Sample records for chasing migration genes

  1. Chasing Migration Genes: A Brain Expressed Sequence Tag Resource for Summer and Migratory Monarch Butterflies (Danaus plexippus)

    PubMed Central

    Zhu, Haisun; Casselman, Amy; Reppert, Steven M.

    2008-01-01

    North American monarch butterflies (Danaus plexippus) undergo a spectacular fall migration. In contrast to summer butterflies, migrants are juvenile hormone (JH) deficient, which leads to reproductive diapause and increased longevity. Migrants also utilize time-compensated sun compass orientation to help them navigate to their overwintering grounds. Here, we describe a brain expressed sequence tag (EST) resource to identify genes involved in migratory behaviors. A brain EST library was constructed from summer and migrating butterflies. Of 9,484 unique sequences, 6068 had positive hits with the non-redundant protein database; the EST database likely represents ∼52% of the gene-encoding potential of the monarch genome. The brain transcriptome was cataloged using Gene Ontology and compared to Drosophila. Monarch genes were well represented, including those implicated in behavior. Three genes involved in increased JH activity (allatotropin, juvenile hormone acid methyltransfersase, and takeout) were upregulated in summer butterflies, compared to migrants. The locomotion-relevant turtle gene was marginally upregulated in migrants, while the foraging and single-minded genes were not differentially regulated. Many of the genes important for the monarch circadian clock mechanism (involved in sun compass orientation) were in the EST resource, including the newly identified cryptochrome 2. The EST database also revealed a novel Na+/K+ ATPase allele predicted to be more resistant to the toxic effects of milkweed than that reported previously. Potential genetic markers were identified from 3,486 EST contigs and included 1599 double-hit single nucleotide polymorphisms (SNPs) and 98 microsatellite polymorphisms. These data provide a template of the brain transcriptome for the monarch butterfly. Our “snap-shot” analysis of the differential regulation of candidate genes between summer and migratory butterflies suggests that unbiased, comprehensive transcriptional profiling

  2. Pursuit tracks chase: exploring the role of eye movements in the detection of chasing

    PubMed Central

    Träuble, Birgit

    2015-01-01

    We explore the role of eye movements in a chase detection task. Unlike the previous studies, which focused on overall performance as indicated by response speed and chase detection accuracy, we decompose the search process into gaze events such as smooth eye movements and use a data-driven approach to separately describe these gaze events. We measured eye movements of four human subjects engaged in a chase detection task displayed on a computer screen. The subjects were asked to detect two chasing rings among twelve other randomly moving rings. Using principal component analysis and support vector machines, we looked at the template and classification images that describe various stages of the detection process. We showed that the subjects mostly search for pairs of rings that move one after another in the same direction with a distance of 3.5–3.8 degrees. To find such pairs, the subjects first looked for regions with a high ring density and then pursued the rings in this region. Most of these groups consisted of two rings. Three subjects preferred to pursue the pair as a single object, while the remaining subject pursued the group by alternating the gaze between the two individual rings. In the discussion, we argue that subjects do not compare the movement of the pursued pair to a singular preformed template that describes a chasing motion. Rather, subjects bring certain hypotheses about what motion may qualify as chase and then, through feedback, they learn to look for a motion pattern that maximizes their performance. PMID:26401454

  3. Gambling goals predict chasing behavior during slot machine play.

    PubMed

    Lister, Jamey J; Nower, Lia; Wohl, Michael J A

    2016-11-01

    The purpose of this study was to test the effect of gambling goals (i.e., gambling achievement-orientation) on chasing behavior (i.e., decision to chase, chasing spins) over and above known antecedents (e.g., problem gambling severity, winning money motivations, approach/avoidance motivation). Young adult gamblers (N=121) were provided $20 and invited to use those funds on a slot machine situated in an immersive virtual reality casino. Unbeknownst to participants, outcomes were manipulated such that a nominal amount of money was either won or lost (depending on experimental condition) after 30 spins. Before the 31st spin, participants were asked if they wished to continue play. If they agreed, all successive spin outcomes were a loss. This permitted an assessment of what factors influence a player's: (1) decision to chase and (2) the number of chasing spins played in the face of loss. Almost all participants (n=95, 78.5%) screened positive for problem gambling symptoms. The majority of gamblers decided to chase (n=67, 55.4%). In bivariate analyses, higher gambling goal and problem gambling severity scores (but not approach/avoidance nor 'loss/win' condition) were positively related to both forms of chasing. Gamblers 'motivated to win money' were more likely to decide to chase. In multivariate analyses, higher gambling goals best accounted for both forms of chasing independent of known antecedents. This study provides the first evidence that gambling goals can influence chasing. Implications for shaping responsible gambling approaches to be more consistent with motivations for play are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Tornado chasing: an introduction to risk tourism opportunities

    Treesearch

    Heather Cantillon; Robert S. Bristow

    2001-01-01

    Tours devoted to tornado storm chasing have become popular in recent years, especially with the emergence of many profit and non-profit storm chasing organizations. While most literature in risk recreation has been directed toward rock climbing or other high-risk outdoor recreation activities, tours devoted to storm chasing are quite unlike these traditional activities...

  5. Tornado Chasing.

    ERIC Educational Resources Information Center

    Faidley, Warren

    1991-01-01

    Presents the rationale and purposes behind the phenomenon known as storm chasing, as well as the contributions that tornado chasers have made to both scientific knowledge and public safety. Provides statistical information on tornado frequencies and locations and contact addresses for storm chasers. (JJK)

  6. Chasing as a model of psychogenic stress: characterization of physiological and behavioral responses.

    PubMed

    Lee, Ji-Hye; Kimm, Sunwhi; Han, Jung-Soo; Choi, June-Seek

    2018-03-25

    Being chased by a predator or a dominant conspecific can induce significant stress. However, only a limited number of laboratory studies have employed chasing by itself as a stressor. In this study, we developed a novel stress paradigm in which rats were chased by a fast-moving object in an inescapable maze. In Experiment 1, defensive behaviors and stress hormone changes induced by chasing stress were measured. During the chasing stress, the chasing-stress group (n = 9) froze and emitted 22-kHz ultrasonic vocalizations (USVs), but the no-chasing control group (n = 10) did not. Plasma corticosterone levels significantly increased following the chasing and were comparable to those of the restraint-stress group (n = 6). In Experiment 2, the long-lasting memory of the chasing event was tested after three weeks. The chasing-stress group (n = 15) showed higher levels of freezing and USV than the no-chasing group (n = 14) when they were presented with the tone associated with the object's chasing action. Subsequently, the rats were subjected to Pavlovian threat conditioning with a tone as a conditioned stimulus and footshock as an unconditioned stimulus. The chasing-stress group showed higher levels of freezing and USV during the conditioning session than the no-chasing group, indicating sensitized defensive reactions in a different threat situation. Taken together, the current results suggest that chasing stress can induce long-lasting memory and sensitization of defensive responses to a new aversive event as well as immediate, significant stress responses.

  7. An application of importance-performance analysis to recreational storm chasing

    Treesearch

    Jiawen Chen; Sonja Wilhelm Stanis; Carla Barbieri; Shuangyu Xu

    2012-01-01

    Since the release of the movie "Twister" in 1996, storm chasing has become an increasingly popular form of recreation. Storm chasing tour agencies have emerged to provide technical assistance and guidance to individuals wishing to participate in this activity. However, little is known about the participants' perceptions of their storm chasing tours....

  8. The illusion of handy wins: Problem gambling, chasing, and affective decision-making.

    PubMed

    Nigro, Giovanna; Ciccarelli, Maria; Cosenza, Marina

    2018-01-01

    Chasing losses is a behavioral marker and a diagnostic criterion for gambling disorder. It consists in continuing gambling to recoup previous losses. Although chasing has been recognized playing a central role in gambling disorder, research on this topic is relatively scarce, and it remains unclear whether chasing affects decision-making in behavioral tasks in which participants gain or loss some money. Even if several studies found that the more the gambling involvement, the poorer the decision-making, to date no research investigated the role of chasing in decision-making. The study aimed to first investigate the relation between chasing and decision-making in adult gamblers. One hundred and four VLT players were administered the South Oaks Gambling Screen (SOGS), a computerized task measuring chasing, and the Iowa Gambling Task (IGT). Correlation analysis showed that the higher the SOGS scores, the higher the propensity to chase, and the poorer the decision-making performance. Regression analysis revealed that chasing propensity and gambling severity predicted IGT performance. Mediation analysis indicated that the association between gambling severity and poor decision-making is mediated by chasing. Gambling severity was assessed by means of a self-report measure. The generalizability of findings is limited, since the study focused only on VLT players. This study provides the first evidence that chasing, along with gambling severity, affects decision-making, at least in behavioral tasks involving money. Since chasers and non-chasers could be two different sub-types of gamblers, treatment protocols should take into account the additive role of chasing in gambling disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. On the role of PDZ domain-encoding genes in Drosophila border cell migration.

    PubMed

    Aranjuez, George; Kudlaty, Elizabeth; Longworth, Michelle S; McDonald, Jocelyn A

    2012-11-01

    Cells often move as collective groups during normal embryonic development and wound healing, although the mechanisms governing this type of migration are poorly understood. The Drosophila melanogaster border cells migrate as a cluster during late oogenesis and serve as a powerful in vivo genetic model for collective cell migration. To discover new genes that participate in border cell migration, 64 out of 66 genes that encode PDZ domain-containing proteins were systematically targeted by in vivo RNAi knockdown. The PDZ domain is one of the largest families of protein-protein interaction domains found in eukaryotes. Proteins that contain PDZ domains participate in a variety of biological processes, including signal transduction and establishment of epithelial apical-basal polarity. Targeting PDZ proteins effectively assesses a larger number of genes via the protein complexes and pathways through which these proteins function. par-6, a known regulator of border cell migration, was a positive hit and thus validated the approach. Knockdown of 14 PDZ domain genes disrupted migration with multiple RNAi lines. The candidate genes have diverse predicted cellular functions and are anticipated to provide new insights into the mechanisms that control border cell movement. As a test of this concept, two genes that disrupted migration were characterized in more detail: big bang and the Dlg5 homolog CG6509. We present evidence that Big bang regulates JAK/STAT signaling, whereas Dlg5/CG6509 maintains cluster cohesion. Moreover, these results demonstrate that targeting a selected class of genes by RNAi can uncover novel regulators of collective cell migration.

  10. Alexithymia predicts loss chasing for people at risk for problem gambling.

    PubMed

    Bibby, Peter A; Ross, Katherine E

    2017-12-01

    Background and aims The aim of this research was to investigate the relationship between alexithymia and loss-chasing behavior in people at risk and not at risk for problem gambling. Methods An opportunity sample of 58 (50 males and 8 females) participants completed the Problem Gambling Severity Index and the Toronto Alexithymia Scale (TAS-20). They then completed the Cambridge Gambling Task from which a measure of loss-chasing behavior was derived. Results Alexithymia and problem gambling risk were significantly positively correlated. Subgroups of non-alexithymic and at or near caseness for alexithymia by low risk and at risk for problem gambling were identified. The results show a clear difference for loss-chasing behavior for the two alexithymia conditions, but there was no evidence that low and at-risk problem gamblers were more likely to loss chase. The emotion-processing components of the TAS-20 were shown to correlate with loss chasing. Discussion and conclusion These findings suggest that loss-chasing behavior may be particularly prevalent in a subgroup of problem gamblers those who are high in alexithymia.

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

    PubMed

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

    1996-10-01

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

  12. 75 FR 31510 - Fox Chase Bancorp, Inc., Hatboro, PA; Approval of Conversion

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-03

    ... DEPARTMENT OF THE TREASURY Office of Thrift Supervision [AC-43: OTS No. H-4707] Fox Chase Bancorp, Inc., Hatboro, PA; Approval of Conversion Application Notice is hereby given that on May 14, 2010, the Office of Thrift Supervision approved the application of Fox Chase MHC and Fox Chase Bank, Hatboro...

  13. Paper Chase and the Socratic Method of Teaching Law.

    ERIC Educational Resources Information Center

    Dillon, J. T.

    1980-01-01

    It is argued that the Socratic method of teaching law as depicted in the book, movie, and TV series "Paper Chase" is not really the Socratic method at all. The genuine Socratic method and the questioning technique used in "Paper Chase" are examined and their appropriateness and effectiveness as methods for teaching contract law…

  14. The CHASE laboratory search for chameleon dark energy

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

    Steffen, Jason H.; /Fermilab

    2010-11-01

    A scalar field is a favorite candidate for the particle responsible for dark energy. However, few theoretical means exist that can simultaneously explain the observed acceleration of the Universe and evade tests of gravity. The chameleon mechanism, whereby the properties of a particle depend upon the local environment, is one possible avenue. We present the results of the Chameleon Afterglow Search (CHASE) experiment, a laboratory probe for chameleon dark energy. CHASE marks a significant improvement other searches for chameleons both in terms of its sensitivity to the photon/chameleon coupling as well as its sensitivity to the classes of chameleon darkmore » energy models and standard power-law models. Since chameleon dark energy is virtually indistinguishable from a cosmological constant, CHASE tests dark energy models in a manner not accessible to astronomical surveys.« less

  15. Child and adolescent service experience (ChASE): measuring service quality and therapeutic process.

    PubMed

    Day, Crispin; Michelson, Daniel; Hassan, Imren

    2011-11-01

    OBJECTIVES. Dissatisfaction with services has been associated with poorer child mental health outcomes, early treatment termination as well as disagreements over the nature of mental health difficulties, reasons for referral and therapy goals. The development of straightforward, reliable, and accurate methods of eliciting service users' views is essential within child and adolescent mental health care. This paper describes the development of the child and adolescent service experience (ChASE), a tool to measure children and young people's service experience DESIGN. The study comprises a non-experimental, cross-sectional design. METHODS. Participants were 132 mental health service users aged 8-18 years. Participants and their main carer completed the ChASE, Parent Satisfaction Questionnaire (PSQ) (Stallard, 1996) and Strengths and Difficulties (SDQ) Impact Supplement. Clinicians completed the SDQ Impact Supplement and provided clinical activity data. A sub-sample of participants completed the ChASE on a second occasion, 6 weeks after the completion of the first questionnaire. RESULTS. Scrutiny of ChASE data indicated high levels of completion. Principal axis factoring identified three factors within the ChASE: Relationship, Privacy, and Session Activity. The ChASE has good internal consistency and test-retest reliability. Significant correlations were found between the ChASE and carer satisfaction, service use, and youth clinical outcomes. CONCLUSIONS. The ChASE is a short, psychometrically robust tool for routine measurement of children, and young people's experience of mental health services, which users can complete easily. The results underline the importance of alliance factors to children and young people and their association with clinical improvement as well as the potential for the ChASE to be used a measure of children's therapeutic progress and alliance. ©2011 The British Psychological Society.

  16. Olfactory gene expression in migrating adult sockeye salmon Oncorhynchus nerka.

    PubMed

    Bett, N N; Hinch, S G; Kaukinen, K H; Li, S; Miller, K M

    2018-04-16

    Expression of 12 olfactory genes was analysed in adult sockeye salmon Oncorhynchus nerka nearing spawning grounds and O. nerka that had strayed from their natal migration route. Variation was found in six of these genes, all of which were olfc olfactory receptors and had lower expression levels in salmon nearing spawning grounds. The results may reflect decreased sensitivity to natal water olfactory cues as these fish are no longer seeking the correct migratory route. The expression of olfactory genes during the olfactory-mediated spawning migration of Pacific salmon Oncorhynchus spp. is largely unexplored and these findings demonstrate a link between migratory behaviours and olfactory plasticity that provides a basis for future molecular research on salmon homing. © 2018 The Fisheries Society of the British Isles.

  17. Amyloid precursor protein regulates migration and metalloproteinase gene expression in prostate cancer cells

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

    Miyazaki, Toshiaki; Ikeda, Kazuhiro; Horie-Inoue, Kuniko

    Highlights: • APP knockdown reduced proliferation and migration of prostate cancer cells. • APP knockdown reduced expression of metalloproteinase and EMT-related genes. • APP overexpression promoted LNCaP cell migration. • APP overexpression increased expression of metalloproteinase and EMT-related genes. - Abstract: Amyloid precursor protein (APP) is a type I transmembrane protein, and one of its processed forms, β-amyloid, is considered to play a central role in the development of Alzheimer’s disease. We previously showed that APP is a primary androgen-responsive gene in prostate cancer and that its increased expression is correlated with poor prognosis for patients with prostate cancer. APPmore » has also been implicated in several human malignancies. Nevertheless, the mechanism underlying the pro-proliferative effects of APP on cancers is still not well-understood. In the present study, we explored a pathophysiological role for APP in prostate cancer cells using siRNA targeting APP (siAPP). The proliferation and migration of LNCaP and DU145 prostate cancer cells were significantly suppressed by siAPP. Differentially expressed genes in siAPP-treated cells compared to control siRNA-treated cells were identified by microarray analysis. Notably, several metalloproteinase genes, such as ADAM10 and ADAM17, and epithelial–mesenchymal transition (EMT)-related genes, such as VIM, and SNAI2, were downregulated in siAPP-treated cells as compared to control cells. The expression of these genes was upregulated in LNCaP cells stably expressing APP when compared with control cells. APP-overexpressing LNCaP cells exhibited enhanced migration in comparison to control cells. These results suggest that APP may contribute to the proliferation and migration of prostate cancer cells by modulating the expression of metalloproteinase and EMT-related genes.« less

  18. What are the underlying units of perceived animacy? Chasing detection is intrinsically object-based.

    PubMed

    van Buren, Benjamin; Gao, Tao; Scholl, Brian J

    2017-10-01

    One of the most foundational questions that can be asked about any visual process is the nature of the underlying 'units' over which it operates (e.g., features, objects, or spatial regions). Here we address this question-for the first time, to our knowledge-in the context of the perception of animacy. Even simple geometric shapes appear animate when they move in certain ways. Do such percepts arise whenever any visual feature moves appropriately, or do they require that the relevant features first be individuated as discrete objects? Observers viewed displays in which one disc (the "wolf") chased another (the "sheep") among several moving distractor discs. Critically, two pairs of discs were also connected by visible lines. In the Unconnected condition, both lines connected pairs of distractors; but in the Connected condition, one connected the wolf to a distractor, and the other connected the sheep to a different distractor. Observers in the Connected condition were much less likely to describe such displays using mental state terms. Furthermore, signal detection analyses were used to explore the objective ability to discriminate chasing displays from inanimate control displays in which the wolf moved toward the sheep's mirror-image. Chasing detection was severely impaired on Connected trials: observers could readily detect an object chasing another object, but not a line-end chasing another line-end, a line-end chasing an object, or an object chasing a line-end. We conclude that the underlying units of perceived animacy are discrete visual objects.

  19. Correlates of frequent gambling and gambling-related chasing behaviors in individuals with schizophrenia-spectrum disorders.

    PubMed

    Yakovenko, Igor; Fortgang, Rebecca; Prentice, Jennifer; Hoff, Rani A; Potenza, Marc N

    2018-05-23

    Background and aims Published research on the relationship between disordered gambling and schizophrenia is limited. However, existing data suggest that individuals with schizophrenia/schizoaffective disorder may have a high prevalence of co-occurring disordered gambling. As such, effective strategies for screening and assessing gambling-related problems in individuals with psychosis are needed. The goal of this study was to explore the correlates of increased gambling frequency and chasing behavior, a hallmark feature of gambling disorder, in a sample of individuals with schizophrenia and schizoaffective disorders. Methods Data from 336 participants who met DSM-IV criteria for schizophrenia or schizoaffective disorder were used to examine differences between non-gamblers, infrequent gamblers, frequent gamblers who do not report chasing, and frequent gamblers who report chasing on a variety of associated features and symptoms of schizophrenia and disordered gambling. Results and discussion The results of the study support the conclusion that chasing behavior in individuals with schizophrenia/schizoaffective disorder lies on a continuum of severity, with more frequent gamblers endorsing greater chasing. Chasing was also associated with indicators of lower functioning across co-occurring disorders, such as greater problems with alcohol and drugs, greater gambling involvement, and a family history of gambling problems. The findings from the study suggest the utility of screening for chasing behavior as a brief and efficient strategy for assessing risk of gambling problems in individuals with psychotic-spectrum disorders.

  20. Alterations in functional brain networks associated with loss-chasing in gambling disorder and cocaine-use disorder.

    PubMed

    Worhunsky, Patrick D; Potenza, Marc N; Rogers, Robert D

    2017-09-01

    Continued, persistent gambling to recover accumulating losses, or 'loss-chasing', is a behavioral pattern linked particularly closely to gambling disorder (GD) but may reflect impaired decision-making processes relevant to drug addictions like cocaine-use disorder (CUD). However, little is known regarding the neurocognitive mechanisms of this complex, maladaptive behavior, particularly in individuals with addictive disorders. Seventy participants (25 GD, 18 CUD, and 27 healthy comparison (HC)) completed a loss-chase task during fMRI. Engagement of functional brain networks in response to losing outcomes and during decision-making periods preceding choices to loss-chase or to quit chasing losses were investigated using independent component analysis (ICA). An exploratory factor analysis was performed to examine patterns of coordinated engagement across identified networks. In GD relative to HC and CUD participants, choices to quit chasing were associated with greater engagement of a medial frontal executive-processing network. By comparison, CUD participants exhibited altered engagement of a striato-amygdala motivational network in response to losing outcomes as compared to HC, and during decision-making as compared to GD. Several other networks were differentially engaged during loss-chase relative to quit-chasing choices, but did not differ across participant groups. Exploratory factor analysis identified a system of coordinated activity across prefrontal executive-control networks that was greater in GD and CUD relative to HC participants and was associated with increased chasing persistence across all participants. Results provide evidence of shared and distinct neurobiological mechanisms in substance and behavioral addictions, and lend insight into potential cognitive interventions targeting loss-chasing behavior in GD. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Following isotopes in pulse-chase enriched aspen seedlings

    NASA Astrophysics Data System (ADS)

    Norris, C. E.; Wasylishen, R. E.; Landhäusser, S.; Quideau, S. A.

    2011-12-01

    One method to quantitatively trace biogeochemical fluxes through ecosystems, such as organic matter decomposition, is to use plant material enriched with stable isotopes. However, as plant macromolecules are known to vary in their rate of formation and decomposition, both the enrichment levels and the location of enrichment within the plant material should be characterized prior to decomposition and tracing studies. Aspen (Populus tremuloides Michx.) is a common tree species with a diverse organic matter chemical structure found in the western Canadian boreal forest. This study used a multi pulse and multi chase enrichment of stable isotopes (15N and 13C) on aspen seedlings to determine the seedling enrichment, isotope movement among plant tissues and translocation of isotopes within plant macromolecules e.g., carbohydrates and lignin. As expected, all tissues experienced increased enrichment with multiple pulses. An initial enrichment with 13C was observed in the leaves followed by translocation to the stems and roots while the 15N moved upward from the roots to leaves. The macromolecular chemistry of the organic carbon was further characterized using 13C solid state nuclear magnetic resonance spectroscopy. After the initial two hour chase period enrichment of the O-alkyl type (carbohydrate) carbon within the leaves was identified, followed by redistribution to more complex carbon compounds after the one week chase period. Root and stem tissues did not show the same pattern. Rather, changes in 13C enrichment were observed in shifting ethyl and methyl alkyl (lipid) carbon peak intensities for the stem samples while roots did not preferentially allocate 13C to a specific macromolecule. These results confirm that stable isotope enrichment of plants was non-uniform across macromolecules and tissue types. Enrichment of aspen seedlings was therefore dependant on the pulse-chase sequence used.

  2. CHASE Survey of Technology Needs

    DTIC Science & Technology

    2017-03-01

    CHASE Survey of Technology Needs Shahed Enamul Quadir ECE Department University of Connecticut Storrs, CT, USA Daniel DiMase Honeywell, Inc...based on a survey conducted in late 2015. Counterfeits and Hardware Trojans have been identified as areas needing continued research and focus... survey of its advisory board and industry professionals to determine the technology needs in the area of IC counterfeits, hardware assurance

  3. Chinese Learning Journeys: Chasing the Dream

    ERIC Educational Resources Information Center

    Su, Feng, Ed.

    2011-01-01

    Eight students from mainland China chart their learning journeys across national and continental boundaries and socio-cultural contexts. The five women and three men structure their experiences of studying in China and the West around the turning points and life changing choices they made in chasing their dreams. They embody its emergent…

  4. New Wnt/β-catenin target genes promote experimental metastasis and migration of colorectal cancer cells through different signals.

    PubMed

    Qi, Jingjing; Yu, Yong; Akilli Öztürk, Özlem; Holland, Jane D; Besser, Daniel; Fritzmann, Johannes; Wulf-Goldenberg, Annika; Eckert, Klaus; Fichtner, Iduna; Birchmeier, Walter

    2016-10-01

    We have previously identified a 115-gene signature that characterises the metastatic potential of human primary colon cancers. The signature included the canonical Wnt target gene BAMBI, which promoted experimental metastasis in mice. Here, we identified three new direct Wnt target genes from the signature, and studied their functions in epithelial-mesenchymal transition (EMT), cell migration and experimental metastasis. We examined experimental liver metastases following injection of selected tumour cells into spleens of NOD/SCID mice. Molecular and cellular techniques were used to identify direct transcription target genes of Wnt/β-catenin signals. Microarray analyses and experiments that interfered with cell migration through inhibitors were performed to characterise downstream signalling systems. Three new genes from the colorectal cancer (CRC) metastasis signature, BOP1, CKS2 and NFIL3, were identified as direct transcription targets of β-catenin/TCF4. Overexpression and knocking down of these genes in CRC cells promoted and inhibited, respectively, experimental metastasis in mice, EMT and cell motility in culture. Cell migration was repressed by interfering with distinct signalling systems through inhibitors of PI3K, JNK, p38 mitogen-activated protein kinase and/or mTOR. Gene expression profiling identified a series of migration-promoting genes, which were induced by BOP1, CKS2 and NFIL3, and could be repressed by inhibitors that are specific to these pathways. We identified new direct Wnt/β-catenin target genes, BOP1, CKS2 and NFIL3, which induced EMT, cell migration and experimental metastasis of CRC cells. These genes crosstalk with different downstream signalling systems, and activate migration-promoting genes. These pathways and downstream genes may serve as therapeutic targets in the treatment of CRC metastasis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  5. Pattern production through a chiral chasing mechanism

    NASA Astrophysics Data System (ADS)

    Woolley, Thomas E.

    2017-09-01

    Recent experiments on zebrafish pigmentation suggests that their typical black and white striped skin pattern is made up of a number of interacting chromatophore families. Specifically, two of these cell families have been shown to interact through a nonlocal chasing mechanism, which has previously been modeled using integro-differential equations. We extend this framework to include the experimentally observed fact that the cells often exhibit chiral movement, in that the cells chase, and run away, at angles different to the line connecting their centers. This framework is simplified through the use of multiple small limits leading to a coupled set of partial differential equations which are amenable to Fourier analysis. This analysis results in the production of dispersion relations and necessary conditions for a patterning instability to occur. Beyond the theoretical development and the production of new pattern planiforms we are able to corroborate the experimental hypothesis that the global pigmentation patterns can be dependent on the chirality of the chromatophores.

  6. Balancing Cell Migration with Matrix Degradation Enhances Gene Delivery to Cells Cultured Three-Dimensionally Within Hydrogels

    PubMed Central

    Shepard, Jaclyn A.; Huang, Alyssa; Shikanova, Ariella; Shea, Lonnie D.

    2010-01-01

    In regenerative medicine, hydrogels are employed to fill defects and support the infiltration of cells that can ultimately regenerate tissue. Gene delivery within hydrogels targeting infiltrating cells has the potential to promote tissue formation, but the delivery efficiency of nonviral vectors within hydrogels is low hindering their applicability in tissue regeneration. To improve their functionality, we have conducted a mechanistic study to investigate the contribution of cell migration and matrix degradation on gene delivery. In this report, lipoplexes were entrapped within hydrogels based on poly(ethylene glycol) (PEG) crosslinked with peptides containing matrix metalloproteinase degradable sequences. The mesh size of these hydrogels is substantially less than the size of the entrapped lipoplexes, which can function to retain vectors. Cell migration and transfection were simultaneously measured within hydrogels with varying density of cell adhesion sites (Arg-Gly-Asp peptides) and solids content. Increasing RGD density increased expression levels up to 100-fold, while greater solids content sustained expression levels for 16 days. Increasing RGD density and decreasing solids content increased cell migration, which indicates expression levels increase with increased cell migration. Initially exposing cells to vector resulted in transient expression that declined after 2 days, verifying the requirement of migration to sustain expression. Transfected cells were predominantly located within the population of migrating cells for hydrogels that supported cell migration. Although the small mesh size retained at least 70% of the lipoplexes in the absence of cells after 32 days, the presence of cells decreased retention to 10% after 16 days. These results indicate that vectors retained within hydrogels contact migrating cells, and that persistent cell migration can maintain elevated expression levels. Thus matrix degradation and cell migration are fundamental design

  7. Patterning C. elegans: homeotic cluster genes, cell fates and cell migrations.

    PubMed

    Salser, S J; Kenyon, C

    1994-05-01

    Despite its simple body form, the nematode C. elegans expresses homeotic cluster genes similar to those of insects and vertebrates in the patterning of many cell types and tissues along the anteroposterior axis. In the ventral nerve cord, these genes program spatial patterns of cell death, fusion, division and neurotransmitter production; in migrating cells they regulate the direction and extent of movement. Nematode development permits an analysis at the cellular level of how homeotic cluster genes interact to specify cell fates, and how cell behavior can be regulated to assemble an organism.

  8. Aggregation increases prey survival time in group chase and escape

    NASA Astrophysics Data System (ADS)

    Yang, Sicong; Jiang, Shijie; Jiang, Li; Li, Geng; Han, Zhangang

    2014-08-01

    Recently developed chase-and-escape models have addressed a fascinating pursuit-and-evasion problem that may have both theoretical significance and potential applications. We introduce three aggregation strategies for the prey in a group chase model on a lattice. Simulation results show that aggregation dramatically increases the group survival time, even allowing immortal prey. The average survival time τ and the aggregation probability P have a power-law dependence of \\tau \\sim {{(1-P)}^{-1}} for P\\in [0.9,0.997]. With increasing numbers of predators, there is still a phase transition. When the number of predators is less than the critical point value, the prey group survival time increases significantly.

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

    PubMed Central

    2011-01-01

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

  10. Transmembrane protein MIG-13 links the Wnt signaling and Hox genes to the cell polarity in neuronal migration

    PubMed Central

    Wang, Xiangming; Zhou, Fanli; Lv, Sijing; Yi, Peishan; Zhu, Zhiwen; Yang, Yihong; Feng, Guoxin; Li, Wei; Ou, Guangshuo

    2013-01-01

    Directional cell migration is a fundamental process in neural development. In Caenorhabditis elegans, Q neuroblasts on the left (QL) and right (QR) sides of the animal generate cells that migrate in opposite directions along the anteroposterior body axis. The homeobox (Hox) gene lin-39 promotes the anterior migration of QR descendants (QR.x), whereas the canonical Wnt signaling pathway activates another Hox gene, mab-5, to ensure the QL descendants’ (QL.x) posterior migration. However, the regulatory targets of LIN-39 and MAB-5 remain elusive. Here, we showed that MIG-13, an evolutionarily conserved transmembrane protein, cell-autonomously regulates the asymmetric distribution of the actin cytoskeleton in the leading migratory edge. We identified mig-13 as a cellular target of LIN-39 and MAB-5. LIN-39 establishes QR.x anterior polarity by binding to the mig-13 promoter and promoting mig-13 expression, whereas MAB-5 inhibits QL.x anterior polarity by associating with the lin-39 promoter and downregulating lin-39 and mig-13 expression. Thus, MIG-13 links the Wnt signaling and Hox genes that guide migrations, to the actin cytoskeleton, which executes the motility response in neuronal migration. PMID:23784779

  11. Systemic administration of 8-OH-DPAT and eticlopride, but not SCH23390, alters loss-chasing behavior in the rat.

    PubMed

    Rogers, Robert D; Wong, Adeline; McKinnon, Chris; Winstanley, Catharine A

    2013-05-01

    Gambling to recover losses is a common gaming behavior. In a clinical context, however, this phenomenon mediates the relationship between diminished control over gambling and the adverse socioeconomic consequences of gambling problems. Modeling loss-chasing through analogous behaviors in rats could facilitate its pharmacological investigation as a potential therapeutic target. Here, rats were trained to make operant responses that produced both food rewards, and unpredictably, imminent time-out periods in which rewards would be unavailable. At these decision points, rats were offered choices between waiting for these time-out periods to elapse before resuming responding for rewards ('quit' responses), or selecting risky options with a 0.5 probability of avoiding the time-outs altogether and a 0.5 probability of time-out periods twice as long as signaled originally ('chase' responses). Chasing behavior, and the latencies to chase or quit, during sequences of unfavorable outcomes were tested following systemic administration of the 5-HT1A receptor agonist, 8-OH-DPAT, the D2 receptor antagonist, eticlopride, and the D1 receptor antagonist, SCH23390. 8-OH-DPAT and eticlopride significantly reduced the proportion of chase responses, and the mean number of consecutive chase responses, in a dose-dependent manner. 8-OH-DPAT also increased latencies to chase. Increasing doses of eticlopride first speeded, then slowed, latencies to quit while SCH23390 had no significant effects on any measure. Research is needed to identify the precise cognitive mechanisms mediating these kinds of risky choices in rats. However, our data provide the first experimental demonstration that 5-HT1A and D2, but not D1, receptor activity influence a behavioral analog of loss-chasing in rats.

  12. 78 FR 69663 - Jonathan and Jayne Chase Troy Mills Hydroelectric Inc.; Notice of Transfer of Exemption

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-20

    ... Jayne Chase Troy Mills Hydroelectric Inc.; Notice of Transfer of Exemption 1. By letter filed October 15, 2013, Jonathan Chase informed the Commission that the exemption from licensing for the Troy Hydroelectric Project, FERC No. 13381, originally issued December 2, 2011,\\1\\ has been transferred to Troy Mills...

  13. Identifying Loci Under Selection Against Gene Flow in Isolation-with-Migration Models

    PubMed Central

    Sousa, Vitor C.; Carneiro, Miguel; Ferrand, Nuno; Hey, Jody

    2013-01-01

    When divergence occurs in the presence of gene flow, there can arise an interesting dynamic in which selection against gene flow, at sites associated with population-specific adaptations or genetic incompatibilities, can cause net gene flow to vary across the genome. Loci linked to sites under selection may experience reduced gene flow and may experience genetic bottlenecks by the action of nearby selective sweeps. Data from histories such as these may be poorly fitted by conventional neutral model approaches to demographic inference, which treat all loci as equally subject to forces of genetic drift and gene flow. To allow for demographic inference in the face of such histories, as well as the identification of loci affected by selection, we developed an isolation-with-migration model that explicitly provides for variation among genomic regions in migration rates and/or rates of genetic drift. The method allows for loci to fall into any of multiple groups, each characterized by a different set of parameters, thus relaxing the assumption that all loci share the same demography. By grouping loci, the method can be applied to data with multiple loci and still have tractable dimensionality and statistical power. We studied the performance of the method using simulated data, and we applied the method to study the divergence of two subspecies of European rabbits (Oryctolagus cuniculus). PMID:23457232

  14. Gene expression profiling and environmental contaminant assessment of migrating Pacific salmon in the Fraser River watershed of British Columbia.

    PubMed

    Veldhoen, Nik; Ikonomou, Michael G; Dubetz, Cory; Macpherson, Nancy; Sampson, Tracy; Kelly, Barry C; Helbing, Caren C

    2010-05-05

    The health and physiological condition of anadromous salmon is of concern as their upriver migration requires navigation of human-impacted waterways and metabolism of stored energy reserves containing anthropogenic contaminants. Such factors may affect reproductive success of fish stocks. This study investigates chemical contaminant burdens and select gene expression profiles in Pacific Sockeye (Oncorhynchus nerka) and Chinook (Oncorhynchus tshawytscha) salmon which traverse the Fraser River watershed during their spawning migration. Chemical analyses of muscle tissue and eggs of salmon collected from the lower Fraser River (pre-migration) and from upstream spawning grounds (post-migration) during the 2007 migration revealed the presence of numerous chemical contaminants, including PCBs, dioxins/furans, pesticides, and heavy metals. However, muscle tissue residue concentrations were well below human health consumption guidelines and 2,3,7,8 TCDD toxic equivalents (SigmaTEQs) in salmon eggs, calculated using WHO toxic equivalency factors (WHO-TEFs) for fish health, did not exceed the 0.3pgg(-1) wet weight toxicological threshold level previously associated with 30% egg mortality in salmon populations. Quantitative real-time PCR probes were generated and used to assess differences in abundance of key mRNA transcripts encoding nine gene products associated with reproduction, stress, metal toxicity, and exposure to environmental contaminants. Gene expression profiles were characterized in liver and muscle tissue of pre- and post-migration Sockeye and Chinook salmon. The results of stock-matched animals indicate that dynamic changes in mRNA levels occur for a number of genes in both species during migration and suggest that Sockeye salmon exhibit a greater level of biological stress compared to the Chinook salmon population. Using a male-specific genotypic marker, we found that out of the 154 animals examined, one Sockeye was genotypically male but phenotypically female

  15. Systemic Administration of 8-OH-DPAT and Eticlopride, but not SCH23390, Alters Loss-Chasing Behavior in the Rat

    PubMed Central

    Rogers, Robert D; Wong, Adeline; McKinnon, Chris; Winstanley, Catharine A

    2013-01-01

    Gambling to recover losses is a common gaming behavior. In a clinical context, however, this phenomenon mediates the relationship between diminished control over gambling and the adverse socioeconomic consequences of gambling problems. Modeling loss-chasing through analogous behaviors in rats could facilitate its pharmacological investigation as a potential therapeutic target. Here, rats were trained to make operant responses that produced both food rewards, and unpredictably, imminent time-out periods in which rewards would be unavailable. At these decision points, rats were offered choices between waiting for these time-out periods to elapse before resuming responding for rewards (‘quit' responses), or selecting risky options with a 0.5 probability of avoiding the time-outs altogether and a 0.5 probability of time-out periods twice as long as signaled originally (‘chase' responses). Chasing behavior, and the latencies to chase or quit, during sequences of unfavorable outcomes were tested following systemic administration of the 5-HT1A receptor agonist, 8-OH-DPAT, the D2 receptor antagonist, eticlopride, and the D1 receptor antagonist, SCH23390. 8-OH-DPAT and eticlopride significantly reduced the proportion of chase responses, and the mean number of consecutive chase responses, in a dose-dependent manner. 8-OH-DPAT also increased latencies to chase. Increasing doses of eticlopride first speeded, then slowed, latencies to quit while SCH23390 had no significant effects on any measure. Research is needed to identify the precise cognitive mechanisms mediating these kinds of risky choices in rats. However, our data provide the first experimental demonstration that 5-HT1A and D2, but not D1, receptor activity influence a behavioral analog of loss-chasing in rats. PMID:23303072

  16. Stare and chase of space debris targets using real-time derived pointing data

    NASA Astrophysics Data System (ADS)

    Steindorfer, Michael A.; Kirchner, Georg; Koidl, Franz; Wang, Peiyuan; Antón, Alfredo; Fernández Sánchez, Jaime; Merz, Klaus

    2017-09-01

    We successfully demonstrate Stare & Chase: Space debris laser ranging to uncooperative targets has been achieved without a priori knowledge of any orbital information. An analog astronomy CCD with a standard objective, piggyback mounted on our 50 cm Graz SLR receive telescope, 'stares' into the sky in a fixed direction. The CCD records the stellar background within a field of view of approx. 7°. From the stellar X/Y positions on the sensor a plate solving algorithm determines the pointing data of the image center with an accuracy of approx. 15 arc seconds. If a sunlit target passes through this field of view, its equatorial coordinates are calculated, stored and a Consolidated Prediction Format (CPF) file is created in near real time. The derived CPF data is used to start laser ranging ('chase' the object) within the same pass to retrieve highly accurate distance information. A comparison of Stare & Chase CPFs with standard TLE predictions shows the possibilities and limits of this method.

  17. Cheetahs, Acinonyx jubatus, balance turn capacity with pace when chasing prey

    PubMed Central

    Wilson, John W.; Mills, Michael G. L.; Wilson, Rory P.; Peters, Gerrit; Mills, Margaret E. J.; Speakman, John R.; Durant, Sarah M.; Bennett, Nigel C.; Marks, Nikki J.; Scantlebury, Michael

    2013-01-01

    Predator–prey interactions are fundamental in the evolution and structure of ecological communities. Our understanding, however, of the strategies used in pursuit and evasion remains limited. Here, we report on the hunting dynamics of the world's fastest land animal, the cheetah, Acinonyx jubatus. Using miniaturized data loggers, we recorded fine-scale movement, speed and acceleration of free-ranging cheetahs to measure how hunting dynamics relate to chasing different sized prey. Cheetahs attained hunting speeds of up to 18.94 m s−1 and accelerated up to 7.5 m s−2 with greatest angular velocities achieved during the terminal phase of the hunt. The interplay between forward and lateral acceleration during chases showed that the total forces involved in speed changes and turning were approximately constant over time but varied with prey type. Thus, rather than a simple maximum speed chase, cheetahs first accelerate to decrease the distance to their prey, before reducing speed 5–8 s from the end of the hunt, so as to facilitate rapid turns to match prey escape tactics, varying the precise strategy according to prey species. Predator and prey thus pit a fine balance of speed against manoeuvring capability in a race for survival. PMID:24004493

  18. Cheetahs, Acinonyx jubatus, balance turn capacity with pace when chasing prey.

    PubMed

    Wilson, John W; Mills, Michael G L; Wilson, Rory P; Peters, Gerrit; Mills, Margaret E J; Speakman, John R; Durant, Sarah M; Bennett, Nigel C; Marks, Nikki J; Scantlebury, Michael

    2013-10-23

    Predator-prey interactions are fundamental in the evolution and structure of ecological communities. Our understanding, however, of the strategies used in pursuit and evasion remains limited. Here, we report on the hunting dynamics of the world's fastest land animal, the cheetah, Acinonyx jubatus. Using miniaturized data loggers, we recorded fine-scale movement, speed and acceleration of free-ranging cheetahs to measure how hunting dynamics relate to chasing different sized prey. Cheetahs attained hunting speeds of up to 18.94 m s(-1) and accelerated up to 7.5 m s(-2) with greatest angular velocities achieved during the terminal phase of the hunt. The interplay between forward and lateral acceleration during chases showed that the total forces involved in speed changes and turning were approximately constant over time but varied with prey type. Thus, rather than a simple maximum speed chase, cheetahs first accelerate to decrease the distance to their prey, before reducing speed 5-8 s from the end of the hunt, so as to facilitate rapid turns to match prey escape tactics, varying the precise strategy according to prey species. Predator and prey thus pit a fine balance of speed against manoeuvring capability in a race for survival.

  19. Chasing losses in online poker and casino games: characteristics and game play of Internet gamblers at risk of disordered gambling.

    PubMed

    Gainsbury, Sally M; Suhonen, Niko; Saastamoinen, Jani

    2014-07-30

    Disordered Internet gambling is a psychological disorder that represents an important public health issue due to the increase in highly available and conveniently accessible Internet gambling sites. Chasing losses is one of the few observable markers of at-risk and problem gambling that may be used to detect early signs of disordered Internet gambling. This study examined loss chasing behaviour in a sample of Internet casino and poker players and the socio-demographic variables, irrational beliefs, and gambling behaviours associated with chasing losses. An online survey was completed by 10,838 Internet gamblers (58% male) from 96 countries. The results showed that Internet casino players had a greater tendency to report chasing losses than poker players and gamblers who reported chasing losses were more likely to hold irrational beliefs about gambling and spend more time and money gambling than those who reported that they were unaffected by previous losses. Gamblers who played for excitement and to win money were more likely to report chasing losses. This study is one of the largest ever studies of Internet gamblers and the results are highly significant as they provide insight into the characteristics and behaviours of gamblers using this mode of access. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Validity of chase car data used in developing emissions cycles

    DOT National Transportation Integrated Search

    2000-09-01

    Air quality policies, driving cycles and profiles of average driving behavior have been constructed to characterize the driving behavior of the overall fleet in an effort to ensure vehicle compliance. Chase car data and speed-time profiles of in-use ...

  1. 6. CONSTRUCTION PROGRESS VIEW (EXTERIOR) OF TANK, CABLE CHASE, AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. CONSTRUCTION PROGRESS VIEW (EXTERIOR) OF TANK, CABLE CHASE, AND MOUNDED BUNKER. CONSTRUCTION WAS 99 PERCENT COMPLETE. CAMERA IS FACING WEST. INEL PHOTO NUMBER 65-5435, TAKEN OCTOBER 20, 1965. - Idaho National Engineering Laboratory, Advanced Reentry Vehicle Fusing System, Scoville, Butte County, ID

  2. A compilation of chase work characterizes this image, looking south, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    A compilation of chase work characterizes this image, looking south, in the niche which slightly separates E Building form R Building, on the north side - Department of Energy, Mound Facility, Electronics Laboratory Building (E Building), One Mound Road, Miamisburg, Montgomery County, OH

  3. Lower levels of interleukin-1β gene expression are associated with impaired Langerhans' cell migration in aged human skin.

    PubMed

    Pilkington, Suzanne M; Ogden, Stephanie; Eaton, Laura H; Dearman, Rebecca J; Kimber, Ian; Griffiths, Christopher E M

    2018-01-01

    Langerhans' cells (LC) play pivotal roles in skin immune responses, linking innate and adaptive immunity. In aged skin there are fewer LC and migration is impaired compared with young skin. These changes may contribute to declining skin immunity in the elderly, including increased skin infections and skin cancer. Interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) are mandatory signals for LC migration and previous studies suggest that IL-1β signalling may be dysregulated in aged skin. Therefore, we sought to explore the mechanisms underlying these phenomena. In skin biopsies of photoprotected young (< 30 years) and aged (> 70 years) human skin ex vivo, we assessed the impact of trauma, and mandatory LC mobilizing signals on LC migration and gene expression. Biopsy-related trauma induced LC migration from young epidermis, whereas in aged skin, migration was greatly reduced. Interleukin-1β treatment restored LC migration in aged epidermis whereas TNF-α was without effect. In uncultured, aged skin IL-1β gene expression was lower compared with young skin; following culture, IL-1βmRNA remained lower in aged skin under control and TNF-α conditions but was elevated after culture with IL-1β. Interleukin-1 receptor type 2 (IL1R2) gene expression was significantly increased in aged, but not young skin, after cytokine treatment. Keratinocyte-derived factors secreted from young and aged primary cells did not restore or inhibit LC migration from aged and young epidermis, respectively. These data suggest that in aged skin, IL-1β signalling is diminished due to altered expression of IL1B and decoy receptor gene IL1R2. © 2017 The Authors. Immunology Published by John Wiley & Sons Ltd., Immunology.

  4. Normal radial migration and lamination are maintained in dyslexia-susceptibility candidate gene homolog Kiaa0319 knockout mice.

    PubMed

    Martinez-Garay, Isabel; Guidi, Luiz G; Holloway, Zoe G; Bailey, Melissa A G; Lyngholm, Daniel; Schneider, Tomasz; Donnison, Timothy; Butt, Simon J B; Monaco, Anthony P; Molnár, Zoltán; Velayos-Baeza, Antonio

    2017-04-01

    Developmental dyslexia is a common disorder with a strong genetic component, but the underlying molecular mechanisms are still unknown. Several candidate dyslexia-susceptibility genes, including KIAA0319, DYX1C1, and DCDC2, have been identified in humans. RNA interference experiments targeting these genes in rat embryos have shown impairments in neuronal migration, suggesting that defects in radial cortical migration could be involved in the disease mechanism of dyslexia. Here we present the first characterisation of a Kiaa0319 knockout mouse line. Animals lacking KIAA0319 protein do not show anatomical abnormalities in any of the layered structures of the brain. Neurogenesis and radial migration of cortical projection neurons are not altered, and the intrinsic electrophysiological properties of Kiaa0319-deficient neurons do not differ from those of wild-type neurons. Kiaa0319 overexpression in cortex delays radial migration, but does not affect final neuronal position. However, knockout animals show subtle differences suggesting possible alterations in anxiety-related behaviour and in sensorimotor gating. Our results do not reveal a migration disorder in the mouse model, adding to the body of evidence available for Dcdc2 and Dyx1c1 that, unlike in the rat in utero knockdown models, the dyslexia-susceptibility candidate mouse homolog genes do not play an evident role in neuronal migration. However, KIAA0319 protein expression seems to be restricted to the brain, not only in early developmental stages but also in adult mice, indicative of a role of this protein in brain function. The constitutive and conditional knockout lines reported here will be useful tools for further functional analyses of Kiaa0319.

  5. A Vicious Cycle: A Cross-Sectional Study of Canine Tail-Chasing and Human Responses to It, Using a Free Video-Sharing Website

    PubMed Central

    Burn, Charlotte C.

    2011-01-01

    Tail-chasing is widely celebrated as normal canine behaviour in cultural references. However, all previous scientific studies of tail-chasing or ‘spinning’ have comprised small clinical populations of dogs with neurological, compulsive or other pathological conditions; most were ultimately euthanased. Thus, there is great disparity between scientific and public information on tail-chasing. I gathered data on the first large (n = 400), non-clinical tail-chasing population, made possible through a vast, free, online video repository, YouTube™. The demographics of this online population are described and discussed. Approximately one third of tail-chasing dogs showed clinical signs, including habitual (daily or ‘all the time’) or perseverative (difficult to distract) performance of the behaviour. These signs were observed across diverse breeds. Clinical signs appeared virtually unrecognised by the video owners and commenting viewers; laughter was recorded in 55% of videos, encouragement in 43%, and the commonest viewer descriptors were that the behaviour was ‘funny’ (46%) or ‘cute’ (42%). Habitual tail-chasers had 6.5+/−2.3 times the odds of being described as ‘Stupid’ than other dogs, and perseverative dogs were 6.8+/−2.1 times more frequently described as ‘Funny’ than distractible ones were. Compared with breed- and age-matched control videos, tail-chasing videos were significantly more often indoors and with a computer/television screen switched on. These findings highlight that tail-chasing is sometimes pathological, but can remain untreated, or even be encouraged, because of an assumption that it is ‘normal’ dog behaviour. The enormous viewing figures that YouTube™ attracts (mean+/−s.e. = 863+/−197 viewings per tail-chasing video) suggest that this perception will be further reinforced, without effective intervention. PMID:22096487

  6. β-Globin gene sequencing of hemoglobin Austin revises the historically reported electrophoretic migration pattern.

    PubMed

    Racsa, Lori D; Luu, Hung S; Park, Jason Y; Mitui, Midori; Timmons, Charles F

    2014-06-01

    Hemoglobin (Hb) Austin was defined in 1977, using amino acid sequencing of samples from 3 unrelated Mexican-Americans, as a substitution of serine for arginine at position 40 of the β-globin chain (Arg40Ser). Its electrophoretic migration on both cellulose acetate (pH 8.4) and citrate agar (pH 6.2) was reported between Hb F and Hb A, and this description persists in reference literature. OBJECTIVES.-To review the clinical features and redefine the diagnostic characteristics of Hb Austin. Eight samples from 6 unrelated individuals and 2 siblings, all with Hispanic surnames, were submitted for abnormal Hb identification between June 2010 and September 2011. High-performance liquid chromatography, isoelectric focusing (IEF), citrate agar electrophoresis, and bidirectional DNA sequencing of the entire β-globin gene were performed. DNA sequencing confirmed all 8 individuals to be heterozygous for Hb Austin (Arg40Ser). Retention time on high-performance liquid chromatography and migration on citrate agar electrophoresis were consistent with that identification. Migration on IEF, however, was not between Hb F and Hb A, as predicted from the report of cellulose acetate electrophoresis. By IEF, Hb Austin migrated anodal to ("faster than") Hb A. Hemoglobin Austin (Arg40Ser) appears on IEF as a "fast," anodally migrating, Hb variant, just as would be expected from its amino acid substitution. The cited historic report is, at best, not applicable to IEF and is probably erroneous. Our observation of 8 cases in 16 months suggests that this variant may be relatively common in some Hispanic populations, making its recognition important. Furthermore, gene sequencing is proving itself a powerful and reliable tool for definitive identification of Hb variants.

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

    PubMed

    Salser, S J; Kenyon, C

    1992-01-16

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

  8. The Effect of Laziness in Group Chase and Escape

    NASA Astrophysics Data System (ADS)

    Masuko, Makoto; Hiraoka, Takayuki; Ito, Nobuyasu; Shimada, Takashi

    2017-08-01

    The effect of laziness in the group chase and escape problem is studied using a simple model. Laziness is introduced as random walks in two ways: uniformly and in a "division of labor" way. It is shown that while the former is always ineffective, the latter can improve the efficiency of catching, through the formation of pincer attack configuration by diligent and lazy chasers.

  9. Scenes of Devastation: Chasing Hawaii's Deadly Ohia Fungus | Hawaii Public

    Science.gov Websites

    Scenes of Devastation: Chasing Hawaii's Deadly Ohia Fungus By Molly Solomon * Mar 25, 2016 TweetShareGoogle+Email Molly Solomon Rapid Ohia Death has devastated native forests on Hawaii Island, especially in Lower Puna subdivisions like Leilani Estates. Credit Molly Solomon One of Hawai'i's oldest and most

  10. The autism susceptibility gene met regulates zebrafish cerebellar development and facial motor neuron migration

    PubMed Central

    Elsen, Gina E.; Choi, Louis Y.; Prince, Victoria E.; Ho, Robert K.

    2009-01-01

    During development, Met signaling regulates a range of cellular processes including growth, differentiation, survival and migration. The Met gene encodes a tyrosine kinase receptor, which is activated by Hgf (hepatocyte growth factor) ligand. Altered regulation of human MET expression has been implicated in autism. In mouse, Met signaling has been shown to regulate cerebellum development. Since abnormalities in cerebellar structure have been reported in some autistic patients, we have used the zebrafish to address the role of Met signaling during cerebellar development and thus further our understanding of the molecular basis of autism. We find that zebrafish met is expressed in the cerebellar primordium, later localizing to the ventricular zone (VZ), with the hgf1 and hgf2 ligand genes expressed in surrounding tissues. Morpholino knockdown of either Met or its Hgf ligands leads to a significant reduction in the size of the cerebellum, primarily as a consequence of reduced proliferation. Met signaling knockdown disrupts specification of VZ-derived cell types, and also reduces granule cell numbers, due to an early effect on cerebellar proliferation and/or as an indirect consequence of loss of signals from VZ-derived cells later in development. These patterning defects preclude analysis of cerebellar neuronal migration, but we have found that Met signaling is necessary for migration of hindbrain facial motor neurons. In summary, we have described roles for Met signaling in coordinating growth and cell type specification within the developing cerebellum, and in migration of hindbrain neurons. These functions may underlie the correlation between altered MET regulation and Autism Spectrum Disorders. PMID:19732764

  11. A gene delivery system with a human artificial chromosome vector based on migration of mesenchymal stem cells towards human glioblastoma HTB14 cells.

    PubMed

    Kinoshita, Yusuke; Kamitani, Hideki; Mamun, Mahabub Hasan; Wasita, Brian; Kazuki, Yasuhiro; Hiratsuka, Masaharu; Oshimura, Mitsuo; Watanabe, Takashi

    2010-05-01

    Mesenchymal stem cells (MSCs) have been expected to become useful gene delivery vehicles against human malignant gliomas when coupled with an appropriate vector system, because they migrate towards the lesion. Human artificial chromosomes (HACs) are non-integrating vectors with several advantages for gene therapy, namely, no limitations on the size and number of genes that can be inserted. We investigated the migration of human immortalized MSCs bearing a HAC vector containing the herpes simplex virus thymidine kinase gene (HAC-tk-hiMSCs) towards malignant gliomas in vivo. Red fluorescence protein-labeled human glioblastoma HTB14 cells were implanted into a subcortical region in nude mice. Four days later, green fluorescence protein-labeled HAC-tk-hiMSCs were injected into a contralateral subcortical region (the HTB14/HAC-tk-hiMSC injection model). Tropism to the glioma mass and the route of migration were visualized by fluorescence microscopy and immunohistochemical staining. HAC-tk-hiMSCs began to migrate toward the HTB14 glioma area via the corpus callosum on day 4, and gathered around the HTB14 glioma mass on day 7. To test whether the delivered gene could effectively treat glioblastoma in vivo, HTB14/HAC-tk-hiMSC injected mice were treated with ganciclovir (GCV) or PBS. The HTB14 glioma mass was significantly reduced by GCV treatment in mice injected with HAC-tk-hiMSCs. It was confirmed that gene delivery by our HAC-hiMSC system was effective after migration of MSCs to the glioma mass in vivo. Therefore, MSCs containing HACs carrying an anticancer gene or genes may provide a new tool for the treatment of malignant gliomas and possibly of other tumor types.

  12. Candidate genes have sex-specific effects on timing of spring migration and moult speed in a long-distance migratory bird.

    PubMed

    Bazzi, Gaia; Podofillini, Stefano; Gatti, Emanuele; Gianfranceschi, Luca; Cecere, Jacopo G; Spina, Fernando; Saino, Nicola; Rubolini, Diego

    2017-10-01

    The timing of major life-history events, such as migration and moult, is set by endogenous circadian and circannual clocks, that have been well characterized at the molecular level. Conversely, the genetic sources of variation in phenology and in other behavioral traits have been sparsely addressed. It has been proposed that inter-individual variability in the timing of seasonal events may arise from allelic polymorphism at phenological candidate genes involved in the signaling cascade of the endogenous clocks. In this study of a long-distance migratory passerine bird, the willow warbler Phylloscopus trochilus , we investigated whether allelic variation at 5 polymorphic loci of 4 candidate genes ( Adcyap1 , Clock , Creb1 , and Npas2 ), predicted 2 major components of the annual schedule, namely timing of spring migration across the central Mediterranean sea and moult speed, the latter gauged from ptilochronological analyses of tail feathers moulted in the African winter quarters. We identified a novel Clock gene locus ( Clock region 3) showing polyQ polymorphism, which was however not significantly associated with any phenotypic trait. Npas2 allele size predicted male (but not female) spring migration date, with males bearing longer alleles migrating significantly earlier than those bearing shorter alleles. Creb1 allele size significantly predicted male (but not female) moult speed, longer alleles being associated with faster moult. All other genotype-phenotype associations were statistically non-significant. These findings provide new evidence for a role of candidate genes in modulating the phenology of different circannual activities in long-distance migratory birds, and for the occurrence of sex-specific candidate gene effects.

  13. Environmental Effects on Compulsive Tail Chasing in Dogs

    PubMed Central

    Tiira, Katriina; Hakosalo, Osmo; Kareinen, Lauri; Thomas, Anne; Hielm-Björkman, Anna; Escriou, Catherine; Arnold, Paul; Lohi, Hannes

    2012-01-01

    Obsessive Compulsive Disorder (OCD) is a neuropsychiatric disorder observed both in humans and animals. Examples of Canine Compulsive Disorder (CD) include excessive tail chasing (TC), light/shadow chasing and flank sucking. We performed a questionnaire survey to investigate the characteristics of compulsive (TC) and its possible associations with environmental correlates and personality in a pet population of 368 dogs from four dog breeds. We observed an early onset of TC at 3–6 months of age and a large variation in TC frequency in all breeds, with an overrepresentation of milder cases. Almost half of the TC dogs showed lowered responsiveness during bouts and displayed also other types of compulsions more often than the controls. Interestingly, dogs that received dietary supplements, especially vitamins and minerals, expressed less TC compared to dogs that did not receive any supplements. Neutered females had less TC, suggesting an influence of ovarian hormones on TC. Tail chasers were shyer and had separated earlier from their mothers than the controls. Finally, our genetic study did not find an association between TC and CDH2, a locus previously associated with the canine flank sucking compulsion. In conclusion, the early-onset and the variable nature of the repetitive behaviour, which is affected by environmental factors such as micronutrients, neutering and maternal care, share several similar components between canine and human compulsions and supports canine TC as a model for human OCD. PMID:22844513

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

    PubMed

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

    2008-11-08

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

  15. If and when: intrinsic differences and environmental stressors influence migration in brown trout (Salmo trutta).

    PubMed

    Peiman, Kathryn S; Birnie-Gauvin, Kim; Midwood, Jonathan D; Larsen, Martin H; Wilson, Alexander D M; Aarestrup, Kim; Cooke, Steven J

    2017-06-01

    Partial migration is a common phenomenon, yet the causes of individual differences in migratory propensity are not well understood. We examined factors that potentially influence timing of migration and migratory propensity in a wild population of juvenile brown trout (Salmo trutta) by combining experimental manipulations with passive integrated transponder telemetry. Individuals were subjected to one of six manipulations: three designed to mimic natural stressors (temperature increase, food deprivation, and chase by a simulated predator), an injection of exogenous cortisol designed to mimic an extreme physiological challenge, a sham injection, and a control group. By measuring length and mass of 923 individuals prior to manipulation and by monitoring tagged individuals as they left the stream months later, we assessed whether pre-existing differences influenced migratory tendency and timing of migration, and whether our manipulations affected growth, condition, and timing of migration. We found that pre-existing differences predicted migration, with smaller individuals and individuals in poor condition having a higher propensity to migrate. Exogenous cortisol manipulation had the largest negative effect on growth and condition, and resulted in an earlier migration date. Additionally, low-growth individuals within the temperature and food deprivation treatments migrated earlier. By demonstrating that both pre-existing differences in organism state and additional stressors can affect whether and when individuals migrate, we highlight the importance of understanding individual differences in partial migration. These effects may carry over to influence migration success and affect the evolutionary dynamics of sub-populations experiencing different levels of stress, which is particularly relevant in a changing world.

  16. Impact of transgene genome location on gene migration from herbicide-resistant wheat (Triticum aestivum L.) to jointed goatgrass (Aegilops cylindrica Host).

    PubMed

    Rehman, Maqsood; Hansen, Jennifer L; Mallory-Smith, Carol A; Zemetra, Robert S

    2017-08-01

    Wheat (Triticum aestivum) (ABD) and jointed goatgrass (Aegilops cylindrica) (CD) can cross and produce hybrids that can backcross to either parent. Such backcrosses can result in progeny with chromosomes and/or chromosome segments retained from wheat. Thus, a herbicide resistance gene could migrate from wheat to jointed goatgrass. In theory, the risk of gene migration from herbicide-resistant wheat to jointed goatgrass is more likely if the gene is located on the D genome and less likely if the gene is located on the A or B genome of wheat. BC 1 populations (jointed goatgrass as a recurrent parent) were analyzed for chromosome numbers and transgene transmission rates under sprayed and non-sprayed conditions. Transgene retention in the non-sprayed BC 1 generation for the A, B and D genomes was 84, 60 and 64% respectively. In the sprayed populations, the retention was 81, 59 and 74% respectively. The gene transmission rates were higher than the expected 50% or less under sprayed and non-sprayed conditions, possibly owing to meiotic chromosome restitution and/or chromosome non-disjunction. Such high transmission rates in the BC 1 generation negates the benefits of gene placement for reducing the potential of gene migration from wheat to jointed goatgrass. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  17. Gene flow from domesticated species to wild relatives: migration load in a model of multivariate selection.

