Sample records for potential migration effect

  1. Modeled microgravity suppressed invasion and migration of human glioblastoma U87 cells through downregulating store-operated calcium entry

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

    Shi, Zi-xuan; Rao, Wei; Wang, Huan

    Glioblastoma is the most common brain tumor and is characterized with robust invasion and migration potential resulting in poor prognosis. Previous investigations have demonstrated that modeled microgravity (MMG) could decline the cell proliferation and attenuate the metastasis potential in several cell lines. In this study, we studied the effects of MMG on the invasion and migration potentials of glioblastoma in human glioblastoma U87 cells. We found that MMG stimulation significantly attenuated the invasion and migration potentials, decreased thapsigargin (TG) induced store-operated calcium entry (SOCE) and downregulated the expression of Orai1 in U87 cells. Inhibition of SOCE by 2-APB or stromalmore » interaction molecule 1 (STIM1) downregulation both mimicked the effects of MMG on the invasion and migration potentials in U87 cells. Furthermore, upregulation of Orai1 significantly weakened the effects of MMG on the invasion and migration potentials in U87 cells. Therefore, these findings indicated that MMG stimulation inhibited the invasion and migration potentials of U87 cells by downregulating the expression of Orai1 and sequentially decreasing the SOCE, suggesting that MMG might be a new potential therapeutic strategy in glioblastoma treatment in the future. - Highlights: • Modeled microgravity (MMG) suppressed migration and invasion in U87 cells. • MMG downregulated the SOCE and the expression of Orai1. • SOCE inhibition mimicked the effects of MMG on migration and invasion potentials. • Restoration of SOCE diminished the effects of MMG on migration and invasion.« less

  2. Chlorambucil (nitrogen mustard) induced impairment of early vascular endothelial cell migration - effects of α-linolenic acid and N-acetylcysteine.

    PubMed

    Steinritz, Dirk; Schmidt, Annette; Simons, Thilo; Ibrahim, Marwa; Morguet, Christian; Balszuweit, Frank; Thiermann, Horst; Kehe, Kai; Bloch, Wilhelm; Bölck, Birgit

    2014-08-05

    Alkylating agents (e.g. sulfur and nitrogen mustards) cause a variety of cell and tissue damage including wound healing disorder. Migration of endothelial cells is of utmost importance for effective wound healing. In this study we investigated the effects of chlorambucil (a nitrogen mustard) on early endothelial cells (EEC) with special focus on cell migration. Chlorambucil significantly inhibited migration of EEC in Boyden chamber and wound healing experiments. Cell migration is linked to cytoskeletal organization. We therefore investigated the distribution pattern of the Golgi apparatus as a marker of cell polarity. Cells are polarized under control conditions, whereas chlorambucil caused an encircling perinuclear position of the Golgi apparatus, indicating non-polarized cells. ROS are discussed to be involved in the pathophysiology of alkylating substances and are linked to cell migration and cell polarity. Therefore we investigated the influence of ROS-scavengers (α-linolenic acid (ALA) and N-acetylcysteine (NAC)) on the impaired EEC migration. Both substances, in particular ALA, improved EEC migration. Notably ALA restored cell polarity. Remarkably, investigations of ROS and RNS biomarkers (8-isoprostane and nitrotyrosine) did not reveal a significant increase after chlorambucil exposure when assessed 24h post exposure. A distinct breakdown of mitochondrial membrane potential (measured by TMRM) that recovered under ALA treatment was observed. In conclusion our results provide compelling evidence that the alkylating agent chlorambucil dramatically impairs directed cellular migration, which is accompanied by perturbations of cell polarity and mitochondrial membrane potential. ALA treatment was able to reconstitute cell polarity and to stabilize mitochondrial potential resulting in improved cell migration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Exogenous S100A8 protein inhibits PDGF-induced migration of airway smooth muscle cells in a RAGE-dependent manner.

    PubMed

    Xu, Yu-Dong; Wei, Ying; Wang, Yu; Yin, Lei-Miao; Park, Gyoung-Hee; Liu, Yan-Yan; Yang, Yong-Qing

    2016-03-25

    S100A8 is an important member of the S100 protein family, which is involved in intracellular and extracellular regulatory activities. We previously reported that the S100A8 protein was differentially expressed in the asthmatic respiratory tracts. To understand the potential role of S100A8 in asthma, we investigated the effect of recombinant S100A8 protein on the platelet-derived growth factor (PDGF)-induced migration of airway smooth muscle cells (ASMCs) and the underlying molecular mechanism by using multiple methods, such as impedance-based xCELLigence migration assay, transwell migration assays and wound-healing assays. We found that exogenous S100A8 protein significantly inhibited PDGF-induced ASMC migration. Furthermore, the migration inhibition effect of S100A8 was blocked by neutralizing antibody against the receptor for advanced glycation end-products (RAGE), a potential receptor for the S100A8 protein. These findings provide direct evidence that exogenous S100A8 protein inhibits the PDGF-induced migration of ASMCs through the membrane receptor RAGE. Our study highlights a novel role of S100A8 as a potential means of counteracting airway remodeling in chronic airway diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Pre-migration and post-migration factors associated with mental health in humanitarian migrants in Australia and the moderation effect of post-migration stressors: findings from the first wave data of the BNLA cohort study.

    PubMed

    Chen, Wen; Hall, Brian J; Ling, Li; Renzaho, Andre Mn

    2017-03-01

    The process of becoming a humanitarian migrant is potentially damaging to mental health. We examined the association between pre-migration and post-migration potentially traumatic events and stressors and mental health, and assessed the moderating effect of post-migration stressors in humanitarian migrants in Australia. In this study, we used the first wave of data between 2013 and 2014 from the Building a New Life in Australia survey. The survey included 2399 migrants who had arrived in Australia holding a permanent humanitarian visa 3-6 months preceding the survey, with 77% and 23% of participants being granted visas through offshore and onshore humanitarian programmes, respectively. Post-traumatic stress disorder (PTSD) was measured with the Post-traumatic Stress Disorder 8 items (PTSD-8) and severe mental illness was measured with the Kessler Screening Scale for Psychological Distress (K6). Pre-migration potentially traumatic events and post-migration stressors related to asylum process and resettlement were measured with a self-reported questionnaire. Of the 2399 participants, 762 (31%; 95% CI 29·4-33·2) had PTSD and 394 (16%; 95% CI 14·2-17·2) had severe mental illness. The mean number of pre-migration potentially traumatic events was 2·1 (SD 1·4). 64%, 59%, 49%, and 18% of participants reported poor social integration, economic problems, worrying about family or friends overseas, and loneliness as post-migration stressors. Pre-migration potentially traumatic events and post-migration stressors were positively associated with PTSD and severe mental illness. Factors significantly modifying the association between pre-migration potentially traumatic events and mental health after controlling for confounding factors were resettlement related stressors, including loneliness (odds ratio 1·17, 95% CI 1·05-1·28 for PTSD and 1·28, 1·16-1·41 for severe mental illness) and the number of social integration stressors (1·10, 1·05-1·16 for PTSD). Our data suggest that post-migration resettlement-related stressors were the most important correlates of mental health in humanitarian migrants, accounting for both direct and indirect associations. Targeting resettlement-related stressors through augmenting psychosocial care programmes and social integration would be a key approach to improve humanitarian migrants' mental health. None. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Biliary stent migration: a brief review of potential complications and possible etiological factors.

    PubMed

    Cheruvu, Srinivas; Kennedy, Robert; Moshenyat, Yitzak; Momen, Mojdeh; Krishnaiah, Mahesh; Anand, Sury

    2014-01-01

    Biliary endoprostheses continue to demonstrate their utility and simplicity in daily therapeutic endoscopy. However, the transient nature of these foreign bodies also underscores their potential detrimental effects even after successful deployment. Stent related factors, such as type, length and caliber offer potential avenues to minimize the risk of migration. However, a patient related factor such as the presence of prior abdominal surgeries makes it paramount for endoscopists to ascertain the location of a migrated stent. There is a ripe niche for continued research and development in biodegradable stents.

  6. Plasma rich in growth factors (PRGF-Endoret) stimulates tendon and synovial fibroblasts migration and improves the biological properties of hyaluronic acid.

    PubMed

    Anitua, E; Sanchez, M; De la Fuente, M; Zalduendo, M M; Orive, G

    2012-09-01

    Cell migration plays an essential role in development, wound healing, and tissue regeneration. Plasma rich in growth factors (PRGF-Endoret) technology offers a potential source of growth factors involved in tissue regeneration. Here, we evaluate the potential of PRGF-Endoret over tendon cells and synovial fibroblasts migration and study whether the combination of this autologous technology with hyaluronic acid (HA) improves the effect and potential of the biomaterials over the motility of both types of fibroblasts. Migration of primary tendon cells and synovial fibroblasts after culturing with either PRGF or PPGF (plasma poor in growth factors) at different doses was evaluated. Furthermore, the migratory capacity induced by the combination of PPGF and PRGF with HA was tested. PPGF stimulated migration of both types of cells but this effect was significantly higher when PRGF was used. Tendon cells showed an increase of 212% in migratory ability when HA was combined with PPGF and of 335% in the case of HA + PRGF treatment compared with HA alone. PRGF-Endoret stimulates migration of tendon cells and synovial fibroblasts and improves the biological properties of HA.

  7. Disentangling fathers’ absences from household remittances in international migration: The case of educational attainment in Guatemala

    PubMed Central

    Davis, Jason; Brazil, Noli

    2016-01-01

    Estimating the effects of international migration on left-behind children’s educational attainment is complicated by the potential offsetting effects of fathers’ absences and household remittances. Most research has not separated these aspects of international migration on children’s human capital outcomes. We address this deficiency by using instrumental variables to isolate the effects of fathers’ international migration absences from international household remittances on student enrollment and grade progression in Guatemala. Results indicate that fathers’ absences and household international remittances are negatively related to enrollment, providing evidence for a culture of migration effect. For students who remain in school, household international remittances neutralize the harmful influence of fathers’ absences on grade progression. PMID:27293309

  8. 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.

  9. A pilgrim's progress: Seeking meaning in primordial germ cell migration.

    PubMed

    Cantú, Andrea V; Laird, Diana J

    2017-10-01

    Comparative studies of primordial germ cell (PGC) development across organisms in many phyla reveal surprising diversity in the route of migration, timing and underlying molecular mechanisms, suggesting that the process of migration itself is conserved. However, beyond the perfunctory transport of cellular precursors to their later arising home of the gonads, does PGC migration serve a function? Here we propose that the process of migration plays an additional role in quality control, by eliminating PGCs incapable of completing migration as well as through mechanisms that favor PGCs capable of responding appropriately to migration cues. Focusing on PGCs in mice, we explore evidence for a selective capacity of migration, considering the tandem regulation of proliferation and migration, cell-intrinsic and extrinsic control, the potential for tumors derived from failed PGC migrants, the potential mechanisms by which migratory PGCs vary in their cellular behaviors, and corresponding effects on development. We discuss the implications of a selective role of PGC migration for in vitro gametogenesis. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Mental health consequences of international migration for Vietnamese Americans and the mediating effects of physical health and social networks: results from a natural experiment approach.

    PubMed

    Fu, Hongyun; VanLandingham, Mark J

    2012-05-01

    Although the existing literature on immigrant mental health is extensive, major substantive and methodological gaps remain. Substantively, there is little population-based research that focuses on the mental health consequences of migration for Vietnamese Americans. More generally, although a wide range of mental health problems among immigrants has been identified, the potential causal or mediating mechanisms underlying these problems remain elusive. This latter substantive shortcoming is related to a key methodological challenge involving the potentially confounding effects of selection on migration-related outcomes. This article addresses these challenges by employing a "natural experiment" design, involving comparisons among three population-based samples of Vietnamese immigrants, never-leavers, and returnees (N=709). Data were collected in Ho Chi Minh City and in New Orleans between 2003 and 2005. The study investigates the long-term impact of international migration on Vietnamese mental health, and the potential mediating effects of social networks and physical health on these migration-related outcomes. The results reveal both mental health advantages and disadvantages among Vietnamese immigrants relative to the two groups of Vietnamese nationals. Selection can be ruled out for some of these differences, and both social networks and physical health are found to play important explanatory roles.

  11. Focus on environmental risks and migration: causes and consequences

    NASA Astrophysics Data System (ADS)

    Adger, W. Neil; Arnell, Nigel W.; Black, Richard; Dercon, Stefan; Geddes, Andrew; Thomas, David S. G.

    2015-06-01

    Environmental change poses risks to societies, including disrupting social and economic systems such as migration. At the same time, migration is an effective adaptation to environmental and other risks. We review novel science on interactions between migration, environmental risks and climate change. We highlight emergent findings, including how dominant flows of rural to urban migration mean that populations are exposed to new risks within destination areas and the requirement for urban sustainability. We highlight the issue of lack of mobility as a major issue limiting the effectiveness of migration as an adaptation strategy and leading to potentially trapped populations. The paper presents scenarios of future migration that show both displacement and trapped populations over the incoming decades. Papers in the special issue bring new insights from demography, human geography, political science and environmental science to this emerging field.

  12. Nonlinear permanent migration response to climatic variations but minimal response to disasters

    PubMed Central

    Bohra-Mishra, Pratikshya; Oppenheimer, Michael; Hsiang, Solomon M.

    2014-01-01

    We present a microlevel study to simultaneously investigate the effects of variations in temperature and precipitation along with sudden natural disasters to infer their relative influence on migration that is likely permanent. The study is made possible by the availability of household panel data from Indonesia with an exceptional tracking rate combined with frequent occurrence of natural disasters and significant climatic variations, thus providing a quasi-experiment to examine the influence of environment on migration. Using data on 7,185 households followed over 15 y, we analyze whole-household, province-to-province migration, which allows us to understand the effects of environmental factors on permanent moves that may differ from temporary migration. The results suggest that permanent migration is influenced by climatic variations, whereas episodic disasters tend to have much smaller or no impact on such migration. In particular, temperature has a nonlinear effect on migration such that above 25 °C, a rise in temperature is related to an increase in outmigration, potentially through its impact on economic conditions. We use these results to estimate the impact of projected temperature increases on future permanent migration. Though precipitation also has a similar nonlinear effect on migration, the effect is smaller than that of temperature, underscoring the importance of using an expanded set of climatic factors as predictors of migration. These findings on the minimal influence of natural disasters and precipitation on permanent moves supplement previous findings on the significant role of these variables in promoting temporary migration. PMID:24958887

  13. Nonlinear permanent migration response to climatic variations but minimal response to disasters.

    PubMed

    Bohra-Mishra, Pratikshya; Oppenheimer, Michael; Hsiang, Solomon M

    2014-07-08

    We present a microlevel study to simultaneously investigate the effects of variations in temperature and precipitation along with sudden natural disasters to infer their relative influence on migration that is likely permanent. The study is made possible by the availability of household panel data from Indonesia with an exceptional tracking rate combined with frequent occurrence of natural disasters and significant climatic variations, thus providing a quasi-experiment to examine the influence of environment on migration. Using data on 7,185 households followed over 15 y, we analyze whole-household, province-to-province migration, which allows us to understand the effects of environmental factors on permanent moves that may differ from temporary migration. The results suggest that permanent migration is influenced by climatic variations, whereas episodic disasters tend to have much smaller or no impact on such migration. In particular, temperature has a nonlinear effect on migration such that above 25 °C, a rise in temperature is related to an increase in outmigration, potentially through its impact on economic conditions. We use these results to estimate the impact of projected temperature increases on future permanent migration. Though precipitation also has a similar nonlinear effect on migration, the effect is smaller than that of temperature, underscoring the importance of using an expanded set of climatic factors as predictors of migration. These findings on the minimal influence of natural disasters and precipitation on permanent moves supplement previous findings on the significant role of these variables in promoting temporary migration.

  14. Health and demographic surveillance systems: contributing to an understanding of the dynamics in migration and health

    PubMed Central

    Gerritsen, Annette; Bocquier, Philippe; White, Michael; Mbacké, Cheikh; Alam, Nurul; Beguy, Donatien; Odhiambo, Frank; Sacoor, Charfudin; Phuc, Ho Dang; Punpuing, Sureeporn; Collinson, Mark A.

    2013-01-01

    Background Migration is difficult to measure because it is highly repeatable. Health and Demographic Surveillance Systems (HDSSs) provide a unique opportunity to study migration as multiple episodes of migration are captured over time. A conceptual framework is needed to show the public health implications of migration. Objective/design Research conducted in seven HDSS centres [International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH) Network], published in a peer-reviewed volume in 2009, is summarised focussing on the age–sex profile of migrants, the relation between migration and livelihoods, and the impact of migration on health. This illustrates the conceptual structure of the implications of migration. The next phase is described, the Multi-centre Analysis of the Dynamics In Migration And Health (MADIMAH) project, consisting of workshops focussed on preparing data and conducting the analyses for comparative studies amongst HDSS centres in Africa and Asia. The focus here is on the (standardisation of) determinants of migration and the impact of migration on adult mortality. Results The findings in the volume showed a relatively regular age structure for migration among all HDSS centres. Furthermore, migration generally contributes to improved living conditions at the place of origin. However, there are potential negative consequences of migration on health. It was concluded that there is a need to compare results from multiple centres using uniform covariate definitions as well as longitudinal analysis techniques. This was the starting point for the on-going MADIMAH initiative, which has increased capacity at the participating HDSS centres to produce the required datasets and conduct the analyses. Conclusions HDSS centres brought together within INDEPTH Network have already provided strong evidence of the potential negative consequences of migration on health, which contrast with the beneficial impacts of migration on livelihoods. Future comparative evidence using standardised tools will help design policies for mitigating the negative effects, and enhancing the positive effects, of migration on health. PMID:23849188

  15. Restoration of miR-1305 relieves the inhibitory effect of nicotine on periodontal ligament-derived stem cell proliferation, migration, and osteogenic differentiation.

    PubMed

    Chen, Zhuo; Liu, Hui-Li

    2017-04-01

    Nicotine hinders the regenerative potentials of human periodontal ligament-derived stem cells (PDLSCs) and delays the healing process of periodontal diseases, but the underlying mechanism remains unclear. miR-1305 upregulation and its potential target RUNX2 downregulation exist in the PDLSCs exposed to nicotine. In this study, we aimed to investigate whether nicotine inhibits PDLSC proliferation, migration, and osteogenic differentiation by increasing miR-1305 level and decreasing RUNX2 level. Quantitative real-time PCR (qRT-PCR) and Western blot assays were performed to detect the expression levels of miR-1305 and RUNX2 in the PDLSCs exposed to nicotine, respectively. PDLSCs with miR-1305 overexpression, low expression, or RUNX2 overexpression were constructed by lipofectin transfection. MTT, migration, and Western blot assays were applied to assess the effect of miR-1305 on PDLSC proliferation, migration, and osteogenic differentiation, respectively. Target prediction and luciferase reporter assays were performed to investigate the targets of miR-1305. Nicotine promoted miR-1305 expression and inhibited RUNX2 expression in PDLSCs. Cell proliferation, migration, and differentiation detection showed that nicotine suppressed proliferation, migration, and osteogenic differentiation of PDLSCs, and restoration of miR-1305 relieved the inhibitory effect of nicotine on PDLSCs. Moreover, we identified and validated that RUNX2 was a direct target of miR-1305, and upregulation of RUNX2 had similar effects with the downregulation of miR-1305 on relieving the inhibitory effect of nicotine on PDLSCs. Nicotine suppresses proliferation, migration, and osteogenic differentiation of PDLSCs, and restoration of miR-1305 relieves the inhibitory effect of nicotine on PDLSCs depending on its target RUNX2. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. 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

  17. 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.

  18. Medical tourism's impacts on health worker migration in the Caribbean: five examples and their implications for global justice.

    PubMed

    Snyder, Jeremy; Crooks, Valorie A; Johnston, Rory; Adams, Krystyna; Whitmore, Rebecca

    2015-01-01

    Medical tourism is a practice where individuals cross international borders in order to access medical care. This practice can impact the global distribution of health workers by potentially reducing the emigration of health workers from destination countries for medical tourists and affecting the internal distribution of these workers. Little has been said, however, about the impacts of medical tourism on the immigration of health workers to medical tourism destinations. We discuss five patterns of medical tourism-driven health worker migration to medical tourism destinations: 1) long-term international migration; 2) long-term diasporic migration; 3) long-term migration and 'black sheep'; 4) short-term migration via time share; and 5) short-term migration via patient-provider dyad. These patterns of health worker migration have repercussions for global justice that include potential negative impacts on the following: 1) health worker training; 2) health worker distributions; 3) local provision of care; and 4) local economies. In order to address these potential negative impacts, policy makers in destination countries should work to ensure that changes in health worker training and licensure aimed at promoting the medical tourism sector are also supportive of the health needs of the domestic population. Policy makers in both source and destination countries should be aware of the effects of medical tourism on health worker flows both into and out of medical tourism destinations and work to ensure that the potential harms of these worker flows to both groups are mitigated.

  19. Medical tourism's impacts on health worker migration in the Caribbean: five examples and their implications for global justice

    PubMed Central

    Snyder, Jeremy; Crooks, Valorie A.; Johnston, Rory; Adams, Krystyna; Whitmore, Rebecca

    2015-01-01

    Medical tourism is a practice where individuals cross international borders in order to access medical care. This practice can impact the global distribution of health workers by potentially reducing the emigration of health workers from destination countries for medical tourists and affecting the internal distribution of these workers. Little has been said, however, about the impacts of medical tourism on the immigration of health workers to medical tourism destinations. We discuss five patterns of medical tourism-driven health worker migration to medical tourism destinations: 1) long-term international migration; 2) long-term diasporic migration; 3) long-term migration and ‘black sheep’; 4) short-term migration via time share; and 5) short-term migration via patient-provider dyad. These patterns of health worker migration have repercussions for global justice that include potential negative impacts on the following: 1) health worker training; 2) health worker distributions; 3) local provision of care; and 4) local economies. In order to address these potential negative impacts, policy makers in destination countries should work to ensure that changes in health worker training and licensure aimed at promoting the medical tourism sector are also supportive of the health needs of the domestic population. Policy makers in both source and destination countries should be aware of the effects of medical tourism on health worker flows both into and out of medical tourism destinations and work to ensure that the potential harms of these worker flows to both groups are mitigated. PMID:25865122

  20. International migration as a determinant of emergency caesarean.

    PubMed

    Merry, Lisa; Semenic, Sonia; Gyorkos, Theresa W; Fraser, William; Small, Rhonda; Gagnon, Anita J

    2016-10-01

    High caesarean rates are of concern given associated risks. International migrant women (women born abroad) represent a substantial proportion of women giving birth in high-income countries (HICs) and face social conditions that may exacerbate childbearing health risks. Among migrant women, emergency rather than planned caesareans, tend to be more prevalent. This method of delivery can be stressful, physically harmful and result in an overall negative birth experience. Research establishing evidence of risk factors for emergency caesareans in migrants is insufficient. (1) Describe potential pathways (with a focus on modifiable factors) by which migration, using internationally recommended migration indicators: country of birth, length of time in country, fluency in receiving-country language, migration classification and ethnicity, may lead to emergency caesarean; and (2) propose a framework to guide future research for understanding "potentially preventable" emergency caesareans in migrant women living in HICs. "Potentially preventable" emergency caesareans in migrant women are likely due to several modifiable, interrelated factors pre-pregnancy, during pregnancy and during labour. Migration itself is a determinant and also shapes other determinants. Complications and ineffective labour progress and/or foetal distress and ultimately the decision to perform an emergency caesarean may be the result of poor health (i.e., physiological effects), lack of support and disempowerment (i.e., psychological effects) and sub-optimal care. Understanding the direct and indirect effects of migration on emergency caesarean is crucial so that targeted strategies can be developed and implemented for reducing unnecessary caesareans in this vulnerable population. Copyright © 2016 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  1. 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 consequences of delays at the barriers for those individuals that successfully navigate them.

  2. 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 consequences of delays at the barriers for those individuals that successfully navigate them. ??2011 by the Ecological Society of America.

  3. Coastal wetland adaptation to sea level rise: Quantifying potential for landward migration and coastal squeeze

    USGS Publications Warehouse

    Borchert, Sinéad M.; Osland, Michael J.; Enwright, Nicholas M.; Griffith, Kereen

    2018-01-01

    Coastal wetland ecosystems are expected to migrate landwards in response to rising seas. However, due to differences in topography and coastal urbanization, estuaries vary in their ability to accommodate migration. Low‐lying urban areas can constrain migration and lead to wetland loss (i.e. coastal squeeze), especially where existing wetlands cannot keep pace with rising seas via vertical adjustments. In many estuaries, there is a pressing need to identify landward migration corridors and better quantify the potential for landward migration and coastal squeeze.We quantified and compared the area available for landward migration of tidal saline wetlands and the area where urban development is expected to prevent migration for 39 estuaries along the wetland‐rich USA Gulf of Mexico coast. We did so under three sea level rise scenarios (0.5, 1.0, and 1.5 m by 2100).Within the region, the potential for wetland migration is highest within certain estuaries in Louisiana and southern Florida (e.g. Atchafalaya/Vermilion Bays, Mermentau River, Barataria Bay, and the North and South Ten Thousand Islands estuaries).The potential for coastal squeeze is highest in estuaries containing major metropolitan areas that extend into low‐lying lands. The Charlotte Harbor, Tampa Bay, and Crystal‐Pithlachascotee estuaries (Florida) have the highest amounts of urban land expected to constrain wetland migration. Urban barriers to migration are also high in the Galveston Bay (Texas) and Atchafalaya/Vermilion Bays (Louisiana) estuaries.Synthesis and applications. Coastal wetlands provide many ecosystem services that benefit human health and well‐being, including shoreline protection and fish and wildlife habitat. As the rate of sea level rise accelerates in response to climate change, coastal wetland resources could be lost in areas that lack space for landward migration. Migration corridors are particularly important in highly urbanized estuaries where, due to low‐lying coastal development, there is not space for wetlands to move and adapt to sea level rise. Future‐focused landscape conservation plans that incorporate the protection of wetland migration corridors can increase the adaptive capacity of these valuable ecosystems and simultaneously decrease the vulnerability of coastal human communities to the harmful effects of rising seas.

  4. Reverse transendothelial cell migration in inflammation: to help or to hinder?

    PubMed

    Burn, Thomas; Alvarez, Jorge Ivan

    2017-05-01

    The endothelium provides a strong barrier separating circulating blood from tissue. It also provides a significant challenge for immune cells in the bloodstream to access potential sites of infection. To mount an effective immune response, leukocytes traverse the endothelial layer in a process known as transendothelial migration. Decades of work have allowed dissection of the mechanisms through which immune cells gain access into peripheral tissues, and subsequently to inflammatory foci. However, an often under-appreciated or potentially ignored question is whether transmigrated leukocytes can leave these inflammatory sites, and perhaps even return across the endothelium and re-enter circulation. Although evidence has existed to support "reverse" transendothelial migration for a number of years, it is only recently that mechanisms associated with this process have been described. Here we review the evidence that supports both reverse transendothelial migration and reverse interstitial migration within tissues, with particular emphasis on some of the more recent studies that finally hint at potential mechanisms. Additionally, we postulate the biological significance of retrograde migration, and whether it serves as an additional mechanism to limit pathology, or provides a basis for the dissemination of systemic inflammation.

  5. Animal migration and risk of spread of viral infections: Chapter 9

    USGS Publications Warehouse

    Prosser, Diann J.; Nagel, Jessica; Takekawa, John Y.; Edited by Singh, Sunit K.

    2013-01-01

    The potential contribution of migration towards the spread of disease is as varied as the ecology of the pathogens themselves and their host populations. This chapter outlines multiple examples of viral diseases in animal populations and their mechanisms of viral spread. Many species of insects, mammals, fish, and birds exhibit migratory behavior and have the potential to disperse diseases over long distances. The majority of studies available on viral zoonoses have focused on birds and bats, due to their highly migratory life histories. A number of studies have reported evidence of changes in the timing of animal migrations in response to climate change. The majority indicate an advancement of spring migration, with few or inconclusive results for fall migration. Predicting the combined effects of climate change on migratory patterns of host species and epidemiology of viral pathogens is complex and not fully realistic.

  6. Predator-prey interaction reveals local effects of high-altitude insect migration

    USDA-ARS?s Scientific Manuscript database

    High-altitude nocturnal insect migrations represent significant pulses of resources, yet are difficult to study and poorly understood. Predator-prey interactions, specifically migratory moth consumption by high-flying bats, potentially reveal flows of migratory insects across a landscape. In North...

  7. Potential silver nanoparticles migration from commercially available polymeric baby products into food simulants.

    PubMed

    Choi, Jeong In; Chae, Song Ji; Kim, Jung Min; Choi, Jae Chun; Park, Se Jong; Choi, Hee Ju; Bae, Hojae; Park, Hyun Jin

    2018-05-01

    In recent years, silver nanoparticles (AgNPs) have been extensively employed in food packaging systems as a potential antibacterial agent. Although proven to be highly effective, the increased number of AgNP-containing products raises concerns among consumers regarding the migration of AgNPs from the packaging material into foods, which may exert toxic effects. To address this, five baby products were chosen (baby bottle A, baby bottle B, pacifier A, pacifier B and breastmilk storage bag) to investigate AgNPs migration into three food simulants (deionised water, 4% acetic acid (w/v) and 50% ethanol (v/v)) using inductively coupled plasma mass spectrometry (ICP-MS). As a result, the highest level of migrated Ag was observed for 4% acetic acid in the case of baby bottle B, pacifier A, pacifier B and the breastmilk storage bag, with the detection amount ranging from 1.05-2.25 ng/mL. On the other hand, baby bottle A showed the maximum migration for 50% ethanol due to the polymer nature. Finally, a centrifugal ultrafiltration experiment was conducted to determine the fraction of dissolved Ag in acidic simulant and it was found that migrated Ag was predominantly in Ag + form, with a small fraction of non-ionic AgNPs. Thus, it has been found that the amount of migrated Ag in baby products was low; however, the migration was dependent on the type of food simulant and polymer nature.

  8. Magnolol Inhibits Human Glioblastoma Cell Migration by Regulating N-Cadherin.

    PubMed

    Cheng, Yu-Chen; Tsao, Min-Jen; Chiu, Chen-Yang; Kan, Po-Chieh; Chen, Ying

    2018-06-01

    Glioblastoma is a primary malignant brain tumor with a poor prognosis. An effective treatment for glioblastoma is needed. Magnolol is a natural compound from Magnolia officinalis suggested to have antiproliferative activity. The aim of this research was to investigate the anticancer effects of magnolol in glioma, with an emphasis on migration and the underlying mechanism. Magnolol decreased the expression of focal adhesion-related proteins and inhibited LN229 and U87MG glioma cell migration. The levels of phosphorylated myosin light chain (p-MLC), phosphorylated myosin light chain kinase and myosin phosphatase target subunit 1 were reduced in response to magnolol treatment. In addition, immunostaining and membrane fractionation showed that the distribution of N-cadherin at the glioma cell membrane was decreased by magnolol. In an orthotropic xenograft animal model, magnolol treatment not only inhibited tumor progression but also reduced p-MLC and N-cadherin protein expression. In conclusion, magnolol reduces cell migration, potentially through regulating focal adhesions and N-cadherin in glioma cells. Magnolol is a potential candidate for glioma treatment.

  9. 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

  10. CLIMATE VARIABILITY, LAND OWNERSHIP AND MIGRATION: EVIDENCE FROM THAILAND ABOUT GENDER IMPACTS

    PubMed Central

    Curran, Sara R.; Meijer-Irons, Jacqueline

    2016-01-01

    Scholars point to climate change, often in the form of more frequent and severe drought, as a potential driver of migration in the developing world, particularly for places where populations rely on agriculture for their livelihoods. To date, however, there have been few large-scale, longitudinal studies that explore the relationship between climate change and migration. This study significantly extends current scholarship by evaluating distinctive effects of climatic variation and models these effects on men’s and women’s responsiveness to drought and rainfall. Our study also investigates how land ownership moderates these effects. We find small, but significant, increases in migration above existing migratory levels during periods of prolonged climatic stress, and that these patterns differ both by gender and land tenure. PMID:27547492

  11. The Effect of Skeletal Maturity on the Regenerative Function of Intrinsic ACL Cells

    PubMed Central

    Mastrangelo, Ashley N.; Magarian, Elise M.; Palmer, Matthew P.; Vavken, Patrick; Murray, Martha M.

    2010-01-01

    Anterior cruciate ligament (ACL) injuries are an important clinical problem, particularly for adolescent patients. The effect of skeletal maturity on the potential for ACL healing is as yet unknown. In this study, we hypothesized that fibroblastic cells from the ACLs of skeletally immature animals would proliferate and migrate more quickly than cells from adolescent and adult animals. ACL tissue from skeletally immature, adolescent, and adult pigs and sheep were obtained and cells obtained using explant culture. Cell proliferation within a collagen–platelet scaffold was measured at days 2, 7, and 14 of culture using AMMTT assay. Cellular migration was measured at 4 and 24 h using a modified Boyden chamber assay, and cell outgrowth from the explants also measured at 1 week. ACL cells from skeletally immature animals had higher proliferation between 7 and 14 days (p < 0.01 for all comparisons) and higher migration potential at all time points in both species (p < 0.01 for all comparisons).ACL cells from skeletally immature animals have greater cellular proliferation and migration potential than cells from adolescent or adult animals. These experiments suggest that skeletal maturity may influence the biologic repair capacity of intrinsic ACL cells. PMID:19890988

  12. Meisoindigo, but not its core chemical structure indirubin, inhibits zebrafish interstitial leukocyte chemotactic migration.

    PubMed

    Ye, Baixin; Xiong, Xiaoxing; Deng, Xu; Gu, Lijuan; Wang, Qiongyu; Zeng, Zhi; Gao, Xiang; Gao, Qingping; Wang, Yueying

    2017-12-01

    Inflammatory disease is a big threat to human health. Leukocyte chemotactic migration is required for efficient inflammatory response. Inhibition of leukocyte chemotactic migration to the inflammatory site has been shown to provide therapeutic targets for treating inflammatory diseases. Our study was designed to discover effective and safe compounds that can inhibit leukocyte chemotactic migration, thus providing possible novel therapeutic strategy for treating inflammatory diseases. In this study, we used transgenic zebrafish model (Tg:zlyz-EGFP line) to visualize the process of leukocyte chemotactic migration. Then, we used this model to screen the hit compound and evaluate its biological activity on leukocyte chemotactic migration. Furthermore, western blot analysis was performed to evaluate the effect of the hit compound on the AKT or ERK-mediated pathway, which plays an important role in leukocyte chemotactic migration. In this study, using zebrafish-based chemical screening, we identified that the hit compound meisoindigo (25 μM, 50 μM, 75 μM) can significantly inhibit zebrafish leukocyte chemotactic migration in a dose-dependent manner (p = 0.01, p = 0.0006, p < 0.0001). Also, we found that meisoindigo did not affect the process of leukocyte reverse migration (p = 0.43). Furthermore, our results unexpectedly showed that indirubin, the core structure of meisoindigo, had no significant effect on zebrafish leukocyte chemotactic migration (p = 0.6001). Additionally, our results revealed that meisoindigo exerts no effect on the Akt or Erk-mediated signalling pathway. Our results suggest that meisoindigo, but not indirubin, is effective for inhibiting leukocyte chemotactic migration, thus providing a potential therapeutic agent for treating inflammatory diseases.

