on thickness; another model parameter. Additional physics, e.g., surface migration, is not warranted at this time. At t approx. 14 yrs, model produced 0.22 grams of contaminant, 0.085 grams remaining within ACIS cavity; 7 percent (6mg) on OBFs.

  17. The mitochondrial proteins AtHscB and AtIsu1 involved in Fe-S cluster assembly interact with the Hsp70-type chaperon AtHscA2 and modulate its catalytic activity.

    PubMed

    Leaden, Laura; Busi, Maria V; Gomez-Casati, Diego F

    2014-11-01

    Arabidopsis plants contain two genes coding for mitochondrial Hsp70-type chaperon-like proteins, AtHscA1 (At4g37910) and AtHscA2 (At5g09590). Both genes are homologs of the Ssq1 gene involved in Fe-S cluster assembly in yeast. Protein-protein interaction studies showed that AtHscA2 interacts with AtIsu1 and AtHscB, two Arabidopsis homologs of the Isu1 protein and the Jac1 yeast co-chaperone. Moreover, this interaction could modulate the activity of AtHscA2. In the presence of a 1:5:5 molar ratio of AtHscA2:AtIsu1:AtHscB we observed an increase in the V(max) and a decrease in the S(0.5) for ATP of AtHscA2. Furthermore, an increase of about 28-fold in the catalytic efficiency of AtHscA2 was also observed. Results suggest that AtHscA2 in cooperation with AtIsu1 and AtHscB play an important role in the regulation of the Fe-S assembly pathway in plant mitochondria. Copyright © 2014 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  18. Analyzing bat migration

    USGS Publications Warehouse

    Cryan, Paul M.; Diehl, Robert H.

    2009-01-01

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

  19. Safety, Tolerability, and Pharmacokinetics of SMT C1100, a 2-Arylbenzoxazole Utrophin Modulator, following Single- and Multiple-Dose Administration to Pediatric Patients with Duchenne Muscular Dystrophy

    PubMed Central

    Ricotti, Valeria; Spinty, Stefan; Roper, Helen; Hughes, Imelda; Tejura, Bina; Robinson, Neil; Layton, Gary; Davies, Kay

    2016-01-01

    Purpose SMT C1100 is a utrophin modulator being evaluated as a treatment for Duchenne muscular dystrophy (DMD). This study, the first in pediatric DMD patients, reports the safety, tolerability and PK parameters of single and multiple doses of SMT C1100, as well as analyze potential biomarkers of muscle damage. Methods This multicenter, Phase 1 study enrolled 12 patients, divided equally into three groups (A–C). Group A were given 50 mg/kg on Days 1 and 11, and 50 mg/kg bid on Days 2 to 10. Group B and C received 100 mg/kg on Days 1 and 11; Group B and Group C were given 100 mg/kg bid and 100 mg/kg tid, respectively, on Days 2 to 10. A safety review was performed on all patients following the single dose and there was at least 2 weeks between each dose escalation, for safety and PK review. Adverse events (AEs) were monitored throughout the study. Results Most patients experienced mild AEs and there were no serious AEs. Two patients required analgesia for pain (headache, ear pain and toothache). One patient experienced moderate psychiatric AEs (abnormal behaviour and mood swings). Plasma concentrations of SMT C1100 at Days 1 and 11 indicated a high degree of patient variability regardless of dose. Unexpectedly the SMT C1100 levels were significantly lower than similar doses administered to healthy volunteers in an earlier clinical study. In general, individual baseline changes of creatine phosphokinase, alanine aminotransferase, aspartate aminotransferase levels fell with SMT C1100 dosing. Conclusions SMT C1100 was well tolerated in pediatric DMD patients. Trial Registration ClinicalTrials.gov NCT02383511 PMID:27055247

  20. Modulation of CYP1A2 and CYP3A6 catalytic activities by serum from rabbits with a turpentine-induced inflammatory reaction and interleukin 6.

    PubMed

    Kourylko, Oksana; Fradette, Caroline; Arcand, Mathieu; du Souich, Patrick

    2006-01-01

    Inflammatory reactions reduce the activity of cytochrome P450 isoforms. The aim of the study was to determine the mechanisms underlying the decrease in CYP1A2 and CYP3A6 catalytic activities produced by serum from rabbits with a turpentine-induced inflammatory reaction (S(TIIR)) and interleukin 6 (IL-6). S(TIIR) and IL-6 were incubated with cultured primary hepatocytes from control rabbits (H(CONT)), and from rabbits with a turpentine-induced inflammatory reaction (H(TIIR)) in the absence or presence of pyrrolidine dithiocarbamate (PDTC), an antioxidant and inhibitor of nuclear factor kappaB transcription; 2'-amino-3'-methoxyflavone (PD98059), an inhibitor of extracellular signal-related kinase (Erk1/2); 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580), an inhibitor of p38MAPK; Nomega-nitro-L-arginine methyl ester, an inhibitor of nitric-oxide synthase 2 (NOS2); the combination of PDTC, PD98059, and SB203580; and genistein, an inhibitor of Janus-associated protein tyrosine kinase (JAK). After 4 and 24 h of incubation of H(CONT) with S(TIIR) and IL-6, CYP1A2 activity was reduced without changes in expression; the reduction in activity was partially prevented by the inhibition of JAK, Erk1/2, and NOS2. In H(CONT), S(TIIR) and IL-6 did not affect CYP3A6 activity; however, PDTC reduced CYP3A6 activity by 40 and 80% after 4 and 24 h of incubation. In H(TIIR), S(TIIR) and IL-6 reduced both CYP1A2 and CYP3A6 activities; this decrease is partially prevented by inhibitors of protein tyrosine kinases, Erk1/2, and NOS2. In H(TIIR), SB203580 increased CYP3A6 activity in a dose-dependent manner without changes in protein expression. These results show that the signal transduction pathways mediating the decrease in CYP1A2 and 3A6 activity, produced by S(TIIR) and IL-6, involve JAK, Erk1/2, and NOS2.

  1. Determinants of the Egyptian labour migration.

    PubMed

    Kandil, M; Metwally, M

    1992-03-01

    The objective is to summarize the pattern of Egyptian migration to Arab oil-producing countries (AOPC), to review some factors that are important determinants of labor movement based on theory, and to empirically model the migration rate to AOPC and to Saudi Arabia. Factors are differentiated as to their relative importance. Push factors are the low wages, high inflation rate, and high population density in Egypt; pull factors are higher wages. It is predicted that an increase in income from destination countries has a significant positive impact on the migration rate. An increase in population density stimulates migration. An increase in inflation acts to increase out-migration with a 2-year lag, which accommodates departure preparation. Egypt's experience with labor migration is described for the pre-oil boom, and the post-oil boom. Several estimates of labor migration are given. Government policy toward migration is positive. Theory postulates migration to be determined by differences in the availability of labor, labor rewards between destination and origin, and the cost of migration. In the empirical model, push factors are population density, the current inflation rate, and the ratio of income/capita in AOPC to Egypt. The results indicate that the ratio of income/capita had a strong pull impact and population density had a strong push impact. The inflation rate has a positive impact with a lag estimated at 2 years. Prior to the Camp David Accord, there was a significant decrease in the number of Egyptian migrants due to political tension. The findings support the classical theory of factor mobility. The consequences of migration on the Egyptian economy have been adverse. Future models should disaggregate data because chronic shortages exist in some parts of the labor market. Manpower needs assessment would be helpful for policy makers.

  2. The A2B Adenosine Receptor Modulates the Epithelial– Mesenchymal Transition through the Balance of cAMP/PKA and MAPK/ERK Pathway Activation in Human Epithelial Lung Cells

    PubMed Central

    Giacomelli, Chiara; Daniele, Simona; Romei, Chiara; Tavanti, Laura; Neri, Tommaso; Piano, Ilaria; Celi, Alessandro; Martini, Claudia; Trincavelli, Maria L.

    2018-01-01

    The epithelial-mesenchymal transition (EMT) is a complex process in which cell phenotype switches from the epithelial to mesenchymal one. The deregulations of this process have been related with the occurrence of different diseases such as lung cancer and fibrosis. In the last decade, several efforts have been devoted in understanding the mechanisms that trigger and sustain this transition process. Adenosine is a purinergic signaling molecule that has been involved in the onset and progression of chronic lung diseases and cancer through the A2B adenosine receptor subtype activation, too. However, the relationship between A2BAR and EMT has not been investigated, yet. Herein, the A2BAR characterization was carried out in human epithelial lung cells. Moreover, the effects of receptor activation on EMT were investigated in the absence and presence of transforming growth factor-beta (TGF-β1), which has been known to promote the transition. The A2BAR activation alone decreased and increased the expression of epithelial markers (E-cadherin) and the mesenchymal one (Vimentin, N-cadherin), respectively, nevertheless a complete EMT was not observed. Surprisingly, the receptor activation counteracted the EMT induced by TGF-β1. Several intracellular pathways regulate the EMT: high levels of cAMP and ERK1/2 phosphorylation has been demonstrated to counteract and promote the transition, respectively. The A2BAR stimulation was able to modulated these two pathways, cAMP/PKA and MAPK/ERK, shifting the fine balance toward activation or inhibition of EMT. In fact, using a selective PKA inhibitor, which blocks the cAMP pathway, the A2BAR-mediated EMT promotion were exacerbated, and conversely the selective inhibition of MAPK/ERK counteracted the receptor-induced transition. These results highlighted the A2BAR as one of the receptors involved in the modulation of EMT process. Nevertheless, its activation is not enough to trigger a complete transition, its ability to affect different

  3. Stimulatory effects of histamine on migration of nasal fibroblasts.

    PubMed

    Hong, Sung-Moon; Park, Il-Ho; Um, Ji-Young; Shin, Jae-Min; Lee, Heung-Man

    2015-10-01

    Fibroblast migration is crucial for normal wound repair after sinonasal surgery. Histamine is known to be involved in wound healing by its effects on cell proliferation and migration. This study aimed to determine whether histamine affects the migration of nasal fibroblasts and to investigate the mechanism of action of histamine on nasal fibroblasts. Primary cultures of nasal fibroblasts were established from inferior turbinate samples. Fibroblast migration was evaluated with scratch assays. Cells were treated with histamine and/or histamine receptor-selective antagonists. U-73122 and pertussis toxin, which are selective inhibitors of the lower signaling pathway of H1R and H4R, were used to confirm the modulation of nasal fibroblast migration by histamine. Fibroblast cytoskeletal structures were visualized with immunocytochemistry. Histamine significantly stimulated the migration of nasal fibroblasts. Antagonists selective for HR1 and HR4 significantly reduced nasal fibroblast migration. In immunocytochemical staining, histamine treatment increased membrane ruffling and pyrilamine, diphenhydramine, fexofenadine, and JNJ7777120 decreased histamine-induced membrane ruffling. U-73122 and pertussis toxin also decreased histamine-induced migration of fibroblasts. Histamine maintains its stimulatory effects on fibroblast migration in the presence of mitomycin C, which blocks proliferation of cells. We showed that histamine stimulates fibroblast migration in nasal fibroblasts. This effect appeared to be mediated by HR1 and HR4. However, because fibroblast migration also can be involved in scaring and fibrosis, more research is necessary to determine the effects of antihistamine on wound healing after sinus surgery. © 2015 ARS-AAOA, LLC.

  4. Modulation of in vivo distribution through chelator: Synthesis and evaluation of a 2-nitroimidazole-dipicolylamine-(99m)Tc(CO)3 complex for detecting tumor hypoxia.

    PubMed

    Mallia, Madhava B; Mittal, Sweety; Sarma, Haladhar D; Banerjee, Sharmila

    2016-01-01

    Previous studies have clearly demonstrated strong correlation between in vivo distribution and blood clearance of radiopharmaceuticals for the detection of hypoxia. Present study describes an attempt to improve the in vivo distribution of a previously reported 2-nitroimidazole-(99m)Tc(CO)3 complex by tuning its blood clearance pattern through structural modification of the ligand. Herein, a 2-nitroimidazole-dipicolylamine ligand (2-nitroimidazole-DPA) was synthesized in a two-step procedure and radiolabeled with (99m)Tc(CO)3 core. Subsequently, the complex was evaluated in Swiss mice bearing fibrosarcoma tumor. As intended by its design, 2-nitroimidazole-DPA-(99m)Tc(CO)3 complex was more lipophilic than previously reported 2-nitroimidazole-DETA-(99m)Tc(CO)3 complex (DETA-diethylenetriamine) and showed slower blood clearance. Consequently it showed higher tumor uptake than 2-nitroimidazole-DETA-(99m)Tc(CO)3 complex. Significantly, despite structural modifications, other parameters such as the tumor to blood ratio and tumor to muscle ratio of the 2-nitroimidazole-DPA-(99m)Tc(CO)3 complex remained comparable to that of 2-nitroimidazole-DETA-(99m)Tc(CO)3 complex. Present study demonstrates the feasibility of structural modifications for improving in vivo tumor uptake of hypoxia detecting radiopharmaceuticals. This might encourage researchers to improve suboptimal properties of a potential radiopharmaceuticals rather than ignoring it altogether. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2012-07-01

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

  6. Apolipoprotein A2 -265 T>C polymorphism interacts with dietary fatty acids intake to modulate inflammation in type 2 diabetes mellitus patients.

    PubMed

    Keramat, Laleh; Sadrzadeh-Yeganeh, Haleh; Sotoudeh, Gity; Zamani, Elham; Eshraghian, Mohammadreza; Mansoori, Anahita; Koohdani, Fariba

    2017-05-01

    Several investigations have been conducted regarding the interaction between Apolipoprotein A2 (APOA2) -265 T>C polymorphism and dietary intake of saturated fatty acids (SFAs) on obesity in healthy individuals or type 2 diabetes mellitus (T2 DM) patients. The aim of the present study is to examine the effect of this interaction on inflammatory markers in T2 DM patients. This is a comparative cross-sectional study on 180 T2 DM patients with known APOA2 genotype. Dietary intake was assessed by food-frequency questionnaire and serum levels of inflammatory markers (interleukin [IL]-18, pentraxin 3, and high-sensitivity C-reactive protein [hs-CRP]) were measured. The subjects were dichotomized into "high" and "low" categories, based on the median dietary intake of polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), and SFAs. The data were analyzed by analysis of covariance multivariate interaction model. In CC genotype, higher median intake of ω-3 PUFAs and MUFAs was associated with decreased serum levels of IL-18 and hs-CRP (P = 0.014 and 0.008, respectively). In T-allele carriers, higher median intake of SFAs was associated with increased serum hs-CRP level (P < 0.001). There was a significant relationship between APOA2 polymorphism and ω-3 PUFA intake on serum IL-18 level (P interaction = 0.03). Moreover, the relationship between this polymorphism and SFA and MUFA intake on serum hs-CRP level was statistically significant (P interaction = 0.03 and 0.024, respectively). In T2 DM patients, the dietary intake of antiinflammatory fatty acids, such as ω-3 PUFAs and MUFAs, could reduce the inflammatory effects associated with the CC genotype. In addition, proinflammatory fatty acids, such as SFAs, could overcome the antiinflammatory effect of the T-allele. Further studies are needed to confirm these findings. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. 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.

  8. Migration to Windows NT.

    ERIC Educational Resources Information Center

    Doles, Daniel T.

    In the constantly changing world of technology, migration is not only inevitable but many times necessary for survival, especially when the end result is simplicity for both users and IT support staff. This paper describes the migration at Franklin College (Indiana). It discusses the reasons for selecting Windows NT, the steps taken to complete…

  9. The Future of Migration.

    ERIC Educational Resources Information Center

    Organisation for Economic Cooperation and Development, Paris (France).

    This book comprises papers delivered at a conference of National Experts on Migration. The principle objective of the conference was twofold: to examine significant trends that will affect the future of migration in countries in the Organization for Economic Co-operation and Development (OCED), and to identify the relevant issues that will have to…

  10. College Student Migration.

    ERIC Educational Resources Information Center

    Fenske, R. H.; And Others

    This study examines the background characteristics of two large national samples of first-time enrolled freshmen who (a) attended college within their state of residence but away from their home community, (b) migrated to a college in an adjacent state, (c) migrated to a college in a distant state, and (d) attended college in their home community.…

  11. The Great Migration.

    ERIC Educational Resources Information Center

    Trotter, Joe William, Jr.

    2002-01-01

    Describes the migration of African Americans in the United States and the reasons why African Americans migrated from the south. Focuses on issues, such as the effect of World War I, the opportunities offered in the north, and the emergence of a black industrial working class. (CMK)

  12. Migration and Environmental Hazards

    PubMed Central

    Hunter, Lori M.

    2011-01-01

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

  13. On marriage and migration.

    PubMed

    Stark, O

    1988-09-01

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

  14. Migration and AIDS.

    PubMed

    1998-01-01

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

  15. Migration without migraines

    SciTech Connect

    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

  16. 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.

  17. Impact of ER520, a candidate of selective estrogen receptor modulators, on in vitro cell growth, migration, invasion, angiogenesis and in vivo tumor xenograft of human breast cancer cells.

    PubMed

    Wang, Lijun; Wang, Ying; Du, Huaqing; Jiang, Yao; Tang, Zhichao; Liu, Hongyi; Xiang, Hua; Xiao, Hong

    2015-12-01

    ER520, a derivative of indenoisoquinoline, is a patented compound. This study was designed to screen its biological properties and to evaluate its antineoplastic and antiangiogenic effect. Western blot was employed to monitor the ERα and ERβ protein expression in human breast cancer MCF-7 cells and endometrial carcinoma Ishikawa cells. MTT assay was employed to determine cell proliferation. Cell adhesion, scratch and Transwell assay were utilized to estimate the ability of cellular adhesion, migration and invasion. ELISA kit was applied to detect the VEGF products in culture medium. In addition, the inhibitory effect of ER520 on the vessel-like construction of HUVEC cells and the angiogenesis of chicken embryos was investigated. The efficiency of ER520 on tumor growth in nude mice was also assessed. ER520 inhibited the expression of ERα in MCF-7 and Ishikawa cells, while it increased ERβ protein level. ER520 also suppressed the proliferation of MCF-7 and Ishikawa cells. Due to its remarkably negative role in cell adhesion, migration and invasion, ER520 showed a potential ability of inhibiting tumor metastasis. Meanwhile, ER520 reduced the VEGF secretion of MCF-7 and Ishikawa cells, prevented the formation of VEGF-stimulated tubular structure and the cell migration of HUVEC cells, and inhibited the angiogenesis of chicken chorioallantoic membrane. Animal experiment also demonstrated that ER520 could frustrate the in vivo tumor growth and the inhibitory ratio was 48.5 % compared with control group. Our findings indicate that ER520 possesses the competence to be a candidate against breast cancer and angiogenesis.

  18. Glossary: migration and health.

    PubMed

    Urquia, Marcelo L; Gagnon, Anita J

    2011-05-01

    The literature on migration and health is quite heterogeneous in how migrants are labelled and how the relation between migration and health is conceptualised. A narrative review has been carried out. This glossary presents the most commonly used terms in the field of migration and health, along with synonyms and related concepts, and discusses the suitability of their use in epidemiological studies. The terminology used in migrant health is ambiguous in many cases. Studies on migrant health should avoid layman terms and strive to use internationally defined concepts.

  19. Menadione (Vitamin K3) induces apoptosis of human oral cancer cells and reduces their metastatic potential by modulating the expression of epithelial to mesenchymal transition markers and inhibiting migration.

    PubMed

    Suresh, Shruthy; Raghu, Dinesh; Karunagaran, Devarajan

    2013-01-01

    Oral cancer is one of the most commonly occurring cancers worldwide, decreasing the patient's survival rate due to tumor recurrence and metastasis. Menadione (Vitamin K3) is known to exhibit cytotoxicity in various cancer cells but the present study focused on its effects on viability, apoptosis, epithelial to mesenchymal transition (EMT), anchorage independent growth and migration of oral cancer cells. The results show that menadione is more cytotoxic to SAS (oral squamous carcinoma) cells but not to non-tumorigenic HEK293 and HaCaT cells. Menadione treatment increased the expression of pro-apoptotic proteins, Bax and p53, with a concurrent decrease in anti-apoptotic proteins, Bcl-2 and p65. Menadione induced the expression of E-cadherin but reduced the expression of EMT markers, vimentin and fibronectin. Menadione also inhibited anchorage independent growth and migration in SAS cells. These findings reveal and confirm that menadione is a potential candidate in oral cancer therapy as it exhibits cytotoxic, antineoplastic and antimigratory effects besides effectively blocking EMT in oral cancer cells.

  20. Indonesia's migration transition.

    PubMed

    Hugo, G

    1995-01-01

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

  1. Repeat migration and disappointment.

    PubMed

    Grant, E K; Vanderkamp, J

    1986-01-01

    This article investigates the determinants of repeat migration among the 44 regions of Canada, using information from a large micro-database which spans the period 1968 to 1971. The explanation of repeat migration probabilities is a difficult task, and this attempt is only partly successful. May of the explanatory variables are not significant, and the overall explanatory power of the equations is not high. In the area of personal characteristics, the variables related to age, sex, and marital status are generally significant and with expected signs. The distance variable has a strongly positive effect on onward move probabilities. Variables related to prior migration experience have an important impact that differs between return and onward probabilities. In particular, the occurrence of prior moves has a striking effect on the probability of onward migration. The variable representing disappointment, or relative success of the initial move, plays a significant role in explaining repeat migration probabilities. The disappointment variable represents the ratio of actural versus expected wage income in the year after the initial move, and its effect on both repeat migration probabilities is always negative and almost always highly significant. The repeat probabilities diminish after a year's stay in the destination region, but disappointment in the most recent year still has a bearing on the delayed repeat probabilities. While the quantitative impact of the disappointment variable is not large, it is difficult to draw comparisons since similar estimates are not available elsewhere.

  2. Environmental concerns and international migration.

    PubMed

    Hugo, G

    1996-01-01

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

  3. Biometrics and international migration.

    PubMed

    Redpath, Jillyanne

    2007-01-01

    This paper will focus on the impact of the rapid expansion in the use of biometric systems in migration management on the rights of individuals; it seeks to highlight legal issues for consideration in implementing such systems, taking as the starting point that the security interests of the state and the rights of the individual are not, and should not be, mutually exclusive. The first part of this paper briefly describes the type of biometric applications available, how biometric systems function, and those used in migration management. The second part examines the potential offered by biometrics for greater security in migration management, and focuses on developments in the use of biometrics as a result of September 11. The third part discusses the impact of the use of biometrics in the management of migration on the individual's right to privacy and ability to move freely and lawfully. The paper highlights the increasing need for domestic and international frameworks to govern the use of biometric applications in the migration/security context, and proposes a number of issues that such frameworks could address.

  4. Migration and pension.

    PubMed

    Razin, A; Sadka, E

    1998-11-01

    "Migration has important implications for the financial soundness of the pension system.... While it is common sense to expect that young migrants, even if low-skilled, can help society pay the benefits to the currently elderly, it may nevertheless be reasonable to argue that these migrants would adversely affect current young since, after all, the migrants are net beneficiaries of the welfare state. In contrast to the adverse effects of low skilled migration in a static model, [the authors] show that in a Samuelsonian overlapping generations model...migration is a Pareto-improving measure. All the existing income (low and high) and age (young and old) groups living at the time of the migrant's arrival would be better off." excerpt

  5. [Phagocyte migration: an overview].

    PubMed

    Le Cabec, Véronique; Van Goethem, Emeline; Guiet, Romain; Maridonneau-Parini, Isabelle

    2011-12-01

    Phagocytes are the first line of host defense thanks to their capacity to infiltrate infected and wounded tissues, where they exert their bactericidal and tissue repair functions. However, tissue infiltration of phagocytes also stimulates the progression of pathologies such as cancer and chronic inflammatory diseases. It is therefore necessary to identify the molecular and cellular mechanisms that control this process to identify new therapeutic targets. Phagocytes leave the blood stream by crossing the vascular wall and infiltrate interstitial tissues, a three-dimensional environment. A state-of-the-art of the different steps of phagocyte tissue recruitment in vivo and of the different in vitro models is developed in this synthesis. We focus on recent data concerning the migration of phagocytes in three-dimensional environments. The use of two different migration modes, amoeboid and mesenchymal, by macrophages and the role of podosomes and proteases in the mesenchymal migration are discussed. © 2011 médecine/sciences – Inserm / SRMS.

  6. Insulin promotes cell migration by regulating PSA-NCAM

    SciTech Connect

    Monzo, Hector J.; Coppieters, Natacha; Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland

    Cellular interactions with the extracellular environment are modulated by cell surface polysialic acid (PSA) carried by the neural cell adhesion molecule (NCAM). PSA-NCAM is involved in cellular processes such as differentiation, plasticity, and migration, and is elevated in Alzheimer's disease as well as in metastatic tumour cells. Our previous work demonstrated that insulin enhances the abundance of cell surface PSA by inhibiting PSA-NCAM endocytosis. In the present study we have identified a mechanism for insulin-dependent inhibition of PSA-NCAM turnover affecting cell migration. Insulin enhanced the phosphorylation of the focal adhesion kinase leading to dissociation of αv-integrin/PSA-NCAM clusters, and promoted cellmore » migration. Our results show that αv-integrin plays a key role in the PSA-NCAM turnover process. αv-integrin knockdown stopped PSA-NCAM from being endocytosed, and αv-integrin/PSA-NCAM clusters co-labelled intracellularly with Rab5, altogether indicating a role for αv-integrin as a carrier for PSA-NCAM during internalisation. Furthermore, inhibition of p-FAK caused dissociation of αv-integrin/PSA-NCAM clusters and counteracted the insulin-induced accumulation of PSA at the cell surface and cell migration was impaired. Our data reveal a functional association between the insulin/p-FAK-dependent regulation of PSA-NCAM turnover and cell migration through the extracellular matrix. Most importantly, they identify a novel mechanism for insulin-stimulated cell migration. - Highlights: • Insulin modulates PSA-NCAM turnover through upregulation of p-FAK. • P-FAK modulates αv-integrin/PSA-NCAM clustering. • αv-integrin acts as a carrier for PSA-NCAM endocytosis. • Cell migration is promoted by cell surface PSA. • Insulin promotes PSA-dependent migration in vitro.« less

  7. 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

  8. [Migration, climate and health].

    PubMed

    Tellier, Siri; Carballo, Manuel; Calballo, Manuel

    2009-10-26

    Many tentative connections have been postulated between migration and climate. This article points to rural-urban migration, particularly into low elevation urban slums prone to flooding as an issue needing urgent attention by health professionals. It also notes the no-man's land in which environmental refugees find themselves and the consequences this may have. Finally, it points to the urgent need to reform health systems in both developing and developed countries to adapt to rapidly changing disease patterns and to become more responsive to them.

  9. What's driving migration?

    PubMed

    Kane, H

    1995-01-01

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

  10. [Migration and diabetes].

    PubMed

    Aydinkoc-Tuzcu, Kadriye; Schindler, Karin; Kautzky-Willer, Alexandra; Ludvik, Bernhard; Fasching, Peter

    2016-04-01

    The article deals with the demographic data of migration in Austria and with therapeutic advice concerning drug therapy and diabetes education for patients with migration background. In this context socio-cultural specifics are discussed. These suggestions are seen complementary to the general treatment guidelines of the Austrian Diabetes Association.Especially for the fast months Ramadan there are a lot of informations. The most important point is that the patient care must be highly individualized and the management plan may differ for each patient.

  11. Extrinsic ion migration in perovskite solar cells

    DOE PAGES

    Li, Zhen; Xiao, Chuanxiao; Yang, Ye; ...

    2017-04-10

    In this study, the migration of intrinsic ions (e.g., MA +, Pb 2+, I –) in organic–inorganic hybrid perovskites has received significant attention with respect to the critical roles of these ions in the hysteresis and degradation in perovskite solar cells (PSCs). Here, we demonstrate that extrinsic ions (e.g., Li +, H +, Na +), when used in the contact layers in PSCs, can migrate across the perovskite layer and strongly impact PSC operation. In a TiO 2/perovskite/spiro-OMeTAD-based PSC, Li +-ion migration from spiro-OMeTAD to the perovskite and TiO 2 layer is illustrated by time-of-flight secondary-ion mass spectrometry. The movementmore » of Li + ions in PSCs plays an important role in modulating the solar cell performance, tuning TiO 2 carrier-extraction properties, and affecting hysteresis in PSCs. The influence of Li +-ion migration was investigated using time-resolved photoluminescence, Kelvin probe force microscopy, and external quantum efficiency spectra. Other extrinsic ions such as H + and Na + also show a clear impact on the performance and hysteresis in PSCs. Understanding the impacts of extrinsic ions in perovskite-based devices could lead to new material and device designs to further advance perovskite technology for various applications.« less

  12. Brain Migration Revisited

    ERIC Educational Resources Information Center

    Vinokur, Annie

    2006-01-01

    The "brain drain/brain gain" debate has been going on for the past 40 years, with irresolvable theoretical disputes and unenforceable policy recommendations that economists commonly ascribe to the lack of reliable empirical data. The recent report of the World Bank, "International migration, remittances and the brain drain", documents the…

  13. Strain effects on oxygen migration in perovskites.

    PubMed

    Mayeshiba, Tam; Morgan, Dane

    2015-01-28

    Fast oxygen transport materials are necessary for a range of technologies, including efficient and cost-effective solid oxide fuel cells, gas separation membranes, oxygen sensors, chemical looping devices, and memristors. Strain is often proposed as a method to enhance the performance of oxygen transport materials, but the magnitude of its effect and its underlying mechanisms are not well-understood, particularly in the widely-used perovskite-structured oxygen conductors. This work reports on an ab initio prediction of strain effects on migration energetics for nine perovskite systems of the form LaBO3, where B = [Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Ga]. Biaxial strain, as might be easily produced in epitaxial systems, is predicted to lead to approximately linear changes in migration energy. We find that tensile biaxial strain reduces the oxygen vacancy migration barrier across the systems studied by an average of 66 meV per percent strain for a single selected hop, with a low of 36 and a high of 89 meV decrease in migration barrier per percent strain across all systems. The estimated range for the change in migration barrier within each system is ±25 meV per percent strain when considering all hops. These results suggest that strain can significantly impact transport in these materials, e.g., a 2% tensile strain can increase the diffusion coefficient by about three orders of magnitude at 300 K (one order of magnitude at 500 °C or 773 K) for one of the most strain-responsive materials calculated here (LaCrO3). We show that a simple elasticity model, which assumes only dilative or compressive strain in a cubic environment and a fixed migration volume, can qualitatively but not quantitatively model the strain dependence of the migration energy, suggesting that factors not captured by continuum elasticity play a significant role in the strain response.

  14. Engineered Models of Confined Cell Migration

    PubMed Central

    Paul, Colin D.; Hung, Wei-Chien; Wirtz, Denis; Konstantopoulos, Konstantinos

    2017-01-01

    Cells in the body are physically confined by neighboring cells, tissues, and the extracellular matrix. Although physical confinement modulates intracellular signaling and the underlying mechanisms of cell migration, it is difficult to study in vivo. Furthermore, traditional two-dimensional cell migration assays do not recapitulate the complex topographies found in the body. Therefore, a number of experimental in vitro models that confine and impose forces on cells in well-defined microenvironments have been engineered. We describe the design and use of microfluidic microchannel devices, grooved substrates, micropatterned lines, vertical confinement devices, patterned hydrogels, and micropipette aspiration assays for studying cell responses to confinement. Use of these devices has enabled the delineation of changes in cytoskeletal reorganization, cell–substrate adhesions, intracellular signaling, nuclear shape, and gene expression that result from physical confinement. These assays and the physiologically relevant signaling pathways that have been elucidated are beginning to have a translational and clinical impact. PMID:27420571

  15. Method of migrating seismic records

    DOEpatents

    Ober, Curtis C.; Romero, Louis A.; Ghiglia, Dennis C.