    PubMed

    Tufto, Jarle

    2010-01-01

    Domesticated species frequently spread their genes into populations of wild relatives through interbreeding. The domestication process often involves artificial selection for economically desirable traits. This can lead to an indirect response in unknown correlated traits and a reduction in fitness of domesticated individuals in the wild. Previous models for the effect of gene flow from domesticated species to wild relatives have assumed that evolution occurs in one dimension. Here, I develop a quantitative genetic model for the balance between migration and multivariate stabilizing selection. Different forms of correlational selection consistent with a given observed ratio between average fitness of domesticated and wild individuals offsets the phenotypic means at migration-selection balance away from predictions based on simpler one-dimensional models. For almost all parameter values, correlational selection leads to a reduction in the migration load. For ridge selection, this reduction arises because the distance the immigrants deviates from the local optimum in effect is reduced. For realistic parameter values, however, the effect of correlational selection on the load is small, suggesting that simpler one-dimensional models may still be adequate in terms of predicting mean population fitness and viability.

  18. Chicken HOXA3 Gene: Its Expression Pattern and Role in Branchial Nerve Precursor Cell Migration

    PubMed Central

    Watari-Goshima, Natsuko; Chisaka, Osamu

    2011-01-01

    In vertebrates, the proximal and distal sensory ganglia of the branchial nerves are derived from neural crest cells (NCCs) and placodes, respectively. We previously reported that in Hoxa3 knockout mouse embryos, NCCs and placode-derived cells of the glossopharyngeal nerve were defective in their migration. In this report, to determine the cell-type origin for this Hoxa3 knockout phenotype, we blocked the expression of the gene with antisense morpholino oligonucleotides (MO) specifically in either NCCs/neural tube or placodal cells of chicken embryos. Our results showed that HOXA3 function was required for the migration of the epibranchial placode-derived cells and that HOXA3 regulated this cell migration in both NCCs/neural tube and placodal cells. We also report that the expression pattern of chicken HOXA3 was slightly different from that of mouse Hoxa3. PMID:21278919

  19. The CHilean Automatic Supernova sEarch (CHASE)

    NASA Astrophysics Data System (ADS)

    Pignata, G.; Maza, J.; Hamuy, M.; Antezana, R.; Gonzales, L.

    2009-05-01

    One of the most important challenges in modern cosmology will be to figure out the origin of the dark energy, to measure its equation of state and the time rate with which it changes (described by parameters w and w'). The measurement of these parameters will require high levels of accuracy in the Supernova (SN) Type Ia distances and various sources of systematic error such as reddening corrections and possible evolution in the SNcharacteristics which could couple with redshift and mimic the cosmological signal of interest. Fortunately, these concerns can be fully addressed through the comprehensive study of SNe in the local (z < 0.05) universe. Although Type II plateau SNe are not as luminous as SNe Ia, they afford two important, independent routes to cosmological distances using the Expanding Photosphere Method and the Standardized Candle Method. To assess the performance of these techniques a nearby sample of Type II SNe is necessary. With the purpose of addressing these issues the Millennium Center for Supernova Studies (MCSS) is teaming up with the Carnegie Supernova Project (CSP) to carry out an optical and near infrared (photometry, spectroscopy and polarimetry) follow up of nearby SNe. Unfortunately, the majority of the SNe observed by the MCSS and the CSP are discovered by searches carried out from the northern hemisphere. This entails a number of observational difficulties, in particular, it reduces the number of SNe for which the follow-up starts at very early epochs. The aim of the CHASE project is to remove this search bias by discovering young Southern SNe that will be extensively observed by the MCSS and the CSP. In the first nine-months of operation, CHASE has discovered two SNe: SN007oc (CBET 1114) and SN007pl (CBET 1130), thus demonstrating the feasibility of the survey.

  20. The Chase to Capture Gamma Ray Bursts

    NASA Technical Reports Server (NTRS)

    Gehrels, Neil

    2008-01-01

    Gamma-ray bursts are the most powerful explosions in the universe, thought to be the birth cries of black holes. It has taken 40 years of international cooperation and competition to begin to unravel the mystery of their origin. The most recent chapter in this field is being written by the SWIFT mission, a fast-response satellite with 3 power telescopes. An international team from countries all over the world participates in the chase to capture the fading light of bursts detected by SWIFT. This talk will discuss the challenges and excitement of building this space observatory. New results will be presented on our growing understanding of exploding stars and fiery mergers of orbiting stars.

  1. Biosynthesis, targeting, and processing of lysosomal proteins: pulse-chase labeling and immune precipitation.

    PubMed

    Pohl, Sandra; Hasilik, Andrej

    2015-01-01

    Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. A prerequisite in application of these techniques to lysosomal enzymes is the availability of an avid and specific antibody, because lysosomal proteins represent a very minor fraction of the cellular protein and must be purified without a significant loss many 1000-fold as conveniently as possible. Pulse-chase labeling and good knowledge on organelle-specific modifications of lysosomal proteins may enhance the information that can be obtained from such experiments. We describe procedures for pulse-chase labeling experiments that have proven to work with a commercially available antibody against a mouse and a human lysosomal protease and can be used as a reference in establishing the technique in any laboratory that has an access to a certified isotope facility and the knowledge to handle radioactivity safely. We discuss the crucial steps and refer to alternatives described in the literature. The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. A pulse-chase experiment demonstrates the conversion of the precursor into the mature form. In addition, results on deglycosylation of metabolically labeled cathepsin Z are shown and the alterations in the apparent size of the glycopeptides are explained. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. High-resolution gadolinium-enhanced 3D MRA of the infrapopliteal arteries. Lessons for improving bolus-chase peripheral MRA.

    PubMed

    Hood, Maureen N; Ho, Vincent B; Foo, Thomas K F; Marcos, Hani B; Hess, Sandra L; Choyke, Peter L

    2002-09-01

    Peripheral magnetic resonance angiography (MRA) is growing in use. However, methods of performing peripheral MRA vary widely and continue to be optimized, especially for improvement in illustration of infrapopliteal arteries. The main purpose of this project was to identify imaging factors that can improve arterial visualization in the lower leg using bolus chase peripheral MRA. Eighteen healthy adults were imaged on a 1.5T MR scanner. The calf was imaged using conventional three-station bolus chase three-dimensional (3D) MRA, two dimensional (2D) time-of-flight (TOF) MRA and single-station Gadolinium (Gd)-enhanced 3D MRA. Observer comparisons of vessel visualization, signal to noise ratios (SNR), contrast to noise ratios (CNR) and spatial resolution comparisons were performed. Arterial SNR and CNR were similar for all three techniques. However, arterial visualization was dramatically improved on dedicated, arterial-phase Gd-enhanced 3D MRA compared with the multi-station bolus chase MRA and 2D TOF MRA. This improvement was related to optimization of Gd-enhanced 3D MRA parameters (fast injection rate of 2 mL/sec, high spatial resolution imaging, the use of dedicated phased array coils, elliptical centric k-space sampling and accurate arterial phase timing for image acquisition). The visualization of the infrapopliteal arteries can be substantially improved in bolus chase peripheral MRA if voxel size, contrast delivery, and central k-space data acquisition for arterial enhancement are optimized. Improvements in peripheral MRA should be directed at these parameters.

  3. Pilots' Attention Distributions Between Chasing a Moving Target and a Stationary Target.

    PubMed

    Li, Wen-Chin; Yu, Chung-San; Braithwaite, Graham; Greaves, Matthew

    2016-12-01

    Attention plays a central role in cognitive processing; ineffective attention may induce accidents in flight operations. The objective of the current research was to examine military pilots' attention distributions between chasing a moving target and a stationary target. In the current research, 37 mission-ready F-16 pilots participated. Subjects' eye movements were collected by a portable head-mounted eye-tracker during tactical training in a flight simulator. The scenarios of chasing a moving target (air-to-air) and a stationary target (air-to-surface) consist of three operational phases: searching, aiming, and lock-on to the targets. The findings demonstrated significant differences in pilots' percentage of fixation during the searching phase between air-to-air (M = 37.57, SD = 5.72) and air-to-surface (M = 33.54, SD = 4.68). Fixation duration can indicate pilots' sustained attention to the trajectory of a dynamic target during air combat maneuvers. Aiming at the stationary target resulted in larger pupil size (M = 27,105, SD = 6565), reflecting higher cognitive loading than aiming at the dynamic target (M = 23,864, SD = 8762). Pilots' visual behavior is not only closely related to attention distribution, but also significantly associated with task characteristics. Military pilots demonstrated various visual scan patterns for searching and aiming at different types of targets based on the research settings of a flight simulator. The findings will facilitate system designers' understanding of military pilots' cognitive processes during tactical operations. They will assist human-centered interface design to improve pilots' situational awareness. The application of an eye-tracking device integrated with a flight simulator is a feasible and cost-effective intervention to improve the efficiency and safety of tactical training.Li W-C, Yu C-S, Braithwaite G, Greaves M. Pilots' attention distributions between chasing a moving target and a stationary target. Aerosp Med

  4. Cryptic sexual conflict in gift-giving insects: chasing the chase-away.

    PubMed

    Sakaluk, Scott K; Avery, Rachel L; Weddle, Carie B

    2006-01-01

    The chase-away model of sexual selection posits that elaborate male sexual displays arise because they exploit preexisting biases in females' sensory systems and induce females to mate in a suboptimal manner. An essential element of this hypothesis is that such manipulation should quickly lead to female resistance to male displays. Nuptial food gifts may be a frequent conduit by which males attempt to influence the mating behavior of females against females' own reproductive interests. In decorated crickets Gryllodes sigillatus, such inducements come in the form of a spermatophylax, a gelatinous mass forming part of the male's spermatophore and consumed by the female after mating. We conducted experiments in which spermatophylaxes obtained from male G. sigillatus were offered as novel food gifts to females of a non-gift-giving species (Acheta domesticus) having no evolutionary history of spermatophylax consumption. Female A. domesticus that were allowed to consume the spermatophylax took significantly longer to remate than when given no such opportunity. In contrast, when female G. sigillatus were prevented from consuming their partners' nuptial gifts, there was no difference in their propensity to remate relative to females permitted to consume a food gift after mating. These results suggest that the spermatophylax synthesized by male G. sigillatus contains substances designed to inhibit the sexual receptivity of their mates but that female G. sigillatus have evolved reduced responsiveness to these substances.

  5. The Psychophysics of Chasing: A Case Study in the Perception of Animacy

    ERIC Educational Resources Information Center

    Gao, Tao; Newman, George E.; Scholl, Brian J.

    2009-01-01

    Psychologists have long been captivated by the perception of animacy--the fact that even simple moving shapes may appear to engage in animate, intentional, and goal-directed movements. Here we report several new types of studies of a particularly salient form of perceived animacy: "chasing", in which one shape (the "wolf") pursues another shape…

  6. Hox paralog group 2 genes control the migration of mouse pontine neurons through slit-robo signaling.

    PubMed

    Geisen, Marc J; Di Meglio, Thomas; Pasqualetti, Massimo; Ducret, Sebastien; Brunet, Jean-François; Chedotal, Alain; Rijli, Filippo M

    2008-06-10

    The pontine neurons (PN) represent a major source of mossy fiber projections to the cerebellum. During mouse hindbrain development, PN migrate tangentially and sequentially along both the anteroposterior (AP) and dorsoventral (DV) axes. Unlike DV migration, which is controlled by the Netrin-1/Dcc attractive pathway, little is known about the molecular mechanisms guiding PN migration along the AP axis. Here, we show that Hoxa2 and Hoxb2 are required both intrinsically and extrinsically to maintain normal AP migration of subsets of PN, by preventing their premature ventral attraction towards the midline. Moreover, the migration defects observed in Hoxa2 and Hoxb2 mutant mice were phenocopied in compound Robo1;Robo2, Slit1;Slit2, and Robo2;Slit2 knockout animals, indicating that these guidance molecules act downstream of Hox genes to control PN migration. Indeed, using chromatin immunoprecipitation assays, we further demonstrated that Robo2 is a direct target of Hoxa2 in vivo and that maintenance of high Robo and Slit expression levels was impaired in Hoxa2 mutant mice. Lastly, the analysis of Phox2b-deficient mice indicated that the facial motor nucleus is a major Slit signaling source required to prevent premature ventral migration of PN. These findings provide novel insights into the molecular control of neuronal migration from transcription factor to regulation of guidance receptor and ligand expression. Specifically, they address the question of how exposure to multiple guidance cues along the AP and DV axes is regulated at the transcriptional level and in turn translated into stereotyped migratory responses during tangential migration of neurons in the developing mammalian brain.

  7. Hox Paralog Group 2 Genes Control the Migration of Mouse Pontine Neurons through Slit-Robo Signaling

    PubMed Central

    Pasqualetti, Massimo; Ducret, Sebastien; Brunet, Jean-François; Chedotal, Alain; Rijli, Filippo M

    2008-01-01

    The pontine neurons (PN) represent a major source of mossy fiber projections to the cerebellum. During mouse hindbrain development, PN migrate tangentially and sequentially along both the anteroposterior (AP) and dorsoventral (DV) axes. Unlike DV migration, which is controlled by the Netrin-1/Dcc attractive pathway, little is known about the molecular mechanisms guiding PN migration along the AP axis. Here, we show that Hoxa2 and Hoxb2 are required both intrinsically and extrinsically to maintain normal AP migration of subsets of PN, by preventing their premature ventral attraction towards the midline. Moreover, the migration defects observed in Hoxa2 and Hoxb2 mutant mice were phenocopied in compound Robo1;Robo2, Slit1;Slit2, and Robo2;Slit2 knockout animals, indicating that these guidance molecules act downstream of Hox genes to control PN migration. Indeed, using chromatin immunoprecipitation assays, we further demonstrated that Robo2 is a direct target of Hoxa2 in vivo and that maintenance of high Robo and Slit expression levels was impaired in Hoxa2 mutant mice. Lastly, the analysis of Phox2b-deficient mice indicated that the facial motor nucleus is a major Slit signaling source required to prevent premature ventral migration of PN. These findings provide novel insights into the molecular control of neuronal migration from transcription factor to regulation of guidance receptor and ligand expression. Specifically, they address the question of how exposure to multiple guidance cues along the AP and DV axes is regulated at the transcriptional level and in turn translated into stereotyped migratory responses during tangential migration of neurons in the developing mammalian brain. PMID:18547144

  8. F-18 chase craft with NASA test pilots Schneider and Fulton

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Ed Schneider, (left), is the project pilot for the F-18 High Angle of Attack program at NASA's Dryden Flight Research Center, Edwards, California. He has been a NASA research pilot at Dryden since 1983. In addition to his assignment with the F-18 High Angle of Attack program, Schneider is a project pilot for the F-15B aeronautical research aircraft, the NASA NB-52B launch aircraft, and the SR-71 'Blackbird' aircraft. He is a Fellow and was the 1994 President of the Society of Experimental Test Pilots. In 1996 he was awarded the NASA Exceptional Service Medal. Schneider is seen here with Fitzhugh L. Fulton Jr., (right), who was a civilian research pilot at Dryden. from August 1, 1966, until July 3, 1986, following 23 years of service as a pilot in the U.S. Air Force. Fulton was the project pilot on all early tests of the 747 Shuttle Carrier Aircraft (SCA) used to air launch the Space Shuttle prototype Enterprise in the Approach and Landing Tests (ALT) at Dryden in l977. For his work in the ALT program, Fulton received NASA's Exceptional Service Medal. He also received the Exceptional Service Medal again in 1983 for flying the 747 SCA during the European tour of the Space Shuttle Enterprise. During his career at Dryden, Fulton was project pilot on NASA's NB-52B launch aircraft used to air launch a variety of piloted and unpiloted research aircraft, including the X-15s and lifting bodies. He flew the XB-70 prototype supersonic bomber on both NASA-USAF tests and NASA research flights during the late 1960s, attaining speeds exceeding Mach 3. He was also a project pilot on the YF-12A and YF-12C research program from April 14, 1969, until September 25, 1978. The F/A-18 Hornet seen behind them is used primarily as a safety chase and support aircraft at NASA's Dryden Flight Research Center, Edwards, Calif. As support aircraft, the F-18's are used for safety chase, pilot proficiency and aerial photography. As a safety chase aircraft, F-18's, flown by research pilots

  9. Engaging Experiential Service Learning through a Co-Curricular Club: The Chase Charlie Races

    ERIC Educational Resources Information Center

    Judge, Lawrence W.; Pierce, David; Petersen, Jeffrey; Bellar, David; Wanless, Elizabeth; Gilreath, Erin; Simon, Laura

    2011-01-01

    The efficacy of the "Chase Charlie Races" (an experiential learning activity) was demonstrated via program assessment. This was achieved via post-event evaluations of race participants and student club members, and with fitness assessments of 76 elementary students who participated in an eight-week training program. Paired sample t-tests revealed…

  10. The effects of old and recent migration waves in the distribution of HBB*S globin gene haplotypes

    PubMed Central

    Lindenau, Juliana D.; Wagner, Sandrine C.; de Castro, Simone M.; Hutz, Mara H.

    2016-01-01

    Abstract Sickle cell hemoglobin is the result of a mutation at the sixth amino acid position of the beta (β) globin chain. The HBB*S gene is in linkage disequilibrium with five main haplotypes in the β-globin-like gene cluster named according to their ethnic and geographic origins: Bantu (CAR), Benin (BEN), Senegal (SEN), Cameroon (CAM) and Arabian-Indian (ARAB). These haplotypes demonstrated that the sickle cell mutation arose independently at least five times in human history. The distribution of βS haplotypes among Brazilian populations showed a predominance of the CAR haplotype. American populations were clustered in two groups defined by CAR or BEN haplotype frequencies. This scenario is compatible with historical records about the slave trade in the Americas. When all world populations where the sickle cell gene occurs were analyzed, three clusters were disclosed based on CAR, BEN or ARAB haplotype predominance. These patterns may change in the next decades due to recent migrations waves. Since these haplotypes show different clinical characteristics, these recent migrations events raise the necessity to develop optimized public health programs for sickle cell disease screening and management. PMID:27706371

  11. The Pseudomonas aeruginosa quorum sensing signal molecule N-(3-oxododecanoyl) homoserine lactone enhances keratinocyte migration and induces Mmp13 gene expression in vitro

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

    Paes, Camila, E-mail: camilaquinetti@gmail.com; Nakagami, Gojiro, E-mail: gojiron-tky@umin.ac.jp; Minematsu, Takeo, E-mail: tminematsu-tky@umin.ac.jp

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer An evidence of the positive effect of AHL on epithelialization process is provided. Black-Right-Pointing-Pointer AHL enhances keratinocyte's ability to migrate in an in vitro scratch wound model. Black-Right-Pointing-Pointer AHL induces the expression of Mmp13. Black-Right-Pointing-Pointer Topical application of AHL represents a possible strategy to treat chronic wounds. -- Abstract: Re-epithelialization is an essential step of wound healing involving three overlapping keratinocyte functions: migration, proliferation and differentiation. While quorum sensing (QS) is a cell density-dependent signaling system that enables bacteria to regulate the expression of certain genes, the QS molecule N-(3-oxododecanoyl) homoserine lactone (AHL) exerts effects also on mammalianmore » cells in a process called inter-kingdom signaling. Recent studies have shown that AHL improves epithelialization in in vivo wound healing models but detailed understanding of the molecular and cellular mechanisms are needed. The present study focused on the AHL as a candidate reagent to improve wound healing through direct modulation of keratinocyte's activity in the re-epithelialization process. Results indicated that AHL enhances the keratinocyte's ability to migrate in an in vitro scratch wound healing model probably due to the high Mmp13 gene expression analysis after AHL treatment that was revealed by real-time RT-PCR. Inhibition of activator protein 1 (AP-1) signaling pathway completely prevented the migration of keratinocytes, and also resulted in a diminished Mmp13 gene expression, suggesting that AP-1 might be essential in the AHL-induced migration. Taken together, these results imply that AHL is a promising candidate molecule to improve re-epithelialization through the induction of migration of keratinocytes. Further investigation is needed to clarify the mechanism of action and molecular pathway of AHL on the keratinocyte migration process.« less

  12. Toxic leucoencephalopathy after 'chasing the dragon'.

    PubMed

    Singh, Rajinder; Saini, Monica

    2015-06-01

    Toxic leucoencephalopathy (TLE) is a rare neurological complication of heroin abuse. 'Chasing the dragon' is an inhalational mode of heroin abuse that originated in Southeast Asia. Intriguingly, no cases of TLE have been reported from this region, although the inhalational mode of heroin abuse is common. We herein report the case of a middle-aged man with a history of polysubstance abuse who presented with progressive neurological symptoms and progressed to an uncommunicative state. While the initial impression was that of iatrogenic parkinsonism, diffuse leucoencephalopathy with sparing of the cerebellum was noted on magnetic resonance imaging. In view of his history of inhalational heroin abuse close to the onset of the neurological symptoms, a diagnosis of TLE was made. No clinical improvement was noted with administration of a dopaminergic agent. This is the first known case of delayed TLE following heroin inhalation from Southeast Asia with the unusual feature of cerebellar sparing.

  13. Significance chasing in research practice: causes, consequences and possible solutions.

    PubMed

    Ware, Jennifer J; Munafò, Marcus R

    2015-01-01

    The low reproducibility of findings within the scientific literature is a growing concern. This may be due to many findings being false positives which, in turn, can misdirect research effort and waste money. We review factors that may contribute to poor study reproducibility and an excess of 'significant' findings within the published literature. Specifically, we consider the influence of current incentive structures and the impact of these on research practices. The prevalence of false positives within the literature may be attributable to a number of questionable research practices, ranging from the relatively innocent and minor (e.g. unplanned post-hoc tests) to the calculated and serious (e.g. fabrication of data). These practices may be driven by current incentive structures (e.g. pressure to publish), alongside the preferential emphasis placed by journals on novelty over veracity. There are a number of potential solutions to poor reproducibility, such as new publishing formats that emphasize the research question and study design, rather than the results obtained. This has the potential to minimize significance chasing and non-publication of null findings. Significance chasing, questionable research practices and poor study reproducibility are the unfortunate consequence of a 'publish or perish' culture and a preference among journals for novel findings. It is likely that top-down change implemented by those with the ability to modify current incentive structure (e.g. funders and journals) will be required to address problems of poor reproducibility. © 2014 Society for the Study of Addiction.

  14. Significance chasing in research practice: Causes, consequences, and possible solutions

    PubMed Central

    Ware, Jennifer J.; Munafò, Marcus R.

    2016-01-01

    Background and Aims The low reproducibility of findings within the scientific literature is a growing concern. This may be due to many findings being false positives, which in turn can misdirect research effort and waste money. Methods We review factors that may contribute to poor study reproducibility and an excess of ‘significant’ findings within the published literature. Specifically, we consider the influence of current incentive structures, and the impact of these on research practices. Results The prevalence of false positives within the literature may be attributable to a number of questionable research practices, ranging from the relatively innocent and minor (e.g., unplanned post hoc tests), to the calculated and serious (e.g., fabrication of data). These practices may be driven by current incentive structures (e.g. pressure to publish), alongside the preferential emphasis placed by journals on novelty over veracity. There are a number of potential solutions to poor reproducibility, such as new publishing formats that emphasise the research question and study design, rather than the results obtained. This has the potential to minimise significance chasing and non-publication of null findings. Conclusions Significance chasing, questionable research practices, and poor study reproducibility are the unfortunate consequence of a “publish or perish” culture and a preference among journals for novel findings. It is likely that top-down change implemented by those with the ability to modify current incentive structure (e.g., funders and journals) will be required to address problems of poor reproducibility. PMID:25040652

  15. Increased asthma and adipose tissue inflammatory gene expression with obesity and Inuit migration to a western country.

    PubMed

    Backer, Vibeke; Baines, Katherine J; Powell, Heather; Porsbjerg, Celeste; Gibson, Peter G

    2016-02-01

    An overlap between obesity and asthma exists, and inflammatory cells in adipose tissue could drive the development of asthma. Comparison of adipose tissue gene expression among Inuit living in Greenland to those in Denmark provides an opportunity to assess how changes in adipose tissue inflammation can be modified by migration and diet. To examine mast cell and inflammatory markers in adipose tissue and the association with asthma. Two Inuit populations were recruited, one living in Greenland and another in Denmark. All underwent adipose subcutaneous biopsy, followed by clinical assessment of asthma, and measurement of AHR. Adipose tissue biopsies were homogenised, RNA extracted, and PCR was performed to determine the relative gene expression of mast cell (tryptase, chymase, CPA3) and inflammatory markers (IL-6, IL-1β, and CD163). Of the 1059 Greenlandic Inuit participants, 556 were living in Greenland and 6.4% had asthma. Asthma was increased in Denmark (9%) compared to Greenland (3.6%, p < 0.0001) and associated with increased adipose tissue IL-6 gene expression and increased BMI. There was no association between asthma and adipose tissue mast cell gene expression. Pro-inflammatory gene expression (IL-6, IL-1β) was higher in those living in Denmark, and with increasing BMI and dietary changes. The anti-inflammatory (M2) macrophage marker, CD163, was higher in Greenland-dwelling Inuit (p < 0.01). No association was found between gene expression of mast cell markers in adipose tissue and asthma. Among Greenlandic Inuit, adipose tissue inflammation is also increased in those who migrate to Denmark, possibly as a result of dietary changes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Fox Chase Cancer Center's Genitourinary Division: a national resource for research, innovation and patient care.

    PubMed

    Uzzo, Robert G; Horwitz, Eric M; Plimack, Elizabeth R

    2016-04-01

    Founded in 1904, Fox Chase Cancer Center remains committed to its mission. It is one of 41 centers in the country designated as a Comprehensive Cancer Center by the National Cancer Institute, is a founding member of the National Comprehensive Cancer Network, holds the magnet designation for nursing excellence, is one of the first to establish a family cancer risk assessment program, and has achieved national distinction because of the scientific discoveries made there that have advanced clinical care. Two of its researchers have won Nobel prizes. The Genitourinary Division is nationally recognized and viewed as one of the top driving forces behind the growth of Fox Chase due to its commitment to initiating and participating in clinical trials, its prolific contributions to peer-reviewed publications and presentations at scientific meetings, its innovations in therapies and treatment strategies, and its commitment to bringing cutting-edge therapies to patients.

  17. A Factor Increasing Venous Contamination on Bolus Chase Three-dimensional Magnetic Resonance Imaging: Charcot Neuroarthropathy.

    PubMed

    Çildağ, Mehmet B; Ertuğrul, Mustafa B; Köseoğlu, Ömer Fk; Armstrong, David G

    2018-01-01

    The study aimed to evaluate the ratio of venous contamination in diabetic cases without foot lesion, with foot lesion and with Charcot neuroarthropathy (CN). Bolus-chase three-dimensional magnetic resonance (MR) of 396 extremities of patients with diabetes mellitus was analyzed, retrospectively. Extremities were divided into three groups as follows: diabetic patients without foot ulcer or Charcot arthropathy (Group A), patients with diabetic foot ulcers (Group B) and patients with CN accompanying diabetic foot ulcers (Group C). Furthermore, amount of venous contamination classified as no venous contamination, mild venous contamination, and severe venous contamination. The relationship between venous contamination and extremity groups was investigated. Severe venous contamination was seen in Group A, Group B, and Group C, 5.6%, 15.2%, and 34.1%, respectively. Statistically significant difference was seen between groups with regard to venous contamination. Venous contamination following bolus chase MR was higher in patients with CN.

  18. Clock gene polymorphism and scheduling of migration: a geolocator study of the barn swallow Hirundo rustica

    PubMed Central

    Bazzi, Gaia; Ambrosini, Roberto; Caprioli, Manuela; Costanzo, Alessandra; Liechti, Felix; Gatti, Emanuele; Gianfranceschi, Luca; Podofillini, Stefano; Romano, Andrea; Romano, Maria; Scandolara, Chiara; Saino, Nicola; Rubolini, Diego

    2015-01-01

    Circannual rhythms often rely on endogenous seasonal photoperiodic timers involving ‘clock’ genes, and Clock gene polymorphism has been associated to variation in phenology in some bird species. In the long-distance migratory barn swallow Hirundo rustica, individuals bearing the rare Clock allele with the largest number of C-terminal polyglutamine repeats found in this species (Q8) show a delayed reproduction and moult later. We explored the association between Clock polymorphism and migration scheduling, as gauged by light-level geolocators, in two barn swallow populations (Switzerland; Po Plain, Italy). Genetic polymorphism was low: 91% of the 64 individuals tracked year-round were Q7/Q7 homozygotes. We compared the phenology of the rare genotypes with the phenotypic distribution of Q7/Q7 homozygotes within each population. In Switzerland, compared to Q7/Q7, two Q6/Q7 males departed earlier from the wintering grounds and arrived earlier to their colony in spring, while a single Q7/Q8 female was delayed for both phenophases. On the other hand, in the Po Plain, three Q6/Q7 individuals had a similar phenology compared to Q7/Q7. The Swiss data are suggestive for a role of genetic polymorphism at a candidate phenological gene in shaping migration traits, and support the idea that Clock polymorphism underlies phenological variation in birds. PMID:26197782

  19. 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

  20. Social grouping: perceptual grouping of objects by cooperative but not competitive relationships in dynamic chase.

    PubMed

    Yin, Jun; Ding, Xiaowei; Zhou, Jifan; Shui, Rende; Li, Xinyu; Shen, Mowei

    2013-10-01

    Historically, perceptual grouping is associated with physical principles. This article reports a novel finding that social information-cooperative but not competitive relationships-can drive perceptual grouping of objects in dynamic chase. Particularly, each relationship was constructed with human-generated chasing motions (i.e., two predators and one prey), and its role on perceptual grouping was examined by grouping-induced effect-attentional consequences. The results showed that: (1) Predators can be perceived as a group due to their cooperative relationship, causing attention to automatically spread within grouped predators, thus the response to target appearing on uncued predator is also facilitated; and (2) The attentional effect on competitive predators has no difference from any condition which controls low-level motion patterns, even including the random-motion condition wherein no grouping factor was contained. These findings extend perceptual grouping into the social field, implying that social information gets involved in visual cognition at an early perceptual stage. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Knockout Mice for Dyslexia Susceptibility Gene Homologs KIAA0319 and KIAA0319L have Unaffected Neuronal Migration but Display Abnormal Auditory Processing

    PubMed Central

    Guidi, Luiz G; Mattley, Jane; Martinez-Garay, Isabel; Monaco, Anthony P; Linden, Jennifer F; Velayos-Baeza, Antonio

    2017-01-01

    Abstract Developmental dyslexia is a neurodevelopmental disorder that affects reading ability caused by genetic and non-genetic factors. Amongst the susceptibility genes identified to date, KIAA0319 is a prime candidate. RNA-interference experiments in rats suggested its involvement in cortical migration but we could not confirm these findings in Kiaa0319-mutant mice. Given its homologous gene Kiaa0319L (AU040320) has also been proposed to play a role in neuronal migration, we interrogated whether absence of AU040320 alone or together with KIAA0319 affects migration in the developing brain. Analyses of AU040320 and double Kiaa0319;AU040320 knockouts (dKO) revealed no evidence for impaired cortical lamination, neuronal migration, neurogenesis or other anatomical abnormalities. However, dKO mice displayed an auditory deficit in a behavioral gap-in-noise detection task. In addition, recordings of click-evoked auditory brainstem responses revealed suprathreshold deficits in wave III amplitude in AU040320-KO mice, and more general deficits in dKOs. These findings suggest that absence of AU040320 disrupts firing and/or synchrony of activity in the auditory brainstem, while loss of both proteins might affect both peripheral and central auditory function. Overall, these results stand against the proposed role of KIAA0319 and AU040320 in neuronal migration and outline their relationship with deficits in the auditory system. PMID:29045729

  2. Chase and NYANA: A Partnership To Remove Barriers to Job Performance 1993-94. Final Report.

    ERIC Educational Resources Information Center

    Auerbach, Charles

    A workplace literacy program implemented cooperatively by the New York Association for New Americans, Inc. (NYANA) and Chase Manhattan Bank is reported. The federally-funded project provided individualized communication workplace behavior and skills training in English as a Second Language for 30 limited-English-proficient bank employees working…

  3. Overexpression of the growth arrest-specific homeobox gene Gax inhibits proliferation, migration, cell cycle progression, and apoptosis in serum-induced vascular smooth muscle cells.

    PubMed

    Zheng, H; Xue, S; Hu, Z L; Shan, J G; Yang, W G

    2014-03-24

    The Gax gene has been implicated in a variety of cell-developmental and biological processes, and aberrant Gax expression is linked to many diseases. In this study, to provide important insights for Gax-based gene therapy in vein graft restenosis and its anti-restenotic mechanism, we used rabbit vascular smooth muscle cells (VSMCs) to investigate the effects of Gax overexpression on proliferation, migration, cell cycle, and apoptosis in a serum-stimulated culture. Rabbit VSMC lines that stably overexpressed Gax were established by transfection with recombinant adenoviral vector Ad5-Gax. The effect of Gax overexpression on in vitro serum-induced VSMCs proliferation, migration, cell cycle, and apoptosis was assessed by MTT, wound healing, and flow cytometry assays, respectively. To investigate the effect of Gax overexpression on PCNA and MMP-2 in serum-induced VSMCs, immunocytochemistry, RT-PCR, and gelatin zymography were performed. The results clearly showed that Gax overexpression decreases PCNA expression in serum-induced VSMCs. Gax overexpression also significantly inhibited cell proliferation by blocking entry into the S-phase of the cell cycle, promoted cell apoptosis, and reduced cell migration activity by downregulating MMP-2 release and activity. These findings indicate that Gax would be an optimal target gene for gene therapy to treat vein graft restenosis.

  4. The JNM1 gene in the yeast Saccharomyces cerevisiae is required for nuclear migration and spindle orientation during the mitotic cell cycle

    PubMed Central

    1994-01-01

    JNM1, a novel gene on chromosome XIII in the yeast Saccharomyces cerevisiae, is required for proper nuclear migration. jnm1 null mutants have a temperature-dependent defect in nuclear migration and an accompanying alteration in astral microtubules. At 30 degrees C, a significant proportion of the mitotic spindles is not properly located at the neck between the mother cell and the bud. This defect is more severe at low temperature. At 11 degrees C, 60% of the cells accumulate with large buds, most of which have two DAPI staining regions in the mother cell. Although mitosis is delayed and nuclear migration is defective in jnm1 mutant, we rarely observe more than two nuclei in a cell, nor do we frequently observe anuclear cells. No loss of viability is observed at 11 degrees C and cells continue to grow exponentially with increased doubling time. At low temperature the large budded cells of jnm1 mutants exhibit extremely long astral microtubules that often wind around the periphery of the cell. jnm1 mutants are not defective in chromosome segregation during mitosis, as assayed by the rate of chromosome loss, or nuclear migration during conjugation, as assayed by the rate of mating and cytoduction. The phenotype of a jnm1 mutant is strikingly similar to that for mutants in the dynein heavy chain gene (Eshel, D., L. A. Urrestarazu, S. Vissers, J.-C. Jauniaux, J. C. van Vliet-Reedijk, R. J. Plants, and I. R. Gibbons. 1993. Proc. Natl. Acad. Sci. USA. 90:11172-11176; Li, Y. Y., E. Yeh, T. Hays, and K. Bloom. 1993. Proc. Natl. Acad. Sci. USA. 90:10096-10100). The JNM1 gene product is predicted to encode a 44-kD protein containing three coiled coil domains. A JNM1:lacZ gene fusion is able to complement the cold sensitivity and microtubule phenotype of a jnm1 deletion strain. This hybrid protein localizes to a single spot in the cell, most often near the spindle pole body in unbudded cells and in the bud in large budded cells. Together these results point to a specific role

  5. A mutant p53/let-7i-axis-regulated gene network drives cell migration, invasion and metastasis

    PubMed Central

    Subramanian, M; Francis, P; Bilke, S; Li, XL; Hara, T; Lu, X; Jones, MF; Walker, RL; Zhu, Y; Pineda, M; Lee, C; Varanasi, L; Yang, Y; Martinez, LA; Luo, J; Ambs, S; Sharma, S; Wakefield, LM; Meltzer, PS; Lal, A

    2015-01-01

    Most p53 mutations in human cancers are missense mutations resulting in a full-length mutant p53 protein. Besides losing tumor suppressor activity, some hotspot p53 mutants gain oncogenic functions. This effect is mediated in part, through gene expression changes due to inhibition of p63 and p73 by mutant p53 at their target gene promoters. Here, we report that the tumor suppressor microRNA let-7i is downregulated by mutant p53 in multiple cell lines expressing endogenous mutant p53. In breast cancer patients, significantly decreased let-7i levels were associated with missense mutations in p53. Chromatin immunoprecipitation and promoter luciferase assays established let-7i as a transcriptional target of mutant p53 through p63. Introduction of let-7i to mutant p53 cells significantly inhibited migration, invasion and metastasis by repressing a network of oncogenes including E2F5, LIN28B, MYC and NRAS. Our findings demonstrate that repression of let-7i expression by mutant p53 has a key role in enhancing migration, invasion and metastasis. PMID:24662829

  6. Dynamic properties of chasers in a moving queue based on a delayed chasing model

    NASA Astrophysics Data System (ADS)

    Ning, Guo; Jian-Xun, Ding; Xiang, Ling; Qin, Shi; Reinhart, Kühne

    2016-05-01

    A delayed chasing model is proposed to simulate the chase behavior in the queue, where each member regards the closest one ahead as the target, and the leader is attracted to a target point with slight fluctuation. When the initial distances between neighbors possess an identical low value, the fluctuating target of the leader can cause an amplified disturbance in the queue. After a long period of time, the queue recovers the stable state from the disturbance, forming a straight-line-like pattern again, but distances between neighbors grow. Whether the queue can keep stable or not depends on initial distance, desired velocity, and relaxation time. Furthermore, we carry out convergence analysis to explain the divergence transformation behavior and confirm the convergence conditions, which is in approximate agreement with simulations. Project supported by the National Natural Science Foundation of China (Grant Nos. 71071044, 71001001, 71201041, and 11247291), the Doctoral Program of the Ministry of Education of China (Grant Nos. 20110111120023 and 20120111120022), the Postdoctoral Fund Project of China (Grant No. 2013M530295), the National Basic Research Program of China (Grant No. 2012CB725404), and 1000 Plan for Foreign Talent, China (Grant No. WQ20123400070).

  7. A Novel Pulse-Chase Paradigm to Visualize the Trafficking of Transport Vesicles in Neurons

    NASA Astrophysics Data System (ADS)

    Al-Bassam, Sarmad

    In neurons transmembrane proteins are targeted to dendrites in vesicles that traffic solely within the somatodendritic compartment. How these vesicles are retained within the somatodendritic domain is unknown. Here we adapt a novel pulse chase system that allows synchronous release of exogenous transmembrane proteins from the endoplasmic reticulum using FKBP12 and Rapamycin. We demonstrate proof-of-concept and establish protein trafficking controls in incremental steps. We demonstrate the utility of this approach in studying protein trafficking and establish parameters for analysis of time-lapse images. We implement this novel pulse-chase strategy to track the movements of post-Golgi transport vesicles. Surprisingly, we found that post-Golgi vesicles carrying dendritic proteins were equally likely to enter axons and dendrites. However, once such vesicles entered the axon they very rarely moved beyond the axon initial segment, but instead either halted or reversed direction in an actin and Myosin Va-dependent manner. In contrast, vesicles carrying either an axonal or a nonspecifically localized protein only rarely halted or reversed and instead generally proceeded to the distal axon. Thus, our results are consistent with the axon initial segment behaving as a vesicle filter that mediates the differential trafficking of transport vesicles.

  8. Migration of cochlear lateral wall cells.

    PubMed

    Dunaway, George; Mhaskar, Yashanad; Armour, Gary; Whitworth, Craig; Rybak, Leonard

    2003-03-01

    The role of apoptosis and proliferation in maintenance of cochlear lateral wall cells was examined. The methods employed for detection of apoptosis were the Hoechst fluorescence stain and TUNEL (TdT-mediated dUTP-biotin nick-end-labeling) assay, and proliferations were 5-bromo-2'-deoxyuridine (BrdU) incorporation and presence of the proliferating cell nuclear antigen. The incidence of apoptosis in the strial marginal cell was 50% greater (32.9+/-3.7%) than strial intermediate and basal cells but similar to spiral ligament cells. Although division of marginal strial cells was rarely detected, a significant number of proliferating cells in the remaining stria vascularis and spiral ligament were observed. These data implied that replacement of marginal cells arose elsewhere and could be followed by a BrdU-deoxythymidine pulse-chase study. At 2 h post injection, nuclear BrdU in marginal cells was not detected; however, by 24 h post injection, 20-25% of marginal cell nuclei were BrdU-positive. These observations are consistent with the hypothesis that marginal cells were replaced by underlying cells. Cell migration appears to be an important mechanism for preserving the function and structure of the stria vascularis.

  9. History Run Wild: The Alternate World of Joan Aiken's "The Wolves of Willoughby Chase" Series

    ERIC Educational Resources Information Center

    Dams, Isobel

    2005-01-01

    This article examines the historical fantasy world created by Joan Aiken in the eleven volumes of her "Wolves of Willoughby Chase" series. In particular it looks at her subversion of historical reality by the creation of an alternative yet recognisable representation of our own world, using a wide range of events, and the remoulding of aspects of…

  10. Solution or suspension - Does it matter for lipid based systems? In vivo studies of chase dosing lipid vehicles with aqueous suspensions of a poorly soluble drug.

    PubMed

    Larsen, A T; Holm, R; Müllertz, A

    2017-08-01

    In this study, the potential of co-administering an aqueous suspension with a placebo lipid vehicle, i.e. chase dosing, was investigated in rats relative to the aqueous suspension alone or a solution of the drug in the lipid vehicle. The lipid investigated in the present study was Labrafil M2125CS and three evaluated poorly soluble model compounds, danazol, cinnarizine and halofantrine. For cinnarizine and danazol the oral bioavailability in rats after chase dosing or dosing the compound dissolved in Labrafil M21515CS was similar and significantly higher than for the aqueous suspension. For halofantrine the chase dosed group had a tendency towards a low bioavailability relative to the Labrafil M2125CS solution, but still a significant higher bioavailability relative to the aqueous suspension. This could be due to factors such as a slower dissolution rate in the intestinal phase of halofantrine or a lower solubility in the colloidal structures formed during digestion, but other mechanisms may also be involved. The study thereby supported the potential of chase dosing as a potential dosing regimen in situations where it is beneficial to have a drug in the solid state, e.g. due to chemical stability issues in the lipid vehicle. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Abhydrolase domain containing 2, an androgen target gene, promotes prostate cancer cell proliferation and migration.

    PubMed

    Obinata, Daisuke; Takada, Shogo; Takayama, Ken-ichi; Urano, Tomohiko; Ito, Akiko; Ashikari, Daisaku; Fujiwara, Kyoko; Yamada, Yuta; Murata, Taro; Kumagai, Jinpei; Fujimura, Tetsuya; Ikeda, Kazuhiro; Horie-Inoue, Kuniko; Homma, Yukio; Takahashi, Satoru; Inoue, Satoshi

    2016-04-01

    The androgen receptor (AR) plays a key role in the development of prostate cancer. AR signalling mediates the expression of androgen-responsive genes, which are involved in prostate cancer development and progression. Our previous chromatin immunoprecipitation study showed that the region of abhydrolase domain containing 2 (ABHD2) includes a functional androgen receptor binding site. In this study, we demonstrated that ABHD2 is a novel androgen-responsive gene that is overexpressed in human prostate cancer tissues. The expression levels of ABHD2 in androgen-sensitive cells were evaluated by quantitative reverse transcription polymerase chain reaction and western-blot analyses. LNCaP and VCaP cells with ABHD2 overexpression or short interfering RNA (siRNA) knockdown were used for functional analyses. ABHD2 expression was examined in clinical samples of prostate cancer by immunohistochemistry. We showed that ABHD2 expression is increased by androgen in LNCaP and VCaP cells. This androgen-induced ABHD2 expression was diminished by bicalutamide. While stable expression of ABHD2 affected the enhancement of LNCaP cell proliferation and migration, siRNA-mediated ABHD2 knockdown suppressed cell proliferation and migration. In addition, the siRNA treatment significantly repressed the tumour growth derived from LNCaP cells in athymic mice. Immunohistochemical analysis of ABHD2 expression in tumour specimens showed a positive correlation of ABHD2 immunoreactivity with high Gleason score and pathological N stage. Moreover, patients with high immunoreactivity of ABHD2 showed low cancer-specific survival rates and a resistance to docetaxel-based chemotherapy. ABHD2 is a novel androgen-regulated gene that can promote prostate cancer growth and resistance to chemotherapy, and is a novel target for diagnosis and treatment of prostate cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. NRC, SPI, and chasing arrows: Is there common ground

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

    Rabasca, L.

    After negotiating for 15 months, issuing three white papers, and conducting consumer research, the National Recycling Coalition (NRC, Washington, DC) and the Society of the Plastics Industry, Inc. (SPI, Washington, DC), have agreed to disagree on the use of the familiar chasing arrows logo in SPI's seven-number resin identification code. The desired end result of the talks and debates was supposed to be a plan to change legislation requiring 39 states to use SPI's current resin identification code and a commitment to remove the old code from durable goods and flexible packaging. Ultimately, these actions could have improved markets formore » polyethylene terephthalate (PET) and high-density polyethylene (HDPE) by reducing contamination caused by confusion over what is actually recycled versus what is merely recyclable.« less

  13. 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.

  14. 76 FR 31955 - Jonathan and Jayne Chase; Notice of Application Accepted for Filing With the Commission, Intent...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-02

    .... c. Date filed: July 23, 2010. d. Applicant: Jonathan and Jayne Chase. e. Name of Project: Troy Hydropower Project. f. Location: On the Missisquoi River, in the Town of Troy, Orleans County, Vermont. The... filing and is now ready for environmental analysis. l. Project Description: The Troy Project would...

  15. Structural characterization and chromosomal location of the mouse macrophage migration inhibitory factor gene and pseudogenes

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

    Bozza, M.; Gerard, C.; Kolakowski, L.F. Jr.

    1995-06-10

    Macrophage migration inhibitory factor, MIF, is a cytokine released by T-lymphocytes, macrophages, and the pituitary gland that serves to integrate peripheral and central inflammatory responses. Ubiquitous expression and developmental regulation suggest that MIF may have additional roles outside of the immune system. Here we report the structure and chromosomal location of the mouse Mif gene and the partial characterization of five Mif pseudogenes. The mouse Mif gene spans less than 0.7 kb of chromosomal DNA and is composed of three exons. A comparison between the mouse and the human genes shows a similar gene structure and common regulatory elements inmore » both promoter regions. The mouse Mif gene maps to the middle region of chromosome 10, between Bcr and S100b, which have been mapped to human chromosomes 22q11 and 21q22.3, respectively. The entire sequence of two pseudogenes demonstrates the absence of introns, the presence of the 5{prime} untranslated region of the cDNA, a 3{prime} poly(A) tail, and the lack of sequence similarity with untranscribed regions of the gene. The five pseudogenes are highly homologous to the cDNA, but contain a variable number of mutations that would produce mutated or truncated MIF-like proteins. Phylogenetic analyses of MIF genes and pseudogenes indicate several independent genetic events that can account for multiple genomic integrations. Three of the Mif pseudogenes were also mapped by interspecific backcross to chromosomes 1, 9, and 17. These results suggest that Mif pseudogenes originated by retrotransposition. 46 refs., 5 figs., 1 tab.« less

  16. 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

  17. 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.

  18. Maximum Likelihood Implementation of an Isolation-with-Migration Model for Three Species.

    PubMed

    Dalquen, Daniel A; Zhu, Tianqi; Yang, Ziheng

    2017-05-01

    We develop a maximum likelihood (ML) method for estimating migration rates between species using genomic sequence data. A species tree is used to accommodate the phylogenetic relationships among three species, allowing for migration between the two sister species, while the third species is used as an out-group. A Markov chain characterization of the genealogical process of coalescence and migration is used to integrate out the migration histories at each locus analytically, whereas Gaussian quadrature is used to integrate over the coalescent times on each genealogical tree numerically. This is an extension of our early implementation of the symmetrical isolation-with-migration model for three species to accommodate arbitrary loci with two or three sequences per locus and to allow asymmetrical migration rates. Our implementation can accommodate tens of thousands of loci, making it feasible to analyze genome-scale data sets to test for gene flow. We calculate the posterior probabilities of gene trees at individual loci to identify genomic regions that are likely to have been transferred between species due to gene flow. We conduct a simulation study to examine the statistical properties of the likelihood ratio test for gene flow between the two in-group species and of the ML estimates of model parameters such as the migration rate. Inclusion of data from a third out-group species is found to increase dramatically the power of the test and the precision of parameter estimation. We compiled and analyzed several genomic data sets from the Drosophila fruit flies. Our analyses suggest no migration from D. melanogaster to D. simulans, and a significant amount of gene flow from D. simulans to D. melanogaster, at the rate of ~0.02 migrant individuals per generation. We discuss the utility of the multispecies coalescent model for species tree estimation, accounting for incomplete lineage sorting and migration. © The Author(s) 2016. Published by Oxford University Press, on

  19. The Zebrafish G12 Gene is required for Nuclear Positioning and Cell Migrations during Early Development

    NASA Technical Reports Server (NTRS)

    Reinsch, S. S.; Conway, G. C.

    2003-01-01

    After fertilization Zebrafish embryos undergo synchronous cleavage to form a blastula of cells sitting upon a single multinucleate yolk cell. At the beginning of gastrulation these cells undergo extensive cell migrations to form the major body axes. We have discovered a gene, G12, which is required for cell migrations and positioning of nuclei in the large syncytial yolk cell. Overexpression of a G12-GFP fusion protein is not toxic and shows that the protein localizes inside the yolk cell to the yolk nuclei, microtubules, and to the margin between the blastomeres and the large yolk cell. Morpholino (MO) injection into the 1-cell embryo or into just the yolk syncytium conipletely inhibits cell migrations, doming of the yolk cell, and positioning of nuclei around the margin. This effect can be partially rescued by injection of G12-GFP encoding RNA. Given the known role of microtubules in nuclear positioning of yolk nuclei in Zebrafish, we investigated the microtubules in morpholiiio injected and rescued embryos. We find that microtubules are sparse and disorganized in MO-injected embryos and are restored to normal organization upon G12-GFP rescue. G12 plays a pivotal role in organization of inicrotubules during early development. G12 is highly conserved in vertebrates and two homologues exist in the human genome. One of the human hoinologues is amplified in aggressive breast tumors.

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

    PubMed

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

    2017-07-04

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

  1. Coplanar tail-chase aerial combat as a differential game

    NASA Technical Reports Server (NTRS)

    Merz, A. W.; Hague, D. S.

    1977-01-01

    A reduced-order version of the one-on-one aerial combat problem is studied as a pursuit-evasion differential game. The coplanar motion takes place at given speeds and given maximum available turn rates, and is described by three state equations which are equivalent to the range, bearing, and heading of one aircraft relative to the other. The purpose of the study is to determine those relative geometries from which either aircraft can be guaranteed a win, regardless of the maneuver strategies of the other. Termination is specified by the tail-chase geometry, at which time the roles of pursuer and evader are known. The roles are found in general, together with the associated optimal turn maneuvers, by solution of the differential game of kind. For the numerical parameters chosen, neither aircraft can win from the majority of possible initial conditions if the other turns optimally in certain critical geometries.

  2. Role of the p55-gamma subunit of PI3K in ALK-induced cell migration: RNAi-based selection of cell migration regulators.

    PubMed

    Seo, Minchul; Kim, Jong-Heon; Suk, Kyoungho

    2017-05-04

    Recently, unbiased functional genetic selection identified novel cell migration-regulating genes. This RNAi-based functional selection was performed using 63,996 pooled lentiviral shRNAs targeting 21,332 mouse genes. After five rounds of selection using cells with accelerated or impaired migration, shRNAs were retrieved and identified by half-hairpin barcode sequencing using cells with the selected phenotypes. This selection process led to the identification of 29 novel cell migration regulators. One of these candidates, anaplastic lymphoma kinase (ALK), was further investigated. Subsequent studies revealed that ALK promoted cell migration through the PI3K-AKT pathway via the p55γ regulatory subunit of PI3K, rather than more commonly used p85 subunit. Western blot and immunohistochemistry studies using mouse brain tissues revealed similar temporal expression patterns of ALK, phospho-p55γ, and phospho-AKT during different stages of development. These data support an important role for the p55γ subunit of PI3K in ALK-induced cell migration during brain development.

  3. Global analysis of saliva as a source of bacterial genes for insights into human population structure and migration studies.

    PubMed

    Henne, Karsten; Li, Jing; Stoneking, Mark; Kessler, Olga; Schilling, Hildegard; Sonanini, Anne; Conrads, Georg; Horz, Hans-Peter

    2014-08-22

    The genetic diversity of the human microbiome holds great potential for shedding light on the history of our ancestors. Helicobacter pylori is the most prominent example as its analysis allowed a fine-scale resolution of past migration patterns including some that could not be distinguished using human genetic markers. However studies of H. pylori require stomach biopsies, which severely limits the number of samples that can be analysed. By focussing on the house-keeping gene gdh (coding for the glucose-6-phosphate dehydrogenase), on the virulence gene gtf (coding for the glucosyltransferase) of mitis-streptococci and on the 16S-23S rRNA internal transcribed spacer (ITS) region of the Fusobacterium nucleatum/periodonticum-group we here tested the hypothesis that bacterial genes from human saliva have the potential for distinguishing human populations. Analysis of 10 individuals from each of seven geographic regions, encompassing Africa, Asia and Europe, revealed that the genes gdh and ITS exhibited the highest number of polymorphic sites (59% and 79%, respectively) and most OTUs (defined at 99% identity) were unique to a given country. In contrast, the gene gtf had the lowest number of polymorphic sites (21%), and most OTUs were shared among countries. Most of the variation in the gdh and ITS genes was explained by the high clonal diversity within individuals (around 80%) followed by inter-individual variation of around 20%, leaving the geographic region as providing virtually no source of sequence variation. Conversely, for gtf the variation within individuals accounted for 32%, between individuals for 57% and among geographic regions for 11%. This geographic signature persisted upon extension of the analysis to four additional locations from the American continent. Pearson correlation analysis, pairwise Fst-cluster analysis as well as UniFrac analyses consistently supported a tree structure in which the European countries clustered tightly together and branched

  4. Functional characterization of the turkey macrophage migration inhibitory factor

    USDA-ARS?s Scientific Manuscript database

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

  5. Cytoglobin inhibits migration through PI3K/AKT/mTOR pathway in fibroblast cells.

    PubMed

    Demirci, Selami; Doğan, Ayşegül; Apdik, Hüseyin; Tuysuz, Emre Can; Gulluoglu, Sukru; Bayrak, Omer Faruk; Şahin, Fikrettin

    2018-01-01

    Cell proliferation and migration are crucial in many physiological processes including development, cancer, tissue repair, and wound healing. Cell migration is regulated by several signaling molecules. Identification of genes related to cell migration is required to understand molecular mechanism of non-healing chronic wounds which is a major concern in clinics. In the current study, the role of cytoglobin (CYGB) gene in fıbroblast cell migration and proliferation was described. L929 mouse fibroblast cells were transduced with lentiviral particles for CYGB and GFP, and analyzed for cell proliferation and migration ability. Fibroblast cells overexpressing CYGB displayed decreased cell proliferation, colony formation capacity, and cell migration. Phosphorylation levels of mTOR and two downstream effectors S6 and 4E-BP1 which take part in PI3K/AKT/mTOR signaling declined in CYGB-overexpressing cells. Microarray analysis indicated that CYGB overexpression leads to downregulation of cell proliferation, migration, and tumor growth associated genes in L929 cell line. This study demonstrated the role of CYGB in fibroblast cell motility and proliferation. CYGB could be a promising candidate for further studies as a potential target for diseases related to cell migration such as cancer and chronic wound treatment.

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

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

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

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

  7. Genetic susceptibility to Chagas disease cardiomyopathy: involvement of several genes of the innate immunity and chemokine-dependent migration pathways

    PubMed Central

    2013-01-01

    Background Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America. Thirty percent of infected individuals develop chronic Chagas cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy that is, by far, the most important clinical consequence of T. cruzi infection. The others remain asymptomatic (ASY). A possible genetic component to disease progression was suggested by familial aggregation of cases and the association of markers of innate and adaptive immunity genes with CCC development. Migration of Th1-type T cells play a major role in myocardial damage. Methods Our genetic analysis focused on CCR5, CCL2 and MAL/TIRAP genes. We used the Tag SNPs based approach, defined to catch all the genetic information from each gene. The study was conducted on a large Brazilian population including 315 CCC cases and 118 ASY subjects. Results The CCL2rs2530797A/A and TIRAPrs8177376A/A were associated to an increase susceptibility whereas the CCR5rs3176763C/C genotype is associated to protection to CCC. These associations were confirmed when we restricted the analysis to severe CCC, characterized by a left ventricular ejection fraction under 40%. Conclusions Our data show that polymorphisms affecting key molecules involved in several immune parameters (innate immunity signal transduction and T cell/monocyte migration) play a role in genetic susceptibility to CCC development. This also points out to the multigenic character of CCC, each polymorphism imparting a small contribution. The identification of genetic markers for CCC will provide information for pathogenesis as well as therapeutic targets. PMID:24330528

  8. Animal tracking meets migration genomics: transcriptomic analysis of a partially migratory bird species.

    PubMed

    Franchini, Paolo; Irisarri, Iker; Fudickar, Adam; Schmidt, Andreas; Meyer, Axel; Wikelski, Martin; Partecke, Jesko

    2017-06-01

    Seasonal migration is a widespread phenomenon, which is found in many different lineages of animals. This spectacular behaviour allows animals to avoid seasonally adverse environmental conditions to exploit more favourable habitats. Migration has been intensively studied in birds, which display astonishing variation in migration strategies, thus providing a powerful system for studying the ecological and evolutionary processes that shape migratory behaviour. Despite intensive research, the genetic basis of migration remains largely unknown. Here, we used state-of-the-art radio-tracking technology to characterize the migratory behaviour of a partially migratory population of European blackbirds (Turdus merula) in southern Germany. We compared gene expression of resident and migrant individuals using high-throughput transcriptomics in blood samples. Analyses of sequence variation revealed a nonsignificant genetic structure between blackbirds differing by their migratory phenotype. We detected only four differentially expressed genes between migrants and residents, which might be associated with hyperphagia, moulting and enhanced DNA replication and transcription. The most pronounced changes in gene expression occurred between migratory birds depending on when, in relation to their date of departure, blood was collected. Overall, the differentially expressed genes detected in this analysis may play crucial roles in determining the decision to migrate, or in controlling the physiological processes required for the onset of migration. These results provide new insights into, and testable hypotheses for, the molecular mechanisms controlling the migratory phenotype and its underlying physiological mechanisms in blackbirds and other migratory bird species. © 2017 John Wiley & Sons Ltd.

  9. Increased dermal collagen bundle alignment in systemic sclerosis is associated with a cell migration signature and role of Arhgdib in directed fibroblast migration on aligned ECMs

    PubMed Central

    Lafyatis, Robert; Burkly, Linda C.

    2017-01-01

    Systemic sclerosis (SSc) is a devastating disease affecting the skin and internal organs. Dermal fibrosis manifests early and Modified Rodnan Skin Scores (MRSS) correlate with disease progression. Transcriptomics of SSc skin biopsies suggest the role of the in vivo microenvironment in maintaining the pathological myofibroblasts. Therefore, defining the structural changes in dermal collagen in SSc patients could inform our understanding of fibrosis pathogenesis. Here, we report a method for quantitative whole-slide image analysis of dermal collagen from SSc patients, and our findings of more aligned dermal collagen bundles in diffuse cutaneous SSc (dcSSc) patients. Using the bleomycin-induced mouse model of SSc, we identified a distinct high dermal collagen bundle alignment gene signature, characterized by a concerted upregulation in cell migration, adhesion, and guidance pathways, and downregulation of spindle, replication, and cytokinesis pathways. Furthermore, increased bundle alignment induced a cell migration gene signature in fibroblasts in vitro, and these cells demonstrated increased directed migration on aligned ECM fibers that is dependent on expression of Arhgdib (Rho GDP-dissociation inhibitor 2). Our results indicate that increased cell migration is a cellular response to the increased collagen bundle alignment featured in fibrotic skin. Moreover, many of the cell migration genes identified in our study are shared with human SSc skin and may be new targets for therapeutic intervention. PMID:28662216

  10. NO2 DOAS Measurements of Traffic Emissions by Chasing Cars

    NASA Astrophysics Data System (ADS)

    Zhu, Ying; Lipkowitsch, Ivo; Chan, Ka Lok; Bräu, Melanie; Wenig, Mark

    2016-04-01

    On this poster we present NO2 measurements using a Cavity-Enhanced DOAS on a measurement bus which we used to chase other vehicles to measure their NO2 emissions. Emissions of nitrogen oxides from on-road vehicles have received highly attention recently due to the increasing trend of ambient NOx level. It is particularly important to identify and quantify the direct emission and secondary formation of NO2 contributed by traffic emissions, in order to study the impact to the local air quality. We sampled on-road emissions in different environments and different driving conditions (e.g. urban, highway, different speeds). We analyse the data set in terms of spatial and temporal variability to search for temporal and spatial patterns. We present mean values sorted for different vehicle types, distance to the target car and travelling speeds to provide an emission data base from this measurement study.

  11. Platelets Inhibit Migration of Canine Osteosarcoma Cells.

    PubMed

    Bulla, S C; Badial, P R; Silva, R C; Lunsford, K; Bulla, C

    2017-01-01

    The interaction between platelets and tumour cells is important for tumour growth and metastasis. Thrombocytopenia or antiplatelet treatment negatively impact on cancer metastasis, demonstrating potentially important roles for platelets in tumour progression. To our knowledge, there is no information regarding the role of platelets in cancer progression in dogs. This study was designed to test whether canine platelets affected the migratory behaviour of three canine osteosarcoma cell lines and to give insights of molecular mechanisms. Intact platelets, platelet lysate and platelet releasate inhibited the migration of canine osteosarcoma cell lines. Addition of blood leucocytes to the platelet samples did not alter the inhibitory effect on migration. Platelet treatment also significantly downregulated the transcriptional levels of SNAI2 and TWIST1 genes. The interaction between canine platelets or molecules released during platelet activation and these tumour cell lines inhibits their migration, which suggests that canine platelets might antagonize metastasis of canine osteosarcoma. This effect is probably due to, at least in part, downregulation of genes related to epithelial-mesenchymal transition. Copyright © 2016. Published by Elsevier Ltd.