  13. A framework for understanding semi-permeable barrier effects on migratory ungulates

    USGS Publications Warehouse

    Sawyer, Hall; Kauffman, Matthew J.; Middleton, Arthur D.; Morrison, Thomas A.; Nielson, Ryan M.; Wyckoff, Teal B.

    2013-01-01

    1. Impermeable barriers to migration can greatly constrain the set of possible routes and ranges used by migrating animals. For ungulates, however, many forms of development are semi-permeable, and making informed management decisions about their potential impacts to the persistence of migration routes is difficult because our knowledge of how semi-permeable barriers affect migratory behaviour and function is limited. 2. Here, we propose a general framework to advance the understanding of barrier effects on ungulate migration by emphasizing the need to (i) quantify potential barriers in terms that allow behavioural thresholds to be considered, (ii) identify and measure behavioural responses to semi-permeable barriers and (iii) consider the functional attributes of the migratory landscape (e.g. stopovers) and how the benefits of migration might be reduced by behavioural changes. 3. We used global position system (GPS) data collected from two subpopulations of mule deer Odocoileus hemionus to evaluate how different levels of gas development influenced migratory behaviour, including movement rates and stopover use at the individual level, and intensity of use and width of migration route at the population level. We then characterized the functional landscape of migration routes as either stopover habitat or movement corridors and examined how the observed behavioural changes affected the functionality of the migration route in terms of stopover use. 4. We found migratory behaviour to vary with development intensity. Our results suggest that mule deer can migrate through moderate levels of development without any noticeable effects on migratory behaviour. However, in areas with more intensive development, animals often detoured from established routes, increased their rate of movement and reduced stopover use, while the overall use and width of migration routes decreased. 5. Synthesis and applications. In contrast to impermeable barriers that impede animal movement, semi-permeable barriers allow animals to maintain connectivity between their seasonal ranges. Our results identify the mechanisms (e.g. detouring, increased movement rates, reduced stopover use) by which semi-permeable barriers affect the functionality of ungulate migration routes and emphasize that the management of semi-permeable barriers may play a key role in the conservation of migratory ungulate populations.

  14. Women in Mauritania: The Effects of Drought and Migration on Their Economic Status and Implications for Development Programs.

    ERIC Educational Resources Information Center

    Smale, Melinda

    In order to indicate potential income-generating programs for women, 67 women in the river region and selected sites in the Assaba and the Guidimakha were interviewed in 1980 to illuminate effects of the 1970s-80s drought and male migration on Mauritanian women. Hypotheses were based on the drought causing unprecedented disruption to Mauritanian…

  15. GABAergic anxiolytic drug in water increases migration behaviour in salmon

    NASA Astrophysics Data System (ADS)

    Hellström, Gustav; Klaminder, Jonatan; Finn, Fia; Persson, Lo; Alanärä, Anders; Jonsson, Micael; Fick, Jerker; Brodin, Tomas

    2016-12-01

    Migration is an important life-history event in a wide range of taxa, yet many migrations are influenced by anthropogenic change. Although migration dynamics are extensively studied, the potential effects of environmental contaminants on migratory physiology are poorly understood. In this study we show that an anxiolytic drug in water can promote downward migratory behaviour of Atlantic salmon (Salmo salar) in both laboratory setting and in a natural river tributary. Exposing salmon smolt to a dilute concentration of a GABAA receptor agonist (oxazepam) increased migration intensity compared with untreated smolt. These results implicate that salmon migration may be affected by human-induced changes in water chemical properties, such as acidification and pharmaceutical residues in wastewater effluent, via alterations in the GABAA receptor function.

  16. Comparison of electrokinetic soil remediation methods using one fixed anode and approaching anodes.

    PubMed

    Shen, Zhemin; Chen, Xuejun; Jia, Jinping; Qu, Liya; Wang, Wenhua

    2007-11-01

    During the cation exchange membrane (CEM) enhanced electrokinetic (EK) soil remediation, the nearer to the anode, the higher are the H+ concentrations and the redox potentials. As both low pH and high redox potential are helpful to speed-up Cd electro-migration, soils near the anode can be quickly remedied. Usually EK process is operated with one fixed anode (FA). A novel CEM enhanced EK method with approaching anodes (AAs) is proposed to accelerate electro-migration effect. Several mesh Ti/Ru anodes were inserted as AAs in the treated soil. They were switched in turn from the anode towards the cathode. Thus high H+ ions concentrations and high redox potentials quickly migrate to the cathode. Consequently, soil remediation is accelerated and nearly 44% of energy and 40% of time can be saved. The mechanism of Cd electro-migration behavior in soils during CEM enhanced EK is described as the elution in an electrokinetically driven chromatogram.

  17. Effect of sunlight exposure on the release of intentionally and/or non-intentionally added substances from polyethylene terephthalate (PET) bottles into water: chemical analysis and in vitro toxicity.

    PubMed

    Bach, Cristina; Dauchy, Xavier; Severin, Isabelle; Munoz, Jean-François; Etienne, Serge; Chagnon, Marie-Christine

    2014-11-01

    The effect of sunlight exposure on chemical migration into PET-bottled waters was investigated. Bottled waters were exposed to natural sunlight for 2, 6 and 10 days. Migration was dependent on the type of water. Formaldehyde, acetaldehyde and Sb migration increased with sunlight exposure in ultrapure water. In carbonated waters, carbon dioxide promoted migration and only formaldehyde increased slightly due to sunlight. Since no aldehydes were detected in non-carbonated waters, we conclude that sunlight exposure has no effect. Concerning Sb, its migration levels were higher in carbonated waters. No unpredictable NIAS were identified in PET-bottled water extracts. Cyto-genotoxicity (Ames and micronucleus assays) and potential endocrine disruption effects (transcriptional-reporter gene assays) were checked in bottled water extracts using bacteria (Salmonella typhimurium) and human cell lines (HepG2 and MDA-MB453-kb2). PET-bottled water extracts did not induce any toxic effects (cyto-genotoxicity, estrogenic or anti-androgenic activity) in vitro at relevant consumer-exposure levels. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Review of Recent Literature Relevant to the Environmental Effects of Marine and Hydrokinetic Energy Devices Task 2.1.3: Effects on Aquatic Organisms – Fiscal Year 2011 Progress Report Environmental Effects of Marine and Hydrokinetic Energy

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

    Kropp, Roy K.

    2011-09-30

    A literature search was conducted by using the Web of Science® Databases component of the ISI Web of KnowledgeSM to identify recent articles that would be useful to help assess the potential environmental effects of renewable energy development in the ocean, with emphasis on marine mammals, seabirds, and fish. Several relatively recent general review articles that included possible effects of marine renewable energy devices on marine mammals and seabirds were examined to begin the search process (e.g., Boehlert et al. 2008; Thompson et al. 2008; Simas et al. 2009). From these articles, several general topics of potential environmental effects onmore » marine mammals, seabirds, and fish were derived. These topics were used as the primary search factors. Searches were conducted with reference to the potential effects of offshore wind farms and MHK devices on marine mammals, seabirds, and fish. Additional sources were identified by cross-checking the Web of Science databases for articles that cited the review articles. It also became clear that often the potential effects were offered as hypotheses that often were not supported by the presentation of appropriate documentation. Therefore, the search was refined and focused on trying to obtain the necessary information to support or challenge a proposed potential effect to a specific concern. One of the expressed concerns regarding MHK devices is that placing wave parks in coastal waters could compromise the migration patterns of whales. Disruption of the annual migration of the gray whale (Eschrichtius robustus), which swims at least 30,000 km on its round trip from breeding grounds in Baja California to feeding areas in the Bering Sea, is of particular concern. Among the hypothesized effects on the migrating gray whales are increased predation risk by constricting migration corridor to between array and shore or by forcing the whales to swim into deeper waters, increased metabolic energy costs and delays in reaching the destinations, and interrupting feeding by blocking access to benthic areas under arrays. The literature search focused on identifying published studies that could provide information to evaluate these concerns. The results were developed into a case study that evaluated the potential effects of the placement of wave parks in coastal waters along the migration route of the gray whale. Wave parks and other MHK arrays may have additional effects on gray whales and other marine mammals, including entanglement in mooring lines and interference with communications among other effects, that were not included in this case study. The case study results were rewritten into a simpler form that would be suitable for placement on a web blog« less

  19. Brain-derived Neurotrophic Factor Promotes the Migration of Olfactory Ensheathing Cells Through TRPC Channels.

    PubMed

    Wang, Ying; Teng, Hong-Lin; Gao, Yuan; Zhang, Fan; Ding, Yu-Qiang; Huang, Zhi-Hui

    2016-12-01

    Olfactory ensheathing cells (OECs) are a unique type of glial cells with axonal growth-promoting properties in the olfactory system. Organized migration of OECs is essential for neural regeneration and olfactory development. However, the molecular mechanism of OEC migration remains unclear. In the present study, we examined the effects of brain-derived neurotrophic factor (BDNF) on OEC migration. Initially, the "scratch" migration assay, the inverted coverslip and Boyden chamber migration assays showed that BDNF could promote the migration of primary cultured OECs. Furthermore, BDNF gradient attracted the migration of OECs in single-cell migration assays. Mechanistically, TrkB receptor expressed in OECs mediated BDNF-induced OEC migration, and BDNF triggered calcium signals in OECs. Finally, transient receptor potential cation channels (TRPCs) highly expressed in OECs were responsible for BDNF-induced calcium signals, and required for BDNF-induced OEC migration. Taken together, these results demonstrate that BDNF promotes the migration of cultured OECs and an unexpected finding is that TRPCs are required for BDNF-induced OEC migration. GLIA 2016;64:2154-2165. © 2016 Wiley Periodicals, Inc.

  20. Serial migration and its implications for the parent-child relationship: a retrospective analysis of the experiences of the children of Caribbean immigrants.

    PubMed

    Smith, Andrea; Lalonde, Richard N; Johnson, Simone

    2004-05-01

    This study addressed the potential impact of serial migration for parent-children relationships and for children's psychological well-being. The experience of being separated from their parents during childhood and reunited with them at a later time was retrospectively examined for 48 individuals. A series of measures (e.g., self-esteem, parental identification) associated with appraisals at critical time periods during serial migration (separation, reunion, current) revealed that serial migration can potentially disrupt parent-child bonding and unfavorably affect children's self-esteem and behavior. Time did not appear to be wholly effective in repairing rifts in the parent-child relationship. Risk factors for less successful reunions included lengthy separations and the addition of new members to the family unit in the child's absence. (c) 2004 APA

  1. Effects of nicotinamide N-methyltransferase on PANC-1 cells proliferation, metastatic potential and survival under metabolic stress.

    PubMed

    Yu, Tao; Wang, Yong-Tao; Chen, Pan; Li, Yu-Hua; Chen, Yi-Xin; Zeng, Hang; Yu, Ai-Ming; Huang, Min; Bi, Hui-Chang

    2015-01-01

    Aberrant expression of Nicotinamide N-methyltransferase (NNMT) has been reported in pancreatic cancer. However, the role of NNMT in pancreatic cancer development remains elusive. Therefore, the present study was to investigate the impact of NNMT on pancreatic cancer cell proliferation, metastatic potential and survival under metabolic stress. Pancreatic cancer cell line PANC-1 was transfected with NNMT expression plasmid or small interfering RNA of NNMT to overexpress or knockdown intracellular NNMT expression, respectively. Rate of cell proliferation was monitored. Transwell migration and matrigel invasion assays were conducted to assess cell migration and invasion capacity. Resistance to glucose deprivation, sensitivity to glycolytic inhibition, mitochondrial inhibtion and resistance to rapamycin were examined to evaluate cell survival under metabolic stress. NNMT silencing markedly reduced cell proliferation, whereas NNMT overexpression promoted cell growth moderately. Knocking down NNMT also significantly suppressed the migration and invasion capacities of PANC-1 cells. Conversely, NNMT upregulation enhanced cell migration and invasion capacities. In addition, NNMT knockdown cells were much less resistant to glucose deprivation and rapamycin as well as glycolytic inhibitor 2-deoxyglucose whereas NNMT-expressing cells showed opposite effects although the effects were not so striking. These data sugguest that NNMT plays an important role in PANC-1 cell proliferation, metastatic potential and survival under metabolic stress. © 2015 S. Karger AG, Basel.

  2. Suppression of Calpain Expression by NSAIDs is Associated with Inhibition of Cell Migration in Rat Duodenum

    PubMed Central

    Silver, Kristopher; Littlejohn, A.; Thomas, Laurel; Bawa, Bhupinder; Lillich, James D.

    2017-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the alleviation of pain and inflammation, but these drugs are also associated with a suite of negative side effects. Gastrointestinal (GI) toxicity is particularly concerning since it affects an estimated 70% of individuals taking NSAIDs routinely, and evidence suggests the majority of toxicity is occurring in the small intestine. Traditionally, NSAID-induced GI toxicity has been associated with indiscriminate inhibition of cyclooxygenase isoforms, but other mechanisms, including inhibition of cell migration, intestinal restitution, and wound healing, are likely to contribute to toxicity. Previous efforts demonstrated that treatment of cultured intestinal epithelial cells (IEC) with NSAIDs inhibits expression and activity of calpain proteases, but the effects of specific inhibition of calpain expression in vitro or the effects of NSAIDs on intestinal cell migration in vivo remain to be determined. Accordingly, we examined the effect of suppression of calpain protease expression with siRNA on cell migration in cultured IECs and evaluated the effects of NSAID treatment on epithelial cell migration and calpain protease expression in rat duodenum. Our results show that calpain siRNA inhibits protease expression and slows migration in cultured IECs. Additionally, NSAID treatment of rats slowed migration up the villus axis and suppressed calpain expression in duodenal epithelial cells. Our results are supportive of the hypothesis that suppression of calpain expression leading to slowing of cell migration is a potential mechanism through which NSAIDs cause GI toxicity. PMID:28342779

  3. Consequences of Out-Migration for Land Use in Rural Ecuador

    PubMed Central

    Gray, Clark L.; Bilsborrow, Richard E.

    2013-01-01

    In rural Ecuador and elsewhere in Latin America, the departure of migrants and the receipt of migrant remittances have led to declining rural populations and increasing cash incomes. It is commonly assumed that these processes will lead to agricultural abandonment and the regrowth of native vegetation, thus undermining traditional livelihoods and providing a boon for biodiversity conservation. However, an increasing number of household-level studies have found mixed and complex effects of out-migration and remittances on agriculture. We advance this literature by using household survey data and satellite imagery from three study areas in rural Ecuador to investigate the effects of migration and remittances on agricultural land use. Multivariate methods are used to disaggregate the effects of migration and remittances, to account for other influences on land use and to correct for the potential endogeneity of migration and remittances. Contrary to common assumptions but consistent with previous studies, we find that migrant departure has a positive effect on agricultural activities that is offset by migrant remittances. These results suggest that rural out-migration alone is not likely to lead to a forest transition in the study areas. PMID:24187416

  4. Gender, Educational Attainment, and the Impact of Parental Migration on Children Left Behind.

    PubMed

    Antman, Francisca M

    2012-10-01

    Estimation of the causal effect of parental migration on children's educational attainment is complicated by the fact that migrants and non-migrants are likely to differ in unobservable ways that also affect children's educational outcomes. This paper suggests a novel way of addressing this selection problem by looking within the family to exploit variation in siblings' ages at the time of parental migration. The basic assumption underlying the analysis is that parental migration will have no effect on the educational outcomes of children who are at least 20 because they have already completed their educations. Their younger siblings, in contrast, may still be in school, and thus will be affected by the parental migration experience. The results point to a statistically significant positive effect of paternal U.S. migration on education for girls, suggesting that pushing a father's U.S. migration earlier in his daughter's life can lead to an increase in her educational attainment of up to 1 year relative to delaying migration until after she has turned 20. In contrast, paternal domestic migration has no statistically significant effect on educational attainment for girls or boys, suggesting that father absence does not play a major role in determining children's educational outcomes. Instead, these results suggest that the marginal dollars from U.S. migrant remittances appear to enable families to further educate their daughters. Thus, policymakers should view international migration as a potential pathway by which families raise educational attainments of girls in particular. JEL: O15; J12; J13; J16; J24; F22.

  5. Gender, Educational Attainment, and the Impact of Parental Migration on Children Left Behind*

    PubMed Central

    Antman, Francisca M.

    2016-01-01

    Estimation of the causal effect of parental migration on children’s educational attainment is complicated by the fact that migrants and non-migrants are likely to differ in unobservable ways that also affect children’s educational outcomes. This paper suggests a novel way of addressing this selection problem by looking within the family to exploit variation in siblings’ ages at the time of parental migration. The basic assumption underlying the analysis is that parental migration will have no effect on the educational outcomes of children who are at least 20 because they have already completed their educations. Their younger siblings, in contrast, may still be in school, and thus will be affected by the parental migration experience. The results point to a statistically significant positive effect of paternal U.S. migration on education for girls, suggesting that pushing a father’s U.S. migration earlier in his daughter’s life can lead to an increase in her educational attainment of up to 1 year relative to delaying migration until after she has turned 20. In contrast, paternal domestic migration has no statistically significant effect on educational attainment for girls or boys, suggesting that father absence does not play a major role in determining children’s educational outcomes. Instead, these results suggest that the marginal dollars from U.S. migrant remittances appear to enable families to further educate their daughters. Thus, policymakers should view international migration as a potential pathway by which families raise educational attainments of girls in particular. JEL: O15; J12; J13; J16; J24; F22 PMID:27616818

  6. Protocatechuic aldehyde inhibits migration and proliferation of vascular smooth muscle cells and intravascular thrombosis

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

    Moon, Chang Yoon; Endocrinology, Brain Korea 21 Project for Medical Science, Institute of Endocrine Research, and Severance Integrative Research Institute for Cerebral and Cardiovascular Disease, Yonsei University College of Medicine, Seoul; Ku, Cheol Ryong

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer Protocatechuic aldehyde (PCA) inhibits ROS production in VSMCs. Black-Right-Pointing-Pointer PCA inhibits proliferation and migration in PDGF-induced VSMCs. Black-Right-Pointing-Pointer PCA has anti-platelet effects in ex vivo rat whole blood. Black-Right-Pointing-Pointer We report the potential therapeutic role of PCA in atherosclerosis. -- Abstract: The migration and proliferation of vascular smooth muscle cells (VSMCs) and formation of intravascular thrombosis play crucial roles in the development of atherosclerotic lesions. This study examined the effects of protocatechuic aldehyde (PCA), a compound isolated from the aqueous extract of the root of Salvia miltiorrhiza, an herb used in traditional Chinese medicine to treat a varietymore » of vascular diseases, on the migration and proliferation of VSMCs and platelets due to platelet-derived growth factor (PDGF). DNA 5-bromo-2 Prime -deoxy-uridine (BrdU) incorporation and wound-healing assays indicated that PCA significantly attenuated PDGF-induced proliferation and migration of VSMCs at a pharmacologically relevant concentration (100 {mu}M). On a molecular level, we observed down-regulation of the phosphatidylinositol 3-kinase (PI3K)/Akt and the mitogen-activated protein kinase (MAPK) pathways, both of which regulate key enzymes associated with migration and proliferation. We also found that PCA induced S-phase arrest of the VSMC cell cycle and suppressed cyclin D2 expression. In addition, PCA inhibited PDGF-BB-stimulated reactive oxygen species production in VSMCs, indicating that PCA's antioxidant properties may contribute to its suppression of PDGF-induced migration and proliferation in VSMCs. Finally, PCA exhibited an anti-thrombotic effect related to its inhibition of platelet aggregation, confirmed with an aggregometer. Together, these findings suggest a potential therapeutic role of PCA in the treatment of atherosclerosis and angioplasty-induced vascular restenosis.« less

  7. Climate Variability and Human Migration in the Netherlands, 1865–1937

    PubMed Central

    Jennings, Julia A.; Gray, Clark L.

    2014-01-01

    Human migration is frequently cited as a potential social outcome of climate change and variability, and these effects are often assumed to be stronger in the past when economies were less developed and markets more localized. Yet, few studies have used historical data to test the relationship between climate and migration directly. In addition, the results of recent studies that link demographic and climate data are not consistent with conventional narratives of displacement responses. Using longitudinal individual-level demographic data from the Historical Sample of the Netherlands (HSN) and climate data that cover the same period, we examine the effects of climate variability on migration using event history models. Only internal moves in the later period and for certain social groups are associated with negative climate conditions, and the strength and direction of the observed effects change over time. International moves decrease with extreme rainfall, suggesting that the complex relationships between climate and migration that have been observed for contemporary populations extend into the nineteenth century. PMID:25937689

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

    PubMed

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

    1998-12-01

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

  9. Migration of magnetotactic bacteria in porous media.

    PubMed

    Rismani Yazi, Saeed; Nosrati, Reza; Stevens, Corey A; Vogel, David; Escobedo, Carlos

    2018-01-01

    Magnetotactic bacteria (MTB) migrate in complex porous sediments where fluid flow is ubiquitous. Here, we demonstrate that magnetotaxis enables MTB to migrate effectively through porous micromodels. Directed MTB can circumvent curved obstacles by traveling along the boundaries and pass flat obstacles by repeatedly switching between forward and backward runs. Magnetotaxis enables directed motion of MTB through heterogeneous porous media, overcoming tortuous flow fields with local velocities as high as 250  μ m s -1 . Our findings bring new insights into the migration behaviour of MTB in their natural habitats and their potential in vivo applications as microbiorobots.

  10. 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.

  11. Resveratrol inhibits IL-6-induced ovarian cancer cell migration through epigenetic up-regulation of autophagy.

    PubMed

    Ferraresi, Alessandra; Phadngam, Suratchanee; Morani, Federica; Galetto, Alessandra; Alabiso, Oscar; Chiorino, Giovanna; Isidoro, Ciro

    2017-03-01

    Interleukin-6 (IL-6), a pro-inflammatory cytokine released by cancer-associated fibroblasts, has been linked to the invasive and metastatic behavior of ovarian cancer cells. Resveratrol is a naturally occurring polyphenol with the potential to inhibit cancer cell migration. Here we show that Resveratrol and IL-6 affect in an opposite manner the expression of RNA messengers and of microRNAs involved in cell locomotion and extracellular matrix remodeling associated with the invasive properties of ovarian cancer cells. Among the several potential candidates responsible for the anti-invasive effect promoted by Resveratrol, here we focused our attention on ARH-I (DIRAS3), that encodes a Ras homolog GTPase of 26-kDa. This protein is known to inhibit cell motility, and it has been shown to regulate autophagy by interacting with BECLIN 1. IL-6 down-regulated the expression of ARH-I and inhibited the formation of LC3-positive autophagic vacuoles, while promoting cell migration. On opposite, Resveratrol could counteract the IL-6 induction of cell migration in ovarian cancer cells through induction of autophagy in the cells at the migration front, which was paralleled by up-regulation of ARH-I and down-regulation of STAT3 expression. Spautin 1-mediated disruption of BECLIN 1-dependent autophagy abrogated the effects of Resveratrol, while promoting cell migration. The present data indicate that Resveratrol elicits its anti-tumor effect through epigenetic mechanisms and support its inclusion in the chemotherapy regimen for highly aggressive ovarian cancers. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. The Effects of Gravitational Instabilities on Gas Giant Planet Migration in Protoplanetary Disks

    NASA Astrophysics Data System (ADS)

    Michael, Scott A.; Durisen, R. H.

    2010-05-01

    In this paper we conduct several three-dimensional radiative hydrodynamic simulations to explore the effect of the inclusion of gas giant planets in gravitationally unstable protoplanetary disks. We compare several simulations carried out with the CHYMERA code including: a baseline simulation without a planet, and three simulations including planets of various masses 0.3, 1 and 3 Jupiter masses. The planets are inserted into the baseline simulation after the gravitational instabilities (GIs) have grown to non-linear amplitude. The planets are inserted at the same radius, which coincides with the co-rotation radius of the dominant global mode in the baseline simulation. We examine the effect that the GIs have on migration rates as well as the potential of halting inward migration. We also examine the effect the insertion of the planet has on the global torques caused by the GIs. Furthermore, we explore the relationship between planet mass and migration rates and effect on GIs.

  13. Impacts of planet migration models on planetary populations. Effects of saturation, cooling and stellar irradiation

    NASA Astrophysics Data System (ADS)

    Dittkrist, K.-M.; Mordasini, C.; Klahr, H.; Alibert, Y.; Henning, T.

    2014-07-01

    Context. Several recent studies have found that planet migration in adiabatic disks differs significantly from migration in isothermal disks. Depending on the thermodynamic conditions, that is, the effectiveness of radiative cooling, and on the radial surface density profile, planets migrate inward or outward. Clearly, this will influence the semimajor-axis-to-mass distribution of planets predicted by population-synthesis simulations. Aims: Our goal is to study the global effects of radiative cooling, viscous torque desaturation, gap opening, and stellar irradiation on the tidal migration of a synthetic planet population. Methods: We combined results from several analytical studies and 3D hydrodynamic simulations in a new semi-analytical migration model for the application in our planet population synthesis calculations. Results: We find a good agreement of our model with torques obtained in 3D radiative hydrodynamic simulations. A typical disk has three convergence zones to which migrating planets move from the in- and outside. This strongly affects the migration behavior of low-mass planets. Interestingly, this leads to a slow type II like migration behavior for low-mass planets captured in these zones even without an ad hoc migration rate reduction factor or a yet-to-be-defined halting mechanism. This means that the new prescription of migration that includes nonisothermal effects makes the previously widely used artificial migration rate reduction factor obsolete. Conclusions: Outward migration in parts of a disk helps some planets to survive long enough to become massive. The convergence zones lead to potentially observable accumulations of low-mass planets at certain semimajor axes. Our results indicate that more studies of the mass at which the corotation torque saturates are needed since its value has a main impact on the properties of planet populations. Appendices A and B are available in electronic form at http://www.aanda.org

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

    PubMed

    Zhang, Ying; Miao, Ju-Mei

    2018-05-19

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

  15. Bromelain treatment decreases neutrophil migration to sites of inflammation.

    PubMed

    Fitzhugh, David J; Shan, Siqing; Dewhirst, Mark W; Hale, Laura P

    2008-07-01

    Bromelain, a mixture of proteases derived from pineapple stem, has been reported to have therapeutic benefits in a variety of inflammatory diseases, including murine inflammatory bowel disease. The purpose of this work was to understand potential mechanisms for this anti-inflammatory activity. Exposure to bromelain in vitro has been shown to remove a number of cell surface molecules that are vital to leukocyte trafficking, including CD128a/CXCR1 and CD128b/CXCR2 that serve as receptors for the neutrophil chemoattractant IL-8 and its murine homologues. We hypothesized that specific proteolytic removal of CD128 molecules by bromelain would inhibit neutrophil migration to IL-8 and thus decrease acute responses to inflammatory stimuli. Using an in vitro chemotaxis assay, we demonstrated a 40% reduction in migration of bromelain- vs. sham-treated human neutrophils in response to rhIL-8. Migration to the bacterial peptide analog fMLP was unaffected, indicating that bromelain does not induce a global defect in leukocyte migration. In vivo bromelain treatment generated a 50-85% reduction in neutrophil migration in 3 different murine models of leukocyte migration into the inflamed peritoneal cavity. Intravital microscopy demonstrated that although in vivo bromelain treatment transiently decreased leukocyte rolling, its primary long-term effect was abrogation of firm adhesion of leukocytes to blood vessels at the site of inflammation. These changes in adhesion were correlated with rapid re-expression of the bromelain-sensitive CD62L/L-selectin molecules that mediate rolling following in vivo bromelain treatment and minimal re-expression of CD128 over the time period studied. Taken together, these studies demonstrate that bromelain can effectively decrease neutrophil migration to sites of acute inflammation and support the specific removal of the CD128 chemokine receptor as a potential mechanism of action.

  16. Bromelain Treatment Decreases Neutrophil Migration to Sites of Inflammation

    PubMed Central

    Fitzhugh, David J.; Shan, Siqing; Dewhirst, Mark W.; Hale, Laura P.

    2008-01-01

    Bromelain, a mixture of proteases derived from pineapple stem, has been reported to have therapeutic benefits in a variety of inflammatory diseases, including murine inflammatory bowel disease. The purpose of this work was to understand potential mechanisms for this anti-inflammatory activity. Exposure to bromelain in vitro has been shown to remove a number of cell surface molecules that are vital to leukocyte trafficking, including CD128a/CXCR1 and CD128b/CXCR2 that serve as receptors for the neutrophil chemoattractant IL-8 and its murine homologues. We hypothesized that specific proteolytic removal of CD128 molecules by bromelain would inhibit neutrophil migration to IL-8 and thus decrease acute responses to inflammatory stimuli. Using an in vitro chemotaxis assay, we demonstrated a 40% reduction in migration of bromelain- vs. sham-treated human neutrophils in response to rhIL-8. Migration to the bacterial peptide analog fMLP was unaffected, indicating that bromelain does not induce a global defect in leukocyte migration. In vivo bromelain treatment generated a 50 – 85% reduction in neutrophil migration in 3 different murine models of leukocyte migration into the inflamed peritoneal cavity. Intravital microscopy demonstrated that although in vivo bromelain treatment transiently decreased leukocyte rolling, its primary long-term effect was abrogation of firm adhesion of leukocytes to blood vessels at the site of inflammation. These changes in adhesion were correlated with rapid re-expression of the bromelain-sensitive CD62L/L-selectin molecules that mediate rolling following in vivo bromelain treatment and minimal re-expression of CD128 over the time period studied. Taken together, these studies demonstrate that bromelain can effectively decrease neutrophil migration to sites of acute inflammation and support the specific removal of the CD128 chemokine receptor as a potential mechanism of action. PMID:18482869

  17. Impurity migration pattern under RF sheath potential in tokamak and the response of Plasma to RMP

    NASA Astrophysics Data System (ADS)

    Xiao, Xiaotao; Gui, Bin; Xia, Tianyang; Xu, Xueqiao; Sun, Youwen

    2017-10-01

    The migration pattern of impurity sputtered from RF guarder limiter, is simulated by a test particle module. The electric potential with RF sheath boundary condition on the guard limiter and the thermal sheath boundary condition on the divertor surface are used. The turbulence transport is implemented by random walk model. It is found the RF sheath potential enhances the impurity percentage lost at low filed side middle plane, and decreases impurity percentage drifting into core region. This beneficial effect is stronger when sheath potential is large. When turbulence transport is strong enough, their migration pattern will be dominated by transport, not by sheath potential. The Resonant Magnetic field Perturbation (RMP) is successfully applied in EAST experiment and the suppression and mitigation effect on ELM is obtained. A two field fluid model is used to simulate the plasma response to RMP in EAST geometry. The current sheet on the resonance surface is obtained initially and the resonant component of radial magnetic field is suppressed there. With plasma rotation, the Alfven resonance occurs and the current is separated into two current sheets. The simulation result will be integrated with the ELM simulations to study the effects of RMP on ELM. Prepared by LLNL under Contract DE-AC52-07NA27344 and the China Natural Science Foundation under Contract No. 11405215, 11505236 and 11675217.

  18. Effects of Radiation on Metastasis and Tumor Cell Migration

    PubMed Central

    Vilalta, Marta; Rafat, Marjan; Graves, Edward E.

    2016-01-01

    It is well known that tumor cells migrate from the primary lesion to distant sites to form metastases and that these lesions limit patient outcome in a majority of cases. However the extent to which radiation influences this process and to which migration in turn alters radiation response remains controversial. There are preclinical and clinical reports showing that focal radiotherapy can both increase the development of distant metastasis, as well as that it can induce the regression of established metastases through the abscopal effect. More recently, preclinical studies have suggested that radiation can attract migrating tumor cells and may thereby facilitate tumor recurrence. In this review, we summarize these phenomena and their potential mechanisms of action, and evaluate their significance for modern radiation therapy strategies. PMID:27022944

  19. Higher cell stiffness indicating lower metastatic potential in B16 melanoma cell variants and in (-)-epigallocatechin gallate-treated cells.

    PubMed

    Watanabe, Tatsuro; Kuramochi, Hiromi; Takahashi, Atsushi; Imai, Kazue; Katsuta, Naoko; Nakayama, Tomonobu; Fujiki, Hirota; Suganuma, Masami

    2012-05-01

    To understand how nanomechanical stiffness affects metastatic potential, we studied the relationship between cell migration, a characteristic of metastasis, and cell stiffness using atomic force microscopy (AFM), which can measure stiffness (elasticity) of individual living cells. Migration and cell stiffness of three metastatic B16 melanoma variants (B16-F10, B16-BL6, and B16-F1 cells), and also effects of (-)-epigallocatechin gallate (EGCG), were studied using Transwell assay and AFM. Migration of B16-F10 and B16-BL6 cells was 3 and 2 times higher than that of B16-F1 cells in Transwell assay, and cell stiffness determined by AFM was also different among the three variants, although they have similar morphologies and the same growth rates: Means of Young's modulus were 350.8 ± 4.8 Pa for B16-F10 cells, 661.9 ± 16.5 Pa for B16-BL6 cells, and 727.2 ± 13.0 Pa for B16-F1 cells. AFM measurements revealed that highly motile B16-F10 cells have low cell stiffness, and low motile and metastatic B16-F1 cells have high cell stiffness: Nanomechanical stiffness is inversely correlated with migration potential. Treatment of highly motile B16-F10 cells with EGCG increased cell stiffness 2-fold and inhibited migration of the cells. Our study with AFM clearly demonstrates that cell stiffness is a reliable quantitative indicator of migration potential, and very likely metastatic potential, even in morphologically similar cells. And increased cell stiffness may be a key nanomechanical feature in inhibition of metastasis.

  20. Taspine derivative TAS9 regulates cell growth and metastasis of human hepatocellular carcinoma.

    PubMed

    Liu, Rui; Wang, Wenjie; Dai, Bingling; Liu, Yanping; Zhang, Yanmin

    2015-11-01

    Taspine has been indicated to be a potential anti‑carcinogenic agent. The present study investigated the effects of TAS9, a modified taspine derivative, on the proliferation and migration of the SMMC‑7721 human liver cancer cell line. First, the effects of TAS9 on SMMC‑7721 cell growth were examined using MTT and colony formation assaya. In vivo Transwell and wound healing assays were then performed to assess the inhibitory effects of TAS9 on cell invasion and migration, respectively. The expression of cell proliferation‑ and migration‑associated signaling molecules was investigated by western blot analysis. The results indicated that TAS9 inhibited SMMC‑7721 cell growth by downregulating the signaling molecules protein kinase Cβ (PKCβ), Akt, mammalian target of rapamycin, mitogen‑activated protein kinase kinase 2, RAF and c‑Jun N‑terminal kinase‑1, and inhibiting SMMC‑7721 cell migration by suppressing the expression of matrix metalloproteinase (MMP)‑2, MMP‑9, chemokine (C‑X‑C motif) receptor 4, nuclear factor κB, p38 and p53. Small interfering RNA‑mediated knockdown of PKCβ in the SMMC‑7721 cells significantly attenuated the tumor inhibitory effects of TAS9. In conclusion, the results of the present study suggested that TAS9 may have inhibitory effects on the proliferation and migration of SMMC‑7721 cells, and may serve as a potential candidate for cancer treatment.