    2000-01-01

    The present invention provides a method of migrating seismic records that retains the information in the seismic records and allows migration with significant reductions in computing cost. The present invention comprises phase encoding seismic records and combining the encoded seismic records before migration. Phase encoding can minimize the effect of unwanted cross terms while still allowing significant reductions in the cost to migrate a number of seismic records.

  16. The OPEN Migration Platform Architecture

    NASA Astrophysics Data System (ADS)

    Martin, Miquel

    This chapter establishes a common understanding of the meaning of migration, and introduces the OPEN functionalities, which enable application migration. We start by discussing the various definitions of migration, before focusing on the OPEN take on the concept. The chapter then covers our proposed architecture , as well as the functionality required, both from the server and the client side (i.e. the applications) in order to enable application migration.

  17. The commercialization of migration.

    PubMed

    Abrera-mangahas, M A

    1989-01-01

    International migration is not new to the Philippines. In the recent outflow of contract workers to the Middle East, there is a shift from individual and family initiated migrations to the more organized, highly commercial variety. While profit-taking intermediaries have played some role in the past, the increase in the number and influence of these intermediaries has altered the story of migration decision-making. In 1975, the signing of the bilateral labor agreement between the governments of Iran and the Philippines signalled the rising demand for Filipino contract workers. From 1970 to 1975, the number of Asian migrant workers in the Gulf countries rose from about 120,000 to 370,000. These figures rose dramatically to 3.3 million in 1985. The growing share of organized and commercialized migration has altered migration decision making. Primarily, intermediaries are able to broaden access to foreign job and high wage opportunities. Commercialization effectively raises the transaction costs for contract migration. Studies on recruitment costs and fees show that self-solicited foreign employment costs less than employment obtained through recruitment agents and intermediaries. The difference in the 2 prices is due, not only to overhead costs of intermediation, but more importantly to the rent exacted by agents from having job information and placement rights. In the Philippines in October 1987 the average placement fee was P8000, greatly exceeding the mandated maximum fee level of P5000. This average is understated because the computation includes the 17% who do not pay any fees. The widespread and popular view of recruitment intermediaries is negative, dominated by images of abuses and victims. Private intermediaries and the government bureaucracy need each other. Intermediaries need government; their consistent demand for incentives and protection is indicative. On the other hand, government expands its supervision of control of overseas employment via the

  18. Gβ1 is required for neutrophil migration in zebrafish.

    PubMed

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

    2017-08-01

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

  19. Refugee children's play: Before and after migration to Australia.

    PubMed

    MacMillan, Kelli K; Ohan, Jeneva; Cherian, Sarah; Mutch, Raewyn C

    2015-08-01

    Play is vital to children's development, health and resilience. Play modulates cognitive, emotional and social well-being. Children constitute approximately half of all humanitarian refugee entrants resettled in Australia. Refugee children are commonly victims and witnesses of war and persecution, living across resource-poor environs during transit. Little is known about the effects of refugee migration on play. This study explores how refugee children engaged in play pre-migration (in their home country) and post-migration (Australia). Refugee children attending the Refugee Health Clinic of a tertiary children's hospital were invited to complete a qualitative descriptive study of play. The children were asked to draw how they played pre- and post-migration. Drawings were analysed for (i) the presence of play; (ii) location of play; and (iii) drawing detail. Nineteen refugee children were recruited (mean age 8.5 years ± standard deviation 6.4 months). Significantly fewer children drew play pre- versus post-migration (11/19, 58% vs. 18/19, 95% P < 0.03). Girls had greater comparative changes in play with migration (pre: 2/8, 25% vs. post: 7/8, 87%, P = 0.06), trending to significance. Of those children who drew play, almost all drew playing outside (pre-migration: 10/11, 90.9%; post-migration: 17/18, 94.4%). Drawings showed equivalent detail pre- and post-migration. Resettled refugee children, especially girls, demonstrated limited play pre-migration, with higher levels of engagement post-resettlement. Facilitating opportunities for variety of play may strengthen positive resettlement outcomes for children and parents. Larger longitudinal studies examining play in refugee children and associations with physical, development and psychological well-being are warranted. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  20. Forced Migration: Refugee Populations

    PubMed Central

    Boyle, Joyceen S.

    2015-01-01

    Undocumented migration is a global phenomenon that manifests in various contexts. This article describes the impact of the movement of large numbers of people in several African countries, producing a unique type of migrant—the refugee. We describe issues that refugee movements create on fragile health care systems, situations that precipitate refugee movements, certain human rights violations that are of particular concern such as gender based violence (GBV) and child soldiers, and lastly, implications for nursing practice and policy. We use examples from several countries in Sub-Saharan Africa, including the Democratic Republic of the Congo, Rwanda, Liberia, Sierra Leone, and Mozambique. Drawing on key documents from the United Nations High Commissioner for Refugees, current literature, as well as the international experience of the authors, this article presents an overview of forced migration and discusses opportunities for nurses to impact research, practice and policy related to refugee health. PMID:25645484

  1. Migration and stratification

    PubMed Central

    Jasso, Guillermina

    2011-01-01

    Migration and stratification are increasingly intertwined. One day soon it will be impossible to understand one without the other. Both focus on life chances. Stratification is about differential life chances - who gets what and why - and migration is about improving life chances - getting more of the good things of life. To examine the interconnections of migration and stratification, we address a mix of old and new questions, carrying out analyses newly enabled by a unique new data set on recent legal immigrants to the United States (the New Immigrant Survey). We look at immigrant processing and lost documents, depression due to the visa process, presentation of self, the race-ethnic composition of an immigrant cohort (made possible by the data for the first time since 1961), black immigration from Africa and the Americas, skin-color diversity among couples formed by U.S. citizen sponsors and immigrant spouses, and English fluency among children age 8–12 and their immigrant parents. We find, inter alia, that children of previously illegal parents are especially more likely to be fluent in English, that native-born U.S. citizen women tend to marry darker, that immigrant applicants who go through the visa process while already in the United States are more likely to have their documents lost and to suffer visa depression, and that immigration, by introducing accomplished black immigrants from Africa (notably via the visa lottery), threatens to overturn racial and skin color associations with skill. Our analyses show the mutual embeddedness of migration and stratification in the unfolding of the immigrants' and their children's life chances and the impacts on the stratification structure of the United States. PMID:26321771

  2. Computational model of mesenchymal migration in 3D under chemotaxis.

    PubMed

    Ribeiro, F O; Gómez-Benito, M J; Folgado, J; Fernandes, P R; García-Aznar, J M

    2017-01-01

    Cell chemotaxis is an important characteristic of cellular migration, which takes part in crucial aspects of life and development. In this work, we propose a novel in silico model of mesenchymal 3D migration with competing protrusions under a chemotactic gradient. Based on recent experimental observations, we identify three main stages that can regulate mesenchymal chemotaxis: chemosensing, dendritic protrusion dynamics and cell-matrix interactions. Therefore, each of these features is considered as a different module of the main regulatory computational algorithm. The numerical model was particularized for the case of fibroblast chemotaxis under a PDGF-bb gradient. Fibroblasts migration was simulated embedded in two different 3D matrices - collagen and fibrin - and under several PDGF-bb concentrations. Validation of the model results was provided through qualitative and quantitative comparison with in vitro studies. Our numerical predictions of cell trajectories and speeds were within the measured in vitro ranges in both collagen and fibrin matrices. Although in fibrin, the migration speed of fibroblasts is very low, because fibrin is a stiffer and more entangling matrix. Testing PDGF-bb concentrations, we noticed that an increment of this factor produces a speed increment. At 1 ng mL -1 a speed peak is reached after which the migration speed diminishes again. Moreover, we observed that fibrin exerts a dampening behavior on migration, significantly affecting the migration efficiency.

  3. Conservation physiology of animal migration

    PubMed Central

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

    2016-01-01

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

  4. Conservation physiology of animal migration.

    PubMed

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

    2016-01-01

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

  5. Gender and migration from Albania.

    PubMed

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

    2010-11-01

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

  6. Gender and Migration from Albania

    PubMed Central

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

    2010-01-01

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

  7. Presynaptic muscarinic acetylcholine autoreceptors (M1, M2 and M4 subtypes), adenosine receptors (A1 and A2A) and tropomyosin-related kinase B receptor (TrkB) modulate the developmental synapse elimination process at the neuromuscular junction.

    PubMed

    Nadal, Laura; Garcia, Neus; Hurtado, Erica; Simó, Anna; Tomàs, Marta; Lanuza, Maria A; Santafé, Manel; Tomàs, Josep

    2016-06-23

    The development of the nervous system involves an initially exuberant production of neurons that make an excessive number of synaptic contacts. The initial overproduction of synapses promotes connectivity. Hebbian competition between axons with different activities (the least active are punished) leads to the loss of roughly half of the overproduced elements and this refines connectivity and increases specificity. The neuromuscular junction is innervated by a single axon at the end of the synapse elimination process and, because of its relative simplicity, has long been used as a model for studying the general principles of synapse development. The involvement of the presynaptic muscarinic ACh autoreceptors may allow for the direct competitive interaction between nerve endings through differential activity-dependent acetylcholine release in the synaptic cleft. Then, the most active ending may directly punish the less active ones. Our previous results indicate the existence in the weakest axons on the polyinnervated neonatal NMJ of an ACh release inhibition mechanism based on mAChR coupled to protein kinase C and voltage-dependent calcium channels. We suggest that this mechanism plays a role in the elimination of redundant neonatal synapses. Here we used confocal microscopy and quantitative morphological analysis to count the number of brightly fluorescent axons per endplate in P7, P9 and P15 transgenic B6.Cg-Tg (Thy1-YFP)16 Jrs/J mice. We investigate the involvement of individual mAChR M1-, M2- and M4-subtypes in the control of axonal elimination after the Levator auris longus muscle had been exposed to agonist and antagonist in vivo. We also analysed the role of adenosine receptor subtypes (A1 and A2A) and the tropomyosin-related kinase B receptor. The data show that postnatal axonal elimination is a regulated multireceptor mechanism that guaranteed the monoinnervation of the neuromuscular synapses. The three receptor sets considered (mAChR, AR and TrkB receptors

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

    PubMed

    Fukurai, H

    1991-01-01

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

  9. ILO - International Migration Programme.

    PubMed

    Boudraa, Miriam

    2011-01-01

    In a wide International Context characterised not only by the economical development but also by the social, cultural, political and individual development, we witness more and more to a exchange between the developed and the developing countries, which can be translated especially in the migration of the work force. In theory, all countries are either countries of origin either countries of transit or destination, and they are all responsible for the rights of migrant workers by promoting the rights, by monitoring and by preventing the abusive conditions. The process of migration of the workforce can be divided into three stages: the first coincides with the period prior to departure, the second is represented by the aftermath of the departure and the period of stay in the country of destination, the third stage corresponds to the return in the country of origin. The workers must be protected throughout this process by the international organizations that perform the catalytic role of communication and exchange between countries, for the only purpose of protecting the rights of immigrant and/or immigrants workers. The responsibility for the protection of workers is divided among the various players in the International Labour Organisation. Every country has to apply measures according to the international standards regarding workers' rights, standards that guide the various countries in the formulation and implementation of their policies and legislation. These standards are suggested by International Conventions, the ILO Conventions and other international instruments such as the human rights instrument. There has been a big step forward once the ILO Fundamental Conventions and Conventions on Migrant Workers where implemented and this implementation represented the use of the Guidelines "ILO Multilateral Framework on Labour Migration".

  10. Lines of evidence for environmentally driven human migration

    NASA Astrophysics Data System (ADS)

    Davis, K. F.; D'Odorico, P.

    2012-12-01

    determine additional factors that may help explain migration at global, regional, continental and community-based (i.e. maximized module) scales. Lastly, we explore the relationship between migration and natural disasters (e.g. drought, flooding) to identify instances in which the environment is a proximate cause of human displacement and in turn use this information to determine if a subsequent cascade of human movements appears in neighboring countries as a result of the elevated inflow of migrants from the initial country of interest. In this way, we seek to gain a fuller picture of the environmental factors driving the dynamics of modern human migration.

  11. Migration of Asteroidal Dust

    NASA Technical Reports Server (NTRS)

    Ipatov, S. I.; Mather, J. C.

    2003-01-01

    Using the Bulirsh Stoer method of integration, we investigated the migration of dust particles under the gravitational influence of all planets, radiation pressure, Poynting Robertson drag and solar wind drag for equal to 0.01, 0.05, 0.1, 0.25, and 0.4. For silicate particles such values of correspond to diameters equal to about 40, 9, 4, 2, and 1 microns, respectively [1]. The relative error per integration step was taken to be less than 10sup-8. Initial orbits of the particles were close to the orbits of the first numbered mainbelt asteroids.

  12. Migration and AIDS.

    PubMed

    Decosas, J; Kane, F; Anarfi, J K; Sodji, K D; Wagner, H U

    1995-09-23

    A successful short-term solution to transmission of AIDS in Western Africa by migrants involves provision of accessible and acceptable basic health and social services to migrants at their destination. The aim is to establish a sense of security and community, which is a health requirement. When migrants are excluded from community life or victimized as carriers of HIV infections, they will be driven by basic survival needs and dysfunctional social organization, which results in the rapid spread of HIV. Closing borders and mass deportation may not be an option. The long-term solution is population policy, environmental protection, and economic development. The focus on mapping the spread of AIDS must shift to a consideration of the migrant social conditions that make them vulnerable to AIDS. The issue of migration and AIDS will be addressed at the First European Conference on Tropical Medicine in October 1995 in Hamburg, Germany. In Uganda, HIV seroprevalence rates ranged from 5.5% among the stable population to 12.4% among internal migrants moving between villages to 16.3% among migrants from other areas. A World Bank project is operating in Western Africa, which traces seasonal male migration from the Cameroon to Liberia, Senegal to Nigeria, and from the Sahel to the coast during dry seasons. National border rules may influence the routes but not the extent of migration. A major destination place is Cote d' Ivoire, which has 25% of total population comprised of migrants from other countries and one of the highest HIV prevalence rates in Western Africa. On plantations prostitutes are brought in. Each prostitute serves about 25 workers. The pattern of sexual mixing contributes to the high HIV rates. Female migration is smaller and usually concentrated in prostitution at place of destination. Illiteracy and poverty drive women migrants into the trade. Their frequent health problems are malaria, pelvic pain, menstrual irregularity, vaginal discharge, and genital

  13. Excitation mechanism of non-migrating tides

    NASA Astrophysics Data System (ADS)

    Miyoshi, Yasunobu; Pancheva, Dora; Mukhtarov, Plamen; Jin, Hidekatsu; Fujiwara, Hitoshi; Shinagawa, Hiroyuki

    2017-04-01

    Using an atmosphere-ionosphere coupled model, the excitation source and temporal (seasonal and interannual) variations in non-migrating tides are investigated in this study. We first focus our attention on temporal variations in eastward moving diurnal tide with zonal wavenumber 3 (DE3), which is the largest of all the non-migrating tides in the mesosphere and lower thermosphere (MLT). Our simulation results indicate that upward propagation of the DE3 excited in the troposphere is sensitive to the zonal mean zonal wind in the stratosphere and mesosphere. The DE3 amplitude is enhanced in the region where the vertical shear of the zonal mean zonal wind is positive (westerly shear). Quasi-2-year variation in the DE3 amplitude in the MLT region is generated by quasi-2-year variation in the zonal mean zonal wind between 40 and 70 km, which is modulated by the stratospheric QBO. The excitation mechanisms of SW3 (westward moving semidiurnal tide with zonal wavenumber 3) and SW1 (westward moving semidiurnal tide with zonal wavenumber 1) are also investigated. During equinoxes, the SW3 and SW1 are excited by tropospheric heating (latent heat release and solar radiative heating) associated with cumulus convection in the tropics, and propagate upward into the MLT region. On the other hand, during solstices, SW3 and SW1 are generated in the winter stratosphere and mesosphere through the nonlinear interaction between the stationary planetary wave and migrating semidiurnal tide, and propagate upward to the lower thermosphere. The excitation sources of other non-migrating tides are also discussed.

  14. Collective cell migration in development

    PubMed Central

    Scarpa, Elena

    2016-01-01

    During embryonic development, tissues undergo major rearrangements that lead to germ layer positioning, patterning, and organ morphogenesis. Often these morphogenetic movements are accomplished by the coordinated and cooperative migration of the constituent cells, referred to as collective cell migration. The molecular and biomechanical mechanisms underlying collective migration of developing tissues have been investigated in a variety of models, including border cell migration, tracheal branching, blood vessel sprouting, and the migration of the lateral line primordium, neural crest cells, or head mesendoderm. Here we review recent advances in understanding collective migration in these developmental models, focusing on the interaction between cells and guidance cues presented by the microenvironment and on the role of cell–cell adhesion in mechanical and behavioral coupling of cells within the collective. PMID:26783298

  15. Nuclear Migration During Retinal Development

    PubMed Central

    Baye, Lisa M.; Link, Brian A.

    2009-01-01

    In this review we focus on the mechanisms, regulation, and cellular consequences of nuclear migration in the developing retina. In the nervous system, nuclear migration is prominent during both proliferative and post-mitotic phases of development. Interkinetic nuclear migration is the process where the nucleus oscillates from the apical to basal surfaces in proliferative neuroepithelia. Proliferative nuclear movement occurs in step with the cell cycle, with M-phase being confined to the apical surface and G1-, S-, and G2-phases occurring at more basal locations. Later, following cell cycle exit, some neuron precursors migrate by nuclear translocation. In this mode of cellular migration, nuclear movement is the driving force for motility. Following discussion of the key components and important regulators for each of these processes, we present an emerging model where interkinetic nuclear migration functions to distinguish cell fates among retinal neuroepithelia. PMID:17560964

  16. An ill wind? Climate change, migration, and health.

    PubMed

    McMichael, Celia; Barnett, Jon; McMichael, Anthony J

    2012-05-01

    Climate change is projected to cause substantial increases in population movement in coming decades. Previous research has considered the likely causal influences and magnitude of such movements and the risks to national and international security. There has been little research on the consequences of climate-related migration and the health of people who move. In this review, we explore the role that health impacts of climate change may play in population movements and then examine the health implications of three types of movements likely to be induced by climate change: forcible displacement by climate impacts, resettlement schemes, and migration as an adaptive response. This risk assessment draws on research into the health of refugees, migrants, and people in resettlement schemes as analogs of the likely health consequences of climate-related migration. Some account is taken of the possible modulation of those health risks by climate change. Climate-change-related migration is likely to result in adverse health outcomes, both for displaced and for host populations, particularly in situations of forced migration. However, where migration and other mobility are used as adaptive strategies, health risks are likely to be minimized, and in some cases there will be health gains. Purposeful and timely policy interventions can facilitate the mobility of people, enhance well-being, and maximize social and economic development in both places of origin and places of destination. Nevertheless, the anticipated occurrence of substantial relocation of groups and communities will underscore the fundamental seriousness of human-induced climate change.

  17. Bacterial migration along solid surfaces.

    PubMed Central

    Harkes, G; Dankert, J; Feijen, J

    1992-01-01

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

  18. Process migration in UNIX environments

    NASA Technical Reports Server (NTRS)

    Lu, Chin; Liu, J. W. S.

    1988-01-01

    To support process migration in UNIX environments, the main problem is how to encapsulate the location dependent features of the system in such a way that a host independent virtual environment is maintained by the migration handlers on the behalf of each migrated process. An object-oriented approach is used to describe the interaction between a process and its environment. More specifically, environmental objects were introduced in UNIX systems to carry out the user-environment interaction. The implementation of the migration handlers is based on both the state consistency criterion and the property consistency criterion.

  19. 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

  20. 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

  1. The future scenario for international labour migration.

    PubMed

    Tassello, G

    1989-01-01

    The study of migration helps us to grasp the social evolution and the political and economic strategies required to meet the new economic trends. The issue of permanent or temporary migration, long debated in the 1960s, now tends to disappear. Migrants are compared more to commuters on the international labor markets. Besides the economic out-migration flows, there are also the refugee migrations or the ever present phenomenon of persons uprooted from their home country as a result of natural disasters and famine. The worldwide economic crisis in the 1970s, the recession affecting some industrialized countries which used to be traditional labor-importing countries have barred many potential immigrant workers from entering these countries. If, on 1 hand, the persistent high rate of unemployment due to the transformation of industry and the computerization process has caused the dismissal of numerous unskilled--mainly immigrants--on the other hand, it has created the exigency of highly qualified personnel. The children of the indigenous population are therefore favored because of their better scholastic training. A 2nd generation is now condemned to remain marginal even though they have been brought up to the ideals of social improvement and integration into higher standards of living. A highly dissatisfied category of young people is now an integral part of many labor-importing countries. Many industrial countries are flirting with zero population growth. Considering the demographic, economic, social, and political imbalances which exist and tend to grow, the world now has all the prerequisites for huge and prolonged migration flows originating from the South and moving almost exclusively toward the megacities and the industrial countries in the North. As long as technological as well as social inequalities persist, inner and international migration flows will continue. It is evident that the aim of many highly industrialized countries is the total ceasing of all

  2. Module Configuration

    DOEpatents

    Oweis, Salah; D'Ussel, Louis; Chagnon, Guy; Zuhowski, Michael; Sack, Tim; Laucournet, Gaullume; Jackson, Edward J.

    2002-06-04

    A stand alone battery module including: (a) a mechanical configuration; (b) a thermal management configuration; (c) an electrical connection configuration; and (d) an electronics configuration. Such a module is fully interchangeable in a battery pack assembly, mechanically, from the thermal management point of view, and electrically. With the same hardware, the module can accommodate different cell sizes and, therefore, can easily have different capacities. The module structure is designed to accommodate the electronics monitoring, protection, and printed wiring assembly boards (PWAs), as well as to allow airflow through the module. A plurality of modules may easily be connected together to form a battery pack. The parts of the module are designed to facilitate their manufacture and assembly.

  3. ANTIGENIC MODULATION

    PubMed Central

    Old, Lloyd J.; Stockert, Elisabeth; Boyse, Edward A.; Kim, Jae Ho

    1968-01-01

    Antigenic modulation (the loss of TL antigens from TL+ cells exposed to TL antibody in the absence of lytic complement) has been demonstrated in vitro. An ascites leukemia, phenotype TL.1,2,3, which modulates rapidly and completely when incubated with TL antiserum in vitro, was selected for further study of the phenomenon. Over a wide range of TL antibody concentrations modulation at 37°C was detectable within 10 min and was complete within approximately 1 hr. The cells were initially sensitized to C' by their contact with antibody, thereafter losing this sensitivity to C' lysis together with their sensitivity to TL antibody and C' in the cytotoxic test. The capacity of the cells to undergo modulation was abolished by actinomycin D and by iodoacetamide, and by reducing the temperature of incubation to 0°C. Thus modulation apparently is an active cellular process. Antigens TL. 1,2, and 3 are all modulated by anti-TL.1,3 serum and by anti-TL.3 serum. This modulation affects all three TL components together, even when antibody to one or two of them is lacking. aAnti-TL.2 serum does not induce modulation and in fact impairs modulation by the other TL antibodies. The influence of the TL phenotype of cells upon the demonstrable content of H-2 (D region) isoantigen, first shown in cells modulated in vivo, has been observed with cells modulated in vitro. Cells undergoing modulation show a progressive increase in H-2 (D region) antigen over a period of 4 hr, with no change in H-2 antigens of the K region. Restoration of the TL+ phenotype of modulated cells after removal of antibody is less rapid than TL+ → TL- modulation and may require several cell divisions. PMID:5636556

  4. Africa: Setting for Human Migration

    ERIC Educational Resources Information Center

    Buuba, Babacar Diop

    2007-01-01

    Analysis of African migrations can help to understand prehistoric, historical, ancient modern and contemporaneous migrations. Movements of populations were and continue to be so intense that, for some analysts, they constitute one of the dominant trends of the history and destiny of the very old continent. African and non-African states, whether…

  5. Regulation of Cell Migration in Breast Cancer

    DTIC Science & Technology

    2011-04-01

    the wound healing, assay by scarring and Oris plate migration assay, transwell migration assay and live - cell imaging studies. Cell migration capacity...evaluated by the use of techniques that include the wound healing assay by scarring and Oris plate migration assay, transwell migration assay and live - cell imaging studies

  6. Stimulatory effect of boron and manganese salts on keratinocyte migration.

    PubMed

    Chebassier, Nathalie; Ouijja, El Houssein; Viegas, Isabelle; Dreno, Brigitte

    2004-01-01

    Keratinocyte proliferation and migration are essential for the reconstruction of the cutaneous barrier after skin injury. Interestingly, thermal waters which are rich in trace elements (e.g. boron and manganese), are known to be able to improve wound healing. In order to understand the mechanism of action of this effect, our study investigated the in vitro modulation of keratinocyte migration and proliferation by boron and manganese salts, which are present in high concentrations in a thermal water (Saint Gervais). Our in vitro study demonstrated that incubating keratinocytes for 24 h with boron salts at concentrations between 0.5 and 10 microg/ml or manganese salts at concentrations between 0.1 and 1.5 microg/ml accelerated wound closure compared with control medium (+20%). As this acceleration was not related to an increase in keratinocyte proliferation we suggest that boron and manganese act on wound healing mainly by increasing the migration of keratinocytes.

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

    PubMed

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

    2016-09-01

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

  8. Migration of dispersive GPR data

    USGS Publications Warehouse

    Powers, M.H.; Oden, C.P.; ,

    2004-01-01

    Electrical conductivity and dielectric and magnetic relaxation phenomena cause electromagnetic propagation to be dispersive in earth materials. Both velocity and attenuation may vary with frequency, depending on the frequency content of the propagating energy and the nature of the relaxation phenomena. A minor amount of velocity dispersion is associated with high attenuation. For this reason, measuring effects of velocity dispersion in ground penetrating radar (GPR) data is difficult. With a dispersive forward model, GPR responses to propagation through materials with known frequency-dependent properties have been created. These responses are used as test data for migration algorithms that have been modified to handle specific aspects of dispersive media. When either Stolt or Gazdag migration methods are modified to correct for just velocity dispersion, the results are little changed from standard migration. For nondispersive propagating wavefield data, like deep seismic, ensuring correct phase summation in a migration algorithm is more important than correctly handling amplitude. However, the results of migrating model responses to dispersive media with modified algorithms indicate that, in this case, correcting for frequency-dependent amplitude loss has a much greater effect on the result than correcting for proper phase summation. A modified migration is only effective when it includes attenuation recovery, performing deconvolution and migration simultaneously.

  9. Vulnerable to HIV / AIDS. Migration.

    PubMed

    Fernandez, I

    1998-01-01

    This special report discusses the impact of globalization, patterns of migration in Southeast Asia, gender issues in migration, the links between migration and HIV/AIDS, and spatial mobility and social networks. Migrants are particularly marginalized in countries that blame migrants for transmission of infectious and communicable diseases and other social ills. Effective control of HIV/AIDS among migrant and native populations requires a multisectoral approach. Programs should critically review the privatization of health care services and challenge economic models that polarize the rich and the poor, men and women, North and South, and migrant and native. Programs should recognize the equality between locals and migrants in receipt of health services. Countermeasures should have input from migrants in order to reduce the conditions that increase vulnerability to HIV/AIDS. Gender-oriented research is needed to understand women's role in migration. Rapid assessment has obscured the human dimension of migrants' vulnerability to HIV. Condom promotion is not enough. Migration is a major consequence of globalization, which holds the promise, real or imagined, of prosperity for all. Mass migration can be fueled by explosive regional developments. In Southeast Asia, migration has been part of the process of economic development. The potential to emigrate increases with greater per capita income. "Tiger" economies have been labor importers. Safe sex is not practiced in many Asian countries because risk is not taken seriously. Migrants tend to be used as economic tools, without consideration of social adjustment and sex behavior among singles.

  10. Dynamic contact guidance of migrating cells

    NASA Astrophysics Data System (ADS)

    Losert, Wolfgang; Sun, Xiaoyu; Guven, Can; Driscoll, Meghan; Fourkas, John

    2014-03-01

    We investigate the effects of nanotopographical surfaces on the cell migration and cell shape dynamics of the amoeba Dictyostelium discoideum. Amoeboid motion exhibits significant contact guidance along surfaces with nanoscale ridges or grooves. We show quantitatively that nanoridges spaced 1.5 μm apart exhibit the greatest contact guidance efficiency. Using principal component analysis, we characterize the dynamics of the cell shape modulated by the coupling between the cell membrane and ridges. We show that motion parallel to the ridges is enhanced, while the turning, at the largest spatial scales, is suppressed. Since protrusion dynamics are principally governed by actin dynamics, we imaged the actin polymerization of cells on ridges. We found that actin polymerization occurs preferentially along nanoridges in a ``monorail'' like fashion. The ridges then provide us with a tool to study actin dynamics in an effectively reduced dimensional system.

  11. Migration of accreting giant planets

    NASA Astrophysics Data System (ADS)

    Robert, C.; Crida, A.; Lega, E.; Méheut, H.

    2017-09-01

    Giant planets forming in protoplanetary disks migrate relative to their host star. By repelling the gas in their vicinity, they form gaps in the disk's structure. If they are effectively locked in their gap, it follows that their migration rate is governed by the accretion of the disk itself onto the star, in a so-called type II fashion. Recent results showed however that a locking mechanism was still lacking, and was required to understand how giant planets may survive their disk. We propose that planetary accretion may play this part, and help reach this slow migration regime.

  12. [Helminth migration in the host].

    PubMed

    Horák, Petr

    2006-08-01

    Helminths belong to important human pathogens in tropical and subtropical countries. They have simple one-host life cycles or they use several hosts for their development. There are two main entry points for human helminths: the skin and the oral cavity. Skin penetration is followed by tissue migration of helminth stages towards target organs. Also some perorally acquired helminths migrate throughout the human body and then (a) they return to and mature in the intestine or (b) they search for specific final location in other (extraintestinal) tissues/organs. Particular developmental stages having different migration routes, and different roles of human beings as final, intermediate and paratenic hosts are briefly mentioned.