  12. Spatial pattern analysis of nuclear migration in remodelled muscles during Drosophila metamorphosis.

    PubMed

    Kuleesha; Feng, Lin; Wasser, Martin

    2017-07-10

    Many human muscle wasting diseases are associated with abnormal nuclear localization. During metamorphosis in Drosophila melanogaster, multi-nucleated larval dorsal abdominal muscles either undergo cell death or are remodeled to temporary adult muscles. Muscle remodeling is associated with anti-polar nuclear migration and atrophy during early pupation followed by polar migration and muscle growth during late pupation. Muscle remodeling is a useful model to study genes involved in myonuclear migration. Previously, we showed that loss of Cathepsin-L inhibited anti-polar movements, while knockdown of autophagy-related genes affected nuclear positioning along the medial axis in late metamorphosis. To compare the phenotypic effects of gene perturbations on nuclear migration more objectively, we developed new descriptors of myonuclear distribution. To obtain nuclear pattern features, we designed an algorithm to detect and track nuclear regions inside live muscles. Nuclear tracks were used to distinguish between fast moving nuclei associated with fragments of dead muscles (sarcolytes) and slow-moving nuclei inside remodelled muscles. Nuclear spatial pattern features, such as longitudinal (lonNS) and lateral nuclear spread (latNS), allowed us to compare nuclear migration during muscle remodelling in different genetic backgrounds. Anti-polar migration leads to a lonNS decrease. As expected, lack of myonuclear migration caused by the loss of Cp1 was correlated with a significantly lower lonNS decrease. Unexpectedly, the decrease in lonNS was significantly enhanced by Atg9, Atg5 and Atg18 silencing, indicating that the loss of autophagy promotes the migration and clustering of nuclei. Loss of autophagy also caused a scattering of nuclei along the lateral axis, leading to a two-row as opposed to single row distribution in control muscles. Increased latNS resulting from knockdown of Atg9 and Atg18 was correlated with increased muscle diameter, suggesting that the wider muscle

  13. Combat History Analysis Study Effort (CHASE) Data Enhancement Study (CDES). Volume 1. Introductory Materials and Bioliography.

    DTIC Science & Technology

    1986-01-31

    Operations, France and Belgium, 1914: Mons, the Retreat to the Seine , the Marne , the Aisne, August-October 1914. London, 1922. Edmonds, Brig. Gen...7-175 712 COMBAT HISTORY ANAL YSIS STUDY EFFORT (CHASE) DATA l/f ENHANCEMENT STUDY CDES (U) DATA MEMORY SYSTEMS INC FAIRFAX VA HERO DIV B R BADER ET ...Fleville 350 Noyon-Montdidier 378 Hill 212 351 Champagne- Marne 379 Bois de Boyon- 352 Aisne- Marne I Montrefagne 353 Missy aux Bois Ravine 380 Hill 272 354

  14. Silencing the hsp25 Gene Eliminates Migration Capability of the Highly Metastatic Murine 4T1 Breast Adenocarcinoma Cell

    PubMed Central

    Bausero, Maria A.; Bharti, Ajit; Page, Diana T.; Perez, Kristen D.; Eng, Jason W.-L.; Ordonez, Susana L.; Jantschitsch, Christian; Kindas-Muegge, Ingela; Ciocca, Daniel; Asea, Alexzander

    2006-01-01

    The 25-kDa heat shock protein (Hsp25) is associated with various malignancies and is expressed at high levels in biopsies as well as circulating in the serum of breast cancer patients. In this study, we used RNA interference technology to silence the hsp25 gene in 4T1 breast adenocarcinoma cells, known as a poorly immunogenic, highly metastatic cell line. We demonstrate that transfection of 4T1 cells with short interference RNA-Hsp25 dramatically inhibits proliferation as compared with control transfected cells. In addition, we show that 4T1 cells transfected with short interference RNA-Hsp25 abrogates tumor migration potential by a mechanism that is in part due to the repression of matrix metalloproteinase 9 expression and a concomitant upregulation of its antagonist, tissue inhibitor metalloproteinase 1. Taken together, these findings provide a model system for the study of metastatic potential of tumors and are suggestive of an earlier unrecognized role for Hsp25 in tumor migration. PMID:16340246

  15. Amphioxus and lamprey AP-2 genes: implications for neural crest evolution and migration patterns

    NASA Technical Reports Server (NTRS)

    Meulemans, Daniel; Bronner-Fraser, Marianne

    2002-01-01

    The neural crest is a uniquely vertebrate cell type present in the most basal vertebrates, but not in cephalochordates. We have studied differences in regulation of the neural crest marker AP-2 across two evolutionary transitions: invertebrate to vertebrate, and agnathan to gnathostome. Isolation and comparison of amphioxus, lamprey and axolotl AP-2 reveals its extensive expansion in the vertebrate dorsal neural tube and pharyngeal arches, implying co-option of AP-2 genes by neural crest cells early in vertebrate evolution. Expression in non-neural ectoderm is a conserved feature in amphioxus and vertebrates, suggesting an ancient role for AP-2 genes in this tissue. There is also common expression in subsets of ventrolateral neurons in the anterior neural tube, consistent with a primitive role in brain development. Comparison of AP-2 expression in axolotl and lamprey suggests an elaboration of cranial neural crest patterning in gnathostomes. However, migration of AP-2-expressing neural crest cells medial to the pharyngeal arch mesoderm appears to be a primitive feature retained in all vertebrates. Because AP-2 has essential roles in cranial neural crest differentiation and proliferation, the co-option of AP-2 by neural crest cells in the vertebrate lineage was a potentially crucial event in vertebrate evolution.

  16. Migration phenology and breeding success are predicted by methylation of a photoperiodic gene in the barn swallow

    PubMed Central

    Saino, Nicola; Ambrosini, Roberto; Albetti, Benedetta; Caprioli, Manuela; De Giorgio, Barbara; Gatti, Emanuele; Liechti, Felix; Parolini, Marco; Romano, Andrea; Romano, Maria; Scandolara, Chiara; Gianfranceschi, Luca; Bollati, Valentina; Rubolini, Diego

    2017-01-01

    Individuals often considerably differ in the timing of their life-cycle events, with major consequences for individual fitness, and, ultimately, for population dynamics. Phenological variation can arise from genetic effects but also from epigenetic modifications in DNA expression and translation. Here, we tested if CpG methylation at the poly-Q and 5′-UTR loci of the photoperiodic Clock gene predicted migration and breeding phenology of long-distance migratory barn swallows (Hirundo rustica) that were tracked year-round using light-level geolocators. Increasing methylation at Clock poly-Q was associated with earlier spring departure from the African wintering area, arrival date at the European breeding site, and breeding date. Higher methylation levels also predicted increased breeding success. Thus, we showed for the first time in any species that CpG methylation at a candidate gene may affect phenology and breeding performance. Methylation at Clock may be a candidate mechanism mediating phenological responses of migratory birds to ongoing climate change. PMID:28361883

  17. Migration phenology and breeding success are predicted by methylation of a photoperiodic gene in the barn swallow.

    PubMed

    Saino, Nicola; Ambrosini, Roberto; Albetti, Benedetta; Caprioli, Manuela; De Giorgio, Barbara; Gatti, Emanuele; Liechti, Felix; Parolini, Marco; Romano, Andrea; Romano, Maria; Scandolara, Chiara; Gianfranceschi, Luca; Bollati, Valentina; Rubolini, Diego

    2017-03-31

    Individuals often considerably differ in the timing of their life-cycle events, with major consequences for individual fitness, and, ultimately, for population dynamics. Phenological variation can arise from genetic effects but also from epigenetic modifications in DNA expression and translation. Here, we tested if CpG methylation at the poly-Q and 5'-UTR loci of the photoperiodic Clock gene predicted migration and breeding phenology of long-distance migratory barn swallows (Hirundo rustica) that were tracked year-round using light-level geolocators. Increasing methylation at Clock poly-Q was associated with earlier spring departure from the African wintering area, arrival date at the European breeding site, and breeding date. Higher methylation levels also predicted increased breeding success. Thus, we showed for the first time in any species that CpG methylation at a candidate gene may affect phenology and breeding performance. Methylation at Clock may be a candidate mechanism mediating phenological responses of migratory birds to ongoing climate change.

  18. Geology and hydrogeology of Naval Air Station Chase Field and Naval Auxiliary Landing Field Goliad, Bee and Goliad counties, Texas

    USGS Publications Warehouse

    Snyder, G.L.

    1995-01-01

    Large vertical hydraulic-head gradients are present between the unconfined Evangeline aquifer and confined Fleming aquifers at Naval Air Station Chase Field and Naval Auxiliary Landing Field Goliad. These gradients, together with the results of the aquifer test at Naval Air Station Chase Field and assumed characteristics of the confining units, indicate that downward flow of ground water probably occurs from the water-table aquifer to the underlying aquifers. The rate of downward flow between the two confined Fleming aquifers (from A-sand to B-sand) can be approximated using an estimate of vertical hydraulic conductivity of the intervening confining unit obtained from assumed storage characteristics and data from the aquifer test. Under the relatively high vertical hydraulic-head gradient induced by the aquifer test, ground-water movement from the A-sand aquifer to the B-sand aquifer could require about 490 years; and about 730 years under the natural gradient. Future increases in ground-water withdrawals from the B-sand aquifer might increase downward flow in the aquifer system of the study area.

  19. Noninvasive electromagnetic fields on keratinocyte growth and migration.

    PubMed

    Huo, Ran; Ma, Qianli; Wu, James J; Chin-Nuke, Kayla; Jing, Yuqi; Chen, Juan; Miyar, Maria E; Davis, Stephen C; Li, Jie

    2010-08-01

    Although evidence has shown that very small electrical currents produce a beneficial therapeutic result for wounds, noninvasive electromagnetic field (EMF) therapy has consisted mostly of anecdotal clinical reports, with very few well-controlled laboratory mechanistic studies. In this study, we evaluate the effects and potential mechanisms of a noninvasive EMF device on skin wound repair. The effects of noninvasive EMF on keratinocytes and fibroblasts were assessed via proliferation and incisional wound model migration assays. cDNA microarray and RT-PCR were utilized to assess genetic expression changes in keratinocytes after noninvasive EMF treatment. In vitro analyses with human skin keratinocyte cultures demonstrated that noninvasive EMFs have a strong effect on accelerating keratinocyte migration and a relatively weaker effect on promoting keratinocyte proliferation. The positive effects of noninvasive EMFs on cell migration and proliferation seem keratinocyte-specific without such effects seen on dermal fibroblasts. cDNA microarray and RT-PCR performed revealed increased expression of CRK7 and HOXC8 genes in treated keratinocytes. This study suggests that a noninvasive EMF accelerates wound re-epithelialization through a mechanism of promoting keratinocyte migration and proliferation, possibly due to upregulation of CRK7 and HOXC8 genes. Copyright 2010 Elsevier Inc. All rights reserved.

  20. Systematic Analysis of the Transcriptional Switch Inducing Migration of Border Cells

    PubMed Central

    Borghese, Lodovica; Fletcher, Georgina; Mathieu, Juliette; Atzberger, Ann; Eades, William C.; Cagan, Ross L.; Rørth, Pernille

    2010-01-01

    Summary Cell migration within a natural context is tightly controlled, often by specific transcription factors. However, the switch from stationary to migratory behavior is poorly understood. Border cells perform a spatially and temporally controlled invasive migration during Drosophila oogenesis. Slbo, a C/EBP family transcriptional activator, is required for them to become migratory. We purified wild-type and slbo mutant border cells as well as nonmigratory follicle cells and performed comparative whole-genome expression profiling, followed by functional tests of the contributions of identified targets to migration. About 300 genes were significantly upregulated in border cells, many dependent on Slbo. Among these, the microtubule regulator Stathmin was strongly upregulated and was required for normal migration. Actin cytoskeleton regulators were also induced, including, surprisingly, a large cluster of “muscle-specific” genes. We conclude that Slbo induces multiple cytoskeletal effectors, and that each contributes to the behavioral changes in border cells. PMID:16580994

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

    PubMed Central

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

    2014-01-01

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

  2. Tumor-specific detection of an optically targeted antibody combined with a quencher-conjugated neutravidin "quencher-chaser": a dual "quench and chase" strategy to improve target to nontarget ratios for molecular imaging of cancer.

    PubMed

    Ogawa, Mikako; Kosaka, Nobuyuki; Choyke, Peter L; Kobayashi, Hisataka

    2009-01-01

    In vivo molecular cancer imaging with monoclonal antibodies has great potential not only for cancer detection, but also for cancer characterization. However, the prolonged retention of intravenously injected antibody in the blood causes low target tumor-to-background ratio (TBR). Avidin has been used as a "chase" to clear the unbound, circulating biotinylated antibody and decrease the background signal. Here, we utilize a combined approach of a fluorescence resonance energy transfer (FRET) quenched antibody with an "avidin chase" to increase TBR. Trastuzumab, a humanized monoclonal antibody against human epidermal growth factor receptor type 2 (HER2), was biotinylated and conjugated with the near-infrared (NIR) fluorophore Alexa680 to synthesize Tra-Alexa680-biotin. Next, the FRET quencher, QSY-21, was conjugated to avidin, neutravidin (nAv), or streptavidin (sAv), thus creating Av-QSY21, nAv-QSY21, or sAv-QSY21 as "chasers". The fluorescence was quenched in vitro by binding Tra-Alexa680-biotin to Av-QSY21, nAv-QSY21, or sAv-QSY21. To evaluate if the injection of quencher-conjugated avidin derivatives can improve target TBR by using a dual "quench and chase" strategy, both target (3T3/HER2+) and nontarget (Balb3T3/ZsGreen) tumor-bearing mice were employed. The "FRET quench" effect induced by all the QSY21 avidin-based conjugates reduced but did not totally eliminate background signal from the blood pool. The addition of nAv-QSY21 administration increased target TBR mainly because of the "chase" effect where unbound conjugated antibody was preferentially cleared to the liver. The relatively slow clearance of unbound nAv-QSY21 leads to further reductions in background signal by leaking out of the vascular space and binding to unbound antibodies in the extravascular space of tumors, resulting in decreased nontarget tumor-to-background ratios but increased target TBR due to the "FRET quench" effect, because target-bound antibodies were internalized and could not bind

  3. Migration in Afro-Brazilian rural communities: crossing demographic and genetic data.

    PubMed

    Amorim, Carlos Eduardo G; Gontijo, Carolina C; Falcão-Alencar, Gabriel; Godinho, Neide M O; Toledo, Rafaela C P; Pedrosa, Maria Angélica F; Luizon, Marcelo R; Simões, Aguinaldo L; Klautau-Guimãres, Maria N; Oliveira, Silviene F

    2011-08-01

    Many studies have used genetic markers to understand global migration patterns of our species. However, there are only few studies of human migration on a local scale. We, therefore, researched migration dynamics in three Afro-Brazilian rural communities, using demographic data and ten Ancestry Informative Markers. In addition to the description of migration and marriage structures, we carried out genetic comparisons between the three populations, as well as between locals and migrants from each community. Genetic admixture analyses were conducted according to the gene-identity method, with Sub-Saharan Africans, Amerindians, and Europeans as parental populations. The three analyzed Afro-Brazilian rural communities consisted of 16% to 30% of migrants, most of them women. The age pyramid revealed a gap in the segment of men aged between 20 to 30 yrs. While endogamous marriages predominated, exogamous marriages were mainly patrilocal. Migration dynamics are apparently associated with matrimonial customs and other social practices of such communities. The impact of migration upon the populations' genetic composition was low but showed an increase in European alleles with a concomitant decrease in the Amerindian contribution. Admixture analysis evidenced a higher African contribution to the gene pool of the studied populations, followed by the contribution of Europeans and Amerindians, respectively.

  4. CCDC-55 is required for larval development and distal tip cell migration in Caenorhabditis elegans.

    PubMed

    Kovacevic, Ismar; Ho, Richard; Cram, Erin J

    2012-01-01

    The Caenorhabditis elegans distal tip cells (DTCs) are an in vivo model for the study of developmentally regulated cell migration. In this study, we characterize a novel role for CCDC-55, a conserved coiled-coil domain containing protein, in DTC migration and larval development in C. elegans. Although animals homozygous for a probable null allele, ccdc-55(ok2851), display an early larval arrest, RNAi depletion experiments allow the analysis of later phenotypes and suggest that CCDC-55 is needed within the DTC for migration to cease at the end of larval morphogenesis. The ccdc-55 gene is found in an operon with rnf-121 and rnf-5, E3 ubiquitin ligases that target cell migration genes such as the β-integrin PAT-3. Genetic interaction studies using RNAi depletion and the deletion alleles rnf-121(ok848) and rnf-5(tm794) indicate that CCDC-55 and the RNF genes act at least partially in parallel to promote termination of cell migration in the adult DTC. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  5. CCDC-55 is required for larval development and distal tip cell migration in C. elegans

    PubMed Central

    Kovacevic, Ismar; Ho, Richard; Cram, Erin J.

    2012-01-01

    The C. elegans distal tip cells (DTCs) are an in vivo model for the study of developmentally regulated cell migration. In this study we characterize a novel role for CCDC-55, a conserved coiled-coil domain containing protein, in DTC migration and larval development in C. elegans. Although animals homozygous for a probable null allele, ccdc-55(ok2851), display an early larval arrest, RNAi depletion experiments allow the analysis of later phenotypes and suggest that CCDC-55 is needed within the DTC for migration to cease at the end of larval morphogenesis. The ccdc-55 gene is found in an operon with rnf-121 and rnf-5, E3 ubiquitin ligases that target cell migration genes such as the β-integrin PAT-3. Genetic interaction studies using RNAi depletion and the deletion alleles rnf-121(ok848) and rnf-5(tm794) indicate that CCDC-55 and the RNF genes act at least partially in parallel to promote termination of cell migration in the adult DTC. PMID:22285439

  6. 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

  7. Real-time measurements of nitrogen oxide emissions from in-use New York City transit buses using a chase vehicle.

    PubMed

    Shorter, Joanne H; Herndon, Scott; Zahniser, Mark S; Nelson, David D; Wormhoudt, Joda; Demerjian, Kenneth L; Kolb, Charles E

    2005-10-15

    New diesel engine technologies and alternative fuel engines are being introduced into fleets of mass transit buses to try to meet stricter emission regulations of nitrogen oxides and particulates: Real-time instruments including an Aerodyne Research tunable infrared laser differential absorption spectrometer (TILDAS) were deployed in a mobile laboratory to assess the impact of the implementation of the new technologies on nitrogen oxide emissions in real world driving conditions. Using a "chase" vehicle sampling strategy, the mobile laboratory followed target vehicles, repeatedly sampling their exhaust. Nitrogen oxides from approximately 170 in-use New York City mass transit buses were sampled during the field campaigns. Emissions from conventional diesel buses, diesel buses with continuously regenerating technology (CRT), diesel hybrid electric buses, and compressed natural gas (CNG) buses were compared. The chase vehicle sampling method yields real world emissions that can be included in more realistic emission inventories. The NO, emissions from the diesel and CNG buses were comparable. The hybrid electric buses had approximately one-half the NOx emissions. In CRT diesels, NO2 accounts for about one-third of the NOx emitted in the exhaust, while for non-CRT buses the NO2 fraction is less than 10%.

  8. Biosynthesis of yeast glycoproteins. Processing of the oligosaccharides transferred from dolichol derivatives.

    PubMed

    Parodi, A J

    1979-10-25

    The oligosaccharides previously bound to dolichol diphosphate were isolated from Saccharomyces cerevisiae cells incubated with [U-14C]glucose. Five compounds were obtained that migrated with RGlucose of 0.100, 0.120, 0.145, 0.180, and 0.215 on paper chromatography. All of them contained mannose and 2 N-acetylhexosamine residues. The substances that migrated with the three lower RGlucose values had, in addition, glucose units. The structure of the oligosacchardies was very similar if not identical with that of the oligosaccharides isolated from the dolichol diphosphate derivatives synthesized "in vitro" by yeast or rat liver particulate preparations or "in vivo" by dog thyroid or rat liver slices as judged by their migration on paper chromatography, monosaccharide composition, and degradation compounds produced by alpha-mannosidase treatment or acetolysis. The oligosaccharides previously bound to asparagine residues in proteins were isolated from yeast cells which had been pulsed with [U-14C]glucose and chased with medium containing the unlabeled monosaccharide. The samples taken after very short pulses contained four oligosaccharides that migrated with RGlucose of 0.100, 0.120, 0.145, and 0.180 on paper chromatography. The first three compounds contained glucose, mannose, and 2 N-acetylhexosamine residues whereas the one that migrated with a RGlucose of 0.180 was devoid of the former monosaccharide. Samples taken after short chase periods revealed that the compounds that migrated with the lower RGlucose values gradually disappeared and were converted to the oligosaccharide with the higher RGlucose value was they lost their glucose residues. Similar analysis as those mentioned above showed that the structures of these compounds were similar to those of the dolichol diphosphate-bound oligosaccharides. Samples taken after longer chase periods revealed that the oligosaccharide that migrated with a RGlucose of 0.180 was subsequently either enlarged by the addition of

  9. JC Virus Mediates Invasion and Migration in Colorectal Metastasis

    PubMed Central

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

    2009-01-01

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

  10. Cellular Migration and Invasion Uncoupled: Increased Migration Is Not an Inexorable Consequence of Epithelial-to-Mesenchymal Transition

    PubMed Central

    Schaeffer, Daneen; Somarelli, Jason A.; Hanna, Gabi; Palmer, Gregory M.

    2014-01-01

    Metastatic dissemination requires carcinoma cells to detach from the primary tumor and invade through the basement membrane. To acquire these characteristics, epithelial tumor cells undergo epithelial-to-mesenchymal transitions (EMT), whereby cells lose polarity and E-cadherin-mediated cell-cell adhesion. Post-EMT cells have also been shown, or assumed, to be more migratory; however, there have been contradictory reports on an immortalized human mammary epithelial cell line (HMLE) that underwent EMT. In the context of carcinoma-associated EMT, it is not yet clear whether the change in migration and invasion must be positively correlated during EMT or whether enhanced migration is a necessary consequence of having undergone EMT. Here, we report that pre-EMT rat prostate cancer (PC) and HMLE cells are more migratory than their post-EMT counterparts. To determine a mechanism for increased epithelial cell migration, gene expression analysis was performed and revealed an increase in epidermal growth factor receptor (EGFR) expression in pre-EMT cells. Indeed, inhibition of EGFR in PC epithelial cells slowed migration. Importantly, while post-EMT PC and HMLE cell lines are less migratory, both remain invasive in vitro and, for PC cells, in vivo. Our study demonstrates that enhanced migration is not a phenotypic requirement of EMT, and migration and invasion can be uncoupled during carcinoma-associated EMT. PMID:25002532

  11. Redox sensor CtBP mediates hypoxia-induced tumor cell migration

    PubMed Central

    Zhang, Qinghong; Wang, Su-Yan; Nottke, Amanda C.; Rocheleau, Jonathan V.; Piston, David W.; Goodman, Richard H.

    2006-01-01

    The rapid growth and poor vascularization of solid tumors expose cancer cells to hypoxia, which promotes the metastatic phenotype by reducing intercellular adhesion and increasing cell motility and invasiveness. In this study, we found that hypoxia increased free NADH levels in cancer cells, promoting CtBP recruitment to the E-cadherin promoter. This effect was blocked by pyruvate, which prevents the NADH increase. Furthermore, hypoxia repressed E-cadherin gene expression and increased tumor cell migration, effects that were blocked by CtBP knockdown. We propose that CtBP senses levels of free NADH to control expression of cell adhesion genes, thereby promoting tumor cell migration under hypoxic stress. PMID:16740659

  12. RNA interference-mediated survivin gene knockdown induces growth arrest and reduced migration of vascular smooth muscle cells.

    PubMed

    Nabzdyk, Christoph S; Lancero, Hope; Nguyen, Khanh P; Salek, Sherveen; Conte, Michael S

    2011-11-01

    Survivin (SVV) is a multifunctional protein that has been implicated in the development of neointimal hyperplasia. Nuclear SVV is essential for mitosis, whereas in mitochondria SVV has a cytoprotective function. Here, we investigated the effects of RNA interference (RNAi)-mediated SVV knockdown on cell cycle kinetics, apoptosis, migration, and gene expression in primary cultured vascular smooth muscle cells (VSMCs) from the human saphenous vein. Primary Human VSMCs were obtained from saphenous veins and cultured under standard conditions. SVV knockdown was achieved by either small interfering RNA or lentiviral transduction of short hairpin RNA, reducing SVV gene expression by quantitative PCR (>75%, P < 0.01) without a loss of cell viability. Subcellular fractionation revealed that RNAi treatment effectively targeted the nuclear SVV pool, whereas the larger mitochondrial pool was much less sensitive to transient knockdown. Both p53 and p27 protein levels were notably increased. SVV RNAi treatment significantly blocked VSMC proliferation in response to serum and PDGF-AB, arresting VSMC growth. Cell cycle analysis revealed an increased G(2)/M fraction consistent with a mitotic defect; 4',6-diamidino-2-phenylindole staining confirmed an increased frequency of polyploid and abnormal nuclei. In a transwell assay, SVV knockdown reduced migration to PDGF-AB, and actin-phalloidin staining revealed disorganized actin filaments and polygonal cell shape. However, apoptosis (DNA content and annexin V flow cytometry) was not directly induced by SVV RNAi, and sensitivity to apoptotic agonists (e.g., staurosporine and cytokines) was unchanged. In conclusion, RNAi-mediated SVV knockdown in VSMCs leads to profound cell cycle arrest at G(2)/M and impaired chemotaxis without cytotoxicity. The regulation of mitosis and apoptosis in VSMC involves differentially regulated subcellular pools of SVV. Thus, treatment of VSMC with RNAi targeting SVV might limit the response to vascular

  13. RNA interference-mediated survivin gene knockdown induces growth arrest and reduced migration of vascular smooth muscle cells

    PubMed Central

    Nabzdyk, Christoph S.; Lancero, Hope; Nguyen, Khanh P.; Salek, Sherveen

    2011-01-01

    Survivin (SVV) is a multifunctional protein that has been implicated in the development of neointimal hyperplasia. Nuclear SVV is essential for mitosis, whereas in mitochondria SVV has a cytoprotective function. Here, we investigated the effects of RNA interference (RNAi)-mediated SVV knockdown on cell cycle kinetics, apoptosis, migration, and gene expression in primary cultured vascular smooth muscle cells (VSMCs) from the human saphenous vein. Primary Human VSMCs were obtained from saphenous veins and cultured under standard conditions. SVV knockdown was achieved by either small interfering RNA or lentiviral transduction of short hairpin RNA, reducing SVV gene expression by quantitative PCR (>75%, P < 0.01) without a loss of cell viability. Subcellular fractionation revealed that RNAi treatment effectively targeted the nuclear SVV pool, whereas the larger mitochondrial pool was much less sensitive to transient knockdown. Both p53 and p27 protein levels were notably increased. SVV RNAi treatment significantly blocked VSMC proliferation in response to serum and PDGF-AB, arresting VSMC growth. Cell cycle analysis revealed an increased G2/M fraction consistent with a mitotic defect; 4′,6-diamidino-2-phenylindole staining confirmed an increased frequency of polyploid and abnormal nuclei. In a transwell assay, SVV knockdown reduced migration to PDGF-AB, and actin-phalloidin staining revealed disorganized actin filaments and polygonal cell shape. However, apoptosis (DNA content and annexin V flow cytometry) was not directly induced by SVV RNAi, and sensitivity to apoptotic agonists (e.g., staurosporine and cytokines) was unchanged. In conclusion, RNAi-mediated SVV knockdown in VSMCs leads to profound cell cycle arrest at G2/M and impaired chemotaxis without cytotoxicity. The regulation of mitosis and apoptosis in VSMC involves differentially regulated subcellular pools of SVV. Thus, treatment of VSMC with RNAi targeting SVV might limit the response to vascular injury

  14. Douglas Lowy and Nirali Shah discuss advancements in cancer treatment at the second annual Chasing Cancer Summit | Center for Cancer Research

    Cancer.gov

    On Monday, September 18, 2017, the second annual Chasing Cancer Summit was held at the Washington Post headquarters in downtown Washington, D.C. The live event brought together a group of experts, including CCR’s Douglas Lowy, M.D., and Nirali Shah, M.D., for discussions on the latest developments in cancer detection and treatment.  Read more...

  15. Differential gene expression in migratory streams of cortical interneurons

    PubMed Central

    Antypa, Mary; Faux, Clare; Eichele, Gregor; Parnavelas, John G; Andrews, William D

    2011-01-01

    Cortical interneurons originate in the ganglionic eminences of the subpallium and migrate into the cortex in well-defined tangential streams. At the start of corticogenesis, two streams of migrating neurons are evident: a superficial one at the level of the preplate (PPL), and a deeper one at the level of the intermediate zone (IZ). Currently, little is known about the signalling mechanisms that regulate interneuron migration, and almost nothing is known about the molecules that may be involved in their choice of migratory stream. Here, we performed a microarray analysis, comparing the changes in gene expression between cells migrating in the PPL and those migrating in the IZ at embryonic day 13.5. This analysis identified genes, many of them novel, that were upregulated in one of the two streams. Moreover, polymerase chain reaction, in situ hybridization experiments and immunohistochemistry showed the expression of these genes in interneurons migrating within the PPL or IZ, suggesting that they play a role in their migration and choice of stream. PMID:22103416

  16. Silencing the hsp25 gene eliminates migration capability of the highly metastatic murine 4T1 breast adenocarcinoma cell.

    PubMed

    Bausero, Maria A; Bharti, Ajit; Page, Diana T; Perez, Kristen D; Eng, Jason W-L; Ordonez, Susana L; Asea, Edwina E; Jantschitsch, Christian; Kindas-Muegge, Ingela; Ciocca, Daniel; Asea, Alexzander

    2006-01-01

    The 25-kDa heat shock protein (Hsp25) is associated with various malignancies and is expressed at high levels in biopsies as well as circulating in the serum of breast cancer patients. In this study, we used RNA interference technology to silence the hsp25 gene in 4T1 breast adenocarcinoma cells, known as a poorly immunogenic, highly metastatic cell line. We demonstrate that transfection of 4T1 cells with short interference RNA-Hsp25 dramatically inhibits proliferation as compared with control transfected cells. In addition, we show that 4T1 cells transfected with short interference RNA-Hsp25 abrogates tumor migration potential by a mechanism that is in part due to the repression of matrix metalloproteinase 9 expression and a concomitant upregulation of its antagonist, tissue inhibitor metalloproteinase 1. Taken together, these findings provide a model system for the study of metastatic potential of tumors and are suggestive of an earlier unrecognized role for Hsp25 in tumor migration. Copyright 2006 S. Karger AG, Basel.

  17. PRK1/PKN1 controls migration and metastasis of androgen-independent prostate cancer cells

    PubMed Central

    Jilg, Cordula A.; Ketscher, Anett; Metzger, Eric; Hummel, Barbara; Willmann, Dominica; Rüsseler, Vanessa; Drendel, Vanessa; Imhof, Axel; Jung, Manfred; Franz, Henriette; Hölz, Stefanie; Krönig, Malte; Müller, Judith M.; Schüle, Roland

    2014-01-01

    The major threat in prostate cancer is the occurrence of metastases in androgen-independent tumor stage, for which no causative cure is available. Here we show that metastatic behavior of androgen-independent prostate tumor cells requires the protein-kinase-C-related kinase (PRK1/PKN1) in vitro and in vivo. PRK1 regulates cell migration and gene expression through its kinase activity, but does not affect cell proliferation. Transcriptome and interactome analyses uncover that PRK1 regulates expression of migration-relevant genes by interacting with the scaffold protein sperm-associated antigen 9 (SPAG9/JIP4). SPAG9 and PRK1 colocalize in human cancer tissue and are required for p38-phosphorylation and cell migration. Accordingly, depletion of either ETS domain-containing protein Elk-1 (ELK1), an effector of p38-signalling or p38 depletion hinders cell migration and changes expression of migration-relevant genes as observed upon PRK1-depletion. Importantly, a PRK1 inhibitor prevents metastases in mice, showing that the PRK1-pathway is a promising target to hamper prostate cancer metastases in vivo. Statement of significance Here we describe a novel mechanism controlling the metastatic behavior of PCa cells and identify PRK1 as a promising therapeutic target to treat androgen-independent metastatic prostate cancer. PMID:25504435

  18. Migration features of Ips typographus in the Tatra Mountains: using a genetic method

    Treesearch

    Ferenc Lakatos

    2003-01-01

    The genetic structure of Ips typographus populations in the Tatra Mountains was studied based on the observed differences of gene flow and migration rate. It was a highlighted question as to what extent different natural barriers influence the migration potential of the species.

  19. ALK is a MYCN target gene and regulates cell migration and invasion in neuroblastoma

    PubMed Central

    Hasan, Md. Kamrul; Nafady, Asmaa; Takatori, Atsushi; Kishida, Satoshi; Ohira, Miki; Suenaga, Yusuke; Hossain, Shamim; Akter, Jesmin; Ogura, Atsushi; Nakamura, Yohko; Kadomatsu, Kenji; Nakagawara, Akira

    2013-01-01

    Human anaplastic lymphoma kinase (ALK) has been identified as an oncogene that is mutated or amplified in NBLs. To obtain a better understanding of the molecular events associated with ALK in the pathogenesis of NBL, it is necessary to clarify how ALK gene contributes to NBL progression. In the present study, we found that ALK expression was significantly high in NBL clinical samples with amplified MYCN (n = 126, P < 0.01) and in developing tumors of MYCN-transgenic mice. Indeed, promoter analysis revealed that ALK is a direct transcriptional target of MYCN. Overexpression and knockdown of ALK demonstrated its function in cell proliferation, migration and invasion. Moreover, treatment with an ALK inhibitor, TAE-684, efficiently suppressed such biological effects in MYCN amplified cells and tumor growth of the xenograft in mice. Our present findings explore the fundamental understanding of ALK in order to develop novel therapeutic tools by targeting ALK for aggressive NBL treatment. PMID:24356251

  20. RNAi Screening with Self-Delivering, Synthetic siRNAs for Identification of Genes That Regulate Primary Human T Cell Migration.

    PubMed

    Freeley, Michael; Derrick, Emily; Dempsey, Eugene; Hoff, Antje; Davies, Anthony; Leake, Devin; Vermeulen, Annaleen; Kelleher, Dermot; Long, Aideen

    2015-09-01

    Screening of RNA interference (RNAi) libraries in primary T cells is labor-intensive and technically challenging because these cells are hard to transfect. Chemically modified, self-delivering small interfering RNAs (siRNAs) offer a solution to this problem, because they enter hard-to-transfect cell types without needing a delivery reagent and are available in library format for RNAi screening. In this study, we have screened a library of chemically modified, self-delivering siRNAs targeting the expression of 72 distinct genes in conjunction with an image-based high-content-analysis platform as a proof-of-principle strategy to identify genes involved in lymphocyte function-associated antigen-1 (LFA-1)-mediated migration in primary human T cells. Our library-screening strategy identified the small GTPase RhoA as being crucial for T cell polarization and migration in response to LFA-1 stimulation and other migratory ligands. We also demonstrate that multiple downstream assays can be performed within an individual RNAi screen and have used the remainder of the cells for additional assays, including cell viability and adhesion to ICAM-1 (the physiological ligand for LFA-1) in the absence or presence of the chemokine SDF-1α. This study therefore demonstrates the ease and benefits of conducting siRNA library screens in primary human T cells using self-delivering, chemically modified siRNAs, and it emphasizes the feasibility and potential of this approach for elucidating the signaling pathways that regulate T cell function. © 2015 Society for Laboratory Automation and Screening.

  1. Chasing The 'Like': Adolescent Use Of Social Networking Sites In Australia.

    PubMed

    la Sala, Louise; Skues, Jason; Wise, Lisa; Theiler, Stephen

    2015-01-01

    The current study investigated how adolescents behave on Social Networking Sites (SNSs) and how they interpret the feedback they receive online from others. Thirty-four Australian adolescents (26 girls, 8 boys) aged 13 to 17 years participated in the study. Five semi-structured focus groups (3 mixed groups, 2 all-girl groups) were conducted to explore how adolescents perceive their own and others' SNS behaviours, the motivation underlying these behaviours, and the expected outcomes related to particular behaviours. Teenagers reported that they spend a good deal of time planning their SNS posts, felt that the information they posted was a true reflection of them as a person, and thus interpreted feedback ("likes") as measuring their self-worth. In contrast, some teenagers were perceived as "chasing the like" for status and popularity while not caring about how accurately their posts represented them as a person. A potential gender bias in these findings is discussed.

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

    PubMed Central

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

    2015-01-01

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

  3. Pulse-chase Analysis of N-linked Sugar Chains from Glycoproteins in Mammalian Cells

    PubMed Central

    Avezov, Edward; Ron, Efrat; Izenshtein, Yana; Adan, Yosef; Lederkremer, Gerardo Z.

    2010-01-01

    Attachment of the Glc3Man9GlcNAc2 precursor oligosaccharide to nascent polypeptides in the ER is a common modification for secretory proteins. Although this modification was implicated in several biological processes, additional aspects of its function are emerging, with recent evidence of its role in the production of signals for glycoprotein quality control and trafficking. Thus, phenomena related to N-linked glycans and their processing are being intensively investigated. Methods that have been recently developed for proteomic analysis have greatly improved the characterization of glycoprotein N-linked glycans. Nevertheless, they do not provide insight into the dynamics of the sugar chain processing involved. For this, labeling and pulse-chase analysis protocols are used that are usually complex and give very low yields. We describe here a simple method for the isolation and analysis of metabolically labeled N-linked oligosaccharides. The protocol is based on labeling of cells with [2-3H] mannose, denaturing lysis and enzymatic release of the oligosaccharides from either a specifically immunoprecipitated protein of interest or from the general glycoprotein pool by sequential treatments with endo H and N-glycosidase F, followed by molecular filtration (Amicon). In this method the isolated oligosaccharides serve as an input for HPLC analysis, which allows discrimination between various glycan structures according to the number of monosaccharide units comprising them, with a resolution of a single monosaccharide. Using this method we were able to study high mannose N-linked oligosaccharide profiles of total cell glycoproteins after pulse-chase in normal conditions and under proteasome inhibition. These profiles were compared to those obtained from an immunoprecipitated ER-associated degradation (ERAD) substrate. Our results suggest that most NIH 3T3 cellular glycoproteins are relatively stable and that most of their oligosaccharides are trimmed to Man9-8GlcNAc2. In

  4. Pulse-chase analysis of N-linked sugar chains from glycoproteins in mammalian cells.

    PubMed

    Avezov, Edward; Ron, Efrat; Izenshtein, Yana; Adan, Yosef; Lederkremer, Gerardo Z

    2010-04-27

    Attachment of the Glc3Man9GlcNAc2 precursor oligosaccharide to nascent polypeptides in the ER is a common modification for secretory proteins. Although this modification was implicated in several biological processes, additional aspects of its function are emerging, with recent evidence of its role in the production of signals for glycoprotein quality control and trafficking. Thus, phenomena related to N-linked glycans and their processing are being intensively investigated. Methods that have been recently developed for proteomic analysis have greatly improved the characterization of glycoprotein N-linked glycans. Nevertheless, they do not provide insight into the dynamics of the sugar chain processing involved. For this, labeling and pulse-chase analysis protocols are used that are usually complex and give very low yields. We describe here a simple method for the isolation and analysis of metabolically labeled N-linked oligosaccharides. The protocol is based on labeling of cells with [2-(3)H] mannose, denaturing lysis and enzymatic release of the oligosaccharides from either a specifically immunoprecipitated protein of interest or from the general glycoprotein pool by sequential treatments with endo H and N-glycosidase F, followed by molecular filtration (Amicon). In this method the isolated oligosaccharides serve as an input for HPLC analysis, which allows discrimination between various glycan structures according to the number of monosaccharide units comprising them, with a resolution of a single monosaccharide. Using this method we were able to study high mannose N-linked oligosaccharide profiles of total cell glycoproteins after pulse-chase in normal conditions and under proteasome inhibition. These profiles were compared to those obtained from an immunoprecipitated ER-associated degradation (ERAD) substrate. Our results suggest that most NIH 3T3 cellular glycoproteins are relatively stable and that most of their oligosaccharides are trimmed to Man9-8GlcNAc2

  5. [Overexpression of N-myc downstream regulated gene 2 (NDRG2) inhibits proliferation, migration and promotes apoptosis in SW480 rectal cancer cells].

    PubMed

    Li, Zhiqiang; Sun, Yang; Wan, Hongxing; Chai, Fang

    2017-01-01

    Objective To investigate the role of N-myc downstream regulated gene 2 (NDRG2) gene in the proliferation, migration and apoptosis of rectal cancer cells. Methods Human rectal cancer SW480 cells were cultured and transfected with pCDNA3.1-NDRG2 and empty vector (SW480-Ve). SW480 cells were set as a control group. Cell proliferation was detected in SW480 cells, SW480-Ve cells and SW480-NDRG2 cells by MTT assay; cell migration distance in the three groups at 24, 48, 72 hours was tested by wound healing assay; apoptosis rate was determined in the three groups at 48 hours by flow cytometry; the expressions of Bax, caspase-3, Bcl-2 proteins in the three groups were examined by Western blotting. Results After the cells were cultured for 7 days, cell survival rate in SW480-NDRG2 group was significantly lower than that in SW480 cells and SW480-Ve cells; the cell survival rate decreased gradually with the prolongation of the culture time; and it had no significant difference between SW480-Ve group and SW480 group. Cell migration distance in SW480-NDRG2 group was significantly lower than that in SW480-Ve cells and SW480 cells, and it had also no significant difference between SW480-Ve cells and SW480 cells. The apoptosis rate in SW480-NDRG2 group was significantly higher than that in SW480 group and SW480-Ve group, and SW480 cells and SW480-Ve cells had no significant difference in the rate. The expressions of Bax and caspase-3 proteins in SW480-NDRG2 group were significantly higher than those in SW480 cells and SW480-Ve cells; Bcl-2 protein expression was significantly lower in SW480-NDRG2 group than in SW480 cells and SW480-Ve cells; and the expressions of Bax, caspase-3 and Bcl-2 proteins were not significantly different between SW480 cells and SW480-Ve cells. Conclusion Overexpression of NDRG2 can inhibit the proliferation, reduce cell migration, and promote cell apoptosis by regulating the expressions of Bcl-2, Bax and caspase-3 proteins in SW480 cells.

  6. Macrophage migration inhibitory factor (MIF) gene is associated with adolescents' cortisol reactivity and anxiety.

    PubMed

    Lipschutz, Rebecca; Bick, Johanna; Nguyen, Victoria; Lee, Maria; Leng, Lin; Grigorenko, Elena; Bucala, Richard; Mayes, Linda C; Crowley, Michael J

    2018-05-26

    Emerging evidence points to interactions between inflammatory markers and stress reactivity in predicting mental health risk, but underlying mechanisms are not well understood. Macrophage Migration Inhibitory Factor (MIF) is a pleiotropic cytokine involved in inflammatory signaling and Hypothalamus Pituitary Adrenal (HPA) axis stress-response, and has recently been identified as a candidate biomarker for depression and anxiety risk. We examined polymorphic variations of the MIF gene in association with baseline MIF levels, HPA axis reactivity, and self-reported anxiety responses to a social stressor in 74 adolescents, ages 10-14 years. Genotyping was performed for two polymorphisms, the -794 CATT5-8 tetranucleotide repeat and the -173*G/C single nucleotide polymorphism (SNP). Youth carrying the MIF-173*C and CATT7 alleles displayed attenuated cortisol reactivity when compared with non-carriers. Children with the CATT7-173*C haplotype displayed lower cortisol reactivity to the stressor compared to those without this haplotype. Additionally, the CATT5-173*C and CATT6-173*C haplotypes were associated with lower self-reported anxiety ratings across the stressor. Results extend prior work pointing to the influence of MIF signaling on neuroendocrine response to stress and suggest a potential pathophysiological pathway underlying risk for stress-related physical and mental health disorders. To our knowledge, these are the first data showing associations between the MIF gene, HPA axis reactivity, and anxiety symptoms during adolescence. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Combined Genetic and Telemetry Data Reveal High Rates of Gene Flow, Migration, and Long-Distance Dispersal Potential in Arctic Ringed Seals (Pusa hispida)

    PubMed Central

    Martinez-Bakker, Micaela E.; Sell, Stephanie K.; Swanson, Bradley J.; Kelly, Brendan P.; Tallmon, David A.

    2013-01-01

    Ringed seals (Pusa hispida) are broadly distributed in seasonally ice covered seas, and their survival and reproductive success is intricately linked to sea ice and snow. Climatic warming is diminishing Arctic snow and sea ice and threatens to endanger ringed seals in the foreseeable future. We investigated the population structure and connectedness within and among three subspecies: Arctic (P. hispida hispida), Baltic (P. hispida botnica), and Lake Saimaa (P. hispida saimensis) ringed seals to assess their capacity to respond to rapid environmental changes. We consider (a) the geographical scale of migration, (b) use of sea ice, and (c) the amount of gene flow between subspecies. Seasonal movements and use of sea ice were determined for 27 seals tracked via satellite telemetry. Additionally, population genetic analyses were conducted using 354 seals representative of each subspecies and 11 breeding sites. Genetic analyses included sequences from two mitochondrial regions and genotypes of 9 microsatellite loci. We found that ringed seals disperse on a pan-Arctic scale and both males and females may migrate long distances during the summer months when sea ice extent is minimal. Gene flow among Arctic breeding sites and between the Arctic and the Baltic Sea subspecies was high; these two subspecies are interconnected as are breeding sites within the Arctic subspecies. PMID:24130843

  8. Primordial Germ Cell Specification and Migration

    PubMed Central

    Marlow, Florence

    2015-01-01

    Primordial germ cells are the progenitor cells that give rise to the gametes. In some animals, the germline is induced by zygotic transcription factors, whereas in others, primordial germ cell specification occurs via inheritance of maternally provided gene products known as germ plasm. Once specified, the primordial germ cells of some animals must acquire motility and migrate to the gonad in order to survive. In all animals examined, perinuclear structures called germ granules form within germ cells. This review focuses on some of the recent studies, conducted by several groups using diverse systems, from invertebrates to vertebrates, which have provided mechanistic insight into the molecular regulation of germ cell specification and migration. PMID:26918157

  9. Drosophila gene tao-1 encodes proteins with and without a Ste20 kinase domain that affect cytoskeletal architecture and cell migration differently

    PubMed Central

    Pflanz, Ralf; Voigt, Aaron; Yakulov, Toma; Jäckle, Herbert

    2015-01-01

    Tao-1, the single representative of the Sterile 20 kinase subfamily in Drosophila, is best known for destabilizing microtubules at the actin-rich cortex, regulating the cytoskeletal architecture of cells. More recently, Tao-1 was shown to act in the Salvador–Warts–Hippo pathway by phosphorylating Hippo, regulating cell growth as well as cell polarity. Here, we show that tao-1 encodes two proteins, one with the Sterile 20 kinase domain (Tao-L) and one without it (Tao-S), and that they act in an antagonistic manner. Tao-L expression causes lamellipodia-like cell protrusions, whereas Tao-S expression results in filopodia-like structures that make cells stick to the surface they attach to. Ectopic Tao-1 expression in the anterior region of Drosophila embryos results in pole cell formation as normally observed at the posterior end. Tao-S expression causes primordial germ cells (PGCs) to adhere to the inner wall of the gut primordia and prevents proper transepithelial migration to the gonads. Conversely, RNAi knockdowns of Tao-1 cause disordered migration of PGCs out of the gut epithelium, their dispersal within the embryo and cell death. The results reveal a novel function of Tao-1 in cell migration, which is based on antagonistic activities of two proteins encoded by a single gene. PMID:25589578

  10. X-15 #3 and F-104A chase plane landing

    NASA Technical Reports Server (NTRS)

    1960-01-01

    Followed by a Lockheed F-104A Starfighter chase plane, the North American X-15 ship #3 (56-6672) sinks toward touchdown on Rogers Dry Lake following a research flight. In the foreground is green smoke, used to indicate wind direction. The F-104 chase pilot joined up with the X-15 as it glided to the landing. The chase pilot was there to warn the X-15 pilot of any problems and to call out the altitude above the lakebed. F-104 aircraft were also used for X-15 pilot training to simulate the landing characteristics of the rocket-powered airplane, which landed without engine power since the rocket engine had already burned all of its propellant before the landing. The F-104s could simulate the steep descent of the X-15 as it glided to a landing. They did this by extending the landing gear and speed brakes while setting the throttle to idle. The X-15 was a rocket-powered aircraft. The original three aircraft were about 50 ft long with a wingspan of 22 ft. The modified #2 aircraft (X-15A-2 was longer.) They were a missile-shaped vehicles with unusual wedge-shaped vertical tails, thin stubby wings, and unique side fairings that extended along the side of the fuselage. The X-15 weighed about 14,000 lb empty and approximately 34,000 lb at launch. The XLR-99 rocket engine, manufactured by Thiokol Chemical Corp., was pilot controlled and was rated at 57,000 lb of thrust, although there are indications that it actually achieved up to 60,000 lb. North American Aviation built three X-15 aircraft for the program. The X-15 research aircraft was developed to provide in-flight information and data on aerodynamics, structures, flight controls, and the physiological aspects of high-speed, high-altitude flight. A follow-on program used the aircraft as testbeds to carry various scientific experiments beyond the Earth's atmosphere on a repeated basis. For flight in the dense air of the usable atmosphere, the X-15 used conventional aerodynamic controls such as rudder surfaces on the

  11. Initial description of primate-specific cystine-knot Prometheus genes and differential gene expansions of D-dopachrome tautomerase genes

    PubMed Central

    Premzl, Marko

    2015-01-01

    Using eutherian comparative genomic analysis protocol and public genomic sequence data sets, the present work attempted to update and revise two gene data sets. The most comprehensive third party annotation gene data sets of eutherian adenohypophysis cystine-knot genes (128 complete coding sequences), and d-dopachrome tautomerases and macrophage migration inhibitory factor genes (30 complete coding sequences) were annotated. For example, the present study first described primate-specific cystine-knot Prometheus genes, as well as differential gene expansions of D-dopachrome tautomerase genes. Furthermore, new frameworks of future experiments of two eutherian gene data sets were proposed. PMID:25941635

  12. Predator pursuit strategies: how do falcons and hawks chase prey?

    NASA Astrophysics Data System (ADS)

    Kane, Suzanne Amador; Zamani, Marjon; Fulton, Andrew; Rosenthal, Lee

    2014-03-01

    This study reports on experiments on falcons, goshawks and red-tailed hawks wearing miniature videocameras mounted on their backs or heads while pursuing flying or ground-based prey. Videos of hunts recorded by the raptors were analyzed to determine apparent prey positions on their visual fields during pursuits. These video data then were interpreted using computer simulations of pursuit steering laws observed in insects and mammals. A comparison of the empirical and modeling data indicates that falcons use cues due to the apparent motion of prey on the falcon's visual field to track and capture flying prey via a form of motion camouflage. The falcons also were found to maintain their prey's image at visual angles consistent with using their shallow fovea. Results for goshawks and red-tailed hawks were analyzed for a comparative study of how pursuits of ground-based prey by accipeters and buteos differ from those used by falcons chasing flying prey. These results should prove relevant for understanding the coevolution of pursuit and evasion, as well as the development of computer models of predation on flocks,and the integration of sensory and locomotion systems in biomimetic robots.

  13. Conserved pattern of tangential neuronal migration during forebrain development.

    PubMed

    Métin, Christine; Alvarez, Chantal; Moudoux, David; Vitalis, Tania; Pieau, Claude; Molnár, Zoltán

    2007-08-01

    Origin, timing and direction of neuronal migration during brain development determine the distinct organization of adult structures. Changes in these processes might have driven the evolution of the forebrain in vertebrates. GABAergic neurons originate from the ganglionic eminence in mammals and migrate tangentially to the cortex. We are interested in differences and similarities in tangential migration patterns across corresponding telencephalic territories in mammals and reptiles. Using morphological criteria and expression patterns of Darpp-32, Tbr1, Nkx2.1 and Pax6 genes, we show in slice cultures of turtle embryos that early cohorts of tangentially migrating cells are released from the medial ganglionic eminence between stages 14 and 18. Additional populations migrate tangentially from the dorsal subpallium. Large cohorts of tangentially migrating neurons originate ventral to the dorsal ventricular ridge at stage 14 and from the lateral ganglionic eminence from stage 15. Release of GABAergic cells from these regions was investigated further in explant cultures. Tangential migration in turtle proceeds in a fashion similar to mammals. In chimeric slice culture and in ovo graft experiments, the tangentially migrating cells behaved according to the host environment - turtle cells responded to the available cues in mouse slices and mouse cells assumed characteristic migratory routes in turtle brains, indicating highly conserved embryonic signals between these distant species. Our study contributes to the evaluation of theories on the origin of the dorsal cortex and indicates that tangential migration is universal in mammals and sauropsids.

  14. Transcriptomics of environmental acclimatization and survival in wild adult Pacific sockeye salmon (Oncorhynchus nerka) during spawning migration.

    PubMed

    Evans, Tyler G; Hammill, Edd; Kaukinen, Karia; Schulze, Angela D; Patterson, David A; English, Karl K; Curtis, Janelle M R; Miller, Kristina M

    2011-11-01

    Environmental shifts accompanying salmon spawning migrations from ocean feeding grounds to natal freshwater streams can be severe, with the underlying stress often cited as a cause of increased mortality. Here, a salmonid microarray was used to characterize changes in gene expression occurring between ocean and river habitats in gill and liver tissues of wild migrating sockeye salmon (Oncorhynchus nerka Walbaum) returning to spawn in the Fraser River, British Columbia, Canada. Expression profiles indicate that the transcriptome of migrating salmon is strongly affected by shifting abiotic and biotic conditions encountered along migration routes. Conspicuous shifts in gene expression associated with changing salinity, temperature, pathogen exposure and dissolved oxygen indicate that these environmental variables most strongly impact physiology during spawning migrations. Notably, transcriptional changes related to osmoregulation were largely preparatory and occurred well before salmon encountered freshwater. In the river environment, differential expression of genes linked with elevated temperatures indicated that thermal regimes within the Fraser River are approaching tolerance limits for adult salmon. To empirically correlate gene expression with survival, biopsy sampling of gill tissue and transcriptomic profiling were combined with telemetry. Many genes correlated with environmental variables were differentially expressed between premature mortalities and successful migrants. Parametric survival analyses demonstrated a broad-scale transcriptional regulator, cofactor required for Sp1 transcriptional activation (CRSP), to be significantly predictive of survival. As the environmental characteristics of salmon habitats continue to change, establishing how current environmental conditions influence salmon physiology under natural conditions is critical to conserving this ecologically and economically important fish species. © 2011 Blackwell Publishing Ltd.

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

    PubMed

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

    2016-08-01

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

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

    PubMed Central

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

    2016-01-01

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

  17. A Continuous Method for Gene Flow

    PubMed Central

    Palczewski, Michal; Beerli, Peter

    2013-01-01

    Most modern population genetics inference methods are based on the coalescence framework. Methods that allow estimating parameters of structured populations commonly insert migration events into the genealogies. For these methods the calculation of the coalescence probability density of a genealogy requires a product over all time periods between events. Data sets that contain populations with high rates of gene flow among them require an enormous number of calculations. A new method, transition probability-structured coalescence (TPSC), replaces the discrete migration events with probability statements. Because the speed of calculation is independent of the amount of gene flow, this method allows calculating the coalescence densities efficiently. The current implementation of TPSC uses an approximation simplifying the interaction among lineages. Simulations and coverage comparisons of TPSC vs. MIGRATE show that TPSC allows estimation of high migration rates more precisely, but because of the approximation the estimation of low migration rates is biased. The implementation of TPSC into programs that calculate quantities on phylogenetic tree structures is straightforward, so the TPSC approach will facilitate more general inferences in many computer programs. PMID:23666937

  18. Three-Station Three-dimensional Bolus-Chase MR Angiography with Real-time Fluoroscopic Tracking

    PubMed Central

    Johnson, Casey P.; Weavers, Paul T.; Borisch, Eric A.; Grimm, Roger C.; Hulshizer, Thomas C.; LaPlante, Christine C.; Rossman, Phillip J.; Glockner, James F.; Young, Phillip M.

    2014-01-01

    Purpose To determine the feasibility of using real-time fluoroscopic tracking for bolus-chase magnetic resonance (MR) angiography of peripheral vasculature to image three stations from the aortoiliac bifurcation to the pedal arteries. Materials and Methods This prospective study was institutional review board approved and HIPAA compliant. Eight healthy volunteers (three men; mean age, 48 years; age range, 30–81 years) and 13 patients suspected of having peripheral arterial disease (five men; mean age, 67 years; age range, 47–81 years) were enrolled and provided informed consent. All subjects were imaged with the fluoroscopic tracking MR angiographic protocol. Ten patients also underwent a clinical computed tomographic (CT) angiographic runoff examination. Two readers scored the MR angiographic studies for vessel signal intensity and sharpness and presence of confounding artifacts and venous contamination at 35 arterial segments. Mean aggregate scores were assessed. The paired MR angiographic and CT angiographic studies also were scored for visualization of disease, reader confidence, and overall diagnostic quality and were compared by using a Wilcoxon signed rank test. Results Real-time fluoroscopic tracking performed well technically in all studies. Vessel segments were scored good to excellent in all but the following categories: For vessel signal intensity and sharpness, the abdominal aorta, iliac arteries, distal plantar arteries, and plantar arch were scored as fair to good; and for presence of confounding artifacts, the abdominal aorta and iliac arteries were scored as fair. The MR angiograms and CT angiograms did not differ significantly in any scoring category (reader 1: P = .50, .39, and .39; reader 2: P = .41, .61, and .33, respectively). CT scores were substantially better in 20% (four of 20) and 25% (five of 20) of the pooled evaluations for the visualization of disease and overall image quality categories, respectively, versus 5% (one of 20) for MR

  19. The intranuclear PEX domain of MMP involves proliferation, migration, and metastasis of aggressive adenocarcinoma cells.

    PubMed

    Okusha, Yuka; Eguchi, Takanori; Sogawa, Chiharu; Okui, Tatsuo; Nakano, Keisuke; Okamoto, Kuniaki; Kozaki, Ken-Ichi

    2018-05-15

    Members of matrix metalloproteinase (MMP) family promote cancer cell migration, invasion, and metastasis through alteration of the tumor milieu, intracellular signaling pathways, and transcription. We examined gene expression signatures of colon adenocarcinoma cell lines with different metastatic potentials and found that rapidly metastatic cells powerfully expressed genes encoding MMP3 and MMP9. The non-proteolytic PEX isoform and proteolytic isoforms of MMPs were significantly expressed in the metastatic cells in vitro. Knockdown of MMP3 attenuated cancer cell migration and invasion in vitro and lung metastasis in vivo. Profound nuclear localization of MMP3/PEX was found in tumor-stroma marginal area. In contrast, MMP9 was localized in central area of subcutaneous tumors. Overexpression of the PEX isoform of MMP3 promoted proliferation and migration of the rapidly metastatic cells in vitro. Taken together, the non-proteolytic PEX isoform of MMPs locating in cell nuclei involves proliferation, migration, and subsequent metastasis of aggressive adenocarcinoma cells. © 2018 Wiley Periodicals, Inc.

  20. 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

  1. The genetics of monarch butterfly migration and warning colouration.

    PubMed

    Zhan, Shuai; Zhang, Wei; Niitepõld, Kristjan; Hsu, Jeremy; Haeger, Juan Fernández; Zalucki, Myron P; Altizer, Sonia; de Roode, Jacobus C; Reppert, Steven M; Kronforst, Marcus R

    2014-10-16

    The monarch butterfly, Danaus plexippus, is famous for its spectacular annual migration across North America, recent worldwide dispersal, and orange warning colouration. Despite decades of study and broad public interest, we know little about the genetic basis of these hallmark traits. Here we uncover the history of the monarch's evolutionary origin and global dispersal, characterize the genes and pathways associated with migratory behaviour, and identify the discrete genetic basis of warning colouration by sequencing 101 Danaus genomes from around the globe. The results rewrite our understanding of this classic system, showing that D. plexippus was ancestrally migratory and dispersed out of North America to occupy its broad distribution. We find the strongest signatures of selection associated with migration centre on flight muscle function, resulting in greater flight efficiency among migratory monarchs, and that variation in monarch warning colouration is controlled by a single myosin gene not previously implicated in insect pigmentation.

  2. Shikonin Inhibites Migration and Invasion of Thyroid Cancer Cells by Downregulating DNMT1

    PubMed Central

    Zhang, Yue; Sun, Bin; Huang, Zhi

    2018-01-01

    Background Shikonin is a component of Chinese herbal medicine. The aim of this study was to investigate the effects of shikonin on cell migration of papillary thyroid cancer cells of the TPC-1 cell line in vitro and expression levels of the phosphate and tensin homolog deleted on chromosome 10 (PTEN) and DNA methyltransferase 1 (DNMT1) genes. Material/Methods The Cell Counting Kit-8 (CCK-8) assay was performed to evaluate the proliferation of TPC-1 papillary thyroid cancer cells, and the normal thyroid cells, HTori-3, in vitro. A transwell motility assay was used to analyze the migration of TPC-1 cells. Western blot was performed to determine the expression levels of PTEN and DNMT1 genes. A methylation-specific polymerase chain reaction (PCR) (MSP) assay was used to evaluate the methylation of PTEN. Results Following treatment with shikonin, the cell survival rate of TPC-1 cells decreased in a dose-dependent manner; the inhibitory effects on HTori-3 cells were less marked. Shikonin inhibited TPC-1 cell migration and invasion in a dose-dependent manner. The methylation of PTEN was suppressed by shikonin, which also reduced the expression of DNMT1 in a dose-dependent manner, and increased the expression of PTEN. Overexpression of DNMT1 promoted the migration of TPC-1 cells and the methylation of PTEN. Levels of protein expression of PTEN in TPC-1 cells treated with shikonin decreased, and were increased by DNMT1 knockdown. Conclusions Shikonin suppressed the expression of DNMT1, reduced PTEN gene methylation, and increased PTEN protein expression, leading to the inhibition of TPC-1 cell migration. PMID:29389913

  3. Navigational Mechanisms of Migrating Monarch Butterflies

    PubMed Central

    Reppert, Steven M.; Gegear, Robert J.; Merlin, Christine

    2010-01-01

    Recent studies of the iconic fall migration of monarch butterflies have illuminated the mechanisms behind the navigation south, using a time-compensated sun compass. Skylight cues, such as the sun itself and polarized light, are processed through both eyes and likely integrated in the brain’s central complex, the presumed site of the sun compass. Time compensation is provided by circadian clocks that have a distinctive molecular mechanism and that reside in the antennae. Monarchs may also use a magnetic compass, because they possess two cryptochromes that have the molecular capability for light-dependent magnetoreception. Multiple genomic approaches are being utilized to ultimately identify navigation genes. Monarch butterflies are thus emerging as an excellent model organism to study the molecular and neural basis of long-distance migration. PMID:20627420

  4. Multiscale mechanisms of cell migration during development: theory and experiment.

    PubMed

    McLennan, Rebecca; Dyson, Louise; Prather, Katherine W; Morrison, Jason A; Baker, Ruth E; Maini, Philip K; Kulesa, Paul M

    2012-08-01

    Long-distance cell migration is an important feature of embryonic development, adult morphogenesis and cancer, yet the mechanisms that drive subpopulations of cells to distinct targets are poorly understood. Here, we use the embryonic neural crest (NC) in tandem with theoretical studies to evaluate model mechanisms of long-distance cell migration. We find that a simple chemotaxis model is insufficient to explain our experimental data. Instead, model simulations predict that NC cell migration requires leading cells to respond to long-range guidance signals and trailing cells to short-range cues in order to maintain a directed, multicellular stream. Experiments confirm differences in leading versus trailing NC cell subpopulations, manifested in unique cell orientation and gene expression patterns that respond to non-linear tissue growth of the migratory domain. Ablation experiments that delete the trailing NC cell subpopulation reveal that leading NC cells distribute all along the migratory pathway and develop a leading/trailing cellular orientation and gene expression profile that is predicted by model simulations. Transplantation experiments and model predictions that move trailing NC cells to the migratory front, or vice versa, reveal that cells adopt a gene expression profile and cell behaviors corresponding to the new position within the migratory stream. These results offer a mechanistic model in which leading cells create and respond to a cell-induced chemotactic gradient and transmit guidance information to trailing cells that use short-range signals to move in a directional manner.