  1. Zeta potential control for electrophoresis cells

    NASA Technical Reports Server (NTRS)

    Fogal, G. L.

    1973-01-01

    Zeta potential arises from fact that ions tend to be adsorbed on surface of cell walls. This potential interfaces with electric field sensed by migrating particles and degrades resolution of separation. By regulating sign and magnitude of applied potential induced charge can be used to increase or decrease effective wall zeta potential.

  2. Do estrogenic compounds in drinking water migrating from plastic pipe distribution system pose adverse effects to human? An analysis of scientific literature.

    PubMed

    Liu, Ze-Hua; Yin, Hua; Dang, Zhi

    2017-01-01

    With the widespread application of plastic pipes in drinking water distribution system, the effects of various leachable organic chemicals have been investigated and their occurrence in drinking water supplies is monitored. Most studies focus on the odor problems these substances may cause. This study investigates the potential endocrine disrupting effects of the migrating compound 2,4-di-tert-butylphenol (2,4-d-t-BP). The summarized results show that the migration of 2,4-d-t-BP from plastic pipes could result in chronic exposure and the migration levels varied greatly among different plastic pipe materials and manufacturing brands. Based on estrogen equivalent (EEQ), the migrating levels of the leachable compound 2,4-d-t-BP in most plastic pipes were relative low. However, the EEQ levels in drinking water migrating from four out of 15 pipes may pose significant adverse effects. With the increasingly strict requirements on regulation of drinking water quality, these results indicate that some drinking water transported with plastic pipes may not be safe for human consumption due to the occurrence of 2,4-d-t-BP. Moreover, 2,4-d-t-BP is not the only plastic pipe-migrating estrogenic compound, other compounds such as 2-tert-butylphenol (2-t-BP), 4-tert-butylphenol (4-t-BP), and others may also be leachable from plastic pipes.

  3. 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.

  4. Suppression of calpain expression by NSAIDs is associated with inhibition of cell migration in rat duodenum.

    PubMed

    Silver, Kristopher; Littlejohn, A; Thomas, Laurel; Bawa, Bhupinder; Lillich, James D

    2017-05-15

    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the alleviation of pain and inflammation, but these drugs are also associated with a suite of negative side effects. Gastrointestinal (GI) toxicity is particularly concerning since it affects an estimated 70% of individuals taking NSAIDs routinely, and evidence suggests the majority of toxicity is occurring in the small intestine. Traditionally, NSAID-induced GI toxicity has been associated with indiscriminate inhibition of cyclooxygenase isoforms, but other mechanisms, including inhibition of cell migration, intestinal restitution, and wound healing, are likely to contribute to toxicity. Previous efforts demonstrated that treatment of cultured intestinal epithelial cells (IEC) with NSAIDs inhibits expression and activity of calpain proteases, but the effects of specific inhibition of calpain expression in vitro or the effects of NSAIDs on intestinal cell migration in vivo remain to be determined. Accordingly, we examined the effect of suppression of calpain protease expression with siRNA on cell migration in cultured IECs and evaluated the effects of NSAID treatment on epithelial cell migration and calpain protease expression in rat duodenum. Our results show that calpain siRNA inhibits protease expression and slows migration in cultured IECs. Additionally, NSAID treatment of rats slowed migration up the villus axis and suppressed calpain expression in duodenal epithelial cells. Our results are supportive of the hypothesis that suppression of calpain expression leading to slowing of cell migration is a potential mechanism through which NSAIDs cause GI toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    2013-01-01

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

  6. Implications of nonrandom seed abscission and global stilling for migration of wind-dispersed plant species.

    PubMed

    Thompson, Sally E; Katul, Gabriel G

    2013-06-01

    Migration of plant populations is a potential survival response to climate change that depends critically on seed dispersal. Biological and physical factors determine dispersal and migration of wind-dispersed species. Recent field and wind tunnel studies demonstrate biological adaptations that bias seed release toward conditions of higher wind velocity, promoting longer dispersal distances and faster migration. However, another suite of international studies also recently highlighted a global decrease in near-surface wind speeds, or 'global stilling'. This study assessed the implications of both factors on potential plant population migration rates, using a mechanistic modeling framework. Nonrandom abscission was investigated using models of three seed release mechanisms: (i) a simple drag model; (ii) a seed deflection model; and (iii) a 'wear and tear' model. The models generated a single functional relationship between the frequency of seed release and statistics of the near-surface wind environment, independent of the abscission mechanism. An Inertial-Particle, Coupled Eulerian-Lagrangian Closure model (IP-CELC) was used to investigate abscission effects on seed dispersal kernels and plant population migration rates under contemporary and potential future wind conditions (based on reported global stilling trends). The results confirm that nonrandom seed abscission increased dispersal distances, particularly for light seeds. The increases were mitigated by two physical feedbacks: (i) although nonrandom abscission increased the initial acceleration of seeds from rest, the sensitivity of the seed dispersal to this initial condition declined as the wind speed increased; and (ii) while nonrandom abscission increased the mean dispersal length, it reduced the kurtosis of seasonal dispersal kernels, and thus the chance of long-distance dispersal. Wind stilling greatly reduced the modeled migration rates under biased seed release conditions. Thus, species that require high wind velocities for seed abscission could experience threshold-like reductions in dispersal and migration potential if near-surface wind speeds continue to decline. © 2013 Blackwell Publishing Ltd.

  7. Force dependent internalization of magnetic nanoparticles results in highly loaded endothelial cells for use as potential therapy delivery vectors.

    PubMed

    MacDonald, Cristin; Barbee, Kenneth; Polyak, Boris

    2012-05-01

    To investigate the kinetics, mechanism and extent of MNP loading into endothelial cells and the effect of this loading on cell function. MNP uptake was examined under field on/off conditions, utilizing varying magnetite concentration MNPs. MNP-loaded cell viability and functional integrity was assessed using metabolic respiration, cell proliferation and migration assays. MNP uptake in endothelial cells significantly increased under the influence of a magnetic field versus non-magnetic conditions. Larger magnetite density of the MNPs led to a higher MNP internalization by cells under application of a magnetic field without compromising cellular respiration activity. Two-dimensional migration assays at no field showed that higher magnetite loading resulted in greater cell migration rates. In a three-dimensional migration assay under magnetic field, the migration rate of MNP-loaded cells was more than twice that of unloaded cells and was comparable to migration stimulated by a serum gradient. Our results suggest that endothelial cell uptake of MNPs is a force dependent process. The in vitro assays determined that cell health is not adversely affected by high MNP loadings, allowing these highly magnetically responsive cells to be potentially beneficial therapy (gene, drug or cell) delivery systems.

  8. Amplification or suppression: Social networks and the climate change-migration association in rural Mexico.

    PubMed

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

    2015-11-01

    Increasing rates of climate migration may be of economic and national concern to sending and destination countries. It has been argued that social networks - the ties connecting an origin and destination - may operate as "migration corridors" with the potential to strongly facilitate climate change-related migration. This study investigates whether social networks at the household and community levels amplify or suppress the impact of climate change on international migration from rural Mexico. A novel set of 15 climate change indices was generated based on daily temperature and precipitation data for 214 weather stations across Mexico. Employing geostatistical interpolation techniques, the climate change values were linked to 68 rural municipalities for which sociodemographic data and detailed migration histories were available from the Mexican Migration Project. Multi-level discrete-time event-history models were used to investigate the effect of climate change on international migration between 1986 and 1999. At the household level, the effect of social networks was approximated by comparing the first to the last move, assuming that through the first move a household establishes internal social capital. At the community level, the impact of social capital was explored through interactions with a measure of the proportion of adults with migration experience. The results show that rather than amplifying , social capital may suppress the sensitivity of migration to climate triggers, suggesting that social networks could facilitate climate change adaptation in place.

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  10. Enhanced regeneration potential of mobilized dental pulp stem cells from immature teeth.

    PubMed

    Nakayama, H; Iohara, K; Hayashi, Y; Okuwa, Y; Kurita, K; Nakashima, M

    2017-07-01

    We have previously demonstrated that dental pulp stem cells (DPSCs) isolated from mature teeth by granulocyte colony-stimulating factor (G-CSF)-induced mobilization method can enhance angiogenesis/vasculogenesis and improve pulp regeneration when compared with colony-derived DPSCs. However, the efficacy of this method in immature teeth with root-formative stage has never been investigated. Therefore, the aim of this study was to examine the stemness, biological characteristics, and regeneration potential in mobilized DPSCs compared with colony-derived DPSCs from immature teeth. Mobilized DPSCs isolated from immature teeth were compared to colony-derived DPSCs using methods including flow cytometry, migration assays, mRNA expression of angiogenic/neurotrophic factor, and induced differentiation assays. They were also compared in trophic effects of the secretome. Regeneration potential was further compared in an ectopic tooth transplantation model. Mobilized DPSCs had higher migration ability and expressed more angiogenic/neurotrophic factors than DPSCs. The mobilized DPSC secretome produced a higher stimulatory effect on migration, immunomodulation, anti-apoptosis, endothelial differentiation, and neurite extension. In addition, vascularization and pulp regeneration potential were higher in mobilized DPSCs than in DPSCs. G-CSF-induced mobilization method enhances regeneration potential of colony-derived DPSCs from immature teeth. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. 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 PI3K/AKT pathway. Altogether, these results suggest that CaSO 4 scaffolds could have potential applications for bone regeneration.

  12. Thermochemical Assessment of Oxygen Gettering by SiC or ZrC in PuO2-x TRISO Fuel

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

    Besmann, Theodore M

    2010-01-01

    Particulate nuclear fuel in a modular helium reactor is being considered for the consumption of excess plutonium and related transuranics. In particular, efforts to largely consume transuranics in a single-pass will require the fuel to undergo very high burnup. This deep burn concept will thus make the proposed plutonia TRISO fuel particularly likely to suffer kernel migration where carbon in the buffer layer and inner pyrolytic carbon layer is transported from the high temperature side of the particle to the low temperature side. This phenomenon is oberved to cause particle failure and therefore must be mitigated. The addition of SiCmore » or ZrC in the oxide kernel or in a layer in communication with the kernel will lower the oxygen potential and therefore prevent kernel migration, and this has been demonstrated with SiC. In this work a thermochemical analysis was performed to predict oxygen potential behavior in the plutonia TRISO fuel to burnups of 50% FIMA with and without the presence of oxygen gettering SiC and ZrC. Kernel migration is believed to be controlled by CO gas transporting carbon from the hot side to the cool side, and CO pressure is governed by the oxygen potential in the presence of carbon. The gettering phases significantly reduce the oxygen potential and thus CO pressure in an otherwise PuO2-x kernel, and prevent kernel migration by limiting CO gas diffusion through the buffer layer. The reduction in CO pressure can also reduce the peak pressure within the particles by ~50%, thus reducing the likelihood of pressure-induced particle failure. A model for kernel migration was used to semi-quantitatively assess the effect of controlling oxygen potential with SiC or ZrC and did demonstrated the dramatic effect of the addition of these phases on carbon transport.« less

  13. Using geographic distribution of well-screen depths and hydrogeologic conditions to identify areas of concern for contaminant migration through inactive supply wells

    NASA Astrophysics Data System (ADS)

    Gailey, Robert M.

    2018-02-01

    Contaminant migration through inactive supply wells can negatively affect groundwater quality and the combined effects from groups of such wells may cause greater impacts. Because the number of wells in many basins is often large and the geographic areas involved can be vast, approaches are needed to estimate potential impacts and focus limited resources for investigation and corrective measures on the most important areas. One possibility is to evaluate the geographic distribution of well-screen depths relative to hydrogeologic conditions and assess where contaminant migration through wells may be impacting groundwater quality. This approach is demonstrated for a geographically extensive area in the southern Central Valley of California, USA. The conditions that lead to wells acting as conduits for contaminant migration are evaluated and areas where the problem likely occurs are identified. Although only a small fraction of all wells appear to act as conduits, potential impacts may be significant considering needs to control nonpoint-source pollution and improve drinking water quality for rural residents. Addressing a limited number of areas where contaminant migration rates are expected to be high may cost-effectively accomplish the most beneficial groundwater quality protection and improvement. While this work focuses on a specific region, the results indicate that impacts from groups of wells may occur in other areas with similar conditions. Analyses similar to that demonstrated here may guide efficient investigation and corrective action in such areas with benefits occurring for groundwater quality. Potential benefits may justify expenditures to develop the necessary data for performing the analyses.

  14. 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.

  15. Apigenin inhibits TGF-β1-induced proliferation and migration of airway smooth muscle cells.

    PubMed

    Li, Li-Hua; Lu, Bin; Wu, Hong-Ke; Zhang, Hao; Yao, Fei-Fei

    2015-01-01

    It is well known that the proliferation and migration of ASM cells (ASMCs) plays an important role in the pathogenesis of airway remodeling in asthma. Previous studies reported that apigenin can inhibit airway remodeling in a mouse asthma model. However, its effects on the proliferation and migration of ASMCs in asthma remain unknown. Therefore, the aim of our present study was to investigate the effects of apigenin on ASMC proliferation and migration, and explore the possible molecular mechanism. We found that apigenin inhibited transforming growth factor-β1 (TGF-β1)-induced ASMC proliferation. The cell cycle was blocked at G1/S-interphase by apigenin. It also suppressed TGF-β1-induced ASMCs migration. Furthermore, apigenin inhibited TGF-β1-induced Smad 2 and Smad 3 phosphorylation in ASMCs. Taken together, these results suggested that apigenin inhibited the proliferation and migration of TGF-β1-stimulated ASMCs by inhibiting Smad signaling pathway. These data might provide useful information for treating asthma and show that apigenin has potential for attenuating airway remodeling.

  16. Human lactoferrin stimulates skin keratinocyte function and wound re-epithelialization.

    PubMed

    Tang, L; Wu, J J; Ma, Q; Cui, T; Andreopoulos, F M; Gil, J; Valdes, J; Davis, S C; Li, J

    2010-07-01

    Human lactoferrin (hLF), a member of the transferrin family, is known for its antimicrobial and anti-inflammatory effects. Recent studies on various nonskin cell lines indicate that hLF may have a stimulatory effect on cell proliferation. To study the potential role of hLF in wound re-epithelialization. The effects of hLF on cell growth, migration, attachment and survival were assessed, with a rice-derived recombinant hLF (holo-rhLF), using proliferation analysis, scratch migration assay, calcein-AM/propidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) method, respectively. The mechanisms of hLF on cell proliferation and migration were explored using specific pathway inhibitors. The involvement of lactoferrin receptor low-density lipoprotein receptor-related protein 1 (LRP1) was examined with RNA interference technique. An in vivo swine second-degree burn wound model was also used to assess wound re-epithelialization. Studies revealed that holo-rhLF significantly stimulated keratinocyte proliferation which could be blocked by mitogen-activated protein kinase (MAPK) kinase 1 inhibitor. Holo-rhLF also showed strong promoting effects on keratinocyte migration, which could be blocked by either inhibition of the MAPK, Src and Rho/ROCK pathways, or downregulation of the LRP1 receptor. With cells under starving or 12-O-tetradecanoylphorbol-13-acetate exposure, the addition of holo-rhLF was found greatly to increase cell viability and inhibit cell apoptosis. Additionally, holo-rhLF significantly increased the rate of wound re-epithelialization in swine second-degree burn wounds. Our studies demonstrate the direct effects of holo-rhLF on wound re-epithelialization including the enhancement of keratinocyte proliferation and migration as well as the protection of cells from apoptosis. The data strongly indicate its potential therapeutic applications in wound healing.

  17. In vitro evaluation of wound healing and antimicrobial potential of ozone therapy.

    PubMed

    Borges, Gabriel Álvares; Elias, Silvia Taveira; da Silva, Sandra Márcia Mazutti; Magalhães, Pérola Oliveira; Macedo, Sergio Bruzadelli; Ribeiro, Ana Paula Dias; Guerra, Eliete Neves Silva

    2017-03-01

    Although ozone therapy is extensively applied when wound repair and antimicrobial effect are necessary, little is known about cellular mechanisms regarding this process. Thus, this study aimed to evaluate ozone cytotoxicity in fibroblasts (L929) and keratinocytes (HaCaT) cell lines, its effects on cell migration and its antimicrobial activity. Cells were treated with ozonated phosphate-buffered saline (8, 4, 2, 1, 0.5 and 0.25 μg/mL ozone), chlorhexidine 0.2% or buffered-solution, and cell viability was determined through MTT assay. The effect of ozone on cell migration was evaluated through scratch wound healing and transwell migration assays. The minimum inhibitory concentrations for Candida albicans and Staphylococcus aureus were determined. Ozone showed no cytotoxicity for the cell lines, while chlorhexidine markedly reduced cell viability. Although no significant difference between control and ozone-treated cells was observed in the scratch assay, a considerable increase in fibroblasts migration was noticed on cells treated with 8 μg/mL ozonated solution. Ozone alone did not inhibit growth of microorganisms; however, its association with chlorhexidine resulted in antimicrobial activity. This study confirms the wound healing and antimicrobial potential of ozone therapy and presents the need for studies to elucidate the molecular mechanisms through which it exerts such biological effects. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  18. Timing of seasonal migration in mule deer: effects of climate, plant phenology, and life-history characteristics

    USGS Publications Warehouse

    Monteith, Kevin L.; Bleich, Vernon C.; Stephenson, Thomas R.; Pierce, Beck M.; Conner, Mary M.; Klaver, Robert W.; Bowyer, R. Terry

    2011-01-01

    Phenological events of plants and animals are sensitive to climatic processes. Migration is a life-history event exhibited by most large herbivores living in seasonal environments, and is thought to occur in response to dynamics of forage and weather. Decisions regarding when to migrate, however, may be affected by differences in life-history characteristics of individuals. Long-term and intensive study of a population of mule deer (Odocoileus hemionus) in the Sierra Nevada, California, USA, allowed us to document patterns of migration during 11 years that encompassed a wide array of environmental conditions. We used two new techniques to properly account for interval-censored data and disentangle effects of broad-scale climate, local weather patterns, and plant phenology on seasonal patterns of migration, while incorporating effects of individual life-history characteristics. Timing of autumn migration varied substantially among individual deer, but was associated with the severity of winter weather, and in particular, snow depth and cold temperatures. Migratory responses to winter weather, however, were affected by age, nutritional condition, and summer residency of individual females. Old females and those in good nutritional condition risked encountering severe weather by delaying autumn migration, and were thus risk-prone with respect to the potential loss of foraging opportunities in deep snow compared with young females and those in poor nutritional condition. Females that summered on the west side of the crest of the Sierra Nevada delayed autumn migration relative to east-side females, which supports the influence of the local environment on timing of migration. In contrast, timing of spring migration was unrelated to individual life-history characteristics, was nearly twice as synchronous as autumn migration, differed among years, was related to the southern oscillation index, and was influenced by absolute snow depth and advancing phenology of plants. Plasticity in timing of migration in response to climatic conditions and plant phenology may be an adaptive behavioral strategy, which should reduce the detrimental effects of trophic mismatches between resources and other life-history events of large herbivores. Failure to consider effects of nutrition and other life-history traits may cloud interpretation of phenological patterns of mammals and conceal relationships associated with climate change.

  19. 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.

  20. FK506-binding protein 10 (FKBP10) regulates lung fibroblast migration via collagen VI synthesis.

    PubMed

    Knüppel, Larissa; Heinzelmann, Katharina; Lindner, Michael; Hatz, Rudolf; Behr, Jürgen; Eickelberg, Oliver; Staab-Weijnitz, Claudia A

    2018-04-19

    In idiopathic pulmonary fibrosis (IPF), fibroblasts gain a more migratory phenotype and excessively secrete extracellular matrix (ECM), ultimately leading to alveolar scarring and progressive dyspnea. Here, we analyzed the effects of deficiency of FK506-binding protein 10 (FKBP10), a potential IPF drug target, on primary human lung fibroblast (phLF) adhesion and migration. Using siRNA, FKBP10 expression was inhibited in phLF in absence or presence of 2ng/ml transforming growth factor-β1 (TGF-β1) and 0.1mM 2-phosphoascorbate. Effects on cell adhesion and migration were monitored by an immunofluorescence (IF)-based attachment assay, a conventional scratch assay, and single cell tracking by time-lapse microscopy. Effects on expression of key players in adhesion dynamics and migration were analyzed by qPCR and Western Blot. Colocalization was evaluated by IF microscopy and by proximity ligation assays. FKBP10 knockdown significantly attenuated adhesion and migration of phLF. Expression of collagen VI was decreased, while expression of key components of the focal adhesion complex was mostly upregulated. The effects on migration were 2-phosphoascorbate-dependent, suggesting collagen synthesis as the underlying mechanism. FKBP10 colocalized with collagen VI and coating culture dishes with collagen VI, and to a lesser extent with collagen I, abolished the effect of FKBP10 deficiency on migration. These findings show, to our knowledge for the first time, that FKBP10 interacts with collagen VI and that deficiency of FKBP10 reduces phLF migration mainly by downregulation of collagen VI synthesis. The results strengthen FKBP10 as an important intracellular regulator of ECM remodeling and support the concept of FKBP10 as drug target in IPF.

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

    PubMed Central

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

    2013-01-01

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

  2. 40 CFR 265.90 - Applicability.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... demonstrate that there is a low potential for migration of hazardous waste or hazardous waste constituents... establish the following: (1) The potential for migration of hazardous waste or hazardous waste constituents... the owner or operator can demonstrate that there is no potential for migration of hazardous wastes...

  3. 40 CFR 265.90 - Applicability.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... demonstrate that there is a low potential for migration of hazardous waste or hazardous waste constituents... establish the following: (1) The potential for migration of hazardous waste or hazardous waste constituents... the owner or operator can demonstrate that there is no potential for migration of hazardous wastes...

  4. 40 CFR 265.90 - Applicability.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... demonstrate that there is a low potential for migration of hazardous waste or hazardous waste constituents... establish the following: (1) The potential for migration of hazardous waste or hazardous waste constituents... the owner or operator can demonstrate that there is no potential for migration of hazardous wastes...

  5. A mixed-methods study of health worker migration from Jamaica.

    PubMed

    Tomblin Murphy, Gail; MacKenzie, Adrian; Waysome, Benjamin; Guy-Walker, Joan; Palmer, Rowena; Elliott Rose, Annette; Rigby, Janet; Labonté, Ronald; Bourgeault, Ivy Lynn

    2016-06-30

    This study sought to better understand the drivers of migration, its consequences, and the various strategies countries have employed to mitigate its negative impacts. The study was conducted in four countries-Jamaica, India, the Philippines, and South Africa-that have historically been 'sources' of health workers migrating to other countries. The aim of this paper is to present the findings from the Jamaica portion of the study. Data were collected using surveys of Jamaica's generalist and specialist physicians, nurses, midwives, and dental auxiliaries, as well as structured interviews with key informants representing government ministries, professional associations, regional health authorities, healthcare facilities, and educational institutions. Quantitative data were analyzed using descriptive statistics and regression models. Qualitative data were analyzed thematically. Multiple stakeholder engagement workshops were held across Jamaica to share and validate the study findings and discuss implications for the country. Migration of health workers from Jamaica continues to be prevalent. Its causes are numerous, long-standing, and systemic, and are largely based around differences in living and working conditions between Jamaica and 'destination' countries. There is minimal formal tracking of health worker migration from Jamaica, making scientific analysis of its consequences difficult. Although there is evidence of numerous national and international efforts to manage and mitigate the negative impacts of migration, there is little evidence of the implementation or effectiveness of such efforts. Potential additional strategies for better managing the migration of Jamaica's health workers include the use of information systems to formally monitor migration, updating the national cadre system for employment of health personnel, ensuring existing personnel management policies, such as bonding, are both clearly understood and equitably enforced, and providing greater formal and informal recognition of health personnel. Although historically common, migration of Jamaica's health workers is poorly monitored and understood. Improved management of the migration of Jamaica's health workers requires collaboration from stakeholders across multiple sectors. Indeed, participating stakeholders identified a wide range of potential strategies to better manage migration of Jamaica's health workers, the implementation and testing of which will have potential benefits to Jamaica as well as other 'source' countries.

  6. Raf Kinase Inhibitory Protein protects cells against locostatin-mediated inhibition of migration.

    PubMed

    Shemon, Anne N; Eves, Eva M; Clark, Matthew C; Heil, Gary; Granovsky, Alexey; Zeng, Lingchun; Imamoto, Akira; Koide, Shohei; Rosner, Marsha Rich

    2009-06-24

    Raf Kinase Inhibitory Protein (RKIP, also PEBP1), a member of the Phosphatidylethanolamine Binding Protein family, negatively regulates growth factor signaling by the Raf/MAP kinase pathway. Since an organic compound, locostatin, was reported to bind RKIP and inhibit cell migration by a Raf-dependent mechanism, we addressed the role of RKIP in locostatin function. We analyzed locostatin interaction with RKIP and examined the biological consequences of locostatin binding on RKIP function. NMR studies show that a locostatin precursor binds to the conserved phosphatidylethanolamine binding pocket of RKIP. However, drug binding to the pocket does not prevent RKIP association with its inhibitory target, Raf-1, nor affect RKIP phosphorylation by Protein Kinase C at a regulatory site. Similarly, exposure of wild type, RKIP-depleted HeLa cells or RKIP-deficient (RKIP(-/-)) mouse embryonic fibroblasts (MEFs) to locostatin has no effect on MAP kinase activation. Locostatin treatment of wild type MEFs causes inhibition of cell migration following wounding. RKIP deficiency impairs migration further, indicating that RKIP protects cells against locostatin-mediated inhibition of migration. Locostatin treatment of depleted or RKIP(-/-) MEFs reveals cytoskeletal disruption and microtubule abnormalities in the spindle. These results suggest that locostatin's effects on cytoskeletal structure and migration are caused through mechanisms independent of its binding to RKIP and Raf/MAP kinase signaling. The protective effect of RKIP against drug inhibition of migration suggests a new role for RKIP in potentially sequestering toxic compounds that may have deleterious effects on cells.

  7. A mechanism of apigenin-induced apoptosis is potentially related to anti-angiogenesis and anti-migration in human hepatocellular carcinoma cells.

    PubMed

    Kim, Bo Ra; Jeon, Young Keul; Nam, Myeong Jin

    2011-07-01

    Apigenin (APG) has been shown to have a strong anti-cancer effect on various cancer models via a programmed cell death, apoptosis. However, the fundamental mechanisms of these effects are still unclear. In the present study, we examined the question of whether or not APG can inhibit proliferation of hepatocellular carcinoma (HCC), huh-7 cells, resulting in apoptosis. In APG-treated cells, we observed typical features of apoptosis. To identify the proteins related to APG-induced apoptosis, we performed two-dimensional electrophoresis analysis and identified differentially expressed proteins. Among these proteins, we focused on vimentin, which plays a physiological role, such as cell migration and adhesion. We validated expression of vimentin in both mRNA and protein levels, verifying its decrease. In addition, we observed that APG down-regulated the expression levels of type I collagen, which collaborated with vimentin in cell migration and decreased the releasing amounts of VEGF and MMP-8, which are closely relevant to angiogenic activity. Finally, we confirmed the decreased capacity of cell migration due to down-regulation of vimentin, type I collagen, VEGF, and MMP-8 induced by APG. Based on the overall results, we suggested that vimentin was potentially associated with APG-induced apoptosis, as a key regulator in angiogenesis and migration. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Derivation of safe health-based exposure limits for potential consumer exposure to styrene migrating into food from food containers.

    PubMed

    Gelbke, Heinz-Peter; Banton, Marcy; Faes, Eric; Leibold, Edgar; Pemberton, Mark; Duhayon, Sophie

    2014-02-01

    Residual styrene present in polystyrene food packaging may migrate into food at low levels. To assure safe use, safe exposure levels are derived for consumers potentially exposed via food using No/Low Adverse Effect Levels from animal and human studies and assessment factors proposed by European organisations (EFSA, ECHA, ECETOC). Ototoxicity and developmental toxicity in rats and human ototoxicity and effects on colour discrimination have been identified as the most relevant toxicological properties for styrene health assessments. Safe exposure levels derived from animal studies with assessment factors of EFSA and ECHA were expectedly much lower than those using the ECETOC approach. Comparable safe exposure levels were obtained from human data with all sets of assessment factors while ototoxicity in rats led to major differences. The safe exposure levels finally selected based on criteria of science and health protection converged to the range of 90-120 mg/person/d. Assuming a consumption of 1 kg food/d for an adult, this translates to 90 mg styrene migration into 1 kg food as safe for consumers. This assessment supports a health based Specific Migration Limit of 90 ppm, a value somewhat higher than the current overall migration limit of 60 ppm in the European Union. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Increased Migration of Monocytes in Essential Hypertension Is Associated with Increased Transient Receptor Potential Channel Canonical Type 3 Channels

    PubMed Central

    Chen, Jing; Zhong, Jian; Yu, Hao; Xu, Xingsen; He, Hongbo; Yan, Zhencheng; Scholze, Alexandra; Liu, Daoyan; Zhu, Zhiming; Tepel, Martin

    2012-01-01

    Increased transient receptor potential canonical type 3 (TRPC3) channels have been observed in patients with essential hypertension. In the present study we tested the hypothesis that increased monocyte migration is associated with increased TRPC3 expression. Monocyte migration assay was performed in a microchemotaxis chamber using chemoattractants formylated peptide Met-Leu-Phe (fMLP) and tumor necrosis factor-α (TNF-α). Proteins were identified by immunoblotting and quantitative in-cell Western assay. The effects of TRP channel-inhibitor 2–aminoethoxydiphenylborane (2-APB) and small interfering RNA knockdown of TRPC3 were investigated. We observed an increased fMLP-induced migration of monocytes from hypertensive patients compared with normotensive control subjects (246±14% vs 151±10%). The TNF-α-induced migration of monocytes in patients with essential hypertension was also significantly increased compared to normotensive control subjects (221±20% vs 138±18%). In the presence of 2-APB or after siRNA knockdown of TRPC3 the fMLP-induced monocyte migration was significantly blocked. The fMLP-induced changes of cytosolic calcium were significantly increased in monocytes from hypertensive patients compared to normotensive control subjects. The fMLP-induced monocyte migration was significantly reduced in the presence of inhibitors of tyrosine kinase and phosphoinositide 3-kinase. We conclude that increased monocyte migration in patients with essential hypertension is associated with increased TRPC3 channels. PMID:22438881

  10. Effects of conditioned medium from LL-37 treated adipose stem cells on human fibroblast migration.

    PubMed

    Yang, Eun-Jung; Bang, Sa-Ik

    2017-07-01

    Adipose stem cell-conditioned medium may promote human dermal fibroblast (HDF) proliferation and migration by activating paracrine peptides during the re-epithelization phase of wound healing. Human antimicrobial peptide LL-37 is upregulated in the skin epithelium as part of the normal response to injury. The effects of conditioned medium (CM) from LL-37 treated adipose stem cells (ASCs) on cutaneous wound healing, including the mediation of fibroblast migration, remain to be elucidated, therefore the aim of the present study was to determine how ASCs would react to an LL-37-rich microenvironment and if CM from LL-37 treated ASCs may influence the migration of HDFs. The present study conducted migration assays with HDFs treated with CM from LL-37 treated ASCs. Expression of CXC chemokine receptor 4 (CXCR4), which controls the recruitment of HDFs, was analyzed at the mRNA and protein levels. To further characterize the stimulatory effects of LL-37 on ASCs, the expression of stromal cell-derived factor-1α (SDF-1α), a CXC chemokine, was investigated. CM from LL-37-treated ASCs induced migration of HDFs in a time- and dose-dependent manner, with a maximum difference in migration observed 24 h following stimulation with LL-37 at a concentration of 10 µg/ml. The HDF migration and the expression of CXCR4 in fibroblasts was markedly increased upon treatment with CM from LL-37-treated ASCs compared with CM from untreated ASCs. SDF-1α expression was markedly increased in CM from LL-37 treated ASCs. It was additionally observed that SDF-1α blockade significantly reduced HDF migration. These findings suggest the feasibility of CM from LL-37-treated ASCs as a potential therapeutic for human dermal fibroblast migration.

  11. Amplification or suppression: Social networks and the climate change—migration association in rural Mexico

    PubMed Central

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

    2015-01-01

    Increasing rates of climate migration may be of economic and national concern to sending and destination countries. It has been argued that social networks – the ties connecting an origin and destination – may operate as “migration corridors” with the potential to strongly facilitate climate change-related migration. This study investigates whether social networks at the household and community levels amplify or suppress the impact of climate change on international migration from rural Mexico. A novel set of 15 climate change indices was generated based on daily temperature and precipitation data for 214 weather stations across Mexico. Employing geostatistical interpolation techniques, the climate change values were linked to 68 rural municipalities for which sociodemographic data and detailed migration histories were available from the Mexican Migration Project. Multi-level discrete-time event-history models were used to investigate the effect of climate change on international migration between 1986 and 1999. At the household level, the effect of social networks was approximated by comparing the first to the last move, assuming that through the first move a household establishes internal social capital. At the community level, the impact of social capital was explored through interactions with a measure of the proportion of adults with migration experience. The results show that rather than amplifying, social capital may suppress the sensitivity of migration to climate triggers, suggesting that social networks could facilitate climate change adaptation in place. PMID:26692656

  12. Cleavage of the urokinase receptor (uPAR) on oral cancer cells: regulation by transforming growth factor - β1 (TGF-β1) and potential effects on migration and invasion.

    PubMed

    Magnussen, Synnove Norvoll; Hadler-Olsen, Elin; Costea, Daniela Elena; Berg, Eli; Jacobsen, Cristiane Cavalcanti; Mortensen, Bente; Salo, Tuula; Martinez-Zubiaurre, Inigo; Winberg, Jan-Olof; Uhlin-Hansen, Lars; Svineng, Gunbjorg

    2017-05-19

    Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment regulated uPAR expression, as well as its glycosylation and cleavage. Both full-length- and cleaved uPAR (uPAR (II-III)) are involved in highly regulated processes such as cell signalling, proliferation, migration, stem cell mobilization and invasion. The aim of the current study was to analyse tumour associated factors and their effect on uPAR cleavage, and the potential implications for cell proliferation, migration and invasion. Mouse uPAR was stably overexpressed in the mouse OSCC cell line AT84. The ratio of full-length versus cleaved uPAR as analysed by Western blotting and its regulation was assessed by addition of different protease inhibitors and transforming growth factor - β1 (TGF-β1). The role of uPAR cleavage in cell proliferation and migration was analysed using real-time cell analysis and invasion was assessed using the myoma invasion model. We found that when uPAR was overexpressed a proportion of the receptor was cleaved, thus the cells presented both full-length uPAR and uPAR (II-III). Cleavage was mainly performed by serine proteases and urokinase plasminogen activator (uPA) in particular. When the OSCC cells were stimulated with TGF-β1, the production of the uPA inhibitor PAI-1 was increased, resulting in a reduction of uPAR cleavage. By inhibiting cleavage of uPAR, cell migration was reduced, and by inhibiting uPA activity, invasion was reduced. We could also show that medium containing soluble uPAR (suPAR), and cleaved soluble uPAR (suPAR (II-III)), induced migration in OSCC cells with low endogenous levels of uPAR. These results show that soluble factors in the tumour microenvironment, such as TGF-β1, PAI-1 and uPA, can influence the ratio of full length and uPAR (II-III) and thereby potentially effect cell migration and invasion. Resolving how uPAR cleavage is controlled is therefore vital for understanding how OSCC progresses and potentially provides new targets for therapy.