  13. Contralateral migration of oculomotor neurons is regulated by Slit/Robo signaling.

    PubMed

    Bjorke, Brielle; Shoja-Taheri, Farnaz; Kim, Minkyung; Robinson, G Eric; Fontelonga, Tatiana; Kim, Kyung-Tai; Song, Mi-Ryoung; Mastick, Grant S

    2016-10-22

    Oculomotor neurons develop initially like typical motor neurons, projecting axons out of the ventral midbrain to their ipsilateral targets, the extraocular muscles. However, in all vertebrates, after the oculomotor nerve (nIII) has reached the extraocular muscle primordia, the cell bodies that innervate the superior rectus migrate to join the contralateral nucleus. This motor neuron migration represents a unique strategy to form a contralateral motor projection. Whether migration is guided by diffusible cues remains unknown. We examined the role of Slit chemorepellent signals in contralateral oculomotor migration by analyzing mutant mouse embryos. We found that the ventral midbrain expresses high levels of both Slit1 and 2, and that oculomotor neurons express the repellent Slit receptors Robo1 and Robo2. Therefore, Slit signals are in a position to influence the migration of oculomotor neurons. In Slit 1/2 or Robo1/2 double mutant embryos, motor neuron cell bodies migrated into the ventral midbrain on E10.5, three days prior to normal migration. These early migrating neurons had leading projections into and across the floor plate. In contrast to the double mutants, embryos which were mutant for single Slit or Robo genes did not have premature migration or outgrowth on E10.5, demonstrating a cooperative requirement of Slit1 and 2, as well as Robo1 and 2. To test how Slit/Robo midline repulsion is modulated, we found that the normal migration did not require the receptors Robo3 and CXCR4, or the chemoattractant, Netrin 1. The signal to initiate contralateral migration is likely autonomous to the midbrain because oculomotor neurons migrate in embryos that lack either nerve outgrowth or extraocular muscles, or in cultured midbrains that lacked peripheral tissue. Overall, our results demonstrate that a migratory subset of motor neurons respond to floor plate-derived Slit repulsion to properly control the timing of contralateral migration.

  14. 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

  15. 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.

  16. Fibronectin in cell adhesion and migration via N-glycosylation

    PubMed Central

    Hsiao, Cheng-Te; Cheng, Hung-Wei; Huang, Chi-Ming; Li, Hao-Ru; Ou, Meng-Hsin; Huang, Jie-Rong; Khoo, Kay-Hooi; Yu, Helen Wenshin; Chen, Yin-Quan; Wang, Yang-Kao; Chiou, Arthur; Kuo, Jean-Cheng

    2017-01-01

    Directed cell migration is an important step in effective wound healing and requires the dynamic control of the formation of cell-extracellular matrix interactions. Plasma fibronectin is an extracellular matrix glycoprotein present in blood plasma that plays crucial roles in modulating cellular adhesion and migration and thereby helping to mediate all steps of wound healing. In order to seek safe sources of plasma fibronectin for its practical use in wound dressing, we isolated fibronectin from human (homo) and porcine plasma and demonstrated that both have a similar ability as a suitable substrate for the stimulation of cell adhesion and for directing cell migration. In addition, we also defined the N-glycosylation sites and N-glycans present on homo and porcine plasma fibronectin. These N-glycosylation modifications of the plasma fibronectin synergistically support the integrin-mediated signals to bring about mediating cellular adhesion and directed cell migration. This study not only determines the important function of N-glycans in both homo and porcine plasma fibronectin-mediated cell adhesion and directed cell migration, but also reveals the potential applications of porcine plasma fibronectin if it was applied as a material for clinical wound healing and tissue repair. PMID:29050309

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

    PubMed

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

    2001-11-01

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

  18. NASTRAN migration to UNIX

    NASA Technical Reports Server (NTRS)

    Chan, Gordon C.; Turner, Horace Q.

    1990-01-01

    COSMIC/NASTRAN, as it is supported and maintained by COSMIC, runs on four main-frame computers - CDC, VAX, IBM and UNIVAC. COSMIC/NASTRAN on other computers, such as CRAY, AMDAHL, PRIME, CONVEX, etc., is available commercially from a number of third party organizations. All these computers, with their own one-of-a-kind operating systems, make NASTRAN machine dependent. The job control language (JCL), the file management, and the program execution procedure of these computers are vastly different, although 95 percent of NASTRAN source code was written in standard ANSI FORTRAN 77. The advantage of the UNIX operating system is that it has no machine boundary. UNIX is becoming widely used in many workstations, mini's, super-PC's, and even some main-frame computers. NASTRAN for the UNIX operating system is definitely the way to go in the future, and makes NASTRAN available to a host of computers, big and small. Since 1985, many NASTRAN improvements and enhancements were made to conform to the ANSI FORTRAN 77 standards. A major UNIX migration effort was incorporated into COSMIC NASTRAN 1990 release. As a pioneer work for the UNIX environment, a version of COSMIC 89 NASTRAN was officially released in October 1989 for DEC ULTRIX VAXstation 3100 (with VMS extensions). A COSMIC 90 NASTRAN version for DEC ULTRIX DECstation 3100 (with RISC) is planned for April 1990 release. Both workstations are UNIX based computers. The COSMIC 90 NASTRAN will be made available on a TK50 tape for the DEC ULTRIX workstations. Previously in 1988, an 88 NASTRAN version was tested successfully on a SiliconGraphics workstation.

  19. The Environmental Dimensions of Migration

    PubMed Central

    Hunter, Lori M.; Luna, Jessie K.; Norton, Rachel M.

    2017-01-01

    Research on the environmental dimensions of human migration has made important strides in recent years. However, findings have been spread across multiple disciplines with wide ranging methodologies and limited theoretical development. This article reviews key findings of the field and identifies future directions for sociological research. We contend that the field has moved beyond linear environmental “push” theories towards a greater integration of context, including micro-, meso-, and macro-level interactions. We highlight findings that migration is often a household strategy to diversify risk (NELM), interacting with household composition, individual characteristics, social networks, and historical, political and economic contexts. We highlight promising developments in the field, including the recognition that migration is a long-standing form of environmental adaptation and yet only one among many forms of adaptation. Finally, we argue that sociologists could contribute significantly to migration-environment inquiry through attention to issues of inequality, perceptions, and agency vis-à-vis structure. PMID:29861536

  20. Radar studies of bird migration

    NASA Technical Reports Server (NTRS)

    Williams, T. C.; Williams, J. M.

    1974-01-01

    Observations of bird migration with NASA radars were made at Wallops Island, Va. Simultaneous observations were made at a number of radar sites in the North Atlantic Ocean in an effort to discover what happened to those birds that were observed leaving the coast of North America headed toward Bermuda, the Caribbean and South America. Transatlantic migration, utilizing observations from a large number of radars is discussed. Detailed studies of bird movements at Wallops Island are presented.

  1. Annexin A2 in Proliferative Vitreoretinopathy

    DTIC Science & Technology

    2016-10-01

    migrate in the presence of macrophages in an in vitro system. In addition, analysis of human retinal tissue from subjects undergoing ocular surgery... tissue from subjects undergoing ocular surgery for PVR reveals the presence of A2- immunoreactive cells that express both macrophage and RPE cell...greatly attenuated in the absence of annexin A2. Task 2: Macrophage depletion and tissue specific knockout. We have completed the characterization

  2. 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.

  3. Eccentricity Evolution of Migrating Planets

    NASA Technical Reports Server (NTRS)

    Murray, N.; Paskowitz, M.; Holman, M.

    2002-01-01

    We examine the eccentricity evolution of a system of two planets locked in a mean motion resonance, in which either the outer or both planets lose energy and angular momentum. The sink of energy and angular momentum could be a gas or planetesimal disk. We analytically calculate the eccentricity damping rate in the case of a single planet migrating through a planetesimal disk. When the planetesimal disk is cold (the average eccentricity is much less than 1), the circularization time is comparable to the inward migration time, as previous calculations have found for the case of a gas disk. If the planetesimal disk is hot, the migration time can be an order of magnitude shorter. We show that the eccentricity of both planetary bodies can grow to large values, particularly if the inner body does not directly exchange energy or angular momentum with the disk. We present the results of numerical integrations of two migrating resonant planets showing rapid growth of eccentricity. We also present integrations in which a Jupiter-mass planet is forced to migrate inward through a system of 5-10 roughly Earth-mass planets. The migrating planets can eject or accrete the smaller bodies; roughly 5% of the mass (averaged over all the integrations) accretes onto the central star. The results are discussed in the context of the currently known extrasolar planetary systems.

  4. 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.

  5. Delta modulation

    NASA Technical Reports Server (NTRS)

    Schilling, D. L.

    1971-01-01

    The conclusions of the design research of the song adaptive delta modulator are presented for source encoding voice signals. The variation of output SNR vs input signal power/when 8, 9, and 10 bit internal arithmetic is employed. Voice intelligibility tapes to test the 10-bit system are used. An analysis of a delta modulator is also presented designed to minimize the in-band rms error. This is accomplished by frequency shaping the error signal in the modulator prior to hard limiting. The result is a significant increase in the output SNR measured after low pass filtering.

  6. Rural-Urban Migration in Colombia.

    ERIC Educational Resources Information Center

    Schultz, T. Paul

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  9. Thread Migration in the Presence of Pointers

    NASA Technical Reports Server (NTRS)

    Cronk, David; Haines, Matthew; Mehrotra, Piyush

    1996-01-01

    Dynamic migration of lightweight threads supports both data locality and load balancing. However, migrating threads that contain pointers referencing data in both the stack and heap remains an open problem. In this paper we describe a technique by which threads with pointers referencing both stack and non-shared heap data can be migrated such that the pointers remain valid after migration. As a result, threads containing pointers can now be migrated between processors in a homogeneous distributed memory environment.

  10. Ethical concerns in nurse migration.

    PubMed

    McElmurry, Beverly J; Solheim, Karen; Kishi, Rieko; Coffia, Marcia A; Woith, Wendy; Janepanish, Poolsuk

    2006-01-01

    International nurse migration is natural and to be expected. Recently, however, those who have fostered nurse migration believe that it will solve nursing shortages in developed countries and offer nurse migrants better working conditions and an improved quality of life. Whether natural or manipulated, migration flow patterns largely occur from developing to developed countries. In this article, nurse migration is examined using primary health care (PHC) as an ethical framework. The unmanaged flow of nurse migrants from developing to developed countries is inconsistent with "health for all" principles. Removing key health personnel from countries experiencing resource shortages is contrary to PHC equity. Often, nurse migrants are placed in vulnerable, inequitable work roles, and employing nurse migrants fails to address basic causes of nurse shortages in developed countries, such as dissatisfaction with work conditions and decreased funding for academic settings. Nurse migration policies and procedures can be developed to satisfy PHC ethics criteria if they (1) leave developing countries enhanced rather than depleted, (2) contribute to country health outcomes consistent with essential care for all people, (3) are based on community participation, (4) address common nursing labor issues, and (5) involve equitable and clear financial arrangements.

  11. ESCAP migration study gathers momentum.

    PubMed

    1980-01-01

    A comparative study is being conducted in the ESCAP (Economic and Social Commission for Asia and the Pacific) region on the relationships of migration and urbanization to development. The 1st stage of the study will entail the preparation of country reports on the census analysis of migration, urbanization and development. The 2nd stage will involve preparation of a series of national migration surveys. The 3rd phase will involve assisting member governments to formulate a comprehensive population redistribution policy as part of their national development planning. 1st-phase country reports have been completed in Sri Lanka, South Korea, the Philippines, and Indonesia. Migration in Sri Lanka has largely been rural-to-rural with little urbanization so far. The picture in South Korea has been the opposite, with rapid urbanization in the 1960s and 1970s; the government is hoping to divert some population to smaller cities away from Seoul. The pattern in the Philippines is 1 of urban primacy with the metropolis of Manila accounting for over 1/3 of the country's total population. Indonesia is characterized by a dense heartland in the Java-Bali regions. However, the rate of urbanization here has been slower. Migrants in all the countries studied are preponderantly young. The sex differential varies from country to country. The influence of migration on subsequent fertility is unknown.

  12. Uniqueness of polymorphism for a discrete, selection-migration model with genetic dominance

    Treesearch

    James F. Selgrade; James H. Roberds

    2009-01-01

    The migration into a natural population of a controlled population, e.g., a transgenic population, is studied using a one island selection-migration model. A 2-dimensional system of nonlinear difference equations describes changes in allele frequency and population size between generations. Biologically reasonable conditions are obtained which guarantee the existence...

  13. BM-520, an original TXA2 modulator, inhibits the action of thromboxane A2 and 8-iso-prostaglandin F2alphain vitro and in vivo on human and rodent platelets, and aortic vascular smooth muscles from rodents.

    PubMed

    Rolin, S; Hanson, J; Vastersaegher, C; Cherdon, C; Pratico, D; Masereel, B; Dogne, J M

    2007-08-01

    Thromboxane A(2) (TXA(2)) and 8-iso-PGF(2alpha) are two prostanoid agonists of the thromboxane A(2) receptor (TP), whose activation has been involved in platelet aggregation and atherosclerosis. Agents able to counteract the actions of these agonists are of great interest in the treatment and prevention of cardiovascular events. Here, we investigated in vitro and in vivo the pharmacological profile of BM-520, a new TP antagonist. In our experiments, this compound showed a great binding affinity for human washed platelets TP receptors, and prevented human platelet activation and aggregation induced by U-46619, arachidonic acid and 8-iso-PGF(2alpha). The TP receptor antagonist property of BM-520 was confirmed by its relaxing effect on rat aorta smooth muscle preparations precontracted with U-46619 and 8-iso-PGF(2alpha). Further, its TP antagonism was also demonstrated in vivo in guinea pig after a single intravenous injection (10 mg kg(-1)). We conclude that this novel TP antagonist could be a promising therapeutic tool in pathologies such as atherosclerosis where an increased production of TXA(2) and 8-iso-PGF(2alpha), as well as TP activation are well-established pathogenic events.

  14. Insulin promotes cell migration by regulating PSA-NCAM.

    PubMed

    Monzo, Hector J; Coppieters, Natacha; Park, Thomas I H; Dieriks, Birger V; Faull, Richard L M; Dragunow, Mike; Curtis, Maurice A

    2017-06-01

    Cellular interactions with the extracellular environment are modulated by cell surface polysialic acid (PSA) carried by the neural cell adhesion molecule (NCAM). PSA-NCAM is involved in cellular processes such as differentiation, plasticity, and migration, and is elevated in Alzheimer's disease as well as in metastatic tumour cells. Our previous work demonstrated that insulin enhances the abundance of cell surface PSA by inhibiting PSA-NCAM endocytosis. In the present study we have identified a mechanism for insulin-dependent inhibition of PSA-NCAM turnover affecting cell migration. Insulin enhanced the phosphorylation of the focal adhesion kinase leading to dissociation of αv-integrin/PSA-NCAM clusters, and promoted cell migration. Our results show that αv-integrin plays a key role in the PSA-NCAM turnover process. αv-integrin knockdown stopped PSA-NCAM from being endocytosed, and αv-integrin/PSA-NCAM clusters co-labelled intracellularly with Rab5, altogether indicating a role for αv-integrin as a carrier for PSA-NCAM during internalisation. Furthermore, inhibition of p-FAK caused dissociation of αv-integrin/PSA-NCAM clusters and counteracted the insulin-induced accumulation of PSA at the cell surface and cell migration was impaired. Our data reveal a functional association between the insulin/p-FAK-dependent regulation of PSA-NCAM turnover and cell migration through the extracellular matrix. Most importantly, they identify a novel mechanism for insulin-stimulated cell migration. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. An Ill Wind? Climate Change, Migration, and Health

    PubMed Central

    Barnett, Jon

    2012-01-01

    Background: Climate change is projected to cause substantial increases in population movement in coming decades. Previous research has considered the likely causal influences and magnitude of such movements and the risks to national and international security. There has been little research on the consequences of climate-related migration and the health of people who move. Objectives: In this review, we explore the role that health impacts of climate change may play in population movements and then examine the health implications of three types of movements likely to be induced by climate change: forcible displacement by climate impacts, resettlement schemes, and migration as an adaptive response. Methods: This risk assessment draws on research into the health of refugees, migrants, and people in resettlement schemes as analogs of the likely health consequences of climate-related migration. Some account is taken of the possible modulation of those health risks by climate change. Discussion: Climate-change–related migration is likely to result in adverse health outcomes, both for displaced and for host populations, particularly in situations of forced migration. However, where migration and other mobility are used as adaptive strategies, health risks are likely to be minimized, and in some cases there will be health gains. Conclusions: Purposeful and timely policy interventions can facilitate the mobility of people, enhance well-being, and maximize social and economic development in both places of origin and places of destination. Nevertheless, the anticipated occurrence of substantial relocation of groups and communities will underscore the fundamental seriousness of human-induced climate change. PMID:22266739

  16. Migrating lumbar facet joint cysts.

    PubMed

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

    2006-04-01

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

  17. Focus: Asian migration to Canada.

    PubMed

    Kobayashi, A

    1988-01-01

    This collection of 5 short essays on Asian migration to Canada focuses on the relationships between individual migrants and their social contexts, both Asian and Canadian. Papers by Anderson and Kobayashi adopt research perspectives of outsider and insider, respectively. Vibert provides a historical overview against which the substantive issues introduced in the other 3 papers can be understood, and he illustrates the links between circumstances of migration and the larger issues by which the course of Canadian social progress has been steered. Mercer provides an introduction to issues that dominate the agenda of contemporary research, to show that Canadian communities of Asian heritage continue to grow in size, diversity, and complexity, as they become more established on the Canadian landscape. This collection is as much about the geography of racism as it is about migration.

  18. Families, children, migration and AIDS.

    PubMed

    Haour-Knipe, Mary

    2009-01-01

    Migration is very often a family affair, and often involves children, directly or indirectly. It may give rise to better quality of life for an entire family, or to bitter disappointment, and may also increase vulnerability to HIV and AIDS. This review, carried out for the Joint Learning Initiative on Children and AIDS, links the literature on "migration", on "HIV and AIDS" and on "families". Three themes are sketched: (1) As both HIV prevalence and circular migration increase, former migrant workers affected by AIDS may return to their families for care and support, especially at the end of life, often under crisis conditions. Families thus lose promising members, as well as sources of support. However, very little is known about the children of such migrants. (2) Following patterns of migration established for far different reasons, children may have to relocate to different places, sometimes over long distances, if their AIDS-affected parents can no longer care for them. They face the same adaptation challenges as other children who move, but complicated by loss of parent(s), AIDS stigma, and often poverty. (3) The issue of migrant families living with HIV has been studied to some extent, but mainly in developed countries with a long history of migration, and with little attention paid to the children in such families. Difficulties include involuntary separation from family members, isolation and lack of support, disclosure and planning for children's care should the parent(s) die and differences in treatment access within the same family. Numerous research and policy gaps are defined regarding the three themes, and a call is made for thinking about migration, families and AIDS to go beyond description to include resilience theory, and to go beyond prevention to include care.

  19. Proteolysis of EphA2 Converts It from a Tumor Suppressor to an Oncoprotein.

    PubMed

    Koshikawa, Naohiko; Hoshino, Daisuke; Taniguchi, Hiroaki; Minegishi, Tomoko; Tomari, Taizo; Nam, Sung-Ouk; Aoki, Mikiko; Sueta, Takayuki; Nakagawa, Takashi; Miyamoto, Shingo; Nabeshima, Kazuki; Weaver, Alissa M; Seiki, Motoharu

    2015-08-15

    Eph receptor tyrosine kinases are considered candidate therapeutic targets in cancer, but they can exert opposing effects on cell growth. In the presence of its ligands, Eph receptor EphA2 suppresses signaling by other growth factor receptors, including ErbB, whereas ligand-independent activation of EphA2 augments ErbB signaling. To deploy EphA2-targeting drugs effectively in tumors, the anti-oncogenic ligand-dependent activation state of EphA2 must be discriminated from its oncogenic ligand-independent state. Because the molecular basis for the latter is little understood, we investigated how the activation state of EphA2 can be switched in tumor tissue. We found that ligand-binding domain of EphA2 is cleaved frequently by the membrane metalloproteinase MT1-MMP, a powerful modulator of the pericellular environment in tumor cells. EphA2 immunostaining revealed a significant loss of the N-terminal portion of EphA2 in areas of tumor tissue that expressed MT1-MMP. Moreover, EphA2 phosphorylation patterns that signify ligand-independent activation were observed specifically in these areas of tumor tissue. Mechanistic experiments revealed that processing of EphA2 by MT1-MMP promoted ErbB signaling, anchorage-independent growth, and cell migration. Conversely, expression of a proteolysis-resistant mutant of EphA2 prevented tumorigenesis and metastasis of human tumor xenografts in mice. Overall, our results showed how the proteolytic state of EphA2 in tumors determines its effector function and influences its status as a candidate biomarker for targeted therapy. ©2015 American Association for Cancer Research.

  20. Proteolysis of EphA2 converts it from a tumor suppressor to an oncoprotein

    PubMed Central

    KOSHIKAWA, Naohiko; HOSHINO, Daisuke; TANIGUCHI, Hiroaki; MINEGISHI, Tomoko; TOMARI, Taizo; NAM, Sung-Ouk; AOKI, Mikiko; SUETA, Takayuki; NAKAGAWA, Takashi; MIYAMOTO, Shingo; NABESHIMA, Kazuki; WEAVER, Alissa M.; SEIKI, Motoharu

    2015-01-01

    Eph receptor tyrosine kinases are considered candidate therapeutic targets in cancer, but they can exert opposing effects on cell growth. In presence of its ligands, Eph receptor EphA2 suppresses signaling by other growth factor receptors, including ErbB, whereas ligand-independent activation of EphA2 augments ErbB signaling. To deploy EphA2-targeting drugs effectively in tumors, the anti-oncogenic ligand-dependent activation state of EphA2 must be discriminated from its oncogenic ligand-independent state. Since the molecular basis for the latter is little understood, we investigated how the activation state of EphA2 can be switched in tumor tissue. We found that ligand-binding domain of EphA2 is cleaved frequently by the membrane metalloproteinase MT1-MMP, a powerful modulator of the pericellular environment in tumor cells. EphA2 immunostaining revealed a significant loss of the N-terminal portion of EphA2 in areas of tumor tissue that expressed MT1-MMP. Moreover, EphA2 phosphorylation patterns that signify ligand-independent activation were observed specifically in these areas of tumor tissue. Mechanistic experiments revealed that processing of EphA2 by MT1-MMP promoted ErbB signaling, anchorage-independent growth, and cell migration. Conversely, expression of a proteolysis-resistant mutant of EphA2 prevented tumorigenesis and metastasis of human tumor xenografts in mice. Overall, our results showed how the proteolytic state of EphA2 in tumors determines its effector function and influences its status as a candidate biomarker for targeted therapy. PMID:26130649

  1. Business cycles, migration and health.

    PubMed

    Halliday, Timothy J

    2007-04-01

    We investigate the proposition that illness poses as an obstacle to one's ability to use migration to hedge the business cycle. We employ data on migration, regional unemployment rates and health status from 10 years (1984-1993) of the US Panel Study of Income Dynamics. Our results provide considerable for support this proposition. The evidence is the strongest for men, but we also find weaker evidence for married women. These results suggest that--ceterus paribus--aggregate health outcomes in an area should improve when the regional economy expands.

  2. Climate Migration and Moral Responsibility

    PubMed Central

    Nawrotzki, Raphael

    2016-01-01

    Even though anthropogenic climate change is largely caused by industrialized nations, its burden is distributed unevenly with poor developing countries suffering the most. A common response to livelihood insecurities and destruction is migration. Using Peter Singer’s “historical principle” this paper argues that a morally just evaluation requires taking causality between climate change and migration under consideration. The historical principle is employed to emphasize shortcomings in commonly made philosophical arguments to oppose immigration. The article concludes that none of these arguments is able to override the moral responsibility of industrialized countries to compensate for harms that their actions have caused. PMID:27668124

  3. [International migration in the Americas: intraregional migration grows].

    PubMed

    Zlotnik, H

    1992-01-01

    The principal destinations for intraregional migrants in South America in recent decades have been Argentina, Brazil, and Venezuela, while in North America the U.S. has exerted a growing attraction since 1965. Intraregional migration in Latin America has been irregular and difficult to quantify, and reliable statistics on migratory flows are nonexistent. Census data indicate that most migration to Argentina and Brazil occurred before 1960, while most migration to Venezuela occurred during the 1970s. Between 1960 and 1980, the proportion of migrants from other Latin American countries showed a tendency to increase, despite decreases in the overall level of immigration. The effect of the economic crisis of the 1980s on immigration from Latin American countries will become more apparent as census data for the 1990s become available. Selectivity according to country of origin is an important characteristic of intraregional migration in South America. The U.S. has, however, been the principal destination of Latin American migrants for the past three decades. Between 1965 and 1991 the U.S. granted resident status to more than 7.4 million persons of Latin American and Caribbean origin, and they constituted 47% of immigrants during those years. The great majority of the Latin American immigrants in the U.S. are Mexican. The 3.5 million Mexicans admitted to the U.S. as immigrants between 1965 and 1991 accounted for 22% of all immigrants during this period.

  4. EphA2 signalling following endocytosis: role of Tiam1

    PubMed Central

    Boissier, Pomme; Chen, Jin; Huynh-Do, Uyen

    2013-01-01

    Eph receptors and their membrane-bound ligands, the ephrins, represent a complex subfamily of receptor tyrosine kinases (RTKs). Eph/ephrin binding can lead to various and opposite cellular behaviours such as adhesion versus repulsion, or cell migration versus cell adhesion. Recently, Eph endocytosis has been identified as one of the critical steps responsible for such diversity. Eph receptors, as many RTKs, are rapidly endocytosed following ligand-mediated activation and traffic through endocytic compartments prior to degradation. However, it is becoming obvious that endocytosis controls signalling in many different manners. Here we showed that activated EphA2 are degraded in the lysosomes and that about 35% of internalized receptors are recycled back to the plasma membrane. Our study is also the first to demonstrate that EphA2 retains the capacity to signal in endosomes. In particular, activated EphA2 interacted with the Rho family GEF Tiam1 in endosomes. This association led to Tiam1 activation, which in turn increased Rac1 activity and facilitated Eph/ephrin endocytosis. Disrupting Tiam1 function with RNA interference impaired both ephrinA1-dependent Rac1 activation and ephrinA1-induced EphA2 endocytosis. In summary, our findings shed new light on the regulation of EphA2 endocytosis, intracellular trafficking and signal termination and establish Tiam1 as an important modulator of EphA2 signalling. PMID:24112471

  5. Development of a Fuel Spill/Vapor Migration Modeling System.

    DTIC Science & Technology

    1985-12-01

    transforms resulting in a direct solution of the differential equation. A second order finite * difference approximation to the Poisson equation A2*j is...7 O-A64 043 DEVELOPMENT OF A FUEL SPILL/VPOR MIGRATION MODELING 1/2 SYSTEM(U) TRACER TECHNOLOGIES ESCONDIDO Cflo IL 0 ENGLAND ET AL. DEC 85 RFURL...AFWAL-TR-85-2089 DEVELOPMENT OF A FUEL SPILL/VAPOR MIGRATION MODELING SYSTEM W.G. England * L.H. Teuscher TRACER TECHNOLOGIES DTIC *2120 WEST MISSION

  6. Thermionic modules

    DOEpatents

    King, Donald B.; Sadwick, Laurence P.; Wernsman, Bernard R.

    2002-06-18

    Modules of assembled microminiature thermionic converters (MTCs) having high energy-conversion efficiencies and variable operating temperatures manufactured using MEMS manufacturing techniques including chemical vapor deposition. The MTCs incorporate cathode to anode spacing of about 1 micron or less and use cathode and anode materials having work functions ranging from about 1 eV to about 3 eV. The MTCs also exhibit maximum efficiencies of just under 30%, and thousands of the devices and modules can be fabricated at modest costs.

  7. Trade and migration: the case of NAFTA.

    PubMed

    Martin, P L

    1993-01-01

    "This article provides background information on NAFTA [the North American Free Trade Agreement], reviews data on its economic effects, and summarizes studies and projections of NAFTA's likely effects on Mexico-to-U.S. migration. Migration factors (demand-pull, supply-push, and networks) are examined to determine whether NAFTA's effect on economic development particularly in the border areas will accelerate or retard migration. The conclusion is that NAFTA is likely to produce a temporary migration hump, slightly raising already high migration levels in the 1990s, but reducing the volume of Mexico-to-U.S. migration that would otherwise occur over subsequent decades." excerpt

  8. Nuclear migration events throughout development

    PubMed Central

    Bone, Courtney R.

    2016-01-01

    ABSTRACT Moving the nucleus to a specific position within the cell is an important event during many cell and developmental processes. Several different molecular mechanisms exist to position nuclei in various cell types. In this Commentary, we review the recent progress made in elucidating mechanisms of nuclear migration in a variety of important developmental models. Genetic approaches to identify mutations that disrupt nuclear migration in yeast, filamentous fungi, Caenorhabditis elegans, Drosophila melanogaster and plants led to the identification of microtubule motors, as well as Sad1p, UNC-84 (SUN) domain and Klarsicht, ANC-1, Syne homology (KASH) domain proteins (LINC complex) that function to connect nuclei to the cytoskeleton. We focus on how these proteins and various mechanisms move nuclei during vertebrate development, including processes related to wound healing of fibroblasts, fertilization, developing myotubes and the developing central nervous system. We also describe how nuclear migration is involved in cells that migrate through constricted spaces. On the basis of these findings, it is becoming increasingly clear that defects in nuclear positioning are associated with human diseases, syndromes and disorders. PMID:27182060

  9. Migration of accreting giant planets

    NASA Astrophysics Data System (ADS)

    Crida, A.; Bitsch, B.; Raibaldi, A.

    2016-12-01

    We present the results of 2D hydro simulations of giant planets in proto-planetary discs, which accrete gas at a more or less high rate. First, starting from a solid core of 20 Earth masses, we show that as soon as the runaway accretion of gas turns on, the planet is saved from type I migration : the gap opening mass is reached before the planet is lost into its host star. Furthermore, gas accretion helps opening the gap in low mass discs. Consequently, if the accretion rate is limited to the disc supply, then the planet is already inside a gap and in type II migration. We further show that the type II migration of a Jupiter mass planet actually depends on its accretion rate. Only when the accretion is high do we retrieve the classical picture where no gas crosses the gap and the planet follows the disc spreading. These results impact our understanding of planet migration and planet population synthesis models. The e-poster presenting these results in French can be found here: L'e-poster présentant ces résultats en français est disponible à cette adresse: http://sf2a.eu/semaine-sf2a/2016/posterpdfs/156_179_49.pdf.

  10. Les questions de migrations internationales

    NASA Astrophysics Data System (ADS)

    Samman, Mouna Liliane

    1993-03-01

    International migrations have growing implications for both countries of origin and countries of destination. In the latter, the presence of foreigners and of members of their families today creates problems of integration, causes argument and brings mounting xenophobia. Paralleling political, economic and social measures taken by public authorities to respond to these difficulties, education needs to assist in defusing the resulting social tensions by preparing the minds of learners and helping to develop new attitudes. In particular, when educational programmes address questions of international migration, these should be treated in the framework of historical evolution so that their real significance and their true temporal and spatial dimensions become apparent. It is also important that the growing interdependence between countries should be made plain, that national history should be placed in its international context, and that the true consequences of these developments should be made clear. In this context, learners need to be acquainted with Human Rights, thereby stressing universal moral values and the role of the individual. Lastly, questions relating to international migration are usually presented in the media in a selective and partial manner, and the young people who take in this information often accept the hasty judgments which are made of situations as proven facts. This is why all teaching about international migration needs to be considered or reconsidered in the light of the complementary or competing actions of the media.

  11. Physician Migration: Donor Country Impact

    ERIC Educational Resources Information Center

    Aluwihare, A. P. R.