  5. Higher impact of female than male migration on population structure in large mammals.

    PubMed

    Tiedemann, R; Hardy, O; Vekemans, X; Milinkovitch, M C

    2000-08-01

    We simulated large mammal populations using an individual-based stochastic model under various sex-specific migration schemes and life history parameters from the blue whale and the Asian elephant. Our model predicts that genetic structure at nuclear loci is significantly more influenced by female than by male migration. We identified requisite comigration of mother and offspring during gravidity and lactation as the primary cause of this phenomenon. In addition, our model predicts that the common assumption that geographical patterns of mitochondrial DNA (mtDNA) could be translated into female migration rates (Nmf) will cause biased estimates of maternal gene flow when extensive male migration occurs and male mtDNA haplotypes are included in the analysis.

  6. Directional migration in the Hindu castes: inferences from mitochondrial, autosomal and Y-chromosomal data.

    PubMed

    Wooding, Stephen; Ostler, Christopher; Prasad, B V Ravi; Watkins, W Scott; Sung, Sandy; Bamshad, Mike; Jorde, Lynn B

    2004-08-01

    Genetic, ethnographic, and historical evidence suggests that the Hindu castes have been highly endogamous for several thousand years and that, when movement between castes does occur, it typically consists of females joining castes of higher social status. However, little is known about migration rates in these populations or the extent to which migration occurs between caste groups of low, middle, and high social status. To investigate these aspects of migration, we analyzed the largest collection of genetic markers collected to date in Hindu caste populations. These data included 45 newly typed autosomal short tandem repeat polymorphisms (STRPs), 411 bp of mitochondrial DNA sequence, and 43 Y-chromosomal single-nucleotide polymorphisms that were assayed in more than 200 individuals of known caste status sampled in Andrah Pradesh, in South India. Application of recently developed likelihood-based analyses to this dataset enabled us to obtain genetically derived estimates of intercaste migration rates. STRPs indicated migration rates of 1-2% per generation between high-, middle-, and low-status caste groups. We also found support for the hypothesis that rates of gene flow differ between maternally and paternally inherited genes. Migration rates were substantially higher in maternally than in paternally inherited markers. In addition, while prevailing patterns of migration involved movement between castes of similar rank, paternally inherited markers in the low-status castes were most likely to move into high-status castes. Our findings support earlier evidence that the caste system has been a significant, long-term source of population structuring in South Indian Hindu populations, and that patterns of migration differ between males and females. Copyright 2004 Springer-Verlag

  7. Matrix metalloproteinase-9 plays a role in protecting zebrafish from lethal infection with Listeria monocytogenes by enhancing macrophage migration.

    PubMed

    Shan, Ying; Zhang, Yikai; Zhuo, Xunhui; Li, Xiaoliang; Peng, Jinrong; Fang, Weihuan

    2016-07-01

    Zebrafish could serve as an alternative animal model for pathogenic bacteria in multiple infectious routes. Our previous study showed that immersion infection in zebrafish with Listeria monocytogenes did not cause lethality but induced transient expression of several immune response genes. We used an Affymetrix gene chip to examine the expression profiles of genes of zebrafish immersion-infected with L. monocytogenes. A total of 239 genes were up-regulated and 56 genes down-regulated compared with uninfected fish. Highest expression (>20-fold) was seen with the mmp-9 gene encoding the matrix metalloproteinase-9 (Mmp-9) known to degrade the extracellular matrix proteins. By morpholino knockdown of mmp-9, we found that the morphants showed rapid death with much higher bacterial load after intravenous or intraventricular (brain ventricle) infection with L. monocytogenes. Macrophages in mmp-9-knockdown morphants had significant defect in migrating to the brain cavity upon intraventricular infection. Decreased migration of murine macrophages with knockdown of mmp-9 and cd44 was also seen in transwell inserts with 8-μm pore polycarbonate membrane, as compared with the scrambled RNA. These findings suggest that Mmp-9 is a protective molecule against infection by L. monocytogenes by engaging in migration of zebrafish macrophages to the site of infection via a non-proteolytic role. Further work is required on the molecular mechanisms governing Mmp-9-driven macrophage migration in zebrafish. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. 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

  9. A comparative study of the response to repeated chasing stress in Atlantic salmon (Salmo salar L.) parr and post-smolts.

    PubMed

    Madaro, Angelico; Olsen, Rolf Erik; Kristiansen, Tore S; Ebbesson, Lars O E; Flik, Gert; Gorissen, Marnix

    2016-02-01

    When Atlantic salmon parr migrate from fresh water towards the sea, they undergo extensive morphological, neural, physiological and behavioural changes. Such changes have the potential to affect their responsiveness to various environmental factors that impose stress. In this study we compared the stress responses in parr and post-smolt salmon following exposure to repeated chasing stress (RCS) for three weeks. At the end of this period, all fish were challenged with a novel stressor and sampled before (T0) and after 1h (T1). Parr had a higher growth rate than post-smolts. Plasma cortisol declined in the RCS groups within the first week suggesting a rapid habituation/desensitisation of the endocrine stress axis. As a result of the desensitised HPI axis, RCS groups showed a reduced cortisol response when exposed to the novel stressor. In preoptic area (POA) crf mRNA levels were higher in all post-smolt groups compared to parr. 11βhsd2 decreased by RCS and by the novel stressor in post-smolt controls (T1), whereas no effect of either stress was seen in parr. The grs were low in all groups except for parr controls. In pituitary, parr controls had higher levels of crf1r mRNA than the other parr and post-smolt groups, whilst pomcb was higher in post-smolt control groups. Overall, 11βhsd2 transcript abundance in parr was lower than post-smolt groups; after the novel stressor pomcs, grs and mr were up-regulated in parr control (T1). In summary, we highlight differences in the central stress response between parr and post-smolt salmon following RCS. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Thermal Stress Limit Rafting Migration of Seahorses: Prediction Based on Physiological and Behavioral Responses to Thermal Stress

    NASA Astrophysics Data System (ADS)

    Qin, G.; Li, C.; Lin, Q.

    2017-12-01

    Marine fish species escape from harmful environment by migration. Seahorses, with upright posture and low mobility, could migrate from unfavorable environment by rafting with their prehensile tail. The present study was designed to examine the tolerance of lined seahorse Hippocampus erectus to thermal stress and evaluate the effects of temperature on seahorse migration. The results figured that seahorses' tolerance to thermal stress was time dependent. Acute thermal stress (30°C) increased breathing rate and HSP genes expression significantly, but didn't affect seahorse feeding behavior. Chronic thermal treatment lead to persistent high expression of HSP genes, higher breathing rate, and decreasing feeding, and final higher mortality, suggesting that seahorse cannot adapt to thermal stress by acclimation. No significant negative effects were found in seahorse reproduction in response to chronic thermal stress. Given that seahorses make much slower migration by rafting on sea surface compared to other fishes, we suggest that thermal stress might limit seahorse migration range. and the influence might be magnified by global warming in future.

  11. Navigational mechanisms of migrating monarch butterflies.

    PubMed

    Reppert, Steven M; Gegear, Robert J; Merlin, Christine

    2010-09-01

    Recent studies of the iconic fall migration of monarch butterflies have illuminated the mechanisms behind their southward navigation while using a time-compensated sun compass. Skylight cues, such as the sun itself and polarized light, are processed through both eyes and are probably integrated in the brain's central complex, the presumed site of the sun compass. Time compensation is provided by circadian clocks that have a distinctive molecular mechanism and that reside in the antennae. Monarchs might also use a magnetic compass because they possess two cryptochromes that have the molecular capability for light-dependent magnetoreception. Multiple genomic approaches are now being used with the aim of identifying navigation genes. Monarch butterflies are thus emerging as an excellent model organism in which to study the molecular and neural basis of long-distance migration. Copyright 2010 Elsevier Ltd. All rights reserved.

  12. The giant mottled eel, Anguilla marmorata, uses blue-shifted rod photoreceptors during upstream migration.

    PubMed

    Wang, Feng-Yu; Fu, Wen-Chun; Wang, I-Li; Yan, Hong Young; Wang, Tzi-Yuan

    2014-01-01

    Catadromous fishes migrate between ocean and freshwater during particular phases of their life cycle. The dramatic environmental changes shape their physiological features, e.g. visual sensitivity, olfactory ability, and salinity tolerance. Anguilla marmorata, a catadromous eel, migrates upstream on dark nights, following the lunar cycle. Such behavior may be correlated with ontogenetic changes in sensory systems. Therefore, this study was designed to identify changes in spectral sensitivity and opsin gene expression of A. marmorata during upstream migration. Microspectrophotometry analysis revealed that the tropical eel possesses a duplex retina with rod and cone photoreceptors. The λmax of rod cells are 493, 489, and 489 nm in glass, yellow, and wild eels, while those of cone cells are 508, and 517 nm in yellow, and wild eels, respectively. Unlike European and American eels, Asian eels exhibited a blue-shifted pattern of rod photoreceptors during upstream migration. Quantitative gene expression analyses of four cloned opsin genes (Rh1f, Rh1d, Rh2, and SWS2) revealed that Rh1f expression is dominant at all three stages, while Rh1d is expressed only in older yellow eel. Furthermore, sequence comparison and protein modeling studies implied that a blue shift in Rh1d opsin may be induced by two known (N83, S292) and four putative (S124, V189, V286, I290) tuning sites adjacent to the retinal binding sites. Finally, expression of blue-shifted Rh1d opsin resulted in a spectral shift in rod photoreceptors. Our observations indicate that the giant mottled eel is color-blind, and its blue-shifted scotopic vision may influence its upstream migration behavior and habitat choice.

  13. Factors controlling sperm migration through the oviduct revealed by gene-modified mouse models

    PubMed Central

    Fujihara, Yoshitaka; Miyata, Haruhiko; Ikawa, Masahito

    2018-01-01

    Mammalian fertilization is comprised of many steps including sperm survival in the uterus, sperm migration in the female reproductive tract, physiological and morphological changes to the spermatozoa, and sperm-egg interaction in the oviduct. In vitro studies have revealed essential factors for these fertilization steps for over half a century. However, the molecular mechanism of fertilization has recently been revised by the emergence of genetically modified animals. Here, we focus on essential factors for sperm fertilizing ability and describe recent advances in our knowledge of the mechanisms of mammalian fertilization, especially of sperm migration from the uterus into the oviduct. PMID:29353867

  14. GammeV and GammeV-CHASE

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

    Wester, W.; /Fermilab

    2011-11-01

    Physics beyond the Standard Model might include Weakly Interacting Slim Particles (WISPs) that address questions such as what is the nature of dark matter or even shed insight into the underlying nature of dark energy. WISPs are a general class of particles that include axions, axion-like particles, hidden sector photons, milli-charged particles, chameleons, etc. The GammeV (Gamma to milli-eV) experiment originated in 2007 in order to test a positive anomalous axion-like particle interpretation of the PVLAS experiment which was not evident in subsequent data. The experiment was also motivated as it was realized that the milli-eV scale appears naturally inmore » a see-saw between the electroweak and Planck scales, neutrino mass differences, the dark energy density, and the possible mass for certain dark matter candidates. GammeV was first to exclude both a scalar and pseudoscalar axion-like particle interpretation of the anomalous PVLAS result setting a limit of around 3.1 x 10{sup -7} GeV{sup -1} on the coupling to photons for low mass axion-like particles. It has also been found that the parameter space of a variety of other WISP candidates is both largely unexplored and is accessible by modest experiments employing lasers and possibly accelerator magnets. GammeV data has also been used to set limits on possible hidden sector photons. Further work by the GammeV team has focused on a reconfiguration of the apparatus to be sensitive to possible chameleon particles. Chameleons are scalar (or pseudoscalar) particles that couple to the stress energy tensor in a potential such that their properties depend on their environment. In particular, a chameleon acquires an effective mass which increases with local matter density, {rho}. For a certain class of such potentials, the chameleon field has properties that might explain dark energy. GammeV set the first limits on the coupling of chameleons to photons. A dedicated follow-up experiment, GammeV-CHASE, (CHameleon

  15. 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.

  16. MiR-661 inhibits glioma cell proliferation, migration and invasion by targeting hTERT

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

    Li, Zhen, E-mail: lizhen7111@163.com; Liu, Yun-hui; Diao, Hong-yu

    In this study, we analyzed the functional role of miR-661 in glioma cell proliferation, migration and invasion. We found that overexpression of miR-661 obviously suppressed the proliferation, migration and invasion of glioma cells. MiRNA target prediction algorithms implied that hTERT is a candidate target gene for miR-661. A fluorescent reporter assay confirmed that miR-661 could lead to hTERT gene silencing by recognizing and specifically binding to the predicted site of the hTERT mRNA 3′ untranslated region (3′UTR) specifically. Furthermore, hTERT knockdown significantly decreased the growth and viability of glioma cells. These results indicate that miR-661 can inhibit glioma cell proliferation,more » migration and invasion by targeting hTERT. - Highlights: • MiR-661 was downregulated in glioma tissues and functional as a tumor suppressor. • MiR-661 modulates cell proliferation, invasion and migration of glioma cells. • MiR-661 directly target hTERT in glioma cells. • MiR-661 inhibits glioma cell tumorgenesis by targeting hTERT.« less

  17. Estradiol induces endothelial cell migration and proliferation through estrogen receptor-enhanced RhoA/ROCK pathway.

    PubMed

    Oviedo, Pilar J; Sobrino, Agua; Laguna-Fernandez, Andrés; Novella, Susana; Tarín, Juan J; García-Pérez, Miguel-Angel; Sanchís, Juan; Cano, Antonio; Hermenegildo, Carlos

    2011-03-30

    Migration and proliferation of endothelial cells are involved in re-endothelialization and angiogenesis, two important cardiovascular processes that are increased in response to estrogens. RhoA, a small GTPase which controls multiple cellular processes, is involved in the control of cell migration and proliferation. Our aim was to study the role of RhoA on estradiol-induced migration and proliferation and its dependence on estrogen receptors activity. Human umbilical vein endothelial cells were stimulated with estradiol, in the presence or absence of ICI 182780 (estrogen receptors antagonist) and Y-27632 (Rho kinase inhibitor). Estradiol increased Rho GEF-1 gene expression and RhoA (gene and protein expression and activity) in an estrogen receptor-dependent manner. Cell migration, stress fiber formation and cell proliferation were increased in response to estradiol and were also dependent on the estrogen receptors and RhoA activation. Estradiol decreased p27 levels, and significantly raised the expression of cyclins and CDK. These effects were counteracted by the use of either ICI 182780 or Y-27632. In conclusion, estradiol enhances the RhoA/ROCK pathway and increases cell cycle-related protein expression by acting through estrogen receptors. This results in an enhanced migration and proliferation of endothelial cells. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  18. The evolution of immunity in relation to colonization and migration.

    PubMed

    O'Connor, Emily A; Cornwallis, Charlie K; Hasselquist, Dennis; Nilsson, Jan-Åke; Westerdahl, Helena

    2018-05-01

    Colonization and migration have a crucial effect on patterns of biodiversity, with disease predicted to play an important role in these processes. However, evidence of the effect of pathogens on broad patterns of colonization and migration is limited. Here, using phylogenetic analyses of 1,311 species of Afro-Palaearctic songbirds, we show that colonization events from regions of high (sub-Saharan Africa) to low (the Palaearctic) pathogen diversity were up to 20 times more frequent than the reverse, and that migration has evolved 3 times more frequently from African- as opposed to Palaearctic-resident species. We also found that resident species that colonized the Palaearctic from Africa, as well as African species that evolved long-distance migration to breed in the Palaearctic, have reduced diversity of key immune genes associated with pathogen recognition (major histocompatibility complex class I). These results suggest that changes in the pathogen community that occur during colonization and migration shape the evolution of the immune system, potentially by adjusting the trade-off between the benefits of extensive pathogen recognition and the costs of immunopathology that result from high major histocompatibility complex class I diversity.

  19. Adaptation, migration or extirpation: climate change outcomes for tree populations

    PubMed Central

    Aitken, Sally N; Yeaman, Sam; Holliday, Jason A; Wang, Tongli; Curtis-McLane, Sierra

    2008-01-01

    Abstract Species distribution models predict a wholesale redistribution of trees in the next century, yet migratory responses necessary to spatially track climates far exceed maximum post-glacial rates. The extent to which populations will adapt will depend upon phenotypic variation, strength of selection, fecundity, interspecific competition, and biotic interactions. Populations of temperate and boreal trees show moderate to strong clines in phenology and growth along temperature gradients, indicating substantial local adaptation. Traits involved in local adaptation appear to be the product of small effects of many genes, and the resulting genotypic redundancy combined with high fecundity may facilitate rapid local adaptation despite high gene flow. Gene flow with preadapted alleles from warmer climates may promote adaptation and migration at the leading edge, while populations at the rear will likely face extirpation. Widespread species with large populations and high fecundity are likely to persist and adapt, but will likely suffer adaptational lag for a few generations. As all tree species will be suffering lags, interspecific competition may weaken, facilitating persistence under suboptimal conditions. Species with small populations, fragmented ranges, low fecundity, or suffering declines due to introduced insects or diseases should be candidates for facilitated migration. PMID:25567494

  20. Hubble Chases a Small Stellar Galaxy in the Hunting Dog

    NASA Image and Video Library

    2017-12-08

    On a clear evening in April of 1789, the renowned astronomer William Herschel continued his unrelenting survey of the night sky, hunting for new cosmic objects — and found cause to celebrate! He spotted this bright spiral galaxy, named NGC 4707, lurking in the constellation of Canes Venatici or The Hunting Dog. NGC 4707 lies roughly 22 million light-years from Earth. Over two centuries later, the NASA/ESA Hubble Space Telescope is able to "chase down" and view the same galaxy in far greater detail than Herschel could, allowing us to appreciate the intricacies and characteristics of NGC 4707 as never before. This striking image comprises observations from Hubble’s Advanced Camera for Surveys (ACS), one of a handful of high-resolution instruments currently aboard the space telescope. Herschel himself reportedly described NGC 4707 as a “small, stellar” galaxy; while it is classified as a spiral (type Sm), its overall shape, center, and spiral arms are very loose and undefined, and its central bulge is either very small or non-existent. It instead appears as a rough sprinkling of stars and bright flashes of blue on a dark canvas. The blue smudges seen across the frame highlight regions of recent or ongoing star formation, with newborn stars glowing in bright, intense shades of cyan and turquoise. Image credit: ESA/Hubble & NASA

  1. 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

  2. Optimization of interneuron function by direct coupling of cell migration and axonal targeting.

    PubMed

    Lim, Lynette; Pakan, Janelle M P; Selten, Martijn M; Marques-Smith, André; Llorca, Alfredo; Bae, Sung Eun; Rochefort, Nathalie L; Marín, Oscar

    2018-06-18

    Neural circuit assembly relies on the precise synchronization of developmental processes, such as cell migration and axon targeting, but the cell-autonomous mechanisms coordinating these events remain largely unknown. Here we found that different classes of interneurons use distinct routes of migration to reach the embryonic cerebral cortex. Somatostatin-expressing interneurons that migrate through the marginal zone develop into Martinotti cells, one of the most distinctive classes of cortical interneurons. For these cells, migration through the marginal zone is linked to the development of their characteristic layer 1 axonal arborization. Altering the normal migratory route of Martinotti cells by conditional deletion of Mafb-a gene that is preferentially expressed by these cells-cell-autonomously disrupts axonal development and impairs the function of these cells in vivo. Our results suggest that migration and axon targeting programs are coupled to optimize the assembly of inhibitory circuits in the cerebral cortex.

  3. Spatial distribution and cellular composition of adult brain proliferative zones in the teleost, Gymnotus omarorum

    PubMed Central

    Olivera-Pasilio, Valentina; Peterson, Daniel A.; Castelló, María E.

    2014-01-01

    Proliferation of stem/progenitor cells during development provides for the generation of mature cell types in the CNS. While adult brain proliferation is highly restricted in the mammals, it is widespread in teleosts. The extent of adult neural proliferation in the weakly electric fish, Gymnotus omarorum has not yet been described. To address this, we used double thymidine analog pulse-chase labeling of proliferating cells to identify brain proliferation zones, characterize their cellular composition, and analyze the fate of newborn cells in adult G. omarorum. Short thymidine analog chase periods revealed the ubiquitous distribution of adult brain proliferation, similar to other teleosts, particularly Apteronotus leptorhynchus. Proliferating cells were abundant at the ventricular-subventricular lining of the ventricular-cisternal system, adjacent to the telencephalic subpallium, the diencephalic preoptic region and hypothalamus, and the mesencephalic tectum opticum and torus semicircularis. Extraventricular proliferation zones, located distant from the ventricular-cisternal system surface, were found in all divisions of the rombencephalic cerebellum. We also report a new adult proliferation zone at the caudal-lateral border of the electrosensory lateral line lobe. All proliferation zones showed a heterogeneous cellular composition. The use of short (24 h) and long (30 day) chase periods revealed abundant fast cycling cells (potentially intermediate amplifiers), sparse slow cycling (potentially stem) cells, cells that appear to have entered a quiescent state, and cells that might correspond to migrating newborn neural cells. Their abundance and migration distance differed among proliferation zones: greater numbers and longer range and/or pace of migrating cells were associated with subpallial and cerebellar proliferation zones. PMID:25249943

  4. American white pelicans breeding in the northern plains: productivity, behavior, movements, and migration

    USGS Publications Warehouse

    Sovada, Marsha A.; Pietz, Pamela J.; Woodward, Robert O.; Bartos, Alisa J.; Buhl, Deborah A.; Assenmacher, Michael J.

    2013-01-01

    satellite transmitters that incorporated a Global Positioning System (GPS) foraged primarily in shallow areas of lakes and semipermanent wetlands. These areas coincide with typical habitats of crayfish, salamanders, and rough fish, which were also the foods most commonly seen in pelican regurgitates at the colonies. Several satellite-tracked pelicans made frequent round trips between their breeding colony and foraging areas, most likely to provision their chicks. Typical distances travelled to foraging sites ranged from 30 kilometers to over 90 kilometers. Return times to the colonies (about 1300 and 1500 CST at Bitter Lake and Chase Lake, respectively) supported the colony difference documented at video-monitored nests. Of 28 pelicans tagged with GPS satellite transmitters in 2005–6, 26 survived the first summer and migrated south during fall. Nineteen of these returned to the breeding region (defined as north of the latitude of South Dakota’s southern border) in at least 1 year during 2006–9; collectively, they returned to the breeding region 33 times. Very few pelicans returned to the colony where they had been tagged; many did not breed and concentrated their activities at wetland complexes in South Dakota and North Dakota, but few tagged pelicans temporally overlapped at specific sites. During 2005–9, tagged pelicans collectively made 56 migratory trips south in the fall. Most wintered in Mexico, near the gulf coast and elsewhere; others wintered in Texas, Louisiana, Mississippi, and Florida. Individuals typically returned to the same general areas each winter. Individuals rarely followed the same migratory path on their way south and north, but they often roughly repeated southerly or northerly routes among years. Ensuring a sustainable population of American white pelicans requires identification and mitigation of known threats. The work described herein has identified WNV and severe weather as important factors that potentially limit reproductive success and

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

    PubMed

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

    2011-04-01

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

  6. Evaluation of diesel fleet emissions and control policies from plume chasing measurements of on-road vehicles

    NASA Astrophysics Data System (ADS)

    Lau, Chui Fong; Rakowska, Agata; Townsend, Thomas; Brimblecombe, Peter; Chan, Tat Leung; Yam, Yat Shing; Močnik, Griša; Ning, Zhi

    2015-12-01

    Vehicle emissions are an important source of urban air pollution. Diesel fuelled vehicles, although constituting a relatively small fraction of fleet population in many cities, are significant contributors to the emission inventory due to their often long mileage for goods and public transport. Recent classification of diesel exhaust as carcinogenic by the World Health Organization also raises attention to more stringent control of diesel emissions to protect public health. Although various mandatory and voluntary based emission control measures have been implemented in Hong Kong, there have been few investigations to evaluate if the fleet emission characteristics have met desired emission reduction objectives and if adoption of an Inspection/Maintenance (I/M) programme has been effective in achieving these objectives. The limitations are partially due to the lack of cost-effective approaches for the large scale characterisation of fleet based emissions to assess the effectiveness of control measures and policy. This study has used a plume chasing method to collect a large amount of on-road vehicle emission data of Hong Kong highways and a detailed analysis was carried out to provide a quantitative evaluation of the emission characteristics in terms of the role of high and super-emitters in total emission reduction, impact of after-treatment on the multi-pollutants reduction strategy and the trend of NO2 emissions with newer emission standards. The study revealed that not all the high-emitters are from those vehicles of older Euro emission standards. Meanwhile, there is clear evidence that high-emitters for one pollutant may not be a high-emitter for another pollutant. Multi-pollutant control strategy needs to be considered in the enactment of the emission control policy which requires more comprehensive retrofitting technological solutions and matching I/M programme to ensure the proper maintenance of fleets. The plume chasing approach used in this study also

  7. Divergence hitchhiking and the spread of genomic isolation during ecological speciation-with-gene-flow

    PubMed Central

    Via, Sara

    2012-01-01

    In allopatric populations, geographical separation simultaneously isolates the entire genome, allowing genetic divergence to accumulate virtually anywhere in the genome. In sympatric populations, however, the strong divergent selection required to overcome migration produces a genetic mosaic of divergent and non-divergent genomic regions. In some recent genome scans, each divergent genomic region has been interpreted as an independent incidence of migration/selection balance, such that the reduction of gene exchange is restricted to a few kilobases around each divergently selected gene. I propose an alternative mechanism, ‘divergence hitchhiking’ (DH), in which divergent selection can reduce gene exchange for several megabases around a gene under strong divergent selection. Not all genes/markers within a DH region are divergently selected, yet the entire region is protected to some degree from gene exchange, permitting genetic divergence from mechanisms other than divergent selection to accumulate secondarily. After contrasting DH and multilocus migration/selection balance (MM/SB), I outline a model in which genomic isolation at a given genomic location is jointly determined by DH and genome-wide effects of the progressive reduction in realized migration, then illustrate DH using data from several pairs of incipient species in the wild. PMID:22201174

  8. SDN-1/syndecan regulates growth factor signaling in distal tip cell migrations in C. elegans.

    PubMed

    Schwabiuk, Megan; Coudiere, Ludivine; Merz, David C

    2009-10-01

    Mutations in the sdn-1/syndecan gene act as genetic enhancers of the ventral-to-dorsal distal tip cell (DTC) migration defects caused by a weak allele of the netrin receptor gene unc-5. The sdn-1(ev697) allele was identified in a genetic screen for enhancers of unc-5 DTC migration defects, and carried a nonsense mutation predicted to truncate the SDN-1 protein prior to the transmembrane domain. The enhancement of unc-5 caused by an sdn-1 mutation was rescued by expression of wild-type sdn-1 in the hypodermis or nervous system rather than the DTCs, indicating a cell non-autonomous function of sdn-1. The enhancement was also partially reversed by mutations in the egl-17/FGF or egl-20/Wnt genes, suggesting that sdn-1 affects UNC-5 function through a mis-regulation of signaling in growth factor pathways. egl-20 reporter constructs exhibited increased and mis-localized EGL-20 distribution in sdn-1 mutants compared to wild-type animals. Finally, using loss of function mutations, we show that egl-17/Fgf and egl-20/Wnt are partially redundant in regulating the migration pattern of the posterior DTC, as double mutants exhibit significant frequencies of defects in migration phases along both the anteroposterior and dorsoventral axes. Together these results suggest that SDN-1 affects UNC-5 function by regulating the proper extracellular distribution of growth factors.

  9. Y chromosome evidence for Anglo-Saxon mass migration.

    PubMed

    Weale, Michael E; Weiss, Deborah A; Jager, Rolf F; Bradman, Neil; Thomas, Mark G

    2002-07-01

    British history contains several periods of major cultural change. It remains controversial as to how much these periods coincided with substantial immigration from continental Europe, even for those that occurred most recently. In this study, we examine genetic data for evidence of male immigration at particular times into Central England and North Wales. To do this, we used 12 biallelic polymorphisms and six microsatellite markers to define high-resolution Y chromosome haplotypes in a sample of 313 males from seven towns located along an east-west transect from East Anglia to North Wales. The Central English towns were genetically very similar, whereas the two North Welsh towns differed significantly both from each other and from the Central English towns. When we compared our data with an additional 177 samples collected in Friesland and Norway, we found that the Central English and Frisian samples were statistically indistinguishable. Using novel population genetic models that incorporate both mass migration and continuous gene flow, we conclude that these striking patterns are best explained by a substantial migration of Anglo-Saxon Y chromosomes into Central England (contributing 50%-100% to the gene pool at that time) but not into North Wales.

  10. GSK3 and Polo-like kinase regulate ADAM13 function during cranial neural crest cell migration

    PubMed Central

    Abbruzzese, Genevieve; Cousin, Hélène; Salicioni, Ana Maria; Alfandari, Dominique

    2014-01-01

    ADAMs are cell surface metalloproteases that control multiple biological processes by cleaving signaling and adhesion molecules. ADAM13 controls cranial neural crest (CNC) cell migration both by cleaving cadherin-11 to release a promigratory extracellular fragment and by controlling expression of multiple genes via its cytoplasmic domain. The latter activity is regulated by γ-secretase cleavage and the translocation of the cytoplasmic domain into the nucleus. One of the genes regulated by ADAM13, the protease calpain8, is essential for CNC migration. Although the nuclear function of ADAM13 is evolutionarily conserved, it is unclear whether the transcriptional regulation is also performed by other ADAMs and how this process may be regulated. We show that ADAM13 function to promote CNC migration is regulated by two phosphorylation events involving GSK3 and Polo-like kinase (Plk). We further show that inhibition of either kinase blocks CNC migration and that the respective phosphomimetic forms of ADAM13 can rescue these inhibitions. However, these phosphorylations are not required for ADAM13 proteolysis of its substrates, γ-secretase cleavage, or nuclear translocation of its cytoplasmic domain. Of significance, migration of the CNC can be restored in the absence of Plk phosphorylation by expression of calpain-8a, pointing to impaired nuclear activity of ADAM13. PMID:25298404

  11. Visualizing spatial population structure with estimated effective migration surfaces

    PubMed Central

    Petkova, Desislava; Novembre, John; Stephens, Matthew

    2015-01-01

    Genetic data often exhibit patterns broadly consistent with “isolation by distance” – a phenomenon where genetic similarity decays with geographic distance. In a heterogeneous habitat this may occur more quickly in some regions than others: for example, barriers to gene flow can accelerate differentiation between neighboring groups. We use the concept of “effective migration” to model the relationship between genetics and geography: in this paradigm, effective migration is low in regions where genetic similarity decays quickly. We present a method to visualize variation in effective migration across the habitat from geographically indexed genetic data. Our approach uses a population genetic model to relate effective migration rates to expected genetic dissimilarities. We illustrate its potential and limitations using simulations and data from elephant, human and A. thaliana populations. The resulting visualizations highlight important spatial features of population structure that are difficult to discern using existing methods for summarizing genetic variation. PMID:26642242

  12. WASP family proteins and formins compete in pseudopod- and bleb-based migration

    PubMed Central

    2018-01-01

    Actin pseudopods induced by SCAR/WAVE drive normal migration and chemotaxis in eukaryotic cells. Cells can also migrate using blebs, in which the edge is driven forward by hydrostatic pressure instead of actin. In Dictyostelium discoideum, loss of SCAR is compensated by WASP moving to the leading edge to generate morphologically normal pseudopods. Here we use an inducible double knockout to show that cells lacking both SCAR and WASP are unable to grow, make pseudopods or, unexpectedly, migrate using blebs. Remarkably, amounts and dynamics of actin polymerization are normal. Pseudopods are replaced in double SCAR/WASP mutants by aberrant filopods, induced by the formin dDia2. Further disruption of the gene for dDia2 restores cells’ ability to initiate blebs and thus migrate, though pseudopods are still lost. Triple knockout cells still contain near-normal F-actin levels. This work shows that SCAR, WASP, and dDia2 compete for actin. Loss of SCAR and WASP causes excessive dDia2 activity, maintaining F-actin levels but blocking pseudopod and bleb formation and migration. PMID:29191847

  13. DAN (NBL1) promotes collective neural crest migration by restraining uncontrolled invasion.

    PubMed

    McLennan, Rebecca; Bailey, Caleb M; Schumacher, Linus J; Teddy, Jessica M; Morrison, Jason A; Kasemeier-Kulesa, Jennifer C; Wolfe, Lauren A; Gogol, Madeline M; Baker, Ruth E; Maini, Philip K; Kulesa, Paul M

    2017-10-02

    Neural crest cells are both highly migratory and significant to vertebrate organogenesis. However, the signals that regulate neural crest cell migration remain unclear. In this study, we test the function of differential screening-selected gene aberrant in neuroblastoma (DAN), a bone morphogenetic protein (BMP) antagonist we detected by analysis of the chick cranial mesoderm. Our analysis shows that, before neural crest cell exit from the hindbrain, DAN is expressed in the mesoderm, and then it becomes absent along cell migratory pathways. Cranial neural crest and metastatic melanoma cells avoid DAN protein stripes in vitro. Addition of DAN reduces the speed of migrating cells in vivo and in vitro, respectively. In vivo loss of function of DAN results in enhanced neural crest cell migration by increasing speed and directionality. Computer model simulations support the hypothesis that DAN restrains cell migration by regulating cell speed. Collectively, our results identify DAN as a novel factor that inhibits uncontrolled neural crest and metastatic melanoma invasion and promotes collective migration in a manner consistent with the inhibition of BMP signaling. © 2017 McLennan et al.

  14. DAN (NBL1) promotes collective neural crest migration by restraining uncontrolled invasion

    PubMed Central

    McLennan, Rebecca; Bailey, Caleb M.; Schumacher, Linus J.; Teddy, Jessica M.; Morrison, Jason A.; Kasemeier-Kulesa, Jennifer C.; Wolfe, Lauren A.; Gogol, Madeline M.; Baker, Ruth E.; Maini, Philip K.

    2017-01-01

    Neural crest cells are both highly migratory and significant to vertebrate organogenesis. However, the signals that regulate neural crest cell migration remain unclear. In this study, we test the function of differential screening-selected gene aberrant in neuroblastoma (DAN), a bone morphogenetic protein (BMP) antagonist we detected by analysis of the chick cranial mesoderm. Our analysis shows that, before neural crest cell exit from the hindbrain, DAN is expressed in the mesoderm, and then it becomes absent along cell migratory pathways. Cranial neural crest and metastatic melanoma cells avoid DAN protein stripes in vitro. Addition of DAN reduces the speed of migrating cells in vivo and in vitro, respectively. In vivo loss of function of DAN results in enhanced neural crest cell migration by increasing speed and directionality. Computer model simulations support the hypothesis that DAN restrains cell migration by regulating cell speed. Collectively, our results identify DAN as a novel factor that inhibits uncontrolled neural crest and metastatic melanoma invasion and promotes collective migration in a manner consistent with the inhibition of BMP signaling. PMID:28811280

  15. MIIP, a cytoskeleton regulator that blocks cell migration and invasion, delays mitosis, and suppresses tumorogenesis.

    PubMed

    Wang, Yingmei; Wen, Jing; Zhang, Wei

    2011-02-01

    The migration and invasion inhibitory protein (MIIP) was initially discovered in a yeast two-hybrid screen for proteins that interact and inhibit the migration and invasion-promoting protein insulin-like growth factor binding protein 2 (IGFBP2). Recent studies have shown that MIIP not only modulates IGFBP2 but also regulates microtubule by binding to and inhibiting HDAC6, a class 2 histone deacetylase that deacetylates α-tubulin, heat-shock protein 90 (HSP90), and cortactin. In addition, MIIP also regulates the mitosis checkpoint, another microtubule-associated process. The location of the MIIP gene in chromosomal region 1p36, a commonly deleted region in a broad spectrum of human cancers, and the observation that MIIP attenuates tumorigenesis in a mouse model suggest that it functions as a tumor-suppressor gene. This review summarizes the recent progress in characterizing this novel protein, which regulates cell migration and mitosis, two processes that rely on the highly coordinated dynamics of the microtubule and cytoskeleton systems.

  16. 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

  17. 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

  18. Migration strategy affects avian influenza dynamics in mallards (Anas platyrhynchos).

    USGS Publications Warehouse

    Takekawa, John Y.; Hill, Nichola J.; Ackerman, Joshua T.; Herring, Garth; Hobson, Keith; Cardona, Carol J.; Runstadler, Jonathan; Boyce, Walter M.

    2012-01-01

    Studies of pathogen transmission typically overlook that wildlife hosts can include both migrant and resident populations when attempting to model circulation. Through the application of stable isotopes in flight feathers, we estimated the migration strategy of mallards (Anas platyrhynchos) occurring on California wintering grounds. Our study demonstrates that mallards- a principal host of avian influenza virus (AIV) in nature, contribute differently to virus gene flow depending on migration strategy. No difference in AIV prevalence was detected between resident (9.6%), intermediate-distance (9.6%) and long-distance migrants (7.4%). Viral diversity among the three groups was also comparable, possibly owing to viral pool mixing when birds converge at wetlands during winter. However, migrants and residents contributed differently to the virus gene pool at wintering wetlands. Migrants introduced virus from northern breeding grounds (Alaska and the NW Pacific Rim) into the wintering population, facilitating gene flow at continental scales, but circulation of imported virus appeared to be limited. In contrast, resident mallards acted as AIV reservoirs facilitating year-round circulation of limited subtypes (i.e. H5N2) at lower latitudes. This study supports a model of virus exchange in temperate regions driven by the convergence of wild birds with separate geographic origins and exposure histories.

  19. Calcium-containing scaffolds induce bone regeneration by regulating mesenchymal stem cell differentiation and migration.

    PubMed

    Aquino-Martínez, Rubén; Angelo, Alcira P; Pujol, Francesc Ventura

    2017-11-16

    Osteoinduction and subsequent bone formation rely on efficient mesenchymal stem cell (MSC) recruitment. It is also known that migration is induced by gradients of growth factors and cytokines. Degradation of Ca 2+ -containing biomaterials mimics the bone remodeling compartment producing a localized calcium-rich osteoinductive microenvironment. The aim of our study was to determine the effect of calcium sulfate (CaSO 4 ) on MSC migration. In addition, to evaluate the influence of CaSO 4 on MSC differentiation and the potential molecular mechanisms involved. A circular calvarial bone defect (5 mm diameter) was created in the parietal bone of 35 Balb-C mice. We prepared and implanted a cell-free agarose/gelatin scaffold alone or in combination with different CaSO 4 concentrations into the bone defects. After 7 weeks, we determined the new bone regenerated by micro-CT and histological analysis. In vitro, we evaluated the CaSO 4 effects on MSC migration by both wound healing and agarose spot assays. Osteoblastic gene expression after BMP-2 and CaSO 4 treatment was also evaluated by qPCR. CaSO 4 increased MSC migration and bone formation in a concentration-dependent manner. Micro-CT analysis showed that the addition of CaSO 4 significantly enhanced bone regeneration compared to the scaffold alone. The histological evaluation confirmed an increased number of endogenous cells recruited into the cell-free CaSO 4 -containing scaffolds. Furthermore, MSC migration in vitro and active AKT levels were attenuated when CaSO 4 and BMP-2 were in combination. Addition of LY294002 and Wortmannin abrogated the CaSO 4 effects on MSC migration. Specific CaSO 4 concentrations induce bone regeneration of calvarial defects in part by acting on the host's undifferentiated MSCs and promoting their migration. Progenitor cell recruitment is followed by a gradual increment in osteoblast gene expression. Moreover, CaSO 4 regulates BMP-2-induced MSC migration by differentially activating the PI3

  20. Quantitative Measurement of GPCR Endocytosis via Pulse-Chase Covalent Labeling

    PubMed Central

    Fujishiro, Mitsuhiro; Okamura, Tomohisa; Fujio, Keishi; Okazaki, Hiroaki; Nomura, Seitaro; Takeda, Norifumi; Harada, Mutsuo; Toko, Haruhiro; Takimoto, Eiki; Akazawa, Hiroshi; Morita, Hiroyuki; Suzuki, Jun-ichi; Yamazaki, Tsutomu; Yamamoto, Kazuhiko; Komuro, Issei; Yanagisawa, Masashi

    2015-01-01

    G protein-coupled receptors (GPCRs) play a critical role in many physiological systems and represent one of the largest families of signal-transducing receptors. The number of GPCRs at the cell surface regulates cellular responsiveness to their cognate ligands, and the number of GPCRs, in turn, is dynamically controlled by receptor endocytosis. Recent studies have demonstrated that GPCR endocytosis, in addition to affecting receptor desensitization and resensitization, contributes to acute G protein-mediated signaling. Thus, endocytic GPCR behavior has a significant impact on various aspects of physiology. In this study, we developed a novel GPCR internalization assay to facilitate characterization of endocytic GPCR behavior. We genetically engineered chimeric GPCRs by fusing HaloTag (a catalytically inactive derivative of a bacterial hydrolase) to the N-terminal end of the receptor (HT-GPCR). HaloTag has the ability to form a stable covalent bond with synthetic HaloTag ligands that contain fluorophores or a high-affinity handle (such as biotin) and the HaloTag reactive linker. We selectively labeled HT-GPCRs at the cell surface with a HaloTag PEG ligand, and this pulse-chase covalent labeling allowed us to directly monitor the relative number of internalized GPCRs after agonist stimulation. Because the endocytic activities of GPCR ligands are not necessarily correlated with their agonistic activities, applying this novel methodology to orphan GPCRs, or even to already characterized GPCRs, will increase the likelihood of identifying currently unknown ligands that have been missed by conventional pharmacological assays. PMID:26020647

  1. 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

  2. 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.

  3. 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.

  4. MACF1 Controls Migration and Positioning of Cortical GABAergic Interneurons in Mice.

    PubMed

    Ka, Minhan; Moffat, Jeffrey J; Kim, Woo-Yang

    2017-12-01

    GABAergic interneurons develop in the ganglionic eminence in the ventral telencephalon and tangentially migrate into the cortical plate during development. However, key molecules controlling interneuron migration remain poorly identified. Here, we show that microtubule-actin cross-linking factor 1 (MACF1) regulates GABAergic interneuron migration and positioning in the developing mouse brain. To investigate the role of MACF1 in developing interneurons, we conditionally deleted the MACF1 gene in mouse interneuron progenitors and their progeny using Dlx5/6-Cre-IRES-EGFP and Nkx2.1-Cre drivers. We found that MACF1 deletion results in a marked reduction and defective positioning of interneurons in the mouse cerebral cortex and hippocampus, suggesting abnormal interneuron migration. Indeed, the speed and mode of interneuron migration were abnormal in the MACF1-mutant brain, compared with controls. Additionally, MACF1-deleted interneurons showed a significant reduction in the length of their leading processes and dendrites in the mouse brain. Finally, loss of MACF1 decreased microtubule stability in cortical interneurons. Our findings suggest that MACF1 plays a critical role in cortical interneuron migration and positioning in the developing mouse brain. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. RNase L Suppresses Androgen Receptor Signaling, Cell Migration and Matrix Metalloproteinase Activity in Prostate Cancer Cells

    PubMed Central

    Dayal, Shubham; Zhou, Jun; Manivannan, Praveen; Siddiqui, Mohammad Adnan; Ahmad, Omaima Farid; Clark, Matthew; Awadia, Sahezeel; Garcia-Mata, Rafael; Shemshedini, Lirim; Malathi, Krishnamurthy

    2017-01-01

    The interferon antiviral pathways and prostate cancer genetics converge on a regulated endoribonuclease, RNase L. Positional cloning and linkage studies mapped Hereditary Prostate Cancer 1 (HPC1) to RNASEL. To date, there is no correlation of viral infections with prostate cancer, suggesting that RNase L may play additional roles in tumor suppression. Here, we demonstrate a role of RNase L as a suppressor of androgen receptor (AR) signaling, cell migration and matrix metalloproteinase activity. Using RNase L mutants, we show that its nucleolytic activity is dispensable for both AR signaling and migration. The most prevalent HPC1-associated mutations in RNase L, R462Q and E265X, enhance AR signaling and cell migration. RNase L negatively regulates cell migration and attachment on various extracellular matrices. We demonstrate that RNase L knockdown cells promote increased cell surface expression of integrin β1 which activates Focal Adhesion Kinase-Sarcoma (FAK-Src) pathway and Ras-related C3 botulinum toxin substrate 1-guanosine triphosphatase (Rac1-GTPase) activity to increase cell migration. Activity of matrix metalloproteinase (MMP)-2 and -9 is significantly increased in cells where RNase L levels are ablated. We show that mutations in RNase L found in HPC patients may promote prostate cancer by increasing expression of AR-responsive genes and cell motility and identify novel roles of RNase L as a prostate cancer susceptibility gene. PMID:28257035

  6. Human migration activities drive the fluctuation of ARGs: Case study of landfills in Nanjing, eastern China.

    PubMed

    Sun, Mingming; Ye, Mao; Schwab, Arthur P; Li, Xu; Wan, Jinzhong; Wei, Zhong; Wu, Jun; Friman, Ville-Petri; Liu, Kuan; Tian, Da; Liu, Manqiang; Li, Huixin; Hu, Feng; Jiang, Xin

    2016-09-05

    Landfills are perfect sites to study the effect of human migration on fluctuation of antibiotic resistance genes (ARGs) as they are the final destination of municipal waste. For example, large-scale human migration during the holidays is often accompanied by changes in waste dumping having potential effects on ARG abundance. Three landfills were selected to examine fluctuation in the abundance of fifteen ARGs and Intl1 genes for 14 months in Nanjing, eastern China. Mass human migration, the amount of dumped waste and temperature exerted the most significant effects on bimonthly fluctuations of ARG levels in landfill sites. As a middle-sized cosmopolitan city in China, millions of college students and workers migrate during holidays, contributing to the dramatic increases in waste production and fluctuation in ARG abundances. In line with this, mass migration explained most of the variation in waste dumping. The waste dumping also affected the bioaccessibility of mixed-compound pollutants that further positively impacted the level of ARGs. The influence of various bioaccessible compounds on ARG abundance followed the order: antibiotics>nutrients>metals>organic pollutants. Concentrations of bioaccessible compounds were more strongly correlated with ARG levels compared to total compound concentrations. Improved waste classification and management strategies could thus help to decrease the amount of bioaccessible pollutants leading to more effective control for urban ARG dissemination. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Purification and differentiation of human adipose-derived stem cells by membrane filtration and membrane migration methods

    PubMed Central

    Lin, Hong Reng; Heish, Chao-Wen; Liu, Cheng-Hui; Muduli, Saradaprasan; Li, Hsing-Fen; Higuchi, Akon; Kumar, S. Suresh; Alarfaj, Abdullah A.; Munusamy, Murugan A.; Hsu, Shih-Tien; Chen, Da-Chung; Benelli, Giovanni; Murugan, Kadarkarai; Cheng, Nai-Chen; Wang, Han-Chow; Wu, Gwo-Jang

    2017-01-01

    Human adipose-derived stem cells (hADSCs) are easily isolated from fat tissue without ethical concerns, but differ in purity, pluripotency, differentiation ability, and stem cell marker expression, depending on the isolation method. We isolated hADSCs from a primary fat tissue solution using: (1) conventional culture, (2) a membrane filtration method, (3) a membrane migration method where the primary cell solution was permeated through membranes, adhered hADSCs were cultured, and hADSCs migrated out from the membranes. Expression of mesenchymal stem cell markers and pluripotency genes, and osteogenic differentiation were compared for hADSCs isolated by different methods using nylon mesh filter membranes with pore sizes ranging from 11 to 80 μm. hADSCs isolated by the membrane migration method had the highest MSC surface marker expression and efficient differentiation into osteoblasts. Osteogenic differentiation ability of hADSCs and MSC surface marker expression were correlated, but osteogenic differentiation ability and pluripotent gene expression were not. PMID:28071738

  8. Insight into the Migration Routes of Plutella xylostella in China Using mtCOI and ISSR Markers

    PubMed Central

    Tian, Lixia; Xu, Baoyun; Xie, Wen; Wang, Shaoli; Zhang, Youjun; Wang, Xiangjing; Wu, Qingjun

    2015-01-01

    The larvae of the diamondback moth, Plutella xylostella, cause major economic losses to cruciferous crops, including cabbage, which is an important vegetable crop in China. In this study, we used the mitochondrial COI gene and 11 ISSR markers to characterize the genetic structure and seasonal migration routes of 23 P. xylostella populations in China. Both the mitochondrial and nuclear markers revealed high haplotype diversity and gene flow among the populations, although some degree of genetic isolation was evident between the populations of Hainan Island and other sampling sites. The dominant haplotypes, LX1 and LX2, differed significantly from all other haplotypes both in terms of the number of individuals with those haplotypes and their distributions. Haplotypes that were shared among populations revealed that P. xylostella migrates from the lower reaches of the Yangtze River to northern China and then to northeastern China. Our results also revealed another potential migration route for P. xylostella, i.e., from southwestern China to both northwestern and southern China. PMID:26098353

  9. Identification of Novel Pro-Migratory, Cancer-Associated Genes Using Quantitative, Microscopy-Based Screening

    PubMed Central

    Naffar-Abu-Amara, Suha; Shay, Tal; Galun, Meirav; Cohen, Naomi; Isakoff, Steven J.; Kam, Zvi; Geiger, Benjamin

    2008-01-01

    Background Cell migration is a highly complex process, regulated by multiple genes, signaling pathways and external stimuli. To discover genes or pharmacological agents that can modulate the migratory activity of cells, screening strategies that enable the monitoring of diverse migratory parameters in a large number of samples are necessary. Methodology In the present study, we describe the development of a quantitative, high-throughput cell migration assay, based on a modified phagokinetic tracks (PKT) procedure, and apply it for identifying novel pro-migratory genes in a cancer-related gene library. In brief, cells are seeded on fibronectin-coated 96-well plates, covered with a monolayer of carboxylated latex beads. Motile cells clear the beads, located along their migratory paths, forming tracks that are visualized using an automated, transmitted-light screening microscope. The tracks are then segmented and characterized by multi-parametric, morphometric analysis, resolving a variety of morphological and kinetic features. Conclusions In this screen we identified 4 novel genes derived from breast carcinoma related cDNA library, whose over-expression induces major alteration in the migration of the stationary MCF7 cells. This approach can serve for high throughput screening for novel ways to modulate cellular migration in pathological states such as tumor metastasis and invasion. PMID:18213366

  10. Analyzing bat migration

    USGS Publications Warehouse

    Cryan, Paul M.; Diehl, Robert H.

    2009-01-01

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

  11. Connectivity in a pond system influences migration and genetic structure in threespine stickleback.

    PubMed

    Seymour, Mathew; Räsänen, Katja; Holderegger, Rolf; Kristjánsson, Bjarni K

    2013-03-01

    Neutral genetic structure of natural populations is primarily influenced by migration (the movement of individuals and, subsequently, their genes) and drift (the statistical chance of losing genetic diversity over time). Migration between populations is influenced by several factors, including individual behavior, physical barriers, and environmental heterogeneity among populations. However, drift is expected to be stronger in populations with low immigration rate and small effective population size. With the technological advancement in geological information systems and spatial analysis tools, landscape genetics now allows the development of realistic migration models and increased insight to important processes influencing diversity of natural populations. In this study, we investigated the relationship between landscape connectivity and genetic distance of threespine stickleback (Gasterosteus aculeatus) inhabiting a pond complex in Belgjarskógur, Northeast Iceland. We used two landscape genetic approaches (i.e., least-cost-path and isolation-by-resistance) and asked whether gene flow, as measured by genetic distance, was more strongly associated with Euclidean distance (isolation-by-distance) or with landscape connectivity provided by areas prone to flooding (as indicated by Carex sp. cover)? We found substantial genetic structure across the study area, with pairwise genetic distances among populations (DPS) ranging from 0.118 to 0.488. Genetic distances among populations were more strongly correlated with least-cost-path and isolation-by-resistance than with Euclidean distance, whereas the relative contribution of isolation-by-resistance and Euclidian distance could not be disentangled. These results indicate that migration among stickleback populations occurs via periodically flooded areas. Overall, this study highlights the importance of transient landscape elements influencing migration and genetic structure of populations at small spatial scales.

  12. EDTA conditioning of dentine promotes adhesion, migration and differentiation of dental pulp stem cells.

    PubMed

    Galler, K M; Widbiller, M; Buchalla, W; Eidt, A; Hiller, K-A; Hoffer, P C; Schmalz, G

    2016-06-01

    To evaluate the effect of dentine conditioning on migration, adhesion and differentiation of dental pulp stem cells. Dentine discs prepared from extracted human molars were pre-treated with EDTA (10%), NaOCl (5.25%) or H2 O. Migration of dental pulp stem cells towards pre-treated dentine after 24 and 48 h was assessed in a modified Boyden chamber assay. Cell adhesion was evaluated indirectly by measuring cell viability. Expression of mineralization-associated genes (COL1A1, ALP, BSP, DSPP, RUNX2) in cells cultured on pre-treated dentine for 7 days was determined by RT-qPCR. Nonparametric statistical analysis was performed for cell migration and cell viability data to compare different groups and time-points (Mann-Whitney U-test, α = 0.05). Treatment of dentine with H2 O or EDTA allowed for cell attachment, which was prohibited by NaOCl with statistical significance (P = 0.000). Furthermore, EDTA conditioning induced cell migration towards dentine. The expression of mineralization-associated genes was increased in dental pulp cells cultured on dentine after EDTA conditioning compared to H2 O-pre-treated dentine discs. EDTA conditioning of dentine promoted the adhesion, migration and differentiation of dental pulp stem cells towards or onto dentine. A pre-treatment with EDTA as the final step of an irrigation protocol for regenerative endodontic procedures has the potential to act favourably on new tissue formation within the root canal. © 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  13. Small heat shock proteins are necessary for heart migration and laterality determination in zebrafish

    PubMed Central

    Lahvic, Jamie L.; Ji, Yongchang; Marin, Paloma; Zuflacht, Jonah P.; Springel, Mark W.; Wosen, Jonathan E.; Davis, Leigh; Hutson, Lara D.; Amack, Jeffrey D.; Marvin, Martha J.

    2013-01-01

    Small heat shock proteins (sHsps) regulate cellular functions not only under stress, but also during normal development, when they are expressed in organ-specific patterns. Here we demonstrate that two small heat shock proteins expressed in embryonic zebrafish heart, hspb7 and hspb12, have roles in the development of left-right asymmetry. In zebrafish, laterality is determined by the motility of cilia in Kupffer’s vesicle (KV), where hspb7 is expressed; knockdown of hspb7 causes laterality defects by disrupting the motility of these cilia. In embryos with reduced hspb7, the axonemes of KV cilia have a 9+0 structure, while control embyros have a predominately 9+2 structure. Reduction of either hspb7 or hspb12 alters the expression pattern of genes that propagate the signals that establish left-right asymmetry: the nodal-related gene southpaw (spaw) in the lateral plate mesoderm, and its downstream targets pitx2, lefty1 and lefty2. Partial depletion of hspb7 causes concordant heart, brain and visceral laterality defects, indicating that loss of KV cilia motility leads causes coordinated but randomized laterality. Reducing hspb12 leads to similar alterations in the expression of downstream laterality genes, but at a lower penetrance. Simultaneous reduction of hspb7 and hspb12 randomizes heart, brain and visceral laterality, suggesting that these two genes have partially redundant functions in the establishment of left-right asymmetry. In addition, both hspb7 and hspb12 are expressed in the precardiac mesoderm and in the yolk syncytial layer, which supports the migration and fusion of mesodermal cardiac precursors. In embryos in which the reduction of hspb7 or hspb12 was limited to the yolk, migration defects predominated, suggesting that the yolk expression of these genes rather than heart expression is responsible for the migration defects. PMID:24140541

  14. adrift, a novel bnl-induced Drosophila gene, required for tracheal pathfinding into the CNS.

    PubMed

    Englund, C; Uv, A E; Cantera, R; Mathies, L D; Krasnow, M A; Samakovlis, C

    1999-04-01

    Neurons and glial cells provide guidance cues for migrating neurons. We show here that migrating epithelial cells also contact specific neurons and glia during their pathfinding, and we describe the first gene required in the process. In wild-type Drosophila embryos, the ganglionic tracheal branch navigates a remarkably complex path along specific neural and glial substrata, switching substrata five times before reaching its ultimate target in the CNS. In adrift mutants, ganglionic branches migrate normally along the intersegmental nerve, but sporadically fail to switch to the segmental nerve and enter the CNS; they wind up meandering along the ventral epidermis instead. adrift encodes a novel nuclear protein with an evolutionarily conserved motif. The gene is required in the trachea and is expressed in the leading cells of migrating ganglionic branches where it is induced by the branchless FGF pathway. We propose that Adrift regulates expression of tracheal genes required for pathfinding on the segmental nerve, and FGF induction of adrift expression in migrating tracheal cells promotes the switch from the intersegmental to the segmental nerve.

  15. Live Imaging of Glial Cell Migration in the Drosophila Eye Imaginal Disc

    PubMed Central

    Cafferty, Patrick; Xie, Xiaojun; Browne, Kristen; Auld, Vanessa J.

    2009-01-01

    Glial cells of both vertebrate and invertebrate organisms must migrate to final target regions in order to ensheath and support associated neurons. While recent progress has been made to describe the live migration of glial cells in the developing pupal wing (1), studies of Drosophila glial cell migration have typically involved the examination of fixed tissue. Live microscopic analysis of motile cells offers the ability to examine cellular behavior throughout the migratory process, including determining the rate of and changes in direction of growth. Paired with use of genetic tools, live imaging can be used to determine more precise roles for specific genes in the process of development. Previous work by Silies et al. (2) has described the migration of glia originating from the optic stalk, a structure that connects the developing eye and brain, into the eye imaginal disc in fixed tissue. Here we outline a protocol for examining the live migration of glial cells into the Drosophila eye imaginal disc. We take advantage of a Drosophila line that expresses GFP in developing glia to follow glial cell progression in wild type and in mutant animals. PMID:19590493

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

    PubMed

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

    2018-06-16

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

  17. 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

  18. National Program for Inspection of Non-Federal Dams. Chase Pond Dam (NH 00255), NHWRB Number 253.02, Merrimack River Basin, Wilmot, New Hampshire. Phase I Inspection Report.

    DTIC Science & Technology

    1980-03-01

    STANDAROS-1963-A L ~.°.. o...... 1....MERRIMACK RIVER BASIN -!. WILMOT , NEW HAMPSHIRE ’,- CHASE POND DAM NH 00255 NHWRB NO. 253.02 r PHASE I...Continue on fewsorsp side #0 .o..oemay and Ientify by black Muthot) - DAMS, NSPECTION, PAM S’AFETY, Merrimack River Basin. * Wilmot , New Hampshire...MERRIMACK RIVER BASIN R WILMOT , NEW HAMPSHIRE - - PHASE I INSPECTION REPORT NATIONAL DAM INSPECTION PROGRAM :: : I

  19. ΔNp63 versatilely regulates a broad NF-κB gene program and promotes squamous epithelial proliferation, migration and inflammation

    PubMed Central

    Yang, Xinping; Lu, Hai; Yan, Bin; Romano, Rose-Anne; Bian, Yansong; Friedman, Jay; Duggal, Praveen; Allen, Clint; Chuang, Ryan; Ehsanian, Reza; Si, Han; Sinha, Satrajit; Van Waes, Carter; Chen, Zhong

    2012-01-01

    Head and neck squamous cell carcinoma (HNSCC) and many epithelial malignancies exhibit increased proliferation, invasion and inflammation, concomitant with aberrant nuclear activation of TP53 and NF-κB family members ΔNp63, c-REL and RELA. However, the mechanisms of crosstalk by which these transcription factors coordinate gene expression and the malignant phenotype remain elusive. Here we demonstrate thatΔNp63 regulates a cohort of genes involved in cell growth, survival, adhesion and inflammation, which substantially overlaps with the NF-κB transcriptome. ΔNp63 with c-REL and/or RELA are recruited to form novel binding complexes on p63 or NF-κB/REL sites of multiple target gene promoters. Overexpressed ΔNp63- or TNF-α-induced NF-κB and inflammatory cytokine IL-8 reporter activation depended upon RELA/c-REL regulatory binding sites. Depletion of RELA or ΔNp63 by siRNA significantly inhibited NF-κB-specific, or TNF-α-induced IL-8 reporter activation. ΔNp63 siRNA significantly inhibited proliferation, survival, and migration by HNSCC cells in vitro. Consistent with the above, an increase in nuclear ΔNp63 accompanied by increased proliferation (Ki67), and adhesion (β4 integrin) markers, and induced inflammatory cell infiltration was observed throughout HNSCC specimens, when compared to the basilar pattern of protein expression and minimal inflammation seen in non-malignant mucosa. Further, overexpression of ΔNp63α in squamous epithelia in transgenic mice leads to increased suprabasilar c-REL, Ki-67, and cytokine expression, together with epidermal hyperplasia and diffuse inflammation, similar to HNSCC. Our study reveals ΔNp63 as a master transcription factor that in coordination with NF-κB/RELs, orchestrates a broad gene program promoting epidermal hyperplasia, inflammation, and the malignant phenotype of HNSCC. PMID:21576089

  20. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-09-13

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

  3. Post-translational modification of Rauscher leukemia virus precursor polyproteins encoded by the gag gene.

    PubMed Central

    Schultz, A M; Rabin, E H; Oroszlan, S

    1979-01-01

    Post-translational modifications of retrovirus gag gene-encoded polyproteins include proteolytic cleavage, phosphorylation, and glycosylation. To study the sequence of these events, we labeled JLS-V9 cells chronically infected with Rauscher murine leukemia virus in pulse-chase experiments with the radioactive precursors [35S]methionine, [14C]mannose, [3H]glucosamine, and [32P]phosphate. Newly synthesized gag polyproteins which incorporated label, and the modified products derived from them, were identified by immunoprecipitation of cell lysates with anti-p30 rabbit serum, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Pulse-chase experiments were carried out in the presence as well as in the absence of tunicamycin, an inhibitor of glycosylation. Among the three major polyproteins synthesized in the absence of tunicamycin, two were found to be glycosylated but not phosphorylated. These were designated gPr80gag and gP94gag. Both shared identical [35S]methionine peptides with Pr65gag and p30. Of the two nonglycosylated precursors, Pr65gag and Pr75gag, only Pr65gag was found to be detectably phosphorylated, and Pr75gag could be readily identified only when glycosylation was inhibited. On the basis of these results, a scheme for the post-translational modification of gag polyproteins is proposed. According to this scheme the gag gene-encoded polyproteins are processed from a common precursor, Pr75gag, by two divergent pathways: one leading through the intermediate Pr65gag to internal virion components via cleavage and phosphorylation and the other via tunicamycin-sensitive mannosylation to the intermediate gPr80gag, which is further glycosylated to yield cell surface polyprotein gP94gag. Images PMID:480454

  4. 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

  5. Focal adhesion kinase is involved in mechanosensing during fibroblast migration

    NASA Technical Reports Server (NTRS)

    Wang, H. B.; Dembo, M.; Hanks, S. K.; Wang, Y.