  13. The consequences of physical post-treatments (microwave and electron-beam) on food/packaging interactions: A physicochemical and toxicological approach.

    PubMed

    Riquet, A M; Breysse, C; Dahbi, L; Loriot, C; Severin, I; Chagnon, M C

    2016-05-15

    The safety of microwave and electron-beam treatments has been demonstrated, in regards to the formation of reaction products that could endanger human health. An integrated approach was used combining the potential toxicity of all the substances likely to migrate to their chemical characterizations. This approach was applied to polypropylene (PP) films prepared with a selection of additives. Components were identified by liquid and gas chromatography using a mass selective detector system. Their potential toxicity was assessed using three in vitro short-term bioassays and their migrations were carried out using a standards-based approach. After the electron-beam treatment some additives decomposed and there was a significant increase in the polyolefin oligomeric saturated hydrocarbons concentration. PP prepared with Irgafos 168 led to a significantly strong cytotoxic effect and PP prepared with Irganox 1076 induced a dose-dependant estrogenic effect in vitro. Migration values were low and below the detection limit of the analytical method applied. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Effect of TRPV2 cation channels on the proliferation, migration and invasion of 5637 bladder cancer cells.

    PubMed

    Liu, Quanliang; Wang, Xinghuan

    2013-11-01

    Transient receptor potential vanilloid 2 (TRPV2), a nonselective cation channel, has become an attractive target gene for tumor studies due to its wide range of physiological and pathological functions. However, its specific role in bladder cancer development and progression remains unclear. The aim of the present study was to investigate the effects of TRPV2 on the proliferation, migration and invasion of 5637 bladder cancer cells in vitro . Rat TRPV2 cDNA was transfected into 5637 bladder cancer cells and changes in the behavior of the cells were detected. It was observed that TRPV2 enhanced bladder cancer cell migration and invasion; however, it did not affect cell proliferation in vitro . TRPV2 activity, which may be mediated by direct matrix metalloproteinase 2 (MMP2) regulation, is important in bladder tumor development and progression. The results of this study suggest that TRPV2 channels are a potential therapeutic target for bladder carcinoma.

  15. Effect of TRPV2 cation channels on the proliferation, migration and invasion of 5637 bladder cancer cells

    PubMed Central

    LIU, QUANLIANG; WANG, XINGHUAN

    2013-01-01

    Transient receptor potential vanilloid 2 (TRPV2), a nonselective cation channel, has become an attractive target gene for tumor studies due to its wide range of physiological and pathological functions. However, its specific role in bladder cancer development and progression remains unclear. The aim of the present study was to investigate the effects of TRPV2 on the proliferation, migration and invasion of 5637 bladder cancer cells in vitro. Rat TRPV2 cDNA was transfected into 5637 bladder cancer cells and changes in the behavior of the cells were detected. It was observed that TRPV2 enhanced bladder cancer cell migration and invasion; however, it did not affect cell proliferation in vitro. TRPV2 activity, which may be mediated by direct matrix metalloproteinase 2 (MMP2) regulation, is important in bladder tumor development and progression. The results of this study suggest that TRPV2 channels are a potential therapeutic target for bladder carcinoma. PMID:24223658

  16. 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.

  17. Flavonoid Fraction of Citrus reticulata Juice Reduces Proliferation and Migration of Anaplastic Thyroid Carcinoma Cells.

    PubMed

    Celano, Marilena; Maggisano, Valentina; De Rose, Roberta Francesca; Bulotta, Stefania; Maiuolo, Jessica; Navarra, Michele; Russo, Diego

    2015-01-01

    Effects of flavonoids extracted from Citrus reticulata (mandarin) juice on proliferation and migration of 3 human anaplastic thyroid carcinoma (ATC) cell lines were evaluated. Flavonoid components of Mandarin juice extract (MJe) were analyzed by uHPLC. Proliferation of CAL-62, C-643, and 8505C cells, measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, was significantly reduced by MJe in a concentration- and time-dependent way, with maximal effect elicited at 0.5 mg/ml concentration after 48 h. Cytofluorimetric analysis showed a block in the G2/M phase of the cell cycle, accompanied by low cell mortality owed to autophagic death. The extract caused also a reduction of cell migration, associated with decreased activity of the metalloproteinase MMP-2. These findings demonstrate that the flavonoid fraction of mandarin juice exerts in vitro antiproliferative effects on ATC cells, associated with a reduction of migration, suggesting for such a functional food a potential use as adjuvant in the treatment of thyroid cancer.

  18. Force Dependent Internalization of Magnetic Nanoparticles Results in Highly Loaded Endothelial Cells for Use as Potential Therapy Delivery Vectors

    PubMed Central

    MacDonald, Cristin; Barbee, Kenneth

    2015-01-01

    Purpose To investigate the kinetics, mechanism and extent of MNP loading into endothelial cells and the effect of this loading on cell function. Methods MNP uptake was examined under field on/off conditions, utilizing varying magnetite concentration MNPs. MNP-loaded cell viability and functional integrity was assessed using metabolic respiration, cell proliferation and migration assays. Results MNP uptake in endothelial cells significantly increased under the influence of a magnetic field versus non-magnetic conditions. Larger magnetite density of the MNPs led to a higher MNP internalization by cells under application of a magnetic field without compromising cellular respiration activity. Two-dimensional migration assays at no field showed that higher magnetite loading resulted in greater cell migration rates. In a three-dimensional migration assay under magnetic field, the migration rate of MNP-loaded cells was more than twice that of unloaded cells and was comparable to migration stimulated by a serum gradient. Conclusions Our results suggest that endothelial cell uptake of MNPs is a force dependent process. The in vitro assays determined that cell health is not adversely affected by high MNP loadings, allowing these highly magnetically responsive cells to be potentially beneficial therapy (gene, drug or cell) delivery systems. PMID:22234617

  19. River meander modeling of the Wabash River near the Interstate 64 Bridge near Grayville, Illinois

    USGS Publications Warehouse

    Lant, Jeremiah G.; Boldt, Justin A.

    2018-01-16

    Natural river channels continually evolve and change shape over time. As a result, channel evolution or migration can cause problems for bridge structures that are fixed in the flood plain. A once-stable bridge structure that was uninfluenced by a river’s shape could be encroached upon by a migrating river channel. The potential effect of the actively meandering Wabash River on the Interstate 64 Bridge at the border with Indiana near Grayville, Illinois, was studied using a river migration model called RVR Meander. RVR Meander is a toolbox that can be used to model river channel meander migration with physically based bank erosion methods. This study assesses the Wabash River meandering processes through predictive modeling of natural meandering over the next 100 years, climate change effects through increased river flows, and bank protection measures near the Interstate 64 Bridge.

  20. Phosphoprotein enriched in diabetes (PED/PEA15) promotes migration in hepatocellular carcinoma and confers resistance to sorafenib

    PubMed Central

    Quintavalle, Cristina; Hindupur, Sravanth Kumar; Quagliata, Luca; Pallante, Pierlorenzo; Nigro, Cecilia; Condorelli, Gerolama; Andersen, Jesper Bøje; Tagscherer, Katrin Elisabeth; Roth, Wilfried; Beguinot, Francesco; Heim, Markus Hermann; Ng, Charlotte Kiu Yan; Piscuoglio, Salvatore; Matter, Matthias Sebastian

    2017-01-01

    Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related death with limited treatment options and frequent resistance to sorafenib, the only drug currently approved for first-line therapy. Therefore, better understanding of HCC tumor biology and its resistance to treatment is urgently needed. Here, we analyzed the role of phosphoprotein enriched in diabetes (PED) in HCC. PED has been shown to regulate cell proliferation, apoptosis and migration in several types of cancer. However, its function in HCC has not been addressed yet. Our study revealed that both transcript and protein levels of PED were significantly high in HCC compared with non-tumoral tissue. Clinico-pathological correlation revealed that PEDhigh HCCs showed an enrichment of gene signatures associated with metastasis and poor prognosis. Further, we observed that PED overexpression elevated the migration potential and PED silencing the decreased migration potential in liver cancer cell lines without effecting cell proliferation. Interestingly, we found that PED expression was regulated by a hepatocyte specific nuclear factor, HNF4α. A reduction of HNF4α induced an increase in PED expression and consequently, promoted cell migration in vitro. Finally, PED reduced the antitumoral effect of sorafenib by inhibiting caspase-3/7 activity. In conclusion, our data suggest that PED has a prominent role in HCC biology. It acts particularly on promoting cell migration and confers resistance to sorafenib treatment. PED may be a novel target for HCC therapy and serve as a predictive marker for treatment response against sorafenib. PMID:29072691

  1. Metastatic potential of melanoma cells is not affected by electrochemotherapy.

    PubMed

    Todorovic, Vesna; Sersa, Gregor; Mlakar, Vid; Glavac, Damjan; Flisar, Karel; Cemazar, Maja

    2011-06-01

    Electrochemotherapy is a local treatment combining chemotherapy and application of electric pulses to the tumour. Electrochemotherapy with bleomycin and cisplatin has shown its effectiveness in controlling local tumour growth in the treatment of malignant melanoma. However, the effect of electrochemotherapy on the metastatic potential of tumour cells is not known. Prevention of metastasis is an important aspect of successful treatment; however, it is known that metastasis can be induced by different treatment modalities. Therefore, the aim of this study was to evaluate the effect of electrochemotherapy with cisplatin on the metastatic potential of human malignant melanoma cells. Cells treated by electrochemotherapy with cisplatin were tested for their ability to migrate and invade through Matrigel-coated porous membrane. In addition, RNA was isolated from cells after treatment and differentially expressed genes were investigated by microarray analysis to evaluate the effect of electrochemotherapy with cisplatin on gene expression. There were no significant changes observed in cell migration and invasion of melanoma cells after electrochemotherapy. In addition, there were no changes observed in cell adhesion on Matrigel. Gene expression analysis showed that a very low number of genes were differentially expressed after electrochemotherapy with cisplatin. Two genes, LAMB3 and CD63 involved in cell migration, were both downregulated after electrochemotherapy with cisplatin and the expression of metastasis promoting genes was not increased after electrochemotherapy. Our data suggest that electrochemotherapy does not increase the metastatic behaviour of human melanoma cells.

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

    PubMed

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

    2017-02-15

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

  3. Coil Migration, Malposition, Stretching and Retrieval

    PubMed Central

    Abe, T.; Hirohata, M.; Tanaka, N.; Uchiyama, Y.; Morimitsu, H.; Kojima, K.; Hayabuchi, N.

    2000-01-01

    Summary In this educational program for complicated coil placements, we report several cases of coil malposition, migration, and retrieval. We emphasize that a decrease in the expected one-to-one motion of the coil is the earliest sign of a possible imminent complication, and the over the core wire technique with a fixed-loop snare (Gooseneck microsnare) is a very effective potential solution for elongated coil retrieval. PMID:20667237

  4. Short-term organic carbon migration from polymeric materials in contact with chlorinated drinking water.

    PubMed

    Mao, Guannan; Wang, Yingying; Hammes, Frederik

    2018-02-01

    Polymeric materials are widely used in drinking water distribution systems. These materials could release organic carbon that supports bacterial growth. To date, the available migration assays for polymeric materials have not included the potential influence of chlorination on organic carbon migration behavior. Hence, we established a migration and growth potential protocol specifically for analysis of carbon migration from materials in contact with chlorinated drinking water. Four different materials were tested, including ethylene propylene dienemethylene (EPDM), poly-ethylene (PEX b and PEX c) and poly-butylene (PB). Chlorine consumption rates decreased gradually over time for EPDM, PEXc and PB. In contrast, no free chlorine was detected for PEXb at any time during the 7 migration cycles. Total organic carbon (TOC) and assimilable organic carbon (AOC) was evaluated in both chlorinated and non-chlorinated migrations. TOC concentrations for EPDM and PEXb in chlorinated migrations were significantly higher than non-chlorinated migrations. The AOC results showed pronounced differences among tested materials. AOC concentrations from chlorinated migration waters of EPDM and PB were higher compared to non-chlorinated migrations, whereas the opposite trend was observed for PEXb and PEXc. There was also a considerable difference between tested materials with regards to bacterial growth potential. The results revealed that the materials exposed to chlorine-influenced migration still exhibited a strong biofilm formation potential. The overall results suggested that the choice in material would make a considerable difference in chlorine consumption and carbon migration behavior in drinking water distribution systems. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. A novel taspine derivative, HMQ1611, suppresses adhesion, migration and invasion of ZR-75-30 human breast cancer cells.

    PubMed

    Zhan, Yingzhuan; Wang, Nan; Liu, Cuicui; Chen, Yinnan; Zheng, Lei; He, Langchong

    2014-05-01

    Taspine was screened for the first time from Radix et Rhizoma leonticis (Hong Mao Qi in Chinese) using cell membrane chromatography in our laboratory. Its anticancer and antiangiogenic properties were demonstrated, and it could serve as a lead compound in anticancer agent development. Here, we investigated the role of one of the derivatives, HMQ1611, with increased activity and solubility, on the regulation of breast cancer cell ZR-75-30 adhesion, migration and invasion. The effect of HMQ1611 on adhesion, invasion and migration of human breast cancer cells ZR-75-30 was examined. The migration and invasive potential of ZR-75-30 cells were examined by wound-healing assays and matrigel invasion chamber assays. The adhesion to type IV collagen and laminin were evaluated by MTT assay. The expression and proteinase activity of two matrix metalloproteinases (MMPs), matrix metalloproteinases 2 (MMP-2) and matrix metalloproteinases 9 (MMP-9), were analyzed by Western blot analysis and gelatin zymography, respectively. HMQ1611 effectively inhibited ZR-75-30 cell invasion and significantly suppressed adhesion to type IV collagen and laminin-coated substrate in a dose-dependent manner. Western blot and gelatin zymography analysis showed that HMQ1611 significantly inhibited the expression and secretion of MMP-2 and MMP-9 in ZR-75-30 cells. Additionally, treatment of ZR-75-30 cells with HMQ1611 downregulated the expression of MMP-2 and MMP-9. HMQ1611 had potential to suppress the adhesion, migration and invasion of ZR-75-30 cancer cells, and it could serve as a potential novel therapeutic candidate for the treatment of metastatic breast cancer.

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

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

    2017-01-01

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

  8. Cancer-suppressive potential of extracts of endemic plant Helichrysum zivojinii: effects on cell migration, invasion and angiogenesis.

    PubMed

    Matić, Ivana Z; Aljancić, Ivana; Vajs, Vlatka; Jadranin, Milka; Gligorijević, Nevenka; Milosavljević, Slobodan; Juranić, Zorica D

    2013-09-01

    Helichrysum zivojinii Cernjavski & Soska is an endemic plant species that grows in the National Park Galicica in Macedonia. Five extracts were isolated as fractions from the aerial parts of the plant: a n-hexane extract (1), a dichloromethane extract (2), an ethyl-acetate extract (3), a n-butanol extract (4) and a methanol extract (5). A dose-dependent cytotoxic activity of the extracts on MDA-MB-231 and EA.hy926 cells was observed. Extracts exhibited more pronounced cytotoxic actions on MDA-MB-231 cells than on EA.hy926 cells. The n-hexane extract (1), at a non-toxic concentration, exhibited an inhibitory effect on the migration as well the invasiveness of MDA-MB-231 cells. The dichloromethane extract (2), at a non-toxic concentration, demonstrated inhibition of MDA-MB-231 cells invasion. Each of the five extracts applied at non-toxic concentrations inhibited migration of EA.hy926 cells. The prominent inhibitory effect of the n-hexane extract on EA.hy926 cells migration was associated with a notable anti-angiogenic action of this extract. The other four tested extracts demonstrated mild anti-angiogenic activity. Our data highlight the prominent anticancer potential of n-hexane (1) and dichloromethane (2) extracts, which could be attributed to their very pronounced and selective cytotoxic activities as well as their anti-invasive and anti-angiogenic properties.

  9. Disruption, not displacement: Environmental variability and temporary migration in Bangladesh

    PubMed Central

    Gray, Clark; Yunus, Mohammad; Emch, Michael

    2018-01-01

    Mass migration is one of the most concerning potential outcomes of global climate change. Recent research into environmentally induced migration suggests that relationship is much more complicated than originally posited by the ‘environmental refugee’ hypothesis. Climate change is likely to increase migration in some cases and reduce it in others, and these movements will more often be temporary and short term than permanent and long term. However, few large-sample studies have examined the evolution of temporary migration under changing environmental conditions. To address this gap, we measure the extent to which temperature, precipitation, and flooding can predict temporary migration in Matlab, Bangladesh. Our analysis incorporates high-frequency demographic surveillance data, a discrete time event history approach, and a range of sociodemographic and contextual controls. This approach reveals that migration declines immediately after flooding but quickly returns to normal. In contrast, optimal precipitation and high temperatures have sustained positive effects on temporary migration that persist over one to two year periods. Building on previous studies of long-term migration, these results challenge the common assumption that flooding, precipitation extremes and high temperatures will consistently increase temporary migration. Instead, our results are consistent with a livelihoods interpretation of environmental migration in which households draw on a range of strategies to cope with environmental variability. PMID:29375196

  10. Disruption, not displacement: Environmental variability and temporary migration in Bangladesh.

    PubMed

    Call, Maia A; Gray, Clark; Yunus, Mohammad; Emch, Michael

    2017-09-01

    Mass migration is one of the most concerning potential outcomes of global climate change. Recent research into environmentally induced migration suggests that relationship is much more complicated than originally posited by the 'environmental refugee' hypothesis. Climate change is likely to increase migration in some cases and reduce it in others, and these movements will more often be temporary and short term than permanent and long term. However, few large-sample studies have examined the evolution of temporary migration under changing environmental conditions. To address this gap, we measure the extent to which temperature, precipitation, and flooding can predict temporary migration in Matlab, Bangladesh. Our analysis incorporates high-frequency demographic surveillance data, a discrete time event history approach, and a range of sociodemographic and contextual controls. This approach reveals that migration declines immediately after flooding but quickly returns to normal. In contrast, optimal precipitation and high temperatures have sustained positive effects on temporary migration that persist over one to two year periods. Building on previous studies of long-term migration, these results challenge the common assumption that flooding, precipitation extremes and high temperatures will consistently increase temporary migration. Instead, our results are consistent with a livelihoods interpretation of environmental migration in which households draw on a range of strategies to cope with environmental variability.

  11. Data on the migration of health-care workers: sources, uses, and challenges.

    PubMed Central

    Diallo, Khassoum

    2004-01-01

    The migration of health workers within and between countries is a growing concern worldwide because of its impact on health systems in developing and developed countries alike. Policy decisions need to be made at the national, regional and international levels to manage more effectively this phenomenon, but those decisions will be effective and correctly implemented and evaluated only if they are based on adequate statistical data. Most statistics on the migration of health-care workers are neither complete nor fully comparable, and they are often underused, limited (because they often give only a broad description of the phenomena) and not as timely as required. There is also a conflict between the wide range of potential sources of data and the poor statistical evidence on the migration of health personnel. There are two major problems facing researchers who wish to provide evidence on this migration: the problems commonly faced when studying migration in general, such as definitional and comparability problems of "worker migrations" and those related to the specific movements of the health workforce. This paper presents information on the uses of statistics and those who use them, the strengths and limitations of the main data sources, and other challenges that need to be met to obtain good evidence on the migration of health workers. This paper also proposes methods to improve the collection, analysis, sharing, and use of statistics on the migration of health workers. PMID:15375450

  12. Raf Kinase Inhibitory Protein Protects Cells against Locostatin-Mediated Inhibition of Migration

    PubMed Central

    Shemon, Anne N.; Eves, Eva M.; Clark, Matthew C.; Heil, Gary; Granovsky, Alexey; Zeng, Lingchun; Imamoto, Akira

    2009-01-01

    Background Raf Kinase Inhibitory Protein (RKIP, also PEBP1), a member of the Phosphatidylethanolamine Binding Protein family, negatively regulates growth factor signaling by the Raf/MAP kinase pathway. Since an organic compound, locostatin, was reported to bind RKIP and inhibit cell migration by a Raf-dependent mechanism, we addressed the role of RKIP in locostatin function. Methods/Findings We analyzed locostatin interaction with RKIP and examined the biological consequences of locostatin binding on RKIP function. NMR studies show that a locostatin precursor binds to the conserved phosphatidylethanolamine binding pocket of RKIP. However, drug binding to the pocket does not prevent RKIP association with its inhibitory target, Raf-1, nor affect RKIP phosphorylation by Protein Kinase C at a regulatory site. Similarly, exposure of wild type, RKIP-depleted HeLa cells or RKIP-deficient (RKIP−/−) mouse embryonic fibroblasts (MEFs) to locostatin has no effect on MAP kinase activation. Locostatin treatment of wild type MEFs causes inhibition of cell migration following wounding. RKIP deficiency impairs migration further, indicating that RKIP protects cells against locostatin-mediated inhibition of migration. Locostatin treatment of depleted or RKIP−/− MEFs reveals cytoskeletal disruption and microtubule abnormalities in the spindle. Conclusions/Significance These results suggest that locostatin's effects on cytoskeletal structure and migration are caused through mechanisms independent of its binding to RKIP and Raf/MAP kinase signaling. The protective effect of RKIP against drug inhibition of migration suggests a new role for RKIP in potentially sequestering toxic compounds that may have deleterious effects on cells. PMID:19551145

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

    PubMed Central

    Flewelling, Samuel A; Sharma, Manu

    2014-01-01

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

  14. Wogonin suppresses TNF-{alpha}-induced MMP-9 expression by blocking the NF-{kappa}B activation via MAPK signaling pathways in human aortic smooth muscle cells

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

    Lee, Syng-Ook; Jeong, Yun-Jeong; Yu, Mi Hee

    2006-12-08

    Matrix metalloproteinase-9 (MMP-9) plays a major role in the pathogenesis of atherosclerosis and restenosis by regulating both migration and proliferation of vascular smooth muscle cells (VSMC) after an arterial injury. In this study, we examined the inhibitory effect of three major flavonoids in Scutellariae Radix, baicalin, baicalein, and wogonin, on TNF-{alpha}-induced MMP-9 expression in human aortic smooth muscle cells (HASMC). Wogonin, but not baicalin and baicalein, significantly and selectively suppressed TNF-{alpha}-induced MMP-9 expression in HASMC. Reporter gene, electrophoretic mobility shift, and Western blotting assays showed that wogonin inhibits MMP-9 gene transcriptional activity by blocking the activation of NF-{kappa}B via MAPKmore » signaling pathways. Moreover, the Matrigel migration assay showed that wogonin reduced TNF-{alpha}-induced HASMC migration. These results suggest that wogonin effectively suppresses TNF-{alpha}-induced HASMC migration through the selective inhibition of MMP-9 expression and represents a potential agent for the prevention of vascular disorders related to the migration of VSMC.« less

  15. Focused tight dressing does not prevent cochlear implant magnet migration under 1.5 Tesla MRI.

    PubMed

    Cuda, D; Murri, A; Succo, G

    2013-04-01

    We report a retrospective case of inner magnet migration, which occurred after 1.5 Tesla MRI scanning in an adult recipient of a bilateral cochlear implant (CI) despite a focused head dressing. The patient, bilaterally implanted with Nucleus 5 CIs (Cochlear LTD, Sydney, Australia), underwent a 1.5 Tesla cholangio-MRI scan for biliary duct pathology. In subsequent days, a focal skin alteration appeared over the left inner coil. Plain skull radiographs showed partial magnet migration on the left side. Surgical exploration confirmed magnet twisting; the magnet was effectively repositioned. Left CI performance was restored to pre-migration level. The wound healed without complications. Thus, focused dressing does not prevent magnet migration in CI recipients undergoing 1.5 Tesla MRI. All patients should be counselled on this potential complication. A minor surgical procedure is required to reposition the magnet. Nevertheless, timely diagnosis is necessary to prevent skin breakdown and subsequent device contamination. Plain skull radiograph is very effective in identifying magnet twisting; it should be performed systematically after MRI or minimally on all suspected cases.

  16. Potential Effects of Hydroelectric Dam Development in the Mekong River Basin on the Migration of Siamese Mud Carp (Henicorhynchus siamensis and H. lobatus) Elucidated by Otolith Microchemistry

    PubMed Central

    Fukushima, Michio; Jutagate, Tuantong; Grudpan, Chaiwut; Phomikong, Pisit; Nohara, Seiichi

    2014-01-01

    The migration of Siamese mud carp (Henicorhynchus siamensis and H. lobatus), two of the most economically important fish species in the Mekong River, was studied using an otolith microchemistry technique. Fish and river water samples were collected in seven regions throughout the whole basin in Thailand, Laos and Cambodia over a 4 year study period. There was coherence between the elements in the ambient water and on the surface of the otoliths, with strontium (Sr) and barium (Ba) showing the strongest correlation. The partition coefficients were 0.409–0.496 for Sr and 0.055 for Ba. Otolith Sr-Ba profiles indicated extensive synchronized migrations with similar natal origins among individuals within the same region. H. siamensis movement has been severely suppressed in a tributary system where a series of irrigation dams has blocked their migration. H. lobatus collected both below and above the Khone Falls in the mainstream Mekong exhibited statistically different otolith surface elemental signatures but similar core elemental signatures. This result suggests a population originating from a single natal origin but bypassing the waterfalls through a passable side channel where a major hydroelectric dam is planned. The potential effects of damming in the Mekong River are discussed. PMID:25099147

  17. Effects from past solid waste disposal practices.

    PubMed Central

    Johnson, L J; Daniel, D E; Abeele, W V; Ledbetter, J O; Hansen, W R

    1978-01-01

    This paper reviews documented environmental effects experience from the disposal of solid waste materials in the U.S. Selected case histories are discussed that illustrate waste migration and its actual or potential effects on human or environmental health. Principal conclusions resulting from this review were: solid waste materials do migrate beyond the geometric confines of the initial placement location; environmental effects have been experienced from disposal of municipal, agricultural, and toxic chemical wastes; and utilization of presently known science and engineering principles in sitting and operating solid waste disposal facilities would make a significant improvement in the containment capability of shallow land disposal facilities. PMID:367769

  18. Autumn Royal and Ribier Grape Juice Extracts Reduced Viability and Metastatic Potential of Colon Cancer Cells.

    PubMed

    Valenzuela, Manuel; Bastias, Lorena; Montenegro, Iván; Werner, Enrique; Madrid, Alejandro; Godoy, Patricio; Párraga, Mario; Villena, Joan

    2018-01-01

    Antioxidants are known to be beneficial to health. This paper evaluates the potential chemopreventive and anticancer properties of phenolic compounds present in grape juice extracts (GJE) from Autumn Royal and Ribier varieties. The effects of these GJE on viability (SRB day assay) and metastatic potential (migration and invasion parameters) of colon cancer cell lines HT-29 and SW-480 were evaluated. The effects of GJE on two matrix metalloproteinase gene expressions (MMP2 and MMP9) were also evaluated via qRT-PCR. In the former, GJE reduced cell viability in both cell lines in a dose-dependent manner. GJE treatment also reduced cell migration and invasion. Moreover, MMP-2 and MMP-9 gene expression diminished depending on extract and on cell type. Conclusions . These results provide novel information concerning anticancer properties of selected GJE by revealing selective cytotoxicity and the ability to reduce invasiveness of colon cancer cells.

  19. Autumn Royal and Ribier Grape Juice Extracts Reduced Viability and Metastatic Potential of Colon Cancer Cells

    PubMed Central

    Valenzuela, Manuel; Bastias, Lorena; Montenegro, Iván; Werner, Enrique; Madrid, Alejandro; Godoy, Patricio

    2018-01-01

    Antioxidants are known to be beneficial to health. This paper evaluates the potential chemopreventive and anticancer properties of phenolic compounds present in grape juice extracts (GJE) from Autumn Royal and Ribier varieties. The effects of these GJE on viability (SRB day assay) and metastatic potential (migration and invasion parameters) of colon cancer cell lines HT-29 and SW-480 were evaluated. The effects of GJE on two matrix metalloproteinase gene expressions (MMP2 and MMP9) were also evaluated via qRT-PCR. In the former, GJE reduced cell viability in both cell lines in a dose-dependent manner. GJE treatment also reduced cell migration and invasion. Moreover, MMP-2 and MMP-9 gene expression diminished depending on extract and on cell type. Conclusions. These results provide novel information concerning anticancer properties of selected GJE by revealing selective cytotoxicity and the ability to reduce invasiveness of colon cancer cells. PMID:29552079

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

    PubMed Central

    Wang, Dan; Tang, Jie

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  2. Fisetin regulates astrocyte migration and proliferation in vitro

    PubMed Central

    Wang, Nan; Yao, Fang; Li, Ke; Zhang, Lanlan; Yin, Guo; Du, Mingjun; Wu, Bingyi

    2017-01-01

    Fisetin (3,3′,4′,7-tetrahydroxyflavone) is a plant flavonol found in fruits and vegetables that has been reported to inhibit migration and proliferation in several types of cancer. Reactive astrogliosis involves astrocyte migration and proliferation, and contributes to the formation of glial scars in central nervous system (CNS) disorders. However, the effect of fisetin on the migration and proliferation of astrocytes remains unclear. In this study, we found that fisetin inhibited astrocyte migration in a scratch-wound assay and diminished the phosphorylation of focal adhesion kinase (FAK; Tyr576/577 and paxillin (Tyr118). It also suppressed cell proliferation, as indicated by the decreased number of 5-ethynyl-2′-deoxyuridine (EdU)-positive cells, induced cell cycle arrest in the G1 phase, reduced the percentage of cells in the G2 and S phase (as measured by flow cytometry), and decreased cyclin D1 expression, but had no effect on apoptosis. Fisetin also decreased the phosphorylation levels of Akt and extracellular signal-regulated kinase (Erk)1/2, but had no effect on the phosphorylation of p38 mitogen-activated protein kinase (MAPK). These results indicate that fisetin inhibits aggressive cell phenotypes by suppressing cell migration and proliferation via the Akt/Erk signaling pathway. Fisetin may thus have potential for use as a therapeutic strategy targeting reactive astrocytes, which may lead to the inhibition of glial scar formation in vitro. PMID:28204814

  3. Assessment of the tumourigenic and metastatic properties of SK-MEL28 melanoma cells surviving electrochemotherapy with bleomycin

    PubMed Central

    Todorovic, Vesna; Sersa, Gregor; Mlakar, Vid; Glavac, Damjan; Cemazar, Maja

    2012-01-01

    Background Electrochemotherapy is a local treatment combining chemotherapy and electroporation and is highly effective treatment approach for subcutaneous tumours of various histologies. Contrary to surgery and radiation, the effect of electrochemotherapy on metastatic potential of tumour cells has not been extensively studied. The aim of the study was to evaluate the effect of electrochemotherapy with bleomycin on the metastatic potential of human melanoma cells in vitro. Materials and methods Viable cells 48 hours after electrochemotherapy were tested for their ability to migrate and invade through Matrigel coated porous membrane. In addition, microarray analysis and quantitative Real-Time PCR were used to detect changes in gene expression after electrochemotherapy. Results Cell migration and invasion were not changed in melanoma cells surviving electrochemotherapy. Interestingly, only a low number of tumourigenesis related genes was differentially expressed after electrochemotherapy. Conclusions Our data suggest that metastatic potential of human melanoma cells is not affected by electrochemotherapy with bleomycin, confirming safe role of electrochemotherapy in the clinics. PMID:22933978

  4. Assessment of the tumourigenic and metastatic properties of SK-MEL28 melanoma cells surviving electrochemotherapy with bleomycin.

    PubMed

    Todorovic, Vesna; Sersa, Gregor; Mlakar, Vid; Glavac, Damjan; Cemazar, Maja

    2012-03-01

    Electrochemotherapy is a local treatment combining chemotherapy and electroporation and is highly effective treatment approach for subcutaneous tumours of various histologies. Contrary to surgery and radiation, the effect of electrochemotherapy on metastatic potential of tumour cells has not been extensively studied. The aim of the study was to evaluate the effect of electrochemotherapy with bleomycin on the metastatic potential of human melanoma cells in vitro. Viable cells 48 hours after electrochemotherapy were tested for their ability to migrate and invade through Matrigel coated porous membrane. In addition, microarray analysis and quantitative Real-Time PCR were used to detect changes in gene expression after electrochemotherapy. Cell migration and invasion were not changed in melanoma cells surviving electrochemotherapy. Interestingly, only a low number of tumourigenesis related genes was differentially expressed after electrochemotherapy. Our data suggest that metastatic potential of human melanoma cells is not affected by electrochemotherapy with bleomycin, confirming safe role of electrochemotherapy in the clinics.

  5. Distributional dynamics of a vulnerable species in response to past and future climate change: a window for conservation prospects

    PubMed Central

    Bai, Yunjun; Wei, Xueping

    2018-01-01

    Background The ongoing change in climate is predicted to exert unprecedented effects on Earth’s biodiversity at all levels of organization. Biological conservation is important to prevent biodiversity loss, especially for species facing a high risk of extinction. Understanding the past responses of species to climate change is helpful for revealing response mechanisms, which will contribute to the development of effective conservation strategies in the future. Methods In this study, we modelled the distributional dynamics of a ‘Vulnerable’ species, Pseudolarix amabilis, in response to late Quaternary glacial-interglacial cycles and future 2080 climate change using an ecological niche model (MaxEnt). We also performed migration vector analysis to reveal the potential migration of the population over time. Results Historical modelling indicates that the range dynamics of P. amabilis is highly sensitive to climate change and that its long-distance dispersal ability and potential for evolutionary adaption are limited. Compared to the current climatically suitable areas for this species, future modelling showed significant migration northward towards future potential climatically suitable areas. Discussion In combination with the predicted future distribution, the mechanism revealed by the historical response suggests that this species will not be able to fully occupy the future expanded areas of suitable climate or adapt to the unsuitable climate across the future contraction regions. As a result, we suggest assisted migration as an effective supplementary means of conserving this vulnerable species in the face of the unprecedentedly rapid climate change of the 21st century. As a study case, this work highlights the significance of introducing historical perspectives while researching species conservation, especially for currently vulnerable or endangered taxa that once had a wider distribution in geological time. PMID:29362700

  6. Forage plants of an Arctic-nesting herbivore show larger warming response in breeding than wintering grounds, potentially disrupting migration phenology.