    2005-01-01

    Physician migration from the developing to developed region of a country or the world occurs for reasons of financial, social, and job satisfaction. It is an old phenomenon that produces many disadvantages for the donor region or nation. The difficulties include inequities with the provision of health services, financial loss, loss of educated…

  12. Migration monitoring with automated technology

    Treesearch

    Rhonda L. Millikin

    2005-01-01

    Automated technology can supplement ground-based methods of migration monitoring by providing: (1) unbiased and automated sampling; (2) independent validation of current methods; (3) a larger sample area for landscape-level analysis of habitat selection for stopover, and (4) an opportunity to study flight behavior. In particular, radar-acoustic sensor fusion can...

  13. Job Migration: A Collaborative Effort

    ERIC Educational Resources Information Center

    Wagoner, Cynthia L.

    2012-01-01

    Music teachers often change jobs several times during their careers. Reasons for job changes vary, but regardless, these changes bring a different set of challenges. Sharing knowledge and learning are part and parcel of collaboration. So what if, as education professionals, music teachers decided to collaborate during job migrations? For all music…

  14. India: 'brain drain' or the migration of talent?

    PubMed

    Oommen, T K

    1989-09-01

    2 views on "brain drain" exist: 1) LDCs lose their enormous investments on higher education when skilled people migrate to other countries and 2) LDCs are exaggerating the problem and only a few skilled people migrate at 1 time. India does not completely lose its investment in education when professionals migrate, since the migrants still contribute to knowledge and also send remittances to relatives in India. Unemployed educated people would cause a greater drain on India's resources than educated migrants. The author prefers the phrase migration of talent to brain drain, since the former indicates a 2-way movement. Most migrants from LDCs are students. About 11,000 university graduates leave India every year for advanced study and/or work. A conservative estimate is that 2500 will remain abroad permanently. Most professionals who migrate go to the US and Canada. Factors promoting migration include 1) unemployment, 2) immigration rules, 3) colonial links, 4) financial incentives and material benefits, 5) pursuit of higher education, 6) improvement of working conditions and facilities, 7) avoidance of excessive bureaucratic procedures, and 8) compensation for the mismatch between Indian education and employment. Reasons for returning to India include 1) deference to wives who were unable to adjust to a foreign way of life, 2) contributing to Indian development, and 3) racial discrimination. It will probably not be possible to lure back migrants who left for material reasons. Attractive job offers could entice back those who left for advanced training. To encourage the return of those who left to pursue high quality research, India must 1) increase expenditure on research and development, possibly through the private industrial sector, 2) promote travel to other countries for professional enrichment, and 3) improve conditions of research work. The article concludes with an analysis of migration of talent from 3 perspectives: 1) the individual, 2) the nation

  15. Irc3 is a mitochondrial DNA branch migration enzyme

    PubMed Central

    Gaidutšik, Ilja; Sedman, Tiina; Sillamaa, Sirelin; Sedman, Juhan

    2016-01-01

    Integrity of mitochondrial DNA (mtDNA) is essential for cellular energy metabolism. In the budding yeast Saccharomyces cerevisiae, a large number of nuclear genes influence the stability of mitochondrial genome; however, most corresponding gene products act indirectly and the actual molecular mechanisms of mtDNA inheritance remain poorly characterized. Recently, we found that a Superfamily II helicase Irc3 is required for the maintenance of mitochondrial genome integrity. Here we show that Irc3 is a mitochondrial DNA branch migration enzyme. Irc3 modulates mtDNA metabolic intermediates by preferential binding and unwinding Holliday junctions and replication fork structures. Furthermore, we demonstrate that the loss of Irc3 can be complemented with mitochondrially targeted RecG of Escherichia coli. We suggest that Irc3 could support the stability of mtDNA by stimulating fork regression and branch migration or by inhibiting the formation of irregular branched molecules. PMID:27194389

  16. [Haitian migration to Santo Domingo].

    PubMed

    Latortue, P R

    1985-01-01

    This work examines the history of Haitian migration to the Dominican Republic, the central role of Haitian migration in Dominican society, working conditions of Haitian migrants in the Dominican Republic, and the relationship of the migration to economic development on the island of Hispaniola. Lack of data, the difficulty of measuring illegal movement, and the problem of defining Haitians in Santo Domingo have impeded understanding of migration to the Dominican Republic. It is believed by many authorities that Haitian migration to Santo Domingo is considerable and perhaps exceeds that to the US. Haitian migration to the Dominican Republic began after 1915 with the fall of the Haitian president, a worsening of economic conditions partly caused by stagnation in the agricultural sector, and the newly dominant role of the US in Haitian economic affairs. The Great Depression of the 1930s was a direct antecedent of the massacre of Haitians by Dominican police in which some 30 thousand persons were killed; the economic recession of the early 1980s has also caused an outburst of antiHaitian feeling in the Dominican Republic although 80% of laborers in the sugar industry are Haitians. Sugar is extremely important to the Dominican economy: in 1974, sugar covered 12% of cultivated land, produced 40% of foreign exchange earnings, and was responsable for 21% of taxable income. Dominicans however refuse to work in sugar plantations under the current technological. conditions and wage system. Although the government periodically demands the Dominicanization of the sugar work force, no such changes have been made. Sugar will probably continue to play a decisive role in the generation of foreign exchange despite introduction of more technologically advanced sectors which benefit from better prices in the international market. Possibilities of mechanizing sugar production in the Dominican Republic appear remote, and failure to modernize an important sector of the economy has

  17. [Migration patterns of health professionals].

    PubMed

    Kingma, Mireille

    2005-01-01

    The past three decades have seen the number of international migrants double, to reach the unprecedented total of 175 million people in 2003. National health systems are often the biggest national employer, responsible for an estimated 35 million workers worldwide. Health professionals are part of the expanding global labour market. Today, foreign-educated health professionals represent more than a quarter of the medical and nursing workforces of Australia, Canada, the United Kingdom and the United States. Destination countries, however, are not limited to industrialised nations. For example, 50 per cent of physicians in the Namibia public services are expatriates and South Africa continues to recruit close to 80% of its rural physicians from other countries. International migration often imitates patterns of internal migration. The exodus from rural to urban areas, from lower to higher income urban neighbourhoods and from lower-income to higher-income sectors contributes challenges to the universal coverage of the population. International migration is often blamed for the dramatic health professional shortages witnessed in the developing countries. A recent OECD study, however, concludes that many registered nurses in South Africa (far exceeding the number that emigrate) are either inactive or unemployed. These dire situations constitute a modern paradox which is for the most part ignored. Shared language, promises of a better quality of life and globalization all support the continued existence of health professionals' international migration. The ethical dimension o this mobility is a sensitive issue that needs to be addressed. A major paradigm shift, however, is required in order to lessen the need to migrate rather than artificially curb the flows.

  18. Sedimentary record of erg migration

    NASA Astrophysics Data System (ADS)

    Porter, M. L.

    1986-06-01

    The sedimentary record of erg (eolian sand sea) migration consists of an idealized threefold division of sand-sea facies sequences. The basal division, here termed the fore-erg, is composed of a hierarchy of eolian sand bodies contained within sediments of the flanking depositional environment. These sand bodies consist of eolian strata deposited by small dune complexes, zibars, and sand sheets. The fore-erg represents the downwind, leading edge of the erg and records the onset of eolian sedimentation. Basin subsidence coupled with erg migration places the medial division, termed the central erg, over the fore-erg strata. The central erg, represented by a thick accumulation of large-scale, cross-stratified sandstone, is the product of large draa complexes. Eolian influence on regional sedimentation patterns is greatest in the central erg, and most of the sand transported and deposited in the erg is contained within this region. Reduction in sand supply and continued erg migration will cover the central-erg deposits with a veneer of back-erg deposits. This upper division of the erg facies sequence resembles closely the fore-erg region. Similar types of eolian strata are present and organized in sand bodies encased in sediments of the upwind flanking depositional environment(s). Back-erg deposits may be thin due to limited eolian influence on sedimentation or incomplete erg migration, or they may be completely absent because of great susceptibility to postdepositional erosion. Tectonic, climatic, and eustatic influences on sand-sea deposition will produce distinctive variations or modifications of the idealized erg facies sequence. The resulting variants in the sedimentary record of erg migration are illustrated with ancient examples from western North America, Europe, southern Africa, and South America.

  19. JEM module

    NASA Image and Video Library

    2008-06-06

    S124-E-006734 (6 June 2008) --- One of a series of digital still images documenting the Japanese Experiment Module, or JEM, also called Kibo, in its new home on the International Space Station, this view depicts Kibo's exterior, backdropped by solar array panels for the orbital outpost and one of its trusses.

  20. JEM module

    NASA Image and Video Library

    2008-06-06

    S124-E-006729 (6 June 2008) --- One of a series of digital still images documenting the Japanese Experiment Module, or JEM, also called Kibo, in its new home on the International Space Station, this view depicts Kibo's exterior, backdropped by solar array panels for the orbital outpost.

  1. JEM module

    NASA Image and Video Library

    2008-06-06

    S124-E-006735 (6 June 2008) --- One of a series of digital still images documenting the Japanese Experiment Module, or JEM, also called Kibo, in its new home on the International Space Station, this view depicts Kibo's exterior, backdropped by solar array panels for the orbital outpost and one of its trusses.

  2. Controlled surface topography regulates collective 3D migration by epithelial-mesenchymal composite embryonic tissues.

    PubMed

    Song, Jiho; Shawky, Joseph H; Kim, YongTae; Hazar, Melis; LeDuc, Philip R; Sitti, Metin; Davidson, Lance A

    2015-07-01

    Cells in tissues encounter a range of physical cues as they migrate. Probing single cell and collective migratory responses to physically defined three-dimensional (3D) microenvironments and the factors that modulate those responses are critical to understanding how tissue migration is regulated during development, regeneration, and cancer. One key physical factor that regulates cell migration is topography. Most studies on surface topography and cell mechanics have been carried out with single migratory cells, yet little is known about the spreading and motility response of 3D complex multi-cellular tissues to topographical cues. Here, we examine the response to complex topographical cues of microsurgically isolated tissue explants composed of epithelial and mesenchymal cell layers from naturally 3D organized embryos of the aquatic frog Xenopus laevis. We control topography using fabricated micropost arrays (MPAs) and investigate the collective 3D migration of these multi-cellular systems in these MPAs. We find that the topography regulates both collective and individual cell migration and that dense MPAs reduce but do not eliminate tissue spreading. By modulating cell size through the cell cycle inhibitor Mitomycin C or the spacing of the MPAs we uncover how 3D topographical cues disrupt collective cell migration. We find surface topography can direct both single cell motility and tissue spreading, altering tissue-scale processes that enable efficient conversion of single cell motility into collective movement. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Health, migration and border management: analysis and capacity-building at Europe's borders.

    PubMed

    Hollings, Jennifer; Samuilova, Mariya; Petrova-Benedict, Roumyana

    2012-04-01

    Three key elements were analysed in Hungary, Poland and Slovakia as a basis for strengthening the capacity of staff and structures related to health, migration and border management: public health concerns linked to migration, health needs and rights of migrants and the occupational health of staff. This IOM project was implemented through an in-depth situation analysis as well as the development of training modules and public health guidelines. Findings indicate a paucity of existing data, gaps in the health care for migrants and few existing tools for border officials and health professionals. Sets of training modules were developed for each of these groups, including common modules on migration and the right to health and intercultural communication, as well as targeted health modules. The guidelines promote good practices in the context of border management and detention. The EU is working towards a common immigration policy and integrated border management; however, a harmonized approach to migration and health is still lacking. Further research and piloting of the developed materials is needed to fully establish an adaptable, common toolkit.

  4. Melt migration modeling in partially molten upper mantle

    NASA Astrophysics Data System (ADS)

    Ghods, Abdolreza

    The objective of this thesis is to investigate the importance of melt migration in shaping major characteristics of geological features associated with the partial melting of the upper mantle, such as sea-floor spreading, continental flood basalts and rifting. The partial melting produces permeable partially molten rocks and a buoyant low viscosity melt. Melt migrates through the partially molten rocks, and transfers mass and heat. Due to its much faster velocity and appreciable buoyancy, melt migration has the potential to modify dynamics of the upwelling partially molten plumes. I develop a 2-D, two-phase flow model and apply it to investigate effects of melt migration on the dynamics and melt generation of upwelling mantle plumes and focusing of melt migration beneath mid-ocean ridges. Melt migration changes distribution of the melt-retention buoyancy force and therefore affects the dynamics of the upwelling plume. This is investigated by modeling a plume with a constant initial melt of 10% where no further melting is considered. Melt migration polarizes melt-retention buoyancy force into high and low melt fraction regions at the top and bottom portions of the plume and therefore results in formation of a more slender and faster upwelling plume. Allowing the plume to melt as it ascends through the upper mantle also produces a slender and faster plume. It is shown that melt produced by decompressional melting of the plume migrates to the upper horizons of the plume, increases the upwelling velocity and thus, the volume of melt generated by the plume. Melt migration produces a plume which lacks the mushroom shape observed for the plume models without melt migration. Melt migration forms a high melt fraction layer beneath the sloping base of the impermeable oceanic lithosphere. Using realistic conditions of melting, freezing and melt extraction, I examine whether the high melt fraction layer is able to focus melt from a wide partial melting zone to a narrow region

  5. Nanoparticles migration in fractured rocks and affects on contaminant migration

    NASA Astrophysics Data System (ADS)

    Missana, Tiziana; Garcia-Gutierrez, Miguel; Alonso, Ursula

    2014-05-01

    In previous studies, the transport behavior of artificial (gold and latex) and natural (smectite clay) colloids, within a planar fracture in crystalline rock, was analyzed. In order to better understand the effects of colloid size, shape and surface charge on nanoparticle migration and especially on filtration processes on natural rock surfaces, different clay colloids and oxide nanoparticles were selected and their transport studied as a function of the residence time. In all the cases, (a fraction of) the nanoparticles travelled in the fracture as fast as or faster than water (with a retardation factor, Rf ≤ 1) and the observed Rf, was related to the Taylor dispersion coefficient, accounting for colloid size, water velocity and fracture width. However, under most of the cases, in contrast to the behavior of a conservative tracer, colloids recovery was much lower than 100 %. Differences in recovery between different nanoparticles, under similar residence times, were analyzed. In order to evaluate the possible consequences, on contaminant migration, of the presence of nanoparticles in the system, transport tests were carried out with both colloids and sorbing radionuclides. The overall capacity for colloids of enhancing radionuclide migration in crystalline rock fractures is discussed. Acknowledgments: The research leading to these results received funding from EU FP7/2007-2011 grant agreement Nº 295487 (BELBAR, Bentonite Erosion: effects on the Long term performance of the engineered Barrier and Radionuclide Transport) and by the Spanish Government under the project NANOBAG (CTM2011-2797).

  6. Capitalist development and internal migration in Nigeria.

    PubMed

    Akor, R I; Mou, D

    1986-12-01

    The authors analyze internal migration trends in Nigeria by examining individual household strategies and how they have adapted to structural changes brought about by colonial rule and capitalist development. The first section of this article describes the structural changes that started the process of labor migration. The second section deals with post-independence industrialization and the consequent rural-urban migration. The final section analyzes the consequences of these migration patterns for urban growth and rural productivity.

  7. 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

  8. miR-200a inhibits migration of triple-negative breast cancer cells through direct repression of the EPHA2 oncogene.

    PubMed

    Tsouko, Efrosini; Wang, Jun; Frigo, Daniel E; Aydoğdu, Eylem; Williams, Cecilia

    2015-09-01

    Triple-negative breast cancer (TNBC) is characterized by aggressiveness and affects 10-20% of breast cancer patients. Since TNBC lacks expression of ERα, PR and HER2, existing targeted treatments are not effective and the survival is poor. In this study, we demonstrate that the tumor suppressor microRNA miR-200a directly regulates the oncogene EPH receptor A2 (EPHA2) and modulates TNBC migration. We show that EPHA2 expression is correlated with poor survival specifically in basal-like breast cancer and that its expression is repressed by miR-200a through direct interaction with the 3'UTR of EPHA2. This regulation subsequently affects the downstream activation of AMP-activated protein kinase (AMPK) and results in decreased cell migration of TNBC. We establish that miR-200a directs cell migration in a dual manner; in addition to regulating the well-characterized E-cadherin pathway it also regulates a EPHA2 pathway. The miR-200a-EPHA2 axis is a novel mechanism highlighting the possibility of utilizing miR-200a delivery to target TNBC metastases. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Migration and Marriage among Puerto Rican Women.

    ERIC Educational Resources Information Center

    Ortiz, Vilma

    1996-01-01

    Examines the effect of family indicators, including marriage, on migration from, and return to, Puerto Rico in the 1980s using data from surveys of 3,175 and 2,032 women. Single women apparently use migration to gain independence, but married women often follow men in the migration stream. (SLD)

  10. [Urban employment and internal migration in Peru].

    PubMed

    Cotlear, D

    1984-06-01

    The relationship between internal migration and employment problems in Peru is examined. The author argues that regional differences in income distribution are the primary causes of migration, particularly to urban areas. A model of the migration process is developed and tested using data from official sources, surveys, and the published literature.

  11. 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

  12. Thermoelectric module

    DOEpatents

    Kortier, William E.; Mueller, John J.; Eggers, Philip E.

    1980-07-08

    A thermoelectric module containing lead telluride as the thermoelectric mrial is encapsulated as tightly as possible in a stainless steel canister to provide minimum void volume in the canister. The lead telluride thermoelectric elements are pressure-contacted to a tungsten hot strap and metallurgically bonded at the cold junction to iron shoes with a barrier layer of tin telluride between the iron shoe and the p-type lead telluride element.

  13. Physicists' Forced Migrations under Hitler

    NASA Astrophysics Data System (ADS)

    Beyerchen, Alan

    2011-03-01

    When the Nazis came to power in early 1933 they initiated formal and informal measures that forced Jews and political opponents from public institutions such as universities. Some physicists retired and others went into industry, but most emigrated. International communication and contact made emigration a viable option despite the desperate economic times in the Great Depression. Another wave of emigrations followed the annexation of Austria in 1938. Individual cases as well as general patterns of migration and adaptation to new environments will be examined in this presentation. One important result of the forced migrations was that many of the physicists expelled under Hitler played important roles in strengthening physics elsewhere, often on the Allied side in World War II.

  14. China: surplus labour and migration.

    PubMed

    Banister, J; Taylor, J R

    1989-12-01

    Surplus labor force and migration trends in China are examined, with emphasis on the impact of underemployment in rural areas. "Government policy encourages surplus labourers to transfer out of crop farming into agricultural sidelines or non-agricultural work. Peasants are urged to stay where they are, shifting jobs without shifting location; however, many rural areas are poorly endowed for providing alternative employment, so their surplus workers must also leave the village to find work. Many do not formally migrate, but rather move on a seasonal basis or set up 'temporary' residence in an urban place. This 'floating' population has been escalating rapidly in recent years....[The authors argue] that China's cities and towns can absorb millions of surplus labourers from rural areas each year, to the mutual benefit of sending and receiving areas." excerpt

  15. miR-302b inhibits tumorigenesis by targeting EphA2 via Wnt/ β-catenin/EMT signaling cascade in gastric cancer.

    PubMed

    Huang, Jin; He, Yijing; Mcleod, Howard L; Xie, Yanchun; Xiao, Desheng; Hu, Huabin; Chen, Pan; Shen, Liangfang; Zeng, Shan; Yin, Xianli; Ge, Jie; Li, Li; Tang, Lanhua; Ma, Jian; Chen, Zihua

    2017-12-22

    EphA2 is a crucial oncogene in gastric cancer (GC) development and metastasis, this study aims to identify microRNAs that target it and serve as key regulators of gastric carcinogenesis. We identified several potential microRNAs targeting EphA2 by bioinformatics websites and then analyzed the role of miR-302b in modulating EphA2 in vitro and in vivo of GC, and it's mechanism. Our analysis identified miR-302b, a novel regulator of EphA2, as one of the most significantly downregulated microRNA (miRNA) in GC tissues. Overexpression of miR-302b impaired GC cell migratory and invasive properties robustly and suppressed cell proliferation by arresting cells at G0-G1 phase in vitro. miR-302b exhibited anti-tumor activity by reversing EphA2 regulation, which relayed a signaling transduction cascade that attenuated the functions of N-cadherin, β-catenin, and Snail (markers of Wnt/β-catenin and epithelial-mesenchymal transition, EMT). This modulation of EphA2 also had distinct effects on cell proliferation and migration in GC in vivo. miR-302b serves as a critical suppressor of GC cell tumorigenesis and metastasis by targeting the EphA2/Wnt/β-catenin/EMT pathway.

  16. Linear modulator

    NASA Technical Reports Server (NTRS)

    1972-01-01

    A study of frequency division multiplexing (FDM) systems was made for the purpose of determining the system performance that can be obtained with available state of the art components. System performance was evaluated on the basis of past experience, system analysis, and component evaluation. The system study was specifically directed to the area of FDM systems using subcarrier channel frequencies from 4 kHz to 200 kHz and channel information bandwidths of dc to 1, 2, 4, 8, and 16 kHz. The evaluation also assumes that the demodulation will be from a tape recorder which produces frequency modulation of + or - 1% on the signal due to the tape recorder wow and flutter. For the modulation system it is assumed that the pilot and carrier channel frequencies are stable to within + or - .005% and that the FM on the channel carriers is negligible. The modulator system was evaluated for the temperature range of -20 degree to +85 degree while the demodulator system was evaluated for operation at room temperature.

  17. Dome: Distributed Object Migration Environment

    DTIC Science & Technology

    1994-05-01

    Best Available Copy AD-A281 134 Computer Science Dome: Distributed object migration environment Adam Beguelin Erik Seligman Michael Starkey May 1994...Beguelin Erik Seligman Michael Starkey May 1994 CMU-CS-94-153 School of Computer Science Carnegie Mellon University Pittsburgh, PA 15213 Abstract Dome... Linda [4], Isis [2], and Express [6] allow a pro- grammer to treat a heterogeneous network of computers as a parallel machine. These tools allow the

  18. Mexican Migration: Assessing Root Causes

    DTIC Science & Technology

    2007-06-01

    surely broaden our understanding of the causes of Mexico–U.S. migration. One writer, Denise Dresser , does go into great detail about the political...change from a civil-authoritarian to a democratic regime.19 Dresser provides much insight into the working of the political transition in Mexico, but...www.nber.org/papers/w11428 (accessed January 25 2006), 9. 19 Denise Dresser , “Mexico: From PRI Predominance to Divided Democracy,” in Constructing

  19. ProBDNF inhibits collective migration and chemotaxis of rat Schwann cells.

    PubMed

    Ding, You-Quan; Li, Xuan-Yang; Xia, Guan-Nan; Ren, Hong-Yi; Zhou, Xin-Fu; Su, Bing-Yin; Qi, Jian-Guo

    2016-10-01

    Schwann cell migration, including collective migration and chemotaxis, is essential for the formation of coordinate interactions between Schwann cells and axons during peripheral nerve development and regeneration. Moreover, limited migration of Schwann cells imposed a serious obstacle on Schwann cell-astrocytes intermingling and spinal cord repair after Schwann cell transplantation into injured spinal cords. Recent studies have shown that mature brain-derived neurotrophic factor, a member of the neurotrophin family, inhibits Schwann cell migration. The precursor form of brain-derived neurotrophic factor, proBDNF, was expressed in the developing or degenerating peripheral nerves and the injured spinal cords. Since "the yin and yang of neurotrophin action" has been established as a common sense, proBDNF would be expected to promote Schwann cell migration. However, we found, in the present study, that exogenous proBDNF also inhibited in vitro collective migration and chemotaxis of RSC 96 cells, a spontaneously immortalized rat Schwann cell line. Moreover, proBDNF suppressed adhesion and spreading of those cells. At molecular level, proBDNF inhibits F-actin polymerization and focal adhesion dynamics in cultured RSC 96 cells. Therefore, our results suggested a special case against the classical opinion of "the yin and yang of neurotrophin action" and implied that proBDNF might modulate peripheral nerve development or regeneration and spinal cord repair through perturbing native or transplanted Schwann cell migration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Tumor cell migration screen identifies SRPK1 as breast cancer metastasis determinant

    PubMed Central

    van Roosmalen, Wies; Le Dévédec, Sylvia E.; Golani, Ofra; Smid, Marcel; Pulyakhina, Irina; Timmermans, Annemieke M.; Look, Maxime P.; Zi, Di; Pont, Chantal; de Graauw, Marjo; Naffar-Abu-Amara, Suha; Kirsanova, Catherine; Rustici, Gabriella; Hoen, Peter A.C. ‘t; Martens, John W.M.; Foekens, John A.; Geiger, Benjamin; van de Water, Bob

    2015-01-01

    Tumor cell migration is a key process for cancer cell dissemination and metastasis that is controlled by signal-mediated cytoskeletal and cell matrix adhesion remodeling. Using a phagokinetic track assay with migratory H1299 cells, we performed an siRNA screen of almost 1,500 genes encoding kinases/phosphatases and adhesome- and migration-related proteins to identify genes that affect tumor cell migration speed and persistence. Thirty candidate genes that altered cell migration were validated in live tumor cell migration assays. Eight were associated with metastasis-free survival in breast cancer patients, with integrin β3–binding protein (ITGB3BP), MAP3K8, NIMA-related kinase (NEK2), and SHC-transforming protein 1 (SHC1) being the most predictive. Examination of genes that modulate migration indicated that SRPK1, encoding the splicing factor kinase SRSF protein kinase 1, is relevant to breast cancer outcomes, as it was highly expressed in basal breast cancer. Furthermore, high SRPK1 expression correlated with poor breast cancer disease outcome and preferential metastasis to the lungs and brain. In 2 independent murine models of breast tumor metastasis, stable shRNA-based SRPK1 knockdown suppressed metastasis to distant organs, including lung, liver, and spleen, and inhibited focal adhesion reorganization. Our study provides comprehensive information on the molecular determinants of tumor cell migration and suggests that SRPK1 has potential as a drug target for limiting breast cancer metastasis. PMID:25774502

  1. Tumor cell migration screen identifies SRPK1 as breast cancer metastasis determinant.

    PubMed

    van Roosmalen, Wies; Le Dévédec, Sylvia E; Golani, Ofra; Smid, Marcel; Pulyakhina, Irina; Timmermans, Annemieke M; Look, Maxime P; Zi, Di; Pont, Chantal; de Graauw, Marjo; Naffar-Abu-Amara, Suha; Kirsanova, Catherine; Rustici, Gabriella; Hoen, Peter A C 't; Martens, John W M; Foekens, John A; Geiger, Benjamin; van de Water, Bob

    2015-04-01

    Tumor cell migration is a key process for cancer cell dissemination and metastasis that is controlled by signal-mediated cytoskeletal and cell matrix adhesion remodeling. Using a phagokinetic track assay with migratory H1299 cells, we performed an siRNA screen of almost 1,500 genes encoding kinases/phosphatases and adhesome- and migration-related proteins to identify genes that affect tumor cell migration speed and persistence. Thirty candidate genes that altered cell migration were validated in live tumor cell migration assays. Eight were associated with metastasis-free survival in breast cancer patients, with integrin β3-binding protein (ITGB3BP), MAP3K8, NIMA-related kinase (NEK2), and SHC-transforming protein 1 (SHC1) being the most predictive. Examination of genes that modulate migration indicated that SRPK1, encoding the splicing factor kinase SRSF protein kinase 1, is relevant to breast cancer outcomes, as it was highly expressed in basal breast cancer. Furthermore, high SRPK1 expression correlated with poor breast cancer disease outcome and preferential metastasis to the lungs and brain. In 2 independent murine models of breast tumor metastasis, stable shRNA-based SRPK1 knockdown suppressed metastasis to distant organs, including lung, liver, and spleen, and inhibited focal adhesion reorganization. Our study provides comprehensive information on the molecular determinants of tumor cell migration and suggests that SRPK1 has potential as a drug target for limiting breast cancer metastasis.

  2. Lessons from the motorized migrations

    USGS Publications Warehouse

    Ellis, D.H.; Gee, G.F.; Clegg, K.R.; Duff, J.W.; Lishman, W.A.; Sladen, William J. L.

    2001-01-01

    Ten experiments have been conducted to determine if cranes can be led on migration and if those so trained will repeat migrations on their own. Results have been mixed as we have experienced the mishaps common to pilot studies. Nevertheless, we have learned many valuable lessons. Chief among these are that cranes can be led long distances behind motorized craft (air and ground), and those led over most or the entire route will return north come spring and south in fall to and from the general area of training. However, they will follow their own route. Groups transported south and flown at intervals along the route will migrate but often miss target termini. If certain protocol restrictions are followed, it is possible to make the trained cranes wild, however, the most practical way of so doing is to introduce them into a flock of wild cranes. We project that it is possible to create or restore wild migratory flocks of cranes by first leading small groups from chosen northern to southern termini.

  3. Postnatal Migration of Cerebellar Interneurons

    PubMed Central

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

    2017-01-01

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

  4. EphA2 Receptor Unliganded Dimers Suppress EphA2 Pro-tumorigenic Signaling*

    PubMed Central

    Singh, Deo R.; Ahmed, Fozia; King, Christopher; Gupta, Nisha; Salotto, Matt; Pasquale, Elena B.; Hristova, Kalina

    2015-01-01

    The EphA2 receptor tyrosine kinase promotes cell migration and cancer malignancy through a ligand- and kinase-independent distinctive mechanism that has been linked to high Ser-897 phosphorylation and low tyrosine phosphorylation. Here, we demonstrate that EphA2 forms dimers in the plasma membrane of HEK293T cells in the absence of ephrin ligand binding, suggesting that the current seeding mechanism model of EphA2 activation is incomplete. We also characterize a dimerization-deficient EphA2 mutant that shows enhanced ability to promote cell migration, concomitant with increased Ser-897 phosphorylation and decreased tyrosine phosphorylation compared with EphA2 wild type. Our data reveal a correlation between unliganded dimerization and tumorigenic signaling and suggest that EphA2 pro-tumorigenic activity is mediated by the EphA2 monomer. Thus, a therapeutic strategy that aims at the stabilization of EphA2 dimers may be beneficial for the treatment of cancers linked to EphA2 overexpression. PMID:26363067

  5. EphA2 Receptor Unliganded Dimers Suppress EphA2 Pro-tumorigenic Signaling.

    PubMed

    Singh, Deo R; Ahmed, Fozia; King, Christopher; Gupta, Nisha; Salotto, Matt; Pasquale, Elena B; Hristova, Kalina

    2015-11-06

    The EphA2 receptor tyrosine kinase promotes cell migration and cancer malignancy through a ligand- and kinase-independent distinctive mechanism that has been linked to high Ser-897 phosphorylation and low tyrosine phosphorylation. Here, we demonstrate that EphA2 forms dimers in the plasma membrane of HEK293T cells in the absence of ephrin ligand binding, suggesting that the current seeding mechanism model of EphA2 activation is incomplete. We also characterize a dimerization-deficient EphA2 mutant that shows enhanced ability to promote cell migration, concomitant with increased Ser-897 phosphorylation and decreased tyrosine phosphorylation compared with EphA2 wild type. Our data reveal a correlation between unliganded dimerization and tumorigenic signaling and suggest that EphA2 pro-tumorigenic activity is mediated by the EphA2 monomer. Thus, a therapeutic strategy that aims at the stabilization of EphA2 dimers may be beneficial for the treatment of cancers linked to EphA2 overexpression. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Modulation of Phospholipase A2 Activity by Actin and Myosin.