    2001-01-01

    Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase localized at focal adhesions and is believed to mediate adhesion-stimulated effects. Although ablation of FAK impairs cell movement, it is not clear whether FAK might be involved in the guidance of cell migration, a role consistent with its putative regulatory function. We have transfected FAK-null fibroblasts with FAK gene under the control of the tetracycline repression system. Cells were cultured on flexible polyacrylamide substrates for the detection of traction forces and the application of mechanical stimulation. Compared with control cells expressing wild-type FAK, FAK-null cells showed a decrease in migration speed and directional persistence. In addition, whereas FAK-expressing cells responded to exerted forces by reorienting their movements and forming prominent focal adhesions, FAK-null cells failed to show such responses. Furthermore, FAK-null cells showed impaired responses to decreases in substrate flexibility, which causes control cells to generate weaker traction forces and migrate away from soft substrates. Cells expressing Y397F FAK, which cannot be phosphorylated at a key tyrosine site, showed similar defects in migration pattern and force-induced reorientation as did FAK-null cells. However, other aspects of F397-FAK cells, including the responses to substrate flexibility and the amplification of focal adhesions upon mechanical stimulation, were similar to that of control cells. Our results suggest that FAK plays an important role in the response of migrating cells to mechanical input. In addition, phosphorylation at Tyr-397 is required for some, but not all, of the functions of FAK in cell migration.

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

    PubMed

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

    1997-09-05

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

  7. Migration without migraines

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

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

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

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

    PubMed Central

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

    2006-01-01

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

  9. Avian influenza H5N1 viral and bird migration networks in Asia

    USGS Publications Warehouse

    Tian, Huaivu; Zhou, Sen; Dong, Lu; Van Boeckel, Thomas P.; Cui, Yujun; Newman, Scott H.; Takekawa, John Y.; Prosser, Diann J.; Xiao, Xiangming; Wu, Yarong; Cazelles, Bernard; Huang, Shanqian; Yang, Ruifu; Grenfell, Bryan T.; Xu, Bing

    2015-01-01

    The spatial spread of the highly pathogenic avian influenza virus H5N1 and its long-term persistence in Asia have resulted in avian influenza panzootics and enormous economic losses in the poultry sector. However, an understanding of the regional long-distance transmission and seasonal patterns of the virus is still lacking. In this study, we present a phylogeographic approach to reconstruct the viral migration network. We show that within each wild fowl migratory flyway, the timing of H5N1 outbreaks and viral migrations are closely associated, but little viral transmission was observed between the flyways. The bird migration network is shown to better reflect the observed viral gene sequence data than other networks and contributes to seasonal H5N1 epidemics in local regions and its large-scale transmission along flyways. These findings have potentially far-reaching consequences, improving our understanding of how bird migration drives the periodic reemergence of H5N1 in Asia.

  10. Avian influenza H5N1 viral and bird migration networks in Asia

    PubMed Central

    Tian, Huaiyu; Zhou, Sen; Dong, Lu; Van Boeckel, Thomas P.; Cui, Yujun; Newman, Scott H.; Takekawa, John Y.; Prosser, Diann J.; Xiao, Xiangming; Wu, Yarong; Cazelles, Bernard; Huang, Shanqian; Yang, Ruifu; Grenfell, Bryan T.; Xu, Bing

    2015-01-01

    The spatial spread of the highly pathogenic avian influenza virus H5N1 and its long-term persistence in Asia have resulted in avian influenza panzootics and enormous economic losses in the poultry sector. However, an understanding of the regional long-distance transmission and seasonal patterns of the virus is still lacking. In this study, we present a phylogeographic approach to reconstruct the viral migration network. We show that within each wild fowl migratory flyway, the timing of H5N1 outbreaks and viral migrations are closely associated, but little viral transmission was observed between the flyways. The bird migration network is shown to better reflect the observed viral gene sequence data than other networks and contributes to seasonal H5N1 epidemics in local regions and its large-scale transmission along flyways. These findings have potentially far-reaching consequences, improving our understanding of how bird migration drives the periodic reemergence of H5N1 in Asia. PMID:25535385

  11. Functional characterization of the turkey macrophage migration inhibitory factor.

    PubMed

    Park, Myeongseon; Kim, Sungwon; Fetterer, Raymond H; Dalloul, Rami A

    2016-08-01

    Macrophage migration inhibitory factor (MIF) is a soluble protein that inhibits the random migration of macrophages and plays a pivotal immunoregulatory function in innate and adaptive immunity. The aim of this study was to clone the turkey MIF (TkMIF) gene, express the active protein, and characterize its basic function. The full-length TkMIF gene was amplified from total RNA extracted from turkey spleen, followed by cloning into a prokaryotic (pET11a) expression vector. Sequence analysis revealed that TkMIF consists of 115 amino acids with 12.5 kDa molecular weight. Multiple sequence alignment revealed 100%, 65%, 95% and 92% identity with chicken, duck, eagle and zebra finch MIFs, respectively. Recombinant TkMIF (rTkMIF) was expressed in Escherichia coli and purified through HPLC and endotoxin removal. SDS-PAGE analysis revealed an approximately 13.5 kDa of rTkMIF monomer containing T7 tag in soluble form. Western blot analysis showed that anti-chicken MIF (ChMIF) polyclonal antisera detected a monomer form of TkMIF at approximately 13.5 kDa size. Further functional analysis revealed that rTkMIF inhibits migration of both mononuclear cells and splenocytes in a dose-dependent manner, but was abolished by the addition of anti-ChMIF polyclonal antisera. qRT-PCR analysis revealed elevated transcripts of pro-inflammatory cytokines by rTkMIF in LPS-stimulated monocytes. rTkMIF also led to increased levels of IFN-γ and IL-17F transcripts in Con A-activated splenocytes, while IL-10 and IL-13 transcripts were decreased. Overall, the sequences of both the turkey and chicken MIF have high similarity and comparable biological functions with respect to migration inhibitory activities of macrophages and enhancement of pro-inflammatory cytokine expression, suggesting that turkey and chicken MIFs would be biologically cross-reactive. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. MicroRNA-29 regulates myocardial microvascular endothelial cells proliferation and migration in association with IGF1 in type 2 diabetes

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

    Li, Zhenjie; Jiang, Runxia; Yue, Qingcai

    Background: In our study, we investigated the expression and function of microRNA-29 in myocardial microvascular endothelial cells (MMEVC) in type 2 diabetic Goto-Kakizaki (GK) rats. Methods: MiR-29 gene expression was compared, by qRT-PCR between diabetic GK rat MMEVC and non-diabetic Wistar rat MMEVC. MiR-29 was downregulated in GK MMEVC and its effect on angiogenic properties of proliferation and migration was examined. Potential downstream target gene of miR-29, insulin growth factor 1 (IGF1), was assessed by dual-luciferase reporter assay, qRT-PCR and western blot in GK MMEVC. IGF1 was also downregulated by siRNA in miR-29-downregulated GK MMEVC. Its effect on miR-29-associated angiogenicmore » regulation on MMEVC proliferation and migration was further investigated. Results: MiR-29 was substantially upregulated in GK MMEVC than in Wistar MMEVC. Transfection of synthetic miR-29 inhibitor successfully downregulate endogenous miR-29 in GK MMEVC, and subsequently promoted angiogenesis by increasing cell proliferation and migration. IGF1 was confirmed to be downstream target gene of miR-29 in GK MMEVC, with its gene and protein expressions both upregulated in miR-29-downregualted GK MMEVC. Conversely, siRNA-mediated IGF1 downregulation reversed the pro-angiogenic effect of miR-29 downregulation in GK MMEVC, as it decreased cell proliferation and migration. Conclusion: Our study suggests that miR-29 downregulation, through its inverse regulation on downstream target of IGF1 gene, is a pro-angiogenic factor in MMEVC in type 2 diabetic rats.« less

  13. 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.

  14. 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…

  15. Mechanisms of Bacterial (Serratia marcescens) Attachment to, Migration along, and Killing of Fungal Hyphae

    PubMed Central

    Hover, Tal; Maya, Tal; Ron, Sapir; Sandovsky, Hani; Shadkchan, Yana; Kijner, Nitzan; Mitiagin, Yulia; Fichtman, Boris; Harel, Amnon; Shanks, Robert M. Q.; Bruna, Roberto E.; García-Véscovi, Eleonora

    2016-01-01

    We have found a remarkable capacity for the ubiquitous Gram-negative rod bacterium Serratia marcescens to migrate along and kill the mycelia of zygomycete molds. This migration was restricted to zygomycete molds and several basidiomycete species. No migration was seen on any molds of the phylum Ascomycota. S. marcescens migration did not require fungal viability or surrounding growth medium, as bacteria migrated along aerial hyphae as well. S. marcescens did not exhibit growth tropism toward zygomycete mycelium. Bacterial migration along hyphae proceeded only when the hyphae grew into the bacterial colony. S. marcescens cells initially migrated along the hyphae, forming attached microcolonies that grew and coalesced to generate a biofilm that covered and killed the mycelium. Flagellum-defective strains of S. marcescens were able to migrate along zygomycete hyphae, although they were significantly slower than the wild-type strain and were delayed in fungal killing. Bacterial attachment to the mycelium does not necessitate type 1 fimbrial adhesion, since mutants defective in this adhesin migrated equally well as or faster than the wild-type strain. Killing does not depend on the secretion of S. marcescens chitinases, as mutants in which all three chitinase genes were deleted retained wild-type killing abilities. A better understanding of the mechanisms by which S. marcescens binds to, spreads on, and kills fungal hyphae might serve as an excellent model system for such interactions in general; fungal killing could be employed in agricultural fungal biocontrol. PMID:26896140

  16. The histone demethylase KDM3A, and its downstream target MCAM, promote Ewing Sarcoma cell migration and metastasis

    PubMed Central

    Sechler, Marybeth; Parrish, Janet K.; Birks, Diane K.; Jedlicka, Paul

    2017-01-01

    Ewing Sarcoma is the second most common solid pediatric malignant neoplasm of bone and soft tissue. Driven by EWS/Ets, or rarely variant, oncogenic fusions, Ewing Sarcoma is a biologically and clinically aggressive disease with a high propensity for metastasis. However, the mechanisms underpinning Ewing Sarcoma metastasis are currently not well understood. In the present study, we identify and characterize a novel metastasis-promotional pathway in Ewing Sarcoma, involving the histone demethylase KDM3A, previously identified by our laboratory as a new cancer-promoting gene in this disease. Using global gene expression profiling, we show that KDM3A positively regulates genes and pathways implicated in cell migration and metastasis, and demonstrate, using functional assays, that KDM3A promotes migration in vitro and experimental, post-intravasation, metastasis in vivo. We further identify the Melanoma Cell Adhesion Molecule (MCAM) as a novel KDM3A target gene in Ewing Sarcoma, and an important effector of KDM3A pro-metastatic action. Specifically, we demonstrate that MCAM depletion, like KDM3A depletion, inhibits cell migration in vitro and experimental metastasis in vivo, and that MCAM partially rescues impaired migration due to KDM3A knock-down. Mechanistically, we show that KDM3A regulates MCAM expression both through a direct mechanism, involving modulation of H3K9 methylation at the MCAM promoter, and an indirect mechanism, via the Ets1 transcription factor. Lastly, we identify an association between high MCAM levels in patient tumors and poor survival, in two different Ewing Sarcoma clinical cohorts. Taken together, our studies uncover a new metastasis-promoting pathway in Ewing Sarcoma, with therapeutically targetable components. PMID:28319067

  17. MicroRNA-137 Affects Proliferation and Migration of Placenta Trophoblast Cells in Preeclampsia by Targeting ERRα.

    PubMed

    Lu, Tan-Min; Lu, Wei; Zhao, Long-Jun

    2016-06-06

    To investigate the effects of microRNA-137 (miRNA-137) in proliferation and migration of placenta trophoblast cells of preeclampsia and the targeting gene of miRNA-137. A total of 134 cases of puerperants were divided into normal pregnancy (n = 50), mild preeclampsia (n = 38), and severe preeclampsia groups (n = 46). MiRNA-137, estrogen-related receptor α (ERRα), and wingless INT (WNT)11 messenger RNAs (mRNAs) were measured in placental tissue and trophoblast cells after transfection, and ERRα protein in placental tissues was detected by immunohistochemistry. The target genes of miRNA-137, trophoblast cell proliferation, migration, and invasion abilities were detected. Both ERRα and WNT11 proteins in the trophoblast cells were measured after transfection. Relative expressions of miRNA-137 were higher, and positive expression rates and relative expression levels of ERRα protein were lower in mild and severe preeclampsia and early- and late-onset preeclampsia than in normal pregnancy group (all P < .05). MiRNA-137 in the placental tissues was negatively correlated with ERRα protein (P < .05). Luciferase reporter gene assay analysis showed that ERRα was a direct target gene of miRNA-137. Absorbance values, relative scratch-covered areas, cell membrane permeable rate, ERRα, and WNT11 mRNA and protein relative expressions were significantly lower, while cells at G1/G0 phase were higher in miRNA-137 mimic group than those in the blank, negative control, and miRNA-137 inhibitor group. MiRNA-137 significantly reduced the proliferation and migration of placenta trophoblast cells of preeclampsia by targeting ERRα, which might be a potential target for gene therapy. © The Author(s) 2016.

  18. Dynamical behaviour of a discrete selection-migration model with arbitrary dominance

    Treesearch

    James F. Selgrade; Jordan West Bostic; James H. Roberds

    2009-01-01

    To study the effects of immigration of genes (possibly transgenic) into a natural population, a one-island selection-migration model with density-dependent regulation is used to track allele frequency and population size. The existence and uniqueness of a polymorphic genetic equilibrium is proved under a general assumption about dominance in fitnesses. Also, conditions...

  19. Mitomycin C retardation of corneal fibroblast migration via sustained dephosphorylation of paxillin at tyrosine 118.

    PubMed

    Chen, Tsan-Chi; Lai, Chien-Hsueh; Chang, Jie-Ling; Chang, Shu-Wen

    2012-03-21

    To investigate how mitomycin C (MMC) modulates corneal fibroblast migration and its molecular mechanisms in the wound healing process. After treatment with 0 and 0.2 mg · mL(-1) MMC for 5 minutes, effect of MMC on cell migration of human corneal fibroblasts (HCFs) was examined with a cell migration assay. Both focal adhesion kinase (FAK) and paxillin (PXN) expressions in HCFs were analyzed by semiquantitative real-time PCR, immunoblotting, and immunofluorescence confocal microscopy. Using gene silencing or gene overexpression with lentiviral-based pseudovirion infection, the phosphorylation level of FAK, PXN, and mutated PXNs at tyrosine sites 31 (Y31F-EGFP) and 118 (Y118F-EGFP) were verified in HCFs. MMC retarded HCF migration at 1 and 2 days posttreatment (dpt). MMC reduced levels of FAK transcript and FAK protein, but increased both transcript and protein expression of PXN at 1 and 2 dpt. Furthermore, MMC upregulated FAK-pY397, which subsequently enhanced PXN-pY31 in a dose-dependent manner at 1 dpt. Concurrently, MMC downregulated PXN-pY118 at 1 dpt. However, MMC treatment resulted in dephosphorylation of FAK-pY397, PXN-pY31, and PXN-pY118 at 2 dpt. The FAK/PXN complex in MMC-treated HCFs was detected at focal adhesion sites more than at the leading edge at 1 and 2 dpt, contributing to retardation of HCF migration. Y118F-EGFP-expressing HCFs exhibited lower mobility than that of PXN-EGFP- or Y31F-EGFP-expressing HCFs. The sustained PXN-pY118 dephosphorylation resulted in steadfastness of an incompletely active FAK/PXN complex at focal adhesion sites and played a pivotal role in MMC-retarded HCF migration.

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

    PubMed Central

    Ellis, Mark

    2014-01-01

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

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

    PubMed

    Ellis, Mark

    2012-03-01

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

  2. The Caenorhabditis elegans Q neuroblasts: A powerful system to study cell migration at single-cell resolution in vivo.

    PubMed

    Rella, Lorenzo; Fernandes Póvoa, Euclides E; Korswagen, Hendrik C

    2016-04-01

    During development, cell migration plays a central role in the formation of tissues and organs. Understanding the molecular mechanisms that drive and control these migrations is a key challenge in developmental biology that will provide important insights into disease processes, including cancer cell metastasis. In this article, we discuss the Caenorhabditis elegans Q neuroblasts and their descendants as a tool to study cell migration at single-cell resolution in vivo. The highly stereotypical migration of these cells provides a powerful system to study the dynamic cytoskeletal processes that drive migration as well as the evolutionarily conserved signaling pathways (including different Wnt signaling cascades) that guide the cells along their specific trajectories. Here, we provide an overview of what is currently known about Q neuroblast migration and highlight the live-cell imaging, genome editing, and quantitative gene expression techniques that have been developed to study this process. © 2016 Wiley Periodicals, Inc.

  3. Recent Historical Migrations Have Shaped the Gene Pool of Arabs and Berbers in North Africa

    PubMed Central

    Arauna, Lara R.; Mendoza-Revilla, Javier; Mas-Sandoval, Alex; Izaabel, Hassan; Bekada, Asmahan; Benhamamouch, Soraya; Fadhlaoui-Zid, Karima; Zalloua, Pierre; Hellenthal, Garrett

    2017-01-01

    North Africa is characterized by its diverse cultural and linguistic groups and its genetic heterogeneity. Genomic data has shown an amalgam of components mixed since pre-Holocean times. Though no differences have been found in uniparental and classical markers between Berbers and Arabs, the two main ethnic groups in the region, the scanty genomic data available have highlighted the singularity of Berbers. We characterize the genetic heterogeneity of North African groups, focusing on the putative differences of Berbers and Arabs, and estimate migration dates. We analyze genome-wide autosomal data in five Berber and six Arab groups, and compare them to Middle Easterns, sub-Saharans, and Europeans. Haplotype-based methods show a lack of correlation between geographical and genetic populations, and a high degree of genetic heterogeneity, without strong differences between Berbers and Arabs. Berbers enclose genetically diverse groups, from isolated endogamous groups with high autochthonous component frequencies, large homozygosity runs and low effective population sizes, to admixed groups with high frequencies of sub-Saharan and Middle Eastern components. Admixture time estimates show a complex pattern of recent historical migrations, with a peak around the 7th century C.E. coincident with the Arabization of the region; sub-Saharan migrations since the 1st century B.C. in agreement with Roman slave trade; and a strong migration in the 17th century C.E., coincident with a huge impact of the trans-Atlantic and trans-Saharan trade of sub-Saharan slaves in the Modern Era. The genetic complexity found should be taken into account when selecting reference groups in population genetics and biomedical studies. PMID:27744413

  4. Nectin-like molecule 1 inhibits the migration and invasion of U251 glioma cells by regulating the expression of an extracellular matrix protein osteopontin.

    PubMed

    Yin, Bin; Li, Ke-han; An, Tai; Chen, Tao; Peng, Xiao-zhong

    2010-06-01

    To investigate the molecular mechanism of nectin-like molecule 1 (NECL1) inhibiting the migration and invasion of U251 glioma cells. We infected U251 glioma cells with adeno-nectin-like molecule 1 (Ad-NECL1) or empty adenovirus (Ad). Transwell and wound healing assays were performed to observe the migration of U251 cells incubated with the cell supernatant from Ad-NECL1 or Ad infected U251 cells. DNA microarray was applied to screen the gene expression profile after the restoration of NECL1 in U251 glioma cell lines. The differential expression of osteopontin (OPN), a gene related to migration and invasion, was further analyzed with semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry. The restoration of NECL1 inhibited migration of U251 cells significantly (P<0.05). Altogether 195 genes were found differentially expressed by microarray, in which 175 were up-regulated and 20 down-regulated, including 9 extracellular matrix proteins involved in the migration of cells. Both mRNA and protein expressions of OPN, the most markedly reduced extracellular matrix protein, were found decreased in U251 cells after restoration of NECL1. Immunohistochemical assay also detected an increase of OPN in glioma tissues, related with the progressing of malignant grade. A link might exist between NECL1 and the extracellular matrix protein OPN in inhibiting the migration and invasion of U251 glioma cells.

  5. Leukocyte-specific protein 1 regulates T-cell migration in rheumatoid arthritis

    PubMed Central

    Hwang, Seong-Hye; Jung, Seung-Hyun; Lee, Saseong; Choi, Susanna; Yoo, Seung-Ah; Park, Ji-Hwan; Hwang, Daehee; Shim, Seung Cheol; Sabbagh, Laurent; Kim, Ki-Jo; Park, Sung Hwan; Cho, Chul-Soo; Kim, Bong-Sung; Leng, Lin; Montgomery, Ruth R.; Bucala, Richard; Chung, Yeun-Jun; Kim, Wan-Uk

    2015-01-01

    Copy number variations (CNVs) have been implicated in human diseases. However, it remains unclear how they affect immune dysfunction and autoimmune diseases, including rheumatoid arthritis (RA). Here, we identified a novel leukocyte-specific protein 1 (LSP1) deletion variant for RA susceptibility located in 11p15.5. We replicated that the copy number of LSP1 gene is significantly lower in patients with RA, which correlates positively with LSP1 protein expression levels. Differentially expressed genes in Lsp1-deficient primary T cells represent cell motility and immune and cytokine responses. Functional assays demonstrated that LSP1, induced by T-cell receptor activation, negatively regulates T-cell migration by reducing ERK activation in vitro. In mice with T-cell–dependent chronic inflammation, loss of Lsp1 promotes migration of T cells into the target tissues as well as draining lymph nodes, exacerbating disease severity. Moreover, patients with RA show diminished expression of LSP1 in peripheral T cells with increased migratory capacity, suggesting that the defect in LSP1 signaling lowers the threshold for T-cell activation. To our knowledge, our work is the first to demonstrate how CNVs result in immune dysfunction and a disease phenotype. Particularly, our data highlight the importance of LSP1 CNVs and LSP1 insufficiency in the pathogenesis of RA and provide previously unidentified insights into the mechanisms underlying T-cell migration toward the inflamed synovium in RA. PMID:26554018

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

    PubMed

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

    2013-10-23

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

  7. Mechanisms of Bacterial (Serratia marcescens) Attachment to, Migration along, and Killing of Fungal Hyphae.

    PubMed

    Hover, Tal; Maya, Tal; Ron, Sapir; Sandovsky, Hani; Shadkchan, Yana; Kijner, Nitzan; Mitiagin, Yulia; Fichtman, Boris; Harel, Amnon; Shanks, Robert M Q; Bruna, Roberto E; García-Véscovi, Eleonora; Osherov, Nir

    2016-05-01

    We have found a remarkable capacity for the ubiquitous Gram-negative rod bacterium Serratia marcescens to migrate along and kill the mycelia of zygomycete molds. This migration was restricted to zygomycete molds and several basidiomycete species. No migration was seen on any molds of the phylum Ascomycota. S. marcescens migration did not require fungal viability or surrounding growth medium, as bacteria migrated along aerial hyphae as well.S. marcescens did not exhibit growth tropism toward zygomycete mycelium. Bacterial migration along hyphae proceeded only when the hyphae grew into the bacterial colony. S. marcescens cells initially migrated along the hyphae, forming attached microcolonies that grew and coalesced to generate a biofilm that covered and killed the mycelium. Flagellum-defective strains of S. marcescens were able to migrate along zygomycete hyphae, although they were significantly slower than the wild-type strain and were delayed in fungal killing. Bacterial attachment to the mycelium does not necessitate type 1 fimbrial adhesion, since mutants defective in this adhesin migrated equally well as or faster than the wild-type strain. Killing does not depend on the secretion of S. marcescens chitinases, as mutants in which all three chitinase genes were deleted retained wild-type killing abilities. A better understanding of the mechanisms by which S. marcescens binds to, spreads on, and kills fungal hyphae might serve as an excellent model system for such interactions in general; fungal killing could be employed in agricultural fungal biocontrol. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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

    PubMed

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

    2015-05-28

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

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

    PubMed Central

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

    2015-01-01

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

  10. 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

  11. 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.

  12. Recent Historical Migrations Have Shaped the Gene Pool of Arabs and Berbers in North Africa.

    PubMed

    Arauna, Lara R; Mendoza-Revilla, Javier; Mas-Sandoval, Alex; Izaabel, Hassan; Bekada, Asmahan; Benhamamouch, Soraya; Fadhlaoui-Zid, Karima; Zalloua, Pierre; Hellenthal, Garrett; Comas, David

    2017-02-01

    North Africa is characterized by its diverse cultural and linguistic groups and its genetic heterogeneity. Genomic data has shown an amalgam of components mixed since pre-Holocean times. Though no differences have been found in uniparental and classical markers between Berbers and Arabs, the two main ethnic groups in the region, the scanty genomic data available have highlighted the singularity of Berbers. We characterize the genetic heterogeneity of North African groups, focusing on the putative differences of Berbers and Arabs, and estimate migration dates. We analyze genome-wide autosomal data in five Berber and six Arab groups, and compare them to Middle Easterns, sub-Saharans, and Europeans. Haplotype-based methods show a lack of correlation between geographical and genetic populations, and a high degree of genetic heterogeneity, without strong differences between Berbers and Arabs. Berbers enclose genetically diverse groups, from isolated endogamous groups with high autochthonous component frequencies, large homozygosity runs and low effective population sizes, to admixed groups with high frequencies of sub-Saharan and Middle Eastern components. Admixture time estimates show a complex pattern of recent historical migrations, with a peak around the 7th century C.E. coincident with the Arabization of the region; sub-Saharan migrations since the 1st century B.C. in agreement with Roman slave trade; and a strong migration in the 17th century C.E., coincident with a huge impact of the trans-Atlantic and trans-Saharan trade of sub-Saharan slaves in the Modern Era. The genetic complexity found should be taken into account when selecting reference groups in population genetics and biomedical studies. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  13. 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.

  14. Vitamin K2 improves proliferation and migration of bovine skeletal muscle cells in vitro.

    PubMed

    Rønning, Sissel Beate; Pedersen, Mona Elisabeth; Berg, Ragnhild Stenberg; Kirkhus, Bente; Rødbotten, Rune

    2018-01-01

    Skeletal muscle function is highly dependent on the ability to regenerate, however, during ageing or disease, the proliferative capacity is reduced, leading to loss of muscle function. We have previously demonstrated the presence of vitamin K2 in bovine skeletal muscles, but whether vitamin K has a role in muscle regulation and function is unknown. In this study, we used primary bovine skeletal muscle cells, cultured in monolayers in vitro, to assess a potential effect of vitamin K2 (MK-4) during myogenesis of muscle cells. Cell viability experiments demonstrate that the amount of ATP produced by the cells was unchanged when MK-4 was added, indicating viable cells. Cytotoxicity analysis show that MK-4 reduced the lactate dehydrogenase (LDH) released into the media, suggesting that MK-4 was beneficial to the muscle cells. Cell migration, proliferation and differentiation was characterised after MK-4 incubation using wound scratch analysis, immunocytochemistry and real-time PCR analysis. Adding MK-4 to the cells led to an increased muscle proliferation, increased gene expression of the myogenic transcription factor myod as well as increased cell migration. In addition, we observed a reduction in the fusion index and relative gene expression of muscle differentiation markers, with fewer complex myotubes formed in MK-4 stimulated cells compared to control cells, indicating that the MK-4 plays a significant role during the early phases of muscle proliferation. Likewise, we see the same pattern for the relative gene expression of collagen 1A, showing increased gene expression in proliferating cells, and reduced expression in differentiating cells. Our results also suggest that MK-4 incubation affect low density lipoprotein receptor-related protein 1 (LRP1) and the low-density lipoprotein receptor (LDLR) with a peak in gene expression after 45 min of MK-4 incubation. Altogether, our experiments show that MK-4 has a positive effect on muscle cell migration and

  15. Girdin Is an Intrinsic Regulator of Neuroblast Chain Migration in the Rostral Migratory Stream of the Postnatal Brain

    PubMed Central

    Wang, Yun; Kaneko, Naoko; Asai, Naoya; Enomoto, Atsushi; Isotani-Sakakibara, Mayu; Kato, Takuya; Asai, Masato; Murakumo, Yoshiki; Ota, Haruko; Hikita, Takao; Namba, Takashi; Kuroda, Keisuke; Kaibuchi, Kozo; Ming, Guo-li; Song, Hongjun; Sawamoto, Kazunobu; Takahashi, Masahide

    2017-01-01

    In postnatally developing and adult brains, interneurons of the olfactory bulb (OB) are continuously generated at the subventricular zone of the forebrain. The newborn neuroblasts migrate tangentially to the OB through a well defined pathway, the rostral migratory stream (RMS), where the neuroblasts undergo collective migration termed “chain migration.” The cell-intrinsic regulatory mechanism of neuroblast chain migration, however, has not been uncovered. Here we show that mice lacking the actin-binding Akt substrate Girdin (a protein that interacts with Disrupted-In-Schizophrenia 1 to regulate neurogenesis in the dentate gyrus) have profound defects in neuroblast chain migration along the RMS. Analysis of two gene knock-in mice harboring Girdin mutants identified unique amino acid residues in Girdin’s C-terminal domain that are responsible for the regulation of neuroblast chain migration but revealed no apparent requirement of Girdin phosphorylation by Akt. Electron microscopic analyses demonstrated the involvement of Girdin in neuroblast cell–cell interactions. These findings suggest that Girdin is an important intrinsic factor that specifically governs neuroblast chain migration along the RMS. PMID:21632933

  16. 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.

  17. In Vivo MR Imaging of Dual MRI Reporter Genes and Deltex-1 Gene-modified Human Mesenchymal Stem Cells in the Treatment of Closed Penile Fracture.

    PubMed

    Guo, Ruomi; Li, Qingling; Yang, Fei; Hu, Xiaojun; Jiao, Ju; Guo, Yu; Wang, Jin; Zhang, Yong

    2018-06-01

    The purpose of this study was to investigate the feasibility of dual magnetic resonance imaging (MRI) reporter genes, including ferritin heavy subunit (Fth) and transferrin receptor (TfR), which provide sufficient MRI contrast for in vivo MRI tracking, and the Deltex-1 (DTX1) gene, which promotes human mesenchymal stem cell (hMSC) differentiation to smooth muscle cells (SMCs), to treat closed penile fracture (CPF). Multi-gene co-expressing hMSCs were generated. The expression of mRNA and proteins was assessed, and the original biological properties of hMSCs were determined and compared. The intracellular uptake of iron was evaluated, and the ability to differentiate into SMCs was detected. Fifty rabbits with CPF were randomly transplanted with PBS, hMSCs, Fth-TfR-hMSCs, DTX1-hMSCs, and Fth-TfR-DTX1-hMSCs. In vivo MRI was performed to detect the distribution and migration of the grafted cells and healing progress of CPF, and the results were correlated with histology. The mRNA and proteins of the multi-gene were highly expressed. The transgenes could not influence the original biological properties of hMSCs. The dual MRI reporter genes increased the iron accumulation capacity, and the DTX1 gene promoted hMSC differentiation into SMCs. The distribution and migration of the dual MRI reporter gene-modified hMSCs, and the healing state of CPF could be obviously detected by MRI and confirmed by histology. The dual MRI reporter genes could provide sufficient MRI contrast, and the distribution and migration of MSCs could be detected in vivo. The DTX1 gene can promote MSC differentiation into SMCs for the treatment of CPF and effectively inhibit granulation tissue formation.

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

    USGS Publications Warehouse

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

    2011-01-01

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

  19. Neural Crest Migration and Survival Are Susceptible to Morpholino-Induced Artifacts

    PubMed Central

    Jette, Cicely A.

    2016-01-01

    The neural crest (NC) is a stem cell-like embryonic population that is essential for generating and patterning the vertebrate body, including the craniofacial skeleton and peripheral nervous system. Defects in NC development underlie many birth defects and contribute to formation of some of the most malignant cancers in humans, such as melanoma and neuroblastoma. For these reasons, significant research efforts have been expended to identify genes that control NC development, as it is expected to lead to a deeper understanding of the genetic mechanisms controlling vertebrate development and identify new treatments for NC-derived diseases and cancers. However, a number of inconsistencies regarding gene function during NC development have emerged from comparative analyses of gene function between mammalian and non-mammalian systems (chick, frog, zebrafish). This poses a significant barrier to identification of single genes and/or redundant pathways to target in NC diseases. Here, we determine whether technical differences, namely morpholino-based approaches used in non-mammalian systems, could contribute to these discrepancies, by examining the extent to which NC phenotypes in fascin1a (fscn1a) morphant embryos are similar to or different from fscn1a null mutants in zebrafish. Analysis of fscn1a morphants showed that they mimicked early NC phenotypes observed in fscn1a null mutants; however, these embryos also displayed NC migration and derivative phenotypes not observed in null mutants, including accumulation of p53-independent cell death. These data demonstrate that morpholinos can cause seemingly specific NC migration and derivative phenotypes, and thus have likely contributed to the inconsistencies surrounding NC gene function between species. We suggest that comparison of genetic mutants between different species is the most rigorous method for identifying conserved genetic mechanisms controlling NC development and is critical to identify new treatments for NC

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. [Regulation of microRNA-199a on adhesion, migration and invasion ability of human endometrial stromal cells].

    PubMed

    Dai, Lan; Gu, Li-ying; Zhu, Jie; Shi, Jun; Wang, Yao; Ji, Fang; Di, Wen

    2011-11-01

    To study the regulation of microRNA 199a (miR-199a) on adhesion, migration and invasion ability of human eutopic endometrial stromal cells (ESC) from patients with endometriosis. ESC were transfected with miR-199a mimics or negative control (NC) RNA by lipofectamine 2000. The adhesion, migration and invasion ability of ESC were detected by cell adhesion assay, scratch assay, cell migration assay and matrigel invasion assay, respectively. Luciferase reporter assay was used to evaluate whether IKKβ was the target gene of miR-199a. The expression of ikappa B kinase beta (IKKβ), inhibitory kappa B alpha (IκB-α), phospho-IκB-α(p-IκB-α) and nuclear factor-kappa B (NF-κB) protein were measured by western blot. (1) Adhesion potential: the adhesion inhibitory rates were (14 ± 4)% in miR-199a group and 0 in control group, which showed significant difference (P < 0.01). (2) Migration and invasion: in the scratch assay, ESC transfected with miR-199a exhibited a lower scratch closure rate than that of controls. In migration and invasion assays, the migration and invasion ability of miR-199a group were significantly decreased compared with those of NC group [130 ± 31 vs. 247 ± 36 (P < 0.01); 63 ± 15 vs. 133 ± 17 (P < 0.01), respectively]. (3) The luciferase activity of miR-199a group was significantly lowered than that of control group [0.160 ± 0.006 vs. 0.383 ± 0.083 (P < 0.01)]. The protein levels of IKKβ, p-IκB-α, IκB-α and NF-κB of 0.350 ± 0.195, 0.443 ± 0.076, 1.970 ± 0.486 and 0.454 ± 0.147 in miR-199a group were significantly different compared with the NC group in which the protein levels were set at 1.000 (P < 0.01). miR-199a can inhibit the adhesion, migration and invasion of the ESC. IKKβ is the target gene of miR-199a in ESC. One of the mechanisms of the inhibition effect is probably that miR-199a inhibits the activation of NF-κB signaling pathway by targeting IKKβ gene.

  5. [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.

  6. Phosphodiesterase 4 regulates the migration of B16-F10 melanoma cells.

    PubMed

    Watanabe, Yoshihiro; Murata, Taku; Shimizu, Kasumi; Morita, Hiroshi; Inui, Madoka; Tagawa, Toshiro

    2012-08-01

    Phosphodiesterases (PDEs) are important regulators of signal transduction processes. Eleven PDE gene families (PDE1-11) have been identified and several PDE isoforms are selectively expressed in various cell types. PDE4 family members specifically hydrolyze cyclic AMP (cAMP). Four genes (PDE4A-D) are known to encode PDE4 enzymes, with additional diversity generated by the use of alternative mRNA splicing and the use of different promoters. While PDE4 selective inhibitors show therapeutic potential for treating major diseases such as asthma and chronic obstructive pulmonary disease, little is known concerning the role of PDE4 in malignant melanoma. In this study, we examined the role of PDE4 in mouse B16-F10 melanoma cells. In these cells, PDE4 activity was found to be ∼60% of total PDE activity. RT-PCR detected only PDE4B and PDE4D mRNA. Cell growth was inhibited by the cAMP analog, 8-bromo-cAMP, but not by the specific PDE4 inhibitors, rolipram and denbufylline, which increased intracellular cAMP concentrations. Finally, migration of the B16-F10 cells was inhibited by the PDE4 inhibitors and 8-bromo-cAMP, while migration was increased by a protein kinase A (PKA) inhibitor, PKI(14-22), and was not affected by 8-pCPT-2'-O-Me-cAMP, which is an analog of exchange protein activated by cAMP (Epac). The inhibitory effect of rolipram on migration was reversed by PKI(14-22). Based on these results, PDE4 appears to play an important role in the migration of B16-F10 cells, and therefore may be a novel target for the treatment of malignant melanoma.

  7. Targeting LC3 and Beclin-1 autophagy genes suppresses proliferation, survival, migration and invasion by inhibition of Cyclin-D1 and uPAR/Integrin β1/ Src signaling in triple negative breast cancer cells.

    PubMed

    Hamurcu, Zuhal; Delibaşı, Nesrin; Geçene, Seda; Şener, Elif Funda; Dönmez-Altuntaş, Hamiyet; Özkul, Yusuf; Canatan, Halit; Ozpolat, Bulent

    2018-03-01

    Autophagy is a catabolic process for degrading dysfunctional proteins and organelles, and closely associated with cancer cell survival under therapeutic, metabolic stress, hypoxia, starvation and lack of growth factors, contributing to resistance to therapies. However, the role of autophagy in breast cancer cells is not well understood. In the present study, we investigated the role of autophagy in highly aggressive and metastatic triple negative breast cancer (TNBC) and non-metastatic breast cancer cells and demonstrated that the knockdown of autophagy-related genes (LC3 and Beclin-1) inhibited autophagy and significantly suppressed cell proliferation, colony formation, migration/invasion and induced apoptosis in MDA-MB-231 and BT-549 TNBC cells. Knockdown of LC3 and Beclin-1 led to inhibition of multiple proto-oncogenic signaling pathways, including cyclin D1, uPAR/integrin-β1/Src, and PARP1. In conclusion, our study suggests that LC3 and Beclin-1 are required for cell proliferation, survival, migration and invasion, and may contribute to tumor growth and progression of highly aggressive and metastatic TNBC cells and therapeutic targeting of autophagy genes may be a potential therapeutic strategy for TNBC in breast cancer.

  8. 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

  9. N-Cadherin and Fibroblast Growth Factor Receptors crosstalk in the control of developmental and cancer cell migrations.

    PubMed

    Nguyen, Thao; Mège, René Marc

    2016-11-01

    Cell migrations are diverse. They constitutemajor morphogenetic driving forces during embryogenesis, but they contribute also to the loss of tissue homeostasis and cancer growth. Capabilities of cells to migrate as single cells or as collectives are controlled by internal and external signalling, leading to the reorganisation of their cytoskeleton as well as by the rebalancing of cell-matrix and cell-cell adhesions. Among the genes altered in numerous cancers, cadherins and growth factor receptors are of particular interest for cell migration regulation. In particular, cadherins such as N-cadherin and a class of growth factor receptors, namely FGFRs cooperate to regulate embryonic and cancer cell behaviours. In this review, we discuss on reciprocal crosstalk between N-cadherin and FGFRs during cell migration. Finally, we aim at clarifying the synergy between N-cadherin and FGFR signalling that ensure cellular reorganization during cell movements, mainly during cancer cell migration and metastasis but also during developmental processes. Copyright © 2016 Elsevier GmbH. All rights reserved.

  10. Promotive Effect of Zinc Ions on the Vitality, Migration, and Osteogenic Differentiation of Human Dental Pulp Cells.

    PubMed

    An, Shaofeng; Gong, Qimei; Huang, Yihua

    2017-01-01

    Zinc is an essential trace element for proper cellular function and bone formation. However, its exact role in the osteogenic differentiation of human dental pulp cells (hDPCs) has not been fully clarified before. Here, we speculated that zinc may be effective to regulate their growth and osteogenic differentiation properties. To test this hypothesis, different concentrations (1 × 10 -5 , 4 × 10 -5 , and 8 × 10 -5  M) of zinc ions (Zn 2+ ) were added to the basic growth culture medium and osteogenic inductive medium. Cell viability and migration were measured by cell counting kit-8 (CCK-8) and transwell migration assay in the basic growth culture medium, respectively. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the gene expression levels of selective osteogenic differentiation markers and zinc transporters. Alkaline phosphatase (ALP) activity analysis and alizarin red S staining were used to investigate the mineralization of hDPCs. Exposure of hDPCs to Zn 2+ stimulated their viability and migration capacity in a dose- and time-dependent manner. RT-qPCR assay revealed elevated expression levels of osteogenic differentiation-related genes and zinc transporters genes in various degrees. ALP activity was also increased with elevated Zn 2+ concentrations and extended culture periods, but enhanced matrix nodules formation were observed only in 4 × 10 -5 and 8 × 10 -5  M Zn 2+ groups. These findings suggest that specific concentrations of Zn 2+ could potentiate the vitality, migration, and osteogenic differentiation of hDPCs. We may combine optimum zinc element into pulp capping materials to improve their biological performance.

  11. SATB2 expression increased anchorage-independent growth and cell migration in human bronchial epithelial cells

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

    Wu, Feng; Jordan, Ashley; Kluz, Thomas

    The special AT-rich sequence-binding protein 2 (SATB2) is a protein that binds to the nuclear matrix attachment region of the cell and regulates gene expression by altering chromatin structure. In our previous study, we reported that SATB2 gene expression was induced in human bronchial epithelial BEAS-2B cells transformed by arsenic, chromium, nickel and vanadium. In this study, we show that ectopic expression of SATB2 in the normal human bronchial epithelial cell-line BEAS-2B increased anchorage-independent growth and cell migration, meanwhile, shRNA-mediated knockdown of SATB2 significantly decreased anchorage-independent growth in Ni transformed BEAS-2B cells. RNA sequencing analyses of SATB2 regulated genes revealedmore » the enrichment of those involved in cytoskeleton, cell adhesion and cell-movement pathways. Our evidence supports the hypothesis that SATB2 plays an important role in BEAS-2B cell transformation. - Highlights: • We performed SATB2 overexpression in the BEAS-2B cell line. • We performed SATB2 knockdown in a Ni transformed BEAS-2B cell line. • SATB2 induced anchorage-independent growth and increased cell migration. • SATB2 knockdown significantly decreased anchorage-independent growth. • We identified alterations in gene involved in cytoskeleton, cell adhesion.« less

  12. 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.

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

    PubMed

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

    2017-07-01

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

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

    PubMed

    Kennedy, Lisa M; Grishok, Alla

    2014-05-01

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

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

    PubMed Central

    Kennedy, Lisa M.; Grishok, Alla

    2014-01-01

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

  16. Ecological Trade-offs between Migration and Reproduction Are Mediated by the Nutrition-Sensitive Insulin-Signaling Pathway.

    PubMed

    Lin, Xinda; Yao, Yun; Wang, Bo; Emlen, Douglas J; Lavine, Laura Corley

    2016-01-01

    Crowding and changes in food availability are two critical environmental conditions that impact an animal's trajectory toward either migration or reproduction. Many insects facing this challenge have evolved wing polyphenisms. When conditions favor reproduction, wing polyphenic species produce adults that either have no wings or short, non-functional wings. Facultative wing growth reflects a physiological and evolutionary trade-off between migration and reproduction, triggered by environmental conditions. How environmental cues are transduced to produce these alternative forms, and their associated ecological shift from migration to reproduction, remains an important unsolved problem in evolutionary ecology. The brown planthopper, a wing polymorphic insect exhibiting strong trade-offs in investment between migration and reproduction, is one of the most serious rice pests in Asia. In this study, we investigated the function of four genes in the insulin-signaling pathway known to couple nutrition with growth, PI3 Kinase (PI3K), PDK1, Akt (Protein Kinase B), and the forkhead gene FOXO. Using a combination of RNA interference and pharmacological inhibitor treatment, we show that all four genes contribute to tissue level regulation of wing polymorphic development in this insect. As predicted, silencing of the NlPI3K, NlAkt and NlPDK1 through dsRNA and with the pharmacological inhibitor Perifosine resulted in short-winged brown planthoppers, whereas knockdown of NlFOXO resulted in long-winged planthoppers. Morphometric analyses confirm that phenotypes from our manipulations mimic what would be found in nature, i.e., major parameters such as bristle number, wing area and body weight are not significantly different from non-experimental animals. Taken together, these data implicate the insulin-signaling pathway in the transduction of environmental factors into condition-dependent patterns of wing growth in insects.

  17. Inhibition of human osteosarcoma cell migration and invasion by a gene silencer, pyrrole-imidazole polyamide, targeted at the human MMP9 NF-κB binding site.

    PubMed

    Kojima, Toshio; Wang, Xiaofei; Fujiwara, Kyoko; Osaka, Shunzo; Yoshida, Yukihiro; Osaka, Eiji; Taniguchi, Masashi; Ueno, Takahiro; Fukuda, Noboru; Soma, Masayoshi; Tokuhashi, Yasuaki; Nagase, Hiroki

    2014-01-01

    Osteosarcoma is one of the most prevalent bone tumors, occurring mostly in adolescence. However, no noticeable progress has been achieved in developing new therapeutic agents for this disease. Matrix metalloproteinase 9 (MMP9), a type IV collagenase, is a known anticancer target and is overexpressed in osteosarcomas. MMPs can degrade components of the extracellular matrix and are known to be involved in tumor invasion and metastasis. In the present study, we designed and synthesized a pyrrole-imidazole polyamide (HN.49), a gene-silencing agent that specifically targets the nuclear factor-kappa B (NF-κB) binding site of the human MMP9 promoter. We then examined the effect of HN.49 on the enzyme activity of MMP9 and the migration activity of osteosarcoma cells in vitro. It was clearly shown that HN.49 polyamide reduced the expression level of MMP9 mRNA and the enzymatic activity of MMP-9 in SaOS-2 cells. Moreover, HN.49 polyamide inhibited migration and invasion by SaOS-2 cells in in vitro wound-closure and matrigel-invasion assays. These results indicate that HN.49 may be a potential therapeutic agent for inhibiting the invasion and metastasis of osteosarcoma.

  18. 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

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

    PubMed

    Traore, S

    1997-10-01

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

  20. 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.

  1. MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling

    PubMed Central

    Ka, Minhan; Jung, Eui-Man; Mueller, Ulrich; Kim, Woo-Yang

    2014-01-01

    Neuronal migration and subsequent differentiation play critical roles for establishing functional neural circuitry in the developing brain. However, the molecular mechanisms that regulate these processes are poorly understood. Here, we show that microtubule actin crosslinking factor 1 (MACF1) determines neuronal positioning by regulating microtubule dynamics and mediating GSK-3 signaling during brain development. First, using MACF1 floxed allele mice and in utero gene manipulation, we find that MACF1 deletion suppresses migration of cortical pyramidal neurons and results in aberrant neuronal positioning in the developing brain. The cell autonomous deficit in migration is associated with abnormal dynamics of leading processes and centrosomes. Furthermore, microtubule stability is severely damaged in neurons lacking MACF1, resulting in abnormal microtubule dynamics. Finally, MACF1 interacts with and mediates GSK-3 signaling in developing neurons. Our findings establish a cellular mechanism underlying neuronal migration and provide insights into the regulation of cytoskeleton dynamics in developing neurons. PMID:25224226

  2. MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling.

    PubMed

    Ka, Minhan; Jung, Eui-Man; Mueller, Ulrich; Kim, Woo-Yang

    2014-11-01

    Neuronal migration and subsequent differentiation play critical roles for establishing functional neural circuitry in the developing brain. However, the molecular mechanisms that regulate these processes are poorly understood. Here, we show that microtubule actin crosslinking factor 1 (MACF1) determines neuronal positioning by regulating microtubule dynamics and mediating GSK-3 signaling during brain development. First, using MACF1 floxed allele mice and in utero gene manipulation, we find that MACF1 deletion suppresses migration of cortical pyramidal neurons and results in aberrant neuronal positioning in the developing brain. The cell autonomous deficit in migration is associated with abnormal dynamics of leading processes and centrosomes. Furthermore, microtubule stability is severely damaged in neurons lacking MACF1, resulting in abnormal microtubule dynamics. Finally, MACF1 interacts with and mediates GSK-3 signaling in developing neurons. Our findings establish a cellular mechanism underlying neuronal migration and provide insights into the regulation of cytoskeleton dynamics in developing neurons. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Transcription Factor SOX5 Promotes the Migration and Invasion of Fibroblast-Like Synoviocytes in Part by Regulating MMP-9 Expression in Collagen-Induced Arthritis.

    PubMed

    Shi, Yumeng; Wu, Qin; Xuan, Wenhua; Feng, Xiaoke; Wang, Fang; Tsao, Betty P; Zhang, Miaojia; Tan, Wenfeng

    2018-01-01

    Fibroblast-like synoviocytes (FLS) exhibit a unique aggressive phenotype in rheumatoid arthritis (RA). Increased FLS migration and subsequent invasion of the extracellular matrix are essential to joint destruction in RA. Our previous research reported that transcription factor SOX5 was highly expressed in RA-FLS. Here, the effects of SOX5 in RA-FLS migration and invasion will be investigated. The migration and invasion of RA-FLS were evaluated using a transwell chamber assay. The expression of several potential SOX5-targeted genes, including matrix metalloproteinases (MMP-1, 2, 3 and 9), chemokines (CCL4, CCL2, CCR5 and CCR2), and pro-inflammatory cytokines (TNF-α and IL-6), were examined in RA-FLS using SOX5 gain- and loss-of-function study. The molecular mechanisms of SOX5-mediated MMP-9 expressions were assayed by luciferase reporter gene and chromatin immunoprecipitation (ChIP) studies. The in vivo effect of SOX5 on FLS migration and invasion was examined using collagen-induced arthritis (CIA) in DBA/1J mice. Knockdown SOX5 decreased lamellipodium formation, migration, and invasion of RA-FLS. The expression of MMP-9 was the only gene tested to be concomitantly affected by silencing or overexpressing SOX5. ChIP assay revealed that SOX5 was bound to the MMP-9 promoter in RA-FLS. The overexpression of SOX5 markedly enhanced the MMP-9 promoter activity, and specific deletion of a putative SOX5-binding site in MMP-9 promoter diminished this promoter-driven transcription in FLS. Locally knocked down SOX5 inhibited MMP-9 expression in the joint tissue and reduced pannus migration and invasion into the cartilage in CIA mice. SOX5 plays a novel role in mediating migration and invasion of FLS in part by regulating MMP-9 expression in RA.

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

    PubMed

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

    2015-11-01

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

  5. 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

  6. Arachidonic acid-induced Ca2+ entry and migration in a neuroendocrine cancer cell line.

    PubMed

    Goswamee, Priyodarshan; Pounardjian, Tamar; Giovannucci, David R

    2018-01-01

    Store-operated Ca 2+ entry (SOCE) has been implicated in the migration of some cancer cell lines. The canonical SOCE is defined as the Ca 2+ entry that occurs in response to near-maximal depletion of Ca 2+ within the endoplasmic reticulum. Alternatively, arachidonic acid (AA) has been shown to induce Ca 2+ entry in a store-independent manner through Orai1/Orai3 hetero-multimeric channels. However, the role of this AA-induced Ca 2+ entry pathway in cancer cell migration has not been adequately assessed. The present study investigated the involvement of AA-induced Ca 2+ entry in migration in BON cells, a model gastro-enteropancreatic neuroendocrine tumor (GEPNET) cell line using pharmacological and gene knockdown methods in combination with live cell fluorescence imaging and standard migration assays. We showed that both the store-dependent and AA-induced Ca 2+ entry modes could be selectively activated and that exogenous administration of AA resulted in Ca 2+ entry that was pharmacologically distinct from SOCE. Also, whereas homomeric Orai1-containing channels appeared to largely underlie SOCE, the AA-induced Ca 2+ entry channel required the expression of Orai3 as well as Orai1. Moreover, we showed that AA treatment enhanced the migration of BON cells and that this migration could be abrogated by selective inhibition of the AA-induced Ca 2+ entry. Taken together, these data revealed that an alternative Orai3-dependent Ca 2+ entry pathway is an important signal for GEPNET cell migration.

  7. Annotating novel genes by integrating synthetic lethals and genomic information

    PubMed Central

    Schöner, Daniel; Kalisch, Markus; Leisner, Christian; Meier, Lukas; Sohrmann, Marc; Faty, Mahamadou; Barral, Yves; Peter, Matthias; Gruissem, Wilhelm; Bühlmann, Peter

    2008-01-01

    Background Large scale screening for synthetic lethality serves as a common tool in yeast genetics to systematically search for genes that play a role in specific biological processes. Often the amounts of data resulting from a single large scale screen far exceed the capacities of experimental characterization of every identified target. Thus, there is need for computational tools that select promising candidate genes in order to reduce the number of follow-up experiments to a manageable size. Results We analyze synthetic lethality data for arp1 and jnm1, two spindle migration genes, in order to identify novel members in this process. To this end, we use an unsupervised statistical method that integrates additional information from biological data sources, such as gene expression, phenotypic profiling, RNA degradation and sequence similarity. Different from existing methods that require large amounts of synthetic lethal data, our method merely relies on synthetic lethality information from two single screens. Using a Multivariate Gaussian Mixture Model, we determine the best subset of features that assign the target genes to two groups. The approach identifies a small group of genes as candidates involved in spindle migration. Experimental testing confirms the majority of our candidates and we present she1 (YBL031W) as a novel gene involved in spindle migration. We applied the statistical methodology also to TOR2 signaling as another example. Conclusion We demonstrate the general use of Multivariate Gaussian Mixture Modeling for selecting candidate genes for experimental characterization from synthetic lethality data sets. For the given example, integration of different data sources contributes to the identification of genetic interaction partners of arp1 and jnm1 that play a role in the same biological process. PMID:18194531

  8. Brazilian Red Propolis Induces Apoptosis-Like Cell Death and Decreases Migration Potential in Bladder Cancer Cells

    PubMed Central

    Begnini, Karine Rech; Moura de Leon, Priscila Marques; Thurow, Helena; Schultze, Eduarda; Campos, Vinicius Farias; Borsuk, Sibele; Dellagostin, Odir Antônio; Savegnago, Lucielli; Moura, Sidnei; Padilha, Francine F.; Pêgas Henriques, João Antonio; Seixas, Fabiana Kömmling

    2014-01-01

    Natural products continue to be an invaluable resource of anticancer drug discovery in recent years. Propolis is known for its biological activities such as antimicrobial and antitumor effects. This study assessed the effects of Brazilian red propolis (BRP) on apoptosis and migration potential in human bladder cancer cells. The effect of BRP ethanolic extract (25, 50, and 100 μg/mL) on 5637 cells was determined by MTT, LIVE/DEAD, and migration (scratch assay) assays. Apoptosis induction was investigated through flow cytometry and gene expression profile was investigated by qRT-PCR. Results showed cytotoxicity on MTT and LIVE/DEAD assays, with IC50 values of 95 μg/mL in 24 h of treatment. Cellular migration of 5637 cells was significantly inhibited through lower doses of BRP ethanolic extract (25 and 50 μg/mL). Flow cytometry analyses showed that BRP induced cytotoxicity through apoptosis-like mechanisms in 5637 cells and qRT-PCR revealed increased levels of Bax/Bcl-2 ratio, p53, AIF, and antioxidant enzymes genes. Data suggest that BRP may be a potential source of drugs to bladder cancer treatment. PMID:25530785

  9. Brazilian red propolis induces apoptosis-like cell death and decreases migration potential in bladder cancer cells.

    PubMed

    Begnini, Karine Rech; Moura de Leon, Priscila Marques; Thurow, Helena; Schultze, Eduarda; Campos, Vinicius Farias; Martins Rodrigues, Fernanda; Borsuk, Sibele; Dellagostin, Odir Antônio; Savegnago, Lucielli; Roesch-Ely, Mariana; Moura, Sidnei; Padilha, Francine F; Collares, Tiago; Pêgas Henriques, João Antonio; Seixas, Fabiana Kömmling

    2014-01-01

    Natural products continue to be an invaluable resource of anticancer drug discovery in recent years. Propolis is known for its biological activities such as antimicrobial and antitumor effects. This study assessed the effects of Brazilian red propolis (BRP) on apoptosis and migration potential in human bladder cancer cells. The effect of BRP ethanolic extract (25, 50, and 100 μg/mL) on 5637 cells was determined by MTT, LIVE/DEAD, and migration (scratch assay) assays. Apoptosis induction was investigated through flow cytometry and gene expression profile was investigated by qRT-PCR. Results showed cytotoxicity on MTT and LIVE/DEAD assays, with IC50 values of 95 μg/mL in 24 h of treatment. Cellular migration of 5637 cells was significantly inhibited through lower doses of BRP ethanolic extract (25 and 50 μg/mL). Flow cytometry analyses showed that BRP induced cytotoxicity through apoptosis-like mechanisms in 5637 cells and qRT-PCR revealed increased levels of Bax/Bcl-2 ratio, p53, AIF, and antioxidant enzymes genes. Data suggest that BRP may be a potential source of drugs to bladder cancer treatment.

  10. 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."

  11. A migration signature and plasma biomarker panel for pancreatic adenocarcinoma.

    PubMed

    Balasenthil, Seetharaman; Chen, Nanyue; Lott, Steven T; Chen, Jinyun; Carter, Jennifer; Grizzle, William E; Frazier, Marsha L; Sen, Subrata; Killary, Ann McNeill

    2011-01-01

    Pancreatic ductal adenocarcinoma is a disease of extremely poor prognosis for which there are no reliable markers of asymptomatic disease. To identify pancreatic cancer biomarkers, we focused on a genomic interval proximal to the most common fragile site in the human genome, chromosome 3p12, which undergoes smoking-related breakage, loss of heterozygosity, and homozygous deletion as an early event in many epithelial tumors, including pancreatic cancers. Using a functional genomic approach, we identified a seven-gene panel (TNC, TFPI, TGFBI, SEL-1L, L1CAM, WWTR1, and CDC42BPA) that was differentially expressed across three different expression platforms, including pancreatic tumor/normal samples. In addition, Ingenuity Pathways Analysis (IPA) and literature searches indicated that this seven-gene panel functions in one network associated with cellular movement/morphology/development, indicative of a "migration signature" of the 3p pathway. We tested whether two secreted proteins from this panel, tenascin C (TNC) and tissue factor pathway inhibitor (TFPI), could serve as plasma biomarkers. Plasma ELISA assays for TFPI/TNC resulted in a combined area under the curve (AUC) of 0.88 and, with addition of CA19-9, a combined AUC for the three-gene panel (TNC/TFPI/CA19-9), of 0.99 with 100% specificity at 90% sensitivity and 97.22% sensitivity at 90% specificity. Validation studies using TFPI only in a blinded sample set increased the performance of CA19-9 from an AUC of 0.84 to 0.94 with the two-gene panel. Results identify a novel 3p pathway-associated migration signature and plasma biomarker panel that has utility for discrimination of pancreatic cancer from normal controls and promise for clinical application. ©2010 AACR.

  12. A Migration Signature and Plasma Biomarker Panel for Pancreatic Adenocarcinoma

    PubMed Central

    Balasenthil, Seetharaman; Chen, Nanyue; Lott, Steven T.; Chen, Jinyun; Carter, Jennifer; Grizzle, William E.; Frazier, Marsha L.; Sen, Subrata; Killary, Ann McNeill

    2013-01-01

    Pancreatic ductal adenocarcinoma is a disease of extremely poor prognosis for which there are no reliable markers of asymptomatic disease. To identify pancreatic cancer biomarkers, we focused on a genomic interval proximal to the most common fragile site in the human genome, chromosome 3p12, which undergoes smoking-related breakage, loss of heterozygosity, and homozygous deletion as an early event in many epithelial tumors, including pancreatic cancers. Using a functional genomic approach, we identified a seven-gene panel (TNC, TFPI, TGFBI, SEL-1L, L1CAM, WWTR1, and CDC42BPA) that was differentially expressed across three different expression platforms, including pancreatic tumor/normal samples. In addition, Ingenuity Pathways Analysis (IPA) and literature searches indicated that this seven-gene panel functions in one network associated with cellular movement/morphology/development, indicative of a “migration signature” of the 3p pathway. We tested whether two secreted proteins from this panel, tenascin C (TNC) and tissue factor pathway inhibitor (TFPI), could serve as plasma biomarkers. Plasma ELISA assays for TFPI/TNC resulted in a combined area under the curve (AUC) of 0.88 and, with addition of CA19-9, a combined AUC for the three-gene panel (TNC/TFPI/CA19-9), of 0.99 with 100% specificity at 90% sensitivity and 97.22% sensitivity at 90% specificity. Validation studies using TFPI only in a blinded sample set increased the performance of CA19-9 from an AUC of 0.84 to 0.94 with the two-gene panel. Results identify a novel 3p pathway–associated migration signature and plasma biomarker panel that has utility for discrimination of pancreatic cancer from normal controls and promise for clinical application. PMID:21071578

  13. Lockheed L-1011 TriStar to support Adaptive Performance Optimization study with NASA F-18 chase plan

    NASA Technical Reports Server (NTRS)

    1995-01-01

    This Lockheed L-1011 Tristar, seen here June 1995, is currently the subject of a new flight research experiment developed by NASA's Dryden Flight Research Center, Edwards, California, to improve the effiecency of large transport aircraft. Shown with a NASA F-18 chase plane over California's Sierra Nevada mountains during an earlier baseline flight, the jetliner operated by Oribtal Sciences Corp., recently flew its first data-gathering mission in the Adaptive Performance Optimization project. The experiment seeks to reduce fuel comsumption of large jetliners by improving the aerodynamic efficiency of their wings at cruise conditions. A research computer employing a sophisticated software program adapts to changing flight conditions by commanding small movements of the L-1011's outboard ailerons to give its wings the most efficient - or optimal - airfoil. Up to a dozen research flights will be flown in the current and follow-on phases of the project over the next couple years.