    PubMed

    Lameris, Thomas K; Jochems, Femke; van der Graaf, Alexandra J; Andersson, Mattias; Limpens, Juul; Nolet, Bart A

    2017-04-01

    During spring migration, herbivorous waterfowl breeding in the Arctic depend on peaks in the supply of nitrogen-rich forage plants, following a "green wave" of grass growth along their flyway to fuel migration and reproduction. The effects of climate warming on forage plant growth are expected to be larger at the Arctic breeding grounds than in temperate wintering grounds, potentially disrupting this green wave and causing waterfowl to mistime their arrival on the breeding grounds. We studied the potential effect of climate warming on timing of food peaks along the migratory flyway of the Russian population of barnacle geese using a warming experiment with open-top chambers. We measured the effect of 1.0-1.7°C experimental warming on forage plant biomass and nitrogen concentration at three sites along the migratory flyway (temperate wintering site, temperate spring stopover site, and Arctic breeding site) during 2 months for two consecutive years. We found that experimental warming increased biomass accumulation and sped up the decline in nitrogen concentration of forage plants at the Arctic breeding site but not at temperate wintering and stop-over sites. Increasing spring temperatures in the Arctic will thus shorten the food peak of nitrogen-rich forage at the breeding grounds. Our results further suggest an advance of the local food peak in the Arctic under 1-2°C climate warming, which will likely cause migrating geese to mistime their arrival at the breeding grounds, particularly considering the Arctic warms faster than the temperate regions. The combination of a shorter food peak and mistimed arrival is likely to decrease goose reproductive success under climate warming by reducing growth and survival of goslings after hatching.

  7. 3′3-Diindolylmethane inhibits migration, invasion and metastasis of hepatocellular carcinoma by suppressing FAK signaling

    PubMed Central

    Li, Wen-Xue; Chen, Li-Ping; Sun, Min-Ying; Li, Jun-Tao; Liu, Hua-Zhang; Zhu, Wei

    2015-01-01

    Late stage hepatocellular carcinoma (HCC) usually has a low survival rate because it has high potential of metastases and there is no effective cure. 3′3-Diindolylmethane (DIM) is the major product of the acid-catalyzed oligomerization of indole-3-carbinol present in cruciferous vegetables. DIM has been proved to exhibit anticancer properties. In this study, we explored the effects and molecular mechanisms of anti-metastasis of DIM on HCC cells both in vitro and in vivo. We chose two HCC cell lines SMMC-7721 and MHCC-97H that have high potential of invasion. The results showed that DIM inhibited the proliferation, migration and invasion of these two cell lines in vitro. In addition, in vivo study demonstrated that DIM significantly decreased the volumes of SMMC-7721 orthotopic liver tumor and suppressed lung metastasis in nude mice. Focal Adhesion Kinase (FAK) is found over activated in HCC cells. We found that DIM decreased the level of phospho-FAK (Tyr397) both in vitro and in vivo. DIM inhibition of phospho-FAK (Tyr397) led to down-regulation of MMP2/9 and decreased potential of metastasis. DIM also repressed the migration and invasion induced by vitronectin through inactivation of FAK pathway and down-regulation of MMP2/9 in vitro. We also found that pTEN plays a role in down-regulation of FAK by DIM. These results demonstrated that DIM blocks HCC cell metastasis by suppressing tumor cell migration and invasion. The anti-metastasis effect of DIM could be explained to be its down-regulated expression and activation of MMP2/9 partly induced by up-regulation of pTEN and inhibition of phospho-FAK (Tyr397). PMID:26068982

  8. Honey dilution impact on in vitro wound healing: Normoxic and hypoxic condition.

    PubMed

    Chaudhary, Amrita; Bag, Swarnendu; Barui, Ananya; Banerjee, Provas; Chatterjee, Jyotirmoy

    2015-01-01

    Honey is known as a popular healing agent against tropical infections and wounds. However, the effects of honey dilutions on keratinocyte (HaCaT) wound healing under hypoxic condition is still not explored. In this study, we examined whether honey dilution have wound healing potential under hypoxic stress. The antioxidant potential and healing efficacy of honey dilution on in vitro wound of human epidermal keratinocyte (HaCaT cells) under hypoxia (3% O2 ), and normoxia is explored by nitro blue tetrazolium assay. The cell survival % quantified by MTT assay to select four honey dilutions like 10, 1, 0.1, and 0.01 v/v% and the changes in cellular function was observed microscopically. Further, the cell proliferation, migration, cell-cell adhesion, and relevant gene expression were studied by flow cytometry, migration/scratch assay, immunocytochemistry, and reverse transcription-polymerase chain reaction, respectively. The expression pattern of cardinal molecular features viz. E-cadherin, cytoskeletal protein F-actin, p63, and hypoxia marker Hif 1α were examined. Honey dilution in 0.1% v/v combat wound healing limitations in vitro under normoxia and hypoxia (3%). Its wound healing potential was quantified by immunocytochemistry and real-time PCR for the associated molecular features that were responsible for cell proliferation and migration. Our data showed that honey dilution can be effective in hypoxic wound healing. Additionally, it reduced superoxide generation and supplied favorable bioambience for cell proliferation, migration, and differentiation during hypoxic wound healing. These findings may reveal the importance of honey as an alternative and cost effective therapeutic natural product for wound healing in hypoxic condition. © 2015 by the Wound Healing Society.

  9. Distributional dynamics of a vulnerable species in response to past and future climate change: a window for conservation prospects.

    PubMed

    Bai, Yunjun; Wei, Xueping; Li, Xiaoqiang

    2018-01-01

    The ongoing change in climate is predicted to exert unprecedented effects on Earth's biodiversity at all levels of organization. Biological conservation is important to prevent biodiversity loss, especially for species facing a high risk of extinction. Understanding the past responses of species to climate change is helpful for revealing response mechanisms, which will contribute to the development of effective conservation strategies in the future. In this study, we modelled the distributional dynamics of a 'Vulnerable' species, Pseudolarix amabilis , in response to late Quaternary glacial-interglacial cycles and future 2080 climate change using an ecological niche model (MaxEnt). We also performed migration vector analysis to reveal the potential migration of the population over time. Historical modelling indicates that the range dynamics of P. amabilis is highly sensitive to climate change and that its long-distance dispersal ability and potential for evolutionary adaption are limited. Compared to the current climatically suitable areas for this species, future modelling showed significant migration northward towards future potential climatically suitable areas. In combination with the predicted future distribution, the mechanism revealed by the historical response suggests that this species will not be able to fully occupy the future expanded areas of suitable climate or adapt to the unsuitable climate across the future contraction regions. As a result, we suggest assisted migration as an effective supplementary means of conserving this vulnerable species in the face of the unprecedentedly rapid climate change of the 21st century. As a study case, this work highlights the significance of introducing historical perspectives while researching species conservation, especially for currently vulnerable or endangered taxa that once had a wider distribution in geological time.

  10. In Vitro Antitumor Effects of AHR Ligands Aminoflavone (AFP 464) and Benzothiazole (5F 203) in Human Renal Carcinoma Cells.

    PubMed

    Luzzani, Gabriela A; Callero, Mariana A; Kuruppu, Anchala I; Trapani, Valentina; Flumian, Carolina; Todaro, Laura; Bradshaw, Tracey D; Loaiza Perez, Andrea I

    2017-12-01

    We investigated activity and mechanism of action of two AhR ligand antitumor agents, AFP 464 and 5F 203 on human renal cancer cells, specifically examining their effects on cell cycle progression, apoptosis, and migration. TK-10, SN12C, Caki-1, and ACHN human renal cancer cell lines were treated with AFP 464 and 5F 203. We evaluated cytotoxicity by MTS assays, cell cycle arrest, and apoptosis by flow cytometry and corroborated a mechanism of action involving AhR signal transduction activation. Changes in migration properties by wound healing assays were investigated: 5F 203-sensitive cells show decreased migration after treatment, therefore, we measured c-Met phosphorylation by Western blot in these cells. A 5F 203 induced a decrease in cell viability which was more marked than AFP 464. This cytotoxicity was reduced after treatment with the AhR inhibitor α-NF for both compounds indicating AhR signaling activation plays a role in the mechanism of action. A 5F 203 is sequestered by TK-10 cells and induces CYP1A1 expression; 5F 203 potently inhibited migration of TK-10, Caki-1, and SN12C cells, and inhibited c-Met receptor phosphorylation in TK-10 cells. AhR ligand antitumor agents AFP 464 and 5F 203 represent potential new candidates for the treatment of renal cancer. A 5F 203 only inhibited migration of sensitive cells and c-Met receptor phosphorylation in TK-10 cells. c-Met receptor signal transduction is important in migration and metastasis. Therefore, we consider that 5F 203 offers potential for the treatment of metastatic renal carcinoma. J. Cell. Biochem. 118: 4526-4535, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Tumor suppressor berberine binds VASP to inhibit cell migration in basal-like breast cancer.

    PubMed

    Su, Ke; Hu, Pengchao; Wang, Xiaolan; Kuang, Changchun; Xiang, Qingmin; Yang, Fang; Xiang, Jin; Zhu, Shan; Wei, Lei; Zhang, Jingwei

    2016-07-19

    Berberine is a plant-derived compound used in traditional Chinese medicine, which has been shown to inhibit cell proliferation and migration in breast cancer. On the other hand, vasodilator-stimulated phosphoprotein (VASP) promotes actin filament elongation and cell migration. We previously showed that VASP is overexpressed in high-motility breast cancer cells. Here we investigated whether the anti-tumorigenic effects of berberine are mediated by binding VASP in basal-like breast cancer. Our results show that berberine suppresses proliferation and migration of MDA-MB-231 cells as well as tumor growth in MDA-MB-231 nude mouse xenografts. We also show that berberine binds to VASP, inducing changes in its secondary structure and inhibits actin polymerization. Our study reveals the mechanism underlying berberine's inhibition of cell proliferation and migration in basal-like breast cancer, highlighting the use of berberine as a potential adjuvant therapeutic agent.

  12. Tumor suppressor berberine binds VASP to inhibit cell migration in basal-like breast cancer

    PubMed Central

    Wang, Xiaolan; Kuang, Changchun; Xiang, Qingmin; Yang, Fang; Xiang, Jin; Zhu, Shan; Wei, Lei; Zhang, Jingwei

    2016-01-01

    Berberine is a plant-derived compound used in traditional Chinese medicine, which has been shown to inhibit cell proliferation and migration in breast cancer. On the other hand, vasodilator-stimulated phosphoprotein (VASP) promotes actin filament elongation and cell migration. We previously showed that VASP is overexpressed in high-motility breast cancer cells. Here we investigated whether the anti-tumorigenic effects of berberine are mediated by binding VASP in basal-like breast cancer. Our results show that berberine suppresses proliferation and migration of MDA-MB-231 cells as well as tumor growth in MDA-MB-231 nude mouse xenografts. We also show that berberine binds to VASP, inducing changes in its secondary structure and inhibits actin polymerization. Our study reveals the mechanism underlying berberine's inhibition of cell proliferation and migration in basal-like breast cancer, highlighting the use of berberine as a potential adjuvant therapeutic agent. PMID:27322681

  13. 4'-Acetoamido-4-hydroxychalcone, a chalcone derivative, inhibits glioma growth and invasion through regulation of the tropomyosin 1 gene

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

    Ku, Bo Mi; Ryu, Hyung Won; Lee, Yeon Kyung

    2010-11-19

    Research highlights: {yields} 4'-Acetoamido-4-hydroxychalcone (AHC) has anti-cancer property for glioma. {yields} 4'-Acetoamido-4-hydroxychalcone (AHC) increased tropomyosin expreesion through activattion of PKA signaling. {yields} 4'-Acetoamido-4-hydroxychalcone (AHC) inhibits glioma cell migration and invasion. {yields} In vivo administration of 4'-acetoamido-4-hydroxychalcone (AHC) reduced tumor growth. -- Abstract: Chalcones are precursors of flavonoids and have been shown to have anti-cancer activity. Here, we identify the synthetic chalcone derivative 4'-acetoamido-4-hydroxychalcone (AHC) as a potential therapeutic agent for the treatment of glioma. Treatment with AHC reduced glioma cell invasion, migration, and colony formation in a concentration-dependent manner. In addition, AHC inhibited vascular endothelial growth factor-induced migration, invasion, andmore » tube formation in HUVECs. To determine the mechanism underlying the inhibitory effect of AHC on glioma cell invasion and migration, we investigated the effect of AHC on the gene expression change and found that AHC affects actin dynamics in U87MG glioma cells. In actin cytoskeleton regulating system, AHC increased tropomyosin expression and stress fiber formation, probably through activation of PKA. Suppression of tropomyosin expression by siRNA or treatment with the PKA inhibitor H89 reduced the inhibitory effects of AHC on glioma cell invasion and migration. In vivo experiments also showed that AHC inhibited tumor growth in a xenograft mouse tumor model. Together, these data suggest that the synthetic chalcone derivative AHC has potent anti-cancer activity through inhibition of glioma proliferation, invasion, and angiogenesis and is therefore a potential chemotherapeutic candidate for the treatment of glioma.« less

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

    PubMed

    Suresh, Shruthy; Raghu, Dinesh; Karunagaran, Devarajan

    2013-01-01

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

  15. Climate change as a driver for future human migration

    NASA Astrophysics Data System (ADS)

    Chen, M.; Ricke, K.; Caldeira, K.

    2016-12-01

    Human migration is driven by a multitude of factors, both socioeconomic and environmental. However, as impacts of anthropogenic climate change emerge and grow, it is widely conjectured that climate change will induce migration of human populations from areas that are adversely affected by climate change to areas that are less adversely or positively affected by climate change. Both low- and high-frequency climate changes have been empirically linked to migration in areas across the globe, but there has been little global-scale quantitative analysis projecting the scale and geography of climate-motivated migration. Considering temperature and precipitation in isolation from all other factors, here we project climate-driven impacts on the areal-density of human population. From this, we infer potential destinations and origins for the climate-motivated migration. Our results indicate that tropical and sub-tropical countries are the largest likely sources of migrants, with India being the country with the greatest number of potential climate emigrants. Global warming has the potential to motivate hundreds of millions of people to migrate in the coming decades, largely from warm tropical and subtropical countries to cooler temperate countries. Migration decisions will depend on many factors beyond climate; nevertheless our work establishes a foundation for quantifying future climate-motivated migration that can act as a starting point of more comprehensive assessments. The large number of potential climate migrants indicated by our analyses provides additional incentive to reduce greenhouse gas emissions, take adaptive measures, and carefully consider migration policy.

  16. Modeling of thin film GaAs growth

    NASA Technical Reports Server (NTRS)

    Heinbockel, J. H.

    1982-01-01

    A potential scaling Monte Carlo model of crystal growth is developed. The model is a modification of the solid-on-solid method for studying crystal growth in that potentials at surface sites are continuously updated on a time scale reflecting the surface events of migration, incorporation and evaporation. The model allows for B on A type of crystal growth and lattice disregistry by the assignment of potential values at various surface sites. The surface adatoms are periodically assigned a random energy from a Boltzmann distribution and this energy determines whether the adatoms evaporate, migrate or remain stationary during the sampling interval. For each addition or migration of an adatom, the surface potentials are adjusted to reflect the adsorption, migration or desorption potential changes.

  17. Progesterone stimulates the long-distance migration of capacitated ram spermatozoa through viscous media under geotactic condition.

    PubMed

    Martínez-Rodríguez, Carmen; Anel-López, Luis; Alvarez, Mercedes; Ortega-Ferrusola, Cristina; Boixo, Juan Carlos; Peña, Fernando J; Anel, Luis; de Paz, Paulino

    2018-05-15

    Forward progressive motility of spermatozoa is an essential prerequisite for reproductive success, and sperm navigation is assisted by guidance mechanisms that may depend on micro-environmental factors. In the present study, we performed an integrated analysis of long-distance ram sperm migration in vitro that combined two environmental factors (10 μM progesterone and a geotactic effect) and the physiological status of the cells (capacitation treatment). A penetration assay was used in which spermatozoa had to travel 20 mm in a viscous medium (two media of differing viscosity: acrylamide and hyaluronic acid) through a tube device. The number of migrating spermatozoa, the physiology of the cells (motility analyzed using a CASA system; acrosomal status, viability and active mitochondria evaluated by flow cytometry; DNA fragmentation index calculated by quantitative PCR) and the morphometry of sperm heads (performed using an image analysis system) were evaluated after long-distance sperm migration. Ram sperm capacitation significantly stimulates cell migration through viscous media under geotactic conditions, and this effect is enhanced by progesterone induction. The rheological characteristics of viscous media have a marked impact on ram sperm migration, and acrylamide more favorably facilitates navigation over a large distance. The migrating spermatozoa are morphologically better adapted (high ellipticity) for displacement in viscous media and exhibit remarkably depleted mitochondrial membrane potential. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Job Scheduling in a Heterogeneous Grid Environment

    NASA Technical Reports Server (NTRS)

    Shan, Hong-Zhang; Smith, Warren; Oliker, Leonid; Biswas, Rupak

    2004-01-01

    Computational grids have the potential for solving large-scale scientific problems using heterogeneous and geographically distributed resources. However, a number of major technical hurdles must be overcome before this potential can be realized. One problem that is critical to effective utilization of computational grids is the efficient scheduling of jobs. This work addresses this problem by describing and evaluating a grid scheduling architecture and three job migration algorithms. The architecture is scalable and does not assume control of local site resources. The job migration policies use the availability and performance of computer systems, the network bandwidth available between systems, and the volume of input and output data associated with each job. An extensive performance comparison is presented using real workloads from leading computational centers. The results, based on several key metrics, demonstrate that the performance of our distributed migration algorithms is significantly greater than that of a local scheduling framework and comparable to a non-scalable global scheduling approach.

  19. Doxycycline reduces the migration of tuberous sclerosis complex-2 null cells - effects on RhoA-GTPase and focal adhesion kinase

    PubMed Central

    Ng, Ho Yin; Oliver, Brian Gregory George; Burgess, Janette Kay; Krymskaya, Vera P; Black, Judith Lee; Moir, Lyn M

    2015-01-01

    Lymphangioleiomyomatosis (LAM) is associated with dysfunction of the tuberous sclerosis complex (TSC) leading to enhanced cell proliferation and migration. This study aims to examine whether doxycycline, a tetracycline antibiotic, can inhibit the enhanced migration of TSC2-deficient cells, identify signalling pathways through which doxycycline works and to assess the effectiveness of combining doxycycline with rapamycin (mammalian target of rapamycin complex 1 inhibitor) in controlling cell migration, proliferation and wound closure. TSC2-positive and TSC2-negative mouse embryonic fibroblasts (MEF), 323-TSC2-positive and 323-TSC2-null MEF and Eker rat uterine leiomyoma (ELT3) cells were treated with doxycycline or rapamycin alone, or in combination. Migration, wound closure and proliferation were assessed using a transwell migration assay, time-lapse microscopy and manual cell counts respectively. RhoA-GTPase activity, phosphorylation of p70S6 kinase (p70S6K) and focal adhesion kinase (FAK) in TSC2-negative MEF treated with doxycycline were examined using ELISA and immunoblotting techniques. The enhanced migration of TSC2-null cells was reduced by doxycycline at concentrations as low as 20 pM, while the rate of wound closure was reduced at 2–59 μM. Doxycycline decreased RhoA-GTPase activity and phosphorylation of FAK in these cells but had no effect on the phosphorylation of p70S6K, ERK1/2 or AKT. Combining doxycycline with rapamycin significantly reduced the rate of wound closure at lower concentrations than achieved with either drug alone. This study shows that doxycycline inhibits TSC2-null cell migration. Thus doxycycline has potential as an anti-migratory agent in the treatment of diseases with TSC2 dysfunction. PMID:26282580

  20. Installation Restoration Program. Remedial Investigation Report. Minnesota Air National Guard Base Duluth International Airport, Duluth, Minnesota. Volume 3

    DTIC Science & Technology

    1990-01-01

    Migration 5-7 5.2.3 Contaminant Persistence 5-8 5.2.4 Contaminant Mobility and Migration 5-9 5.2.4.1 Contaminant Migration in Surface Water 5-9...of Contaminant 5-11 5.3.2 Potential Routes of Migration 5-11 5.3.3 Contaminant Persistence 5-12 5.3.4 Contaminant Mobility and Migration 5-13 5.3.4.1...Contaminant Mobility and Migration in Soil 5-18 5.6 CONTAMINANT FATE AND TRANSPORT 5-18 AT SITE 10 5.6.1 Summary of Contaminants 5-18 5.6.2 Potential Routes

  1. Modeling Invasion Dynamics with Spatial Random-Fitness Due to Micro-Environment

    PubMed Central

    Manem, V. S. K.; Kaveh, K.; Kohandel, M.; Sivaloganathan, S.

    2015-01-01

    Numerous experimental studies have demonstrated that the microenvironment is a key regulator influencing the proliferative and migrative potentials of species. Spatial and temporal disturbances lead to adverse and hazardous microenvironments for cellular systems that is reflected in the phenotypic heterogeneity within the system. In this paper, we study the effect of microenvironment on the invasive capability of species, or mutants, on structured grids (in particular, square lattices) under the influence of site-dependent random proliferation in addition to a migration potential. We discuss both continuous and discrete fitness distributions. Our results suggest that the invasion probability is negatively correlated with the variance of fitness distribution of mutants (for both advantageous and neutral mutants) in the absence of migration of both types of cells. A similar behaviour is observed even in the presence of a random fitness distribution of host cells in the system with neutral fitness rate. In the case of a bimodal distribution, we observe zero invasion probability until the system reaches a (specific) proportion of advantageous phenotypes. Also, we find that the migrative potential amplifies the invasion probability as the variance of fitness of mutants increases in the system, which is the exact opposite in the absence of migration. Our computational framework captures the harsh microenvironmental conditions through quenched random fitness distributions and migration of cells, and our analysis shows that they play an important role in the invasion dynamics of several biological systems such as bacterial micro-habitats, epithelial dysplasia, and metastasis. We believe that our results may lead to more experimental studies, which can in turn provide further insights into the role and impact of heterogeneous environments on invasion dynamics. PMID:26509572

  2. Effects of non-steroidal anti-inflammatory drugs on proliferation, differentiation and migration in equine mesenchymal stem cells.

    PubMed

    Müller, Maike; Raabe, Oksana; Addicks, Klaus; Wenisch, Sabine; Arnhold, Stefan

    2011-03-01

    In equine medicine, stem cell therapies for orthopaedic diseases are routinely accompanied by application of NSAIDs (non-steroidal anti-inflammatory drugs). Thus, it has to be analysed how NSAIDs actually affect the growth and differentiation potential of MSCs (mesenchymal stem cells) in vitro in order to predict the influence of NSAIDs such as phenylbutazone, meloxicam, celecoxib and flunixin on MSCs after grafting in vivo. The effects of NSAIDs were evaluated regarding cell viability and proliferation. Additionally, the multilineage differentiation capacity and cell migration was analysed. NSAIDs at lower concentrations (0.1-1 μM for celecoxib and meloxicam and 10-50 μM for flunixin) exert a positive effect on cell proliferation and migration, while at higher concentrations (10-200 μM for celecoxib and meloxicam and 100-1000 μM for flunixin and phenylbutazone), there is rather a negative influence. While there is hardly any influence on the adipogenic as well as on the chondrogenic MSC differentiation, the osteogenic differentiation potential, as demonstrated with the von Kossa staining, is significantly disturbed. Thus, it can be concluded that the effects of NSAIDs on MSCs are largely dependent on the concentrations used. Additionally, for some differentiation lineages, also the choice of NSAID is critical.

  3. Celastrol Attenuates the Invasion and Migration and Augments the Anticancer Effects of Bortezomib in a Xenograft Mouse Model of Multiple Myeloma

    PubMed Central

    Shanmugam, Muthu K.; Ahn, Kwang S.; Lee, Jong H.; Kannaiyan, Radhamani; Mustafa, Nurulhuda; Manu, Kanjoormana A.; Siveen, Kodappully S.; Sethi, Gautam; Chng, Wee J.; Kumar, Alan P.

    2018-01-01

    Several lines of evidence have demonstrated that deregulated activation of NF-κB plays a pivotal role in the initiation and progression of a variety of cancers including multiple myeloma (MM). Therefore, novel molecules that can effectively suppress deregulated NF-κB upregulation can potentially reduce MM growth. In this study, the effect of celastrol (CSL) on patient derived CD138+ MM cell proliferation, apoptosis, cell invasion, and migration was investigated. In addition, we studied whether CSL can potentiate the apoptotic effect of bortezomib, a proteasome inhibitor in MM cells and in a xenograft mouse model. We found that CSL significantly reduced cell proliferation and enhanced apoptosis when used in combination with bortezomib and upregulated caspase-3 in these cells. CSL also inhibited invasion and migration of MM cells through the suppression of constitutive NF-κB activation and expression of downstream gene products such as CXCR4 and MMP-9. Moreover, CSL when administered either alone or in combination with bortezomib inhibited MM tumor growth and decreased serum IL-6 and TNF-α levels. Overall, our results suggest that CSL can abrogate MM growth both in vitro and in vivo and may serve as a useful pharmacological agent for the treatment of myeloma and other hematological malignancies. PMID:29773987

  4. 40 CFR 264.601 - Environmental performance standards.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... other vegetation; (8) The potential for health risks caused by human exposure to waste constituents; and... effects on human health or the environment due to migration of waste constituents in surface water, or... human exposure to waste constituents; and (11) The potential for damage to domestic animals, wildlife...

  5. 40 CFR 264.601 - Environmental performance standards.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... other vegetation; (8) The potential for health risks caused by human exposure to waste constituents; and... effects on human health or the environment due to migration of waste constituents in surface water, or... human exposure to waste constituents; and (11) The potential for damage to domestic animals, wildlife...

  6. 40 CFR 264.601 - Environmental performance standards.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... other vegetation; (8) The potential for health risks caused by human exposure to waste constituents; and... effects on human health or the environment due to migration of waste constituents in surface water, or... human exposure to waste constituents; and (11) The potential for damage to domestic animals, wildlife...

  7. 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.

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

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

    He Yingbo; Chang Guodong; Zhan Shunli

    2008-06-06

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

  9. Oxygen Migration and Local Structural Changes with Schottky Defects in Pure Zirconium Oxide Crystals

    NASA Astrophysics Data System (ADS)

    Terada, Yayoi; Mohri, Tetsuo

    2018-05-01

    By employing the Buckingham potential, we performed classical molecular-dynamics computer simulations at constant pressure and temperature for a pure ZrO2 crystal without any vacancies and for a pure ZrO2 crystal containing zirconium vacancies and oxygen vacancies. We examined the positions of atoms and vacancies in the steady state, and we investigated the migration behavior of atoms and the local structure of vacancies of the pure ZrO2 crystal. We found that Schottky defects (aggregates consisting of one zirconium vacancy with an effective charge of -4 and two oxygen vacancies each with an effective charge of +2 to maintain charge neutrality) are the main defects formed in the steady state in cubic ZrO2, and that oxygen migration occurs through a mechanism involving vacancies on the oxygen sublattice near such defects. We also found that several oxygen atoms near each defect are displaced far from the sublattice site and induce oxygen migration.

  10. 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.

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

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

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

    1984-08-01

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

  12. Prevention of polydimethylsiloxane microsphere migration using a mussel-inspired polydopamine coating for potential application in injection therapy.

    PubMed

    Chung, Eun-Jae; Jun, Dae-Ryong; Kim, Dong-Wook; Han, Mi-Jung; Kwon, Tack-Kyun; Choi, Sung-Wook; Kwon, Seong Keun

    2017-01-01

    The use of injectable bulking agents is a feasible alternative procedure for conventional surgical therapy. In this study, poly(dimethylsiloxane) (PDMS) microspheres coated with polydopamine (PDA) were developed as a potential injection agent to prevent migration in vocal fold. Uniform PDMS microspheres are fabricated using a simple fluidic device and then coated with PDA. Cell attachment test reveals that the PDA-coated PDMS (PDA-PDMS) substrate favors cell adhesion and attachment. The injected PDA-PDMS microspheres persist without migration on reconstructed axial CT images, whereas, pristine PDMS locally migrates over a period of 12 weeks. The gross appearance of the implants retrieved at 4, 8, 12 and 34 weeks indicates that the PDA-PDMS group maintained their original position without significant migration until 34 weeks after injection. By contrast, there is diffuse local migration of the pristine PDMS group from 4 weeks after injection. The PDA-coated PDMS microspheres can potentially be used as easily injectable, non-absorbable filler without migration.

  13. Prevention of polydimethylsiloxane microsphere migration using a mussel-inspired polydopamine coating for potential application in injection therapy

    PubMed Central

    Kim, Dong-Wook; Han, Mi-Jung; Kwon, Tack-Kyun; Choi, Sung-Wook

    2017-01-01

    The use of injectable bulking agents is a feasible alternative procedure for conventional surgical therapy. In this study, poly(dimethylsiloxane) (PDMS) microspheres coated with polydopamine (PDA) were developed as a potential injection agent to prevent migration in vocal fold. Uniform PDMS microspheres are fabricated using a simple fluidic device and then coated with PDA. Cell attachment test reveals that the PDA-coated PDMS (PDA-PDMS) substrate favors cell adhesion and attachment. The injected PDA-PDMS microspheres persist without migration on reconstructed axial CT images, whereas, pristine PDMS locally migrates over a period of 12 weeks. The gross appearance of the implants retrieved at 4, 8, 12 and 34 weeks indicates that the PDA-PDMS group maintained their original position without significant migration until 34 weeks after injection. By contrast, there is diffuse local migration of the pristine PDMS group from 4 weeks after injection. The PDA-coated PDMS microspheres can potentially be used as easily injectable, non-absorbable filler without migration. PMID:29095854

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

    Jin, Feng-zhen; Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, PR China.; Yu, Chao

    O-GlcNAcylation is a dynamic and reversible posttranslational modification of nuclear and cytoplasmic proteins. In recent years, the roles of O-GlcNAcylation in several human malignant tumors have been investigated, and O-GlcNAcylation was found to be linked to cellular features relevant to metastasis. In this study, we modeled four diverse ovarian cancer cells and investigated the effects of O-GlcNAcylation on ovarian cancer cell migration. We found that total O-GlcNAcylation level was elevated in HO-8910PM cells compared to OVCAR3 cells. Additionally, through altering the total O-GlcNAcylation level by OGT silencing or OGA inhibition, we found that the migration of OVCAR3 cells was dramaticallymore » enhanced by PUGNAc and Thiamet G treatment, and the migration ability of HO-8910PM cells was significantly inhibited by OGT silencing. Furthermore, we also found that the expression of E-cadherin, an O-GlcNAcylated protein in ovarian cancer cells, was reduced by OGA inhibition in OVCAR3 cells and elevated by OGT silencing in HO-8910PM cells. These results indicate that O-GlcNAcylation could enhance ovarian cancer cell migration and decrease the expression of E-cadherin. Our studies also suggest that O-GlcNAcylation might become another potential target for the therapy of ovarian cancer. -- Highlights: • We examine the migration potential of diverse ovarian cancer cells. • We examine the total O-GlcNAcylation level of diverse ovarian cancer cells. • Increasing O-GlcNAcylation level will enhance the migration of ovarian cancer cells. • Reducing O-GlcNAcylation level will inhibit the migration of ovarian cancer cells. • The mechanism explains O-GlcNAcylation enhance ovarian cancer cell migration.« less

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

    PubMed

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

    2017-12-01

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

  16. Overexpression of microRNA-375 impedes platelet-derived growth factor-induced proliferation and migration of human fetal airway smooth muscle cells by targeting Janus kinase 2.

    PubMed

    Ji, Yamei; Yang, Xin; Su, Huixia

    2018-02-01

    The abnormal proliferation and migration of airway smooth muscle (ASM) cells play a critical role in airway remodeling during the development of asthma. MicroRNAs (miRNAs) have emerged as critical regulators of ASM cell proliferation and migration in airway remodeling. In this study, we aimed to investigate the potential role of miR-375 in the regulation of platelet-derived growth factor (PDGF)-induced fetal ASM cell proliferation and migration. Our results showed that miR-375 expression was significantly decreased in fetal ASM cells that were treated with PDGF. Functional data showed that overexpression of miR-375 inhibited the proliferation and migration of fetal ASM cells, whereas inhibition of miR-375 enhanced the proliferation and migration of fetal ASM cells. The results of bioinformatics analysis and a dual-luciferase reporter assay showed that miR-375 binds directly to the 3'-untranslated region of Janus kinase 2 (JAK2). Further data confirmed that miR-375 negatively regulates the expression of JAK2 in fetal ASM cells. Moreover, miR-375 also impeded the PDGF-induced activation of signal transducer and activator of transcription 3 (STAT3) in fetal ASM cells. However, restoration of JAK2 expression partially reversed the inhibitory effect of miR-375 on fetal ASM cell proliferation and migration. Overall, our results demonstrate that miR-375 inhibits fetal ASM cell proliferation and migration by targeting JAK2/STAT3 signaling. Our study provides a potential therapeutic target for the development of novel treatment strategies for pediatric asthma. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Seasonally dynamic diel vertical migrations of Mysis diluviana, coregonine fishes, and siscowet lake trout in the pelagia of western Lake Superior

    USGS Publications Warehouse

    Ahrenstorff, Tyler D.; Hrabik, Thomas R.; Stockwell, Jason D.; Yule, Daniel L.; Sass, Greg G.

    2011-01-01

    Diel vertical migrations are common among many aquatic species and are often associated with changing light levels. The underlying mechanisms are generally attributed to optimizing foraging efficiency or growth rates and avoiding predation risk (μ). The objectives of this study were to (1) assess seasonal and interannual changes in vertical migration patterns of three trophic levels in the Lake Superior pelagic food web and (2) examine the mechanisms underlying the observed variability by using models of foraging, growth, and μ. Our results suggest that the opossum shrimp Mysis diluviana, kiyi Coregonus kiyi, and siscowet lake trout Salvelinus namaycush migrate concurrently during each season, but spring migrations are less extensive than summer and fall migrations. In comparison with M. diluviana, kiyis, and siscowets, the migrations by ciscoes C. artedi were not as deep in the water column during the day, regardless of season. Foraging potential and μ probably drive the movement patterns of M. diluviana, while our modeling results indicate that movements by kiyis and ciscoes are related to foraging opportunity and growth potential and receive a lesser influence from μ. The siscowet is an abundant apex predator in the pelagia of Lake Superior and probably undertakes vertical migrations in the water column to optimize foraging efficiency and growth. The concurrent vertical movement patterns of most species are likely to facilitate nutrient transport in this exceedingly oligotrophic ecosystem, and they demonstrate strong linkages between predators and prey. Fishery management strategies should use an ecosystem approach and should consider how altering the densities of long-lived top predators produces cascading effects on the nutrient cycling and energy flow in lower trophic levels.

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

    Burgess, Antony W., E-mail: burgess@ludwig.edu.au; Faux, Maree C.; Layton, Meredith J.