    DTIC Science & Technology

    1987-04-15

    cord vein. Thromb. Res. 18:787-795. 11. Knull. H.R.. W.F. Taylor. and W.W. Wells. 1974. Insulin effects on brain energy metabolism and the related...cells. Nature 271:549-551. I 14. Martin. T.W.. R.B. Wysolmerski. and D. Lagunoff. 1987. Phosphatidylcholine metabolism in endothelial cells: evidence for

  7. Spreading devices into a 2-D module layout

    SciTech Connect

    Koplow, Jeffrey P.; Gupta, Vipin P.; Nielson, Gregory N.

    An apparatus, method, and system, the apparatus including a receiving member dimensioned to receive an array of microelectronic devices; and a linkage member coupled to the receiving member, the linkage member configured to move the receiving member in at least two dimensions so as to modify a spacing between the electronic devices within the array of microelectronic devices received by the receiving member. The method including coupling an array of microelectronic devices to an expansion assembly; and expanding the expansion assembly so as to expand the array of microelectronic devices in at least two directions within a single plane. Themore » system including a support member; an expansion assembly coupled to the support member, the expansion assembly having a plurality of receiving members configured to move in at least two dimensions within a single plane; and a plurality of microelectronic devices coupled to each of the plurality of receiving members.« less

  8. Photovoltaic module and module arrays

    DOEpatents

    Botkin, Jonathan; Graves, Simon; Lenox, Carl J. S.; Culligan, Matthew; Danning, Matt

    2013-08-27

    A photovoltaic (PV) module including a PV device and a frame, The PV device has a PV laminate defining a perimeter and a major plane. The frame is assembled to and encases the laminate perimeter, and includes leading, trailing, and side frame members, and an arm that forms a support face opposite the laminate. The support face is adapted for placement against a horizontal installation surface, to support and orient the laminate in a non-parallel or tilted arrangement. Upon final assembly, the laminate and the frame combine to define a unitary structure. The frame can orient the laminate at an angle in the range of 3.degree.-7.degree. from horizontal, and can be entirely formed of a polymeric material. Optionally, the arm incorporates integral feature(s) that facilitate interconnection with corresponding features of a second, identically formed PV module.

  9. Photovoltaic module and module arrays

    DOEpatents

    Botkin, Jonathan [El Cerrito, CA; Graves, Simon [Berkeley, CA; Lenox, Carl J. S. [Oakland, CA; Culligan, Matthew [Berkeley, CA; Danning, Matt [Oakland, CA

    2012-07-17

    A photovoltaic (PV) module including a PV device and a frame. The PV device has a PV laminate defining a perimeter and a major plane. The frame is assembled to and encases the laminate perimeter, and includes leading, trailing, and side frame members, and an arm that forms a support face opposite the laminate. The support face is adapted for placement against a horizontal installation surface, to support and orient the laminate in a non-parallel or tilted arrangement. Upon final assembly, the laminate and the frame combine to define a unitary structure. The frame can orient the laminate at an angle in the range of 3.degree.-7.degree. from horizontal, and can be entirely formed of a polymeric material. Optionally, the arm incorporates integral feature(s) that facilitate interconnection with corresponding features of a second, identically formed PV module.

  10. Global migration and health: ecofeminist perspectives.

    PubMed

    McGuire, S

    1998-12-01

    Global migration is occurring at an unprecedented rate. The phenomenon of migration is complex and poorly understood by most people in countries who host immigrants. People migrate for numerous reasons related to social, economic, political, cultural, and physical environmental conditions formed by historical antecedents. Migrating people, especially vulnerable women and children, are exposed to numerous health hazards, a situation calling for a response from nursing. To respond effectively nursing needs knowledge development of global migration and health that includes the precursors to migration in addition to the postmigration experience where nurses encounter immigrants. Ecofeminist perspectives allowing for reflection on historical determinants and interlocking socioeconomic, political, and environmental conditions are used as a prism to examine global migration and health.

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

    PubMed

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

    2014-01-01

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

  12. Longitudinal On-Column Thermal Modulation for Comprehensive Two-Dimensional Liquid Chromatography.

    PubMed

    Creese, Mari E; Creese, Mathew J; Foley, Joe P; Cortes, Hernan J; Hilder, Emily F; Shellie, Robert A; Breadmore, Michael C

    2017-01-17

    Longitudinal on-column thermal modulation for comprehensive two-dimensional liquid chromatography is introduced. Modulation optimization involved a systematic investigation of heat transfer, analyte retention, and migration velocity at a range of temperatures. Longitudinal on-column thermal modulation was realized using a set of alkylphenones and compared to a conventional valve-modulator employing sample loops. The thermal modulator showed a reduced modulation-induced pressure impact than valve modulation, resulting in reduced baseline perturbation by a factor of 6; yielding a 6-14-fold improvement in signal-to-noise. A red wine sample was analyzed to demonstrate the potential of the longitudinal on-column thermal modulator for separation of a complex sample. Discrete peaks in the second dimension using the thermal modulator were 30-55% narrower than with the valve modulator. The results shown herein demonstrate the benefits of an active focusing modulator, such as reduced detection limits and increased total peak capacity.

  13. BAG3 regulates cell proliferation, migration, and invasion in human colorectal cancer.

    PubMed

    Shi, Huiyong; Xu, Haidong; Li, Zengjun; Zhen, Yanan; Wang, Bin; Huo, Shoujun; Xiao, Ruixue; Xu, Zhongfa

    2016-04-01

    Bcl2-associated athanogene 3 (BAG3) has been reported to be elevated in various tumors. However, it is unclear whether BAG3 has a functional role in the initiation and progression of colorectal cancer (CRC). Here, we collected CRC samples and cell lines to validate the pathway by using gene and protein assays. RT-PCR showed that the expression of BAG3 mRNA in CRC tissues was obviously higher than that in non-tumor tissues (p < 0.001). Immunohistochemical analysis showed that immunoreactivity of BAG3 was found in most CRC tissues and strongly correlated with TNM stage (p = 0.001), differentiation (p = 0.003), and metastasis (p = 0.010). Low expression of BAG3 in HCT-8 significantly reduced cellular proliferation, migration, and invasion. The analysis of in vitro cell showed that HCT-8 cells were exposed to si-BAG3, and its growth was inhibited depending on modulation of cell cycle G1/S checkpoints and cell cycle regulators, involving cyclin D1, cyclin A2, and cyclin B1. Furthermore, suppression of the epithelial-mesenchymal transition (EMT) by si-BAG3 is linked to the decreased expression of E-cadherin and the increased expression of N-cadherin, vimentin, and MMP9. In conclusion, in the present study, we demonstrated that BAG3 overexpression plays a critical role in cell proliferation, migration, and invasion of colorectal cancer. Our data suggests targeted inhibition of BAG3 may be useful for patients with CRC.

  14. Lead migration from toys by anodic stripping voltammetry using a bismuth film electrode.

    PubMed

    Leal, M Fernanda C; Catarino, Rita I L; Pimenta, Adriana M; Souto, M Renata S; Afonso, Christelle S; Fernandes, Ana F Q

    2016-09-02

    Metals may be released from toys via saliva during mouthing, via sweat during dermal contact, or via gastric and intestinal fluids after partial or whole ingestion. In this study, we determined the lead migration from toys bought on the Portuguese market for children below 3 years of age. The lead migration was performed according to the European Committee for Standardization EN 71-3, which proposes a 2-hour migration test that simulates human gastric conditions. The voltammetric determination of migrated lead was performed by anodic stripping voltammetry (ASV) at a bismuth film electrode (BiFE). For all the analyzed toys, the values of migrated lead did not exceed the limits imposed by the European Committee for Standardization EN 71-3 (90 mg kg -1 ) and by the EU Directive 2009/48/EC (13.5 mg kg -1 ) on the safety of toys.

  15. Intracellular pH gradients in migrating cells.

    PubMed

    Martin, Christine; Pedersen, Stine F; Schwab, Albrecht; Stock, Christian

    2011-03-01

    Cell polarization along the axis of movement is required for migration. The localization of proteins and regulators of the migratory machinery to either the cell front or its rear results in a spatial asymmetry enabling cells to simultaneously coordinate cell protrusion and retraction. Protons might function as such unevenly distributed regulators as they modulate the interaction of focal adhesion proteins and components of the cytoskeleton in vitro. However, an intracellular pH (pH(i)) gradient reflecting a spatial asymmetry of protons has not been shown so far. One major regulator of pH(i), the Na(+)/H(+) exchanger NHE1, is essential for cell migration and accumulates at the cell front. Here, we test the hypothesis that the uneven distribution of NHE1 activity creates a pH(i) gradient in migrating cells. Using the pH-sensitive fluorescent dye BCECF, pH(i) was measured in five cell lines (MV3, B16V, NIH3T3, MDCK-F1, EA.hy926) along the axis of movement. Differences in pH(i) between the front and the rear end (ΔpH(i) front-rear) were present in all cell lines, and inhibition of NHE1 either with HOE642 or by absence of extracellular Na(+) caused the pH(i) gradient to flatten or disappear. In conclusion, pH(i) gradients established by NHE1 activity exist along the axis of movement.

  16. Endogenous electric fields as guiding cue for cell migration

    PubMed Central

    Funk, Richard H. W.

    2015-01-01

    This review covers two topics: (1) “membrane potential of low magnitude and related electric fields (bioelectricity)” and (2) “cell migration under the guiding cue of electric fields (EF).”Membrane potentials for this “bioelectricity” arise from the segregation of charges by special molecular machines (pumps, transporters, ion channels) situated within the plasma membrane of each cell type (including eukaryotic non-neural animal cells). The arising patterns of ion gradients direct many cell- and molecular biological processes such as embryogenesis, wound healing, regeneration. Furthermore, EF are important as guiding cues for cell migration and are often overriding chemical or topographic cues. In osteoblasts, for instance, the directional information of EF is captured by charged transporters on the cell membrane and transferred into signaling mechanisms that modulate the cytoskeleton and motor proteins. This results in a persistent directional migration along an EF guiding cue. As an outlook, we discuss questions concerning the fluctuation of EF and the frequencies and mapping of the “electric” interior of the cell. Another exciting topic for further research is the modeling of field concepts for such distant, non-chemical cellular interactions. PMID:26029113

  17. Striations, duration, migration and tidal response in deep tremor.

    PubMed

    Ide, Satoshi

    2010-07-15

    Deep tremor in subduction zones is thought to be caused by small repeating shear slip events on the plate interface with significant slow components. It occurs at a depth of about 30 kilometres and provides valuable information on deep plate motion and shallow stress accumulation on the fault plane of megathrust earthquakes. Tremor has been suggested to repeat at a regular interval, migrate at various velocities and be modulated by tidal stress. Here I show that some time-invariant interface property controls tremor behaviour, using precise location of tremor sources with event duration in western Shikoku in the Nankai subduction zone, Japan. In areas where tremor duration is short, tremor is more strongly affected by tidal stress and migration is inhibited. Where tremor lasts longer, diffusive migration occurs with a constant diffusivity of 10(4) m(2) s(-1). The control property may be the ratio of brittle to ductile areas, perhaps determined by the influence of mantle wedge serpentinization on the plate interface. The spatial variation of the controlling property seems to be characterized by striations in tremor source distribution, which follows either the current or previous plate subduction directions. This suggests that the striations and corresponding interface properties are formed through the subduction of inhomogeneous structure, such as seamounts, for periods as long as ten million years.

  18. Agmatine promotes the migration of murine brain endothelial cells via multiple signaling pathways.

    PubMed

    Jung, Hyun-Joo; Jeon, Yong-Heui; Bokara, Kiran Kumar; Koo, Bon-Nyeo; Lee, Won Taek; Park, Kyung Ah; Lee, Jong-Eun

    2013-01-17

    The combination of adhesion and migration of endothelial cells (ECs) is an integral process for evolution, organization, repair and vessel formation in living organisms. Agmatine, a polycationic amine existing in brain, has been investigated to exert neuroprotective effects. Up to date, there are no studies reporting that agmatine modulates murine brain endothelial (bEnd.3) cells migration. In the present study, we intend to investigate the role of agmatine in bEnd.3 cells migration and the molecular mechanism mediating this action. The effect of agmatine on the bEnd.3 cells migration was examined by migration assay, and the mechanism involved for this effect was investigated by western blot analysis and NO contents measurements. Agmatine treatment (50, 100 and 200 μM) significantly accelerated bEnd.3 cells migration in a concentration-dependent manner. Western blotting revealed that agmatine treatment significantly induced vascular endothelial growth factor (VEGF), VEGF receptor 2 (Flk-1/KDR or VEGFR2), phosphatidylinositol 3-kinase (PI3K), Akt/protein kinase B (also known as PKB, PI3K downstream effector protein), endothelial nitric oxide synthase (eNOS) nitric oxide (NO; product by eNOS) and intercellular adhesion molecule 1 (ICAM-1) expressions during bEnd.3 cells migration. The expression of ICAM-1 and migration of bEnd.3 cells, induced by agmatine, were significantly attenuated by treatment of wortmannin, a specific PI3K inhibitor. Taken together, we provide the first evidence that activation of VEGF/VEGFR2 and the consequential PI3K/Akt/eNOS/NO/ICAM-1 signaling pathways are serial events, through which the treatment of agmatine could lead to bEnd.3 cells migration. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Area 2: Inexpensive Monitoring and Uncertainty Assessment of CO2 Plume Migration using Injection Data

    SciTech Connect

    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

  20. 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

  1. Philippine migration policy: dilemmas of a crisis.

    PubMed

    Battistella, G

    1999-04-01

    Philippine migration policy is traced from the early 1970s to the present. The main migration trends in the 1990s are described. An assessment is made of the efficacy and appropriateness of present migration policy in light of the economic crisis. A regional approach to migration policy is necessary in order to encourage placing migration as a greater priority on national agendas and in bilateral agreements. In the Philippines, migrants are considered better paid workers, which diminishes their importance as a legislative or program priority. Santo Tomas (1998) conducted an empirical assessment of migration policies in the Philippines, but refinement is needed. Although migration is a transnational experience, there is little dialogue and cooperation among countries. Philippine migration policy defines its role as an information resource for migrants. Policy shifted from labor export to migrant management in the public and private sectors. Predeparture information program studies are recommending a multi-stage process that would involve all appropriate parties. There is talk of including migration information in the education curriculum. There are a variety of agendas, competing interests, and information resources between migration networks and officiating agencies. The Asian financial crisis may have a mild impact, but there are still issues of reintegration, protection, and employment conditions

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

    PubMed

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

    2007-12-01

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

  3. Deconstructing (and reconstructing) cell migration.

    PubMed

    Maheshwari, G; Lauffenburger, D A

    1998-12-01

    An overriding objective in cell biology is to be able to relate properties of particular molecular components to cell behavioral functions and even physiology. In the "traditional" mode of molecular cell biology, this objective has been tackled on a molecule-by-molecule basis, and in the "future" mode sometimes termed "functional genomics," it might be attacked in a high-throughput, parallel manner. Regardless of the manner of approach, the relationship between molecular-level properties and cell-level function is exceedingly difficult to elucidate because of the large number of relevant components involved, their high degree of interconnectedness, and the inescapable fact that they operate as physico-chemical entities-according to the laws of kinetics and mechanics-in space and time within the cell. Cell migration is a prominent representative example of such a cell behavioral function that requires increased understanding for both scientific and technological advance. This article presents a framework, derived from an engineering perspective regarding complex systems, intended to aid in developing improved understanding of how properties of molecular components influence the function of cell migration. That is, cell population migration behavior can be deconstructed as follows: first in terms of a mathematical model comprising cell population parameters (random motility, chemotaxis/haptotaxis, and chemokinesis/haptokinesis coefficients), which in turn depend on characteristics of individual cell paths that can be analyzed in terms of a mathematical model comprising individual cell parameters (translocation speed, directional persistence time, chemotactic/haptotactic index), which in turn depend on cell-level physical processes underlying motility (membrane extension and retraction, cell/substratum adhesion, cell contractile force, front-vs.-rear asymmetry), which in turn depend on molecular-level properties of the plethora of components involved in governance and

  4. Clandestine labor migration to Taiwan.

    PubMed

    Tsay, C

    1992-01-01

    "Illegal migration to Taiwan is a recent phenomenon but with a rapid rate of increase. Most illegal foreign workers enter on visitor's visas and overstay. This paper's detailed analysis of official data reveals that Malaysia, Philippines, Indonesia and Thailand are the major sources, providing a stock of mostly male workers numbering around 40,000. Sociodemographic and attitudinal changes among Taiwanese workers coupled with labor shortages in low-skilled jobs are pressuring the Taiwanese government to formulate plans for a systematic importation of foreign labor." excerpt

  5. Asian student migration to Australia.

    PubMed

    Shu, J; Hawthorne, L

    1996-01-01

    "This paper presents an overview of Asian student migration to Australia, together with an analysis of political and educational aspects of the overseas student programme. It focuses on some significant consequences of this flow for Australia. The characteristics of key student groups are contrasted to provide some perspective of the diversity of historical and cultural backgrounds, with the source countries of Malaysia, Indonesia and PRC [China] selected as case studies. Since the issue of PRC students in Australia has attracted considerable public attention and policy consideration, particular focus is placed on their experience." (SUMMARY IN FRE AND SPA) excerpt

  6. Pseudomonas aeruginosa ExoU augments neutrophil transepithelial migration.

    PubMed

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

    2017-08-01

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

  7. MEMORY MODULATION

    PubMed Central

    Roozendaal, Benno; McGaugh, James L.

    2011-01-01

    Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive evidence from both animal and human research indicates that emotionally significant experiences activate hormonal and brain systems that regulate the consolidation of newly acquired memories. These effects are integrated through noradrenergic activation of the basolateral amygdala which regulates memory consolidation via interactions with many other brain regions involved in consolidating memories of recent experiences. Modulatory systems not only influence neurobiological processes underlying the consolidation of new information, but also affect other mnemonic processes, including memory extinction, memory recall and working memory. In contrast to their enhancing effects on consolidation, adrenal stress hormones impair memory retrieval and working memory. Such effects, as with memory consolidation, require noradrenergic activation of the basolateral amygdala and interactions with other brain regions. PMID:22122145

  8. [Migration to metropolitan Mexico City].

    PubMed

    Cantu Gutierrez, J J; Luque Gonzalez, R

    1990-01-01

    Accelerated urbanization, especially after 1940, has been among the great transformations in Mexico associated with rapid and sustained economic growth during 1950-80. The urbanization process was highly selective, favoring in particular Mexico City, Guadalajara, and Monterey, which together contain about 25% of Mexico¿s total population. Metropolitan Mexico City alone contained around 18.2% of the total 1990 population on 0.2% of Mexico¿s land area. Mexico City¿s population grew at an average annual rate of 4.2%, from 1.6 million in 1940 to 14.8 million in 1990, largely due to in-migration. Migrants and their reproduction are estimated to have accounted for 51.2% of Mexico City¿s growth since 1940, and physical expansion of the metropolitan zone for another 5.7%. Slightly over 80% of migrants come from 10 states that are mostly rural, relatively densely populated, not distant, and below average in living levels. Women predominate slightly. Nearly half of migrants are aged 15-29 years on arrival. The proportion with no more than primary education is higher than that of Mexico City natives, but the proportion with post-secondary education is similar. Pollution, lack of public safety, and other urban problems will probably combine to discourage migration to Mexico City in the future and encourage departures to less difficult cities.

  9. Force transmission in migrating cells

    PubMed Central

    Sauser, Roger; Ambrosi, Davide; Meister, Jean-Jacques; Verkhovsky, Alexander B.

    2010-01-01

    During cell migration, forces generated by the actin cytoskeleton are transmitted through adhesion complexes to the substrate. To investigate the mechanism of force generation and transmission, we analyzed the relationship between actin network velocity and traction forces at the substrate in a model system of persistently migrating fish epidermal keratocytes. Front and lateral sides of the cell exhibited much stronger coupling between actin motion and traction forces than the trailing cell body. Further analysis of the traction–velocity relationship suggested that the force transmission mechanisms were different in different cell regions: at the front, traction was generated by a gripping of the actin network to the substrate, whereas at the sides and back, it was produced by the network’s slipping over the substrate. Treatment with inhibitors of the actin–myosin system demonstrated that the cell body translocation could be powered by either of the two different processes, actomyosin contraction or actin assembly, with the former associated with significantly larger traction forces than the latter. PMID:20100912

  10. 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.

  11. Focal Adhesion-Independent Cell Migration.

    PubMed

    Paluch, Ewa K; Aspalter, Irene M; Sixt, Michael

    2016-10-06

    Cell migration is central to a multitude of physiological processes, including embryonic development, immune surveillance, and wound healing, and deregulated migration is key to cancer dissemination. Decades of investigations have uncovered many of the molecular and physical mechanisms underlying cell migration. Together with protrusion extension and cell body retraction, adhesion to the substrate via specific focal adhesion points has long been considered an essential step in cell migration. Although this is true for cells moving on two-dimensional substrates, recent studies have demonstrated that focal adhesions are not required for cells moving in three dimensions, in which confinement is sufficient to maintain a cell in contact with its substrate. Here, we review the investigations that have led to challenging the requirement of specific adhesions for migration, discuss the physical mechanisms proposed for cell body translocation during focal adhesion-independent migration, and highlight the remaining open questions for the future.

  12. Political motivations for intra-European migration

    PubMed Central

    Flipo, Aurore

    2016-01-01

    Motivations for migrating within the European Union have mainly been attributed to economic, career and lifestyle choices. This article suggests that political dissatisfaction is also an important motivator of recent intra-European migration. In our analysis of in-depth interviews with Romanian migrants in Spain and with Spanish migrants in Norway, we found a common emphasis on the political dimensions of their decision to migrate. In the interviews, the economic component of migration was often related to bad governance and negative perceptions of the state. The similarities of Spanish and Romanian migration narratives are especially striking because Spain and Romania represent substantially different migratory, political and economic contexts. However, migration is more obviously intertwined with conventional acts of political protest in the Spanish case. We suggest that differences in democratic contexts are pivotal in people’s reactions to and framing of their deep dissatisfaction with domestic politics, as found in many European countries today. PMID:28751786

  13. Political motivations for intra-European migration.

    PubMed

    Bygnes, Susanne; Flipo, Aurore

    2017-08-01

    Motivations for migrating within the European Union have mainly been attributed to economic, career and lifestyle choices. This article suggests that political dissatisfaction is also an important motivator of recent intra-European migration. In our analysis of in-depth interviews with Romanian migrants in Spain and with Spanish migrants in Norway, we found a common emphasis on the political dimensions of their decision to migrate. In the interviews, the economic component of migration was often related to bad governance and negative perceptions of the state. The similarities of Spanish and Romanian migration narratives are especially striking because Spain and Romania represent substantially different migratory, political and economic contexts. However, migration is more obviously intertwined with conventional acts of political protest in the Spanish case. We suggest that differences in democratic contexts are pivotal in people's reactions to and framing of their deep dissatisfaction with domestic politics, as found in many European countries today.

  14. Theories of international labor migration: an overview.

    PubMed

    Stahl, C W

    1995-01-01

    "Emigration pressures are primarily the result of increasing inequalities between countries which, in turn, are the result of factors internal to less developed countries and their relations with developed countries. Both micro (neoclassical) and macrostructural theories of migration are reviewed. It is argued that the neoclassical theory of migration is often unjustly criticized and is sufficiently robust to incorporate those structural considerations which are at the core of macrostructural theories. Moreover, the neoclassical theory, with slight modification, can incorporate the ¿new economics of migration.' The major empirical problem confronting models of international labor migration is that migration flows are constrained by immigration policy. This policy, in turn, is influenced by various special interest groups. The direction and form of migration flows is conditioned by contemporary and historical relationships between source and destination countries." excerpt

  15. Modelling collective cell migration of neural crest

    PubMed Central

    Szabó, András; Mayor, Roberto

    2016-01-01

    Collective cell migration has emerged in the recent decade as an important phenomenon in cell and developmental biology and can be defined as the coordinated and cooperative movement of groups of cells. Most studies concentrate on tightly connected epithelial tissues, even though collective migration does not require a constant physical contact. Movement of mesenchymal cells is more independent, making their emergent collective behaviour less intuitive and therefore lending importance to computational modelling. Here we focus on such modelling efforts that aim to understand the collective migration of neural crest cells, a mesenchymal embryonic population that migrates large distances as a group during early vertebrate development. By comparing different models of neural crest migration, we emphasize the similarity and complementary nature of these approaches and suggest a future direction for the field. The principles derived from neural crest modelling could aid understanding the collective migration of other mesenchymal cell types. PMID:27085004

  16. Modelling collective cell migration of neural crest.

    PubMed

    Szabó, András; Mayor, Roberto

    2016-10-01

    Collective cell migration has emerged in the recent decade as an important phenomenon in cell and developmental biology and can be defined as the coordinated and cooperative movement of groups of cells. Most studies concentrate on tightly connected epithelial tissues, even though collective migration does not require a constant physical contact. Movement of mesenchymal cells is more independent, making their emergent collective behaviour less intuitive and therefore lending importance to computational modelling. Here we focus on such modelling efforts that aim to understand the collective migration of neural crest cells, a mesenchymal embryonic population that migrates large distances as a group during early vertebrate development. By comparing different models of neural crest migration, we emphasize the similarity and complementary nature of these approaches and suggest a future direction for the field. The principles derived from neural crest modelling could aid understanding the collective migration of other mesenchymal cell types. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Sources of international migration statistics in Africa.

    PubMed

    1984-01-01

    The sources of international migration data for Africa may be classified into 2 main categories: administrative records and 2) censuses and survey data. Both categories are sources for the direct measurement of migration, but the 2nd category can be used for the indirect estimation of net international migration. The administrative records from which data on international migration may be derived include 1) entry/departure cards or forms completed at international borders, 2) residence/work permits issued to aliens, and 3) general population registers and registers of aliens. The statistics derived from the entry/departure cards may be described as 1) land frontier control statistics and 2) port control statistics. The former refer to data derived from movements across land borders and the latter refer to information collected at international airports and seaports. Other administrative records which are potential sources of statistics on international migration in some African countries include some limited population registers, records of the registration of aliens, and particulars of residence/work permits issued to aliens. Although frontier control data are considered the most important source of international migration statistics, in many African countries these data are too deficient to provide a satisfactory indication of the level of international migration. Thus decennial population censuses and/or sample surveys are the major sources of the available statistics on the stock and characteristics of international migration. Indirect methods can be used to supplement census data with intercensal estimates of net migration using census data on the total population. This indirect method of obtaining information on migration can be used to evaluate estimates derived from frontier control records, and it also offers the means of obtaining alternative information on international migration in African countries which have not directly investigated migration topics

  18. RSA migration of total knee replacements.

    PubMed

    Pijls, Bart G; Plevier, José W M; Nelissen, Rob G H H

    2018-06-01

    Purpose - We performed a systematic review and meta-analyses to evaluate the early and long-term migration patterns of tibial components of TKR of all known RSA studies. Methods - Migration pattern was defined as at least 2 postoperative RSA follow-up moments. Maximal total point motion (MTPM) at 6 weeks, 3 months, 6 months, 1 year, 2 years, 5 years, and 10 years were considered. Results - The literature search yielded 1,167 hits of which 53 studies were included, comprising 111 study groups and 2,470 knees. The majority of the early migration occurred in the first 6 months postoperatively followed by a period of stability, i.e., no or very little migration. Cemented and uncemented tibial components had different migration patterns. For cemented tibial components there was no difference in migration between all-poly and metal-backed components, between mobile bearing and fixed bearing, between cruciate retaining and posterior stabilized. Furthermore, no difference existed between TKR measured with model-based RSA or marker-based RSA methods. For uncemented TKR there was some variation in migration with the highest migration for uncoated TKR. Interpretation - The results from this meta-analysis on RSA migration of TKR are in line with both the survival analyses results from joint registries of these TKRs as well as revision rates results from meta-analyses, thus providing further proof for the association between early migration and late revision for loosening. The pooled migration patterns can be used both as benchmarks and for defining migration thresholds for future evaluation of new TKR.

  19. Neuronal migration on laminin in vitro.

    PubMed

    Liang, S; Crutcher, K A

    1992-03-20

    Chick sympathetic (E-9) or telencephalic (E-7) neurons were cultured at low density on poly-DL-ornithine (PORN), poly-L-lysine (POLS), laminin or laminin-covered PORN or POLS and monitored with time-lapse videomicroscopy. Neurons migrated on laminin, or laminin-covered PORN or POLS, but not on PORN or POLS alone. Neuronal migration did not involve interactions with other cells indicating that neurons are capable of independent migration when exposed to a laminin substrate.

  20. Bayesian Probabilistic Projection of International Migration.

    PubMed

    Azose, Jonathan J; Raftery, Adrian E

    2015-10-01

    We propose a method for obtaining joint probabilistic projections of migration for all countries, broken down by age and sex. Joint trajectories for all countries are constrained to satisfy the requirement of zero global net migration. We evaluate our model using out-of-sample validation and compare point projections to the projected migration rates from a persistence model similar to the method used in the United Nations' World Population Prospects, and also to a state-of-the-art gravity model.

  1. The mechanism for migration in Poland.

    PubMed

    Rykiel, Z

    1988-01-01

    The author reviews neoclassical theories and models of migration. The mobility theory, which concerns the impact of local labor markets on migration, is discussed in the Polish context. A general model of the regional labor market and a multicausal model are developed to explain the patterns of internal migration. The period of a managed economy (1949-1980) is contrasted with the period since the implementation of a new economic system in 1983.

  2. Navigational Strategies of Migrating Monarch Butterflies

    DTIC Science & Technology

    2014-11-10

    AFRL-OSR-VA-TR-2014-0339 NAVIGATIONAL STRATEGIES OF MIGRATING MONARCH BUTTERFLIES Steven Reppert UNIVERSITY OF MASSACHUSETTS Final Report 11/10/2014...Final Progress Statement to (Dr. Patrick Bradshaw) Contract/Grant Title: Navigational Strategies of Migrating Monarch Butterflies Contract...Grant #: FA9550-10-1-0480 Reporting Period: 01-Sept-10 to 31-Aug-14 Overview of accomplishments: Migrating monarch butterflies (Danaus

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-12-04

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

  5. 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

  6. Intermittent tremor migrations beneath Guerrero, Mexico, and implications for fault healing within the slow slip zone

    NASA Astrophysics Data System (ADS)

    Peng, Yajun; Rubin, Allan M.

    2017-01-01

    Slow slip events exhibit significant complexity in slip evolution and variations in recurrence intervals. Behavior that varies systematically with recurrence interval is likely to reflect different extents of fault healing between these events. Here we use high-resolution tremor catalogs beneath Guerrero, Mexico, to investigate the mechanics of slow slip. We observe complex tremor propagation styles, including rapid tremor migrations propagating either along the main tremor front or backward, reminiscent of those in northern Cascadia. We also find many migrations that originate well behind the front and repeatedly occupy the same source region during a tremor episode, similar to those previously reported from Shikoku, Japan. These migrations could be driven by slow slip in the surrounding regions, with recurrence intervals possibly modulated by tides. The propagation speed of these migrations decreases systematically with time since the previous migration over the same source area. Tremor amplitudes seem consistent with changes in the propagation speeds being controlled primarily by changes in the slip speeds. One interpretation is that the high propagation speeds and inferred high slip speeds during the migrations with short recurrence intervals are caused by incomplete healing within the host rock adjacent to the shear zone, which could lead to high permeability and reduced dilatant strengthening of the fault gouge. Similar processes may operate in other slow slip source regions such as Cascadia.