  14. Genetic Structure and Demographic History Reveal Migration of the Diamondback Moth Plutella xylostella (Lepidoptera: Plutellidae) from the Southern to Northern Regions of China

    PubMed Central

    Wei, Shu-Jun; Shi, Bao-Cai; Gong, Ya-Jun; Jin, Gui-Hua; Chen, Xue-Xin; Meng, Xiang-Feng

    2013-01-01

    The diamondback moth Plutella xylostella (Linnaeus) (Lepidoptera: Plutellidae) is one of the most destructive insect pests of cruciferous plants worldwide. Biological, ecological and genetic studies have indicated that this moth is migratory in many regions around the world. Although outbreaks of this pest occur annually in China and cause heavy damage, little is known concerning its migration. To better understand its migration pattern, we investigated the population genetic structure and demographic history of the diamondback moth by analyzing 27 geographical populations across China using four mitochondrial genes and nine microsatellite loci. The results showed that high haplotype diversity and low nucleotide diversity occurred in the diamondback moth populations, a finding that is typical for migratory species. No genetic differentiation among all populations and no correlation between genetic and geographical distance were found. However, pairwise analysis of the mitochondrial genes has indicated that populations from the southern region were more differentiated than those from the northern region. Gene flow analysis revealed that the effective number of migrants per generation into populations of the northern region is very high, whereas that into populations of the southern region is quite low. Neutrality testing, mismatch distribution and Bayesian Skyline Plot analyses based on mitochondrial genes all revealed that deviation from Hardy-Weinberg equilibrium and sudden expansion of the effective population size were present in populations from the northern region but not in those from the southern region. In conclusion, all our analyses strongly demonstrated that the diamondback moth migrates within China from the southern to northern regions with rare effective migration in the reverse direction. Our research provides a successful example of using population genetic approaches to resolve the seasonal migration of insects. PMID:23565158

  15. 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.

  16. 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

  17. Soluble vascular endothelial growth factor (VEGF) receptor-1 inhibits migration of human monocytic THP-1 cells in response to VEGF.

    PubMed

    Zhu, Cansheng; Xiong, Zhaojun; Chen, Xiaohong; Lu, Zhengqi; Zhou, Guoyu; Wang, Dunjing; Bao, Jian; Hu, Xueqiang

    2011-08-01

    We aimed to investigate the regulation and contribution of vascular endothelial growth factor (VEGF) and sFlt-1(1-3) to human monocytic THP-1 migration. Ad-sFlt-1/FLAG, a recombinant adenovirus carrying the human sFlt-1(1-3) (the first three extracellular domains of FLT-1, the hVEGF receptor-1) gene, was constructed. L929 cells were infected with Ad-sFlt-1/FLAG and the expression of sFlt-1 was detected by immunofluorescent assay and ELISA. Corning(®) Transwell(®) Filter Inserts containing polyethylene terephthalate (PET) membranes with pore sizes of 3 μm were used as an experimental model to simulate THP-1 migration. Five VEGF concentrations (0, 0.1, 1, 10 and 100 ng/ml), four concentrations of sFlt-1(1-3)/FLAG expression supernatants (0.1, 1, 10 and 100 ng/ml), and monocyte chemoattractant protein-1 (MCP-1, 10 ng/ml) were used to test the ability of THP-1 cells to migrate through PET membranes. The sFlt-1(1-3) gene was successfully recombined into Ad-sFlt-1/FLAG. sFlt-1(1-3) was expressed in L929 cells transfected with Ad-sFlt-1/FLAG. THP-1 cell migration increased with increasing concentrations of VEGF, while cell migration decreased with increasing concentrations of sFlt1(1-3)/FLAG. sFlt1(1-3)/FLAG had no effect on MCP-1-induced cell migration. This study demonstrated that VEGF is able to elicit a migratory response in THP-1 cells, and that sFlt-1(1-3) is an effective inhibitor of THP-1 migration towards VEGF.

  18. "Sniffer"—a novel tool for chasing vehicles and measuring traffic pollutants

    NASA Astrophysics Data System (ADS)

    Pirjola, L.; Parviainen, H.; Hussein, T.; Valli, A.; Hämeri, K.; Aaalto, P.; Virtanen, A.; Keskinen, J.; Pakkanen, T. A.; Mäkelä, T.; Hillamo, R. E.

    To measure traffic pollutants with high temporal and spatial resolution under real conditions a mobile laboratory was designed and built in Helsinki Polytechnic in close co-operation with the University of Helsinki. The equipment of the van provides gas phase measurements of CO and NO x, number size distribution measurements of fine and ultrafine particles by an electrical low pressure impactor, an ultrafine condensation particle counter and a scanning mobility particle sizer. Two inlet systems, one above the windshield and the other above the bumper, enable chasing of different type of vehicles. Also, meteorological and geographical parameters are recorded. This paper introduces the construction and technical details of the van, and presents data from the measurements performed during an LIPIKA campaign on the highway in Helsinki. Approximately 90% of the total particle number concentration was due to particles smaller than 50 nm on the highway in Helsinki. The peak concentrations exceeded often 200,000 particles cm -3 and reached sometimes a value of 10 6 cm -3. Typical size distribution of fine particles possessed bimodal structure with the modal mean diameters of 15-20 nm and ˜150 nm. Atmospheric dispersion of traffic pollutions were measured by moving away from the highway along the wind direction. At a distance of 120-140 m from the source the concentrations were diluted to one-tenth from the values at 9 m from the source.

  19. 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.

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

    PubMed

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

    2017-07-01

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

  1. Nuclear alternate estrogen receptor GPR30 mediates 17beta-estradiol-induced gene expression and migration in breast cancer-associated fibroblasts.

    PubMed

    Madeo, Antonio; Maggiolini, Marcello

    2010-07-15

    Fibroblasts are the principal cellular component of connective tissue and are associated with cancer cells at all stages of tumor progression. Structural and functional contributions of fibroblasts to the growth, survival, and invasive capacity of cancer cells are beginning to emerge. In breast carcinoma, approximately 80% of stromal fibroblasts termed cancer-associated fibroblasts (CAF) are thought to manifest an activated phenotype that promotes cancer cell proliferation tumor growth at metastatic sites similar to the primary tumor. In this report, we show that CAFs respond to physiologic concentrations of 17beta-estradiol (E2) by rapidly inducing extracellular signal-regulated kinase phosphorylation and immediate early gene expression, including c-fos and connective tissue growth factor, and cyclin D1. Notably, the E2 response is mediated by the alternate estrogen receptor GPR30, which interfaces with the epidermal growth factor receptor (EGFR) signaling pathway. In particular, E2 stimulates a physical interaction between GPR30 and phosphorylated EGFR, recruiting them to the cyclin D1 gene promoter. Nuclear localization induced by E2 was confirmed by cellular immunofluorescence methods. GPR30 was required for CAF proliferation and migration induced by E2. Our results provide important new mechanistic insights into how CAFs are stimulated by estrogen through a GPR30-mediated nuclear signaling pathway. More generally, they define estrogenic GPR30 signaling as a functionally important component of the tumor microenvironment. (c)2010 AACR.

  2. Interactions between a Candidate Gene for Migration (ADCYAP1), Morphology and Sex Predict Spring Arrival in Blackcap Populations.

    PubMed

    Mettler, Raeann; Segelbacher, Gernot; Schaefer, H Martin

    2015-01-01

    Avian research has begun to reveal associations between candidate genes and migratory behaviors of captive birds, yet few studies utilize genotypic, morphometric, and phenological data from wild individuals. Previous studies have identified an association between ADCYAP1 polymorphism and autumn migratory behavior (restlessness, or zugunruhe), but little is known about the relationship between ADCYAP1 and spring migratory behavior. The timing of spring migration and arrival to the breeding ground are phenological traits which could be particularly favorable for establishing territories and acquiring mates, thus important to fitness and reproductive success. Here, we investigated how individual genotypic ADCYAP1 variation and phenotypic variation (wing length and shape) of blackcaps (Sylvia atricapilla) affect spring arrival date across nine natural populations in Europe. We hypothesized that longer alleles should be associated with earlier spring arrival dates and expected the effect on arrival date to be stronger for males as they arrive earlier. However, we found that longer wings were associated with earlier spring arrival to the breeding grounds for females, but not for males. Another female-specific effect indicated an interaction between ADCYAP1 allele size and wing pointedness on the response of spring arrival: greater allele size had a positive effect on spring arrival date for females with rounder wings, while a negative effect was apparent for females with more pointed wings. Also, female heterozygotes with pointed wing tips arrived significantly earlier than both homozygotes with pointed wings and heterozygotes with round wings. Stable isotope ratios (δ2H) of a subset of blackcaps captured in Freiburg in 2011 allowed us also to assign individuals to their main overwintering areas in northwest (NW) and southwest (SW) Europe. NW males arrived significantly earlier to the Freiburg breeding site than both SW males and females in 2011. NW females had more

  3. Unified reduction principle for the evolution of mutation, migration, and recombination

    PubMed Central

    Altenberg, Lee; Liberman, Uri; Feldman, Marcus W.

    2017-01-01

    Modifier-gene models for the evolution of genetic information transmission between generations of organisms exhibit the reduction principle: Selection favors reduction in the rate of variation production in populations near equilibrium under a balance of constant viability selection and variation production. Whereas this outcome has been proven for a variety of genetic models, it has not been proven in general for multiallelic genetic models of mutation, migration, and recombination modification with arbitrary linkage between the modifier and major genes under viability selection. We show that the reduction principle holds for all of these cases by developing a unifying mathematical framework that characterizes all of these evolutionary models. PMID:28265103

  4. 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

  5. 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

  6. The RhoA Activator GEF-H1/Lfc Is a Transforming Growth Factor-β Target Gene and Effector That Regulates α-Smooth Muscle Actin Expression and Cell Migration

    PubMed Central

    Tsapara, Anna; Luthert, Phillip; Greenwood, John; Hill, Caroline S.

    2010-01-01

    Maintenance of the epithelial phenotype is crucial for tissue homeostasis. In the retina, dedifferentiation and loss of integrity of the retinal pigment epithelium (RPE) leads to retinal dysfunction and fibrosis. Transforming growth factor (TGF)-β critically contributes to RPE dedifferentiation and induces various responses, including increased Rho signaling, up-regulation of α-smooth muscle actin (SMA), and cell migration and dedifferentiation. Cellular TGF-β responses are stimulated by different signal transduction pathways: some are Smad dependent and others Smad independent. Alterations in Rho signaling are crucial to both types of TGF-β signaling, but how TGF-β-stimulates Rho signaling is poorly understood. Here, we show that primary RPE cells up-regulated GEF-H1 in response to TGF-β. GEF-H1 was the only detectable Rho exchange factor increased by TGF-β1 in a genome-wide expression analysis. GEF-H1 induction was Smad4-dependant and led to Rho activation. GEF-H1 inhibition counteracted α-SMA up-regulation and cell migration. In patients with retinal detachments and fibrosis, migratory RPE cells exhibited increased GEF-H1 expression, indicating that induction occurs in diseased RPE in vivo. Our data indicate that GEF-H1 is a target and functional effector of TGF-β by orchestrating Rho signaling to regulate gene expression and cell migration, suggesting that it represents a new marker and possible therapeutic target for degenerative and fibrotic diseases. PMID:20089843

  7. Dynamical Analysis of Density-dependent Selection in a Discrete one-island Migration Model

    Treesearch

    James H. Roberds; James F. Selgrade

    2000-01-01

    A system of non-linear difference equations is used to model the effects of density-dependent selection and migration in a population characterized by two alleles at a single gene locus. Results for the existence and stability of polymorphic equilibria are established. Properties for a genetically important class of equilibria associated with complete dominance in...

  8. Silencing heat shock protein 27 (HSP27) inhibits the proliferation and migration of vascular smooth muscle cells in vitro.

    PubMed

    Huang, Jie; Xie, Liang-di; Luo, Li; Zheng, Su-Li; Wang, Hua-Jun; Xu, Chang-Sheng

    2014-05-01

    The objective of this study was to examine the role of heat shock protein 27 (HSP27) in proliferation and migration of vascular smooth muscle cells (VSMCs). Three complementary DNA sequences targeting rat HSP27 gene were designed, synthesized, and subcloned into lentiviral vector. The interfering efficiency was detected by reverse transcriptase-polymerase chain reaction and Western blot. Methyl thiazolyl tetrazolium bromide assay was used for examining cell proliferation. F-actin polymerization was detected by FITC-Phalloidin staining using confocal microscopy. Modified Boyden chamber technique was used to assess VSMCs migration. The recombinant lentivirus containing RNAi targeting HSP27 gene significantly inhibited expression of HSP27 at both mRNA and protein levels. The interfering efficiencies of pNL-HSP27-EGFP-1, pNL-HSP27-EGFP-2, and pNL-HSP27-EGFP-3 were 71 %, 77 %, and 43 %, respectively. Reorganization of actin stimulated by PDGF-BB was markedly blocked by pretreatment with pNL-HSP27-EGFP-2. Proliferation and migration rates of VSMCs induced by PDGF-BB were inhibited by 30.8 % and 45.6 %, respectively, by pNL-HSP27-EGFP-2 (all P < 0.01). To conclude, these data indicate that HSP27 may regulate the proliferation, actin reorganization, and the migration of VSMCs. RNAi targeting at HSP27 may be a potential approach for inhibition of cell migration involved in pathogenesis of proliferative vascular diseases.

  9. 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…

  10. 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.

  11. [Knock-down of ZEB1 inhibits the proliferation, invasion and migration of gastric cancer cells].

    PubMed

    Chen, Dengyu; Chu, Yifan; Zheng, Qingwei; Xu, Zhiben; Zhou, Ping; Li, Sheng

    2017-08-01

    Objective To down-regulate the expression of zinc-finger E-box binding homeobox 1 (ZEB1) gene by shRNA, and investigate its effect on invasion, migration and proliferation, as well as the related gene expressions of lncRNA HOTAIR and E-cadherin in human gastric cancer BGC823 cells. Methods RNA interfering (RNAi) was used to knock down ZEB1 in gastric cancer BGC823 cells. The recombinant plasmid shZEB1 was constructed and transfected into the gastric cancer BGC823 cells by Lipofectamine TM 2000, and the stably transfected cells were isolated by G418 selection and limited dilution. The expression of ZEB1 mRNA and protein was detected by real-time quantitative PCR and Western blot analysis. Cell proliferation was determined by MTT assay, and the invasion and migration abilities of BGC823 cells were monitored by Transwell TM invasion assay and wound healing assay, respectively. The expressions of lncRNA HOTAIR and E-cadherin mRNA were detected by real-time quantitative PCR. Results After ZEB1 expression was successfully down-regulated in BGC823 cells by siRNA, the proliferation, invasion and migration rates in shZEB1 transfection group were significantly lower than those in control group; meanwhile, the expression of lncRNA HOTAIR was reduced and E-cadherin expression was enhanced. Conclusion Knock-down of ZEB1 expression by RNA interference can decease lncRNA HOTAIR expression and restrain cell proliferation, invasion and migration in gastric cancer BGC823 cells.

  12. Identification of olfactory receptor genes in the Japanese grenadier anchovy Coilia nasus.

    PubMed

    Zhu, Guoli; Wang, Liangjiang; Tang, Wenqiao; Wang, Xiaomei; Wang, Cong

    2017-01-01

    Olfaction is essential for fish to detect odorant elements in the environment and plays a critical role in navigating, locating food and detecting predators. Olfactory function is produced by the olfactory transduction pathway and is activated by olfactory receptors (ORs) through the binding of odorant elements. Recently, four types of olfactory receptors have been identified in vertebrate olfactory epithelium, including main odorant receptors (MORs), vomeronasal type receptors (VRs), trace-amine associated receptors (TAARs) and formyl peptide receptors (FPRs). It has been hypothesized that migratory fish, which have the ability to perform spawning migration, use olfactory cues to return to natal rivers. Therefore, obtaining OR genes from migratory fish will provide a resource for the study of molecular mechanisms that underlie fish spawning migration behaviors. Previous studies of OR genes have mainly focused on genomic data, however little information has been gained at the transcript level. In this study, we identified the OR genes of an economically important commercial fish Coilia nasus through searching for olfactory epithelium transcriptomes. A total of 142 candidate MOR, 52 V2R/OlfC, 32 TAAR and two FPR putative genes were identified. In addition, through genomic analysis we identified several MOR genes containing introns, which is unusual for vertebrate MOR genes. The transcriptome-scale mining strategy proved to be fruitful in identifying large sets of OR genes from species whose genome information is unavailable. Our findings lay the foundation for further research into the possible molecular mechanisms underlying the spawning migration behavior in C. nasus .

  13. A new conservation partnership: conserving the migratory birds of the Americas

    Treesearch

    Jack C. Capp; David Mehlman

    Over five billion birds move each year across the Americas, flying great distances over almost every location and habitat on the continents (Weidensaul 1999). Over 350 of the over 800 bird species in the United States migrate each year to Latin America and the Caribbean (Degraaf and Rappole 1995). Some fly each way over 4000 miles, chasing the seasons across oceans and...

  14. Detecting the existence of gene flow between Spanish and North African goats through a coalescent approach.

    PubMed

    Martínez, Amparo; Manunza, Arianna; Delgado, Juan Vicente; Landi, Vincenzo; Adebambo, Ayotunde; Ismaila, Muritala; Capote, Juan; El Ouni, Mabrouk; Elbeltagy, Ahmed; Abushady, Asmaa M; Galal, Salah; Ferrando, Ainhoa; Gómez, Mariano; Pons, Agueda; Badaoui, Bouabid; Jordana, Jordi; Vidal, Oriol; Amills, Marcel

    2016-12-14

    Human-driven migrations are one of the main processes shaping the genetic diversity and population structure of domestic species. However, their magnitude and direction have been rarely analysed in a statistical framework. We aimed to estimate the impact of migration on the population structure of Spanish and African goats. To achieve this goal, we analysed a dataset of 1,472 individuals typed with 23 microsatellites. Population structure of African and Spanish goats was moderate (mean F ST  = 0.07), with the exception of the Canarian and South African breeds that displayed a significant differentiation when compared to goats from North Africa and Nigeria. Measurement of gene flow with Migrate-n and IMa coalescent genealogy samplers supported the existence of a bidirectional gene flow between African and Spanish goats. Moreover, IMa estimates of the effective number of migrants were remarkably lower than those calculated with Migrate-n and classical approaches. Such discrepancies suggest that recent divergence, rather than extensive gene flow, is the main cause of the weak population structure observed in caprine breeds.

  15. Detecting the existence of gene flow between Spanish and North African goats through a coalescent approach

    PubMed Central

    Martínez, Amparo; Manunza, Arianna; Delgado, Juan Vicente; Landi, Vincenzo; Adebambo, Ayotunde; Ismaila, Muritala; Capote, Juan; El Ouni, Mabrouk; Elbeltagy, Ahmed; Abushady, Asmaa M.; Galal, Salah; Ferrando, Ainhoa; Gómez, Mariano; Pons, Agueda; Badaoui, Bouabid; Jordana, Jordi; Vidal, Oriol; Amills, Marcel

    2016-01-01

    Human-driven migrations are one of the main processes shaping the genetic diversity and population structure of domestic species. However, their magnitude and direction have been rarely analysed in a statistical framework. We aimed to estimate the impact of migration on the population structure of Spanish and African goats. To achieve this goal, we analysed a dataset of 1,472 individuals typed with 23 microsatellites. Population structure of African and Spanish goats was moderate (mean FST = 0.07), with the exception of the Canarian and South African breeds that displayed a significant differentiation when compared to goats from North Africa and Nigeria. Measurement of gene flow with Migrate-n and IMa coalescent genealogy samplers supported the existence of a bidirectional gene flow between African and Spanish goats. Moreover, IMa estimates of the effective number of migrants were remarkably lower than those calculated with Migrate-n and classical approaches. Such discrepancies suggest that recent divergence, rather than extensive gene flow, is the main cause of the weak population structure observed in caprine breeds. PMID:27966592

  16. Evolutionary History of Helicobacter pylori Sequences Reflect Past Human Migrations in Southeast Asia

    PubMed Central

    Breurec, Sebastien; Guillard, Bertrand; Hem, Sopheak; Brisse, Sylvain; Dieye, Fatou Bintou; Huerre, Michel; Oung, Chakravuth; Raymond, Josette; Sreng Tan, Tek; Thiberge, Jean-Michel; Vong, Sirenda; Monchy, Didier; Linz, Bodo

    2011-01-01

    The human population history in Southeast Asia was shaped by numerous migrations and population expansions. Their reconstruction based on archaeological, linguistic or human genetic data is often hampered by the limited number of informative polymorphisms in classical human genetic markers, such as the hypervariable regions of the mitochondrial DNA. Here, we analyse housekeeping gene sequences of the human stomach bacterium Helicobacter pylori from various countries in Southeast Asia and we provide evidence that H. pylori accompanied at least three ancient human migrations into this area: i) a migration from India introducing hpEurope bacteria into Thailand, Cambodia and Malaysia; ii) a migration of the ancestors of Austro-Asiatic speaking people into Vietnam and Cambodia carrying hspEAsia bacteria; and iii) a migration of the ancestors of the Thai people from Southern China into Thailand carrying H. pylori of population hpAsia2. Moreover, the H. pylori sequences reflect iv) the migrations of Chinese to Thailand and Malaysia within the last 200 years spreading hspEasia strains, and v) migrations of Indians to Malaysia within the last 200 years distributing both hpAsia2 and hpEurope bacteria. The distribution of the bacterial populations seems to strongly influence the incidence of gastric cancer as countries with predominantly hspEAsia isolates exhibit a high incidence of gastric cancer while the incidence is low in countries with a high proportion of hpAsia2 or hpEurope strains. In the future, the host range expansion of hpEurope strains among Asian populations, combined with human motility, may have a significant impact on gastric cancer incidence in Asia. PMID:21818291

  17. Evolutionary history of Helicobacter pylori sequences reflect past human migrations in Southeast Asia.

    PubMed

    Breurec, Sebastien; Guillard, Bertrand; Hem, Sopheak; Brisse, Sylvain; Dieye, Fatou Bintou; Huerre, Michel; Oung, Chakravuth; Raymond, Josette; Tan, Tek Sreng; Thiberge, Jean-Michel; Vong, Sirenda; Monchy, Didier; Linz, Bodo

    2011-01-01

    The human population history in Southeast Asia was shaped by numerous migrations and population expansions. Their reconstruction based on archaeological, linguistic or human genetic data is often hampered by the limited number of informative polymorphisms in classical human genetic markers, such as the hypervariable regions of the mitochondrial DNA. Here, we analyse housekeeping gene sequences of the human stomach bacterium Helicobacter pylori from various countries in Southeast Asia and we provide evidence that H. pylori accompanied at least three ancient human migrations into this area: i) a migration from India introducing hpEurope bacteria into Thailand, Cambodia and Malaysia; ii) a migration of the ancestors of Austro-Asiatic speaking people into Vietnam and Cambodia carrying hspEAsia bacteria; and iii) a migration of the ancestors of the Thai people from Southern China into Thailand carrying H. pylori of population hpAsia2. Moreover, the H. pylori sequences reflect iv) the migrations of Chinese to Thailand and Malaysia within the last 200 years spreading hspEasia strains, and v) migrations of Indians to Malaysia within the last 200 years distributing both hpAsia2 and hpEurope bacteria. The distribution of the bacterial populations seems to strongly influence the incidence of gastric cancer as countries with predominantly hspEAsia isolates exhibit a high incidence of gastric cancer while the incidence is low in countries with a high proportion of hpAsia2 or hpEurope strains. In the future, the host range expansion of hpEurope strains among Asian populations, combined with human motility, may have a significant impact on gastric cancer incidence in Asia.

  18. Posttranslational modifications of Sindbis virus glycoproteins: electrophoretic analysis of pulse-chase-labeled infected cells.

    PubMed

    Bonatti, S; Cancedda, F D

    1982-04-01

    Cytoplasmic extracts prepared from Sindbis virus-infected chicken embryo fibroblasts pulse-chase-labeled with [35S]methionine 6 h postinfection were analyzed on a highly resolving sodium dodecyl sulfate-gel either directly or after various treatments. The results we obtained suggest that (i) the proteolytic cleavage which converts PE2 to E2 glycoprotein takes place intracellularly, before or at least during the formation of complex-type oligosaccharide side chains; and (ii) E1 glycoprotein undergoes a complex maturation pattern. Newly synthesized E1 has a molecular weight of 53,000: shortly thereafter, this 53,000 (53K) form was converted to a 50K form. Subsequently, the 50K form decreased its apparent molecular weight progressively and eventually comigrated with E1 glycoprotein present in the extracellular virus, which displays a molecular weight of 51,000 to 52,000. The conversion of the 53K to the 50K form was not the result of a proteolytic processing and did not depend on glycosylation or disulfide bridge formation and exchange. The possible mechanisms of this conversion are discussed. The second conversion step (from the 50K to the 51-52K form) was due to the formation of complex-type oligosaccharide and was reversed by incubating the cellular extracts with neuraminidase before electrophoretic analysis.

  19. Proteoglycans and neuronal migration in the cerebral cortex during development and disease

    PubMed Central

    Maeda, Nobuaki

    2015-01-01

    Chondroitin sulfate proteoglycans and heparan sulfate proteoglycans are major constituents of the extracellular matrix and the cell surface in the brain. Proteoglycans bind with many proteins including growth factors, chemokines, axon guidance molecules, and cell adhesion molecules through both the glycosaminoglycan and the core protein portions. The functions of proteoglycans are flexibly regulated due to the structural variability of glycosaminoglycans, which are generated by multiple glycosaminoglycan synthesis and modifying enzymes. Neuronal cell surface proteoglycans such as PTPζ, neuroglycan C and syndecan-3 function as direct receptors for heparin-binding growth factors that induce neuronal migration. The lectican family, secreted chondroitin sulfate proteoglycans, forms large aggregates with hyaluronic acid and tenascins, in which many signaling molecules and enzymes including matrix proteases are preserved. In the developing cerebrum, secreted chondroitin sulfate proteoglycans such as neurocan, versican and phosphacan are richly expressed in the areas that are strategically important for neuronal migration such as the striatum, marginal zone, subplate and subventricular zone in the neocortex. These proteoglycans may anchor various attractive and/or repulsive cues, regulating the migration routes of inhibitory neurons. Recent studies demonstrated that the genes encoding proteoglycan core proteins and glycosaminoglycan synthesis and modifying enzymes are associated with various psychiatric and intellectual disorders, which may be related to the defects of neuronal migration. PMID:25852466

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

    PubMed Central

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

    2015-01-01

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

  1. Optimization of Dendritic Cell-Mediated Cytotoxic T-Cell Activation by Tracking of Dendritic Cell Migration Using Reporter Gene Imaging.

    PubMed

    Lee, Hongje; Lee, Ho Won; La Lee, You; Jeon, Yong Hyun; Jeong, Shin Young; Lee, Sang-Woo; Lee, Jaetae; Ahn, Byeong-Cheol

    2018-06-01

    The aim of this study is to optimize the dendritic cell (DC)-mediated T-cell activation using reporter gene imaging and flow cytometric analysis in living mice. A murine dendritic cell line (DC2.4) co-expressing effluc and Thy1.1 genes were established by transfection with retroviral vectors. Thy1.1 positive cells were sorted by magnetic bead separation system (DC2.4/effluc). Cell proliferation assay and phenotype analysis to determine the effects of gene transduction on the function of dendritic cells between parental DC2.4 and DC2.4/effluc were performed. To optimize the DC-mediated immune response by cell number or frequency, different cell numbers (5 × 10 5 , 1 × 10 6 , and 2 × 10 6  DC2.4/effluc) or different frequencies of DC2.4/effluc (first, second, and third injections) were injected in the right footpad of mice. The migration of the DC2.4/effluc into the draining popliteal lymph node of mice was monitored by bioluminescence imaging (BLI). Flow cytometric analysis was performed with splenocytes to determine the cytotoxic T-cell population after injection of DC2.4/effluc. Parental DC2.4 and DC2.4/effluc exhibit no significant differences in their proliferation and phenotype. BLI signals were observed in the draining popliteal lymph node at day 1 after injection of DC2.4/effluc in 1 × 10 6 and 2 × 10 6 cells-injected groups. The highest BLI signal intensity was detected in 2 × 10 6 cells-injected mice. On day 11, the BLI signal was detected in only 2 × 10 6 cell-injected group but not in other groups. Optimized cell numbers (2 × 10 6 ) were injected in three animal groups with a different frequency (first, second, and third injection groups). The BLI signal was detected at day 1 and maintained until day 7 in the first injection group, but there is low signal intensity in the second and the third injection groups. Although the expression levels of Thy1.1 gene in the first injection group were very high, there reveals no expression of

  2. Bardoxolone-methyl inhibits migration and metabolism in MCF7 cells.

    PubMed

    Refaat, Alaa; Pararasa, Chathyan; Arif, Muhammed; Brown, James E P; Carmichael, Amtul; Ali, Sameh S; Sakurai, Hiroaki; Griffiths, Helen R

    2017-02-01

    Bardoxolone-methyl (BAR) is reported to have anti-inflammatory, anti-proliferative and anti-fibrotic effects. BAR activates Nrf2 and may ameliorate oxidative stress through induction of antioxidant genes. However, off-target effects, probably concentration and NFkB-dependent, have limited the clinical use of BAR. Nrf2 regulates expression of antioxidant and mitochondrial genes and has been proposed as a target for both obesity and breast cancer. Therefore, we explored whether BAR can alter migration and proliferation in the MCF7 cell line and whether metabolic function is affected by BAR. Incubation with BAR caused a time-dependent migratory inhibition and an associated decrease in mitochondrial respiration. Both migratory and mitochondrial inhibition by BAR were further enhanced in the presence of fatty acids. In addition to the activation of Nrf2, BAR altered the expression of target mRNA GCLC and UCP1. After 24 h, BAR inhibited both glycolytic capacity, reserve (p < 0.05) and oxidative phosphorylation (p < 0.001) with an associated increase in mitochondrial ROS and loss of intracellular glutathione in MCF7 cells; however, impairment of mitochondrial activity was prevented by N-acetyl cysteine. The fatty acid, palmitate, increased mitochondrial ROS, impaired migration and oxidative phosphorylation but palmitate toxicity towards MCF7 could not be inhibited by N-acetyl cysteine suggesting that they exert effects through different pathways. BAR-activated AKT, induced DNA damage and inhibited cell proliferation. When the proteasome was inhibited, there was loss of BAR-mediated changes in p65 phosphorylation and SOD2 expression suggesting non-canonical NFkB signaling effects. These data suggest that BAR-induced ROS are important in inhibiting MCF7 migration and metabolism by negatively affecting glycolytic capacity and mitochondrial function.

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

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

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

  4. 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…

  5. Downregulation of CD9 in Keratinocyte Contributes to Cell Migration via Upregulation of Matrix Metalloproteinase-9

    PubMed Central

    Jiang, Xu-pin; Zhang, Dong-xia; Teng, Miao; Zhang, Qiong; Zhang, Jia-ping; Huang, Yue-sheng

    2013-01-01

    Tetraspanin CD9 has been implicated in various cellular and physiological processes, including cell migration. In our previous study, we found that wound repair is delayed in CD9-null mice, suggesting that CD9 is critical for cutaneous wound healing. However, many cell types, including immune cells, endothelial cells, keratinocytes and fibroblasts undergo marked changes in gene expression and phenotype, leading to cell proliferation, migration and differentiation during wound repair, whether CD9 regulates kerationcytes migration directly remains unclear. In this study, we showed that the expression of CD9 was downregulated in migrating keratinocytes during wound repair in vivo and in vitro. Recombinant adenovirus vector for CD9 silencing or overexpressing was constructed and used to infect HaCaT cells. Using cell scratch wound assay and cell migration assay, we have also demonstrated that downregulation of CD9 promoted keratinocyte migration in vitro, whereas CD9 overexpression inhibited cell migration. Moreover, CD9 inversely regulated the activity and expression of MMP-9 in keratinocytes, which was involved in CD9-regulated keratinocyte migration. Importantly, CD9 silencing-activated JNK signaling was accompanied by the upregulation of MMP-9 activity and expression. Coincidentally, we found that SP600125, a JNK pathway inhibitor, decreased the activity and expression of MMP-9 of CD9-silenced HaCaT cells. Thus, our results suggest that CD9 is downregulated in migrating keratinocytes in vivo and in vitro, and a low level of CD9 promotes keratinocyte migration in vitro, in which the regulation of MMP-9 through the JNK pathway plays an important role. PMID:24147081

  6. 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.

  7. 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…

  8. Standardized Cannabis sativa extract attenuates tau and stathmin gene expression in the melanoma cell line.

    PubMed

    Vaseghi, Golnaz; Taki, Mohamad Javad; Javanmard, Shaghayegh Haghjooy

    2017-10-01

    Metastasis is the main cause of death in patients with melanoma. Cannabis-based medicines are effective adjunctive drugs in cancer patients. Tau and Stathmin proteins are the key proteins in cancer metastasis. Here we have investigated the effect of a standardized Cannabis sativa extract on cell migration and Tau and Stathmin gene expression in the melanoma cell line. In the treatment group, melanoma (B1617) was treated 48 hr with various concentrations of standardized C. sativa extract. Cells with no treatment were considered as the control group, then study was followed by Quantitative RT-Real Time PCR assay. Relative gene expression was calculated by the ΔΔct method. Migration assay was used to evaluate cancer metastasis. Tau and stathmin gene expression was significantly decreased compared to the control group. Cell migration was also significantly reduced compared to controls. C. sativa decreased tau and stathmin gene expression and cancer metastasis. The results may have some clinical relevance for the use of cannabis-based medicines in patients with metastatic melanoma.

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

    PubMed

    De Haas, Hein; Fokkema, Tineke

    2010-01-01

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

  10. 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

  11. 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

  12. Migration in far west Nepal: intergenerational linkages between internal and international migration of rural-to-urban migrants.

    PubMed

    Poertner, Ephraim; Junginger, Mathias; Müller-Böker, Ulrike

    2011-01-01

    In Nepal, international labor migration to India and overseas, as well as internal migration to the rural Nepalese lowlands, is of high socioeconomic significance. Scholarly debates about migration in Nepal have gradually shifted from an economic to a more holistic perspective, also incorporating social dimensions. However, little evidence has been generated about internal migration to urban destinations and the potential linkages between international and internal migration. This article draws on Bourdieu's “Theory of Practice” and sees migration as a social practice. Accordingly, migration practice is regarded as a strategy social agents apply to increase or transfer capitals and ultimately secure or improve their social position. Evidence for this argument is based on a qualitative case study of rural to urban migrants in Far West Nepal conducted in July and August 2009. The study at hand addresses linkages between internal and international migration practices and provides insight about a social stratum that is often neglected in migration research: the middle class and, more precisely, government employees. The authors show that social relations are crucial for channeling internal migration to a specific destination. Furthermore, they unveil how internal migration is connected to the international labor migration of former generations. Finally, the authors examine how migration strategies adopted over generations create multi-local social networks rooted in the family's place of origin.

  13. Mutation in cpsf6/CFIm68 (Cleavage and Polyadenylation Specificity Factor Subunit 6) causes short 3'UTRs and disturbs gene expression in developing embryos, as revealed by an analysis of primordial germ cell migration using the medaka mutant naruto.

    PubMed

    Sasado, Takao; Kondoh, Hisato; Furutani-Seiki, Makoto; Naruse, Kiyoshi

    2017-01-01

    Our previous studies analyzing medaka mutants defective in primordial germ cell (PGC) migration identified cxcr4b and cxcr7, which are both receptors of the chemokine sdf1/cxcl12, as key regulators of PGC migration. Among PGC migration mutants, naruto (nar) is unique in that the mutant phenotype includes gross morphological abnormalities of embryos, suggesting that the mutation affects a broader range of processes. A fine genetic linkage mapping and genome sequencing showed the nar gene encodes Cleavage and Polyadenylation Specificity Factor subunit 6 (CPSF6/CFIm68). CPSF6 is a component of the Cleavage Factor Im complex (CFIm) which plays a key role in pre-mRNA 3'-cleavage and polyadenylation. 3'RACE of sdf1a/b and cxcr7 transcripts in the mutant embryos indicated shorter 3'UTRs with poly A additions occurring at more upstream positions than wild-type embryos, suggesting CPSF6 functions to prevent premature 3'UTR cleavage. In addition, expression of the coding region sequences of sdf1a/b in nar mutants was more anteriorly extended in somites than wild-type embryos, accounting for the abnormally extended distribution of PGCs in nar mutants. An expected consequence of shortening 3'UTR is the escape from the degradation mechanism mediated by microRNAs interacting with distal 3'UTR sequence. The abnormal expression pattern of sdf1a coding sequence may be at least partially accounted for by this mechanism. Given the pleiotropic effects of nar mutation, further analysis using the nar mutant will reveal processes in which CPSF6 plays essential regulatory roles in poly A site selection and involvement of 3'UTRs in posttranscriptional gene regulation in various genes in vivo.

  14. Mutation in cpsf6/CFIm68 (Cleavage and Polyadenylation Specificity Factor Subunit 6) causes short 3'UTRs and disturbs gene expression in developing embryos, as revealed by an analysis of primordial germ cell migration using the medaka mutant naruto

    PubMed Central

    Kondoh, Hisato; Furutani-Seiki, Makoto; Naruse, Kiyoshi

    2017-01-01

    Our previous studies analyzing medaka mutants defective in primordial germ cell (PGC) migration identified cxcr4b and cxcr7, which are both receptors of the chemokine sdf1/cxcl12, as key regulators of PGC migration. Among PGC migration mutants, naruto (nar) is unique in that the mutant phenotype includes gross morphological abnormalities of embryos, suggesting that the mutation affects a broader range of processes. A fine genetic linkage mapping and genome sequencing showed the nar gene encodes Cleavage and Polyadenylation Specificity Factor subunit 6 (CPSF6/CFIm68). CPSF6 is a component of the Cleavage Factor Im complex (CFIm) which plays a key role in pre-mRNA 3'-cleavage and polyadenylation. 3'RACE of sdf1a/b and cxcr7 transcripts in the mutant embryos indicated shorter 3’UTRs with poly A additions occurring at more upstream positions than wild-type embryos, suggesting CPSF6 functions to prevent premature 3’UTR cleavage. In addition, expression of the coding region sequences of sdf1a/b in nar mutants was more anteriorly extended in somites than wild-type embryos, accounting for the abnormally extended distribution of PGCs in nar mutants. An expected consequence of shortening 3'UTR is the escape from the degradation mechanism mediated by microRNAs interacting with distal 3’UTR sequence. The abnormal expression pattern of sdf1a coding sequence may be at least partially accounted for by this mechanism. Given the pleiotropic effects of nar mutation, further analysis using the nar mutant will reveal processes in which CPSF6 plays essential regulatory roles in poly A site selection and involvement of 3'UTRs in posttranscriptional gene regulation in various genes in vivo. PMID:28253363

  15. 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

  16. Pre-Treatment of Human Mesenchymal Stem Cells With Inflammatory Factors or Hypoxia Does Not Influence Migration to Osteoarthritic Cartilage and Synovium.

    PubMed

    Leijs, Maarten J C; van Buul, Gerben M; Verhaar, Jan A N; Hoogduijn, Martin J; Bos, Pieter K; van Osch, Gerjo J V M

    2017-04-01

    Mesenchymal stem cells (MSCs) are promising candidates as a cell-based therapy for osteoarthritis (OA), although current results are modest. Pre-treatment of MSCs before application might improve their therapeutic efficacy. Pre-treatment of MSCs with inflammatory factors or hypoxia will improve their migration and adhesion capacities toward OA-affected tissues. Controlled laboratory study. We used real-time polymerase chain reaction to determine the effects of different fetal calf serum (FCS) batches, platelet lysate (PL), hypoxia, inflammatory factors, factors secreted by OA tissues, and OA synovial fluid (SF) on the expression of 12 genes encoding chemokine or adhesion receptors. Migration of MSCs toward factors secreted by OA tissues was studied in vitro, and attachment of injected MSCs was evaluated in vivo in healthy and OA knees of male Wistar rats. Different FCS batches, PL, or hypoxia did not influence the expression of the migration and adhesion receptor genes. Exposure to inflammatory factors altered the expression of CCR1, CCR4, CD44, PDGFRα, and PDGFRβ. MSCs migrated toward factors secreted by OA tissues in vitro. Neither pre-treatment with inflammatory factors nor the presence of OA influenced MSC migration in vitro or adhesion in vivo. Factors secreted by OA tissues increase MSC migration in vitro. In vivo, no difference in MSC adhesion was found between OA and healthy knees. Pre-treatment with inflammatory factors influenced the expression of migration and adhesion receptors of MSCs but not their migration in vitro or adhesion in vivo. To improve the therapeutic capacity of intra-articular injection of MSCs, they need to remain intra-articular for a longer period of time. Pre-treatment of MSCs with hypoxia or inflammatory factors did not increase the migration or adhesion capacity of MSCs and will therefore not likely prolong their intra-articular longevity. Alternative approaches to prolong the intra-articular presence of MSCs should be developed

  17. Migration pattern of hepatitis A virus genotype IA in North-Central Tunisia.

    PubMed

    Beji-Hamza, Abir; Taffon, Stefania; Mhalla, Salma; Lo Presti, Alessandra; Equestre, Michele; Chionne, Paola; Madonna, Elisabetta; Cella, Eleonora; Bruni, Roberto; Ciccozzi, Massimo; Aouni, Mahjoub; Ciccaglione, Anna Rita

    2015-02-08

    Hepatitis A virus (HAV) epidemiology in Tunisia has changed from high to intermediate endemicity in the last decades. However, several outbreaks continue to occur. The last reported sequences from Tunisian HAV strains date back to 2006. In order to provide an updated overview of the strains currently circulating in Tunisia, a large-scale molecular analysis of samples from hepatitis A cases was performed, the first in Tunisia. Biological samples were collected from patients with laboratory confirmed hepatitis A: 145 sera samples in Tunis, Monastir, Sousse and Kairouan from 2008 to 2013 and 45 stool samples in Mahdia in 2009. HAV isolates were characterised by nested RT-PCR (VP1/2A region) and sequencing. The sequences finally obtained from 81 samples showed 78 genotype IA and 3 genotype IB isolates. A Tunisian genotype IA sequence dataset, including both the 78 newly obtained IA sequences and 51 sequences retrieved from GenBank, was used for phylogenetic investigation, including analysis of migration pattern among six towns. Virus gene flow from Sfax and Monastir was directed to all other towns; in contrast, the gene flows from Sousse, Tunis, Mahdia and Kairouan were directed to three, two, one and no towns, respectively. Several different HAV strains co-circulate in Tunisia, but the predominant genotype still continues to be IA (78/81, 96% isolates). A complex gene flow (migration) of HAV genotype IA was observed, with Sfax and Monastir showing gene flows to all other investigated towns. This approach coupled to a wider sampling can prove useful to investigate the factors underlying the spread of HAV in Tunisia and, thus, to implement appropriate preventing measures.

  18. Genomic Ancestry of North Africans Supports Back-to-Africa Migrations

    PubMed Central

    Gravel, Simon; Wang, Wei; Brisbin, Abra; Byrnes, Jake K.; Fadhlaoui-Zid, Karima; Zalloua, Pierre A.; Moreno-Estrada, Andres; Bertranpetit, Jaume; Bustamante, Carlos D.; Comas, David

    2012-01-01

    North African populations are distinct from sub-Saharan Africans based on cultural, linguistic, and phenotypic attributes; however, the time and the extent of genetic divergence between populations north and south of the Sahara remain poorly understood. Here, we interrogate the multilayered history of North Africa by characterizing the effect of hypothesized migrations from the Near East, Europe, and sub-Saharan Africa on current genetic diversity. We present dense, genome-wide SNP genotyping array data (730,000 sites) from seven North African populations, spanning from Egypt to Morocco, and one Spanish population. We identify a gradient of likely autochthonous Maghrebi ancestry that increases from east to west across northern Africa; this ancestry is likely derived from “back-to-Africa” gene flow more than 12,000 years ago (ya), prior to the Holocene. The indigenous North African ancestry is more frequent in populations with historical Berber ethnicity. In most North African populations we also see substantial shared ancestry with the Near East, and to a lesser extent sub-Saharan Africa and Europe. To estimate the time of migration from sub-Saharan populations into North Africa, we implement a maximum likelihood dating method based on the distribution of migrant tracts. In order to first identify migrant tracts, we assign local ancestry to haplotypes using a novel, principal component-based analysis of three ancestral populations. We estimate that a migration of western African origin into Morocco began about 40 generations ago (approximately 1,200 ya); a migration of individuals with Nilotic ancestry into Egypt occurred about 25 generations ago (approximately 750 ya). Our genomic data reveal an extraordinarily complex history of migrations, involving at least five ancestral populations, into North Africa. PMID:22253600

  19. Characterization of the Photon Counting CHASE Jr., Chip Built in a 40-nm CMOS Process With a Charge Sharing Correction Algorithm Using a Collimated X-Ray Beam

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

    Krzyżanowska, A.; Deptuch, G. W.; Maj, P.

    This paper presents the detailed characterization of a single photon counting chip, named CHASE Jr., built in a CMOS 40-nm process, operating with synchrotron radiation. The chip utilizes an on-chip implementation of the C8P1 algorithm. The algorithm eliminates the charge sharing related uncertainties, namely, the dependence of the number of registered photons on the discriminator’s threshold, set for monochromatic irradiation, and errors in the assignment of an event to a certain pixel. The article presents a short description of the algorithm as well as the architecture of the CHASE Jr., chip. The analog and digital functionalities, allowing for proper operationmore » of the C8P1 algorithm are described, namely, an offset correction for two discriminators independently, two-stage gain correction, and different operation modes of the digital blocks. The results of tests of the C8P1 operation are presented for the chip bump bonded to a silicon sensor and exposed to the 3.5- μm -wide pencil beam of 8-keV photons of synchrotron radiation. It was studied how sensitive the algorithm performance is to the chip settings, as well as the uniformity of parameters of the analog front-end blocks. Presented results prove that the C8P1 algorithm enables counting all photons hitting the detector in between readout channels and retrieving the actual photon energy.« less

  20. Traffic-Sensitive Live Migration of Virtual Machines

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

    Deshpande, Umesh; Keahey, Kate

    2015-01-01

    In this paper we address the problem of network contention between the migration traffic and the VM application traffic for the live migration of co-located Virtual Machines (VMs). When VMs are migrated with pre-copy, they run at the source host during the migration. Therefore the VM applications with predominantly outbound traffic contend with the outgoing migration traffic at the source host. Similarly, during post-copy migration, the VMs run at the destination host. Therefore the VM applications with predominantly inbound traffic contend with the incoming migration traffic at the destination host. Such a contention increases the total migration time of themore » VMs and degrades the performance of VM application. Here, we propose traffic-sensitive live VM migration technique to reduce the contention of migration traffic with the VM application traffic. It uses a combination of pre-copy and post-copy techniques for the migration of the co-located VMs, instead of relying upon any single pre-determined technique for the migration of all the VMs. We base the selection of migration techniques on VMs' network traffic profiles so that the direction of migration traffic complements the direction of the most VM application traffic. We have implemented a prototype of traffic-sensitive migration on the KVM/QEMU platform. In the evaluation, we compare traffic-sensitive migration against the approaches that use only pre-copy or only post-copy for VM migration. We show that our approach minimizes the network contention for migration, thus reducing the total migration time and the application degradation.« less

  1. Expression of WNT genes in cervical cancer-derived cells: Implication of WNT7A in cell proliferation and migration.

    PubMed

    Ramos-Solano, Moisés; Meza-Canales, Ivan D; Torres-Reyes, Luis A; Alvarez-Zavala, Monserrat; Alvarado-Ruíz, Liliana; Rincon-Orozco, Bladimiro; Garcia-Chagollan, Mariel; Ochoa-Hernández, Alejandra B; Ortiz-Lazareno, Pablo C; Rösl, Frank; Gariglio, Patricio; Jave-Suárez, Luis F; Aguilar-Lemarroy, Adriana

    2015-07-01

    According to the multifactorial model of cervical cancer (CC) causation, it is now recognized that other modifications, in addition to Human papillomavirus (HPV) infection, are necessary for the development of this neoplasia. Among these, it has been proposed that a dysregulation of the WNT pathway might favor malignant progression of HPV-immortalized keratinocytes. The aim of this study was to identify components of the WNT pathway differentially expressed in CC vs. non-tumorigenic, but immortalized human keratinocytes. Interestingly, WNT7A expression was found strongly downregulated in cell lines and biopsies derived from CC. Restoration of WNT7A in CC-derived cell lines using a lentiviral gene delivery system or after adding a recombinant human protein decreases cell proliferation. Likewise, WNT7A silencing in non-tumorigenic cells markedly accelerates proliferation. Decreased WNT7A expression was due to hypermethylation at particular CpG sites. To our knowledge, this is the first study reporting reduced WNT7A levels in CC-derived cells and that ectopic WNT7A restoration negatively affects cell proliferation and migration. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. 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.

  3. 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.

  4. ALG2 regulates glioblastoma cell proliferation, migration and tumorigenicity

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

    Zhang, Dunke; Wang, Feng; Pang, Yi

    Apoptosis-linked gene-2 (ALG-2), also known as programmed cell death 6 (PDCD6), has recently been reported to be aberrantly expressed in various tumors and required for tumor cell viability. The aim of the present study was to investigate whether ALG-2 plays a crucial role in tumor cell proliferation, migration and tumorigenicity. In this study, we examined the expression of PDCD6 in glioblastoma cell lines and found that ALG-2 was generally expressed in glioblastoma cell lines. We also performed an analysis of an online database and found that high expression of ALG-2 was associated with poor prognosis (p = 0.039). We found that over-expressionmore » of ALG2 in glioblastoma could inhibit cell proliferation and, conversely, that down-regulation of ALG2 could promote cell proliferation. Further studies showed that over-expression of ALG2 inhibited the migration of tumor cells, whereas down-regulation of ALG2 promoted tumor cell migration. Finally, in vitro and in vivo studies showed that over-expression of ALG2 inhibited the tumorigenic ability of tumor cells, while down-regulation of ALG2 promoted tumor cell tumorigenic ability. In conclusion, ALG2 has a tumor suppressive role in glioblastoma and might be a potential target for the treatment of glioblastoma. - Highlights: • Low ALG2 expression is indicative of poor prognosis in glioblastoma patients. • ALG2 is required for cell proliferation in GBM cells. • ALG2 is involved in GBM cell migration. • ALG2 is involved in GBM cell self-renewal and tumorigenesis in vitro and in vivo.« less

  5. Pre-migration persecution, post-migration stressors and resources, and post-migration mental health: A study of severely traumatized U.S. Arab immigrant women

    PubMed Central

    Norris, Anne E.; Aroian, Karen J.; Nickerson, David

    2015-01-01

    Background Competing theories exist regarding the importance of pre-migration trauma as compared to post-migration stressors and resources with respect to the risk to immigrant mental health. Objective To examine how type of pre-migration trauma, post-migration stressors, and post-migration resources differentially predict PTSD and MDD symptomatology in Arab immigrant women who have been exposed to pre-migration trauma. Design Descriptive; using multinomial logistic regression to explain membership in one of four groups: (a) PTSD only (n = 14); (b) major depressive disorder (MDD) (n = 162), (c) Co-Morbid PTSD-MDD (n = 148), (d) Subclinical Symptoms (n = 209). Results Post-immigration related stressors (as measured by the Demands of Immigration (DI)) had the strongest effect: Parameter estimates indicated that a unit increase in DI scores was associated with a nearly 17 fold increase in the likelihood of being in the Co-morbid relative to the Subclinical group, and a nearly 2.5 increase in the likelihood of being in the Co-Morbid relative to the MDD only group (p < .05). Social support, age and type of pre-migration trauma had smaller effects and only differentiated between Subclinical and Co-Morbid PTSD-MDD groups (p < .05). Conclusion Post-migration stressors exert substantive effects on immigrant mental health outcomes. Nursing interventions are needed to reduce immigration related stressors. Screening Arab immigrant women for depression and PTSD is important given high levels observed in this community based sample. PMID:21835819

  6. 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)

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2011-07-01

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

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

    PubMed Central

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

    2011-01-01

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

  11. The microenvironment induces collective migration in SDHB-silenced mouse pheochromocytoma spheroids.

    PubMed

    D'Antongiovanni, Vanessa; Martinelli, Serena; Richter, Susan; Canu, Letizia; Guasti, Daniele; Mello, Tommaso; Romagnoli, Paolo; Pacak, Karel; Eisenhofer, Graeme; Mannelli, Massimo; Rapizzi, Elena

    2017-10-01

    Pheochromocytomas (Pheos) and paragangliomas (PGLs) are neuroendocrine tumors. Approximately 30-40% of Pheos/PGLs are due to germline mutations in one of the susceptibility genes, including those encoding the succinate dehydrogenase subunits A-D ( SDHA-D ). Up to 2/3 of patients affected by SDHB mutated Pheo/PGL develop metastatic disease with no successful cure at present. Here, for the first time, we evaluated the effects of SDHB silencing in a three dimension (3D) culture using spheroids of a mouse Pheo cell line silenced or not (wild type/wt/control) for the SDHB subunit. We investigated the role of the microenvironment on spheroid growth and migration/invasion by co-culturing SDHB -silenced or wt spheroids with primary cancer-activated fibroblasts (CAFs). When spheroids were co-cultured with fibroblasts, SDHB -silenced cells showed a significant increase in matrigel invasion as demonstrated by the computation of the migratory areas ( P  < 0.001). Moreover, cells detaching from the SDHB -silenced spheroids moved collectively, unlike the cells of wt spheroids that moved individually. Additionally, SDHB- silenced spheroids developed long filamentous formations along which clusters of cells migrated far away from the spheroid, whereas these structures were not present in wt spheroids. We found that lactate, largely secreted by CAFs, plays a specific role in promoting migration only of SDHB -silenced cells. In this study, we demonstrated that SDHB silencing per se increases tumor cell migration/invasion and that microenvironment, as represented by CAFs, plays a pivotal role in enhancing collective migration/invasion in Pheo SDHB -silenced tumor cells, suggesting their role in increasing the tumor metastasizing potential. © 2017 Society for Endocrinology.

  12. 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.

  13. Lasp1 gene disruption is linked to enhanced cell migration and tumor formation Address for reprint requests and other correspondence: C. S. Chew, Inst. of Molecular Medicine and Genetics, Sanders R&E Bldg., Rm. CB 2803, Medical College of Georgia, Augusta, GA 30912-3175 (e-mail: cchew@mcg.edu).

    PubMed Central

    Zhang, Han; Chen, Xunsheng; Bollag, Wendy B.; Bollag, Roni J.; Sheehan, Daniel J.; Chew, Catherine S.

    2009-01-01

    Lasp1 is an actin-binding, signaling pathway-regulated phosphoprotein that is overexpressed in several cancers. siRNA knockdown in cell lines retards cell migration, suggesting the possibility that Lasp1 upregulation influences cancer metastasis. Herein, we utilized a recently developed gene knockout model to assess the role of Lasp1 in modulating nontransformed cell functions. Wound healing and tumor initiation progressed more rapidly in Lasp1−/− mice compared with Lasp1+/+ controls. Embryonic fibroblasts (MEFs) derived from Lasp1−/− mice also migrated more rapidly in vitro. These MEFs characteristically possessed increased focal adhesion numbers and displayed more rapid attachment compared with wild-type MEFs. Differential microarray analyses revealed alterations in message expression for proteins implicated in cell migration, adhesion, and cytoskeletal organization. Notably, the focal adhesion protein, lipoma preferred partner (LPP), a zyxin family member and putative Lasp1 binding protein, was increased about twofold. Because LPP gene disruption reduces cell migration, we hypothesize that LPP plays a role in enhancing the migratory capacity of Lasp1−/− MEFs, perhaps by modifying the subcellular localization of other motility-associated proteins. The striking contrast in the functional effects of loss of Lasp1 in innate cells compared with cell lines reveals distinct differences in mechanisms of motility and attachment in these models. PMID:19531578

  14. Implication of matrix metalloproteinases 2 and 9 in ceramide 1-phosphate-stimulated macrophage migration.

    PubMed

    Ordoñez, Marta; Rivera, Io-Guané; Presa, Natalia; Gomez-Muñoz, Antonio

    2016-08-01

    Cell migration is a complex biological function involved in both physiologic and pathologic processes. Although this is a subject of intense investigation, the mechanisms by which cell migration is regulated are not completely understood. In this study we show that the bioactive sphingolipid ceramide 1-phosphate (C1P), which is involved in inflammatory responses, causes upregulation of metalloproteinases (MMP) -2 and -9 in J774A.1 macrophages. This effect was shown to be dependent on stimulation of phosphatidylinositol 3-kinase (PI3K) and extracellularly regulated kinases 1-2 (ERK1-2) as demonstrated by treating the cells with specific siRNA to knockdown the p85 regulatory subunit of PI3K, or ERK1-2. Inhibition of MMP-2 or MMP-9 pharmacologically or with specific siRNA to silence the genes encoding these MMPs abrogated C1P-stimulated macrophage migration. Also, C1P induced actin polymerization and potently increased phosphorylation of the focal adhesion protein paxillin, which are essential factors in the regulation of cell migration. As expected, blockade of paxillin activation with specific siRNA significantly reduced actin polymerization. In addition, inhibition of actin polymerization with cytochalasin D completely blocked C1P-induced MMP-2 and -9 expression as well as C1P-stimulated macrophage migration. It was also observed that pertussis toxin (Ptx) inhibited Akt, ERK1-2, and paxillin phosphorylation, and completely blocked cell migration. The latter findings support the notion that C1P-stimulated macrophage migration is a receptor mediated effect, and point to MMP-2 and -9 as possible therapeutic targets to control inflammation. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2018-03-29

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

  17. [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.

  18. ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion.

    PubMed

    Chen, Wei-Ta; Ebelt, Nancy D; Stracker, Travis H; Xhemalce, Blerta; Van Den Berg, Carla L; Miller, Kyle M

    2015-06-01

    Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response (DDR) and is associated with cancer suppression. Here we report a cancer-promoting role for ATM. ATM depletion in metastatic cancer cells reduced cell migration and invasion. Transcription analyses identified a gene network, including the chemokine IL-8, regulated by ATM. IL-8 expression required ATM and was regulated by oxidative stress. IL-8 was validated as an ATM target by its ability to rescue cell migration and invasion defects in ATM-depleted cells. Finally, ATM-depletion in human breast cancer cells reduced lung tumors in a mouse xenograft model and clinical data validated IL-8 in lung metastasis. These findings provide insights into how ATM activation by oxidative stress regulates IL-8 to sustain cell migration and invasion in cancer cells to promote metastatic potential. Thus, in addition to well-established roles in tumor suppression, these findings identify a role for ATM in tumor progression.

  19. Effect of NeuroD gene silencing on the migration and invasion of human pancreatic cancer cells PANC-1.

    PubMed

    Wang, Yang; Su, Dong Wei; Gao, Li; Ding, Gui Ling; Ni, Can Rong; Zhu, Ming Hua

    2014-07-01

    The aim of this study is to investigate the influence of Lenti-EGFP-NeuroD-miR, RNAi lentiviral expression vector, on the expression level of NeuroD and migration, and invasion of PANC-1 cell line. PANC-1 cells were cultured and cotransfected with Lenti-EGFP-NeuroD-miR and Lenti-GFP. The infection rate of lentivirus was determined by fluorescence. The interfering effection by the expression of NeuroD mRNA in PANC-1 cells was analyzed by real-time PCR after transfected. Biological behavior of PANC-1 cells transinfected was observed, and the migration and invasion were studied by transwell assay. Intrapancreatic allografts model in nude mice was established to observe the effects of NeuroD on tumorigenesis, tumor growth, and invasion in vivo. The expression of NeuroD mRNA decreased significantly after RNAi lentivirus transinfecting PANC-1 cell. The cell's migration and invasion ability decreased obviously as soon as down regulate of NeuroD in PANC-1 cells. Comparing with control group, the tumors were smaller in size and the invasiveness was inhibited after 8 weeks intrapancreatic allografts in nude mice. Lenti-EGFP-NeuroD-miR transfected into PANC-1 cells shows a stable, effective, and especial blocking expression of NeuroD in mRNA level. The RNAi of lentiviral vector target NeuroD can reduce the migration and invasion abilities of PANC-1 cells.

  20. 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

  1. Genetic mapping of Foxb1-cell lineage shows migration from caudal diencephalon to telencephalon and lateral hypothalamus

    PubMed Central

    Zhao, Tianyu; Szabó, Nora; Ma, Jun; Luo, Lingfei; Zhou, Xunlei; Alvarez-Bolado, Gonzalo

    2008-01-01

    The hypothalamus is a brain region with vital functions, and alterations in its development can cause human disease. However, we still do not have a complete description of how this complex structure is put together during embryonic and early postnatal stages. Radially oriented, outside-in migration of cells is prevalent in the developing hypothalamus. In spite of this, cell contingents from outside the hypothalamus as well as tangential hypothalamic migrations also have an important role. Here we study migrations in the hypothalamic primordium by genetically labeling the Foxb1 diencephalic lineage. Foxb1 is a transcription factor gene expressed in the neuroepithelium of the developing neural tube with a rostral expression boundary between caudal and rostral diencephalon, and therefore appropriate for marking migrations from caudal levels into the hypothalamus. We have found a large, longitudinally oriented migration stream apparently originating in the thalamic region and following an axonal bundle to end in the anterior portion of the lateral hypothalamic area. Additionally, we have mapped a specific expansion of the neuroepithelium into the rostral diencephalon. The expanded neuroepithelium generates abundant neurons for the medial hypothalamus at the tuberal level. Finally, we have uncovered novel diencephalon-to-telencephalon migrations into septum, piriform cortex and amygdala. PMID:19046377

  2. Ancestral Polymorphisms and Sex-Biased Migration Shaped the Demographic History of Brown Bears and Polar Bears

    PubMed Central

    Nakagome, Shigeki; Mano, Shuhei; Hasegawa, Masami

    2013-01-01

    Recent studies have reported discordant gene trees in the evolution of brown bears and polar bears. Genealogical histories are different among independent nuclear loci and between biparentally inherited autosomal DNA (aDNA) and matrilineal mitochondrial DNA (mtDNA). Based on multi-locus genomic sequences from aDNA and mtDNA, we inferred the population demography of brown and polar bears and found that brown bears have 6 times (aDNA) or more than 14 times (mtDNA) larger population sizes than polar bears and that polar bear lineage is derived from within brown bear diversity. In brown bears, the effective population size ratio of mtDNA to aDNA was at least 0.62, which deviated from the expected value of 0.25, suggesting matriarchal population due to female philopatry and male-biased migration. These results emphasize that ancestral polymorphisms and sex-biased migration may have contributed to conflicting branching patterns in brown and polar bears across aDNA genes and mtDNA. PMID:24236053

  3. Ancestral polymorphisms and sex-biased migration shaped the demographic history of brown bears and polar bears.

    PubMed

    Nakagome, Shigeki; Mano, Shuhei; Hasegawa, Masami

    2013-01-01

    Recent studies have reported discordant gene trees in the evolution of brown bears and polar bears. Genealogical histories are different among independent nuclear loci and between biparentally inherited autosomal DNA (aDNA) and matrilineal mitochondrial DNA (mtDNA). Based on multi-locus genomic sequences from aDNA and mtDNA, we inferred the population demography of brown and polar bears and found that brown bears have 6 times (aDNA) or more than 14 times (mtDNA) larger population sizes than polar bears and that polar bear lineage is derived from within brown bear diversity. In brown bears, the effective population size ratio of mtDNA to aDNA was at least 0.62, which deviated from the expected value of 0.25, suggesting matriarchal population due to female philopatry and male-biased migration. These results emphasize that ancestral polymorphisms and sex-biased migration may have contributed to conflicting branching patterns in brown and polar bears across aDNA genes and mtDNA.