    In this brief overview we discuss the association between Wnt signaling and colon cell biology and tumorigenesis. Our current understanding of the role of Apc in the {beta}-catenin destruction complex is compared with potential roles for Apc in cell adhesion and migration. The requirement for phosphorylation in the proteasomal-mediated degradation of {beta}-catenin is contrasted with roles for phospho-{beta}-catenin in the activation of transcription, cell adhesion and migration. The synergy between Myb and {beta}-catenin regulation of transcription in crypt stem cells during Wnt signaling is discussed. Finally, potential effects of growth factor regulatory systems, Apc or truncated-Apc on crypt morphogenesis, stemmore » cell localization and crypt fission are considered.« less

  19. Ring-Shaped Microlanes and Chemical Barriers as a Platform for Probing Single-Cell Migration.

    PubMed

    Schreiber, Christoph; Segerer, Felix J; Wagner, Ernst; Roidl, Andreas; Rädler, Joachim O

    2016-05-31

    Quantification and discrimination of pharmaceutical and disease-related effects on cell migration requires detailed characterization of single-cell motility. In this context, micropatterned substrates that constrain cells within defined geometries facilitate quantitative readout of locomotion. Here, we study quasi-one-dimensional cell migration in ring-shaped microlanes. We observe bimodal behavior in form of alternating states of directional migration (run state) and reorientation (rest state). Both states show exponential lifetime distributions with characteristic persistence times, which, together with the cell velocity in the run state, provide a set of parameters that succinctly describe cell motion. By introducing PEGylated barriers of different widths into the lane, we extend this description by quantifying the effects of abrupt changes in substrate chemistry on migrating cells. The transit probability decreases exponentially as a function of barrier width, thus specifying a characteristic penetration depth of the leading lamellipodia. Applying this fingerprint-like characterization of cell motion, we compare different cell lines, and demonstrate that the cancer drug candidate salinomycin affects transit probability and resting time, but not run time or run velocity. Hence, the presented assay allows to assess multiple migration-related parameters, permits detailed characterization of cell motility, and has potential applications in cell biology and advanced drug screening.

  20. Escin suppresses migration and invasion involving the alteration of CXCL16/CXCR6 axis in human gastric adenocarcinoma AGS cells.

    PubMed

    Lee, Hyun Sook; Hong, Ji Eun; Kim, Eun Ji; Kim, Sun Hyo

    2014-01-01

    Escin, a natural mixture of triterpene saponins isolated from horse chestnut, has been reported to possess anticancer activity in many human cancer cells. However, the effect of escin on the metastasis has not been studied. The present study examined the effect of escin on the migration and invasion of AGS human gastric cancer cells. To examine the effects of escin on metastatic capacities of gastric cancer cells, AGS cells were cultured in the presence of 0-4 μmol/L escin. Escin inhibited cell migration and invasion in AGS cells. However, escin did not affect the viability of these cells at these concentrations. The chemokine receptor and its ligands play an important role in cancer metastasis. Escin decreased the production of soluble C-X-C motif chemokine (CXCL)16 but increased the expression of trans-membranous CXCL16. The expression of C-X-C chemokine receptor (CXCR)6 was not affected by escin treatment. Exogenous CXCL16 reversed escin-induced migration inhibition. In addition, escin inhibited the phosphorylation of focal adhesion kinase and Akt. These results demonstrate that escin inhibited the migration and invasion of AGS cells, which is associated with altered CXCL16/CXCR6 axis. These findings suggest that escin has potential as an antimetastatic agent in gastric cancer.

  1. 40 CFR 264.90 - Applicability.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... care period; or (4) The Regional Administrator finds that there is no potential for migration of liquid... margin of safety in the prediction of potential migration of liquid, the owner or operator must base any predictions made under this paragraph on assumptions that maximize the rate of liquid migration. (5) He...

  2. 40 CFR 264.90 - Applicability.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... care period; or (4) The Regional Administrator finds that there is no potential for migration of liquid... margin of safety in the prediction of potential migration of liquid, the owner or operator must base any predictions made under this paragraph on assumptions that maximize the rate of liquid migration. (5) He...

  3. Human amniotic epithelial stem cells promote wound healing by facilitating migration and proliferation of keratinocytes via ERK, JNK and AKT signaling pathways.

    PubMed

    Zhao, Bin; Liu, Jia-Qi; Zheng, Zhao; Zhang, Jun; Wang, Shu-Yue; Han, Shi-Chao; Zhou, Qin; Guan, Hao; Li, Chao; Su, Lin-Lin; Hu, Da-Hai

    2016-07-01

    Wound healing is a highly orchestrated physiological process consisting in a complex interaction of cellular and biochemical events. Human amniotic epithelial stem cells (HAESCs) have been shown to be an attractive resource for wound healing because they are primitive stem cells. However, the exact effects of amnion-derived stem cells on the migration or proliferation of keratinocytes and their potential mechanism are not fully understood. We have found that HAESCs accelerate the migration of keratinocytes and induce a remarkable increase in the activity of phospho-ERK, phospho-JNK, and phospho-AKT, the blockade of which by their specific inhibitors significantly inhibits migration induced by HAESC-conditioned medium (CM). Furthermore, the co-culture of keratinocytes with HAESCs up-regulates the expression levels of cell proliferation proteins Cyclin D1, Cyclin D3 and Mdm2. In vivo animal experiments have shown that HAESC-CM improves wound healing, whereas blockade with ERK, JNK and AKT inhibitors significantly impairs wound healing. Taken together, these results reveal, for the first time, that HAESCs promote wound healing by facilitating the migration and proliferation of keratinocytes via ERK, JNK and AKT signaling pathways and might be a potential therapy in skin wound healing.

  4. CRKL knockdown promotes in vitro proliferation, migration and invasion, in vivo tumor malignancy and lymph node metastasis of murine hepatocarcinoma Hca-P cells.

    PubMed

    Shi, Ji; Meng, Longlong; Sun, Ming-Zhong; Guo, Chunmei; Sun, Xujuan; Lin, Qiuyue; Liu, Shuqing

    2015-04-01

    Our previous study (Biomed Pharmacother 2015;69:11) demonstrated that the over-expression of CRKL, a chicken tumor virus number 10 regulator of kinase-like protein, suppresses in vitro proliferation, invasion and migration of murine hepatocarcinoma Hca-P cell, a murine HCC cell with lymph node metastatic (LNM) rate of ∼25%. In current work, we investigated the effects of CRKL knockdown on the in vitro cell proliferation, migration and invasion, and on the in vivo tumor malignancy and LNM rate and level for Hca-P cells. Western blotting assay indicated that CRKL was down-regulated by ∼90% in a monoclonal CrkL-shRNA-transfected Hca-P cells. Compared with Hca-P and unrelated-shRNA-transfected Hca-P cell, the in vitro proliferation, migration and invasion potentials were significantly enhanced following CRKL stable deregulation. CRKL knock-down significantly promoted the tumorigenicity malignancy, LNM rates and level of Hca-P-transplanted mice. Consistent with our previous work, it can be concluded CRKL plays an important role in hepatocarcinoma cell proliferation, invasion and migration as well hepatocarcinoma malignancy and metastasis. It functions as a potential tumor suppressor in hepatocarcinoma. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  5. The effect on cardiovascular risk factors of migration from rural to urban areas in Peru: PERU MIGRANT Study

    PubMed Central

    Miranda, J Jaime; Gilman, Robert H; García, Héctor H; Smeeth, Liam

    2009-01-01

    Background Mass-migration observed in Peru from the 1970s occurred because of the need to escape from politically motivated violence and work related reasons. The majority of the migrant population, mostly Andean peasants from the mountainous areas, tends to settle in clusters in certain parts of the capital and their rural environment could not be more different than the urban one. Because the key driver for migration was not the usual economic and work-related reasons, the selection effects whereby migrants differ from non-migrants are likely to be less prominent in Peru. Thus the Peruvian context offers a unique opportunity to test the effects of migration. Methods/Design The PERU MIGRANT (PEru's Rural to Urban MIGRANTs) study was designed to investigate the magnitude of differences between rural-to-urban migrant and non-migrant groups in specific CVD risk factors. For this, three groups were selected: Rural, people who have always have lived in a rural environment; Rural-urban, people who migrated from rural to urban areas; and, Urban, people who have always lived in a urban environment. Discussion Overall response rate at enrolment was 73.2% and overall response rate at completion of the study was 61.6%. A rejection form was obtained in 282/323 people who refused to take part in the study (87.3%). Refusals did not differ by sex in rural and migrant groups, but 70% of refusals in the urban group were males. In terms of age, most refusals were observed in the oldest age-group (>60 years old) in all study groups. The final total sample size achieved was 98.9% of the target sample size (989/1000). Of these, 52.8% (522/989) were females. Final size of the rural, migrant and urban study groups were 201, 589 and 199 urban people, respectively. Migrant's average age at first migration and years lived in an urban environment were 14.4 years (IQR 10–17) and 32 years (IQR 25–39), respectively. This paper describes the PERU MIGRANT study design together with a critical analysis of the potential for bias and confounding in migrant studies, and strategies for reducing these problems. A discussion of the potential advantages provided by the case of migration in Peru to the field of migration and health is also presented. PMID:19505331

  6. The effect of pulsed electric fields on the electrotactic migration of human neural progenitor cells through the involvement of intracellular calcium signaling.

    PubMed

    Hayashi, Hisamitsu; Edin, Fredrik; Li, Hao; Liu, Wei; Rask-Andersen, Helge

    2016-12-01

    Endogenous electric fields (EFs) are required for the physiological control of the central nervous system development. Application of the direct current EFs to neural stem cells has been studied for the possibility of stem cell transplantation as one of the therapies for brain injury. EFs generated within the nervous system are often associated with action potentials and synaptic activity, apparently resulting in a pulsed current in nature. The aim of this study is to investigate the effect of pulsed EF, which can reduce the cytotoxicity, on the migration of human neural progenitor cells (hNPCs). We applied the mono-directional pulsed EF with a strength of 250mV/mm to hNPCs for 6h. The migration distance of the hNPCs exposed to pulsed EF was significantly greater compared with the control not exposed to the EF. Pulsed EFs, however, had less of an effect on the migration of the differentiated hNPCs. There was no significant change in the survival of hNPCs after exposure to the pulsed EF. To investigate the role of Ca 2+ signaling in electrotactic migration of hNPCs, pharmacological inhibition of Ca 2+ channels in the EF-exposed cells revealed that the electrotactic migration of hNPCs exposed to Ca 2+ channel blockers was significantly lower compared to the control group. The findings suggest that the pulsed EF induced migration of hNPCs is partly influenced by intracellular Ca 2+ signaling. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Effects of abdominally implanted radiotransmitters with percutaneous antennas on migration, reproduction, and survival of Canada geese

    USGS Publications Warehouse

    Hupp, Jerry W.; Pearce, John M.; Mulcahy, Daniel M.; Miller, David A.

    2006-01-01

    Abdominally implanted radiotransmitters with percutaneous antennas are increasingly used to monitor movements, survival, and reproduction of waterbirds. However, there has been relatively little assessment of the effects of such radios on avian demographic parameters or migration. We implanted either a 26- or 35-g abdominal transmitter with percutaneous antenna in 198 adult female lesser Canada geese (Branta canadensis parvipes) in Anchorage, Alaska during 2000 and 2001. We compared migration chronology, reproductive effort, and survival of radiomarked females to 118 control females marked with leg bands. Arrival dates following spring migration were similar among females in different treatments in 2001. However, in 2002, wind direction during late migration was less favorable, and arrival of females with 35-g radiotransmitters lagged 1–2 days behind that of control females. Nest initiation dates, clutch size, and mean egg volume were similar for 152 nests of females that lacked radios and 62 nests of radiomarked females. Estimated nesting propensity for females with operable radiotransmitters was 61% and 72% in 2001 and 2002, respectively. Apparent annual survival (ϕ = 0.82, 95% confidence interval: 0.76 to 0.87) was similar among treatments in the first year after geese were marked. In the second and third years after marking, model-averaged estimates for survival of females with large radiotransmitters were 10% lower than estimates for control females. However, the effect of large radios on long-term survival was equivocal because of uncertainty surrounding treatment estimates. We conclude that abdominally implanted radiotransmitters with percutaneous antennas had small effects on migration chronology but no apparent effects on fecundity. Abdominal transmitters can provide unbiased estimates of anserine survival in the first year after deployment. Because of the potentially greater effects of larger transmitters on migration and long-term survival, we recommend that biologists minimize the size of implanted transmitters and deploy radios with caution if long-term survival of marked birds is a concern.

  8. Quantifying the roles of random motility and directed motility using advection-diffusion theory for a 3T3 fibroblast cell migration assay stimulated with an electric field.

    PubMed

    Simpson, Matthew J; Lo, Kai-Yin; Sun, Yung-Shin

    2017-03-17

    Directed cell migration can be driven by a range of external stimuli, such as spatial gradients of: chemical signals (chemotaxis); adhesion sites (haptotaxis); or temperature (thermotaxis). Continuum models of cell migration typically include a diffusion term to capture the undirected component of cell motility and an advection term to capture the directed component of cell motility. However, there is no consensus in the literature about the form that the advection term takes. Some theoretical studies suggest that the advection term ought to include receptor saturation effects. However, others adopt a much simpler constant coefficient. One of the limitations of including receptor saturation effects is that it introduces several additional unknown parameters into the model. Therefore, a relevant research question is to investigate whether directed cell migration is best described by a simple constant tactic coefficient or a more complicated model incorporating saturation effects. We study directed cell migration using an experimental device in which the directed component of the cell motility is driven by a spatial gradient of electric potential, which is known as electrotaxis. The electric field (EF) is proportional to the spatial gradient of the electric potential. The spatial variation of electric potential across the experimental device varies in such a way that there are several subregions on the device in which the EF takes on different values that are approximately constant within those subregions. We use cell trajectory data to quantify the motion of 3T3 fibroblast cells at different locations on the device to examine how different values of the EF influences cell motility. The undirected (random) motility of the cells is quantified in terms of the cell diffusivity, D, and the directed motility is quantified in terms of a cell drift velocity, v. Estimates D and v are obtained under a range of four different EF conditions, which correspond to normal physiological conditions. Our results suggest that there is no anisotropy in D, and that D appears to be approximately independent of the EF and the electric potential. The drift velocity increases approximately linearly with the EF, suggesting that the simplest linear advection term, with no additional saturation parameters, provides a good explanation of these physiologically relevant data. We find that the simplest linear advection term in a continuum model of directed cell motility is sufficient to describe a range of different electrotaxis experiments for 3T3 fibroblast cells subject to normal physiological values of the electric field. This is useful information because alternative models that include saturation effects involve additional parameters that need to be estimated before a partial differential equation model can be applied to interpret or predict a cell migration experiment.

  9. Effects of siRNA-mediated knockdown of jumonji domain containing 2A on proliferation, migration and invasion of the human breast cancer cell line MCF-7

    PubMed Central

    LI, BEI-XU; LUO, CHENG-LIANG; LI, HUI; YANG, PENG; ZHANG, MING-CHANG; XU, HONG-MEI; XU, HONG-FEI; SHEN, YI-WEN; XUE, AI-MIN; ZHAO, ZI-QIN

    2012-01-01

    Jumonji domain containing 2A (JMJD2A) is a potential cancer-associated gene that may be involved in human breast cancer. The present study aimed to investigate suppressive effects on the MCF-7 human breast cancer cell line by transfection with JMJD2A-specific siRNA. Quantitative real-time PCR and western blot analysis were used to detect the expression levels of JMJD2A. Flow cytometric (FCM) analysis and WST-8 assay were used to evaluate cell proliferation. Boyden chambers were used in cell migration and invasion assays to evaluate the cell exercise capacity. Expression levels of JMJD2A mRNA and protein in the siRNA group were both downregulated successfully by transfection. FCM results showed that the percentage of cells in the G0/G1 phase in the siRNA group was significantly greater than that in the blank (P<0.05) and negative control groups (P<0.05). Additionally, the mean absorbance in the siRNA group was significantly lower (P<0.05), as observed by WST-8 assay. Moreover, a decreased number of migrated cells in the siRNA group was observed (P<0.05) using a cell migration and invasion assay. These data indicated that knockdown of JMJD2A may cause inhibition of proliferation, migration and invasion of MCF-7 cells. This study provides a new perspective in understanding the molecular mechanisms underlying the progression of breast cancer and offers a potential therapeutic target for breast cancer. PMID:23170139

  10. 3-Mercaptopyruvate Sulfurtransferase, Not Cystathionine β-Synthase Nor Cystathionine γ-Lyase, Mediates Hypoxia-Induced Migration of Vascular Endothelial Cells.

    PubMed

    Tao, Beibei; Wang, Rui; Sun, Chen; Zhu, Yichun

    2017-01-01

    Hypoxia-induced angiogenesis is a common phenomenon in many physiological and patho-physiological processes. However, the potential differential roles of three hydrogen sulfide producing systems cystathionine γ-lyase (CSE)/H 2 S, cystathionine β-synthase (CBS)/H 2 S, and 3-mercaptopyruvate sulfurtransferase (MPST)/H 2 S in hypoxia-induced angiogenesis are still unknown. We found that minor hypoxia (10% oxygen) significantly increased the migration of vascular endothelial cells while hypoxia (8% oxygen) significantly inhibited cell migration. The present study was performed using cells cultured in 10% oxygen. RNA interference was used to block the endogenous generation of hydrogen sulfide by CSE, CBS, or MPST in a vascular endothelial cell migration model in both normoxia and hypoxia. The results showed that CBS had a promoting effect on the migration of vascular endothelial cells cultured in both normoxic and hypoxic conditions. In contrast, CSE had an inhibitory effect on cell migration. MPST had a promoting effect on the migration of vascular endothelial cells cultured in hypoxia; however, it had no effect on the cells cultured in normoxia. Importantly, it was found that the hypoxia-induced increase in vascular endothelial cell migration was mediated by MPST, but not CSE or CBS. The western blot analyses showed that hypoxia significantly increased MPST protein levels, decreased CSE protein levels and did not change CBS levels, suggesting that these three hydrogen sulfide-producing systems respond differently to hypoxic conditions. Interestingly, MPST protein levels were elevated by hypoxia in a bi-phasic manner and MPST mRNA levels increased later than the first stage elevation of the protein levels, implying that the expression of MPST induced by hypoxia was also regulated at a post-transcriptional level. RNA pull-down assay showed that some candidate RNA binding proteins, such as nucleolin and Annexin A2, were dissociated from the 3'-UTR of MPST mRNA in hypoxia which implied their involvement in MPST mRNA regulation.

  11. α-Lipoic acid inhibits the migration and invasion of breast cancer cells through inhibition of TGFβ signaling.

    PubMed

    Tripathy, Joytirmay; Tripathy, Anindita; Thangaraju, Muthusamy; Suar, Mrutyunjay; Elangovan, Selvakumar

    2018-05-23

    Invasion and metastasis are the main cause of mortality in breast cancer. Hence, novel therapeutic interventions with high specificity toward invasion and metastasis are necessary. α-Lipoic acid showed antiproliferative and cytotoxic effects on several cancers including breast cancer. However, the effect of lipoic acid on breast cancer metastasis remains unclear. In the present study, we examined the effects of lipoic acid on the migration and invasion of MDA-MB-231 and 4 T1 breast cancer cells. Our data showed that lipoic acid effectively inhibited the colony forming ability of highly invasive MDA-MB-231 and 4 T1 cells. Moreover, the nontoxic concentrations of lipoic acid significantly reduced the migration of breast cancer cells. Lipoic acid also inhibited the TGFβ-induced angiopoietin-like 4 (ANGPTL4) expression and reduced the activity of matrix metalloproteinase-9 (MMP-9), an enzyme involved in invasion and metastasis, in both the cell lines. The inhibition of cell migration by lipoic acid is accompanied by the downregulation of FAK, ERK1/2 and AKT phosphorylation, and inhibition of nuclear translocation of β-catenin. Our data demonstrated that lipoic acid inhibited the migration and invasion of metastatic breast cancer cells at least in part through inhibiting ERK1/2 and AKT signaling. Thus, our findings show that the inhibition of TGFβ signaling is a potential mechanism for the anti-invasive effects of lipoic acid. Copyright © 2017. Published by Elsevier Inc.

  12. Transplanted Dental Pulp Stem Cells Migrate to Injured Area and Express Neural Markers in a Rat Model of Cerebral Ischemia.

    PubMed

    Zhang, Xuemei; Zhou, Yinglian; Li, Hulun; Wang, Rui; Yang, Dan; Li, Bing; Cao, Xiaofang; Fu, Jin

    2018-01-01

    Ischemic stroke is a major cause of disability and mortality worldwide, while effective restorative treatments are limited at present. Stem cell transplantation holds therapeutic potential for ischemic vascular diseases and may provide an opportunity for neural regeneration. Dental pulp stem cells (DPSCs) origin from neural crest and have neuro-ectodermal features including proliferation and multilineage differentiation potentials. The rat model of middle cerebral artery occlusion (MCAO) was used to evaluate whether intravenous administration of DPSCs can reduce infarct size and to estimate the migration and trans-differentiation into neuron-like cells in focal cerebral ischemia models. Brain tissues were collected at 4 weeks following cell transplantation and analyzed with immunofluorescence, immunohistochemistry and real-time polymerase chain reaction (RT-PCR) methods. Intravenously administration of rat-derived DPSCs were found to migrate into the boundary of ischemic areas and expressed neural specific markers, reducing infarct volume and cerebral edema. These results suggest that DPSCs treatment may serve as a potential therapy for clinical stroke patients in the future. © 2018 The Author(s). Published by S. Karger AG, Basel.

  13. Fisetin regulates astrocyte migration and proliferation in vitro.

    PubMed

    Wang, Nan; Yao, Fang; Li, Ke; Zhang, Lanlan; Yin, Guo; Du, Mingjun; Wu, Bingyi

    2017-04-01

    Fisetin (3,3',4',7-tetrahydroxyflavone) is a plant flavonol found in fruits and vegetables that has been reported to inhibit migration and proliferation in several types of cancer. Reactive astrogliosis involves astrocyte migration and proliferation, and contributes to the formation of glial scars in central nervous system (CNS) disorders. However, the effect of fisetin on the migration and proliferation of astrocytes remains unclear. In this study, we found that fisetin inhibited astrocyte migration in a scratch-wound assay and diminished the phosphorylation of focal adhesion kinase (FAK; Tyr576/577 and paxillin (Tyr118). It also suppressed cell proliferation, as indicated by the decreased number of 5-ethynyl-2'-deoxyuridine (EdU)-positive cells, induced cell cycle arrest in the G1 phase, reduced the percentage of cells in the G2 and S phase (as measured by flow cytometry), and decreased cyclin D1 expression, but had no effect on apoptosis. Fisetin also decreased the phosphorylation levels of Akt and extracellular signal-regulated kinase (Erk)1/2, but had no effect on the phosphorylation of p38 mitogen-activated protein kinase (MAPK). These results indicate that fisetin inhibits aggressive cell phenotypes by suppressing cell migration and proliferation via the Akt/Erk signaling pathway. Fisetin may thus have potential for use as a therapeutic strategy targeting reactive astrocytes, which may lead to the inhibition of glial scar formation in vitro.

  14. Formononetin, an isoflavone from Astragalus membranaceus inhibits proliferation and metastasis of ovarian cancer cells.

    PubMed

    Zhang, Jing; Liu, Likun; Wang, Jing; Ren, Baoyin; Zhang, Lin; Li, Weiling

    2018-07-15

    Astragalus membranaceus which was originally described in the Shennong's Classic of Materia Medica, the earliest complete Pharmacopoeia of China written from the Warring States Period to Han Dynasty, has been widely used in Chinese medicine for > 2000 years, especially in the prescription of curing cancer. A. membranaceus has various bioactivities, such as anti-tumor, anti-viral, anti-oxidant, anti-diabetes, anti-inflammation, anti-atherosclerosis, immunomodulation, hepatoprotection, hematopoiesis, neuroprotection and so on. As an important component of A. membranaceus, whether formononetin has a close relationship with its tumor-inhibiting effect on ovarian cancer cell has been investigated. The present study aimed to demonstrate the anti-proliferation, anti- migration and invasion effects of formononetin on ovarian cancer cells and further explore the underlying molecular mechanisms associated with apoptosis, migration and invasion. MTT assay was performed to detect the viability of ovarian cancer cells. DAPI staining, Annexin-V assay and assay for mitochondrial membrane potential detected the apoptosis of ovarian cancer cells treated by formononetin. The migration and invasion of ovarian cancer cells which exposed to formononetin were detected by scratch assay and transwell assay. Meanwhile, the protein-level changes of in ovarian cancer cells treated by formononetin were assessed by western blot analysis. MTT assays indicated that cell viability significantly decreased in ovarian cancer cells treated with formononetin. DAPI staining, Annexin-V assay and assay for mitochondrial membrane potential suggested that formononetin suppressed cells proliferation by inducing apoptosis. We detected the expression of apoptosis-related proteins in ovarian cancer cells after treatment with formononetin and found the expression of caspase 3/9 proteins and the ratio of Bax/Bcl-2 were increased in a dose-dependent manner. In addition, wound healing and transwell chamber assays showed that formononetin suppressed the migration and invasion of ovarian cancer cells. And formononetin decreased expression of MMP-2/9 proteins and phosphorylation level of ERK. The present results demonstrated that formononetin have potential effects on induction of apoptosis and suppression of migration and invasion. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Periodic Landau-Zener problem in long-range migration

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

    Oksengendler, B. L.; Turaeva, N. N.

    From studies of radiation effects in semiconductors at low temperatures, it is known that an interstitial atom migrates over a distance of up to 1000 A (Watkins effect). The interpretation of this effect is based on the inversion of potential energy curves of an interstitial atom in semiconductors when it changes its charge. At low temperatures, a cascade of radiationless transitions can occur between the ground and excited states of a relocalized electron, which leads to the coherent tunneling of the interstitial atom through the lattice. The description of this effect using the scattering matrix S leads to the dispersionmore » law and to an equation for the effective mass of such a quasiparticle called an inversion.« less

  16. The agar diffusion scratch assay - A novel method to assess the bioactive and cytotoxic potential of new materials and compounds

    PubMed Central

    Pusnik, Mascha; Imeri, Minire; Deppierraz, Grégoire; Bruinink, Arie; Zinn, Manfred

    2016-01-01

    A profound in vitro evaluation not only of the cytotoxic but also of bioactive potential of a given compound or material is crucial for predicting potential effects in the in vivo situation. However, most of the current methods have weaknesses in either the quantitative or qualitative assessment of cytotoxicity and/or bioactivity of the test compound. Here we describe a novel assay combining the ISO 10993-5 agar diffusion test and the scratch also termed wound healing assay. In contrast to these original tests this assay is able to detect and distinguish between cytotoxic, cell migration modifying and cytotoxic plus cell migration modifying compounds, and this at higher sensitivity and in a quantitative way. PMID:26861591

  17. Signaling through three chemokine receptors triggers the migration of transplanted neural precursor cells in a model of multiple sclerosis.

    PubMed

    Cohen, Mikhal E; Fainstein, Nina; Lavon, Iris; Ben-Hur, Tamir

    2014-09-01

    Multiple sclerosis (MS) is a multifocal disease, and precursor cells need to migrate into the multiple lesions in order to exert their therapeutic effects. Therefore, cell migration is a crucial element in regenerative processes in MS, dictating the route of delivery, when cell transplantation is considered. We have previously shown that inflammation triggers migration of multi-potential neural precursor cells (NPCs) into the white matter of experimental autoimmune encephalomyelitis (EAE) rodents, a widely used model of MS. Here we investigated the molecular basis of this attraction. NPCs were grown from E13 embryonic mouse brains and transplanted into the lateral cerebral ventricles of EAE mice. Transplanted NPC migration was directed by three tissue-derived chemokines. Stromal cell-derived factor-1α, monocyte chemo-attractant protein-1 and hepatocyte growth factor were expressed in the EAE brain and specifically in microglia and astrocytes. Their cognate receptors, CXCR4, CCR2 or c-Met were constitutively expressed on NPCs. Selective blockage of CXCR4, CCR2 or c-Met partially inhibited NPC migration in EAE brains. Blocking all three receptors had an additive effect and resulted in profound inhibition of NPC migration, as compared to extensive migration of control NPCs. The inflammation-triggered NPC migration into white matter tracts was dependent on a motile NPC phenotype. Specifically, depriving NPCs from epidermal growth factor (EGF) prevented the induction of glial commitment and a motile phenotype (as indicated by an in vitro motility assay), hampering their response to neuroinflammation. In conclusion, signaling via three chemokine systems accounts for most of the inflammation-induced, tissue-derived attraction of transplanted NPCs into white matter tracts during EAE. Copyright © 2014. Published by Elsevier B.V.

  18. Liraglutide attenuates the migration of retinal pericytes induced by advanced glycation end products.

    PubMed

    Lin, Wen-Jian; Ma, Xue-Fei; Hao, Ming; Zhou, Huan-Ran; Yu, Xin-Yang; Shao, Ning; Gao, Xin-Yuan; Kuang, Hong-Yu

    2018-07-01

    Retinal pericyte migration represents a novel mechanism of pericyte loss in diabetic retinopathy (DR), which plays a crucial role in the early impairment of the blood-retinal barrier (BRB). Glucagon-like peptide-1 (GLP-1) has been shown to protect the diabetic retina in the early stage of DR; however, the relationship between GLP-1 and retinal pericytes has not been discussed. In this study, advanced glycation end products (AGEs) significantly increased the migration of primary bovine retinal pericytes without influencing cell viability. AGEs also significantly enhanced phosphatidylinositol 3-kinase (PI3K)/Akt activation, and changed the expressions of migration-related proteins, including phosphorylated focal adhesion kinase (p-FAK), matrix metalloproteinase (MMP)-2 and vinculin. PI3K inhibition significantly attenuated the AGEs-induced migration of retinal pericytes and reversed the overexpression of MMP-2. Glucagon-like peptide-1 receptor (Glp1r) was expressed in retinal pericytes, and liraglutide, a GLP-1 analog, significantly attenuated the migration of pericytes by Glp1r and reversed the changes in p-Akt/Akt, p-FAK/FAK, vinculin and MMP-2 levels induced by AGEs, indicating that the protective effect of liraglutide was associated with the PI3K/Akt pathway. These results provided new insights into the mechanism underlying retinal pericyte migration. The early use of liraglutide exerts a potential bebefical effect on regulating pericyte migration, which might contribute to mechanisms that maintain the integrity of vascular barrier and delay the development of DR. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2008-01-01

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

  1. Gender and rural-urban migration in China.

    PubMed

    Davin, D

    1996-02-01

    Many men and women in China are migrating in search of better economic opportunities. Young women who migrate to urban centers in search of opportunity may stay away from their home villages for several years. At some point, however, they are likely to return home. This article considers the effect which such circular migration is having upon gender relations in China. The author's argument is presented in sections on China's 1990 census, migration and the sexual division of labor, migration and child care, the influence of returning migrants, the influence of young female returnees, and the fertility of returnees. She speculates that the demands and expectations of young women who return to their villages after spending some time earning high wages in urban areas will be affected by urban norms. While their return may lead to initial conflict, it is likely that the women will retain greater personal autonomy from their urban experience. Their return is also likely to lead to a higher degree of material consumption in the rural areas. Present circular migration in China has the potential to return human and financial resources to the villages, thereby helping to prevent the urban-rural gap between economic, social, cultural, and educational factors from growing even wider.

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2017-10-07

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

  4. Designed biocompatible nano-inhibitor based on poly(β-cyclodextrin-ester) for reduction of the DEHP migration from plasticized PVC.

    PubMed

    Raeisi, Ahmad; Faghihi, Khalil; Shabanian, Meisam

    2017-10-15

    The easy migration of di(2-ethylhexyl) phthalate (DEHP) from the plasticized PVC (P-PVC) poses a serious threat to human health and the ecosystems. Thus, its control migration from the P-PVC products is very important. In this work, a poly(β-cyclodextrin-ester) network (β-CDP) was synthesized via reaction of β-cyclodextrin with 3,3',4,4'-benzophenone tetracarboxylic dianhydride. As a potential inhibitor for reduction of the DEHP migration, the β-CDP was grafted to Fe 3 O 4 nanoparticles. Poly(β-cyclodextrin-ester) functionalized Fe 3 O 4 nanoparticles (MNP-CDP) has been used in PVC/DEHP system as a reactive nano-inhibitor to reduce DEHP migration. Thermal stability and mechanical properties of obtained films were investigated. DEHP migration tests of the P-PVC films were also carried out by using Gas chromatography. It was found that by incorporating the small amounts of nano-inhibitor in PVC/DEHP system, the migration of DEHP effectively reduced from the P-PVC samples about 65% without any serious changes in mechanical and thermal properties of the P-PVC films. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2016-08-01

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

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

    PubMed

    Burrows, Kate; Kinney, Patrick L

    2016-04-22

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

  7. Exploring the Climate Change, Migration and Conflict Nexus

    PubMed Central

    Burrows, Kate; Kinney, Patrick L.

    2016-01-01

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

  8. Cell and Particle Interactions and Aggregation During Electrophoretic Motion

    NASA Technical Reports Server (NTRS)

    Davis, Robert H.

    2000-01-01

    The objectives of this research were (i) to perform experiments for observing and quantifying electrophoretic aggregation, (ii) to develop a theoretical description to appropriately analyze and compare with the experimental results, (iii) to study the combined effects of electrophoretic and gravitational aggregation of large particles, and the combined effects of electrophoretic and Brownian aggregation of small particles, and (iv) to perform a preliminary design of a potential future flight experiment involving electrophoretic aggregation. Electrophoresis refers to the motion of charged particles, droplets or molecules in response to an applied electric field. Electrophoresis is commonly used for analysis and separation of biological particles or molecules. When particles have different surface charge densities or potentials, they will migrate at different velocities in an electric field. This differential migration leads to the possibility that they will collide and aggregate, thereby preventing separation.

  9. Can migration mitigate the effects of ecosystem change? Patterns of dispersal, energy acquisition and allocation in Great Lakes lake whitefish (Coregonus clupeaformis)

    USGS Publications Warehouse

    Rennie, Michael D.; Ebener, Mark P.; Wagner, Tyler

    2012-01-01

    Migration can be a behavioural response to poor or declining home range habitat quality and can occur when the costs of migration are overcome by the benefi ts of encountering higher-quality resources elsewhere. Despite dramatic ecosystem-level changes in the benthic food web of the Laurentian Great Lakes since the colonization of dreissenid mussels, coincident changes in condition and growth rates among benthivorous lake whitefi sh populations have been variable. We hypothesized that this variation could be in part mitigated by differences in migratory habits among populations, where increased migration distance can result in an increased probability of encountering high-quality habitat (relative to the home range). Results from four Great Lakes populations support this hypothesis; relative growth rates increased regularly with migration distance. The population with the largest average migration distance also had the least reduction in size-at-age during a period of signifi cant ecosystem change and among the highest estimated consumption and activity rates. In comparison, the population with the greatest declines in size-at-age was among the least mobile, demonstrating only moderate rates of consumption and activity. The least mobile population of lake whitefi sh was supported by a remnant Diporeia population and has experienced only moderate temporal growth declines. Our study provides evidence for the potential role of migration in mitigating the effects of ecosystem change on lake whitefi sh populations.