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

    PubMed

    Zaslavska, T; Ribakovski, L

    1983-01-01

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

  8. Nuss bar migrations: occurrence and classification.

    PubMed

    Binkovitz, Lauren E; Zendejas, Benjamin; Moir, Christopher R; Binkovitz, Larry A

    2016-12-01

    Pectus excavatum results from dorsal deviation of the sternum causing narrowing of the anterior-posterior diameter of the chest. It can result in significant cosmetic deformities and cardiopulmonary compromise if severe. The Nuss procedure is a minimally invasive technique that involves placing a thin horizontally oriented metal bar below the dorsal sternal apex for correction of the pectus deformity. To identify the frequency and types of Nuss bar migrations, to present a new categorization of bar migrations, and to present examples of true migrations and pseudomigrations. We retrospectively reviewed the electronic medical records and all pertinent radiologic studies of 311 pediatric patients who underwent a Nuss procedure. We evaluated the frequency and type of bar migrations. Bar migration was demonstrated in 23 of 311 patients (7%) and occurred within a mean period of 26 days after surgery. Bar migrations were subjectively defined as deviation of the bar from the position demonstrated on the immediate postoperative radiographs and categorized as superior, inferior, rotation, lateral or flipped using a new classification system. Sixteen of the 23 migrations required re-operation. Nuss bar migration can be diagnosed with careful evaluation of serial radiographs. Nuss bar migration has a wide variety of appearances and requires exclusion of pseudomigration resulting from changes in patient positioning between radiologic examinations.

  9. Motorized Migrations: the Future or Mere Fantasy?

    USGS Publications Warehouse

    Ellis, D.H.; Sladen, William J. L.; Lishman, W.A.; Clegg, K.R.; Duff, J.W.; Gee, G.F.; Lewis, J.C.

    2003-01-01

    In 15 experiments from 1993-2002, we led cranes, geese, or swans on their first southward migration with either ultralight aircraft or vehicles on the ground. These experiments reveal that large birds can be readily trained to follow and most will return north (and south) in subsequent migrations unassisted. These techniques can now be used to teach birds new (or forgotten) migration paths. Although we are constantly improving our training techniques, we now have an operational program that can be broadly applied to those species where juveniles learn migration routes from their parents.

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

    PubMed Central

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

    2016-01-01

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

  11. Supported PV module assembly

    DOEpatents

    Mascolo, Gianluigi; Taggart, David F.; Botkin, Jonathan D.; Edgett, Christopher S.

    2013-10-15

    A supported PV assembly may include a PV module comprising a PV panel and PV module supports including module supports having a support surface supporting the module, a module registration member engaging the PV module to properly position the PV module on the module support, and a mounting element. In some embodiments the PV module registration members engage only the external surfaces of the PV modules at the corners. In some embodiments the assembly includes a wind deflector with ballast secured to a least one of the PV module supports and the wind deflector. An array of the assemblies can be secured to one another at their corners to prevent horizontal separation of the adjacent corners while permitting the PV modules to flex relative to one another so to permit the array of PV modules to follow a contour of the support surface.

  12. Cancer cell migration within 3D layer-by-layer microfabricated photocrosslinked PEG scaffolds with tunable stiffness.

    PubMed

    Soman, Pranav; Kelber, Jonathan A; Lee, Jin Woo; Wright, Tracy N; Vecchio, Kenneth S; Klemke, Richard L; Chen, Shaochen

    2012-10-01

    Our current understanding of 3-dimensional (3D) cell migration is primarily based on results from fibrous scaffolds with randomly organized internal architecture. Manipulations that change the stiffness of these 3D scaffolds often alter other matrix parameters that can modulate cell motility independently or synergistically, making observations less predictive of how cells behave when migrating in 3D. In order to decouple microstructural influences and stiffness effects, we have designed and fabricated 3D polyethylene glycol (PEG) scaffolds that permit orthogonal tuning of both elastic moduli and microstructure. Scaffolds with log-pile architectures were used to compare the 3D migration properties of normal breast epithelial cells (HMLE) and Twist-transformed cells (HMLET). Our results indicate that the nature of cell migration is significantly impacted by the ability of cells to migrate in the third dimension. 2D ECM-coated PEG substrates revealed no statistically significant difference in cell migration between HMLE and HMLET cells among substrates of different stiffness. However, when cells were allowed to move along the third dimension, substantial differences were observed for cell displacement, velocity and path straightness parameters. Furthermore, these differences were sensitive to both substrate stiffness and the presence of the Twist oncogene. Importantly, these 3D modes of migration provide insight into the potential for oncogene-transformed cells to migrate within and colonize tissues of varying stiffness. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2017-11-01

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

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

    USGS Publications Warehouse

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

    2011-01-01

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

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

    USGS Publications Warehouse

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

    2011-01-01

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

  16. Regulators of Intestinal Epithelial Migration in Sepsis.

    PubMed

    Meng, Mei; Klingensmith, Nathan J; Liang, Zhe; Lyons, John D; Fay, Katherine T; Chen, Ching-Wen; Ford, Mandy L; Coopersmith, Craig M

    2018-02-08

    The gut is a continuously renewing organ, with cell proliferation, migration and death occurring rapidly under basal conditions. Since the impact of critical illness on cell movement from crypt base to villus tip is poorly understood, the purpose of this study was to determine how sepsis alters enterocyte migration. Wild type, transgenic and knockout mice were injected with 5-bromo-2'deoxyuridine (BrdU) to label cells in S phase before and after the onset of cecal ligation and puncture and were sacrificed at pre-determined endpoints to determine distance proliferating cells migrated up the crypt-villus unit. Enterocyte migration rate was decreased from 24-96 hours following sepsis. BrdU was not detectable on villi 6 days after sham laparotomy, meaning all cells had migrated the length of the gut and been exfoliated into its lumen. However, BrdU positive cells were detectable on villi 10 days after sepsis. Multiple components of gut integrity altered enterocyte migration. Sepsis decreased crypt proliferation, which further slowed enterocyte transit as mice injected with BrdU after the onset of sepsis (decreased proliferation) had slower migration than mice injected with BrdU prior to the onset of sepsis (normal proliferation). Decreasing intestinal apoptosis via gut-specific overexpression of Bcl-2 prevented sepsis-induced slowing of enterocyte migration. In contrast, worsened intestinal hyperpermeability by genetic deletion of JAM-A increased enterocyte migration. Sepsis therefore significantly slows enterocyte migration, and intestinal proliferation, apoptosis and permeability all affect migration time, which can potentially be targeted both genetically and pharmacologically.

  17. Morphological constraints on changing avian migration phenology.

    PubMed

    Møller, A P; Rubolini, D; Saino, N

    2017-06-01

    Many organisms at northern latitudes have responded to climate warming by advancing their spring phenology. Birds are known to show earlier timing of spring migration and reproduction in response to warmer springs. However, species show heterogeneous phenological responses to climate warming, with those that have not advanced or have delayed migration phenology experiencing population declines. Although some traits (such as migration distance) partly explain heterogeneity in phenological responses, the factors affecting interspecies differences in the responsiveness to climate warming have yet to be fully explored. In this comparative study, we investigate whether variation in wing aspect ratio (reflecting relative wing narrowness), an ecomorphological trait that is strongly associated with flight efficiency and migratory behaviour, affects the ability to advance timing of spring migration during 1960-2006 in a set of 80 European migratory bird species. Species with larger aspect ratio (longer and narrower wings) showed smaller advancement of timing of spring migration compared to species with smaller aspect ratio (shorter and wider wings) while controlling for phylogeny, migration distance and other life-history traits. In turn, migration distance positively predicted aspect ratio across species. Hence, species that are better adapted to migration appear to be more constrained in responding phenologically to rapid climate warming by advancing timing of spring migration. Our findings corroborate the idea that aspect ratio is a major evolutionary correlate of migration, and suggest that selection for energetically efficient flights, as reflected by high aspect ratio, may hinder phenotypically plastic/microevolutionary adjustments of migration phenology to ongoing climatic changes. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  18. Void migration in fusion materials

    NASA Astrophysics Data System (ADS)

    Cottrell, G. A.

    2002-04-01

    Neutron irradiation in a fusion power plant will cause helium bubbles and voids to form in the armour and blanket structural materials. If sufficiently large densities of such defects accumulate on the grain boundaries of the materials, the strength and the lifetimes of the metals will be reduced by helium embrittlement and grain boundary failure. This Letter discusses void migration in metals, both by random Brownian motion and by biassed flow in temperature gradients. In the assumed five-year blanket replacement time of a fusion power plant, approximate calculations show that the metals most resilient to failure are tungsten and molybdenum, and marginally vanadium. Helium embrittlement and grain boundary failure is expected to be more severe in steel and beryllium.

  19. Seismic migration in generalized coordinates

    NASA Astrophysics Data System (ADS)

    Arias, C.; Duque, L. F.

    2017-06-01

    Reverse time migration (RTM) is a technique widely used nowadays to obtain images of the earth’s sub-surface, using artificially produced seismic waves. This technique has been developed for zones with flat surface and when applied to zones with rugged topography some corrections must be introduced in order to adapt it. This can produce defects in the final image called artifacts. We introduce a simple mathematical map that transforms a scenario with rugged topography into a flat one. The three steps of the RTM can be applied in a way similar to the conventional ones just by changing the Laplacian in the acoustic wave equation for a generalized one. We present a test of this technique using the Canadian foothills SEG velocity model.

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

    PubMed

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

    2015-08-01

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

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

    PubMed Central

    Fussell, Elizabeth; DeWaard, Jack

    2015-01-01

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

  2. Curvature capillary migration of microspheres.

    PubMed

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

    2015-09-14

    We address the question: how does capillarity propel microspheres along curvature gradients? For a particle on a fluid interface, there are two conditions that can apply at the three phase contact line: either the contact line adopts an equilibrium contact angle, or it can be pinned by kinetic trapping, e.g. at chemical heterogeneities, asperities, or other pinning sites on the particle surface. We formulate the curvature capillary energy for both scenarios for particles smaller than the capillary length and far from any pinning boundaries. The scale and range of the distortion made by the particle are set by the particle radius; we use singular perturbation methods to find the distortions and to rigorously evaluate the associated capillary energies. For particles with equilibrium contact angles, contrary to the literature, we find that the capillary energy is negligible, with the first contribution bounded to fourth order in the product of the particle radius and the deviatoric curvature of the host interface. For pinned contact lines, we find curvature capillary energies that are finite, with a functional form investigated previously by us for disks and microcylinders on curved interfaces. In experiments, we show microspheres migrate along deterministic trajectories toward regions of maximum deviatoric curvature with curvature capillary energies ranging from 6 × 10(3)-5 × 10(4)kBT. These data agree with the curvature capillary energy for the case of pinned contact lines. The underlying physics of this migration is a coupling of the interface deviatoric curvature with the quadrupolar mode of nanometric disturbances in the interface owing to the particle's contact line undulations. This work is an example of the major implications of nanometric roughness and contact line pinning for colloidal dynamics.

  3. Bats on a Budget: Torpor-Assisted Migration Saves Time and Energy

    PubMed Central

    McGuire, Liam P.; Jonasson, Kristin A.; Guglielmo, Christopher G.

    2014-01-01

    Bats and birds must balance time and energy budgets during migration. Migrating bats face similar physiological challenges to birds, but nocturnality creates special challenges for bats, such as a conflict between travelling and refueling, which many birds avoid by feeding in daylight and flying at night. As endothermic animals, bats and birds alike must expend substantial amounts of energy to maintain high body temperatures. For migratory birds refueling at stopovers, remaining euthermic during inactive periods reduces the net refuelling rate, thereby prolonging stopover duration and delaying subsequent movement. We hypothesized that bats could mitigate similar ambient-temperature dependent costs by using a torpor-assisted migration strategy. We studied silver-haired bats Lasionycteris noctivagans during autumn migration using a combination of respirometry and temperature-sensitive radiotelemetry to estimate energy costs incurred under ambient temperature conditions, and the energy that bats saved by using torpor during daytime roosting periods. All bats, regardless of sex, age, or body condition used torpor at stopover and saved up to 91% of the energy they would have expended to remain euthermic. Furthermore, bats modulated use of torpor depending on ambient temperature. By adjusting the time spent torpid, bats achieved a rate of energy expenditure independent of the ambient temperature encountered at stopover. By lowering body temperature during inactive periods, fuel stores are spared, reducing the need for refuelling. Optimal migration models consider trade-offs between time and energy. Heterothermy provides a physiological strategy that allows bats to conserve energy without paying a time penalty as they migrate. Although uncommon, some avian lineages are known to use heterothermy, and current theoretical models of migration may not be appropriate for these groups. We propose that thermoregulatory strategies should be an important consideration of future

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

    PubMed

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

    2017-10-10

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

  5. Cloud Migration Experiment Configuration and Results

    DTIC Science & Technology

    2017-12-01

    ARL-TR-8248 ● DEC 2017 US Army Research Laboratory Cloud Migration Experiment Configuration and Results by Michael De Lucia...or reconstruction of the document. ARL-TR-8248 ● DEC 2017 US Army Research Laboratory Cloud Migration Experiment Configuration...and Results by Michael De Lucia Computational and Information Sciences Directorate, ARL Justin Wray and Steven S Collmann ICF International

  6. Phased Migration to Koha: Our Library's Experience

    ERIC Educational Resources Information Center

    Kohn, Karen; McCloy, Eric

    2010-01-01

    Landman Library is two-thirds of the way through a three-stage process of migrating to the Koha open-source integrated library system (http://koha-community.org). We are an academic library with roughly 143,000 volumes, six professional librarians, and three support staff. The migration to open source was driven by the desire to access our own…

  7. Migration and Recognition of Diplomas in Sweden

    ERIC Educational Resources Information Center

    Dingu-Kyrklund, Elena

    2005-01-01

    Trans-national migration is now a global phenomenon, affecting an increasing amount of persons, many of whom have already completed a form of higher education in their country of origin or earlier residence at the time of migration. There is consequently a need to evaluate foreign degrees and assess migrants' professional competence beyond their…

  8. Migration and sorption phenomena in packaged foods.

    PubMed

    Gnanasekharan, V; Floros, J D

    1997-10-01

    Rapidly developing analytical capabilities and continuously evolving stringent regulations have made food/package interactions a subject of intense research. This article focuses on: (1) the migration of package components such as oligomers and monomers, processing aids, additives, and residual reactants in to packaged foods, and (2) sorption of food components such as flavors, lipids, and moisture into packages. Principles of diffusion and thermodynamics are utilized to describe the mathematics of migration and sorption. Mathematical models are developed from first principles, and their applicability is illustrated using numerical simulations and published data. Simulations indicate that available models are system (polymer-penetrant) specific. Furthermore, some models best describe the early stages of migration/sorption, whereas others should be used for the late stages of these phenomena. Migration- and/or sorption-related problems with respect to glass, metal, paper-based and polymeric packaging materials are discussed, and their importance is illustrated using published examples. The effects of migrating and absorbed components on food safety, quality, and the environment are presented for various foods and packaging materials. The impact of currently popular packaging techniques such as microwavable, ovenable, and retortable packaging on migration and sorption are discussed with examples. Analytical techniques for investigating migration and sorption phenomena in food packaging are critically reviewed, with special emphasis on the use and characteristics of food-simulating liquids (FSLs). Finally, domestic and international regulations concerning migration in packaged foods, and their impact on food packaging is briefly presented.

  9. Planning the future's forests with assisted migration

    Treesearch

    Mary I. Williams; R. Kasten Dumroese

    2014-01-01

    Studies show that changes in climate may exceed plant adaptation and migration. The mismatch in rates between climate change and plant adaptation and migration will pose significant challenges for practitioners that select, grow, and outplant native tree species. Native tree species and populations that are planted today must meet the climatic challenges that they will...

  10. Endogenous timing factors in bird migration

    NASA Technical Reports Server (NTRS)

    Gwinner, E. G.

    1972-01-01

    Several species of warbler birds were observed in an effort to determine what initiates and terminates migration. Environmental and endogenous timing mechanisms were analyzed. The results indicate that endogenous stimuli are dominant factors for bird migration especially for long distances. It was concluded that environmental factors act as an assist mechanism.

  11. Parental Migration and Children's Outcomes in Romania

    ERIC Educational Resources Information Center

    Robila, Mihaela

    2011-01-01

    Although Eastern European migration has increased greatly, the research on its impact on children and families has been limited. In this study I examined the impact of parental economic migration on children psychosocial and academic outcomes in Romania, one of largest Eastern European migrant sending country. Surveys were conducted with 382…

  12. The Psychology of Puerto Rican Migration.

    ERIC Educational Resources Information Center

    Prewitt Diaz, Joseph O.

    The psychology of the Puerto Rican migrant to the United States mainland is explored. Puerto Ricans have been migrating to the U.S. mainland and returning to Puerto Rico for more than 125 years, and, in fact, approximately 57% of all Puerto Ricans have migrated at one time or another. The migrant experience, including the circular migration…

  13. Women in Migration: A Third World Focus.

    ERIC Educational Resources Information Center

    Youssef, Nadia; And Others

    Spurred in part by the apparent contradiction between recent data on the magnitude of autonomous female migration and the lack of acknowledgment of that data in recent literature, a 1979 study attempted to define women migrants in 46 Third World Countries in terms of age, marital status, socioeconomic status, factors motivating migration, and…

  14. [Long-term implications of labor migration in Togo].

    PubMed

    De Haan, L

    1986-01-01

    Labor migration in Togo since 1900 is analyzed. The author examines factors affecting the demand for labor in areas of in-migration, the development of systems of production related to population growth in areas of out-migration, and state intervention. Consideration is given to both international and internal migration. The expansion of internal migration since independence is noted. (SUMMARY IN ENG)

  15. Collective cell migration during inflammatory response

    NASA Astrophysics Data System (ADS)

    Wu, Di; Stroka, Kimberly; Aranda-Espinoza, Helim

    2012-02-01

    Wound scratch healing assays of endothelial cell monolayers is a simple model to study collective cell migration as a function of biological signals. A signal of particular interest is the immune response, which after initial wounding in vivo causes the release of various inflammatory factors such as tumor necrosis alpha (TNF-α). TNF-α is an innate inflammatory cytokine that can induce cell growth, cell necrosis, and change cell morphology. We studied the effects of TNF-α on collective cell migration using the wound healing assays and measured several migration metrics, such as rate of scratch closure, velocities of leading edge and bulk cells, closure index, and velocity correlation functions between migrating cells. We observed that TNF-α alters all migratory metrics as a function of the size of the scratch and TNF-α content. The changes observed in migration correlate with actin reorganization upon TNF-α exposure.

  16. Undocumented migration in response to climate change

    PubMed Central

    Riosmena, Fernando; Hunter, Lori M.; Runfola, Daniel M.

    2016-01-01

    In the face of climate change induced economic uncertainty, households may employ migration as an adaptation strategy to diversify their livelihood portfolio through remittances. However, it is unclear whether such climate migration will be documented or undocumented. In this study we combine detailed migration histories with daily temperature and precipitation information for 214 weather stations to investigate whether climate change more strongly impacts undocumented or documented migration from 68 rural Mexican municipalities to the U.S. during the years 1986–1999. We employ two measures of climate change, the warm spell duration index (WSDI) and the precipitation during extremely wet days (R99PTOT). Results from multi-level event-history models demonstrate that climate-related international migration from rural Mexico was predominantly undocumented. We conclude that programs to facilitate climate change adaptation in rural Mexico may be more effective in reducing undocumented border crossings than increased border fortification. PMID:27570840

  17. LHCb migration from Subversion to Git

    NASA Astrophysics Data System (ADS)

    Clemencic, M.; Couturier, B.; Closier, J.; Cattaneo, M.

    2017-10-01

    Due to user demand and to support new development workflows based on code review and multiple development streams, LHCb decided to port the source code management from Subversion to Git, using the CERN GitLab hosting service. Although tools exist for this kind of migration, LHCb specificities and development models required careful planning of the migration, development of migration tools, changes to the development model, and redefinition of the release procedures. Moreover we had to support a hybrid situation with some software projects hosted in Git and others still in Subversion, or even branches of one projects hosted in different systems. We present the way we addressed the special LHCb requirements, the technical details of migrating large non standard Subversion repositories, and how we managed to smoothly migrate the software projects following the schedule of each project manager.

  18. Undocumented migration in response to climate change.

    PubMed

    Nawrotzki, Raphael J; Riosmena, Fernando; Hunter, Lori M; Runfola, Daniel M

    In the face of climate change induced economic uncertainty, households may employ migration as an adaptation strategy to diversify their livelihood portfolio through remittances. However, it is unclear whether such climate migration will be documented or undocumented. In this study we combine detailed migration histories with daily temperature and precipitation information for 214 weather stations to investigate whether climate change more strongly impacts undocumented or documented migration from 68 rural Mexican municipalities to the U.S. during the years 1986-1999. We employ two measures of climate change, the warm spell duration index ( WSDI ) and the precipitation during extremely wet days ( R99PTOT ). Results from multi-level event-history models demonstrate that climate-related international migration from rural Mexico was predominantly undocumented. We conclude that programs to facilitate climate change adaptation in rural Mexico may be more effective in reducing undocumented border crossings than increased border fortification.

  19. The multiple faces of leukocyte interstitial migration

    PubMed Central

    Lämmermann, Tim; Germain, Ronald N.

    2014-01-01

    Spatiotemporal control of leukocyte dynamics within tissues is critical for successful innate and adaptive immune responses. Homeostatic trafficking and coordinated infiltration into and within sites of inflammation and infection rely on signaling in response to extracellular cues that in turn controls a variety of intracellular protein networks regulating leukocyte motility, migration, chemotaxis, positioning, and cell–cell interaction. In contrast to mesenchymal cells, leukocytes migrate in an amoeboid fashion by rapid cycles of actin polymerization and actomyosin contraction, and their migration in tissues is generally referred to as low adhesive and nonproteolytic. The interplay of actin network expansion, contraction, and adhesion shapes the exact mode of amoeboid migration, and in this review, we explore how leukocyte subsets potentially harness the same basic biomechanical mechanisms in a cell-type-specific manner. Most of our detailed understanding of these processes derives from in vitro migration studies in three-dimensional gels and confined spaces that mimic geometrical aspects of physiological tissues. We summarize these in vitro results and then critically compare them to data from intravital imaging of leukocyte interstitial migration in mouse tissues. We outline the technical challenges of obtaining conclusive mechanistic results from intravital studies, discuss leukocyte migration strategies in vivo, and present examples of mode switching during physiological interstitial migration. These findings are also placed in the context of leukocyte migration defects in primary immunodeficiencies. This overview of both in vitro and in vivo studies highlights recent progress in understanding the molecular and biophysical mechanisms that shape robust leukocyte migration responses in physiologically complex and heterogeneous environments. PMID:24573488

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

    PubMed

    Bailey, A J; Cooke, T J

    1998-01-01

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

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

    PubMed

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

    2011-01-01

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

  2. Ballasted photovoltaic module and module arrays

    DOEpatents

    Botkin, Jonathan [El Cerrito, CA; Graves, Simon [Berkeley, CA; Danning, Matt [Oakland, CA

    2011-11-29

    A photovoltaic (PV) module assembly including a PV module and a ballast tray. The PV module includes a PV device and a frame. A PV laminate is assembled to the frame, and the frame includes an arm. The ballast tray is adapted for containing ballast and is removably associated with the PV module in a ballasting state where the tray is vertically under the PV laminate and vertically over the arm to impede overt displacement of the PV module. The PV module assembly can be installed to a flat commercial rooftop, with the PV module and the ballast tray both resting upon the rooftop. In some embodiments, the ballasting state includes corresponding surfaces of the arm and the tray being spaced from one another under normal (low or no wind) conditions, such that the frame is not continuously subjected to a weight of the tray.

  3. Genetics Home Reference: malignant migrating partial seizures of infancy

    MedlinePlus

    ... of infancy (MMPSI) is a severe form of epilepsy that begins very early in life. Recurrent seizures ... infantile epileptic encephalopathy 14 EIEE14 malignant migrating partial epilepsy of infancy migrating partial epilepsy of infancy migrating ...

  4. Antarctic grounding-line migration

    NASA Astrophysics Data System (ADS)

    Slater, T.; Konrad, H.; Shepherd, A.; Gilbert, L.; Hogg, A.; McMillan, M.; Muir, A. S.

    2017-12-01

    Knowledge of grounding-line position is critical for quantifying ice discharge into the ocean, as a boundary condition for numerical models of ice flow, and as an indicator of ice sheet stability. Although geological investigations have documented extensive grounding-line retreat since the period of the Last Glacial Maximum, observations of grounding line migration during the satellite era are restricted to a handful of locations. We combine satellite altimeter observations of ice-elevation change and airborne measurements of ice geometry to track movement of the Antarctic Ice Sheet grounding line. Based on these data, we estimate that 22%, 3%, and 10% of the West Antarctic, East Antarctic, and Antarctic Peninsula ice sheet grounding lines are retreating at rates faster than the typical pace since the Last Glacial Maximum, and that the continent loses over 200 km2 of grounded-ice area per year. Although by far the fastest rates of retreat occurred in the Amundsen Sea Sector, the Pine Island Glacier grounding line has stabilized - likely as a consequence of abated ocean forcing during the survey period.

  5. Multigeneration data migration from legacy systems

    NASA Astrophysics Data System (ADS)

    Ratib, Osman M.; Liu, Brent J.; Kho, Hwa T.; Tao, Wenchao; Wang, Cun; McCoy, J. Michael

    2003-05-01

    The migration of image data from different generations of legacy archive systems represents a technical challenge and in incremental cost in transitions to newer generations of PACS. UCLA medical center has elected to completely replace the existing PACS infrastructure encompassing several generations of legacy systems by a new commercial system providing enterprise-wide image management and communication. One of the most challenging parts of the project was the migration of large volumes of legacy images into the new system. Planning of the migration required the development of specialized software and hardware, and included different phases of data mediation from existing databases to the new PACS database prior to the migration of the image data. The project plan included a detailed analysis of resources and cost of data migration to optimize the process and minimize the delay of a hybrid operation where the legacy systems need to remain operational. Our analysis and project planning showed that the data migration represents the most critical path in the process of PACS renewal. Careful planning and optimization of the project timeline and resources allocated is critical to minimize the financial impact and the time delays that such migrations can impose on the implementation plan.

  6. The international migration of Indian nurses.

    PubMed

    Thomas, P

    2006-12-01

    To identify the factors responsible for the international migration of Indian nurses. The paper is based on the responses of 448 nurse practitioners, nurse educators and nurse administrators to a questionnaire administered to them in December 2004-January 2005. Key factors were identified by the analysis of contingency tables. Apart from economic factors, dissatisfaction with working conditions and unhappiness with prevalent social attitudes towards nurses were identified as being of crucial importance for the international migration of Indian nurses. It was found that nurses working in the private sector and from some linguistic and religious groups were particularly prone to migration. Nurses working in the government sector seemed to be more worried about being unable to adjust to working conditions abroad, and therefore less keen to migrate. The fact that they enjoyed better pay scales, a more relaxed work atmosphere and more facilities may have also played a part here. What seemed to be vital to the decision to migrate for a large number of government sector nurses belonging to the so-called 'Forward' and 'Middle' Castes was that they were being crowded out of promotional avenues as a result of the government's policy of Reservations in Promotions for Scheduled Castes and Tribes. Health policy-makers in India need to take a serious look at the growing migration of nurses to foreign countries. While such migration leads to inflow of foreign exchange, it also implies the loss of medical personnel vital for the fulfilment of national goals.

  7. Migration and mental health: An interface

    PubMed Central

    Virupaksha, H. G.; Kumar, Ashok; Nirmala, Bergai Parthsarathy

    2014-01-01

    Migration is a universal phenomenon, which existed with the subsistence of the human beings on earth. People migrate from one place to another for several reasons, but the goal or main reason behind changing the residence would be improving their living conditions or to escape from debts and poverty. Migration is also a social phenomenon which influences human life and the environment around. Hence, migration has a great impact on any geographical area and it is known as one of the three basic components of population growth of any particular region (the other two are, mortality and fertility). Migration involves certain phases to go through; hence, it is a process. Many times, lack of preparedness, difficulties in adjusting to the new environment, the complexity of the local system, language difficulties, cultural disparities and adverse experiences would cause distress to the migrants. Moreover subsequently it has a negative impact on mental well-being of such population. Due to globalization, modernization, improved technologies and developments in all the sectors, the migration and its impact on human well-being is a contemporary issue; hence, here is an attempt to understand the migration and its impact on the mental health of the migrants based on the studies conducted around. PMID:25097389

  8. 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

  9. Migration and Development: A Theoretical Perspective 1

    PubMed Central

    De Haas, Hein

    2010-01-01

    The debate on migration and development has swung back and forth like a pendulum, from developmentalist optimism in the 1950s and 1960s, to neo‐Marxist pessimism over the 1970s and 1980s, towards more optimistic views in the 1990s and 2000s. This paper argues how such discursive shifts in the migration and development debate should be primarily seen as part of more general paradigm shifts in social and development theory. However, the classical opposition between pessimistic and optimistic views is challenged by empirical evidence pointing to the heterogeneity of migration impacts. By integrating and amending insights from the new economics of labor migration, livelihood perspectives in development studies and transnational perspectives in migration studies – which share several though as yet unobserved conceptual parallels – this paper elaborates the contours of a conceptual framework that simultaneously integrates agency and structure perspectives and is therefore able to account for the heterogeneous nature of migration‐development interactions. The resulting perspective reveals the naivety of recent views celebrating migration as self‐help development “from below”. These views are largely ideologically driven and shift the attention away from structural constraints and the vital role of states in shaping favorable conditions for positive development impacts of migration to occur. PMID:26900199

  10. Can mesenchymal cells undergo collective cell migration?

    PubMed Central

    Theveneau, Eric

    2011-01-01

    Cell migration is critical for proper development of the embryo and is also used by many cell types to perform their physiological function. For instance, cell migration is essential for immune cells to monitor the body and for epithelial cells to heal a wound whereas, in cancer cells, acquisition of migratory capabilities is a critical step toward malignancy. Migratory cells are often categorized into two groups: (1) mesenchymal cells, produced by an epithelium-to-mesenchyme transition, that undergo solitary migration and (2) epithelial-like cells which migrate collectively. However, on some occasions, mesenchymal cells may travel in large, dense groups and exhibit key features of collectively migrating cells such as coordination and cooperation. Here, using data published on neural crest cells, a highly invasive mesenchymal cell population that extensively migrate throughout the embryo, we explore the idea that mesenchymal cells, including cancer cells, might be able to undergo collective cell migration under certain conditions and discuss how they could do so. PMID:22274714

  11. MeltMigrator: A MATLAB-based software for modeling three-dimensional melt migration and crustal thickness variations at mid-ocean ridges following a rules-based approach

    NASA Astrophysics Data System (ADS)

    Bai, Hailong; Montési, Laurent G. J.; Behn, Mark D.