  4. Visual Processing in Rapid-Chase Systems: Image Processing, Attention, and Awareness

    PubMed Central

    Schmidt, Thomas; Haberkamp, Anke; Veltkamp, G. Marina; Weber, Andreas; Seydell-Greenwald, Anna; Schmidt, Filipp

    2011-01-01

    Visual stimuli can be classified so rapidly that their analysis may be based on a single sweep of feedforward processing through the visuomotor system. Behavioral criteria for feedforward processing can be evaluated in response priming tasks where speeded pointing or keypress responses are performed toward target stimuli which are preceded by prime stimuli. We apply this method to several classes of complex stimuli. (1) When participants classify natural images into animals or non-animals, the time course of their pointing responses indicates that prime and target signals remain strictly sequential throughout all processing stages, meeting stringent behavioral criteria for feedforward processing (rapid-chase criteria). (2) Such priming effects are boosted by selective visual attention for positions, shapes, and colors, in a way consistent with bottom-up enhancement of visuomotor processing, even when primes cannot be consciously identified. (3) Speeded processing of phobic images is observed in participants specifically fearful of spiders or snakes, suggesting enhancement of feedforward processing by long-term perceptual learning. (4) When the perceived brightness of primes in complex displays is altered by means of illumination or transparency illusions, priming effects in speeded keypress responses can systematically contradict subjective brightness judgments, such that one prime appears brighter than the other but activates motor responses as if it was darker. We propose that response priming captures the output of the first feedforward pass of visual signals through the visuomotor system, and that this output lacks some characteristic features of more elaborate, recurrent processing. This way, visuomotor measures may become dissociated from several aspects of conscious vision. We argue that “fast” visuomotor measures predominantly driven by feedforward processing should supplement “slow” psychophysical measures predominantly based on visual awareness

  5. 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.

  6. Gene Flow within and between Catchments in the Threatened Riparian Plant Myricaria germanica

    PubMed Central

    Werth, Silke; Scheidegger, Christoph

    2014-01-01

    One of the major distinctions of riparian habitats is their linearity. In linear habitats, gene flow is predicted to follow a one-dimensional stepping stone model, characterized by bidirectional gene flow between neighboring populations. Here, we studied the genetic structure of Myricaria germanica, a threatened riparian shrub which is capable of both wind and water dispersal. Our data led us to reject the ‘one catchment – one gene pool’ hypothesis as we found support for two gene pools, rather than four as expected in a study area including four catchments. This result also implies that in the history of the studied populations, dispersal across catchments has occurred. Two contemporary catchment-crossing migration events were detected, albeit between spatially proximate catchments. Allelic richness and inbreeding coefficients differed substantially between gene pools. There was significant isolation by distance, and our data confirmed the one-dimensional stepping-stone model of gene flow. Contemporary migration was bidirectional within the studied catchments, implying that dispersal vectors other than water are important for M. germanica. PMID:24932520

  7. 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.

  8. 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

  9. 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

  10. The monarch butterfly genome yields insights into long-distance migration

    PubMed Central

    Zhan, Shuai; Merlin, Christine; Boore, Jeffrey L.; Reppert, Steven M.

    2011-01-01

    SUMMARY We present the draft 273 Mb genome of the migratory monarch butterfly (Danaus plexippus) and a set of 16, 866 protein-coding genes. Orthology properties suggest that the Lepidoptera are the fastest evolving insect order yet examined. Compared to the silkmoth Bombyx mori, the monarch genome shares prominent similarity in orthology content, microsynteny, and protein family sizes. The monarch genome reveals: a vertebrate-like opsin whose existence in insects is widespread; a full repertoire of molecular components for the monarch circadian clockwork; all members of the juvenile hormone biosynthetic pathway whose regulation shows unexpected sexual dimorphism; additional molecular signatures of oriented flight behavior; microRNAs that are differentially expressed between summer and migratory butterflies; monarch-specific expansions of chemoreceptors potentially important for long-distance migration; and a variant of the sodium/potassium pump that underlies a valuable chemical defense mechanism. The monarch genome enhances our ability to better understand the genetic and molecular basis of long-distance migration. PMID:22118469

  11. Suppression subtractive hybridization identified differentially expressed genes in lung adenocarcinoma: ERGIC3 as a novel lung cancer-related gene

    PubMed Central

    2013-01-01

    Background To understand the carcinogenesis caused by accumulated genetic and epigenetic alterations and seek novel biomarkers for various cancers, studying differentially expressed genes between cancerous and normal tissues is crucial. In the study, two cDNA libraries of lung cancer were constructed and screened for identification of differentially expressed genes. Methods Two cDNA libraries of differentially expressed genes were constructed using lung adenocarcinoma tissue and adjacent nonmalignant lung tissue by suppression subtractive hybridization. The data of the cDNA libraries were then analyzed and compared using bioinformatics analysis. Levels of mRNA and protein were measured by quantitative real-time polymerase chain reaction (q-RT-PCR) and western blot respectively, as well as expression and localization of proteins were determined by immunostaining. Gene functions were investigated using proliferation and migration assays after gene silencing and gene over-expression. Results Two libraries of differentially expressed genes were obtained. The forward-subtracted library (FSL) and the reverse-subtracted library (RSL) contained 177 and 59 genes, respectively. Bioinformatic analysis demonstrated that these genes were involved in a wide range of cellular functions. The vast majority of these genes were newly identified to be abnormally expressed in lung cancer. In the first stage of the screening for 16 genes, we compared lung cancer tissues with their adjacent non-malignant tissues at the mRNA level, and found six genes (ERGIC3, DDR1, HSP90B1, SDC1, RPSA, and LPCAT1) from the FSL were significantly up-regulated while two genes (GPX3 and TIMP3) from the RSL were significantly down-regulated (P < 0.05). The ERGIC3 protein was also over-expressed in lung cancer tissues and cultured cells, and expression of ERGIC3 was correlated with the differentiated degree and histological type of lung cancer. The up-regulation of ERGIC3 could promote cellular migration

  12. The heparan sulfate-modifying enzyme glucuronyl C5-epimerase HSE-5 controls Caenorhabditis elegans Q neuroblast polarization during migration.

    PubMed

    Wang, Xiangming; Liu, Jianhong; Zhu, Zhiwen; Ou, Guangshuo

    2015-03-15

    Directional cell migration is fundamental for neural development, and extracellular factors are pivotal for this process. Heparan sulfate proteoglycans (HSPGs) that carry long chains of differentially modified sugar residues contribute to extracellular matrix; however, the functions of HSPG in guiding cell migration remain elusive. Here, we used the Caenorhabditis elegans mutant pool from the Million Mutation Project and isolated a mutant allele of the heparan sulfate-modifying enzyme glucuronyl C5-epimerase HSE-5. Loss-of-function of this enzyme resulted in defective Q neuroblast migration. We showed that hse-5 controlled Q cell migration in a cell non-autonomous manner. By performing live cell imaging in hse-5 mutant animals, we found that hse-5 controlled initial polarization during Q neuroblast migration. Furthermore, our genetic epistasis analysis demonstrated that lon-2 might act downstream of hse-5. Finally, rescue of the hse-5 mutant phenotype by expression of human and mouse hse-5 homologs suggested a conserved function for this gene in neural development. Taken together, our results indicated that proper HSPG modification in the extracellular matrix by HSE-5 is essential for neuroblast polarity during migration. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Biometrics and international migration.

    PubMed

    Redpath, Jillyanne

    2007-01-01

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

  14. 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

  15. Silencing of the integrin-linked kinase gene suppresses the proliferation, migration and invasion of pancreatic cancer cells (Panc-1).

    PubMed

    Zhu, Xiang-Yu; Liu, Ning; Liu, Wei; Song, Shao-Wei; Guo, Ke-Jian

    2012-04-01

    Integrin-linked kinase (ILK) is an ankyrin repeat-containing serine-threonine protein kinase that is involved in the regulation of integrin-mediated processes such as cancer cell proliferation, migration and invasion. In this study, we examined the effect of a lentivirus-mediated knockdown of ILK on the proliferation, migration and invasion of pancreatic cancer (Panc-1) cells. Immunohistochemical staining showed that ILK expression was enhanced in pancreatic cancer tissue. The silencing of ILK in human Panc-1 cells led to cell cycle arrest in the G0/G1 phase and delayed cell proliferation, in addition to down-regulating cell migration and invasion. The latter effects were mediated by up-regulating the expression of E-cadherin, a key protein in cell adhesion. These findings indicate that ILK may be a new diagnostic marker for pancreatic cancer and that silencing ILK could be a potentially useful therapeutic approach for treating pancreatic cancer.

  16. MicroRNA Let-7b inhibits keratinocyte migration in cutaneous wound healing by targeting IGF2BP2.

    PubMed

    Wu, Yan; Zhong, Julia Li; Hou, Ning; Sun, Yaolan; Ma, Benting; Nisar, Muhammad Farrukh; Teng, Yan; Tan, Zhaoli; Chen, Keping; Wang, Youliang; Yang, Xiao

    2017-02-01

    Wound healing is a complex process which involves proliferation and migration of keratinocyte for closure of epidermal injuries. A member of microRNA family, let-7b, has been expressed in mammalian skin, but its exact role in keratinocyte migration is still not in knowledge. Here, we showed that let-7b regulates keratinocyte migration by targeting the insulin-like growth factor IGF2BP2. Overexpression of let-7b led to reduced HaCaT cell migration, while knockdown of let-7b resulted in enhanced migration. Furthermore, let-7b was decreased during wound healing in wild-type mice, which led us to construct the transgenic mice with overexpression of let-7b in skin. The re-epithelialization of epidermis of let-7b transgenic mice was reduced during wound healing. Using bioinformatics prediction software and a reporter gene assay, we found that IGF2BP2 was a target of let-7b, which contributes to keratinocyte migration. Introduction of an expression vector of IGF2BP2 also rescued let-7b-induced migration deficiency, which confirms that IGF2BP2 is an important target for let-7b regulation. Our findings suggest that let-7b significantly delayed the re-epithelialization possibly due to reduction of keratinocyte migration and restraints IGF2BP2 during skin wound healing. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. 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.…

  18. Philopatry and migration of Pacific white sharks

    PubMed Central

    Jorgensen, Salvador J.; Reeb, Carol A.; Chapple, Taylor K.; Anderson, Scot; Perle, Christopher; Van Sommeran, Sean R.; Fritz-Cope, Callaghan; Brown, Adam C.; Klimley, A. Peter; Block, Barbara A.

    2010-01-01

    Advances in electronic tagging and genetic research are making it possible to discern population structure for pelagic marine predators once thought to be panmictic. However, reconciling migration patterns and gene flow to define the resolution of discrete population management units remains a major challenge, and a vital conservation priority for threatened species such as oceanic sharks. Many such species have been flagged for international protection, yet effective population assessments and management actions are hindered by lack of knowledge about the geographical extent and size of distinct populations. Combining satellite tagging, passive acoustic monitoring and genetics, we reveal how eastern Pacific white sharks (Carcharodon carcharias) adhere to a highly predictable migratory cycle. Individuals persistently return to the same network of coastal hotspots following distant oceanic migrations and comprise a population genetically distinct from previously identified phylogenetic clades. We hypothesize that this strong homing behaviour has maintained the separation of a northeastern Pacific population following a historical introduction from Australia/New Zealand migrants during the Late Pleistocene. Concordance between contemporary movement and genetic divergence based on mitochondrial DNA demonstrates a demographically independent management unit not previously recognized. This population's fidelity to discrete and predictable locations offers clear population assessment, monitoring and management options. PMID:19889703

  19. SR-71B - in Flight with F-18 Chase Aircraft - View from Air Force Tanker

    NASA Technical Reports Server (NTRS)

    1996-01-01

    NASA 831, an SR-71B operated by the Dryden Flight Research Center, Edwards, California, cruises over the Mojave Desert with an F/A-18 Hornet flying safety chase. They were photographed on a 1996 mission from an Air Force refueling tanker The F/A-18 Hornet is used primarily as a safety chase and support aircraft at Dryden. As support aircraft, the F-18s are used for safety chase, pilot proficiency and aerial photography. Two SR-71 aircraft have been used by NASA as testbeds for high-speed and high-altitude aeronautical research. The aircraft, an SR-71A and an SR-71B pilot trainer aircraft, have been based here at NASA's Dryden Flight Research Center, Edwards, California. They were transferred to NASA after the U.S. Air Force program was cancelled. As research platforms, the aircraft can cruise at Mach 3 for more than one hour. For thermal experiments, this can produce heat soak temperatures of over 600 degrees Fahrenheit (F). This operating environment makes these aircraft excellent platforms to carry out research and experiments in a variety of areas -- aerodynamics, propulsion, structures, thermal protection materials, high-speed and high-temperature instrumentation, atmospheric studies, and sonic boom characterization. The SR-71 was used in a program to study ways of reducing sonic booms or over pressures that are heard on the ground, much like sharp thunderclaps, when an aircraft exceeds the speed of sound. Data from this Sonic Boom Mitigation Study could eventually lead to aircraft designs that would reduce the 'peak' overpressures of sonic booms and minimize the startling affect they produce on the ground. One of the first major experiments to be flown in the NASA SR-71 program was a laser air data collection system. It used laser light instead of air pressure to produce airspeed and attitude reference data, such as angle of attack and sideslip, which are normally obtained with small tubes and vanes extending into the airstream. One of Dryden's SR-71s was used

  20. Recruitment and retention: factors that affect pericyte migration

    PubMed Central

    Aguilera, Kristina Y.

    2013-01-01

    Pericytes are critical for vascular morphogenesis and contribute to several pathologies, including cancer development and progression. The mechanisms governing pericyte migration and differentiation are complex and have not been fully established. Current literature suggests that platelet-derived growth factor/platelet-derived growth factor receptor-β, sphingosine 1-phosphate/endothelial differentiation gene-1, angiopoietin-1/tyrosine kinase with immunoglobulin-like and EGF-like domains 2, angiopoietin-2/tyros-ine kinase with immunoglobulin-like and EGF-like domains 2, transforming growth factor β/activin receptor-like kinase 1, transforming growth factor β/activin receptor-like kinase 5, Semaphorin-3A/Neuropilin, and matrix metalloproteinase activity regulate the recruitment of pericytes to nascent vessels. Interestingly, many of these pathways are directly affected by secreted protein acidic and rich in cysteine (SPARC). Here, we summarize the function of these factors in pericyte migration and discuss if and how SPARC might infuence these activities and thus provide an additional layer of control for the recruitment of vascular support cells. Additionally, the consequences of targeted inhibition of pericytes in tumors and the current understanding of pericyte recruitment in pathological environments are discussed. PMID:23912898

  1. 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.

  2. Fascin1-Dependent Filopodia are Required for Directional Migration of a Subset of Neural Crest Cells

    PubMed Central

    Boer, Elena F.; Howell, Elizabeth D.; Schilling, Thomas F.; Jette, Cicely A.; Stewart, Rodney A.

    2015-01-01

    Directional migration of neural crest (NC) cells is essential for patterning the vertebrate embryo, including the craniofacial skeleton. Extensive filopodial protrusions in NC cells are thought to sense chemo-attractive/repulsive signals that provide directionality. To test this hypothesis, we generated null mutations in zebrafish fascin1a (fscn1a), which encodes an actin-bundling protein required for filopodia formation. Homozygous fscn1a zygotic null mutants have normal NC filopodia due to unexpected stability of maternal Fscn1a protein throughout NC development and into juvenile stages. In contrast, maternal/zygotic fscn1a null mutant embryos (fscn1a MZ) have severe loss of NC filopodia. However, only a subset of NC streams display migration defects, associated with selective loss of craniofacial elements and peripheral neurons. We also show that fscn1a-dependent NC migration functions through cxcr4a/cxcl12b chemokine signaling to ensure the fidelity of directional cell migration. These data show that fscn1a-dependent filopodia are required in a subset of NC cells to promote cell migration and NC derivative formation, and that perdurance of long-lived maternal proteins can mask essential zygotic gene functions during NC development. PMID:25607881

  3. 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

  4. microRNA-150 Regulates Mobilization and Migration of Bone Marrow-Derived Mononuclear Cells by Targeting Cxcr4

    PubMed Central

    Tano, Nobuko; Kim, Ha Won; Ashraf, Muhammad

    2011-01-01

    The interaction between chemokine receptor type 4 (CXCR4) and its ligand, stromal cell-derived factor (SDF)-1, plays an important role in stem cell mobilization and migration in ischemic tissues. MicroRNAs (miRs) are key regulators of stem cell function and are involved in regulation of stem cell survival and differentiation to adopt different cell lineages. In this study, we show that ischemia inhibits the expression of miR-150 in BM-derived mononuclear cells (MNC) and activates its target Cxcr4 gene. Our results show that miR-150/CXCR4 cascade enhances MNC mobilization and migration. By using mouse acute myocardial infarction (MI) model, we found that MNCs in peripheral blood (PB) were increased significantly at day 5 after AMI as compared to control group and the number of CXCR4 positive MNCs both in bone marrow (BM) and PB was also markedly increased after MI. Analysis by microarray-based miRNA profiling and real-time PCR revealed that the expression of miR-150 which targets Cxcr4 gene as predicted was significantly downregulated in BM-MNCs after MI. Abrogation of miR-150 markedly increased CXCR4 protein expression suggesting its target gene. To show that miR-150 regulates MNC mobilization, knockdown of miR-150 in BM-MNCs by specific antisense inhibitor resulted in their higher migration ability in vitro as compared to scramble-transfected MNCs. Furthermore, in vivo BM transplantation of MNCs lacking miR-150 expression by lentiviral vector into the irradiated wild type mice resulted in the increased number of MNCs in PB after AMI as compared to control. In conclusion, this study demonstrates that ischemia mobilizes BM stem cells via miR-150/CXCR4 dependent mechanism and miR-150 may be a novel therapeutic target for stem cell migration to the ischemic tissue for neovascularization and repair. PMID:22039399

  5. 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.

  6. 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

  7. Rodent Zic Genes in Neural Network Wiring.

    PubMed

    Herrera, Eloísa

    2018-01-01

    The formation of the nervous system is a multistep process that yields a mature brain. Failure in any of the steps of this process may cause brain malfunction. In the early stages of embryonic development, neural progenitors quickly proliferate and then, at a specific moment, differentiate into neurons or glia. Once they become postmitotic neurons, they migrate to their final destinations and begin to extend their axons to connect with other neurons, sometimes located in quite distant regions, to establish different neural circuits. During the last decade, it has become evident that Zic genes, in addition to playing important roles in early development (e.g., gastrulation and neural tube closure), are involved in different processes of late brain development, such as neuronal migration, axon guidance, and refinement of axon terminals. ZIC proteins are therefore essential for the proper wiring and connectivity of the brain. In this chapter, we review our current knowledge of the role of Zic genes in the late stages of neural circuit formation.

  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. Black carbon, particle number concentration and nitrogen oxide emission factors of random in-use vehicles measured with the on-road chasing method

    NASA Astrophysics Data System (ADS)

    Ježek, I.; Katrašnik, T.; Westerdahl, D.; Močnik, G.

    2015-10-01

    The chasing method was used in an on-road measurement campaign, and emission factors (EF) of black carbon (BC), particle number (PN) and nitrogen oxides (NOx) were determined for 139 individual vehicles of different types encountered on the roads. The aggregated results provide EFs for BC, NOx and PN for three vehicle categories: goods vehicles, gasoline and diesel passenger cars. This is the first on-road measurement study where BC EFs of numerous individual diesel cars were determined in real-world driving conditions. We found good agreement between EFs of goods vehicles determined in this campaign and the results of previous studies that used either chasing or remote-sensing measurement techniques. The composition of the sampled car fleet determined from the national vehicle registry information is reflective of Eurostat statistical data on the Slovenian and European vehicle fleet. The median BC EF of diesel and gasoline cars that were in use for less than 5 years decreased by 60 and 47 % from those in use for 5-10 years, respectively; the median NOx and PN EFs of goods vehicles that were in use for less than 5 years decreased from those in use for 5-10 years by 52 and 67 %, respectively. Surprisingly, we found an increase of BC EFs in the newer goods vehicle fleet compared to the 5-10-year old one. The influence of engine maximum power of the measured EFs showed an increase in NOx EF from least to more powerful vehicles with diesel engines. Finally, a disproportionate contribution of high emitters to the total emissions of the measured fleet was found; the top 25 % of emitting diesel cars contributed 63, 47 and 61 % of BC, NOx and PN emissions respectively. With the combination of relatively simple on-road measurements and sophisticated post processing, individual vehicle EF can be determined and useful information about the fleet emissions can be obtained by exactly representing vehicles which contribute disproportionally to vehicle fleet emissions; and

  10. Black carbon, particle number concentration and nitrogen oxide emission factors of random in-use vehicles measured with the on-road chasing method

    NASA Astrophysics Data System (ADS)

    Ježek, I.; Katrašnik, T.; Westerdahl, D.; Močnik, G.

    2015-06-01

    The chasing method was used in an on-road measurement campaign, and emission factors (EF) of black carbon (BC), particle number (PN) and nitrogen oxides (NOx) were determined for 139 individual vehicles of different types encountered on the roads. The aggregated results provide EFs for BC, NOx and PN for three vehicle categories: goods vehicles, gasoline and diesel passenger cars. This is the first on-road measurement study where BC EFs of numerous individual diesel cars were determined in real-world driving conditions. We found good agreement between EFs of goods vehicles determined in this campaign and the results of previous studies that used either chasing or remote sensing measurement techniques. The composition of the sampled car fleet determined from the national vehicle registry information is reflective of Eurostat statistical data on the Slovenian and European vehicle fleet. The median BC EF of diesel and gasoline cars that were in use for less than 5 years, decreased by 60 and 47% from those in use for 5-10 years, respectively, the median NOx and PN EFs, of goods vehicles that were in use for less than five years, decreased from those in use for 5-10 years by 52 and 67%, respectively. The influence of engine maximum power of the measured EFs showed an increase in NOx EF from least to more powerful vehicles with diesel engines. Finally a disproportionate contribution of high emitters to the total emissions of the measured fleet was found; the top 25% of emitting diesel cars contributed 63, 47 and 61% of BC, NOx and PN emissions respectively. With the combination of relatively simple on-road measurements with sophisticated post processing individual vehicles EF can be determined and useful information about the fleet emissions can be obtained by exactly representing vehicles which contribute disproportionally to vehicle fleet emissions; and monitor how the numerous emission reduction approaches are reflected in on-road driving conditions.

  11. Climate change-related migration and infectious disease.

    PubMed

    McMichael, Celia

    2015-01-01

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

  12. Isolation with Migration Models for More Than Two Populations

    PubMed Central

    Hey, Jody

    2010-01-01

    A method for studying the divergence of multiple closely related populations is described and assessed. The approach of Hey and Nielsen (2007, Integration within the Felsenstein equation for improved Markov chain Monte Carlo methods in population genetics. Proc Natl Acad Sci USA. 104:2785–2790) for fitting an isolation-with-migration model was extended to the case of multiple populations with a known phylogeny. Analysis of simulated data sets reveals the kinds of history that are accessible with a multipopulation analysis. Necessarily, processes associated with older time periods in a phylogeny are more difficult to estimate; and histories with high levels of gene flow are particularly difficult with more than two populations. However, for histories with modest levels of gene flow, or for very large data sets, it is possible to study large complex divergence problems that involve multiple closely related populations or species. PMID:19955477

  13. Isolation with migration models for more than two populations.

    PubMed

    Hey, Jody

    2010-04-01

    A method for studying the divergence of multiple closely related populations is described and assessed. The approach of Hey and Nielsen (2007, Integration within the Felsenstein equation for improved Markov chain Monte Carlo methods in population genetics. Proc Natl Acad Sci USA. 104:2785-2790) for fitting an isolation-with-migration model was extended to the case of multiple populations with a known phylogeny. Analysis of simulated data sets reveals the kinds of history that are accessible with a multipopulation analysis. Necessarily, processes associated with older time periods in a phylogeny are more difficult to estimate; and histories with high levels of gene flow are particularly difficult with more than two populations. However, for histories with modest levels of gene flow, or for very large data sets, it is possible to study large complex divergence problems that involve multiple closely related populations or species.

  14. Examining Pre-migration Health Among Filipino Nurses

    PubMed Central

    de Castro, A. B.; Gee, Gilbert; Fujishiro, Kaori; Rue, Tessa

    2014-01-01

    The healthy immigrant hypothesis asserts that immigrants arrive in the receiving country healthier than same race/ethnic counterparts born there. Contemporary research, however, has not evaluated pre-migration health among migrants, nor has explicitly considered comparisons with non-migrants in the country of origin. Pre-migration health was examined among 621 Filipino nurses, including self-reported physical health, mental health, health behaviors, and social stress. Measures were compared by intention to migrate and also tested as predictors of actual migration using time-to-event analysis. Nurses intending to migrate had higher proportion of depression and reported higher general perceived stress compared to those not. Predictors of actual migration included age, mentally unhealthy days, social strain, and social support. Physical health and health behavior measures had no association with migration intention or actual migration. Findings suggest that, relative to those not intending to migrate, nurses intending to migrate have worse mental health status and social stress; and, do not have a physical health advantage. Future research must span the pre- to post-migration continuum to better understand the impact of moving from one country to another on health and well-being. PMID:25385090

  15. Examining Pre-migration Health Among Filipino Nurses.

    PubMed

    de Castro, A B; Gee, Gilbert; Fujishiro, Kaori; Rue, Tessa

    2015-12-01

    The healthy immigrant hypothesis asserts that immigrants arrive in the receiving country healthier than same race/ethnic counterparts born there. Contemporary research, however, has not evaluated pre-migration health among migrants, nor has explicitly considered comparisons with non-migrants in the country of origin. Pre-migration health was examined among 621 Filipino nurses, including self-reported physical health, mental health, health behaviors, and social stress. Measures were compared by intention to migrate and also tested as predictors of actual migration using time-to-event analysis. Nurses intending to migrate had higher proportion of depression and reported higher general perceived stress compared to those not. Predictors of actual migration included age, mentally unhealthy days, social strain, and social support. Physical health and health behavior measures had no association with migration intention or actual migration. Findings suggest that, relative to those not intending to migrate, nurses intending to migrate have worse mental health status and social stress; and, do not have a physical health advantage. Future research must span the pre- to post-migration continuum to better understand the impact of moving from one country to another on health and well-being.

  16. HIV Migration Between Blood and Cerebrospinal Fluid or Semen Over Time

    PubMed Central

    Chaillon, Antoine; Gianella, Sara; Wertheim, Joel O.; Richman, Douglas D.; Mehta, Sanjay R.; Smith, David M.

    2014-01-01

    Previous studies reported associations between neuropathogenesis and human immunodeficiency virus (HIV) compartmentalization in cerebrospinal fluid (CSF) and between sexual transmission and human immunodeficiency virus type 1 (HIV) compartmentalization in semen. It remains unclear, however, how compartmentalization dynamics change over time. To address this, we used statistical methods and Bayesian phylogenetic approaches to reconstruct temporal dynamics of HIV migration between blood and CSF and between blood and the male genital tract. We investigated 11 HIV-infected individuals with paired semen and blood samples and 4 individuals with paired CSF and blood samples. Aligned partial HIV env sequences were analyzed by (1) phylogenetic reconstruction, using a Bayesian Markov-chain Monte Carlo approach; (2) evaluation of viral compartmentalization, using tree-based and distance-based methods; and (3) analysis of migration events, using a discrete Bayesian asymmetric phylogeographic approach of diffusion with Markov jump counts estimation. Finally, we evaluated potential correlates of viral gene flow across anatomical compartments. We observed bidirectional replenishment of viral compartments and asynchronous peaks of viral migration from and to blood over time, suggesting that disruption of viral compartment is transient and directionally selected. These findings imply that viral subpopulations in anatomical sites are an active part of the whole viral population and that compartmental reservoirs could have implications in future eradication studies. PMID:24302756

  17. Pre-migration Trauma Exposure and Psychological Distress for Asian American Immigrants: Linking the Pre- and Post-migration Contexts.

    PubMed

    Li, Miao; Anderson, James G

    2016-08-01

    Drawing on the life course perspective and the assumptive world theory, this paper examines whether pre-migration trauma exposure is associated with psychological distress through post-migration perceived discrimination for Asian American immigrants. The study is based on cross-sectional data from the National Latino and Asian American Study (N = 1639). Structural equation model is used to estimate the relationship between pre-migration trauma, post-migration perceived discrimination, and psychological distress. Additional models are estimated to explore possible variations across ethnic groups as well as across different types of pre-migration trauma experience. Pre-migration trauma exposure is associated with higher levels of psychological distress, both directly and indirectly through higher level of perceived discrimination, even after controlling for demographic/acculturative factors and post-migration trauma exposure. This pattern holds for the following sub-types of pre-migration trauma: political trauma, crime victimization, physical violence, accidental trauma, and relational trauma. Multi-group analyses show that this pattern holds for all Asian immigrant subgroups except the Vietnamese. Studies of immigrant mental health primarily focus on post-migration stressors. Few studies have considered the link between pre- and post-migration contexts in assessing mental health outcomes. The study illustrates the usefulness of bridging the pre- and post-migration context in identifying the mental health risks along the immigrant life course.

  18. TGF-β-Induced Transcription Sustains Amoeboid Melanoma Migration and Dissemination

    PubMed Central

    Cantelli, Gaia; Orgaz, Jose L.; Rodriguez-Hernandez, Irene; Karagiannis, Panagiotis; Maiques, Oscar; Matias-Guiu, Xavier; Nestle, Frank O.; Marti, Rosa M.; Karagiannis, Sophia N.; Sanz-Moreno, Victoria

    2015-01-01

    Summary Cell migration underlies metastatic dissemination of cancer cells, and fast “amoeboid” migration in the invasive fronts of tumors is controlled by high levels of actomyosin contractility. How amoeboid migration is regulated by extracellular signals and sustained over time by transcriptional changes is not fully understood. Transforming growth factor β (TGF-β) is well known to promote epithelial-to-mesenchymal transition (EMT) and contribute to metastasis, but melanocytes are neural crest derivatives that have undergone EMT during embryonic development. Surprisingly, we find that in melanoma, TGF-β promotes amoeboid features such as cell rounding, membrane blebbing, high levels of contractility, and increased invasion. Using genome-wide transcriptomics, we find that amoeboid melanoma cells are enriched in a TGF-β-driven signature. We observe that downstream of TGF-β, SMAD2 and its adaptor CITED1 control amoeboid behavior by regulating the expression of key genes that activate contractile forces. Moreover, CITED1 is highly upregulated during melanoma progression, and its high expression is associated with poor prognosis. CITED1 is coupled to a contractile-rounded, amoeboid phenotype in a panel of 16 melanoma cell lines, in mouse melanoma xenografts, and in 47 human melanoma patients. Its expression is also enriched in the invasive fronts of lesions. Functionally, we show how the TGF-β-SMAD2-CITED1 axis promotes different steps associated with progression: melanoma detachment from keratinocytes, 2D and 3D migration, attachment to endothelial cells, and in vivo lung metastatic initial colonization and outgrowth. We propose a novel mechanism by which TGF-β-induced transcription sustains actomyosin force in melanoma cells and thereby promotes melanoma progression independently of EMT. PMID:26526369

  19. The roles of HOXB7 in promoting migration, invasion, and anti-apoptosis in gastric cancer.

    PubMed

    Joo, Moon Kyung; Park, Jong-Jae; Yoo, Hyo Soon; Lee, Beom Jae; Chun, Hoon Jai; Lee, Sang Woo; Bak, Young-Tae

    2016-10-01

    The aim of this study was to compare HOXB7 expression level between gastric cancer and non-cancerous gastric tissues. Additionally, the functional effects of HOXB7, including its pro-migration or invasion and anti-apoptosis roles, were evaluated in gastric cancer cells. Both gene and protein expression levels of HOXB7 were examined in gastric cancer cell lines, and HOXB7 expression was compared between primary or metastatic gastric cancer tissues and chronic gastritis or intestinal metaplasia tissues. Functional studies included a wound healing assay, a Matrigel invasion assay, and an Annexin-V assay were performed, and Akt/PTEN activity was measured by western blotting. Both gene and protein expression levels of HOXB7 could be clearly detected in various gastric cancer cell lines except MKN-28 cell. HOXB7 expression was significantly higher in primary or metastatic gastric cancer tissues than in chronic gastritis or intestinal metaplasia tissues. HOXB7 knockdown led to inhibition of cell invasion and migration, had an apoptotic effect, downregulated phosphor-Akt, and upregulated PTEN in AGS and SNU-638 cells. Reinforced expression of HOXB7 caused the opposite effects in MKN-28 and MKN-45 cells. Our study suggests that HOXB7 has an oncogenic role in gastric cancer, which might be related to the modulation of Akt/PTEN activity to induce cell migration/invasion and anti-apoptotic effects. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  20. Climate change-related migration and infectious disease

    PubMed Central

    McMichael, Celia

    2015-01-01

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

  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. Probabilistic migration modelling focused on functional barrier efficiency and low migration concepts in support of risk assessment.

    PubMed

    Brandsch, Rainer

    2017-10-01

    Migration modelling provides reliable migration estimates from food-contact materials (FCM) to food or food simulants based on mass-transfer parameters like diffusion and partition coefficients related to individual materials. In most cases, mass-transfer parameters are not readily available from the literature and for this reason are estimated with a given uncertainty. Historically, uncertainty was accounted for by introducing upper limit concepts first, turning out to be of limited applicability due to highly overestimated migration results. Probabilistic migration modelling gives the possibility to consider uncertainty of the mass-transfer parameters as well as other model inputs. With respect to a functional barrier, the most important parameters among others are the diffusion properties of the functional barrier and its thickness. A software tool that accepts distribution as inputs and is capable of applying Monte Carlo methods, i.e., random sampling from the input distributions of the relevant parameters (i.e., diffusion coefficient and layer thickness), predicts migration results with related uncertainty and confidence intervals. The capabilities of probabilistic migration modelling are presented in the view of three case studies (1) sensitivity analysis, (2) functional barrier efficiency and (3) validation by experimental testing. Based on the predicted migration by probabilistic migration modelling and related exposure estimates, safety evaluation of new materials in the context of existing or new packaging concepts is possible. Identifying associated migration risk and potential safety concerns in the early stage of packaging development is possible. Furthermore, dedicated material selection exhibiting required functional barrier efficiency under application conditions becomes feasible. Validation of the migration risk assessment by probabilistic migration modelling through a minimum of dedicated experimental testing is strongly recommended.

  3. 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.

  4. Gpx 4 is involved in the proliferation, migration and apoptosis of glioma cells.

    PubMed

    Zhao, Hongyu; Ji, Bin; Chen, Jianguo; Huang, Qingfeng; Lu, Xueguan

    2017-06-01

    Glioma is one of the most common and aggressive types of human brain tumor, it is important to explore novel glioma-associated genes. In this report, we defined Gpx4 as a therapeutic target for glioma. Western blot and immunohistochemistry(IHC) analysis revealed that the protein level of Gpx4 was higher in glioma tissues and cell lines. In addition, IHC stain revealed that there was statistical significance between the expression of Gpx4 and the WHO grade (P=0.004) and Ki-67(P=0.000) expression. Kaplan-Meier curve showed that high expression of Gpx4 was associated with poor prognosis of glioma patients (P<0.01). To determine whether Gpx4 could regulate the proliferation and migration of glioma cells, we transfected glioma cells with Gpx4-siRNA and then investigated cell proliferation with cell counting kit (CCK) -8, flow cytometry assay and colony formation analyses, and we used wound-healing and transwell assays to investigate cell migration. Our results indicated that knockdown of Gpx4 would inhibit the proliferation and migration of glioma cells. Besides, silencing of Gpx4 could induce the apoptosis of glioma cells. This research indicated that Gpx4 might be thought of as a new prognostic factor in glioma and be closely correlated with glioma cell proliferation, migration and apoptosis. Copyright © 2017 Elsevier GmbH. All rights reserved.

  5. 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.

  6. Cohort profile: internal migration in sub-Saharan Africa—The Migration and Health in Malawi (MHM) study

    PubMed Central

    Anglewicz, Philip; VanLandingham, Mark; Manda-Taylor, Lucinda; Kohler, Hans-Peter

    2017-01-01

    Purpose The Migration and Health in Malawi (MHM) study focuses on a key challenge in migration research: although it has long been established that migration and health are closely linked, identifying the effect of migration on various health outcomes is complicated by methodological challenges. The MHM study uses a longitudinal panel premigration and postmigration study design (with a non-migrant comparison group) to measure and/or control for important characteristics that affect both migration and health outcomes. Participants Data are available for two waves. The MHM interviewed 398 of 715 migrants in 2007 (55.7%) and 722 of 1013 in 2013 (71.3%); as well as 604 of 751 (80.4%) for a non-migrant reference group in 2013. The total interviewed sample size for the MHM in both waves is 1809. These data include extensive information on lifetime migration, socioeconomic and demographic characteristics, sexual behaviours, marriage, household/family structure, social networks and social capital, HIV/AIDS biomarkers and other dimensions of health. Findings to date Our result for the relationship between migration and health differs by health measure and analytic approach. Migrants in Malawi have a significantly higher HIV prevalence than non-migrants, which is primarily due to the selection of HIV-positive individuals into migration. We find evidence for health selection; physically healthier men and women are more likely to move, partly because migration selects younger individuals. However, we do not find differences in physical or mental health between migrants and non-migrants after moving. Future plans We are preparing a third round of data collection for these (and any new) migrants, which will take place in 2018. This cohort will be used to examine the effect of migration on various health measures and behaviours, including general mental and physical health, smoking and alcohol use, access to and use of health services and use of antiretroviral therapy. PMID

  7. Costs of locomotion in polar bears: when do the costs outweigh the benefits of chasing down terrestrial prey?

    PubMed

    Gormezano, Linda J; McWilliams, Scott R; Iles, David T; Rockwell, Robert F

    2016-01-01

    Trade-offs between locomotory costs and foraging gains are key elements in determining constraints on predator-prey interactions. One intriguing example involves polar bears pursuing snow geese on land. As climate change forces polar bears to spend more time ashore, they may need to expend more energy to obtain land-based food. Given that polar bears are inefficient at terrestrial locomotion, any extra energy expended to pursue prey could negatively impact survival. However, polar bears have been regularly observed engaging in long pursuits of geese and other land animals, and the energetic worth of such behaviour has been repeatedly questioned. We use data-driven energetic models to examine how energy expenditures vary across polar bear mass and speed. For the first time, we show that polar bears in the 125-235 kg size range can profitably pursue geese, especially at slower speeds. We caution, however, that heat build-up may be the ultimate limiting factor in terrestrial chases, especially for larger bears, and this limit would be reached more quickly with warmer environmental temperatures.

  8. Costs of locomotion in polar bears: when do the costs outweigh the benefits of chasing down terrestrial prey?

    PubMed Central

    Gormezano, Linda J.; McWilliams, Scott R.; Iles, David T.; Rockwell, Robert F.

    2016-01-01

    Trade-offs between locomotory costs and foraging gains are key elements in determining constraints on predator–prey interactions. One intriguing example involves polar bears pursuing snow geese on land. As climate change forces polar bears to spend more time ashore, they may need to expend more energy to obtain land-based food. Given that polar bears are inefficient at terrestrial locomotion, any extra energy expended to pursue prey could negatively impact survival. However, polar bears have been regularly observed engaging in long pursuits of geese and other land animals, and the energetic worth of such behaviour has been repeatedly questioned. We use data-driven energetic models to examine how energy expenditures vary across polar bear mass and speed. For the first time, we show that polar bears in the 125–235 kg size range can profitably pursue geese, especially at slower speeds. We caution, however, that heat build-up may be the ultimate limiting factor in terrestrial chases, especially for larger bears, and this limit would be reached more quickly with warmer environmental temperatures. PMID:27757238

  9. Chasing the Mirage: a grounded theory of the clinical reasoning processes that Registered Nurses use to recognize delirium.

    PubMed

    El Hussein, Mohamed; Hirst, Sandra

    2016-02-01

    The aim of this study was to construct a grounded theory that explains the clinical reasoning processes that registered nurses use to recognize delirium in older adults in acute care hospitals. Delirium is under-recognized in acute hospital settings, this may stem from underdeveloped clinical reasoning processes. Little is known about registered nurses' (RNs) clinical reasoning processes in complex situations such as delirium recognition. A grounded theory approach was used to analyse interview data about the clinical reasoning processes of RNs in acute hospital settings. Seventeen RNs were recruited. Concurrent data collection and comparative analysis and theoretical sampling were conducted in 2013-2014. The core category to emerge from the data was 'chasing the mirage', which describes RNs' clinical reasoning processes to recognize delirium during their interaction with older adults. Understanding the reasoning that contributes to delirium under-recognition provides a strategy by which, this problem can be brought to the forefront of RNs' awareness and intervention. Delirium recognition will contribute to quality care for older adults. © 2015 John Wiley & Sons Ltd.

  10. Co-culture with Sertoli cells promotes proliferation and migration of umbilical cord mesenchymal stem cells

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

    Zhang, Fenxi, E-mail: fxzhang0824@gmail.com; Hong, Yan; Liang, Wenmei

    Highlights: Black-Right-Pointing-Pointer Co-culture of Sertoli cells (SCs) with human umbilical cord mesenchymal stem cells (UCMSCs). Black-Right-Pointing-Pointer Presence of SCs dramatically increased proliferation and migration of UCMSCs. Black-Right-Pointing-Pointer Presence of SCs stimulated expression of Mdm2, Akt, CDC2, Cyclin D, CXCR4, MAPKs. -- Abstract: Human umbilical cord mesenchymal stem cells (hUCMSCs) have been recently used in transplant therapy. The proliferation and migration of MSCs are the determinants of the efficiency of MSC transplant therapy. Sertoli cells are a kind of 'nurse' cells that support the development of sperm cells. Recent studies show that Sertoli cells promote proliferation of endothelial cells and neuralmore » stem cells in co-culture. We hypothesized that co-culture of UCMSCs with Sertoli cells may also promote proliferation and migration of UCMSCs. To examine this hypothesis, we isolated UCMSCs from human cords and Sertoli cells from mouse testes, and co-cultured them using a Transwell system. We found that UCMSCs exhibited strong proliferation ability and potential to differentiate to other cell lineages such as osteocytes and adipocytes. The presence of Sertoli cells in co-culture significantly enhanced the proliferation and migration potential of UCMSCs (P < 0.01). Moreover, these phenotypic changes were accompanied with upregulation of multiple genes involved in cell proliferation and migration including phospho-Akt, Mdm2, phospho-CDC2, Cyclin D1, Cyclin D3 as well as CXCR4, phospho-p44 MAPK and phospho-p38 MAPK. These findings indicate that Sertoli cells boost UCMSC proliferation and migration potential.« less

  11. Coevolutionary arms race versus host defense chase in a tropical herbivore-plant system.

    PubMed

    Endara, María-José; Coley, Phyllis D; Ghabash, Gabrielle; Nicholls, James A; Dexter, Kyle G; Donoso, David A; Stone, Graham N; Pennington, R Toby; Kursar, Thomas A

    2017-09-05

    Coevolutionary models suggest that herbivores drive diversification and community composition in plants. For herbivores, many questions remain regarding how plant defenses shape host choice and community structure. We addressed these questions using the tree genus Inga and its lepidopteran herbivores in the Amazon. We constructed phylogenies for both plants and insects and quantified host associations and plant defenses. We found that similarity in herbivore assemblages between Inga species was correlated with similarity in defenses. There was no correlation with phylogeny, a result consistent with our observations that the expression of defenses in Inga is independent of phylogeny. Furthermore, host defensive traits explained 40% of herbivore community similarity. Analyses at finer taxonomic scales showed that different lepidopteran clades select hosts based on different defenses, suggesting taxon-specific histories of herbivore-host plant interactions. Finally, we compared the phylogeny and defenses of Inga to phylogenies for the major lepidopteran clades. We found that closely related herbivores fed on Inga with similar defenses rather than on closely related plants. Together, these results suggest that plant defenses might be more evolutionarily labile than the herbivore traits related to host association. Hence, there is an apparent asymmetry in the evolutionary interactions between Inga and its herbivores. Although plants may evolve under selection by herbivores, we hypothesize that herbivores may not show coevolutionary adaptations, but instead "chase" hosts based on the herbivore's own traits at the time that they encounter a new host, a pattern more consistent with resource tracking than with the arms race model of coevolution.

  12. Human Umbilical Cord Perivascular Cells Exhibited Enhanced Migration Capacity towards Hepatocellular Carcinoma in Comparison with Bone Marrow Mesenchymal Stromal Cells: A Role for Autocrine Motility Factor Receptor

    PubMed Central

    Aquino, Jorge B.; Malvicini, Mariana; Bolontrade, Marcela; Podhajcer, Osvaldo; Garcia, Mariana G.; Mazzolini, Guillermo

    2014-01-01

    Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Unfortunately, the incidence and mortality associated with HCC are increasing. Therefore, new therapeutic strategies are urgently needed and the use of mesenchymal stromal cells (MSCs) as carrier of therapeutic genes is emerging as a promising option. Different sources of MSCs are being studied for cell therapy and bone marrow-derived cells are the most extensively explored; however, birth associated-tissues represent a very promising source. The aim of this work was to compare the in vitro and in vivo migration capacity between bone marrow MSCs (BM-MSCs) and human umbilical cord perivascular cells (HUCPVCs) towards HCC. We observed that HUCPVCs presented higher in vitro and in vivo migration towards factors released by HCC. The expression of autocrine motility factor (AMF) receptor, genes related with the availability of the receptor on the cell surface (caveolin-1 and -2) and metalloproteinase 3, induced by the receptor activation and important for cell migration, was increased in HUCPVCs. The chemotactic response towards recombinant AMF was increased in HUCPVCs compared to BM-MSCs, and its inhibition in the conditioned medium from HCC induced higher decrease in HUCPVC migration than in BM-MSC. Our results indicate that HUCPVCs could be a useful cellular source to deliver therapeutic genes to HCC. PMID:25147818

  13. Human umbilical cord perivascular cells exhibited enhanced migration capacity towards hepatocellular carcinoma in comparison with bone marrow mesenchymal stromal cells: a role for autocrine motility factor receptor.

    PubMed

    Bayo, Juan; Fiore, Esteban; Aquino, Jorge B; Malvicini, Mariana; Rizzo, Manglio; Peixoto, Estanislao; Alaniz, Laura; Piccioni, Flavia; Bolontrade, Marcela; Podhajcer, Osvaldo; Garcia, Mariana G; Mazzolini, Guillermo

    2014-01-01

    Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Unfortunately, the incidence and mortality associated with HCC are increasing. Therefore, new therapeutic strategies are urgently needed and the use of mesenchymal stromal cells (MSCs) as carrier of therapeutic genes is emerging as a promising option. Different sources of MSCs are being studied for cell therapy and bone marrow-derived cells are the most extensively explored; however, birth associated-tissues represent a very promising source. The aim of this work was to compare the in vitro and in vivo migration capacity between bone marrow MSCs (BM-MSCs) and human umbilical cord perivascular cells (HUCPVCs) towards HCC. We observed that HUCPVCs presented higher in vitro and in vivo migration towards factors released by HCC. The expression of autocrine motility factor (AMF) receptor, genes related with the availability of the receptor on the cell surface (caveolin-1 and -2) and metalloproteinase 3, induced by the receptor activation and important for cell migration, was increased in HUCPVCs. The chemotactic response towards recombinant AMF was increased in HUCPVCs compared to BM-MSCs, and its inhibition in the conditioned medium from HCC induced higher decrease in HUCPVC migration than in BM-MSC. Our results indicate that HUCPVCs could be a useful cellular source to deliver therapeutic genes to HCC.

  14. Suppression of the Epidermal Growth Factor-like Domain 7 and Inhibition of Migration and Epithelial-Mesenchymal Transition in Human Pancreatic Cancer PANC-1 Cells.

    PubMed

    Wang, Yun-Liang; Dong, Feng-Lin; Yang, Jian; Li, Zhi; Zhi, Qiao-Ming; Zhao, Xin; Yang, Yong; Li, De-Chun; Shen, Xiao-Chun; Zhou, Jin

    2015-01-01

    Epidermal growth factor-like domain multiple 7 (EGFL7), a secreted protein specifically expressed by endothelial cells during embryogenesis, recently was identified as a critical gene in tumor metastasis. Epithelial-mesenchymal transition (EMT) was found to be closely related with tumor progression. Accordingly, it is important to investigate the migration and EMT change after knock-down of EGFL7 gene expression in human pancreatic cancer cells. EGFL7 expression was firstly testified in 4 pancreatic cancer cell lines by real-time polymerase chain reaction (Real-time PCR) and western blot, and the highest expression of EGFL7 was found in PANC-1 cell line. Then, PANC-1 cells transfected with small interference RNA (siRNA) of EGFL7 using plasmid vector were named si-PANC-1, while transfected with negative control plasmid vector were called NC-PANC-1. Transwell assay was used to analyze the migration of PANC-1 cells. Real-time PCR and western blotting were used to detect the expression change of EGFL7 gene, EMT markers like E-Cadherin, N-Cadherin, Vimentin, Fibronectin and transcription factors like snail, slug in PANC-1, NC- PANC-1, and si-PANC-1 cells, respectively. After successful plasmid transfection, EGFL7 gene were dramatically knock-down by RNA interference in si-PANC-1 group. Meanwhile, migration ability decreased significantly, compared with PANC-1 and NC-PANC-1 group. Meanwhile, the expression of epithelial phenotype marker E-Cadherin increased and that of mesenchymal phenotype markers N-Cadherin, Vimentin, Fibronectin dramatically decreased in si-PANC-1 group, indicating a reversion of EMT. Also, transcription factors snail and slug decreased significantly after RNA interference. Current study suggested that highly-expressed EGFL7 promotes migration of PANC-1 cells and acts through transcription factors snail and slug to induce EMT, and further study is needed to confirm this issue.

  15. A global evolutionary and metabolic analysis of human obesity gene risk variants.

    PubMed

    Castillo, Joseph J; Hazlett, Zachary S; Orlando, Robert A; Garver, William S

    2017-09-05

    It is generally accepted that the selection of gene variants during human evolution optimized energy metabolism that now interacts with our obesogenic environment to increase the prevalence of obesity. The purpose of this study was to perform a global evolutionary and metabolic analysis of human obesity gene risk variants (110 human obesity genes with 127 nearest gene risk variants) identified using genome-wide association studies (GWAS) to enhance our knowledge of early and late genotypes. As a result of determining the mean frequency of these obesity gene risk variants in 13 available populations from around the world our results provide evidence for the early selection of ancestral risk variants (defined as selection before migration from Africa) and late selection of derived risk variants (defined as selection after migration from Africa). Our results also provide novel information for association of these obesity genes or encoded proteins with diverse metabolic pathways and other human diseases. The overall results indicate a significant differential evolutionary pattern for the selection of obesity gene ancestral and derived risk variants proposed to optimize energy metabolism in varying global environments and complex association with metabolic pathways and other human diseases. These results are consistent with obesity genes that encode proteins possessing a fundamental role in maintaining energy metabolism and survival during the course of human evolution. Copyright © 2017. Published by Elsevier B.V.

  16. Return Migration as Failure or Success?: The Determinants of Return Migration Intentions Among Moroccan Migrants in Europe.

    PubMed

    de Haas, Hein; Fokkema, Tineke; Fihri, Mohamed Fassi

    Different migration theories generate competing hypotheses with regard to determinants of return migration. While neoclassical migration theory associates migration to the failure to integrate at the destination, the new economics of labour migration sees return migration as the logical stage after migrants have earned sufficient assets and knowledge and to invest in their origin countries. The projected return is then likely to be postponed for sustained or indefinite periods if integration is unsuccessful. So, from an indication or result of integration failure return is rather seen as a measure of success. Drawing on recent survey data ( N  = 2,832), this article tests these hypotheses by examining the main determinants of return intention among Moroccan migrants across Europe. The results indicate that structural integration through labour market participation, education and the maintenance of economic and social ties with receiving countries do not significantly affect return intentions. At the same time, investments and social ties to Morocco are positively related, and socio-cultural integration in receiving countries is negatively related to return migration intentions. The mixed results corroborate the idea that there is no uniform process of (return) migration and that competing theories might therefore be partly complementary.

  17. Dioscin Inhibits HSC-T6 Cell Migration via Adjusting SDC-4 Expression: Insights from iTRAQ-Based Quantitative Proteomics.

    PubMed

    Yin, Lianhong; Qi, Yan; Xu, Youwei; Xu, Lina; Han, Xu; Tao, Xufeng; Song, Shasha; Peng, Jinyong

    2017-01-01

    Hepatic stellate cells (HSCs) migration, an important bioprocess, contributes to the development of liver fibrosis. Our previous studies have found the potent activity of dioscin against liver fibrosis by inhibiting HSCs proliferation, triggering the senescence and inducing apoptosis of activated HSCs, but the molecular mechanisms associated with cell migration were not clarified. In this work, iTRAQ (isobaric tags for relative and absolution quantitation)-based quantitative proteomics study was carried out, and a total of 1566 differentially expressed proteins with fold change ≥2.0 and p < 0.05 were identified in HSC-T6 cells treated by dioscin (5.0 μg/mL). Based on Gene Ontology classification, String and KEGG pathway assays, the effects of dioscin to inhibit cell migration via regulating SDC-4 were carried out. The results of wound-healing, cell migration and western blotting assays indicated that dioscin significantly inhibit HSC-T6 cell migration through SDC-4-dependent signal pathway by affecting the expression levels of Fn, PKCα, Src, FAK, and ERK1/2. Specific SDC-4 knockdown by shRNA also blocked HSC-T6 cell migration, and dioscin slightly enhanced the inhibiting effect. Taken together, the present work showed that SDC-4 played a crucial role on HSC-T6 cell adhesion and migration of dioscin against liver fibrosis, which may be one potent therapeutic target for fibrotic diseases.

  18. MicroRNA-21 promotes bone mesenchymal stem cells migration in vitro by activating PI3K/Akt/MMPs pathway.

    PubMed

    Lv, Chen; Yang, Shengwu; Chen, Xin; Zhu, Xiongbai; Lin, Wenjun; Wang, Lu; Huang, Zhengxiang; Wang, Mingyue; Tu, Guanjun

    2017-12-01

    MicroRNA-21 (miR-21) contributes to anti-apoptosis in bone marrow mesenchymal stem cells (BMSC), but its role in the migration of BMSCs remains vague. The aim of this study was to determine the possible effect of miR-21 on regulating BMSCs directional migration and the expression of MMP-2/MMP-9 in BMSCs in vitro. BMSCs were successfully infected with miR-21-up lentivirus. Cell migration using Transwell assay indicated that upregulated expression of miR-21 could significantly promote BMSCs migration. Western blot analysis indicated that miR-21 significantly upregulated the expression of MMP-2 and MMP-9, which were related to metastasis-associated genes. GM6001, the specific MMPs inhibitor, abrogated the upregulated expression of MMP-2/MMP-9 and abolished the positive effect of miR-21 on promoting BMSCs migration. Meanwhile, miR-21 significantly enhanced Akt phosphorylation, as measured by Western blot analysis. LY294002, an inhibitor of Akt activation, abrogated the phosphorylation of Akt and abolished the positive effect of miR-21 on promoting BMSCs migration and upregulating MMP-2/MMP-9 expression. These results suggest that miR-21 contributes to BMSCs migration by upregulating MMP-2/MMP-9, potentially via the PI3K/Akt pathway. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Mental health of newly arrived Burmese refugees in Australia: contributions of pre-migration and post-migration experience.

    PubMed

    Schweitzer, Robert D; Brough, Mark; Vromans, Lyn; Asic-Kobe, Mary

    2011-04-01

    This study documents the mental health status of people from Burmese refugee backgrounds recently arrived in Australia, then examines the contributions of gender, pre-migration and post-migration factors in predicting mental health. Structured interviews, including a demographic questionnaire, the Harvard Trauma Questionnaire, the Post-migration Living Difficulties Checklist and Hopkins Symptom Checklist assessed pre-migration trauma, post-migration living difficulties, depression, anxiety, somatization and traumatization symptoms in a sample of 70 adults across five Burmese ethnic groups. Substantial proportions of participants reported psychological distress in symptomatic ranges including: post-traumatic stress disorder (9%), anxiety (20%) and depression (36%), as well as significant symptoms of somatization (37%). Participants reported multiple and severe pre-migration traumas. Post-migration living difficulties of greatest concern included communication problems and worry about family not in Australia. Gender did not predict mental health. Level of exposure to traumatic events and post-migration living difficulties each made unique and relatively equal contributions to traumatization symptoms. Post-migration living difficulties made unique contributions to depression, anxiety and somatization symptoms. While exposure to traumatic events impacted on participants' mental well-being, post-migration living difficulties had greater salience in predicting mental health outcomes of people from Burmese refugee backgrounds. Reported rates of post-traumatic stress disorder symptoms were consistent with a large review of adults across seven western countries. High levels of somatization point to a nuanced expression of distress. Findings have implications for service provision in terms of implementing appropriate interventions to effectively meet the needs of this newly arrived group in Australia.

  20. The health impacts of climate-related migration.

    PubMed

    Schwerdtle, Patricia; Bowen, Kathryn; McMichael, Celia

    2017-12-11

    Changes in climate, in conjunction with other drivers of mobility, shape human migration. While there is an increasing focus on the adaptive potential of migration, the health impacts of climate-related migration, including planned relocation and forced displacement, have not been thoroughly examined. The Intergovernmental Panel on Climate Change stated that migration is currently, and will increasingly be, influenced by environmental degradation and climate change, and that it needs to be addressed in a focused and coordinated manner. This paper examines the links between climate change, migration, and health, considering diverse migration responses, including immobility, forced displacement and planned migration, as well as the associated health risks and opportunities in different contexts. Using case studies, the paper illustrates strategies to reduce the health risks associated with climate change-related migration. While there is an increasing body of research examining the climate change-migration nexus, a dual approach is now required. This approach must include debate and further research regarding the health consequences and responses associated with climate migration as well as immediate strengthening of health systems to make them both climate resilient and migrant inclusive.

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

    PubMed

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

    2016-09-01

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

  2. The conveyor belt hypothesis for thymocyte migration: participation of adhesion and de-adhesion molecules.

    PubMed

    Villa-Verde, D M; Calado, T C; Ocampo, J S; Silva-Monteiro, E; Savino, W

    1999-05-01

    Thymocyte differentiation is the process by which bone marrow-derived precursors enter the thymus, proliferate, rearrange the genes and express the corresponding T cell receptors, and undergo positive and/or negative selection, ultimately yielding mature T cells that will represent the so-called T cell repertoire. This process occurs in the context of cell migration, whose cellular and molecular basis is still poorly understood. Kinetic studies favor the idea that these cells leave the organ in an ordered pattern, as if they were moving on a conveyor belt. We have recently proposed that extracellular matrix glycoproteins, such as fibronectin, laminin and type IV collagen, among others, produced by non-lymphoid cells both in the cortex and in the medulla, would constitute a macromolecular arrangement allowing differentiating thymocytes to migrate. Here we discuss the participation of both molecules with adhesive and de-adhesive properties in the intrathymic T cell migration. Functional experiments demonstrated that galectin-3, a soluble beta-galactoside-binding lectin secreted by thymic microenvironmental cells, is a likely candidate for de-adhesion proteins by decreasing thymocyte interaction with the thymic microenvironment.

  3. ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion

    PubMed Central

    Chen, Wei-Ta; Ebelt, Nancy D; Stracker, Travis H; Xhemalce, Blerta; Van Den Berg, Carla L; Miller, Kyle M

    2015-01-01

    Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response (DDR) and is associated with cancer suppression. Here we report a cancer-promoting role for ATM. ATM depletion in metastatic cancer cells reduced cell migration and invasion. Transcription analyses identified a gene network, including the chemokine IL-8, regulated by ATM. IL-8 expression required ATM and was regulated by oxidative stress. IL-8 was validated as an ATM target by its ability to rescue cell migration and invasion defects in ATM-depleted cells. Finally, ATM-depletion in human breast cancer cells reduced lung tumors in a mouse xenograft model and clinical data validated IL-8 in lung metastasis. These findings provide insights into how ATM activation by oxidative stress regulates IL-8 to sustain cell migration and invasion in cancer cells to promote metastatic potential. Thus, in addition to well-established roles in tumor suppression, these findings identify a role for ATM in tumor progression. DOI: http://dx.doi.org/10.7554/eLife.07270.001 PMID:26030852

  4. Altruism Can Proliferate through Population Viscosity despite High Random Gene Flow

    PubMed Central

    Schonmann, Roberto H.; Vicente, Renato; Caticha, Nestor

    2013-01-01

    The ways in which natural selection can allow the proliferation of cooperative behavior have long been seen as a central problem in evolutionary biology. Most of the literature has focused on interactions between pairs of individuals and on linear public goods games. This emphasis has led to the conclusion that even modest levels of migration would pose a serious problem to the spread of altruism through population viscosity in group structured populations. Here we challenge this conclusion, by analyzing evolution in a framework which allows for complex group interactions and random migration among groups. We conclude that contingent forms of strong altruism that benefits equally all group members, regardless of kinship and without greenbeard effects, can spread when rare under realistic group sizes and levels of migration, due to the assortment of genes resulting only from population viscosity. Our analysis combines group-centric and gene-centric perspectives, allows for arbitrary strength of selection, and leads to extensions of Hamilton’s rule for the spread of altruistic alleles, applicable under broad conditions. PMID:23991035

  5. Gendered Patterns of Migration in Rural South Africa

    PubMed Central

    Camlin, Carol S.; Snow, Rachel C.; Hosegood, Victoria

    2013-01-01

    Gender is increasingly recognized as fundamental to understanding migration processes, causes and consequences. In South Africa, it is intrinsic to the social transformations fueling high levels of internal migration and complex forms of mobility. While female migration in Africa has often been characterized as less prevalent than male migration, and primarily related to marriage, in South Africa a feminization of internal migration is underway, fueled by women’s increasing labor market participation. In this paper, we report sex differences in patterns, trends and determinants of internal migration based on data collected in a demographic surveillance system between 2001 and 2006 in rural KwaZulu-Natal. We show that women were somewhat more likely than men to undertake any migration, but sex differences in migration trends differed by migration flow, with women more likely to migrate into the area than men, and men more likely to out-migrate. Out-migration was suppressed by marriage particularly for women, but most women were not married; both men’s and women’s out-migrations were undertaken mainly for purposes of employment. Over half of female out-migrations (versus 35% of male out-migrations) were to nearby rural areas. The findings highlight the high mobility of this population and the extent to which gender is intimately related to the processes determining migration. We consider the implications of these findings for the measurement of migration and mobility, in particular for health and social policy and research among highly mobile populations in southern Africa. PMID:25332690

  6. Effects of silencing S100A8 and S100A9 with small interfering RNA on the migration of CNE1 nasopharyngeal carcinoma cells.