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2011-01-01

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

  12. Temperature-influenced energetics model for migrating waterfowl

    USGS Publications Warehouse

    Aagaard, Kevin; Thogmartin, Wayne E.; Lonsdorg, Eric V.

    2018-01-01

    Climate and weather affect avian migration by influencing when and where birds fly, the energy costs and risks of flight, and the ability to sense cues necessary for proper navigation. We review the literature of the physiology of avian migration and the influence of climate, specifically temperature, on avian migration dynamics. We use waterfowl as a model guild because of the ready availability of empirical physiological data and their enormous economic value, but our discussion and expectations are broadly generalizable to migratory birds in general. We detail potential consequences of an increasingly warm climate on avian migration, including the possibility of the cessation of migration by some populations and species. Our intent is to lay the groundwork for including temperature effects on energetic gains and losses of migratory birds with the expected consequences of increasing temperatures into a predictive modeling framework. To this end, we provide a simulation of migration progression exclusively focused on the influence of temperature on the physiological determinants of migration. This simulation produced comparable results to empirically derived and observed values for different migratory factors (e.g., body fat content, flight range, departure date). By merging knowledge from the arenas of avian physiology and migratory theory we have identified a clear need for research and have developed hypotheses for a path forward.

  13. Migration intentions of Ghanaian medical students: the influence of existing funding mechanisms of medical education ("the fee factor").

    PubMed

    Eliason, S; Tuoyire, D A; Awusi-Nti, C; Bockarie, A S

    2014-06-01

    To explore the effects of fee paying status on migration intentions of Ghanaian medical students. Cross sectional questionnaire based survey. All established Ghanaian medical schools with students in their clinical years. Fee-paying and non-fee-paying Ghanaian medical students in their clinical years. None. Migration intentions of Ghanaian medical students after graduation, Allegiance to Government of Ghana. Approximately half (49%) of the medical students surveyed had intentions of migrating after school. Over 48% of those with migration intentions plan on doing so immediately after completing their house job, while 44% plan to migrate at least one year after their house job. The most popular destination chosen by the potential migrant doctors was North America (38%). Fee-paying students were significantly more likely (OR=2.11, CI=1.32, 3.38) than non-fee-paying students to have intentions of migrating after their training. Secondly, fee-paying students were more likely (OR=9.66, CI=4.42, 21.12) than non-fee paying students to feel they owe no allegiance to the Government of Ghana because of their fee-paying status. Medical Students' fee-paying status affects their intentions to migrate and their allegiance to the country after completion of their training.

  14. Despite available habitat at range edge, yellow-cedar migration is punctuated with a past pulse tied to colder conditions

    Treesearch

    John Krapek; Paul E. Hennon; David V. D' Amore; Brian Buma

    2017-01-01

    Aim: To explore the recent (past ~1,000 year) migration history of yellow-cedar (Callitropsis nootkatensis), a climate-threatened tree, which appears to lag behind its potential climatic niche at a leading northern range edge, and infer its continued migration potential under changing climate. Location:...

  15. Regularized wave equation migration for imaging and data reconstruction

    NASA Astrophysics Data System (ADS)

    Kaplan, Sam T.

    The reflection seismic experiment results in a measurement (reflection seismic data) of the seismic wavefield. The linear Born approximation to the seismic wavefield leads to a forward modelling operator that we use to approximate reflection seismic data in terms of a scattering potential. We consider approximations to the scattering potential using two methods: the adjoint of the forward modelling operator (migration), and regularized numerical inversion using the forward and adjoint operators. We implement two parameterizations of the forward modelling and migration operators: source-receiver and shot-profile. For both parameterizations, we find requisite Green's function using the split-step approximation. We first develop the forward modelling operator, and then find the adjoint (migration) operator by recognizing a Fredholm integral equation of the first kind. The resulting numerical system is generally under-determined, requiring prior information to find a solution. In source-receiver migration, the parameterization of the scattering potential is understood using the migration imaging condition, and this encourages us to apply sparse prior models to the scattering potential. To that end, we use both a Cauchy prior and a mixed Cauchy-Gaussian prior, finding better resolved estimates of the scattering potential than are given by the adjoint. In shot-profile migration, the parameterization of the scattering potential has its redundancy in multiple active energy sources (i.e. shots). We find that a smallest model regularized inverse representation of the scattering potential gives a more resolved picture of the earth, as compared to the simpler adjoint representation. The shot-profile parameterization allows us to introduce a joint inversion to further improve the estimate of the scattering potential. Moreover, it allows us to introduce a novel data reconstruction algorithm so that limited data can be interpolated/extrapolated. The linearized operators are expensive, encouraging their parallel implementation. For the source-receiver parameterization of the scattering potential this parallelization is non-trivial. Seismic data is typically corrupted by various types of noise. Sparse coding can be used to suppress noise prior to migration. It is a method that stems from information theory and that we apply to noise suppression in seismic data.

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

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

    Wiedon, Annette; Toelle, Markus; Bastine, Joschika

    2012-01-20

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

  17. Quantitative and qualitative approaches to identifying migration chronology in a continental migrant

    USGS Publications Warehouse

    Beatty, William S.; Kesler, Dylan C.; Webb, Elisabeth B.; Raedeke, Andrew H.; Naylor, Luke W.; Humburg, Dale D.

    2013-01-01

    The degree to which extrinsic factors influence migration chronology in North American waterfowl has not been quantified, particularly for dabbling ducks. Previous studies have examined waterfowl migration using various methods, however, quantitative approaches to define avian migration chronology over broad spatio-temporal scales are limited, and the implications for using different approaches have not been assessed. We used movement data from 19 female adult mallards (Anas platyrhynchos) equipped with solar-powered global positioning system satellite transmitters to evaluate two individual level approaches for quantifying migration chronology. The first approach defined migration based on individual movements among geopolitical boundaries (state, provincial, international), whereas the second method modeled net displacement as a function of time using nonlinear models. Differences in migration chronologies identified by each of the approaches were examined with analysis of variance. The geopolitical method identified mean autumn migration midpoints at 15 November 2010 and 13 November 2011, whereas the net displacement method identified midpoints at 15 November 2010 and 14 November 2011. The mean midpoints for spring migration were 3 April 2011 and 20 March 2012 using the geopolitical method and 31 March 2011 and 22 March 2012 using the net displacement method. The duration, initiation date, midpoint, and termination date for both autumn and spring migration did not differ between the two individual level approaches. Although we did not detect differences in migration parameters between the different approaches, the net displacement metric offers broad potential to address questions in movement ecology for migrating species. Ultimately, an objective definition of migration chronology will allow researchers to obtain a comprehensive understanding of the extrinsic factors that drive migration at the individual and population levels. As a result, targeted conservation plans can be developed to support planning for habitat management and evaluation of long-term climate effects.

  18. Quantitative and qualitative approaches to identifying migration chronology in a continental migrant.

    PubMed

    Beatty, William S; Kesler, Dylan C; Webb, Elisabeth B; Raedeke, Andrew H; Naylor, Luke W; Humburg, Dale D

    2013-01-01

    The degree to which extrinsic factors influence migration chronology in North American waterfowl has not been quantified, particularly for dabbling ducks. Previous studies have examined waterfowl migration using various methods, however, quantitative approaches to define avian migration chronology over broad spatio-temporal scales are limited, and the implications for using different approaches have not been assessed. We used movement data from 19 female adult mallards (Anas platyrhynchos) equipped with solar-powered global positioning system satellite transmitters to evaluate two individual level approaches for quantifying migration chronology. The first approach defined migration based on individual movements among geopolitical boundaries (state, provincial, international), whereas the second method modeled net displacement as a function of time using nonlinear models. Differences in migration chronologies identified by each of the approaches were examined with analysis of variance. The geopolitical method identified mean autumn migration midpoints at 15 November 2010 and 13 November 2011, whereas the net displacement method identified midpoints at 15 November 2010 and 14 November 2011. The mean midpoints for spring migration were 3 April 2011 and 20 March 2012 using the geopolitical method and 31 March 2011 and 22 March 2012 using the net displacement method. The duration, initiation date, midpoint, and termination date for both autumn and spring migration did not differ between the two individual level approaches. Although we did not detect differences in migration parameters between the different approaches, the net displacement metric offers broad potential to address questions in movement ecology for migrating species. Ultimately, an objective definition of migration chronology will allow researchers to obtain a comprehensive understanding of the extrinsic factors that drive migration at the individual and population levels. As a result, targeted conservation plans can be developed to support planning for habitat management and evaluation of long-term climate effects.

  19. Integration of genotoxicity and population genetic analyses in kangaroo rats (Dipodomys merriami) exposed to radionuclide contamination at the Nevada Test Site, USA

    USGS Publications Warehouse

    Theodorakis, Christopher W.; Bickham, John W.; Lamb, Trip; Medica, Philip A.; Lyne, T. Barrett

    2001-01-01

    We examined effects of radionuclide exposure at two atomic blast sites on kangaroo rats (Dipodomys merriami) at the Nevada Test Site, Nevada, USA, using genotoxicity and population genetic analyses. We assessed chromosome damage by micronucleus and flow cytometric assays and genetic variation by randomly amplified polymorphic DNA (RAPD) and mitochondrial DNA (mtDNA) analyses. The RAPD analysis showed no population structure, but mtDNA exhibited differentiation among and within populations. Genotoxicity effects were not observed when all individuals were analyzed. However, individuals with mtDNA haplotypes unique to the contaminated sites had greater chromosomal damage than contaminated-site individuals with haplotypes shared with reference sites. When interpopulation comparisons used individuals with unique haplotypes, one contaminated site had greater levels of chromosome damage than one or both of the reference sites. We hypothesize that shared-haplotype individuals are potential migrants and that unique-haplotype individuals are potential long-term residents. A parsimony approach was used to estimate the minimum number of migration events necessary to explain the haplotype distributions on a phylogenetic tree. The observed predominance of migration events into the contaminated sites supported our migration hypothesis. We conclude the atomic blast sites are ecological sinks and that immigration masks the genotoxic effects of radiation on the resident populations.

  20. Migration from printing inks in multilayer food packaging materials by GC-MS analysis and pattern recognition with chemometrics.

    PubMed

    Clemente, Isabel; Aznar, Margarita; Nerín, Cristina; Bosetti, Osvaldo

    2016-01-01

    Inks and varnishes used in food packaging multilayer materials can contain different substances that are potential migrants when packaging is in contact with food. Although printing inks are applied on the external layer, they can migrate due to set-off phenomena. In order to assess food safety, migration tests were performed from two materials sets: set A based on paper and set B based on PET; both contained inks. Migration was performed to four food simulants (EtOH 50%, isooctane, EtOH 95% and Tenax(®)) and the volatile compounds profile was analysed by GC-MS. The effect of presence/absence of inks and varnishes and also their position in the material was studied. A total of 149 volatile compounds were found in migration from set A and 156 from set B materials, some of them came from inks. Quantitative analysis and a principal component analysis were performed in order to identify patterns among sample groups.

  1. 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

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

    NASA Astrophysics Data System (ADS)

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

    2017-12-01

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

  3. TEMPORAL MOISTURE CONTENT VARIABILITY BENEATH AND EXTERNAL TO A BUILDING AND THE POTENTIAL EFFECTS ON VAPOR INTRUSION RISK ASSESSMENT

    EPA Science Inventory

    Migration of vapors from organic chemicals residing in the subsurface into overlying buildings is known as vapor intrusion. Because of the difficulty in evaluating vapor intrusion by indoor air sampling, models are often employed to determine if a potential indoor inhalation exp...

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

    PubMed

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

    2017-09-01

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

  5. Different effects of 25-kDa amelogenin on the proliferation, attachment and migration of various periodontal cells

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

    Li, Xiting; Shu, Rong, E-mail: shurong123@hotmail.com; Liu, Dali

    Previous studies have assumed that amelogenin is responsible for the therapeutic effect of the enamel matrix derivative (EMD) in periodontal tissue healing and regeneration. However, it is difficult to confirm this hypothesis because both the EMD and the amelogenins are complex mixtures of multiple proteins. Further adding to the difficulties is the fact that periodontal tissue regeneration involves various types of cells and a sequence of associated cellular events including the attachment, migration and proliferation of various cells. In this study, we investigated the potential effect of a 25-kDa recombinant porcine amelogenin (rPAm) on primarily cultured periodontal ligament fibroblasts (PDLF),more » gingival fibroblasts (GF) and gingival epithelial cells (GEC). The cells were treated with 25-kDa recombinant porcine amelogenin at a concentration of 10 {mu}g/mL. We found that rPAm significantly promoted the proliferation and migration of PDLF, but not their adhesion. Similarly, the proliferation and adhesion of GF were significantly enhanced by treatment with rPAm, while migration was greatly inhibited. Interestingly, this recombinant protein inhibited the growth rate, cell adhesion and migration of GEC. These data suggest that rPAm may play an essential role in periodontal regeneration through the activation of periodontal fibroblasts and inhibition of the cellular behaviors of gingival epithelial cells.« less

  6. Integrin Expression Regulates Neuroblastoma Attachment and Migration1

    PubMed Central

    Meyer, Amy; van Golen, Cynthia M.; Kim, Bhumsoo; van Golen, Kenneth L.; Feldman, Eva L.

    2004-01-01

    Abstract Neuroblastoma (NBL) is the most common malignant disease of infancy, and children with bone metastasis have a mortality rate greater than 90%. Two major classes of proteins, integrins and growth factors, regulate the metastatic process. We have previously shown that tumorigenic NBL cells express higher levels of the type I insulin-like growth factor receptor (IGF-IR) and that β1 integrin expression is inversely proportional to tumorigenic potential in NBL. In the current study, we analyze the effect of β1 integrin and IGF-IR on NBL cell attachment and migration. Nontumorigenic S-cells express high levels of β1 integrin, whereas tumorigenic N-cells express little β1 integrin. Alterations in β1 integrin are due to regulation at the protein level, as translation is decreased in N-type cells. Moreover, inhibition of protein synthesis shows that β1 integrin is degraded more slowly in S-type cells (SHEP) than in N-type cells (SH-SY5Y and IMR32). Inhibition of α5β1 integrin prevents SHEP (but not SH-SY5Y or IMR32) cell attachment to fibronectin and increases SHEP cell migration. Increases in IGF-IR decrease β1 integrin expression, and enhance SHEP cell migration, potentially through increased expression of αvβ3. These data suggest that specific classes of integrins in concert with IGF-IR regulate NBL attachment and migration. PMID:15256055

  7. Long-term study of migration of volatile organic compounds from cross-linked polyethylene (PEX) pipes and effects on drinking water quality.

    PubMed

    Lund, Vidar; Anderson-Glenna, Mary; Skjevrak, Ingun; Steffensen, Inger-Lise

    2011-09-01

    The objectives of this study were to investigate migration of volatile organic compounds (VOCs) from cross-linked polyethylene (PEX) pipes used for drinking water produced by different production methods, and to evaluate their potential risk for human health and/or influence on aesthetic drinking water quality. The migration tests were carried out in accordance with EN-1420-1, and VOCs were analysed by gas chromatography-mass spectrometry. The levels of VOC migrating from new PEX pipes were generally low, and decreasing with time of pipe use. No association was found between production method of PEX pipes and concentration of migration products. 2,4-di-tert-butyl phenol and methyl tert-butyl ether (MTBE) were two of the major individual components detected. In three new PEX pipes, MTBE was detected in concentrations above the recommended US EPA taste and odour value for drinking water, but decreased below this value after 5 months in service. However, the threshold odour number (TON) values for two pipes were similar to new pipes even after 1 year in use. For seven chemicals for which conclusions on potential health risk could be drawn, this was considered of no or very low concern. However, odour from some of these pipes could negatively affect drinking water for up to 1 year.

  8. Balance between fibroblast growth factor 10 and secreted frizzled-relate protein-1 controls the development of hair follicle by competitively regulating β-catenin signaling.

    PubMed

    Zhang, Haihua; Nan, Weixiao; Wang, Shiyong; Si, Huazhe; Li, Guangyu

    2018-07-01

    Growth of hairs depends on the regular development of hair follicles which are hypothesized to be regulated by fibroblast growth factor 10 (FGF10) and secreted frizzled-relate protein-1 (sFRP1). In the current study, the effect of FGF10 or sFRP1 on hair follicle cells was assessed and the possible mechanism mediating the interaction between FGF10 and sFRP1 in hair follicle cells was explored. Out root sheath (ORS) and dermal papilla (DP) cells were isolated from mink skin tissues and subjected to administrations of FGF10 (50 ng/ml) or sFRP1 (10 ng/ml). Then proliferation, cell cycle distribution, and migration potentials of both cell types were detected. Moreover, the nuclear translocation of β-catenin was determined. The results showed that the administration of FGF10 increased cell proliferation and migration potential in both cell types, which was associated with the up-regulated nuclear level of β-catenin. To the contrary, the administration of sFRP1 decreased cell proliferation and migration potentials while induced the G1 cell cycle arrest in both cell types by inhibiting nuclear translocation of β-catenin. Compared with the sole administrations, the co-treatment of FGF10 and sFRP1 had a medium effect on cell proliferation, cell cycle distribution, cell migration, and nuclear β-catenin level, representing an antagonistic interaction between the two factors, which was exerted by competitively regulating β-catenin pathway. Conclusively, the cycle of hair follicles was promoted by FGF10 while blocked by sFRP1 and the interplay between the two factors controlled the development of hair follicles by competitively regulating β-catenin signaling. Copyright © 2018. Published by Elsevier Masson SAS.

  9. Testosterone, migration distance, and migratory timing in song sparrows Melospiza melodia.

    PubMed

    Lymburner, Alannah H; Kelly, Tosha R; Hobson, Keith A; MacDougall-Shackleton, Elizabeth A; MacDougall-Shackleton, Scott A

    2016-09-01

    In seasonally migratory animals, migration distance often varies substantially within populations such that individuals breeding at the same site may overwinter different distances from the breeding grounds. Shorter migration may allow earlier return to the breeding grounds, which may be particularly advantageous to males competing to acquire a breeding territory. However, little is known about potential mechanisms that may mediate migration distance. We investigated naturally-occurring variation in androgen levels at the time of arrival to the breeding site and its relationship to overwintering latitude in male and female song sparrows (Melospiza melodia). We used stable isotope analysis of hydrogen (δ(2)H) in winter-grown claw tissue to infer relative overwintering latitude (migration distance), combined with 14years of capture records from a long-term study population to infer the arrival timing of males versus females. Relative to females, males had higher circulating androgen levels, migrated shorter distances, and were more likely to be caught early in the breeding season. Males that migrate short distances may benefit from early arrival at the breeding grounds, allowing them to establish a breeding territory. Even after controlling for sex and date, androgen levels were highest in individuals that migrated shorter distances. Our findings indicate that androgens and migration distance are correlated traits within and between sexes that may reflect individual variation within an integrated phenotype in which testosterone has correlated effects on behavioral traits such as migration. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Quantitative impedimetric monitoring of cell migration under the stimulation of cytokine or anti-cancer drug in a microfluidic chip

    PubMed Central

    Xiao, Xia; Lei, Kin Fong; Huang, Chia-Hao

    2015-01-01

    Cell migration is a cellular response and results in various biological processes such as cancer metastasis, that is, the primary cause of death for cancer patients. Quantitative investigation of the correlation between cell migration and extracellular stimulation is essential for developing effective therapeutic strategies for controlling invasive cancer cells. The conventional method to determine cell migration rate based on comparison of successive images may not be an objective approach. In this work, a microfluidic chip embedded with measurement electrodes has been developed to quantitatively monitor the cell migration activity based on the impedimetric measurement technique. A no-damage wound was constructed by microfluidic phenomenon and cell migration activity under the stimulation of cytokine and an anti-cancer drug, i.e., interleukin-6 and doxorubicin, were, respectively, investigated. Impedance measurement was concurrently performed during the cell migration process. The impedance change was directly correlated to the cell migration activity; therefore, the migration rate could be calculated. In addition, a good match was found between impedance measurement and conventional imaging analysis. But the impedimetric measurement technique provides an objective and quantitative measurement. Based on our technique, cell migration rates were calculated to be 8.5, 19.1, and 34.9 μm/h under the stimulation of cytokine at concentrations of 0 (control), 5, and 10 ng/ml. This technique has high potential to be developed into a powerful analytical platform for cancer research. PMID:26180566

  11. Band Alignment and Controllable Electron Migration between Rutile and Anatase TiO2

    PubMed Central

    Mi, Yang; Weng, Yuxiang

    2015-01-01

    TiO2 is the most promising semiconductor for photocatalytic splitting of water for hydrogen and degradation of pollutants. The highly photocatalytic active form is its mixed phase of two polymorphs anatase and rutile rather than their pristine compositions. Such a synergetic effect is understood by the staggered band alignment favorable to spatial charge separation. However, electron migration in either direction between the two phases has been reported, the reason of which is still unknown. We determined the band alignment by a novel method, i.e., transient infrared absorption-excitation energy scanning spectra, showing their conduction bands being aligned, thus the electron migration direction is controlled by dynamical factors, such as varying the particle size of anatase, putting electron or hole scavengers on either the surface of anatase or rutile phases, or both. A quantitative criterion capable of predicting the migration direction under various conditions including particle size and surface chemical reactions is proposed, the predictions have been verified experimentally in several typical cases. This would give rise to a great potential in designing more effective titania photocatalysts. PMID:26169699

  12. Potential Hydrogeomechanical Impacts of Geological CO2 Sequestration

    NASA Astrophysics Data System (ADS)

    McPherson, B. J.; Haerer, D.; Han, W.; Heath, J.; Morse, J.

    2006-12-01

    Long-term sequestration of anthropogenic "greenhouse gases" such as CO2 is a proposed approach to managing climate change. Deep brine reservoirs in sedimentary basins are possible sites for sequestration, given their ubiquitous nature. We used a mathematical sedimentary basin model, including coupling of multiphase CO2-groundwater flow and rock deformation, to evaluate residence times in possible brine reservoir storage sites, migration patterns and rates away from such sites, and effects of CO2 injection on fluid pressures and rock strain. Study areas include the Uinta and Paradox basins of Utah, the San Juan basin of New Mexico, and the Permian basin of west Texas. Regional-scale hydrologic and mechanical properties, including the presence of fracture zones, were calibrated using laboratory and field data. Our initial results suggest that, in general, long-term (~100 years or more) sequestration in deep brine reservoirs is possible, if guided by robust structural and hydrologic data. However, specific processes must be addressed to characterize and minimize risks. In addition to CO2 migration from target sequestration reservoirs into other reservoirs or to the land surface, another environmental issue is displacement of brines into freshwater aquifers. We evaluated the potential for such unintended aquifer contamination by displacement of brines out of adjacent sealing layers such as marine shales. Results suggest that sustained injection of CO2 may incur significant brine displacement out of adjacent sealing layers, depending on the injection history, initial brine composition, and hydrologic properties of both reservoirs and seals. Model simulations also suggest that as injection-induced overpressures migrate, effective stresses may follow this migration under some conditions, as will associated rock strain. Such "strain migration" may lead to induced or reactivated fractures or faults, but can be controlled through reservoir engineering.

  13. Characterisation and potential migration of silver nanoparticles from commercially available polymeric food contact materials.

    PubMed

    Addo Ntim, Susana; Thomas, Treye A; Begley, Timothy H; Noonan, Gregory O

    2015-01-01

    The potential for consumer exposure to nano-components in food contact materials (FCMs) is dependent on the migration of nanomaterials into food. Therefore, characterising the physico-chemical properties and potential for migration of constituents is an important step in assessing the safety of FCMs. A number of commercially available food storage products, purchased domestically within the United States and internationally, that claim to contain nanosilver were evaluated. The products were made of polyethylene, polypropylene and polyphenylene ether sulfone and all contained silver (0.001-36 mg kg(-1) of polymer). Silver migration was measured under various conditions, including using 3% acetic acid and water as food simulants. Low concentrations (sub-ppb levels) of silver were detected in the migration studies generally following a trend characterised by a surface desorption phenomenon, where the majority of the silver migration occurred in the first of three consecutive exposures. Silver nanoparticles were not detected in food simulants, suggesting that the silver migration may be due solely to ionic silver released into solution from oxidation of the silver nanoparticle surface. The absence of detectable silver nanoparticles was consistent with expectations from a physico-chemical view point. For the products tested, current USFDA guidance for evaluating migration from FCMs was applicable.

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

    PubMed

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

    2006-09-01

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

  15. ELECTROPHORESIS OF BACTERIA AS INFLUENCED BY HYDROGEN ION CONCENTRATION AND THE PRESENCE OF SODIUM AND CALCIUM SALTS

    PubMed Central

    Winslow, C.-E. A.; Falk, I. S.; Caulfield, M. F.

    1923-01-01

    1. We have confirmed the results of earlier workers particularly of Northrop and De Kruif in regard to the following points: (a) the general tendency of the bacterial cell when suspended in distilled water near the zone of neutrality to move toward the anode of an electrical field; (b) the fact that the migration of bacterial cells in the electrical field is a function of the reaction of the menstruum. The curve obtained by plotting velocity of migration against pH passes through an isoelectric point at about pH 3.0, at greater acidity the direction of migration becomes reversed (toward the cathode) and in still more acid solution (pH = 1.0) again disappears; while at reactions less acid than pH 3.0 the velocity is toward the anode and increases with increasing alkalinity; (c) the fact that neutral salts depress the velocity of migration, calcium salts being much more effective than sodium salts of the same concentration. 2. We further find: (a) that on the extreme alkaline side of the curve of velocity of migration plotted against pH a maximum value is reached at about pH 10 with a fall at about pH 12.0 which in many experiments reaches an isopotential point; (b) that the depressing effect of salts is accompanied by a general shifting of the curve of migration velocity so that a maximum velocity (of course absolutely less than that manifest in the absence of salts) appears at about pH 7.0 and an abolition of velocity at pH 9.0 to 10.0; (c) that an apparent "antagonistic" effect is indicated between CaCl2 and NaCl, the presence of a certain concentration of the latter salt diminishing to a slight but definite degree the depressing effect produced by the former; (d) that heat-killed bacterial cells exhibit essentially the same curve of migration velocity as that of the living cells; (e) that bacterial spores exhibit the same general curve of migration velocity as vegetative cells, although the actual velocity is apparently slightly less. 3. All of the observed phenomena appear to be in accord with the assumption that marked differences in dielectric constants did not appear under the conditions studied and if this assumption be granted the results are in accord with the fundamental postulates of the Donnan equilibrium as applied to the explanation of the origin of potential difference between a bacterial cell and its enveloping menstruum. It is possible but not at all certain that the phenomenon of antagonism may require the introduction of additional assumptions for its explanation. Professor Donnan and other investigators have clearly understood the importance of applying the concept of membrane equilibria in the elucidation of physiological phenomena. Our findings add to the numerous vindications favoring this view and emphasize the importance of further study of membrane equilibria in bacterial suspensions. We have pointed out that certain potential differences between bacteria and their menstrua are apparently associated with some of the phenomena of viability. Viability and potential differences may, however, under certain conditions vary quite independently as evidenced by the fact that normal rates of migration are demonstrable after the cells have been killed by heat. Thus, considerable caution must be exercised in relating the existence of these charges to the metabolism of the cell. PMID:19872061

  16. Atractylenolide I restores HO-1 expression and inhibits Ox-LDL-induced VSMCs proliferation, migration and inflammatory responses in vitro

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

    Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Zhi, Wenbing; Liu, Fang

    Pathogenesis of atherosclerosis is characterized by the proliferation and migration of vascular smooth muscle cells (VSMCs) and inflammatory lesions. The aim of this study is to elucidate the effect of atractylenolide I (AO-I) on smooth muscle cell inflammation, proliferation and migration induced by oxidized modified low density lipoprotein (Ox-LDL). Here, We found that atractylenolide I inhibited Ox-LDL-induced VSMCs proliferation and migration in a dose-dependent manner, and decreased the production of inflammatory cytokines and the expression of monocyte chemoattractant protein-1 (MCP-1) in VSMCs. The study also identified that AO-I prominently inhibited p38-MAPK and NF-κB activation. More importantly, the specific heme oxygenase-1more » (HO-1) inhibitor zinc protoporphyrin (ZnPP) IX partially abolished the beneficial effects of atractylenolide I on Ox-LDL-induced VSMCs. Furthermore, atractylenolide I blocked the foam cell formation in macrophages induced by Ox-LDL. In summary, inhibitory roles of AO-I in VSMCs proliferation and migration, lipid peroxidation and subsequent inflammatory responses might contribute to the anti-atherosclerotic property of AO-I. - Highlights: • AO-I inhibited Ox-LDL-induced VSMCs proliferation and migration. • AO-I alleviated inflammatory response via inhibiting TNF-α, IL-6 and NO production. • AO-I restored HO-1 expression and down-regulated PCNA expression. • MCP-1 overexpression is potentially regulated by NF-κB and p38 MAPK pathway. • AO-I possesses strong anti-lipid peroxidation effect.« less

  17. Breaking mean-motion resonances during Type I planet migration

    NASA Astrophysics Data System (ADS)

    Hands, T. O.; Alexander, R. D.

    2018-03-01

    We present 2D hydrodynamical simulations of pairs of planets migrating simultaneously in the Type I regime in a protoplanetary disc. Convergent migration naturally leads to the trapping of these planets in mean-motion resonances. Once in resonance the planets' eccentricity grows rapidly, and disc-planet torques cause the planets to escape resonance on a time-scale of a few hundred orbits. The effect is more pronounced in highly viscous discs, but operates efficiently even in inviscid discs. We attribute this resonance-breaking to overstable librations driven by moderate eccentricity damping, but find that this mechanism operates differently in hydrodynamic simulations than in previous analytic calculations. Planets escaping resonance in this manner can potentially explain the observed paucity of resonances in Kepler multitransiting systems, and we suggest that simultaneous disc-driven migration remains the most plausible means of assembling tightly packed planetary systems.

  18. KAI1 overexpression promotes apoptosis and inhibits proliferation, cell cycle, migration, and invasion in nasopharyngeal carcinoma cells.

    PubMed

    Guo, Zheng; Wang, Yili; Yang, Jing; Zhong, Jinghua; Liu, Xia; Xu, Mingjun

    The purpose of this study is to characterize the effect of KAI1 overexpression on the biological behavior of nasopharyngeal carcinoma (NPC) cells. Nasopharyngeal carcinoma is a highly malignant tumor with a high rate of incidence in China. Currently, there are no ideal therapeutic options for patients with NPC, but a targeted therapy would have great potential for treating it. Therefore, there is an urgent need for novel therapeutic targets to provide new options for treating NPC. The KAI1 gene was originally identified as a metastasis suppressor gene for advanced human cancer. In NPC cell lines and tissues, the expression of KAI1 decreased as the metastatic potential of cells increased, but its potential as a therapeutic target has not been elucidated. Non-transformed nasopharyngeal epithelium cell NP69 and NPC cell line C666-1 were cultured and KAI1 expression in these cells was detected by qRT-PCR and Western blot. After the transfection of KAI1-pCDNA3.1 to NP69 and C666-1, the KAI1 expression in these cells was detected by qRT-PCR and Western blot, the proliferation was performed by MTS, the cell cycle and apoptosis were performed by flow cytometry, the migration and invasion were examined by transwell. Our results showed that KAI1 was significantly upregulated in C666-1 cells compared to that in NP69 cells. In addition, KAI1 overexpression significantly inhibited the proliferation, cell cycle, migration, and invasion, and promoted apoptosis of C666-1 cells, but had no significant effect on NP69 cells. Our findings suggest that KAI1 overexpression promotes apoptosis and inhibits proliferation, cell cycle, migration, and invasion in NPC cells. We hypothesize that KAI1 overexpression could be a potential therapeutic target for NPC. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Risk factors for proximal migration of biliary tube stents.

    PubMed

    Kawaguchi, Yoshiaki; Ogawa, Masami; Kawashima, Yohei; Mizukami, Hajime; Maruno, Atsuko; Ito, Hiroyuki; Mine, Tetsuya

    2014-02-07

    To analyze the risk factors for biliary stent migration in patients with benign and malignant strictures. Endoscopic stent placement was performed in 396 patients with bile duct stenosis, at our institution, between June 2003 and March 2009. The indications for bile duct stent implantation included common bile duct stone in 190 patients, malignant lesions in 112, chronic pancreatitis in 62, autoimmune pancreatitis in 14, trauma in eight, surgical complications in six, and primary sclerosing cholangitis (PSC) in four. We retrospectively examined the frequency of stent migration, and analyzed the patient factors (disease, whether endoscopic sphincterotomy was performed, location of bile duct stenosis and diameter of the bile duct) and stent characteristics (duration of stent placement, stent type, diameter and length). Moreover, we investigated retrieval methods for migrated stents and their associated success rates. The frequency of tube stent migration in the total patient population was 3.5%. The cases in which tube stent migration occurred included those with common bile duct stones (3/190; 1.6%), malignant lesions (2/112; 1.8%), chronic pancreatitis (4/62; 6.5%), autoimmune pancreatitis (2/14; 14.3%), trauma (1/8; 12.5%), surgical complications (2/6; 33.3%), and PSC (0/4; 0%). The potential risk factors for migration included bile duct stenosis secondary to benign disease such as chronic pancreatitis and autoimmune pancreatitis (P = 0.030); stenosis of the lower bile duct (P = 0.031); bile duct diameter > 10 mm (P = 0.023); duration of stent placement > 1 mo (P = 0.007); use of straight-type stents (P < 0.001); and 10-Fr sized stents (P < 0.001). Retrieval of the migrated stents was successful in all cases. The grasping technique, using a basket or snare, was effective for pig-tailed or thin and straight stents, whereas the guidewire cannulation technique was effective for thick and straight stents. Migration of tube stents within the bile duct is rare but possible, and it is important to determine the risk factors involved in stent migration.

  20. 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 vertical CO2 migration at injection point, the reverse time migration yields better images than Kirchhoff migration does. On the other hand, Kirchhoff migration images horizontal CO2 migration clearer than the reverse time migration does. From these results, we can conclude that the reverse-time migration and Kirchhoff migration can complement with each other to describe the behavior of CO2 in the subsurface. Acknowledgement This work was financially supported by the Brain Korea 21 project of Energy Systems Engineering, the "Development of Technology for CO2 Marine Geological Storage" program funded by the Ministry of Land, Transport and Maritime Affairs (MLTM) of Korea and the Korea CCS R&D Center (KCRC) grant funded by the Korea government (Ministry of Education, Science and Technology) (No. 2012-0008926).

  1. Doxycycline reduces the migration of tuberous sclerosis complex-2 null cells - effects on RhoA-GTPase and focal adhesion kinase.