    2017-01-01

    MeltMigrator is a MATLAB®-based melt migration software developed to process three-dimensional mantle temperature and velocity data from user-supplied numerical models of mid-ocean ridges, calculate melt production and melt migration trajectories in the mantle, estimate melt flux along plate boundaries, and predict crustal thickness distribution on the seafloor. MeltMigrator is also capable of calculating compositional evolution depending on the choice of petrologic melting model. Programmed in modules, MeltMigrator is highly customizable and can be expanded to a wide range of applications. We have applied it to complex mid-ocean ridge model settings, including transform faults, oblique segments, ridge migration, asymmetrical spreading, background mantle flow, and ridge-plume interaction. In this technical report, we include an example application to a segmented mid-ocean ridge. MeltMigrator is available as a supplement to this paper, and it is also available from GitHub and the University of Maryland Geodynamics Group website.

  12. The accretion of migrating giant planets

    NASA Astrophysics Data System (ADS)

    Dürmann, Christoph; Kley, Wilhelm

    2017-02-01

    Aims: Most studies concerning the growth and evolution of massive planets focus either on their accretion or their migration only. In this work we study both processes concurrently to investigate how they might mutually affect one another. Methods: We modeled a two-dimensional disk with a steady accretion flow onto the central star and embedded a Jupiter mass planet at 5.2 au. The disk is locally isothermal and viscosity is modeled using a constant α. The planet is held on a fixed orbit for a few hundred orbits to allow the disk to adapt and carve a gap. After this period, the planet is released and free to move according to the gravitational interaction with the gas disk. The mass accretion onto the planet is modeled by removing a fraction of gas from the inner Hill sphere, and the removed mass and momentum can be added to the planet. Results: Our results show that a fast migrating planet is able to accrete more gas than a slower migrating planet. Utilizing a tracer fluid we analyzed the origin of the accreted gas originating predominantly from the inner disk for a fast migrating planet. In the case of slower migration, the fraction of gas from the outer disk increases. We also found that even for very high accretion rates, in some cases gas crosses the planetary gap from the inner to the outer disk. Our simulations show that the crossing of gas changes during the migration process as the migration rate slows down. Therefore, classical type II migration where the planet migrates with the viscous drift rate and no gas crosses the gap is no general process but may only occur for special parameters and at a certain time during the orbital evolution of the planet.

  13. Metallic nanoparticles reduce the migration of human fibroblasts in vitro

    NASA Astrophysics Data System (ADS)

    Vieira, Larissa Fernanda de Araújo; Lins, Marvin Paulo; Viana, Iana Mayane Mendes Nicácio; dos Santos, Jeniffer Estevão; Smaniotto, Salete; Reis, Maria Danielma dos Santos

    2017-03-01

    Nanoparticles have extremely wide applications in the medical and biological fields. They are being used in biosensors, local drug delivery, diagnostics, and medical therapy. However, the potential effects of nanoparticles on target cell and tissue function, apart from cytotoxicity, are not completely understood. Thus, the aim of this study was to investigate the in vitro effects of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) on human fibroblasts with respect to their interaction with the extracellular matrix and in cell migration. Immunofluorescence analysis revealed that treatment with AgNPs or AuNPs decreased collagen and laminin production at all the concentrations tested (0.1, 1, and 10 μg/mL). Furthermore, cytofluorometric analysis showed that treatment with AgNPs reduced the percentage of cells expressing the collagen receptor very late antigen 2, α2β1 integrin (VLA-2) and the laminin receptor very late antigen 6, α6β1 integrin (VLA-6). In contrast, AuNP treatment increased and decreased the percentages of VLA-2-positive and VLA-6-positive cells, respectively, as compared to the findings for the controls. Analysis of cytoskeletal reorganization showed that treatment with both types of nanoparticles increased the formation of stress fibres and number of cell protrusions and impaired cell polarity. Fibroblasts exposed to different concentrations of AuNPs and AgNPs showed reduced migration through transwell chambers in the functional chemotaxis assay. These results demonstrated that metal nanoparticles may influence fibroblast function by negatively modulating the deposition of extracellular matrix molecules (ECM) and altering the expression of ECM receptors, cytoskeletal reorganization, and cell migration.

  14. Metallic nanoparticles reduce the migration of human fibroblasts in vitro.

    PubMed

    Vieira, Larissa Fernanda de Araújo; Lins, Marvin Paulo; Viana, Iana Mayane Mendes Nicácio; Dos Santos, Jeniffer Estevão; Smaniotto, Salete; Reis, Maria Danielma Dos Santos

    2017-12-01

    Nanoparticles have extremely wide applications in the medical and biological fields. They are being used in biosensors, local drug delivery, diagnostics, and medical therapy. However, the potential effects of nanoparticles on target cell and tissue function, apart from cytotoxicity, are not completely understood. Thus, the aim of this study was to investigate the in vitro effects of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) on human fibroblasts with respect to their interaction with the extracellular matrix and in cell migration. Immunofluorescence analysis revealed that treatment with AgNPs or AuNPs decreased collagen and laminin production at all the concentrations tested (0.1, 1, and 10 μg/mL). Furthermore, cytofluorometric analysis showed that treatment with AgNPs reduced the percentage of cells expressing the collagen receptor very late antigen 2, α 2 β 1 integrin (VLA-2) and the laminin receptor very late antigen 6, α 6 β 1 integrin (VLA-6). In contrast, AuNP treatment increased and decreased the percentages of VLA-2-positive and VLA-6-positive cells, respectively, as compared to the findings for the controls. Analysis of cytoskeletal reorganization showed that treatment with both types of nanoparticles increased the formation of stress fibres and number of cell protrusions and impaired cell polarity. Fibroblasts exposed to different concentrations of AuNPs and AgNPs showed reduced migration through transwell chambers in the functional chemotaxis assay. These results demonstrated that metal nanoparticles may influence fibroblast function by negatively modulating the deposition of extracellular matrix molecules (ECM) and altering the expression of ECM receptors, cytoskeletal reorganization, and cell migration.

  15. Migration of legacy mumps applications to relational database servers.

    PubMed

    O'Kane, K C

    2001-07-01

    An extended implementation of the Mumps language is described that facilitates vendor neutral migration of legacy Mumps applications to SQL-based relational database servers. Implemented as a compiler, this system translates Mumps programs to operating system independent, standard C code for subsequent compilation to fully stand-alone, binary executables. Added built-in functions and support modules extend the native hierarchical Mumps database with access to industry standard, networked, relational database management servers (RDBMS) thus freeing Mumps applications from dependence upon vendor specific, proprietary, unstandardized database models. Unlike Mumps systems that have added captive, proprietary RDMBS access, the programs generated by this development environment can be used with any RDBMS system that supports common network access protocols. Additional features include a built-in web server interface and the ability to interoperate directly with programs and functions written in other languages.

  16. 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.

  17. [The European migration situation and its perspectives].

    PubMed

    Mesic, M

    1988-01-01

    "The present migration situation is analysed in regard to the labour market, the legal status of migrants, return flows and reintegration, and the position of second generation migrants.... In the second part of the paper the author attempts to discern the future of migration in Europe on the basis of existing demographic trends in Europe and the world, present trends [in] the labour market, and current technological changes. In this context he offers an outline for the Yugoslav migration perspective." (SUMMARY IN ENG) excerpt

  18. Macrophage migration inhibition test in untreated syphilis.

    PubMed

    Bowszyc, J

    1975-01-01

    Two modifications of macrophage migration inhibition test, one of George and Vaughan and the other one of Svejcar, were performed on a total of 78 cases of untreated syphilis at various stages. As specific antigens were used: Treponema Pallidum ultrasonate and cardiolipin. Inhibition of migration was observed in 87 percent patients with primary syphillis and in all patients with late and late congenital syphilis. After improving and standardisation of the technique of Treponema Pallidum antigen-the migration inhibition test may be recommended as a specific in vitro-test for detection of cell mediated immunity in syphilis.

  19. Probabilistic population projections with migration uncertainty

    PubMed Central

    Azose, Jonathan J.; Ševčíková, Hana; Raftery, Adrian E.

    2016-01-01

    We produce probabilistic projections of population for all countries based on probabilistic projections of fertility, mortality, and migration. We compare our projections to those from the United Nations’ Probabilistic Population Projections, which uses similar methods for fertility and mortality but deterministic migration projections. We find that uncertainty in migration projection is a substantial contributor to uncertainty in population projections for many countries. Prediction intervals for the populations of Northern America and Europe are over 70% wider, whereas prediction intervals for the populations of Africa, Asia, and the world as a whole are nearly unchanged. Out-of-sample validation shows that the model is reasonably well calibrated. PMID:27217571

  20. Migration, development and remittances in rural Mexico.

    PubMed

    Rubenstein, H

    1992-06-01

    The argument is that remittances to Mexico from migrants in the US contribute to household prosperity and lessen the balance of payments problem. The purpose of this article is to provide an overview of the incentives and constraints to development and individual economic well-being in rural Mexico. Examination is made of the financial amount of remittances, the use of remittances, the impact on development of remittances, models of migration, and migration historically. The viewpoint is that migration satisfies labor needs in developed countries to the detriment of underdeveloped countries. $2 billion a year are sent by illegal migrants from the US to Mexico. This sum is 4 times the net earning of Mexico's tourist trade. 21.1% of the Mexican population depend in part on money sent from the US. 79% of illegal migrants remitted money to relatives in Jalisco state. 70% of migrant families receive $170/month. In Guadalupe, 73% of families depended on migrant income. In Villa Guerrero, 50% of households depended on migrant income. Migrant income supported 1 out of 5 households in Mexico. Money is usually spent of household subsistence items. Sometimes money is also spent on community religious festivals, marriage ceremonies, and education of children or improved living conditions. Examples are given of money being used for investment in land and livestock. Migration affects community solidarity, and comparative ethic, and the influence on others to migrate. Employment opportunities are not expanded and cottage and community industries are threatened. Land purchases did not result in land improvements. Migration models are deficient. There is a macro/micro dichotomy. The push-and-pull system is not controllable by individual migrants. The migration remittance model is a product of unequal development and a mechanism feeding migration. Mexican migration has occurred since the 1880's; seasonal migration was encouraged. There was coercion to return to Mexico after the

  1. Urban squatting and migration in Peninsular Malaysia.

    PubMed

    Johnstone, M

    1983-01-01

    "This article examines some of the links between the phenomena of urban migration and squatter settlements in the Third World city. This will be done by demonstrating that both are outcomes of fundamental social and political forces that have operated on these societies. Migration and squatting are placed in a context of the historical processes that led to the uneven development of Malaysia. The article offers some explanation for the origin of the inequalities observed in spatial structures--in this case urban housing--by focusing on one of the contributory factors, namely migration." excerpt

  2. 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

  3. Inhibition of EphA2/EphrinA1 signal attenuates lipopolysaccharide-induced lung injury.

    PubMed

    Hong, Ji Young; Shin, Mi Hwa; Douglas, Ivor S; Chung, Kyung Soo; Kim, Eun Young; Jung, Ji Ye; Kang, Young Ae; Kim, Se Kyu; Chang, Joon; Kim, Young Sam; Park, Moo Suk

    2016-11-01

    Eph-Ephrin signalling mediates various cellular processes, including vasculogenesis, angiogenesis, cell migration, axon guidance, fluid homoeostasis and repair after injury. Although previous studies have demonstrated that stimulation of the EphA receptor induces increased vascular permeability and inflammatory response in lung injury, the detailed mechanisms of EphA2 signalling are unknown. In the present study, we evaluated the role of EphA2 signalling in mice with lipopolysaccharide (LPS)-induced lung injury. Acute LPS exposure significantly up-regulated EphA2 and EphrinA1 expression. Compared with LPS+IgG mice (IgG instillation after LPS exposure), LPS+EphA2 mAb mice [EphA2 monoclonal antibody (mAb) instillation posttreatment after LPS exposure] had attenuated lung injury and reduced cell counts and protein concentration of bronchoalveolar lavage fluid (BALF). EphA2 mAb posttreatment down-regulated the expression of phosphoinositide 3-kinases (PI3K) 110γ, phospho-Akt, phospho-NF-κB p65, phospho-Src and phospho-S6K in lung lysates. In addition, inhibiting the EphA2 receptor augmented the expression of E-cadherin, which is involved in cell-cell adhesion. Our study identified EphA2 receptor as an unrecognized modulator of several signalling pathways-including PI3K-Akt-NF-kB, Src-NF-κB, E-cadherin and mTOR-in LPS-induced lung injury. These results suggest that EphA2 receptor inhibitors may function as novel therapeutic agents for LPS-induced lung injury. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  6. The Role of 2D Circulation in Sand Bar Migration

    NASA Astrophysics Data System (ADS)

    Splinter, K. D.; Holman, R. A.; Plant, N. G.; Holland, K. T.

    2006-12-01

    position, sinuosity, and incident wave conditions, over a one-year period of time-exposure images of Palm Beach, Australia. The resulting analysis produces clear links between bar sinuosity and the rate of change of mean bar position, suggesting a 2DH approach should be used when modeling bar migration. Gallagher, E. L., et al. (1998), Observations of sand bar evolution on a natural beach, Journal of Geophysical Research, 103, 3203-3215. Plant, N. G., et al. (in review), A dynamical attractor governs beach response to storms, Journal of Geophysical Research.

  7. Module utilization committee

    NASA Technical Reports Server (NTRS)

    Volkmer, K.; Praver, G.

    1984-01-01

    Photovoltaic collector modules were declared surplus to the needs of the U.S. Dept. of Energy. The Module Utilization Committee was formed to make appropriate disposition of the surplus modules on a national basis and to act as a broker for requests for these modules originating outside of the National Photovoltaics Program.

  8. Podoplanin increases migration and angiogenesis in malignant glioma

    PubMed Central

    Grau, Stefan J; Trillsch, Fabian; Tonn, Joerg-Christian; Goldbrunner, Roland H; Noessner, Elfriede; Nelson, Peter J; von Luettichau, Irene

    2015-01-01

    Expression of podoplanin in glial brain tumors is grade dependent. While serving as a marker for tumor progression and modulating invasion in various neoplasms, little is known about podoplanin function in gliomas. Therefore we stably transfected two human glioma cell lines (U373MG and U87MG) with expression plasmids encoding podoplanin. The efficacy of transfection was confirmed by FACS analysis, PCR and immunocytochemistry. Cells were then sorted for highly podoplanin expressing cells (U373Phigh/U87Phigh). Transfection did not influence the production of pro-angiogenic factors including VEGF, VEGF-C and D. Also, expression of VEGF receptors (VEGFR) remained unchanged except for U87Phigh, where a VEGFR3 expression was induced. U373Phigh showed significantly reduced proliferation as compared to mock transfected group. By contrast, podoplanin significantly increased migration and invasion into collagen matrix. Furthermore, conditioned media from Phigh glioma cells strongly induced tube formation on matrigel. In conclusion, podoplanin increased migration of tumor cells and enhanced tube formation activity in endothelial cells independent from VEGF. Thus, podoplanin expression may be an important step in tumor progression. PMID:26339454

  9. 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

  10. 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

  11. 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.

  12. ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site.

    PubMed

    Abbruzzese, Genevieve; Becker, Sarah F; Kashef, Jubin; Alfandari, Dominique

    2016-07-15

    The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell-cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo. Copyright © 2015. Published by Elsevier Inc.

  13. Leading Process Branch Instability in Lis1+/− Nonradially Migrating Interneurons

    PubMed Central

    Gopal, Pallavi P.; Simonet, Jacqueline C.; Shapiro, William

    2010-01-01

    Mammalian forebrain development requires extensive migration, yet the mechanisms through which migrating neurons sense and respond to guidance cues are not well understood. Similar to the axon growth cone, the leading process and branches of neurons may guide migration, but the cytoskeletal events that regulate branching are unknown. We have previously shown that loss of microtubule-associated protein Lis1 reduces branching during migration compared with wild-type neurons. Using time-lapse imaging of Lis1+/− and Lis1+/+ cells migrating from medial ganglionic eminence explant cultures, we show that the branching defect is not due to a failure to initiate branches but a defect in the stabilization of new branches. The leading processes of Lis1+/− neurons have reduced expression of stabilized, acetylated microtubules compared with Lis1+/+ neurons. To determine whether Lis1 modulates branch stability through its role as the noncatalytic β regulatory subunit of platelet-activating factor (PAF) acetylhydrolase 1b, exogenous PAF was applied to wild-type cells. Excess PAF added to wild-type neurons phenocopies the branch instability observed in Lis1+/− neurons, and a PAF antagonist rescues leading process branching in Lis1+/− neurons. These data highlight a role for Lis1, acting through the PAF pathway, in leading process branching and microtubule stabilization. PMID:19861636

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

    PubMed Central

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

    2008-01-01

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

  15. 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

  16. ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site

    PubMed Central

    Kashef, Jubin; Alfandari, Dominique

    2015-01-01

    The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell–cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo. PMID:26206614

  17. Migration of polyethylene debris along well-fixed cemented implants.

    PubMed

    Massin, P; Viguier, E; Flautre, B; Hardouin, P; Astoin, E; Duponchel, B

    2004-02-15

    Implants, consisting of smooth Inox cylinders, were cemented into the lower femur and upper tibia of nine sheep to study the distal migration of polyethylene particles. Some implants had a titanium-bead porous coat at the proximal end. These were of three types: In the first type, the porous coat was covered with hydroxyapatite to obtain a bony seal; the second type was prepared for a polymethylmethacrylate seal; in the third type, the porous zone was surrounded by a 2-mm-thick space to allow the formation of a fibrous seal. Small polyethylene particles were injected into the knees once a week during the third and fourth months after implantation. The animals were euthanized 2 months later. Major longitudinal sections of the implants and the surrounding bone were examined under a polarized light microscope. Birefringent particles were counted at the cement-bone and cement-implant interfaces. Osteolysis was not observed. None of the seals significantly decreased the migration of particles around the cemented part of the implants. Particles were observed in cement fissures and vacuoles. They migrated at both interfaces and in the bone itself. They were visible in marrow spaces between bone trabeculae. Copyright 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 68B: 140-148, 2004

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

    NASA Astrophysics Data System (ADS)

    Houghton, Isabel A.; Dabiri, John O.

    2016-11-01

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

  19. Acoustic Reverse Time Migration of the Cascadia Subduction Zone Dataset

    NASA Astrophysics Data System (ADS)

    Jia, L.; Mallick, S.

    2017-12-01

    Reverse time migration (RTM) is a wave-equation based migration method, which provides more accurate images than ray-based migration methods, especially for the structures in deep areas, making it an effective tool for imaging the subduction plate boundary. In this work, we extend the work of Fortin (2015) and applied acoustic finite-element RTM on the Cascadia Subduction Zone (CSZ) dataset. The dataset was acquired by Cascadia Open-Access Seismic Transects (COAST) program, targeting the megathrust in the central Cascadia subduction zone (Figure 1). The data on a 2D seismic reflection line that crosses the Juan de Fuca/North American subduction boundary off Washington (Line 5) were pre-processed and worked through Kirchhoff prestack depth migration (PSDM). Figure 2 compares the depth image of Line 5 of the CSZ data using Kirchhoff PSDM (top) and RTM (bottom). In both images, the subducting plate is indicated with yellow arrows. Notice that the RTM image is much superior to the PSDM image by several aspects. First, the plate boundary appears to be much more continuous in the RTM image than the PSDM image. Second, the RTM image indicates the subducting plate is relatively smooth on the seaward (west) side between 0-50 km. Within the deformation front of the accretionary prism (50-80 km), the RTM image shows substantial roughness in the subducting plate. These features are not clear in the PSDM image. Third, the RTM image shows a lot of fine structures below the subducting plate which are almost absent in the PSDM image. Finally, the RTM image indicates that the plate is gently dipping within the undeformed sediment (0-50 km) and becomes steeply dipping beyond 50 km as it enters the deformation front of the accretionary prism. Although the same conclusion could be drawn from the discontinuous plate boundary imaged by PSDM, RTM results are far more convincing than the PSDM.

  20. Religiosity and Migration Aspirations among Mexican Youth.

    PubMed

    Hoffman, Steven; Marsiglia, Flavio Francisco; Ayers, Stephanie L

    2015-02-01

    International migration has become an important topic of discussion from a policy and humanitarian perspective. Part of the debate includes a renewed interest in understanding the factors that influence decisions about migration to the US among Mexican youth still residing in their country of origin. The purpose of this study was to advance knowledge specifically about internal and external religiosity and their influence on youths' migration aspirations. The data for this study were collected in 2007 from students enrolled in an alternative high school program located in the state of Guanajuato, Mexico. The findings indicated that as external religiosity increases, the desire to work or live in the USA decreases. Furthermore, as internal religiosity increases, the desire to work or live in the USA and plans to migrate increase. The results are interpreted and discussed in light of previous research on religious and cultural norm adherence.

  1. International nurse migration: lessons from the Philippines.

    PubMed

    Brush, Barbara L; Sochalski, Julie

    2007-02-01

    Developed countries facing nursing shortages have increasingly turned to aggressive foreign nurse recruitment, primarily from developing nations, to offset their lagging domestic nurse supplies and meet growing health care demands. Few donor nations are prepared to manage the loss of their nurse workforce to migration. The sole country with an explicit nurse export policy and the world's leading donor of nurse labor - the Philippines - is itself facing serious provider maldistribution and countrywide health disparities. Examining the historical roots of Philippines nurse migration provides lessons from which other nurse exporting countries may learn. The authors discuss factors that have predicated nurse migration and policies that have eased the way. Furthermore, the authors analyze how various stakeholders influence migratory patterns, the implications of migration for nurses and the public in their care, and the challenges that future social policy and political systems face in addressing global health issues engendered by unfettered recruitment of nurses and other health workers.

  2. Urbanism, Migration, and Tolerance: A Reassessment.

    ERIC Educational Resources Information Center

    Wilson, Thomas C.

    1991-01-01

    Urbanism's impact on the personality may be stronger than previously thought. Finds that urban residence has a strong positive effect on tolerance. Migration also promotes tolerance, regardless of the size of the destination community. (DM)

  3. Glial cell migration in the eye disc.

    PubMed

    Silies, Marion; Yuva, Yeliz; Engelen, Daniel; Aho, Annukka; Stork, Tobias; Klämbt, Christian

    2007-11-28

    Any complex nervous system is made out of two major cell types, neurons and glial cells. A hallmark of glial cells is their pronounced ability to migrate. En route to their final destinations, glial cells are generally guided by neuronal signals. Here we show that in the developing visual system of Drosophila glial cell migration is largely controlled by glial-glial interactions and occurs independently of axonal contact. Differentiation into wrapping glia is initiated close to the morphogenetic furrow. Using single cell labeling experiments we identified six distinct glial cell types in the eye disc. The migratory glial population is separated from the wrapping glial cells by the so-called carpet cells, extraordinary large glial cells, each covering a surface area of approximately 10,000 epithelial cells. Subsequent cell ablation experiments demonstrate that the carpet glia regulates glial migration in the eye disc epithelium and suggest a new model underlying glial migration and differentiation in the developing visual system.

  4. International Migration of Labor: Boon or Bane?

    ERIC Educational Resources Information Center

    Martin, Philip L.; Richards, Alan

    1980-01-01

    According to international trade theory, free labor flows across national borders should benefit workers, employers, and societies. But recent evidence indicates that such migration may not provide these desired benefits. (Author/SK)

  5. Internal migration for recent immigrants to Canada.

    PubMed

    Nogle, J M

    1994-01-01

    "This study examines the extent to which internal migration among recent immigrants to Canada is affected and constrained by characteristics related to admission. By examining measures of information and personal ties, it may be possible to establish that migration behavior is rational regardless of economic incentives." It is suggested that "internal migration in the first year after arrival is strongly affected by characteristics such as admission status, destination at arrival, reason for immigration, and area of origin. With increasing length of residence in Canada, though, the effect of these admission factors on internal migration behavior diminishes." This is a revised version of a paper originally presented at the 1992 Annual Meeting of the Population Association of America. excerpt

  6. Migration in Deltas: An Integrated Analysis

    NASA Astrophysics Data System (ADS)

    Nicholls, Robert J.; Hutton, Craig W.; Lazar, Attila; Adger, W. Neil; Allan, Andrew; Arto, Inaki; Vincent, Katharine; Rahman, Munsur; Salehin, Mashfiqus; Sugata, Hazra; Ghosh, Tuhin; Codjoe, Sam; Appeaning-Addo, Kwasi

    2017-04-01

    Deltas and low-lying coastal regions have long been perceived as vulnerable to global sea-level rise, with the potential for mass displacement of exposed populations. The assumption of mass displacement of populations in deltas requires a comprehensive reassessment in the light of present and future migration in deltas, including the potential role of adaptation to influence these decisions. At present, deltas are subject to multiple drivers of environmental change and often have high population densities as they are accessible and productive ecosystems. Climate change, catchment management, subsidence and land cover change drive environmental change across all deltas. Populations in deltas are also highly mobile, with significant urbanization trends and the growth of large cities and mega-cities within or adjacent to deltas across Asia and Africa. Such migration is driven primarily by economic opportunity, yet environmental change in general, and climate change in particular, are likely to play an increasing direct and indirect role in future migration trends. The policy challenges centre on the role of migration within regional adaptation strategies to climate change; the protection of vulnerable populations; and the future of urban settlements within deltas. This paper reviews current knowledge on migration and adaptation to environmental change to discern specific issues pertinent to delta regions. It develops a new integrated methodology to assess present and future migration in deltas using the Volta delta in Ghana, Mahanadi delta in India and Ganges-Brahmaputra-Meghna delta across India and Bangladesh. The integrated method focuses on: biophysical changes and spatial distribution of vulnerability; demographic changes and migration decision-making using multiple methods and data; macro-economic trends and scenarios in the deltas; and the policies and governance structures that constrain and enable adaptation. The analysis is facilitated by a range of

  7. Multicore Considerations for Legacy Flight Software Migration

    NASA Technical Reports Server (NTRS)

    Vines, Kenneth; Day, Len

    2013-01-01

    In this paper we will discuss potential benefits and pitfalls when considering a migration from an existing single core code base to a multicore processor implementation. The results of this study present options that should be considered before migrating fault managers, device handlers and tasks with time-constrained requirements to a multicore flight software environment. Possible future multicore test bed demonstrations are also discussed.

  8. Nocturnal bird migration in opaque clouds

    NASA Technical Reports Server (NTRS)

    Griffin, D. R.

    1972-01-01

    The use of a tracking radar to measure the flight paths of migrating birds on nights with opaque clouds is discussed. The effects of wind and lack of visual references are examined. The limitations of the radar observations are described, and samples of tracks obtained during radar observations are included. It is concluded that nonvisual mechanisms of orientation make it possible for birds to migrate in opaque clouds, but the exact nature of the sensory information cannot be determined by radar observations.

  9. Visualizing Human Migration Trhough Space and Time

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

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

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

    PubMed

    Corona Vazquez, R

    1991-01-01

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

  11. Migration, urban growth, and development: Pakistan's experience.

    PubMed

    Shah, N M; Karim, M S

    1982-11-01

    The authors "focus primarily on voluntary, peacetime migration [in Pakistan], both internal and international, and attempt to analyze some of its possible socioeconomic consequences." The importance of the role of migration in urban population growth is discussed, with attention to implications for social and economic development. The impact of large-scale emigration of workers to the Middle East is also assessed. The analysis is based on data from the 1951, 1961, 1972, and 1981 censuses as well as from secondary sources. excerpt

  12. Cell migration in microengineered tumor environments.

    PubMed

    Um, Eujin; Oh, Jung Min; Granick, Steve; Cho, Yoon-Kyoung

    2017-12-05

    Recent advances in microengineered cell migration platforms are discussed critically with a focus on how cell migration is influenced by engineered tumor microenvironments, the medical relevance being to understand how tumor microenvironments may promote or suppress the progression of cancer. We first introduce key findings in cancer cell migration under the influence of the physical environment, which is systematically controlled by microengineering technology, followed by multi-cues of physico-chemical factors, which represent the complexity of the tumor environment. Recognizing that cancer cells constantly communicate not only with each other but also with tumor-associated cells such as vascular, fibroblast, and immune cells, and also with non-cellular components, it follows that cell motility in tumor microenvironments, especially metastasis via the invasion of cancer cells into the extracellular matrix and other tissues, is closely related to the malignancy of cancer-related mortality. Medical relevance of forefront research realized in microfabricated devices, such as single cell sorting based on the analysis of cell migration behavior, may assist personalized theragnostics based on the cell migration phenotype. Furthermore, we urge development of theory and numerical understanding of single or collective cell migration in microengineered platforms to gain new insights in cancer metastasis and in therapeutic strategies.

  13. Labor migration and child mortality in Mozambique

    PubMed Central

    Yabiku, Scott T.; Agadjanian, Victor; Cau, Boaventura

    2013-01-01

    Male labor migration is widespread in many parts of the world, yet its consequences for child outcomes and especially childhood mortality remain unclear. Male labor migration could bring benefits, in the form of remittances, to the families that remain behind and thus help child survival. Alternatively, the absence of a male adult could imperil the household's well-being and its ability to care for its members, increasing child mortality risks. In this analysis, we use longitudinal survey data from Mozambique collected in 2006 and 2009 to examine the association between male labor migration and under-five mortality in families that remain behind. Using a simple migrant/non-migrant dichotomy, we find no difference in mortality rates across migrant and non-migrant men's children. When we separated successful from unsuccessful migration based on the wife's perception, however, stark contrasts emerge: children of successful migrants have the lowest mortality, followed by children of non-migrant men, followed by the children of unsuccessful migrants. Our results illustrate the need to account for the diversity of men's labor migration experience in examining the effects of migration on left-behind households. PMID:23121856

  14. Physicians' Migration: Perceptions of Pakistani Medical Students.

    PubMed

    Hossain, Nazli; Shah, Nusrat; Shah, Tahira; Lateef, Sidra Binte

    2016-08-01

    To study the perceptions of medical students about factors responsible for physicians'migration. Cross-sectional survey. Dow Medical College and Civil Hospital, Karachi, from April to May 2015. Aself-administered structured questionnaire was used including demographic details, attitudes about push and pull factors of migration, and reasons for migrating or not migrating abroad. Final year students and interns were included. Likert scale from 1 to 4 (1=strongly disagree to 4=strongly agree) was used to assess attitudes. Data was analyzed by SPSS version 16. Atotal of 240 medical students, mostly females (n=181, 75%) (60% final year and 40% interns), participated in the study. Majority wished to go abroad (n=127; 54%) with United States being the favourite destination (n=80; 66.1%) and internal medicine fields being the preferred choice for specialization (n=126; 54%). The major pull factors were better quality of postgraduate education abroad (n=110; 48.2%) and economic prospects (80; 35.2%); while the push factors were a weak healthcare system (n=219; 94.3%), inadequate salary structure (n=205; 88.3%), insecurity (n=219; 93.9%) and increasing religious intolerance in Pakistan (n=183; 78.5%). This survey highlights the continuing trend of physician migration from Pakistan owing to an interplay of various push and pull factors. Majority of our medical students wish to migrate, mainly due to low salaries, poor job structure, and insecurity. Urgent interventions are required to reverse this trend of medical brain-drain.