    PubMed

    Yan, Lin-Lin; Huang, Yuan-Jiao; Yi, Xiang; Yan, Xue-Min; Cai, Yan; He, Qin; Han, Zi-Jian

    2015-06-01

    The calcium-binding S100 proteins are involved in functions such as cell growth, differentiation, migration, adhesion and signal transduction. S100A8 and S100A9 are highly expressed in a variety of tumor cells, and are implicated in tumor development and progression. However, the role of S100A8 and S100A9 in nasopharyngeal carcinoma (NPC) cell migration is unclear. The present study investigated the effect of S100A8 and S100A9 on migration using a NPC cell line, CNE1. The CNE1 cells were transfected with S100A8 or S100A9 small interfering RNA (siRNA). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect S100A8 and S100A9 gene expression. Following the downregulation of S100A8 or S100A9, the effects on cell migration were determined using wound-healing assays. The expression of matrix metalloproteinase-7 (MMP7), a member of the MMP family that is associated with tumor cell invasion and migration, was also detected by RT-qPCR. S100A8 and S100A9 siRNAs effectively suppressed S100A8 and S100A9 gene expression, and substantially inhibited the migration of the CNE1 cells. In addition, MMP7 expression was reduced to varying extents in S100A8 and S100A9 siRNA-treated cells compared with controls. Thus, S100A8 and S100A9 promoted the migration of CNE1 NPC cells.

  7. Effects of silencing S100A8 and S100A9 with small interfering RNA on the migration of CNE1 nasopharyngeal carcinoma cells

    PubMed Central

    YAN, LIN-LIN; HUANG, YUAN-JIAO; YI, XIANG; YAN, XUE-MIN; CAI, YAN; HE, QIN; HAN, ZI-JIAN

    2015-01-01

    The calcium-binding S100 proteins are involved in functions such as cell growth, differentiation, migration, adhesion and signal transduction. S100A8 and S100A9 are highly expressed in a variety of tumor cells, and are implicated in tumor development and progression. However, the role of S100A8 and S100A9 in nasopharyngeal carcinoma (NPC) cell migration is unclear. The present study investigated the effect of S100A8 and S100A9 on migration using a NPC cell line, CNE1. The CNE1 cells were transfected with S100A8 or S100A9 small interfering RNA (siRNA). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect S100A8 and S100A9 gene expression. Following the downregulation of S100A8 or S100A9, the effects on cell migration were determined using wound-healing assays. The expression of matrix metalloproteinase-7 (MMP7), a member of the MMP family that is associated with tumor cell invasion and migration, was also detected by RT-qPCR. S100A8 and S100A9 siRNAs effectively suppressed S100A8 and S100A9 gene expression, and substantially inhibited the migration of the CNE1 cells. In addition, MMP7 expression was reduced to varying extents in S100A8 and S100A9 siRNA-treated cells compared with controls. Thus, S100A8 and S100A9 promoted the migration of CNE1 NPC cells. PMID:26137102

  8. MicroRNA-9 promotes the proliferation, migration, and invasion of breast cancer cells via down-regulating FOXO1.

    PubMed

    Liu, D-Z; Chang, B; Li, X-D; Zhang, Q-H; Zou, Y-H

    2017-09-01

    The objective of the study was to investigate the role of microRNA-9 (miR-9) targeting forkhead box O1 (FOXO1) in the proliferation, migration, and invasion of breast cancer cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expressions of miR-9 and FOXO1 mRNA in breast cancer tissues, normal breast tissues, breast cancer cell lines, and normal breast epithelial cells. After the up-regulation of miR-9 expression, qRT-PCR and Western blotting were used to determine the expression of FOXO1. The luciferase reporter gene assay was used to validate the target gene. The CCK-8 assay, scratch-wound healing assay, and Transwell invasion assay were used to investigate the changes in the proliferation, migration, and invasion of breast cancer cells, respectively. MicroRNA-9 expression was significantly up-regulated in breast cancer tissues and breast cancer cell lines when compared with normal breast tissues and normal breast epithelial cells (both P < 0.05). FOXO1 mRNA and protein expressions were substantially down-regulated in breast cancer tissues and breast cancer cell lines when compared with normal breast tissues and normal breast epithelial cells (both P < 0.05). There can be a negative correlation between miR-9 and FOXO1 mRNA in breast cancer. Luciferase reporter gene assay indicated that miR-9 can down-regulate FOXO1 expression at a post-transcriptional level through binding specifically to FOXO1 3'UTR. The results of CCK-8 assay, scratch-wound healing assay, and Transwell invasion assay revealed that the inhibition of miR-9 can suppress MCF7 cell proliferation, migration, and invasion. Additionally, the expression of miR-9 increased significantly whilst that of FOXO1 decreased substantially as the disease progressed (P < 0.05). Our study provides evidence that miR-9 can promote the proliferation, migration, and invasion of breast cancer cells via down-regulating FOXO1.

  9. 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.

  10. Regulation of tumor cell migration by protein tyrosine phosphatase (PTP)-proline-, glutamate-, serine-, and threonine-rich sequence (PEST)

    PubMed Central

    Zheng, Yanhua; Lu, Zhimin

    2013-01-01

    Protein tyrosine phosphatase (PTP)–proline-, glutamate-, serine-, and threonine-rich sequence (PEST) is ubiquitously expressed and is a critical regulator of cell adhesion and migration. PTP-PEST activity can be regulated transcriptionally via gene deletion or mutation in several types of human cancers or via post-translational modifications, including phosphorylation, oxidation, and caspase-dependent cleavage. PTP-PEST interacts with and dephosphorylates cytoskeletal and focal adhesion-associated proteins. Dephosphorylation of PTP-PEST substrates regulates their enzymatic activities and/or their interaction with other proteins and plays an essential role in the tumor cell migration process. PMID:23237212

  11. 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.

  12. Individual versus Household Migration Decision Rules: Gender and Marital Status Differences in Intentions to Migrate in South Africa.

    PubMed

    Gubhaju, Bina; De Jong, Gordon F

    2009-03-01

    This research tests the thesis that the neoclassical micro-economic and the new household economic theoretical assumptions on migration decision-making rules are segmented by gender, marital status, and time frame of intention to migrate. Comparative tests of both theories within the same study design are relatively rare. Utilizing data from the Causes of Migration in South Africa national migration survey, we analyze how individually held "own-future" versus alternative "household well-being" migration decision rules effect the intentions to migrate of male and female adults in South Africa. Results from the gender and marital status specific logistic regressions models show consistent support for the different gender-marital status decision rule thesis. Specifically, the "maximizing one's own future" neoclassical microeconomic theory proposition is more applicable for never married men and women, the "maximizing household income" proposition for married men with short-term migration intentions, and the "reduce household risk" proposition for longer time horizon migration intentions of married men and women. Results provide new evidence on the way household strategies and individual goals jointly affect intentions to move or stay.

  13. 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

  14. 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

  15. 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

  16. Candidate genes for panhypopituitarism identified by gene expression profiling

    PubMed Central

    Mortensen, Amanda H.; MacDonald, James W.; Ghosh, Debashis

    2011-01-01

    Mutations in the transcription factors PROP1 and PIT1 (POU1F1) lead to pituitary hormone deficiency and hypopituitarism in mice and humans. The dysmorphology of developing Prop1 mutant pituitaries readily distinguishes them from those of Pit1 mutants and normal mice. This and other features suggest that Prop1 controls the expression of genes besides Pit1 that are important for pituitary cell migration, survival, and differentiation. To identify genes involved in these processes we used microarray analysis of gene expression to compare pituitary RNA from newborn Prop1 and Pit1 mutants and wild-type littermates. Significant differences in gene expression were noted between each mutant and their normal littermates, as well as between Prop1 and Pit1 mutants. Otx2, a gene critical for normal eye and pituitary development in humans and mice, exhibited elevated expression specifically in Prop1 mutant pituitaries. We report the spatial and temporal regulation of Otx2 in normal mice and Prop1 mutants, and the results suggest Otx2 could influence pituitary development by affecting signaling from the ventral diencephalon and regulation of gene expression in Rathke's pouch. The discovery that Otx2 expression is affected by Prop1 deficiency provides support for our hypothesis that identifying molecular differences in mutants will contribute to understanding the molecular mechanisms that control pituitary organogenesis and lead to human pituitary disease. PMID:21828248

  17. Downregulation of Axl in non-MYCN amplified neuroblastoma cell lines reduces migration.

    PubMed

    Duijkers, Floor A M; Meijerink, Jules P P; Pieters, Rob; van Noesel, Max M

    2013-05-25

    Neuroblastomas (NBL) are common pediatric solid tumors with a variable clinical course. At diagnosis half of all neuroblastoma patients presents with metastatic disease. The mechanisms of metastasis are largely unknown. Gene expression profiles (HU133plus2.0 arrays, Affymetrix) of 17 NBL and 5 peripheral neuro-ectodermal cell lines were used to identify a subgroup of non-MYCN amplified (non-NMA) NBL cell lines with a distinct gene expression profile and characterized by high expression of AXL. Axl is a tyrosine kinase receptor which plays a role in the metastatic process of several types of cancer. We hypothesized that Axl contributes to the metastasizing potential of non-NMA NBL and tested if AXL silencing diminishes malignant properties of high Axl expressing cell lines. AXL was silenced in two non-NMA NBL cell lines by using a lentiviral shRNA construct that was able to transduce these cell lines with more than 90% infection efficiency. Axl mRNA and protein level were efficiently knocked-down resulting in a decrease of migration of Axl positive cell lines GI-M-EN and SH-EP-2, and decreased invasion of GI-M-EN. Morphologically, Axl knockdown induced more rounded cells with a loss of contact. Intracellularly, we observed induction of stress fibers (immunofluorescence F-actin). These changes in cytoskeleton were associated with decreased migration, but were not accompanied by changes in genes involved in epithelial to mesenchymal transition such as CDH2, VIM or MMP9. No effects were observed for cell proliferation, apoptosis or downstream pathways. In conclusion, AXL is identified as a possible mediator of NBL metastasis. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. CXCL12 Gene Therapy Ameliorates Ischemia-Induced White Matter Injury in Mouse Brain.

    PubMed

    Li, Yaning; Tang, Guanghui; Liu, Yanqun; He, Xiaosong; Huang, Jun; Lin, Xiaojie; Zhang, Zhijun; Yang, Guo-Yuan; Wang, Yongting

    2015-10-01

    Remyelination is an important repair process after ischemic stroke-induced white matter injury. It often fails because of the insufficient recruitment of oligodendrocyte progenitor cells (OPCs) to the demyelinated site or the inefficient differentiation of OPCs to oligodendrocytes. We investigated whether CXCL12 gene therapy promoted remyelination after middle cerebral artery occlusion in adult mice. The results showed that CXCL12 gene therapy at 1 week after ischemia could protect myelin sheath integrity in the perifocal region, increase the number of platelet-derived growth factor receptor-α (PDGFRα)-positive and PDGFRα/bromodeoxyuridine-double positive OPCs in the subventricular zone, and further enhance their migration to the ischemic lesion area. Coadministration of AMD3100, the antagonist for CXCL12 receptor CXCR4, eliminated the beneficial effect of CXCL12 on myelin sheath integrity and negatively influenced OPC proliferation and migration. At 5 weeks after ischemia, CXCR4 was found on the PDGFRα- and/or neuron/glia type 2 (NG2)-positive OPCs but not on the myelin basic protein-positive mature myelin sheaths, and CXCR7 was only expressed on the mature myelin sheath in the ischemic mouse brain. Our data indicated that CXCL12 gene therapy effectively protected white matter and promoted its repair after ischemic injury. The treatment at 1 week after ischemia is effective, suggesting that this strategy has a longer therapeutic time window than the treatments currently available. This study has demonstrated for the first time that CXCL12 gene therapy significantly ameliorates brain ischemia-induced white matter injury and promotes oligodendrocyte progenitor cell proliferation in the subventricular zone and migration to the perifocal area in the ischemic mouse brain. Additional data showed that CXCR4 receptor plays an important role during the proliferation and migration of oligodendrocyte progenitor cells, and CXCR7 might play a role during maturation. In

  19. Defective eyelid leading edge cell migration in C57BL/6-corneal opacity mice with an "eye open at birth" phenotype.

    PubMed

    Wu, L C; Liu, C; Jiang, M R; Jiang, Y M; Wang, Q H; Lu, Z Y; Wang, S J; Yang, W L; Shao, Y X

    2016-08-26

    Development of the eyelid requires coordination of the cellular processes involved in proliferation, cell size alteration, migration, and cell death. C57BL/6J-corneal opacity (B6-Co) mice are mutant mice generated by the administration of N-ethyl-N-nitrosourea (100 mg/kg). They exhibit the eyelids open at birth phenotype, abnormal round cell shape from tightened F-actin bundles in leading edge keratinocytes at E16.5, and gradual corneal opacity with neovessels. The tip of the leading edge in B6-Co mice did not move forward, and demonstrated a sharp peak shape without obvious directionality. Analysis of the biological characteristics of B6-Co mice demonstrated that abnormal migration of keratinocytes could affect eyelid development, but proliferation and apoptosis in B6-Co mice had no effect. Mutant gene mapping and sequence analysis demonstrated that in B6-Co mice, adenosine was inserted into the untranslated regions, between 3030 and 3031, in the mRNA 3'-terminal of Fgf10. In addition, guanine 7112 was substituted by adenine in the Mtap1B mRNA, and an A2333T mutation was identified in Mtap1B. Quantitative real-time polymerase chain reaction analysis showed that expression of the Hbegf gene was significantly down-regulated in the eyelids of B6- Co mice at E16.5, compared to B6 mice. However, the expression of Rock1, Map3k1, and Jnk1 genes did not show any significant changes. Abnormal keratinocyte migration and down-regulated expression of the Hbegf gene might be associated with impaired eyelid development in B6-Co mice.

  20. 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.

  1. Fringe chasing by three-point spatial phase shifting for discrimination of the motion direction in the long-range homodyne laser Doppler vibrometry

    NASA Astrophysics Data System (ADS)

    Daemi, Mohammad Hossein; Rasouli, Saifollah

    2018-07-01

    In this work, a three-point spatial phase shifting (SPS) method is implemented for chasing of the moving interference fringes in the homodyne laser Doppler vibrometry (HoLDV). By the use of SPS method, we remove disability of the HoLDV in the discrimination of the motion direction for long-range displacements. From the phase increments histogram, phase unwrapping tolerance value is selected, and adequacy of the data acquisition rate and required bandwidth limit are determined. Also in this paper, a detailed investigation on the effect of detectors positioning errors and influence of the Gaussian profile of the interfering beams on the measurements are presented. Performance of the method is verified by measuring a given harmonic vibration produced by a loudspeaker. Also, by the proposed method, vibration of mounting system of a disk laser gain medium is characterized.

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

    PubMed

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

    2013-01-01

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

  3. 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

  4. 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.

  5. Individual versus Household Migration Decision Rules: Gender and Marital Status Differences in Intentions to Migrate in South Africa

    PubMed Central

    Gubhaju, Bina; De Jong, Gordon F.

    2009-01-01

    This research tests the thesis that the neoclassical micro-economic and the new household economic theoretical assumptions on migration decision-making rules are segmented by gender, marital status, and time frame of intention to migrate. Comparative tests of both theories within the same study design are relatively rare. Utilizing data from the Causes of Migration in South Africa national migration survey, we analyze how individually held “own-future” versus alternative “household well-being” migration decision rules effect the intentions to migrate of male and female adults in South Africa. Results from the gender and marital status specific logistic regressions models show consistent support for the different gender-marital status decision rule thesis. Specifically, the “maximizing one’s own future” neoclassical microeconomic theory proposition is more applicable for never married men and women, the “maximizing household income” proposition for married men with short-term migration intentions, and the “reduce household risk” proposition for longer time horizon migration intentions of married men and women. Results provide new evidence on the way household strategies and individual goals jointly affect intentions to move or stay. PMID:20161187

  6. Inhibition of vascular smooth muscle cell proliferation and migration in vitro and neointimal hyperplasia in vivo by adenoviral-mediated atrial natriuretic peptide delivery.

    PubMed

    Larifla, Laurent; Déprez, Isabelle; Pham, Isabelle; Rideau, Dominique; Louzier, Vanessa; Adam, Micheline; Eloit, Marc; Foucan, Lydia; Adnot, Serge; Teiger, Emmanuel

    2012-07-01

    Vascular smooth muscle cell (VSMC) proliferation and migration are important components of the remodeling process in atherosclerosis or following angioplasty. Atrial natriuretic peptide (ANP) inhibits the growth of VSMCs in vitro but this effect has not been proven in vivo. In the present study, we examined the effects of local overexpression of ANP following gene transfer on in vitro VSMC proliferation and migration and in vivo neointimal formation in a rat carotid artery model of vascular injury. ANP gene transfer was performed using a recombinant adenovirus containing the ANP cDNA controlled by the Rous sarcoma virus (RSV) long terminal repeat (Ad-RSV-ANP). A recombinant adenovirus expressing the RSV-controlled β-galactosidase gene (Ad-RSV-β-gal) was used as the control. Rat VSMC culture was used for in vitro studies. In the in vivo experiments, carotid arteries were analyzed after balloon injury and local infusion of the viral solution. VSMCs transfected by Ad-RSV-ANP produced a significant amount of ANP detected by immunoreactive assay and accumulated about 6.5 times more cGMP than the viral control. VSMC proliferation stimulated with 10% fetal calf serum was reduced by 31% and migration by 25%. Fourteen days after injury, neointimal formation and the intima/media ratio were reduced by 25% and 28%, respectively, in the Ad-RSV-ANP-treated group compared to the control group. The present study demonstrates the efficacy of recombinant adenovirus Ad-RSV-ANP with respect to inhibiting rat VSMC proliferation and migration. Our findings also provide evidence that ANP is implicated in the modulation of vascular remodeling following endothelial injury. Copyright © 2012 John Wiley & Sons, Ltd.

  7. Induction of type 1 iodothyronine deiodinase expression inhibits proliferation and migration of renal cancer cells.

    PubMed

    Poplawski, Piotr; Rybicka, Beata; Boguslawska, Joanna; Rodzik, Katarzyna; Visser, Theo J; Nauman, Alicja; Piekielko-Witkowska, Agnieszka

    2017-02-15

    Type 1 iodothyronine deiodinase (DIO1) regulates peripheral metabolism of thyroid hormones that control cellular proliferation, differentiation and metabolism. The significance of DIO1 in cancer is unknown. In this study we hypothesized that diminished expression of DIO1, observed in renal cancer, contributes to the carcinogenic process in the kidney. Here, we demonstrate that ectopic expression of DIO1 in renal cancer cells changes the expression of genes controlling cell cycle, including cyclin E1 and E2F5, and results in inhibition of proliferation. The expression of genes encoding collagens (COL1A1, COL4A2, COL5A1), integrins (ITGA4, ITGA5, ITGB3) and transforming growth factor-β-induced (TGFBI) is significantly altered in renal cancer cells with induced expression of DIO1. Finally, we show that overexpression of DIO1 inhibits migration of renal cancer cells. In conclusion, we demonstrate for the first time that loss of DIO1 contributes to renal carcinogenesis and that its induced expression protects cells against cancerous proliferation and migration. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. 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.

  9. Grhl3 and Lmo4 play coordinate roles in epidermal migration.

    PubMed

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

    2008-09-01

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

  10. 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

  11. Membrane Type 1 Matrix Metalloproteinase Regulates Monocyte Migration and Collagen Destruction in Tuberculosis.

    PubMed

    Sathyamoorthy, Tarangini; Tezera, Liku B; Walker, Naomi F; Brilha, Sara; Saraiva, Luisa; Mauri, Francesco A; Wilkinson, Robert J; Friedland, Jon S; Elkington, Paul T

    2015-08-01

    Tuberculosis (TB) remains a global pandemic and drug resistance is rising. Multicellular granuloma formation is the pathological hallmark of Mycobacterium tuberculosis infection. The membrane type 1 matrix metalloproteinase (MT1-MMP or MMP-14) is a collagenase that is key in leukocyte migration and collagen destruction. In patients with TB, induced sputum MT1-MMP mRNA levels were increased 5.1-fold compared with matched controls and correlated positively with extent of lung infiltration on chest radiographs (r = 0.483; p < 0.05). M. tuberculosis infection of primary human monocytes increased MT1-MMP surface expression 31.7-fold and gene expression 24.5-fold. M. tuberculosis-infected monocytes degraded collagen matrix in an MT1-MMP-dependent manner, and MT1-MMP neutralization decreased collagen degradation by 73%. In human TB granulomas, MT1-MMP immunoreactivity was observed in macrophages throughout the granuloma. Monocyte-monocyte networks caused a 17.5-fold increase in MT1-MMP surface expression dependent on p38 MAPK and G protein-coupled receptor-dependent signaling. Monocytes migrating toward agarose beads impregnated with conditioned media from M. tuberculosis-infected monocytes expressed MT1-MMP. Neutralization of MT1-MMP activity decreased this M. tuberculosis network-dependent monocyte migration by 44%. Taken together, we demonstrate that MT1-MMP is central to two key elements of TB pathogenesis, causing collagen degradation and regulating monocyte migration. Copyright © 2015 The Authors.

  12. MiR-525-3p Enhances the Migration and Invasion of Liver Cancer Cells by Downregulating ZNF395

    PubMed Central

    Pang, Fei; Zha, Ruopeng; Zhao, Yingjun; Wang, Qifeng; Chen, Di; Zhang, Zhenfeng; Chen, Taoyang; Yao, Ming; Gu, Jianren; He, Xianghuo

    2014-01-01

    Liver cancer is one of leading causes of cancer-related deaths. A deeper mechanistic understanding of liver cancer could lead to the development of more effective therapeutic strategies. In our previous work, we screened 646 miRNAs and identified 11 that regulate liver cancer cell migration. The current study shows that miR-525-3p is frequently up-regulated in liver cancer tissues, and enhanced expression of miR-525-3p can promote liver cancer cell migration and invasion. Zinc finger protein 395 (ZNF395) is the direct functional target gene for miR-525-3p, and it is frequently down-regulated in liver cancer tissues. High expression of ZNF395 can significantly inhibit while knockdown of ZNF395 expression can markedly enhance the migration and invasion of liver cancer cells, suggesting that ZNF395 suppresses metastasis in liver cancer. Down-regulation of ZNF395 can mediate miR-525-3p induced liver cancer cell migration and invasion. In conclusion, miR-525-3p promotes liver cancer cell migration and invasion by directly targeting ZNF395, and the fact that miR-525-3p and ZNF395 both play important roles in liver cancer progression makes them potential therapeutic targets. PMID:24599008

  13. Actin capping protein CAPZB regulates cell morphology, differentiation, and neural crest migration in craniofacial morphogenesis†

    PubMed Central

    Mukherjee, Kusumika; Ishii, Kana; Pillalamarri, Vamsee; Kammin, Tammy; Atkin, Joan F.; Hickey, Scott E.; Xi, Qiongchao J.; Zepeda, Cinthya J.; Gusella, James F.; Talkowski, Michael E.; Morton, Cynthia C.; Maas, Richard L.; Liao, Eric C.

    2016-01-01

    CAPZB is an actin-capping protein that caps the growing end of F-actin and modulates the cytoskeleton and tethers actin filaments to the Z-line of the sarcomere in muscles. Whole-genome sequencing was performed on a subject with micrognathia, cleft palate and hypotonia that harbored a de novo, balanced chromosomal translocation that disrupts the CAPZB gene. The function of capzb was analyzed in the zebrafish model. capzb−/− mutants exhibit both craniofacial and muscle defects that recapitulate the phenotypes observed in the human subject. Loss of capzb affects cell morphology, differentiation and neural crest migration. Differentiation of both myogenic stem cells and neural crest cells requires capzb. During palate morphogenesis, defective cranial neural crest cell migration in capzb−/− mutants results in loss of the median cell population, creating a cleft phenotype. capzb is also required for trunk neural crest migration, as evident from melanophores disorganization in capzb−/− mutants. In addition, capzb over-expression results in embryonic lethality. Therefore, proper capzb dosage is important during embryogenesis, and regulates both cell behavior and tissue morphogenesis. PMID:26758871

  14. 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.

  15. 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…

  16. 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…

  17. 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

  18. 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.

  19. [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.

  20. 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.

  1. ADAM13 function is required in the 3 dimensional context of the embryo during cranial neural crest cell migration in Xenopus laevis

    PubMed Central

    Cousin, Hélène; Abbruzzese, Genevieve; McCusker, Catherine; Alfandari, Dominique

    2012-01-01

    The cranial neural crest (CNC) is a population of cells that arises from the lateral part of the developing brain, migrates ventrally and coordinates the entire craniofacial development of vertebrates. Many molecules are involved in CNC migration including the transmembrane metalloproteases ADAM13 and 19. We have previously shown that these ADAMs cleave a number of extracellular proteins and modify the transcription of a number of genes, and that both of these activities are important for cell migration. Here we show that the knock down of ADAM13 inhibits CNC migration in vivo but not in vitro, indicating that ADAM13 function is required in the 3-dimentional context of the embryo. We further show that the migration of CNC that do not express ADAM13 and ADAM19 can be rescued in vivo by co-grafting wild type CNC. Furthermore, the migration of CNC lacking ADAM13 can be rescued by mechanically separating the CNC from the surrounding ectoderm and mesoderm. Finally, we show that ADAM13 function is autonomous to CNC tissue, as the migration of morphant CNC can only be rescued by ADAM13 expression in the CNC and not the surrounding tissues. Together our results suggest that ADAM13 changes CNC interaction with the extracellular environment and that this change is necessary for their migration in vivo. PMID:22683825

  2. EBF factors drive expression of multiple classes of target genes governing neuronal development.

    PubMed

    Green, Yangsook S; Vetter, Monica L

    2011-04-30

    Early B cell factor (EBF) family members are transcription factors known to have important roles in several aspects of vertebrate neurogenesis, including commitment, migration and differentiation. Knowledge of how EBF family members contribute to neurogenesis is limited by a lack of detailed understanding of genes that are transcriptionally regulated by these factors. We performed a microarray screen in Xenopus animal caps to search for targets of EBF transcriptional activity, and identified candidate targets with multiple roles, including transcription factors of several classes. We determined that, among the most upregulated candidate genes with expected neuronal functions, most require EBF activity for some or all of their expression, and most have overlapping expression with ebf genes. We also found that the candidate target genes that had the most strongly overlapping expression patterns with ebf genes were predicted to be direct transcriptional targets of EBF transcriptional activity. The identification of candidate targets that are transcription factor genes, including nscl-1, emx1 and aml1, improves our understanding of how EBF proteins participate in the hierarchy of transcription control during neuronal development, and suggests novel mechanisms by which EBF activity promotes migration and differentiation. Other candidate targets, including pcdh8 and kcnk5, expand our knowledge of the types of terminal differentiated neuronal functions that EBF proteins regulate.

  3. The pH-sensing receptor OGR1 improves barrier function of epithelial cells and inhibits migration in an acidic environment.

    PubMed

    de Vallière, Cheryl; Vidal, Solange; Clay, Ieuan; Jurisic, Giorgia; Tcymbarevich, Irina; Lang, Silvia; Ludwig, Marie-Gabrielle; Okoniewski, Michal; Eloranta, Jyrki J; Kullak-Ublick, Gerd A; Wagner, Carsten A; Rogler, Gerhard; Seuwen, Klaus

    2015-09-15

    The pH-sensing receptor ovarian cancer G protein-coupled receptor 1 (OGR1; GPR68) is expressed in the gut. Inflammatory bowel disease is typically associated with a decrease in local pH, which may lead to altered epithelial barrier function and subsequent gastrointestinal repair involving epithelial cell adhesion and migration. As the mechanisms underlying the response to pH changes are not well understood, we have investigated OGR1-mediated, pH-dependent signaling pathways in intestinal epithelial cells. Caco-2 cells stably overexpressing OGR1 were created and validated as tools to study OGR1 signaling. Barrier function, migration, and proliferation were measured using electric cell-substrate impedance-sensing technology. Localization of the tight junction proteins zonula occludens protein 1 and occludin and the rearrangement of cytoskeletal actin were examined by confocal microscopy. Paracellular permeability and protein and gene expression analysis using DNA microarrays were performed on filter-grown Caco-2 monolayers. We report that an acidic pH shift from pH 7.8 to 6.6 improved barrier function and stimulated reorganization of filamentous actin with prominent basal stress fiber formation. Cell migration and proliferation during in vitro wound healing were inhibited. Gene expression analysis revealed significant upregulation of genes related to cytoskeleton remodeling, cell adhesion, and growth factor signaling. We conclude that acidic extracellular pH can have a signaling function and impact the physiology of intestinal epithelial cells. The deconstruction of OGR1-dependent signaling may aid our understanding of mucosal inflammation mechanisms. Copyright © 2015 the American Physiological Society.

  4. Lake-specific variation in growth, migration timing and survival of juvenile sockeye salmon Oncorhynchus nerka: separating environmental from genetic influences.

    PubMed

    Reed, T E; Martinek, G; Quinn, T P

    2010-08-01

    Time series on juvenile life-history traits obtained from sockeye salmon Oncorhynchus nerka were analysed to assess lake-specific environmental influences on juvenile migration timing, size and survival of fish from a common gene pool. Every year for the past two decades, O. nerka have been spawned at a hatchery facility, and the progeny released into two lakes that differ in average summer temperatures, limnological attributes and growth opportunities. Juveniles reared in the warmer, more productive Crosswind Lake were larger and heavier as smolts compared to those from the cooler, less productive Summit Lake and had higher in-lake and subsequent marine survival. Crosswind Lake smolts migrated from the lake to sea slightly earlier in the season but the migration timing distributions overlapped considerably across years. Fry stocking density had a negative effect on smolt length for both lakes, and a negative effect on in-lake survival in Summit Lake. Taken together, the results revealed a strong effect of lake-rearing environment on the expression of life-history variation in O. nerka. The stocking of these lakes each year with juveniles from a single mixed-source population provided a large-scale reverse common-garden experiment, where the same gene pool was exposed to different environments, rather than the different gene pools in the same environment approach typical of evolutionary ecology studies. Other researchers are encouraged to seek and exploit similar serendipitous situations, which might allow environmental and genetic influences on ecologically important traits to be distinguished in natural or semi-natural settings.

  5. The long non-coding RNA HOTTIP enhances pancreatic cancer cell proliferation, survival and migration.

    PubMed

    Cheng, Yating; Jutooru, Indira; Chadalapaka, Gayathri; Corton, J Christopher; Safe, Stephen

    2015-05-10

    HOTTIP is a long non-coding RNA (lncRNA) transcribed from the 5' tip of the HOXA locus and is associated with the polycomb repressor complex 2 (PRC2) and WD repeat containing protein 5 (WDR5)/mixed lineage leukemia 1 (MLL1) chromatin modifying complexes. HOTTIP is expressed in pancreatic cancer cell lines and knockdown of HOTTIP by RNA interference (siHOTTIP) in Panc1 pancreatic cancer cells decreased proliferation, induced apoptosis and decreased migration. In Panc1 cells transfected with siHOTTIP, there was a decrease in expression of 757 genes and increased expression of 514 genes, and a limited gene analysis indicated that HOTTIP regulation of genes is complex. For example, Aurora kinase A, an important regulator of cell growth, is coregulated by MLL and not WDR5 and, in contrast to previous studies in liver cancer cells, HOTTIP does not regulate HOXA13 but plays a role in regulation of several other HOX genes including HOXA10, HOXB2, HOXA11, HOXA9 and HOXA1. Although HOTTIP and the HOX-associated lncRNA HOTAIR have similar pro-oncogenic functions, they regulate strikingly different sets of genes in Panc1 cells and in pancreatic tumors.

  6. Effect of acetaminophen on osteoblastic differentiation and migration of MC3T3-E1 cells.

    PubMed

    Nakatsu, Yoshihiro; Nakagawa, Fumio; Higashi, Sen; Ohsumi, Tomoko; Shiiba, Shunji; Watanabe, Seiji; Takeuchi, Hiroshi

    2018-02-01

    N-acetyl-p-aminophenol (APAP, acetaminophen, paracetamol) is a widely used analgesic/antipyretic with weak inhibitory effects on cyclooxygenase (COX) compared to non-steroidal anti-inflammatory drugs (NSAIDs). The mechanism of action of APAP is mediated by its metabolite that activates transient receptor potential channels, including transient receptor potential vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) or the cannabinoid receptor type 1 (CB1). However, the exact molecular mechanism and target underlying the cellular actions of APAP remain unclear. Therefore, we investigated the effect of APAP on osteoblastic differentiation and cell migration, with a particular focus on TRP channels and CB1. Effects of APAP on osteoblastic differentiation and cell migration of MC3T3-E1, a mouse pre-osteoblast cell line, were assessed by the increase in alkaline phosphatase (ALP) activity, and both wound-healing and transwell-migration assays, respectively. APAP dose-dependently inhibited osteoblastic differentiation, which was well correlated with the effects on COX activity compared with other NSAIDs. In contrast, cell migration was promoted by APAP, and this effect was not correlated with COX inhibition. None of the agonists or antagonists of TRP channels and the CB receptor affected the APAP-induced cell migration, while the effect of APAP on cell migration was abolished by down-regulating TRPV4 gene expression. APAP inhibited osteoblastic differentiation via COX inactivation while it promoted cell migration independently of previously known targets such as COX, TRPV1, TRPA1 channels, and CB receptors, but through the mechanism involving TRPV4. APAP may have still unidentified molecular targets that modify cellular functions. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

  7. The spring migration of adult North American Ospreys

    USGS Publications Warehouse

    Martell, Mark S.; Bierregaard, Richard O.; Washburn, Brian E.; Elliott, John E.; Henny, Charles J.; Kennedy, Robert S.; MacLeod, Iain

    2014-01-01

    Most North American Ospreys (Pandion haliaetus) are migratory, breeding in northern latitudes and migrating long distances to and from their wintering grounds in the tropics. Although fall migration patterns of North American Ospreys have been described and studied, very little has been published about the spring migration of these birds. We used satellite telemetry to: (1) determine the characteristics (timing, duration, migratory routes) of spring migrations of Ospreys; (2) determine if differences in spring migration patterns existed between sexes and among three breeding populations (east coast, midwestern, and western); and (3) compare consecutive fall and spring migrations of individual Ospreys. The median dates for departure from the wintering grounds and arrival on the breeding grounds did not differ significantly between adult male and female Ospreys. Compared to their fall migrations, all male and all east coast Ospreys spent fewer days on migration, fewer days in stopover periods along the migration route, traveled shorter distances overall, and traveled farther (on average) each day during spring. In contrast, fall and spring migration characteristics of all female and western Ospreys were similar. Our findings suggest that, although sex and breeding location might influence the spring migration strategy used by individual Ospreys, both males and females minimize the time spent on migration to ensure a timely arrival on the breeding grounds to establish or defend a nesting territory.

  8. [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.

  9. 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.

  10. Intravital multiphoton imaging reveals multicellular streaming as a crucial component of in vivo cell migration in human breast tumors

    PubMed Central

    Patsialou, Antonia; Bravo-Cordero, Jose Javier; Wang, Yarong; Entenberg, David; Liu, Huiping; Clarke, Michael; Condeelis, John S.

    2014-01-01

    Metastasis is the main cause of death in breast cancer patients. Cell migration is an essential component of almost every step of the metastatic cascade, especially the early step of invasion inside the primary tumor. In this report, we have used intravital multiphoton microscopy to visualize the different migration patterns of human breast tumor cells in live primary tumors. We used xenograft tumors of MDA-MB-231 cells as well as a low passage xenograft tumor from orthotopically injected patient-derived breast tumor cells. Direct visualization of human tumor cells in vivo shows two patterns of high-speed migration inside primary tumors: a. single cells and b. multicellular streams (i.e., cells following each other in a single file but without cohesive cell junctions). Critically, we found that only streaming and not random migration of single cells was significantly correlated with proximity to vessels, with intravasation and with numbers of elevated circulating tumor cells in the bloodstream. Finally, although the two human tumors were derived from diverse genetic backgrounds, we found that their migratory tumor cells exhibited coordinated gene expression changes that led to the same end-phenotype of enhanced migration involving activating actin polymerization and myosin contraction. Our data are the first direct visualization and assessment of in vivo migration within a live patient-derived breast xenograft tumor. PMID:25013744

  11. 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

  12. Tropine forming tropinone reductase gene from Withania somnifera (Ashwagandha): biochemical characteristics of the recombinant enzyme and novel physiological overtones of tissue-wide gene expression patterns.

    PubMed

    Kushwaha, Amit Kumar; Sangwan, Neelam Singh; Trivedi, Prabodh Kumar; Negi, Arvind Singh; Misra, Laxminarain; Sangwan, Rajender Singh

    2013-01-01

    Withania somnifera is one of the most reputed medicinal plants of Indian systems of medicine synthesizing diverse types of secondary metabolites such as withanolides, alkaloids, withanamides etc. Present study comprises cloning and E. coli over-expression of a tropinone reductase gene (WsTR-I) from W. somnifera, and elucidation of biochemical characteristics and physiological role of tropinone reductase enzyme in tropane alkaloid biosynthesis in aerial tissues of the plant. The recombinant enzyme was demonstrated to catalyze NADPH-dependent tropinone to tropine conversion step in tropane metabolism, through TLC, GC and GC-MS-MS analyses of the reaction product. The functionally active homodimeric ~60 kDa enzyme catalyzed the reaction in reversible manner at optimum pH 6.7. Catalytic kinetics of the enzyme favoured its forward reaction (tropine formation). Comparative 3-D models of landscape of the enzyme active site contours and tropinone binding site were also developed. Tissue-wide and ontogenic stage-wise assessment of WsTR-I transcript levels revealed constitutive expression of the gene with relatively lower abundance in berries and young leaves. The tissue profiles of WsTR-I expression matched those of tropine levels. The data suggest that, in W. somnifera, aerial tissues as well possess tropane alkaloid biosynthetic competence. In vivo feeding of U-[(14)C]-sucrose to orphan shoot (twigs) and [(14)C]-chasing revealed substantial radiolabel incorporation in tropinone and tropine, confirming the de novo synthesizing ability of the aerial tissues. This inherent independent ability heralds a conceptual novelty in the backdrop of classical view that these tissues acquire the alkaloids through transportation from roots rather than synthesis. The TR-I gene expression was found to be up-regulated on exposure to signal molecules (methyl jasmonate and salicylic acid) and on mechanical injury. The enzyme's catalytic and structural properties as well as gene expression

  13. Antimicrobial susceptibility of Escherichia coli isolated from feces of wild cranes migrating to Kagoshima, Japan.

    PubMed

    Kitadai, Noriyuki; Obi, Takeshi; Yamashita, Shogo; Murase, Toshiyuki; Takase, Kozo

    2012-03-01

    Susceptibility to 13 antimicrobial agents was examined for 138 Escherichia coli isolates obtained from 192 fecal samples of wild cranes that migrated for wintering to the Izumi plain, Kagoshima prefecture in Japan. The numbers of isolates that were resistant to the antimicrobials used in this study are as follows: oxytetracycline (OTC), 22 isolates; minocycline, 7 isolates; ampicillin (ABPC), 4 isolates; nalidixic acid, 4 isolates; enrofloxacin, 2 isolates; kanamycin, one isolate. Multidrug resistant isolates exhibiting 2-4 drug resistances were obtained. All of the OTC-resistant isolates carried either the tet (A) or tet(B) gene. The bla(TEM) gene was found in all of the ABPC-resistant isolates.

  14. Circadian locomotor output cycles kaput affects the proliferation and migration of breast cancer cells by regulating the expression of E-cadherin via IQ motif containing GTPase activating protein 1.

    PubMed

    Li, Xiaoxue; Wang, Siyang; Yang, Shuhong; Ying, Junjie; Yu, Hang; Yang, Chunlei; Liu, Yanyou; Wang, Yuhui; Cheng, Shuting; Xiao, Jing; Guo, Huiling; Jiang, Zhou; Wang, Zhengrong

    2018-05-01

    The circadian rhythm regulates numerous physiological activities, including sleep and wakefulness, behavior, immunity and metabolism. Previous studies have demonstrated that circadian rhythm disorder is associated with the occurrence of tumors. Responsible for regulating a number of functions, the Circadian locomotor output cycles kaput ( Clock ) gene is one of the core regulatory genes of circadian rhythm. The Clock gene has also been implicated in the occurrence and development of tumors in previously studies. The present study evaluated the role of the Clock gene in the proliferation and migration of mouse breast cancer 4T1 cells, and investigated its possible regulatory pathways and mechanisms. It was reported that downregulation of Clock facilitated the proliferation and migration of breast cancer cells. Further investigation revealed the involvement of IQ motif containing GTPase activating protein 1 (IQGAP1) protein expression in the Clock regulatory pathway, further influencing the expression of E-cadherin, a known proprietor of tumor cell migration and invasion. To the best of our knowledge, the present study is the first to report that Clock , acting through the regulation of the scaffolding protein IQGAP1, regulates the downstream expression of E-cadherin, thereby affecting tumor cell structure and motility. These results confirmed the role of Clock in breast cancer tumor etiology and provide insight regarding the molecular avenues of its regulatory nature, which may translate beyond breast cancer into other known functions of the gene.

  15. 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

  16. [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)

  17. Neuronal migration, apoptosis and bipolar disorder.

    PubMed

    Uribe, Ezequiel; Wix, Richard

    2012-01-01

    Bipolar disorder, like the majority of psychiatric disorders, is considered a neurodevelopment disease of neurodevelopment. There is an increased rate of neuronal birth and death during this development period. In the particular case of the processes that determine neuronal death, it is known that those neurons that establish connections have to be removed from the central nervous system. There is a deficit of GABAergic interneurons in the cerebral cortex in bipolar disorder, accompanied by overexpression of proapoptic genes. There is also an alteration in the expression of molecules that mediate in the migration of these neurons and their inclusion in functional synapsis during the foetal stage. The role of these molecules in the neuronal death pathways by apoptosis will be reviewed here in an attempt to establish biological hypotheses of the genesis of bipolar disorder. Copyright © 2011 SEP y SEPB. Published by Elsevier Espana. All rights reserved.

  18. Expression of macrophage migration inhibitory factor in footpad skin lesions with diabetic neuropathy.

    PubMed

    Up Noh, Sun; Lee, Won-Young; Kim, Won-Serk; Lee, Yong-Taek; Jae Yoon, Kyung

    2018-01-01

    , small interfering RNA-transfected knockdown of the migration inhibitory factor gene in methylglyoxal-treated skin keratinocytes increased expression of glyoxalase-I and intraepidermal nerve fibers in comparison with control small interfering RNA-transfected cells, which was decreased by induction of methylglyoxal. Conclusions Our findings suggest that migration inhibitory factor can aggravate diabetic neuropathy by suppressing glyoxalase-I and intraepidermal nerve fibers on the footpad skin lesions and provoke pain. Taken together, migration inhibitory factor might offer a pharmacological approach to alleviate pain syndromes in diabetic neuropathy.

  19. The Nudix Hydrolase CDP-Chase, a CDP-Choline Pyrophosphatase, Is an Asymmetric Dimer with Two Distinct Enzymatic Activities

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

    Duong-Ly, Krisna C.; Gabelli, Sandra B.; Xu, WenLian

    2011-09-06

    A Nudix enzyme from Bacillus cereus catalyzes the hydrolysis of CDP-choline to produce CMP and phosphocholine. Here, we show that in addition, the enzyme has a 3{prime} {yields} 5{prime} RNA exonuclease activity. The structure of the free enzyme, determined to a 1.8-{angstrom} resolution, shows that the enzyme is an asymmetric dimer. Each monomer consists of two domains, an N-terminal helical domain and a C-terminal Nudix domain. The N-terminal domain is placed relative to the C-terminal domain such as to result in an overall asymmetric arrangement with two distinct catalytic sites: one with an 'enclosed' Nudix pyrophosphatase site and the othermore » with a more open, less-defined cavity. Residues that may be important for determining the asymmetry are conserved among a group of uncharacterized Nudix enzymes from Gram-positive bacteria. Our data support a model where CDP-choline hydrolysis is catalyzed by the enclosed Nudix site and RNA exonuclease activity is catalyzed by the open site. CDP-Chase is the first identified member of a novel Nudix family in which structural asymmetry has a profound effect on the recognition of substrates.« less

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. ITGBL1 promotes migration, invasion and predicts a poor prognosis in colorectal cancer.

    PubMed

    Qiu, Xiao; Feng, Jue-Rong; Qiu, Jun; Liu, Lan; Xie, Yang; Zhang, Yu-Peng; Liu, Jing; Zhao, Qiu

    2018-05-14

    Colorectal cancer (CRC) is one of the most common malignancies worldwide; its progression and prognosis are associated with oncogenes. The present study aimed to identify differentially expressed genes (DEGs) and explore the role and potential mechanism of integrin subunit β like 1 (ITGBL1) in CRC. The microarray dataset GSE41258 was used to screen DEGs involved in CRC. Survival analysis was performed to predict the prognosis of CRC patients. To validate ITGBL1 expression, immunohistochemistry, quantitative real-time PCR and western blotting were performed in CRC tissues and cells. Subsequently, the effects of ITGBL1 were evaluated through colony formation, cell proliferation, migration and invasion assays. Finally, we took advantage of Gene Ontology (GO) analysis and Gene Set Enrichment Analysis (GSEA) to explore potential function and mechanism of ITGBL1 in CRC. In our study, 182 primary CRC tissues and 54 normal colon tissues were contained in GSE41258 dataset. A total of 318 DEGs were screened, among which ITGBL1 was found to be significantly up-regulated in CRC, and its high expression was associated with shortened survival of CRC patients. Moreover, knockdown of ITGBL1 promoted CRC cell proliferation, migration and invasion. Finally, GO analysis revealed that ITGBL1 was associated with cell adhesion. GSEA indicated that ITGBL1 was enriched in ECM receptor interaction and focal adhesion. In conclusion, a novel oncogene ITGBL1 was identified and demonstrated to be associated with the progression and prognosis of CRC, which might be a potential therapeutic target and prognostic biomarker for CRC patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  5. Migration within China and from China to the USA: the effects of migration networks, selectivity, and the rural political economy in Fujian Province.

    PubMed

    Liang, Zai; Chunyu, Miao David

    2013-07-01

    This paper tests a new strategy for simultaneously studying internal migration within, and international migration from, China. Our theoretical discussion draws on ideas from migration-networks theory and studies of the transition to a market-oriented economy. Data collection is modelled on the Mexican Migration Project. We find that education is more important in initiating internal migration than international migration. Second, although the role of migration networks at a community level seems similar to that for Mexico-USA migration, the networks at a family level show a different pattern. Third, there is evidence that internal and international migration are competing options. Finally, we find that individuals with cadres (public officials) in the family are less likely to undertake internal migration, but more likely to participate in international migration, a finding that highlights the continuing significance of the cadres in coastal rural China.

  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. 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

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

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

    Bernhart, Eva; Damm, Sabine; Wintersperger, Andrea

    inhibits MAPK signaling. • PRKD2 regulates transcription of gene products implicated in migration and invasion.« less

  9. Anticancer effects of the engineered stem cells transduced with therapeutic genes via a selective tumor tropism caused by vascular endothelial growth factor toward HeLa cervical cancer cells.

    PubMed

    Kim, Hye-Sun; Yi, Bo-Rim; Hwang, Kyung-A; Kim, Seung U; Choi, Kyung-Chul

    2013-10-01

    The aim of the present study was to investigate the therapeutic efficacy of genetically engineered stem cells (GESTECs) expressing bacterial cytosine deaminase (CD) and/or human interferon-beta (IFN-β) gene against HeLa cervical cancer and the migration factors of the GESTECs toward the cancer cells. Anticancer effect of GESTECs was examined in a co-culture with HeLa cells using MTT assay to measure cell viability. A transwell migration assay was performed so as to assess the migration capability of the stem cells to cervical cancer cells. Next, several chemoattractant ligands and their receptors related to a selective migration of the stem cells toward HeLa cells were determined by real-time PCR. The cell viability of HeLa cells was decreased in response to 5-fluorocytosine (5-FC), a prodrug, indicating that 5-fluorouracil (5-FU), a toxic metabolite, was converted from 5-FC by CD gene and it caused the cell death in a co-culture system. When IFN-β was additionally expressed with CD gene by these GESTECs, the anticancer activity was significantly increased. In the migration assay, the GESTECs selectively migrated to HeLa cervical cancer cells. As results of real-time PCR, chemoattractant ligands such as MCP-1, SCF, and VEGF were expressed in HeLa cells, and several receptors such as uPAR, VEGFR2, and c-kit were produced by the GESTECs. These GESTECs transduced with CD gene and IFN-β may provide a potential of a novel gene therapy for anticervical cancer treatments via their selective tumor tropism derived from VEGF and VEGFR2 expressions between HeLa cells and the GESTECs.

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

    PubMed

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

    2012-05-01

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

  11. A case for internal migration policy in India.

    PubMed

    Ram, S

    1993-01-01

    Migration helps to minimize regional, socioeconomic, and cultural disparities, and is considered to be an integral component of the development process. Migration helps to diffuse development, technology, and innovations from more developed areas or cities to rural or less developed areas. Little attention, however, has been paid to migration policy in India. Most studies on migration in India either describe the patterns of migration or analyze reasons for the moves. This paper discusses why migration takes place, what are the consequences of migration, whether India has a migration policy, whether India needs a migration policy, and what type of policy is required. The development and entrenchment of urban slums in India is related to the country's lack of migration policy. A two-pronged policy on migration is thus proposed which would ensure employment opportunities and an improved standard of living in rural areas, while taking into account the planning of cities and city surroundings. Rural areas and small towns need to be provided with more employment opportunities, financial and technological support to process raw materials, infrastructure for agricultural service centers, better education and other facilities to improve local living standards, and the diffusion of industries from big cities to district headquarters and medium-size towns. Commensurate efforts should be made in urban centers to prevent the future development of slums.

  12. Kinesin-related KIP3 of Saccharomyces cerevisiae Is Required for a Distinct Step in Nuclear Migration

    PubMed Central

    DeZwaan, Todd M.; Ellingson, Eric; Pellman, David; Roof, David M.

    1997-01-01

    Spindle orientation and nuclear migration are crucial events in cell growth and differentiation of many eukaryotes. Here we show that KIP3, the sixth and final kinesin-related gene in Saccharomyces cerevisiae, is required for migration of the nucleus to the bud site in preparation for mitosis. The position of the nucleus in the cell and the orientation of the mitotic spindle was examined by microscopy of fixed cells and by time-lapse microscopy of individual live cells. Mutations in KIP3 and in the dynein heavy chain gene defined two distinct phases of nuclear migration: a KIP3-dependent movement of the nucleus toward the incipient bud site and a dynein-dependent translocation of the nucleus through the bud neck during anaphase. Loss of KIP3 function disrupts the unidirectional movement of the nucleus toward the bud and mitotic spindle orientation, causing large oscillations in nuclear position. The oscillatory motions sometimes brought the nucleus in close proximity to the bud neck, possibly accounting for the viability of a kip3 null mutant. The kip3 null mutant exhibits normal translocation of the nucleus through the neck and normal spindle pole separation kinetics during anaphase. Simultaneous loss of KIP3 and kinesin-related KAR3 function, or of KIP3 and dynein function, is lethal but does not block any additional detectable movement. This suggests that the lethality is due to the combination of sequential and possibly overlapping defects. Epitope-tagged Kip3p localizes to astral and central spindle microtubules and is also present throughout the cytoplasm and nucleus. PMID:9281581

  13. [Over-expression of miR-151a-3p inhibits proliferation and migration of PC-3 prostate cancer cells].

    PubMed

    Zhang, Yi; Hao, Tongtong; Zhang, Han; Wei, Pengtao; Li, Xiaohui

    2018-03-01

    Objective To observe the effect of microRNA-151a-3p (miR-151a-3p) up-regulation on the proliferation and migration of prostate cancer cells and explore the possible molecular mechanism. Methods The expression of miR-151a-3p in PC-3M, C4-2B, 22RV1, DU-145, PC-3, LNCap human prostate cancer cells and RWPE-1 human normal prostate epithelial cells was detected by real-time fluorescence quantitative PCR. PC-3 cells with the lowest expression of miR-151a-3p were used for subsequent experiments. Bioinformatics and dual-luciferase reporter assay were performed to predict and test potential target genes of miR-151a-3p. The miR-151a-3p mimics or negative control microRNAs (miR-NCs) were transfected into PC-3 cells. Real-time fluorescence quantitative PCR was used to detect the expression of miR-151a-3p and potential target gene mRNA. The protein expressions of target genes and downstream signaling pathway proteins were analyzed by Western blotting. The proliferation of PC-3 cells was examined by MTT assay, and the migration of PC-3 cells was detected by Transwell TM assay. Results The expression level of miR-151a-3p in the prostate cancer cells was significantly lower than that in RWPE-1 normal human prostate epithelial cells. PC-3 cells had the lowest expression level of miR-151a-3p. The bioinformatics and dual-luciferase reporter assay showed that NEK2 was the potential target gene for miR-151a-3p. After transfection with miR-151a-3p mimics, the expression of miR-151a-3p in PC-3 cells significantly increased and the expression of NEK2 mRNA significantly decreased. The protein expressions of PI3K-AKT-mTOR signaling pathway were also reduced. Up-regulation of miR-151a-3p significantly inhibited the proliferation and migration of PC-3 cells. Conclusion The expression of miR-151a-3p is reduced in prostate cancer cells. Up-regulation of miR-151a-3p can inhibit the proliferation and migration of P-3 in prostate cancer by decreasing the expression of NEK2 and PI3K

  14. Emodin Inhibits Migration and Invasion of Human Endometrial Stromal Cells by Facilitating the Mesenchymal-Epithelial Transition Through Targeting ILK.

    PubMed

    Zheng, Qiaomei; Xu, Ying; Lu, Jingjing; Zhao, Jing; Wei, Xuan; Liu, Peishu

    2016-11-01

    To determine whether emodin facilitates the mesenchymal-epithelial transition (MET) of endometrial stromal cells (ESCs) as well as to explore the mechanism through which emodin favored the MET of ESCs. Cell viability was tested by methyl thiazolyl tetrazolium assay. Cell migration and invasion abilities were detected by transwell assays. Levels of integrin-linked kinase (ILK) and epithelial-mesenchymal transition (EMT)-related proteins were detected by Western blot. Upregulated ILK and increased abilities of migration and invasion were confirmed in the eutopic and ectopic ESCs (EuSCs and EcSCs), especially in the EcSCs. After treated with emodin, the expression of ILK was statistically downregulated in EcSCs, resulting in the MET and decreased migration and invasion abilities of EcSCs. Additionally, silencing of the ILK gene in EcSCs also achieved the above-mentioned effects, which were strengthened by emodin. Furthermore, exogenous expression of ILK in control ESCs (CSCs) resulted in the EMT and increased abilities of migration and invasion of CSCs, which can be abrogated by emodin. Besides, exogenous expression of ILK also abrogated the effects of emodin on CSCs. Emodin inhibits the migration and invasion abilities of human ESCs by facilitating the MET through targeting ILK. © The Author(s) 2016.

  15. [Role of connective tissue growth factor (CTGF) in proliferation and migration of pancreatic cancer cells].

    PubMed

    Bai, Yu-chun; Kang, Quan; Luo, Qing; Wu, Dao-qi; Ye, Wei-xia; Lin, Xue-mei; Zhao, Yong

    2011-10-01

    To explore the expression of connective tissue growth factor (CTGF) in pancreatic cancer and its influence on the proliferation and migration of cancer cells. The expression of CTGF in pancreatic cell line PANC-1 cells was analyzed by real-time PCR and in pancreatic carcinoma (50 cases) tissues by immunohistochemistry. The ability of proliferation and migration in vitro of PANC-1 cells was tested by MTT assay, scratch test and Boyden chamber test after the CTGF gene was overexpressed by Ad5-CTGF or silenced with Ad5-siCTGF transfection. CTGF was overexpressed in both pancreatic cancer cells and tissues. Overxpression of CTGF leads to increased proliferation and migration of PANC-1 cells. The CTGF-transfected PANC-1 cells showed apparent stronger proliferation ability and scratch-repair ability than that of empty vector controls. The results of Boyden chamber test showed that there were 34 cells/field (200× magnificantion) of the CTGF-transfected overexpressing cells, much more than the 11 cells/field of the empty vector control cells; and 6 cells/microscopic field of the Ad5-siCTGF-transfected silenced cells, much less than the 15 cells/field of the control cells. CTGF is overexpressed in both pancreatic cancer cells in vitro and in vivo, indicating that it may play an important role in the cell proliferation and migration in pancreatic cancer.

  16. TRIM16 inhibits proliferation and migration through regulation of interferon beta 1 in melanoma cells

    PubMed Central

    Sutton, Selina K.; Koach, Jessica; Tan, Owen; Liu, Bing; Carter, Daniel R.; Wilmott, James S.; Yosufi, Benafsha; Haydu, Lauren E.; Mann, Graham J.; Thompson, John F.; Long, Georgina V.; Liu, Tao; McArthur, Grant; Zhang, Xu Dong; Scolyer, Richard A.; Cheung, Belamy B.; Marshall, Glenn M.

    2014-01-01

    High basal or induced expression of the tripartite motif protein, TRIM16, leads to reduce cell growth and migration of neuroblastoma and skin squamous cell carcinoma cells. However, the role of TRIM16 in melanoma is currently unknown. TRIM16 protein levels were markedly reduced in human melanoma cell lines, compared with normal human epidermal melanocytes due to both DNA methylation and reduced protein stability. TRIM16 knockdown strongly increased cell migration in normal human epidermal melanocytes, while TRIM16 overexpression reduced cell migration and proliferation of melanoma cells in an interferon beta 1 (IFNβ1)-dependent manner. Chromatin immunoprecipitation assays revealed TRIM16 directly bound the IFNβ1 gene promoter. Low level TRIM16 expression in 91 melanoma patient samples, strongly correlated with lymph node metastasis, and, predicted poor patient prognosis in a separate cohort of 170 melanoma patients with lymph node metastasis. The BRAF inhibitor, vemurafenib, increased TRIM16 protein levels in melanoma cells in vitro, and induced growth arrest in BRAF-mutant melanoma cells in a TRIM16-dependent manner. High levels of TRIM16 in melanoma tissues from patients treated with Vemurafenib correlated with clinical response. Our data, for the first time, demonstrates TRIM16 is a marker of cell migration and metastasis, and a novel treatment target in melanoma. PMID:25333256

  17. Light pollution is greatest within migration passage areas for nocturnally-migrating birds around the world.

    PubMed

    Cabrera-Cruz, Sergio A; Smolinsky, Jaclyn A; Buler, Jeffrey J

    2018-02-19

    Excessive or misdirected artificial light at night (ALAN) produces light pollution that influences several aspects of the biology and ecology of birds, including disruption of circadian rhythms and disorientation during flight. Many migrating birds traverse large expanses of land twice every year at night when ALAN illuminates the sky. Considering the extensive and increasing encroachment of light pollution around the world, we evaluated the association of the annual mean ALAN intensity over land within the geographic ranges of 298 nocturnally migrating bird species with five factors: phase of annual cycle, mean distance between breeding and non-breeding ranges, range size, global hemisphere of range, and IUCN category of conservation concern. Light pollution within geographic ranges was relatively greater during the migration season, for shorter-distance migrants, for species with smaller ranges, and for species in the western hemisphere. Our results suggest that migratory birds may be subject to the effects of light pollution particularly during migration, the most critical stage in their annual cycle. We hope these results will spur further research on how light pollution affects not only migrating birds, but also other highly mobile animals throughout their annual cycle.

  18. 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.

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

    PubMed

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

    2012-04-11

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

  20. Pin1 promotes transforming growth factor-beta-induced migration and invasion.

    PubMed

    Matsuura, Isao; Chiang, Keng-Nan; Lai, Chen-Yu; He, Dongming; Wang, Guannan; Ramkumar, Romila; Uchida, Takafumi; Ryo, Akihide; Lu, Kunping; Liu, Fang

    2010-01-15

    Transforming growth factor-beta (TGF-beta) regulates a wide variety of biological activities. It induces potent growth-inhibitory responses in normal cells but promotes migration and invasion of cancer cells. Smads mediate the TGF-beta responses. TGF-beta binding to the cell surface receptors leads to the phosphorylation of Smad2/3 in their C terminus as well as in the proline-rich linker region. The serine/threonine phosphorylation sites in the linker region are followed by the proline residue. Pin1, a peptidyl-prolyl cis/trans isomerase, recognizes phosphorylated serine/threonine-proline motifs. Here we show that Smad2/3 interacts with Pin1 in a TGF-beta-dependent manner. We further show that the phosphorylated threonine 179-proline motif in the Smad3 linker region is the major binding site for Pin1. Although epidermal growth factor also induces phosphorylation of threonine 179 and other residues in the Smad3 linker region the same as TGF-beta, Pin1 is unable to bind to the epidermal growth factor-stimulated Smad3. Further analysis suggests that phosphorylation of Smad3 in the C terminus is necessary for the interaction with Pin1. Depletion of Pin1 by small hairpin RNA does not significantly affect TGF-beta-induced growth-inhibitory responses and a number of TGF-beta/Smad target genes analyzed. In contrast, knockdown of Pin1 in human PC3 prostate cancer cells strongly inhibited TGF-beta-mediated migration and invasion. Accordingly, TGF-beta induction of N-cadherin, which plays an important role in migration and invasion, is markedly reduced when Pin1 is depleted in PC3 cells. Because Pin1 is overexpressed in many cancers, our findings highlight the importance of Pin1 in TGF-beta-induced migration and invasion of cancer cells.