  15. Migration: a core public health ethics issue.

    PubMed

    Wild, V; Dawson, A

    2018-05-01

    In this article, we outline the link between migration, public health and ethics. Discussing relevant arguments about migration from the perspective of public health and public health ethics. Critical review of theories and frameworks, case-based analysis and systematic identification and discussion of challenges. Migration is a core issue of public health ethics and must take a case-based approach: seeking to identify the specific ethical dimensions and vulnerabilities in each particular context. Public health as a practice, built upon the core value of justice, requires the protection and promotion of migrants' well-being (even if this produces tension with immigration services). Ethical analysis should take all phases of migration into account: before, during and after transit. We argue that migration policies, at least as they relate to migrants' well-being, should be founded upon a shared humanity, respect for human rights and on the idea that effective public health cannot and should not be confined within the borders and to the citizens of any host country. We make the case for migration to be seen as a core issue of public health ethics. Copyright © 2018 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  16. Integrating meteorology into research on migration.

    PubMed

    Shamoun-Baranes, Judy; Bouten, Willem; van Loon, E Emiel

    2010-09-01

    Atmospheric dynamics strongly influence the migration of flying organisms. They affect, among others, the onset, duration and cost of migration, migratory routes, stop-over decisions, and flight speeds en-route. Animals move through a heterogeneous environment and have to react to atmospheric dynamics at different spatial and temporal scales. Integrating meteorology into research on migration is not only challenging but it is also important, especially when trying to understand the variability of the various aspects of migratory behavior observed in nature. In this article, we give an overview of some different modeling approaches and we show how these have been incorporated into migration research. We provide a more detailed description of the development and application of two dynamic, individual-based models, one for waders and one for soaring migrants, as examples of how and why to integrate meteorology into research on migration. We use these models to help understand underlying mechanisms of individual response to atmospheric conditions en-route and to explain emergent patterns. This type of models can be used to study the impact of variability in atmospheric dynamics on migration along a migratory trajectory, between seasons and between years. We conclude by providing some basic guidelines to help researchers towards finding the right modeling approach and the meteorological data needed to integrate meteorology into their own research. © The Author 2010. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved.

  17. Integrating Meteorology into Research on Migration

    PubMed Central

    Shamoun-Baranes, Judy; Bouten, Willem; van Loon, E. Emiel

    2010-01-01

    Atmospheric dynamics strongly influence the migration of flying organisms. They affect, among others, the onset, duration and cost of migration, migratory routes, stop-over decisions, and flight speeds en-route. Animals move through a heterogeneous environment and have to react to atmospheric dynamics at different spatial and temporal scales. Integrating meteorology into research on migration is not only challenging but it is also important, especially when trying to understand the variability of the various aspects of migratory behavior observed in nature. In this article, we give an overview of some different modeling approaches and we show how these have been incorporated into migration research. We provide a more detailed description of the development and application of two dynamic, individual-based models, one for waders and one for soaring migrants, as examples of how and why to integrate meteorology into research on migration. We use these models to help understand underlying mechanisms of individual response to atmospheric conditions en-route and to explain emergent patterns. This type of models can be used to study the impact of variability in atmospheric dynamics on migration along a migratory trajectory, between seasons and between years. We conclude by providing some basic guidelines to help researchers towards finding the right modeling approach and the meteorological data needed to integrate meteorology into their own research. PMID:20811515

  18. Changes in leucocyte migration after renal transplantation

    PubMed Central

    Smith, M. G. M.; Eddleston, A. L. W. F.; Dominguez, J. A.; Evans, D. B.; Bewick, M.; Williams, Roger

    1969-01-01

    The leucocyte migration test, an in-vitro measure of cellular immunity, has been used to follow the changes in cell-mediated hypersensitivity to kidney and histocompatibility antigens in three patients after renal transplantation. Inhibition of leucocyte migration, indicating strong sensitization to the antigens used, occurred in each patient, starting five to seven days after transplantation. Satisfactory renal function had not been established in any of the patients at this time. In one case inhibition of leucocyte migration persisted almost continuously until the 24th day and was associated with poor renal function proved histologically to be due to rejection. Treatment with increased dosage of prednisone was associated with a rapid reversion to normal of the migration index and improvement in renal function. Later, inhibition of migration occurred again, and shortly afterwards the graft ceased to function. In the other two cases the migration index became normal without alteration in immunosuppressive therapy and a satisfactory diuresis followed. It is suggested that this simple test should prove useful in the specific diagnosis of rejection and in control of immunosuppressive therapy. ImagesFig. 3Fig. 4 PMID:4899455

  19. Timescale bias in measuring river migration rate

    NASA Astrophysics Data System (ADS)

    Donovan, M.; Belmont, P.; Notebaert, B.

    2016-12-01

    River channel migration plays an important role in sediment routing, water quality, riverine ecology, and infrastructure risk assessment. Migration rates may change in time and space due to systematic changes in hydrology, sediment supply, vegetation, and/or human land and water management actions. The ability to make detailed measurements of lateral migration over a wide range of temporal and spatial scales has been enhanced from increased availability of historical landscape-scale aerial photography and high-resolution topography (HRT). Despite a surge in the use of historical and contemporary aerial photograph sequences in conjunction with evolving methods to analyze such data for channel change, we found no research considering the biases that may be introduced as a function of the temporal scales of measurement. Unsteady processes (e.g.; sedimentation, channel migration, width changes) exhibit extreme discontinuities over time and space, resulting in distortion when measurements are averaged over longer temporal scales, referred to as `Sadler effects' (Sadler, 1981; Gardner et al., 1987). Using 12 sets of aerial photographs for the Root River (Minnesota), we measure lateral migration over space (110 km) and time (1937-2013) assess whether bias arises from different measurement scales and whether rates shift systematically with increased discharge over time. Results indicate that measurement-scale biases indeed arise from the time elapsed between measurements. We parsed the study reach into three distinct reaches and examine if/how recent increases in river discharge translate into changes in migration rate.

  20. Thermal migration of alloying agents in aluminium

    NASA Astrophysics Data System (ADS)

    Cooil, S. P.; Mørtsell, E. A.; Mazzola, F.; Jorge, M.; Wenner, S.; Edmonds, M. T.; Thomsen, L.; Klemm, H. W.; Peschel, G.; Fuhrich, A.; Prieto, M.; Schmidt, Th; Miwa, J. A.; Holmestad, R.; Wells, J. W.

    2016-11-01

    The in situ thermal migration of alloying agents in an Al-Mg-Si-Li alloy is studied using surface sensitive photo-electron and electron diffraction/imaging techniques. Starting with the preparation of an almost oxide free surface (oxide thickness = 0.1 nm), the relative abundance of alloying agents (Mg, Li and Si) at the surface are recorded at various stages of thermal annealing, from room temperature to melting (which is observed at 550 ◦C). Prior to annealing, the surface abundances are below the detection limit ≪1%, in agreement with their bulk concentrations of 0.423% Si, 0.322% Mg and 0.101% Li (atomic %). At elevated temperatures, all three alloying agents appear at drastically increased concentrations (13.3% Si, 19.7% Mg and 45.3% Li), but decrease again with further elevation of the annealing temperature or after melting. The temperature at which the migration occurs is species dependent, with Li migration occurring at significantly higher temperatures than Si and Mg. The mechanism of migration also appears to be species dependent with Li migration occurring all over the surface but Mg migration being restricted to grain boundaries.

  1. The gravity model of labor migration behavior

    NASA Astrophysics Data System (ADS)

    Alexandr, Tarasyev; Alexandr, Tarasyev

    2017-07-01

    In this article, we present a dynamic inter-regional model, that is based on the gravity approach to migration and describes in continuous time the labor force dynamics between a number of conjugate regions. Our modification of the gravity migration model allows to explain the migration processes and to display the impact of migration on the regional economic development both for regions of origin and attraction. The application of our model allows to trace the dependency between salaries levels, total workforce, the number of vacancies and the number unemployed people in simulated regions. Due to the gravity component in our model the accuracy of prediction for migration flows is limited by the distance range between analyzed regions, so this model is tested on a number of conjugate neighbor regions. Future studies will be aimed at development of a multi-level dynamic model, which allows to construct a forecast for unemployment and vacancies trends on the first modeling level and to use these identified parameters on the second level for describing dynamic trajectories of migration flows.

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

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

    PubMed

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

    2017-05-26

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

  4. Increases in reactive oxygen species enhance vascular endothelial cell migration through a mechanism dependent on the transient receptor potential melastatin 4 ion channel.

    PubMed

    Sarmiento, Daniela; Montorfano, Ignacio; Cerda, Oscar; Cáceres, Mónica; Becerra, Alvaro; Cabello-Verrugio, Claudio; Elorza, Alvaro A; Riedel, Claudia; Tapia, Pablo; Velásquez, Luis A; Varela, Diego; Simon, Felipe

    2015-03-01

    A hallmark of severe inflammation is reactive oxygen species (ROS) overproduction induced by increased inflammatory mediators secretion. During systemic inflammation, inflammation mediators circulating in the bloodstream interact with endothelial cells (ECs) raising intracellular oxidative stress at the endothelial monolayer. Oxidative stress mediates several pathological functions, including an exacerbated EC migration. Because cell migration critically depends on calcium channel-mediated Ca(2+) influx, the molecular identification of the calcium channel involved in oxidative stress-modulated EC migration has been the subject of intense investigation. The transient receptor potential melastatin 4 (TRPM4) protein is a ROS-modulated non-selective cationic channel that performs several cell functions, including regulating intracellular Ca(2+) overload and Ca(2+) oscillation. This channel is expressed in multiple tissues, including ECs, and contributes to the migration of certain immune cells. However, whether the TRPM4 ion channel participates in oxidative stress-mediated EC migration is not known. Herein, we investigate whether oxidative stress initiates or enhances EC migration and study the role played by the ROS-modulated TRPM4 ion channel in oxidative stress-mediated EC migration. We demonstrate that oxidative stress enhances, but does not initiate, EC migration in a dose-dependent manner. Notably, we demonstrate that the TRPM4 ion channel is critical in promoting H2O2-enhanced EC migration. These results show that TRPM4 is a novel pharmacological target for the possible treatment of severe inflammation and other oxidative stress-mediated inflammatory diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Role of the extracellular matrix during neural crest cell migration.

    PubMed

    Perris, R; Perissinotto, D

    2000-07-01

    Once specified to become neural crest (NC), cells occupying the dorsal portion of the neural tube disrupt their cadherin-mediated cell-cell contacts, acquire motile properties, and embark upon an extensive migration through the embryo to reach their ultimate phenotype-specific sites. The understanding of how this movement is regulated is still rather fragmentary due to the complexity of the cellular and molecular interactions involved. An additional intricate aspect of the regulation of NC cell movement is that the timings, modes and patterns of NC cell migration are intimately associated with the concomitant phenotypic diversification that cells undergo during their migratory phase and the fact that these changes modulate the way that moving cells interact with their microenvironment. To date, two interplaying mechanisms appear central for the guidance of the migrating NC cells through the embryo: one involves secreted signalling molecules acting through their cognate protein kinase/phosphatase-type receptors and the other is contributed by the multivalent interactions of the cells with their surrounding extracellular matrix (ECM). The latter ones seem fundamental in light of the central morphogenetic role played by the intracellular signals transduced through the cytoskeleton upon integrin ligation, and the convergence of these signalling cascades with those triggered by cadherins, survival/growth factor receptors, gap junctional communications, and stretch-activated calcium channels. The elucidation of the importance of the ECM during NC cell movement is presently favoured by the augmenting knowledge about the macromolecular structure of the specific ECM assembled during NC development and the functional assaying of its individual constituents via molecular and genetic manipulations. Collectively, these data propose that NC cell migration may be governed by time- and space-dependent alterations in the expression of inhibitory ECM components; the relative ratio

  6. Determination of key diffusion and partition parameters and their use in migration modelling of benzophenone from low-density polyethylene (LDPE) into different foodstuffs.

    PubMed

    Maia, Joaquim; Rodríguez-Bernaldo de Quirós, Ana; Sendón, Raquel; Cruz, José Manuel; Seiler, Annika; Franz, Roland; Simoneau, Catherine; Castle, Laurence; Driffield, Malcolm; Mercea, Peter; Oldring, Peter; Tosa, Valer; Paseiro, Perfecto

    2016-01-01

    The mass transport process (migration) of a model substance, benzophenone (BZP), from LDPE into selected foodstuffs at three temperatures was studied. A mathematical model based on Fick's Second Law of Diffusion was used to simulate the migration process and a good correlation between experimental and predicted values was found. The acquired results contribute to a better understanding of this phenomenon and the parameters so-derived were incorporated into the migration module of the recently launched FACET tool (Flavourings, Additives and Food Contact Materials Exposure Tool). The migration tests were carried out at different time-temperature conditions, and BZP was extracted from LDPE and analysed by HPLC-DAD. With all data, the parameters for migration modelling (diffusion and partition coefficients) were calculated. Results showed that the diffusion coefficients (within both the polymer and the foodstuff) are greatly affected by the temperature and food's physical state, whereas the partition coefficient was affected significantly only by food characteristics, particularly fat content.

  7. Migration characteristics and early clinical results of a novel-finned press-fit acetabular cup.

    PubMed

    Kaipel, Martin; Prenner, Anton; Bachl, Sebastian; Farr, Sebastian; Sinz, Günter

    2014-04-01

    Ana Nova® is a novel-finned press-fit acetabular cup which showed superior biomechanical characteristics in an experimental set-up. Using Einzel Bild Röntgen Analyse (EBRA) measurements should offer the opportunity to predict implant survival at an early stage. The purpose of this study was to assess migration and clinical outcome 2 years after total hip replacement by a novel-finned press-fit acetabular cup. In this study, migration and clinical results of the implant were prospectively assessed in 67 patients. Clinical outcome was assessed using the Harris hip score (HHS). Migration analyses were performed using the computer assisted EBRA system. Data were analyzed for normal distribution using the Kolmogorov-Smirnov test. Group comparisons were performed using the analysis of variance (ANOVA) test. P-values less than 0.05 were considered statistically significant. At 2 years after surgery, none of the implants needed revision and HHS increased from 39.7 up to 92.2. In contrast to the beneficial clinical outcome, 17 of 44 patients showed increased total migration ( 1 mm/2a). Adverse migration data in this study might predict aseptic loosening and decreased survival of the implant. According to previous studies, it is possible that this effect occurred because of limited accuracy of the EBRA system. In our opinion, migration analyses may not be recommended as a screening tool in a 2 year follow-up.

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

    PubMed Central

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

    2014-01-01

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

  9. [Female international migration: the Colombian-Venezuelan case].

    PubMed

    Barrera, C

    1986-01-01

    Trends in female migration in Latin America are analyzed, using the example of migration from Colombia to Venezuela since the 1950s. Consideration is given to the causes of this migration, the economic role of female migrants, and the concept of migration as a survival strategy. Data are from a survey of migrant origin carried out in 1980 in major Colombian cities.

  10. The influence of migration speed on cooperation in spatial games

    NASA Astrophysics Data System (ADS)

    Li, Wen-Jing; Jiang, Luo-Luo; Gu, Changgui; Yang, Huijie

    2017-12-01

    Migration is a common phenomenon in human society which provides a person an opportunity to search for a new life from one area to another. In the framework of game theory, people may migrate to escape from a current adverse environment (evading defection). Since people may migrate at different speeds, it is interesting to figure out the influence of migration speed on the evolution of cooperative behavior. In an attempt to discover the influence, we propose here a model based on an adaptive migration mechanism. In this model, an individual migrates or updates his/her strategy asynchronously, which is tuned by migration frequency. Firstly, it is found that an appropriate migration speed may evoke an effective mechanism, which enables cooperators dominate even in highly adverse conditions. Secondly, we check how migration speed alters the paradigm of cooperation quantitatively in the conditions of different migration frequency. When migration frequency is high, cooperation is promoted only at a small migration speed. However, when migration frequency is low, cooperation is always promoted at any migration speed. In addition, we also investigated the influence of temptation to defect on cooperation for the case of different migration speeds and migration frequencies. Our results may provide a fresh perspective on the understanding of how human behavior affects cooperation.

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

    PubMed

    Bigsten, A

    1988-01-01

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

  12. Cell growth and migration under octenidine-antiseptic treatment.

    PubMed

    Jenull, S; Hojdar, K; Laggner, H; Velimirov, B; Zemann, N; Huettinger, M

    2015-06-01

    The toxicity of octenidine antiseptics in cultured cells contrasts their good tolerability in tissue. This phenomenon prompted us to examine which cell culture conditions allow survival and proliferation and to investigate a possible modulation of toxicity by the extracellular matrix proteoglycan chondroitin sulfate. We tested fibroblasts and MCF7 cells for growth using the MTT test, and assessed wound healing potency with a laceration assay. Expression levels of the genes involved in controlling wound healing were assessed with RT-PCR. A 24 hour exposure to the octenidine-based solution was found incompatible with cell growth. When octenidine solution (0.5-0.5mg/l) was coated on dishes, growth was profoundly reduced after 24 hours, however there was no cytotoxic effect at 0.012 mg/l. Interestingly, when dishes were first coated with chondroitin sulfate the cytotoxicity of octenidine-based solution was modulated. Cell migration was not inhibited by octenidine-based solution treatment (2 minutes; 15 mg/l). No significant changes in gene expression levels in response to the octenidine-based solution treatment were detected. In cell culture conditions application of the octenidine-based solution without toxicity can be observed, comparable to the minimal application required to give full bactericidal effect. Alteration of toxicity by interaction with chondroitin sulfate in cell culture suggests a similar function for extraceullar matrix in intact tissue.

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

    PubMed

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

    2017-09-01

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

  14. Interregional migration in socialist countries: the case of China.

    PubMed

    Wei, Y

    1997-03-01

    "This paper analyzes changing interregional migration in China and reveals that the recent eastward migration reverses patterns of migration under Mao. It finds that investment variables are more important than the conventional variables of income and job opportunities in determining China's recent interregional migration. It suggests that both state policy and the global force influence interregional migration, challenging the popular view that the socialist state is the only critical determinant. This paper also criticizes Mao's approach to interregional migration and discusses the impact of migration on development." excerpt

  15. Theories on migration processes of Cd in Jiaozhou Bay

    NASA Astrophysics Data System (ADS)

    Yang, Dongfang; Li, Haixia; Wang, Qi; Ding, Jun; Zhang, Longlei

    2018-03-01

    Understanding the migration progress is essential to pollution control, while developing theories for the migration progress is the scientific basis. This paper further developed five key theories on migration processes of Cd including homogeneous theory, environmental dynamic theory, horizontal loss theory, migration trend theory and vertical migration theory, respectively. The performance and practical values of these theories were demonstrated in the application of these on analyzing the migration process of Cd in Jiaozhou Bay. Results these theory helpful to better understand the migration progress of pollutants in marine bay.

  16. MIGRATION OF SMALL MOONS IN SATURN's RINGS

    SciTech Connect

    Bromley, Benjamin C.; Kenyon, Scott J., E-mail: bromley@physics.utah.edu, E-mail: skenyon@cfa.harvard.edu

    2013-02-20

    The motions of small moons through Saturn's rings provide excellent tests of radial migration models. In theory, torque exchange between these moons and ring particles leads to radial drift. We predict that moons with Hill radii r {sub H} {approx} 2-24 km should migrate through the A ring in 1000 yr. In this size range, moons orbiting in an empty gap or in a full ring eventually migrate at the same rate. Smaller moons or moonlets-such as the propellers-are trapped by diffusion of disk material into corotating orbits, creating inertial drag. Larger moons-such as Pan or Atlas-do not migrate becausemore » of their own inertia. Fast migration of 2-24 km moons should eliminate intermediate-size bodies from the A ring and may be responsible for the observed large-radius cutoff of r {sub H} {approx} 1-2 km in the size distribution of the A ring's propeller moonlets. Although the presence of Daphnis (r {sub H} Almost-Equal-To 5 km) inside the Keeler gap challenges this scenario, numerical simulations demonstrate that orbital resonances and stirring by distant, larger moons (e.g., Mimas) may be important factors. For Daphnis, stirring by distant moons seems the most promising mechanism to halt fast migration. Alternatively, Daphnis may be a recent addition to the ring that is settling into a low inclination orbit in {approx}10{sup 3} yr prior to a phase of rapid migration. We provide predictions of observational constraints required to discriminate among possible scenarios for Daphnis.« less

  17. Migration in Vulnerable Deltas: A Research Strategy

    NASA Astrophysics Data System (ADS)

    Hutton, C.; Nicholls, R. J.; Allan, A.

    2015-12-01

    C. Hutton1, & R. J. Nicholls1, , 1 University of Southampton, University Road, Southampton, Hampshire, United Kingdom, SO17 1BJ. cwh@geodata. soton.ac.ukAbstractGlobally, deltas contain 500 million people and with rising sea levels often linked to large number of forced migrants are expected in the coming century. However, migration is already a major process in deltas, such as the growth of major cities such as Dhaka and Kolkata. Climate and environmental change interacts with a range of catchment and delta level drivers, which encompass a nexus of sea-level rise, storms, freshwater and sediment supply from the catchment, land degradation, subsidence, agricultural loss and socio-economic stresses. DECCMA (Deltas, Vulnerability and Climate Change: Migration and Adaptation/CARRIA) is investigating migration in the Ganges-Brahmaputra-Meghna (GBM), Mahanadi and Volta Deltas, including the influence of climate change. The research will explore migration from a range of perspectives including governance and stakeholder analysis, demographic analysis, household surveys of sending and receiving areas, macro-economic analysis, and hazards and hotspot analysis both historically and into the future. Migration under climate change will depend on other adaptation in the deltas and this will be examined. Collectively, integrated analysis will be developed to examine migration, other adaptation and development pathways with a particular focus on the implications for the poorest. This will require the development of input scenarios, including expert-derived exogenous scenarios (e.g., climate change) and endogenous scenarios of the delta developed in a participatory manner. This applied research will facilitate decision support methods for the development of deltas under climate change, with a focus on migration and other adaptation strategies.

  18. TOWARD CHEMICAL CONSTRAINTS ON HOT JUPITER MIGRATION

    SciTech Connect

    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

  19. Migration in south Asia: an overview.

    PubMed

    Skeldon, R

    1983-01-01

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

  20. Father's Labour Migration and Children's School Discontinuation in Rural Mozambique.

    PubMed

    Yabiku, Scott T; Agadjanian, Victor

    2017-08-01

    We examine how the discontinuation of schooling among left-behind children is related to multiple dimensions of male labor migration: the accumulation of migration experience, the timing of these migration experiences in the child's life course, and the economic success of the migration. Our setting is rural southern Mozambique, an impoverished area with massive male labor out-migration. Results show that fathers' economically successful labor migration is more beneficial for children's schooling than unsuccessful migration or non-migration. There are large differences, however, by gender: compared to sons of non-migrants, sons of migrant fathers (regardless of migration success) have lower rates of school discontinuation, while daughters of migrant fathers have rates of school discontinuation no different than daughters of non-migrants. Furthermore, accumulated labor migration across the child's life course is beneficial for boys' schooling, but not girls'. Remittances sent in the past year reduce the rate of discontinuation for sons, but not daughters.

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

    PubMed

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

    2014-03-01

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

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

    PubMed Central

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

    2014-01-01

    Hurricane Katrina’s effect on the population of the City of New Orleans provides a model of how severe weather events, which are likely to increase in frequency and strength as the climate warms, might affect other large coastal cities. Our research focuses on changes in the migration system – defined as the system of ties between Orleans Parish and all other U.S. counties – between the pre-disaster (1999–2004) and recovery (2007–2009) periods. Using Internal Revenue Service county-to-county migration flow data, we find that in the recovery period Orleans Parish increased the number of migration ties with and received larger migration flows from nearby counties in the Gulf of Mexico coastal region, thereby spatially concentrating and intensifying the in-migration dimension of this predominantly urban system, while the out-migration dimension contracted and had smaller flows. We interpret these changes as the migration system relying on its strongest ties to nearby and less damaged counties to generate recovery in-migration. PMID:24729651

  3. Spatial-temporal migration laws of Cd in Jiaozhou Bay

    NASA Astrophysics Data System (ADS)

    Yang, Dongfang; Li, Haixia; Zhang, Xiaolong; Wang, Qi; Miao, Zhenqing

    2018-02-01

    Many marine bays have been polluted by various pollutants, and understanding the migration laws is essential to scientific research and pollution control. This paper analyzed the spatial and temporal migration laws of Cd in waters in Jiaozhou Bay during 1979—1983. Results showed that there were twenty spatial-temporal migration law for the migration processes of Cd. These laws were helpful for better understanding the migration of Cd in marine bay, providing basis for scientific research and pollution control.

  4. Electroabsorption optical modulator

    DOEpatents

    Skogen, Erik J.

    2017-11-21

    An electroabsorption modulator incorporates waveguiding regions along the length of the modulator that include quantum wells where at least two of the regions have quantum wells with different bandgaps. In one embodiment of the invention, the regions are arranged such that the quantum wells have bandgaps with decreasing bandgap energy along the length of the modulator from the modulator's input to its output. The bandgap energy of the quantum wells may be decreased in discrete steps or continuously. Advantageously, such an arrangement better distributes the optical absorption as well as the carrier density along the length of the modulator. Further advantageously, the modulator may handle increased optical power as compared with prior art modulators of similar dimensions, which allows for improved link gain when the optical modulator is used in an analog optical communication link.

  5. Roles of EphA2 in Development and Disease

    PubMed Central

    Park, Jeong Eun; Son, Alexander I.; Zhou, Renping

    2013-01-01

    The Eph family of receptor tyrosine kinases (RTKs) has been implicated in the regulation of many aspects of mammalian development. Recent analyses have revealed that the EphA2 receptor is a key modulator for a wide variety of cellular functions. This review focuses on the roles of EphA2 in both development and disease. PMID:24705208

  6. Orion Crew Module Adapter

    NASA Image and Video Library

    2015-11-12

    Offloading of the Orion Crew Module Adapter, CMA, at Plum Brook Station. The adapter will connect Orion’s crew module to a service module provided by ESA (European Space Agency). NASA is preparing for a series of tests that will check out the Orion European Service Module, a critical part of the spacecraft that will be launched on future missions to an asteroid and on toward Mars.

  7. Toward conservation of midcontinental shorebird migrations

    USGS Publications Warehouse

    Skagen, Susan K.; Knopf, Fritz L.

    1993-01-01

    Shorebirds represent a highly diverse group of species, many of which experience tremendous energy demands associated with long-distance migratory flights. Transcontinental migrants are dependant upon dynamic freshwater wetlands for stopover resources essential for replenishment of lipid reserves and completion of migration. Patterns of shorebird migration across midcontinental wetlands were detected from migration reports to American Birds and information provided by U.S. Fish and Wildlife Service national wildlife refuges. Patterns in species composition and abundance varied geographically, emphasizing the uniqueness of different regions to migrating shorebirds. Smaller species and neotropical migrants moved primarily across the Great Plains, whereas larger species and North American migrants predominated in assemblages in the intermountain west. Shorebirds were broadly dispersed in wetland habitats with dynamic water regimes. Whereas populations of shorebirds in coastal system appear to concentrate at sites of seasonally predictable and abundant food resources, we propose that transcontinental shorebirds disperse and use wetlands opportunistically. This migration system exemplifies the need for large-scale, coordinated regional management efforts that recognize the dynamic nature of ecosystem processes.

  8. The Malaysian state's response to migration.

    PubMed

    Pillai, P

    1999-04-01

    This paper aims to provide a profile of migration trends in Malaysia since 1970 and to analyze public policy on migration in the context of economic growth and the labor market. The discussion centers on the impact of the Asian financial crisis. There is long history of immigration to Malaysia. The development strategy of the 1970s and 1980s was to create more jobs and restructure employment to meet equity goals. Labor shortages on plantations and construction booms led to a more organized, sustained effort to import labor. Recession in the mid-1980s led to unemployment, but many Malaysians were unwilling to work on plantations, in construction, or in low paying jobs. Economic growth during 1987-96 was very high, and labor shortages spread to service and manufacturing sectors. Migration policy has shifted over the decades. Both the market and the government's promotion of export-based industrialization require access to low cost migrant labor. Public and official recognition of the large number of migrants was not made until 1995. The financial crisis in 1998 led to enforcement of a new migration policy on illegal migrants and greater outflow of migrants. The economic crisis has increased job and income inequities in the region; this encourages continued migration. It is argued that it would be best for Malaysia to maximize short-term gains while minimizing long-term economic, social, and political costs.

  9. Nurse migration: the effects on nursing education.

    PubMed

    Hancock, P K

    2008-09-01

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

  10. Time-dependent photon migration imaging

    NASA Astrophysics Data System (ADS)

    Sevick, Eva M.; Wang, NaiGuang; Chance, Britton

    1992-02-01

    Recently, the application of both time- and frequency-resolved fluorescence techniques for the determination of photon migration characteristics in strongly scattering media has been used to characterize the optical properties in strongly scattering media. Specifically, Chance and coworkers have utilized measurement of photon migration characteristics to determine tissue hemoglobin absorbance and ultimately oxygenation status in homogeneous tissues. In this study, we present simulation results and experimental measurements for both techniques to show the capacity of time-dependent photon migration characteristics to image optically obscure absorbers located in strongly scattering media. The applications of time-dependent photon imaging in the biomedical community include imaging of light absorbing hematomas, tumors, hypoxic tissue volumes, and other tissue abnormalities. Herein, we show that the time-resolved parameter of mean photon path length, , and the frequency- resolved parameter of phase-shift, (theta) , can be used similarly to obtain three dimensional information of absorber position from two-dimensional measurements. Finally, we show that unlike imaging techniques that monitor the intensity of light without regard to the migration characteristics, the resolution of time-dependent photon migration measurements is enhanced by tissue scattering, further potentiating their use for biomedical imaging.

  11. A Missing Element in Migration Theories.

    PubMed

    Massey, Douglas S

    2015-09-01

    From the mid-1950s through the mid1980s, migration between Mexico and the United States constituted a stable system whose contours were shaped by social and economic conditions well-theorized by prevailing models of migration. It evolved as a mostly circular movement of male workers going to a handful of U.S. states in response to changing conditions of labor supply and demand north and south of the border, relative wages prevailing in each nation, market failures and structural economic changes in Mexico, and the expansion of migrant networks following processes specified by neoclassical economics, segmented labor market theory, the new economics of labor migration, social capital theory, world systems theory, and theoretical models of state behavior. After 1986, however, the migration system was radically transformed, with the net rate of migration increasing sharply as movement shifted from a circular flow of male workers going a limited set of destinations to a nationwide population of settled families. This transformation stemmed from a dynamic process that occurred in the public arena to bring about an unprecedented militarization of the Mexico-U.S. border, and not because of shifts in social, economic, or political factors specified in prevailing theories. In this paper I draw on earlier work to describe that dynamic process and demonstrate its consequences, underscoring the need for greater theoretical attention to the self-interested actions of politicians, pundits, and bureaucrats who benefit from the social construction and political manufacture of immigration crises when none really exist.

  12. Tumor cell migration in complex microenvironments

    PubMed Central

    Polacheck, William J.; Zervantonakis, Ioannis K.; Kamm, Roger D.

    2012-01-01

    Tumor cell migration is essential for invasion and dissemination from primary solid tumors and for the establishment of lethal secondary metastases at distant organs. In vivo and in vitro models enabled identification of different factors in the tumor microenvironment that regulate tumor progression and metastasis. However, the mechanisms by which tumor cells integrate these chemical and mechanical signals from multiple sources to navigate the complex microenvironment remain poorly understood. In this review, we discuss the factors that influence tumor cell migration with a focus on the migra