    PubMed

    Ng, Ho Yin; Oliver, Brian Gregory George; Burgess, Janette Kay; Krymskaya, Vera P; Black, Judith Lee; Moir, Lyn M

    2015-11-01

    Lymphangioleiomyomatosis (LAM) is associated with dysfunction of the tuberous sclerosis complex (TSC) leading to enhanced cell proliferation and migration. This study aims to examine whether doxycycline, a tetracycline antibiotic, can inhibit the enhanced migration of TSC2-deficient cells, identify signalling pathways through which doxycycline works and to assess the effectiveness of combining doxycycline with rapamycin (mammalian target of rapamycin complex 1 inhibitor) in controlling cell migration, proliferation and wound closure. TSC2-positive and TSC2-negative mouse embryonic fibroblasts (MEF), 323-TSC2-positive and 323-TSC2-null MEF and Eker rat uterine leiomyoma (ELT3) cells were treated with doxycycline or rapamycin alone, or in combination. Migration, wound closure and proliferation were assessed using a transwell migration assay, time-lapse microscopy and manual cell counts respectively. RhoA-GTPase activity, phosphorylation of p70S6 kinase (p70S6K) and focal adhesion kinase (FAK) in TSC2-negative MEF treated with doxycycline were examined using ELISA and immunoblotting techniques. The enhanced migration of TSC2-null cells was reduced by doxycycline at concentrations as low as 20 pM, while the rate of wound closure was reduced at 2-59 μM. Doxycycline decreased RhoA-GTPase activity and phosphorylation of FAK in these cells but had no effect on the phosphorylation of p70S6K, ERK1/2 or AKT. Combining doxycycline with rapamycin significantly reduced the rate of wound closure at lower concentrations than achieved with either drug alone. This study shows that doxycycline inhibits TSC2-null cell migration. Thus doxycycline has potential as an anti-migratory agent in the treatment of diseases with TSC2 dysfunction. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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

    PubMed

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

    2017-02-01

    Direct current electrical fields have been shown to be a major factor in the regulation of cell proliferation, differentiation, migration, and survival, as well as in the maturation of dividing cells during development. During adulthood, spinal cord cells are continuously produced in both animals and humans, and they hold great potential for neural restoration following spinal cord injury. While the effects of direct current electrical fields on adult-born spinal cells cultured ex vivo have recently been reported, the effects of direct current electrical fields on adult-born spinal cells in vivo have not been characterized. Here, we provide convincing findings that a therapeutic form of transspinal direct current stimulation (tsDCS) affects the migration and proliferation of adult-born spinal cells in mice. Specifically, cathodal tsDCS attracted the adult-born spinal cells, while anodal tsDCS repulsed them. In addition, both tsDCS polarities caused a significant increase in cell number. Regarding the potential mechanisms involved, both cathodal and anodal tsDCS caused significant increases in expression of brain-derived neurotrophic factor, while expression of nerve growth factor increased and decreased, respectively. In the spinal cord, both anodal and cathodal tsDCS increased blood flow. Since blood flow and angiogenesis are associated with the proliferation of neural stem cells, increased blood flow may represent a major factor in the modulation of newly born spinal cells by tsDCS. Consequently, we propose that the method and novel findings presented in the current study have the potential to facilitate cellular, molecular, and/or bioengineering strategies to repair injured spinal cords. NEW & NOTEWORTHY Our results indicate that transspinal direct current stimulation (tsDCS) affects the migratory pattern and proliferation of adult newly born spinal cells, a cell population which has been implicated in learning and memory. In addition, our results suggest a potential mechanism of action regarding the functional effects of applying direct current. Thus tsDCS may represent a novel method by which to manipulate the migration and cell number of adult newly born cells and restore functions following brain or spinal cord injury. Copyright © 2017 the American Physiological Society.

  3. Doxycycline inhibits leukemic cell migration via inhibition of matrix metalloproteinases and phosphorylation of focal adhesion kinase

    PubMed Central

    WANG, CHUNHUAI; XIANG, RU; ZHANG, XIANGZHONG; CHEN, YUNXIAN

    2015-01-01

    Doxycycline, a tetracycline-based antibiotic, has been reported to attenuate melanoma cell migration through inhibiting the focal adhesion kinase (FAK) signaling pathway. However, it remains to be elucidated whether doxycycline exerts this effect on leukemia cell migration. The present study aimed to examine the role of doxycycline in leukemia cell migration. The invasion capacities of the human leukemia cell lines KG1a (acute myelogenous leukemia) and K562 (chronic myelogenous leukemia) were evaluated using Matrigel® matrix-coated Transwell® chamber assays; leukemic cell lines treated with doxycycline (1 µg/ml) or anti-β1-integrin antibodies were added to the upper chamber, while untreated cells were included as controls. Reverse transcription quantitative polymerase chain reaction was performed in order to further understand the influence of doxycycline treatment on the expression of FAK and gelatinases in the KG1a and K562 leukemic cell lines. In addition, FAK protein expression and phosphorylation were determined using western blot analysis in order to investigate the mechanism by which doxycycline inhibited leukemic cell migration. The results revealed that doxycycline treatment significantly attenuated the migration of KG1a and K562 cells, which was demonstrated to be associated with inhibition of the expression and phosphorylation of FAK. In addition, doxycycline treatment inhibited matrix metalloproteinase (MMP)-2 and MMP-9 expression. Furthermore, incubation with blocking anti-β1-integrin antibodies had an analogous inhibitory effect on leukemic cell migration to that of doxycycline. In conclusion, the results of the present study suggested that doxycycline attenuated leukemic cell migration through inhibiting the FAK signaling pathway. Therefore, doxycycline may have potential for use as a novel strategy for the treatment of leukemia. PMID:26004127

  4. Rescue of neuronal migration deficits in a mouse model of fetal Minamata disease by increasing neuronal Ca2+ spike frequency.

    PubMed

    Fahrion, Jennifer K; Komuro, Yutaro; Li, Ying; Ohno, Nobuhiko; Littner, Yoav; Raoult, Emilie; Galas, Ludovic; Vaudry, David; Komuro, Hitoshi

    2012-03-27

    In the brains of patients with fetal Minamata disease (FMD), which is caused by exposure to methylmercury (MeHg) during development, many neurons are hypoplastic, ectopic, and disoriented, indicating disrupted migration, maturation, and growth. MeHg affects a myriad of signaling molecules, but little is known about which signals are primary targets for MeHg-induced deficits in neuronal development. In this study, using a mouse model of FMD, we examined how MeHg affects the migration of cerebellar granule cells during early postnatal development. The cerebellum is one of the most susceptible brain regions to MeHg exposure, and profound loss of cerebellar granule cells is detected in the brains of patients with FMD. We show that MeHg inhibits granule cell migration by reducing the frequency of somal Ca(2+) spikes through alterations in Ca(2+), cAMP, and insulin-like growth factor 1 (IGF1) signaling. First, MeHg slows the speed of granule cell migration in a dose-dependent manner, independent of the mode of migration. Second, MeHg reduces the frequency of spontaneous Ca(2+) spikes in granule cell somata in a dose-dependent manner. Third, a unique in vivo live-imaging system for cell migration reveals that reducing the inhibitory effects of MeHg on somal Ca(2+) spike frequency by stimulating internal Ca(2+) release and Ca(2+) influxes, inhibiting cAMP activity, or activating IGF1 receptors ameliorates the inhibitory effects of MeHg on granule cell migration. These results suggest that alteration of Ca(2+) spike frequency and Ca(2+), cAMP, and IGF1 signaling could be potential therapeutic targets for infants with MeHg intoxication.

  5. Rescue of neuronal migration deficits in a mouse model of fetal Minamata disease by increasing neuronal Ca2+ spike frequency

    PubMed Central

    Fahrion, Jennifer K.; Ohno, Nobuhiko; Littner, Yoav; Raoult, Emilie; Galas, Ludovic; Vaudry, David; Komuro, Hitoshi

    2012-01-01

    In the brains of patients with fetal Minamata disease (FMD), which is caused by exposure to methylmercury (MeHg) during development, many neurons are hypoplastic, ectopic, and disoriented, indicating disrupted migration, maturation, and growth. MeHg affects a myriad of signaling molecules, but little is known about which signals are primary targets for MeHg-induced deficits in neuronal development. In this study, using a mouse model of FMD, we examined how MeHg affects the migration of cerebellar granule cells during early postnatal development. The cerebellum is one of the most susceptible brain regions to MeHg exposure, and profound loss of cerebellar granule cells is detected in the brains of patients with FMD. We show that MeHg inhibits granule cell migration by reducing the frequency of somal Ca2+ spikes through alterations in Ca2+, cAMP, and insulin-like growth factor 1 (IGF1) signaling. First, MeHg slows the speed of granule cell migration in a dose-dependent manner, independent of the mode of migration. Second, MeHg reduces the frequency of spontaneous Ca2+ spikes in granule cell somata in a dose-dependent manner. Third, a unique in vivo live-imaging system for cell migration reveals that reducing the inhibitory effects of MeHg on somal Ca2+ spike frequency by stimulating internal Ca2+ release and Ca2+ influxes, inhibiting cAMP activity, or activating IGF1 receptors ameliorates the inhibitory effects of MeHg on granule cell migration. These results suggest that alteration of Ca2+ spike frequency and Ca2+, cAMP, and IGF1 signaling could be potential therapeutic targets for infants with MeHg intoxication. PMID:22411806

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

    PubMed

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

    2017-08-01

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

  7. 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 because of the complexity of biological systems, the inherently dynamic nature of the environment and the scale at which many migrations occur and associated threats operate, necessitating improved integration of physiological approaches to the conservation of migratory animals. PMID:27293751

  8. 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 because of the complexity of biological systems, the inherently dynamic nature of the environment and the scale at which many migrations occur and associated threats operate, necessitating improved integration of physiological approaches to the conservation of migratory animals.

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

    PubMed Central

    2013-01-01

    Background Src tyrosine kinase activates inducible nitric oxide synthase (iNOS) and, in turn, nitric oxide production as a means to transduce cell migration. Src tyrosine kinase plays a key proximal role to control α9β1 signaling. Our recent studies have clearly demonstrated the role of α9β1 integrin in matrix metalloproteinase-9 (MMP-9) and/or urokinase plasminogen activator receptor (uPAR)-mediated glioma cell migration. In the present study, we evaluated the involvement of α9β1 integrin-iNOS pathway in MMP-9- and/or uPAR-mediated glioma cell migration. Methods MMP-9 and uPAR shRNAs and overexpressing plasmids were used to downregulate and upregulate these molecules, respectively in U251 glioma cells and 5310 glioma xenograft cells. The effect of treatments on migration and invasion potential of these glioma cells were assessed by spheroid migration, wound healing, and Matrigel invasion assays. In order to attain the other objectives we also performed immunocytochemical, immunohistochemical, RT-PCR, Western blot and fluorescence-activated cell sorting (FACS) analysis. Results Immunohistochemical analysis revealed the prominent association of iNOS with glioblastoma multiforme (GBM). Immunofluorescence analysis showed prominent expression of iNOS in glioma cells. MMP-9 and/or uPAR knockdown by respective shRNAs reduced iNOS expression in these glioma cells. RT-PCR analysis revealed elevated iNOS mRNA expression in either MMP-9 or uPAR overexpressed glioma cells. The migration potential of MMP-9- and/or uPAR-overexpressed U251 glioma cells was significantly inhibited after treatment with L-NAME, an inhibitor of iNOS. Similarly, a significant inhibition of the invasion potential of the control or MMP-9/uPAR-overexpressed glioma cells was noticed after L-NAME treatment. A prominent reduction of iNOS expression was observed in the tumor regions of nude mice brains, which were injected with 5310 glioma cells, after MMP-9 and/or uPAR knockdown. Protein expressions of cSrc, phosphoSrc and p130Cas were reduced with simultaneous knockdown of both MMP-9 and uPAR. Conclusions Taken together, our results from the present and earlier studies clearly demonstrate that α9β1 integrin-mediated cell migration utilizes the iNOS pathway, and inhibition of the migratory potential of glioma cells by simultaneous knockdown of MMP-9 and uPAR could be attributed to the reduced α9β1 integrin and iNOS levels. PMID:24325546

  10. Geographical and temporal flexibility in the response to crosswinds by migrating raptors.

    PubMed

    Klaassen, Raymond H G; Hake, Mikael; Strandberg, Roine; Alerstam, Thomas

    2011-05-07

    Wind and ocean currents may potentially have important effects on travelling animals, as an animal which does not respond to lateral flow will be drifted from its intended direction of movement. By analysing daily movements of migrating ospreys Pandion haliaetus and marsh harriers Circus aeruginosus, as recorded by satellite telemetry, in relation to global wind data, we showed that these raptors allow on average 47 per cent drift. Furthermore, our analyses revealed significant geographical and temporal variation in the response to crosswinds. During some parts of the migration, the birds drifted and in other parts they compensated or even overcompensated. In some regions, the response of marsh harriers depended on the wind direction. They drifted when the wind came from one side and (over)compensated when the wind came from the opposite side, and this flexible response was different in different geographical regions. These results suggest that migrating raptors modulate their response to crosswinds at different places and times during their travels and show that individual birds use a much more varied repertoire of behavioural responses to wind than hitherto assumed. Our results may also explain why contrasting and variable results have been obtained in previous studies of the effect of wind on bird migration.

  11. Geographical and temporal flexibility in the response to crosswinds by migrating raptors

    PubMed Central

    Klaassen, Raymond H. G.; Hake, Mikael; Strandberg, Roine; Alerstam, Thomas

    2011-01-01

    Wind and ocean currents may potentially have important effects on travelling animals, as an animal which does not respond to lateral flow will be drifted from its intended direction of movement. By analysing daily movements of migrating ospreys Pandion haliaetus and marsh harriers Circus aeruginosus, as recorded by satellite telemetry, in relation to global wind data, we showed that these raptors allow on average 47 per cent drift. Furthermore, our analyses revealed significant geographical and temporal variation in the response to crosswinds. During some parts of the migration, the birds drifted and in other parts they compensated or even overcompensated. In some regions, the response of marsh harriers depended on the wind direction. They drifted when the wind came from one side and (over)compensated when the wind came from the opposite side, and this flexible response was different in different geographical regions. These results suggest that migrating raptors modulate their response to crosswinds at different places and times during their travels and show that individual birds use a much more varied repertoire of behavioural responses to wind than hitherto assumed. Our results may also explain why contrasting and variable results have been obtained in previous studies of the effect of wind on bird migration. PMID:20980299

  12. Effects of alluvial knickpoint migration on floodplain ecology and geomorphology

    NASA Astrophysics Data System (ADS)

    Larsen, Annegret; May, Jan-Hendrick

    2016-04-01

    Alluvial knickpoints are well described as erosional mechanism within discontinuous ephemeral streams in the semi-arid SW USA. However, alluvial knickpoints occur globally in a wide range of settings and of climate zones, including temperate SE Australia, subtropical Africa, and tropical Australia. Much attention has been given in the scientific literature to the trigger mechanisms of alluvial knickpoints, which can be summarized as: i) threshold phenomena, ii) climate variability and iii) land-use change, or to a combination of these factors. Recently, studies have focused on the timescale of alluvial knickpoint retreat, and the processes, mechanisms and feedbacks with ecology, geomorphology and hydrology. In this study, we compile data from a global literature review with a case study on a tropical river system in Australia affected by re-occurring, fast migrating (140 myr-1) alluvial knickpoint. We highlight the importance of potential water table declines due to channel incision following knickpoint migration, which in turn leads to the destabilization of river banks, and a shift in floodplain vegetation and fire incursion. We hypothesize that the observed feedbacks might also help to understand the broader impacts of alluvial knickpoint migration in other regions, and might explain the drastic effects of knickpoint migration on land cover and land-use in semi-arid areas.

  13. Father absence due to migration and child illness in rural Mexico.

    PubMed

    Schmeer, Kammi

    2009-10-01

    Little research to date has assessed the importance of the presence of fathers in the household for protecting child health, particularly in developing country contexts. Although divorce and non-marital childbearing are low in many developing countries, migration is a potentially important source of father absence that has yet to be studied in relation to child health. This study utilizes prospective, longitudinal data from Mexico to assess whether father absence due to migration is associated with increased child illness in poor, rural communities. Rural Mexico provides a setting where child illness is related to more serious health problems, and where migration is an important source of father absence. Both state- and individual-level fixed effects regression analyses are used to estimate the relationship between father absence due to migration and child illness while controlling for unobserved contextual and individual characteristics. The state-level models illustrate that the odds of children being ill are 39% higher for any illness and 51% higher for diarrhea when fathers are absent compared with when fathers are present in the household. The individual-level fixed effects models support these findings, indicating that, in the context of rural Mexico, fathers may be important sources of support for ensuring the healthy development of young children.

  14. Advanced glycation end products promote the proliferation and migration of primary rat vascular smooth muscle cells via the upregulation of BAG3

    PubMed Central

    Li, Cunshu; Chang, Ye; Li, Yuan; Chen, Shuang; Chen, Yintao; Ye, Ning; Dai, Dongxue; Sun, Yingxian

    2017-01-01

    The present study was aimed to investigate the role of reactive oxygen species (ROS) on advanced glycation end product (AGE)-induced proliferation and migration of vascular smooth muscle cells (VSMCs) and whether Bcl-2-associated athanogene 3 (BAG3) is involved in the process. Primary rat VSMCs were extracted and cultured in vitro. Cell viability was detected by MTT assay and cell proliferation was detected by EdU incorporation assay. Cell migration was detected by wound healing and Transwell assays. BAG3 was detected using qPCR and western blot analysis. Transcriptional and translational inhibitors (actinomycin D and cycloheximide, respectively) were used to study the effect of AGEs on the expression of BAG3 in VSMCs. Lentiviral plasmids containing short hairpin RNA (shRNA) against rat BAG3 or control shRNA were transduced into VSMCs. Cellular ROS were detected by 2′,7′-dichlorofluorescein diacetate (DCFH-DA) staining. Mitochondrial membrane potential was detected by tetramethylrhodamine methyl ester (TMRE) staining. AGEs significantly increased the expression of BAG3 in a dose-and time-dependent manner. Furthermore, AGEs mainly increased the expression of BAG3 mRNA by increasing the RNA synthesis rather than inhibiting the RNA translation. BAG3 knockdown reduced the proliferation and migration of VSMCs induced by AGEs. BAG3 knockdown reduced the generation of ROS and sustained the mitochondrial membrane potential of VSMCs. Reduction of ROS production by N-acetylcysteine (NAC), a potent antioxidant, also reduced the proliferation and migration of VSMCs. On the whole, the present study demonstrated for the first time that AGEs could increase ROS production and promote the proliferation and migration of VSMCs by upregulating BAG3 expression. This study indicated that BAG3 should be considered as a potential target for the prevention and/or treatment of vascular complications of diabetes. PMID:28350077

  15. Advanced glycation end products promote the proliferation and migration of primary rat vascular smooth muscle cells via the upregulation of BAG3.

    PubMed

    Li, Cunshu; Chang, Ye; Li, Yuan; Chen, Shuang; Chen, Yintao; Ye, Ning; Dai, Dongxue; Sun, Yingxian

    2017-05-01

    The present study was aimed to investigate the role of reactive oxygen species (ROS) on advanced glycation end product (AGE)-induced proliferation and migration of vascular smooth muscle cells (VSMCs) and whether Bcl-2‑associated athanogene 3 (BAG3) is involved in the process. Primary rat VSMCs were extracted and cultured in vitro. Cell viability was detected by MTT assay and cell proliferation was detected by EdU incorporation assay. Cell migration was detected by wound healing and Transwell assays. BAG3 was detected using qPCR and western blot analysis. Transcriptional and translational inhibitors (actinomycin D and cycloheximide, respectively) were used to study the effect of AGEs on the expression of BAG3 in VSMCs. Lentiviral plasmids containing short hairpin RNA (shRNA) against rat BAG3 or control shRNA were transduced into VSMCs. Cellular ROS were detected by 2',7'-dichlorofluorescein diacetate (DCFH-DA) staining. Mitochondrial membrane potential was detected by tetramethylrhodamine methyl ester (TMRE) staining. AGEs significantly increased the expression of BAG3 in a dose-and time-dependent manner. Furthermore, AGEs mainly increased the expression of BAG3 mRNA by increasing the RNA synthesis rather than inhibiting the RNA translation. BAG3 knockdown reduced the proliferation and migration of VSMCs induced by AGEs. BAG3 knockdown reduced the generation of ROS and sustained the mitochondrial membrane potential of VSMCs. Reduction of ROS production by N-acetylcysteine (NAC), a potent antioxidant, also reduced the proliferation and migration of VSMCs. On the whole, the present study demonstrated for the first time that AGEs could increase ROS production and promote the proliferation and migration of VSMCs by upregulating BAG3 expression. This study indicated that BAG3 should be considered as a potential target for the prevention and/or treatment of vascular complications of diabetes.

  16. Modeling the Distribution of Migratory Bird Stopovers to Inform Landscape-Scale Siting of Wind Development

    PubMed Central

    Pocewicz, Amy; Estes-Zumpf, Wendy A.; Andersen, Mark D.; Copeland, Holly E.; Keinath, Douglas A.; Griscom, Hannah R.

    2013-01-01

    Conservation of migratory birds requires understanding the distribution of and potential threats to their migratory habitats. However, although migratory birds are protected under international treaties, few maps have been available to represent migration at a landscape scale useful to target conservation efforts or inform the siting of wind energy developments that may affect migratory birds. To fill this gap, we developed models that predict where four groups of birds concentrate or stopover during their migration through the state of Wyoming, USA: raptors, wetland, riparian and sparse grassland birds. The models were based on existing literature and expert knowledge concerning bird migration behavior and ecology and validated using expert ratings and known occurrences. There was significant agreement between migratory occurrence data and migration models for all groups except raptors, and all models ranked well with experts. We measured the overlap between the migration concentration models and a predictive model of wind energy development to assess the potential exposure of migratory birds to wind development and illustrate the utility of migratory concentration models for landscape-scale planning. Wind development potential is high across 15% of Wyoming, and 73% of this high potential area intersects important migration concentration areas. From 5.2% to 18.8% of each group’s important migration areas was represented within this high wind potential area, with the highest exposures for sparse grassland birds and the lowest for riparian birds. Our approach could be replicated elsewhere to fill critical data gaps and better inform conservation priorities and landscape-scale planning for migratory birds. PMID:24098379

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

    PubMed

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

    2013-06-04

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

  18. Anticipated Job Benefits, Career Aspiration, and Generalized Self-efficacy as Predictors for Migration Decision-Making

    PubMed Central

    Hoppe, Annekatrin; Fujishiro, Kaori

    2015-01-01

    This study aims to identify person-level factors, rather than economic situations, that influence migration decision-making and actual migration. Building on the theory of planned behavior, this study investigated potential migrants’ expectations and attitudes toward migration and career (i.e., anticipated job benefits of migration, career aspiration) as well as beliefs (i.e., generalized self-efficacy) as predictors of migration decision-making conceptualized in three phases: the pre-decisional, pre-actional, and actional phases. This was examined with cross-sectional pre-migration questionnaire data from 1163 potential migrants from Spain to Germany. We also examined whether the migration decision-making phases predicted actual migration with a subsample (n=249) which provided follow-up data within twelve months. For the cross-sectional sample, multinomial logistic regressions revealed that anticipated job benefits and career aspiration are predictive for all migration phases. Self-efficacy predicts the preactional (e.g., gathering information) and actional phases (e.g., making practical arrangements). Finally, for those with low self-efficacy, anticipated job benefits play a stronger role for taking action. For the longitudinal subsample, a logistic regression revealed that being in the preactional and actional phases at baseline is predictive of actual migration within twelve months. This study expands previous research on migration intentions and behaviors by focusing on expectations, values, and beliefs as person-level predictors for migration decision-making. With a longitudinal sample, it shows that international migration is a process that involves multiple phases. PMID:26379343

  19. 3D printing of biomimetic microstructures for cancer cell migration.

    PubMed

    Huang, Tina Qing; Qu, Xin; Liu, Justin; Chen, Shaochen

    2014-02-01

    To understand the physical behavior and migration of cancer cells, a 3D in vitro micro-chip in hydrogel was created using 3D projection printing. The micro-chip has a honeycomb branched structure, aiming to mimic 3D vascular morphology to test, monitor, and analyze differences in the behavior of cancer cells (i.e. HeLa) vs. non-cancerous cell lines (i.e. 10 T1/2). The 3D Projection Printing system can fabricate complex structures in seconds from user-created designs. The fabricated microstructures have three different channel widths of 25, 45, and 120 microns wide to reflect a range of blood vessel diameters. HeLa and 10 T1/2 cells seeded within the micro-chip were then analyzed for morphology and cell migration speed. 10 T1/2 cells exhibited greater changes in morphology due to channel size width than HeLa cells; however, channel width had a limited effect on 10 T1/2 cell migration while HeLa cancer cell migration increased as channel width decreased. This physiologically relevant 3D cancer tissue model has the potential to be a powerful tool for future drug discoveries and cancer migration studies.

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2012-10-01

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

  2. Resveratrol Prevents High Fluence Red Light-Emitting Diode Reactive Oxygen Species-Mediated Photoinhibition of Human Skin Fibroblast Migration.

    PubMed

    Mamalis, Andrew; Koo, Eugene; Isseroff, R Rivkah; Murphy, William; Jagdeo, Jared

    2015-01-01

    Skin fibrosis is a significant medical problem that leads to a functional, aesthetic, and psychosocial impact on quality-of-life. Light-emitting diode-generated 633-nm red light (LED-RL) is part of the visible light spectrum that is not known to cause DNA damage and is considered a safe, non-invasive, inexpensive, and portable potential alternative to ultraviolet phototherapy that may change the treatment paradigm of fibrotic skin disease. The goal of our study was to investigate the how reactive oxygen species (ROS) free radicals generated by high fluence LED-RL inhibit the migration of skin fibroblasts, the main cell type involved in skin fibrosis. Fibroblast migration speed is increased in skin fibrosis, and we studied cellular migration speed of cultured human skin fibroblasts as a surrogate measure of high fluence LED-RL effect on fibroblast function. To ascertain the inhibitory role of LED-RL generated ROS on migration speed, we hypothesized that resveratrol, a potent antioxidant, could prevent the photoinhibitory effects of high fluence LED-RL on fibroblast migration speed. High fluence LED-RL generated ROS were measured by flow cytometry analysis using dihydrorhodamine (DHR). For purposes of comparison, we assessed the effects of ROS generated by hydrogen peroxide (H2O2) on fibroblast migration speed and the ability of resveratrol, a well known antioxidant, to prevent LED-RL and H2O2 generated ROS-associated changes in fibroblast migration speed. To determine whether resveratrol could prevent the high fluence LED-RL ROS-mediated photoinhibition of human skin fibroblast migration, treated cells were incubated with resveratrol at concentrations of 0.0001% and 0.001% for 24 hours, irradiated with high fluences LED-RL of 480, 640, and 800 J/cm2. High fluence LED-RL increases intracellular fibroblast ROS and decreases fibroblast migration speed. LED-RL at 480, 640 and 800 J/cm2 increased ROS levels to 132.8%, 151.0%, and 158.4% relative to matched controls, respectively. These LED-RL associated increases in ROS were prevented by pretreating cells with 0.0001% or 0.001% resveratrol. Next, we quantified the effect of hydrogen peroxide (H2O2)-associated ROS on fibroblast migration speed, and found that while H2O2-associated ROS significantly decreased relative fibroblast migration speed, pretreatment with 0.0001% or 0.001% resveratrol significantly prevented the decreases in migration speed. Furthermore, we found that LED-RL at 480, 640 and 800 J/cm2 decreased fibroblast migration speed to 83.0%, 74.4%, and 68.6% relative to matched controls, respectively. We hypothesized that these decreases in fibroblast migration speed were due to associated increases in ROS generation. Pretreatment with 0.0001% and 0.001% resveratrol prevented the LED-RL associated decreases in migration speed. High fluence LED-RL increases ROS and is associated with decreased fibroblast migration speed. We provide mechanistic support that the decreased migration speed associated with high fluence LED-RL is mediated by ROS, by demonstrating that resveratrol prevents high fluence LED-RL associated migration speed change. These data lend support to an increasing scientific body of evidence that high fluence LED-RL has anti-fibrotic properties. We hypothesize that our findings may result in a greater understanding of the fundamental mechanisms underlying visible light interaction with skin and we anticipate clinicians and other researchers may utilize these pathways for patient benefit.

  3. Interleukin-3 enhances the migration of human mesenchymal stem cells by regulating expression of CXCR4.

    PubMed

    Barhanpurkar-Naik, Amruta; Mhaske, Suhas T; Pote, Satish T; Singh, Kanupriya; Wani, Mohan R

    2017-07-14

    Mesenchymal stem cells (MSCs) represent an important source for cell therapy in regenerative medicine. MSCs have shown promising results for repair of damaged tissues in various degenerative diseases in animal models and also in human clinical trials. However, little is known about the factors that could enhance the migration and tissue-specific engraftment of exogenously infused MSCs for successful regenerative cell therapy. Previously, we have reported that interleukin-3 (IL-3) prevents bone and cartilage damage in animal models of rheumatoid arthritis and osteoarthritis. Also, IL-3 promotes the differentiation of human MSCs into functional osteoblasts and increases their in-vivo bone regenerative potential in immunocompromised mice. However, the role of IL-3 in migration of MSCs is not yet known. In the present study, we investigated the role of IL-3 in migration of human MSCs under both in-vitro and in-vivo conditions. MSCs isolated from human bone marrow, adipose and gingival tissues were used for in-vitro cell migration, motility and wound healing assays in the presence or absence of IL-3. The effect of IL-3 preconditioning on expression of chemokine receptors and integrins was examined by flow cytometry and real-time PCR. The in-vivo migration of IL-3-preconditioned MSCs was investigated using a subcutaneous matrigel-releasing stromal cell-derived factor-1 alpha (SDF-1α) model in immunocompromised mice. We observed that human MSCs isolated from all three sources express IL-3 receptor-α (IL-3Rα) both at gene and protein levels. IL-3 significantly enhances in-vitro migration, motility and wound healing abilities of MSCs. Moreover, IL-3 preconditioning upregulates expression of chemokine (C-X-C motif) receptor 4 (CXCR4) on MSCs, which leads to increased migration of cells towards SDF-1α. Furthermore, CXCR4 antagonist AMD3100 decreases the migration of IL-3-treated MSCs towards SDF-1α. Importantly, IL-3 also induces in-vivo migration of MSCs towards subcutaneously implanted matrigel-releasing-SDF-1α in immunocompromised mice. The present study demonstrates for the first time that IL-3 has an important role in enhancing the migration of human MSCs through regulation of the CXCR4/SDF-1α axis. These findings suggest a potential role of IL-3 in improving the efficacy of MSCs in regenerative cell therapy.

  4. Determination of the wound healing effect of Calendula extracts using the scratch assay with 3T3 fibroblasts.

    PubMed

    Fronza, M; Heinzmann, B; Hamburger, M; Laufer, S; Merfort, I

    2009-12-10

    PHARMACOLOGICAL RELEVANCE: Presentation of the scratch assay as a convenient and inexpensive in vitro tool to gain first insights in the wound healing potential of plant extracts and natural compounds. The present study deals with the optimization of the scratch assay which can be used as an in vitro model for quantification of fibroblast migration to and proliferation into the wounded area. It is suitable for the first evaluation of the wound re-epithelialization potential of crude herbal extracts, isolated compounds and pharmaceutical preparations. As a proof of concept three preparations from traditional medicinal plants were investigated. Swiss 3T3 albino mouse fibroblasts were used in monolayers and platelet derived growth factor as positive control. Hexane and ethanolic extracts from Calendula officinalis and Matricaria recutita, Hypericum oil as well as the triterpenoids faradiol myristate and palmitate were studied. To differentiate between proliferation and migration antimitotic mitomycin C was added. Both extracts of Calendula officinalis stimulated proliferation and migration of fibroblasts at low concentrations, e.g. 10 microg/ml enhanced cell numbers by 64.35% and 70.53%, respectively. Inhibition of proliferation showed that this effect is mainly due to stimulation of migration. Faradiol myristate and palmitate gave comparable stimulation rates at an almost 50 microg/ml concentration, indicating that they contribute partially, but not most significantly to the wound healing effects of Calendula preparations. Extracts from Matricaria recutita were only moderately active. Hypericum oil was cytotoxic at concentrations higher than 0.5 microg/ml. The scratch assay in the present form can be used as a promising scientific approach and platform to differentiate between plant extracts known for their wound healing and their anti-inflammatory properties.

  5. An Aryl Hydrocarbon Receptor-Mediated Amplification Loop That Enforces Cell Migration in ER-/PR-/Her2- Human Breast Cancer Cells.

    PubMed

    Novikov, Olga; Wang, Zhongyan; Stanford, Elizabeth A; Parks, Ashley J; Ramirez-Cardenas, Alejandra; Landesman, Esther; Laklouk, Israa; Sarita-Reyes, Carmen; Gusenleitner, Daniel; Li, Amy; Monti, Stefano; Manteiga, Sara; Lee, Kyongbum; Sherr, David H

    2016-11-01

    The endogenous ligand-activated aryl hydrocarbon receptor (AHR) plays an important role in numerous biologic processes. As the known number of AHR-mediated processes grows, so too does the importance of determining what endogenous AHR ligands are produced, how their production is regulated, and what biologic consequences ensue. Consequently, our studies were designed primarily to determine whether ER - /PR - /Her2 - breast cancer cells have the potential to produce endogenous AHR ligands and, if so, how production of these ligands is controlled. We postulated that: 1) malignant cells produce tryptophan-derived AHR ligand(s) through the kynurenine pathway; 2) these metabolites have the potential to drive AHR-dependent breast cancer migration; 3) the AHR controls expression of a rate-limiting kynurenine pathway enzyme(s) in a closed amplification loop; and 4) environmental AHR ligands mimic the effects of endogenous ligands. Data presented in this work indicate that primary human breast cancers, and their metastases, express high levels of AHR and tryptophan-2,3-dioxygenase (TDO); representative ER - /PR - /Her2 - cell lines express TDO and produce sufficient intracellular kynurenine and xanthurenic acid concentrations to chronically activate the AHR. TDO overexpression, or excess kynurenine or xanthurenic acid, accelerates migration in an AHR-dependent fashion. Environmental AHR ligands 2,3,7,8-tetrachlorodibenzo[p]dioxin and benzo[a]pyrene mimic this effect. AHR knockdown or inhibition significantly reduces TDO2 expression. These studies identify, for the first time, a positive amplification loop in which AHR-dependent TDO2 expression contributes to endogenous AHR ligand production. The net biologic effect of AHR activation by endogenous ligands, which can be mimicked by environmental ligands, is an increase in tumor cell migration, a measure of tumor aggressiveness. Copyright © 2016 by The Author(s).

  6. An Aryl Hydrocarbon Receptor-Mediated Amplification Loop That Enforces Cell Migration in ER−/PR−/Her2− Human Breast Cancer Cells

    PubMed Central

    Novikov, Olga; Wang, Zhongyan; Stanford, Elizabeth A.; Parks, Ashley J.; Ramirez-Cardenas, Alejandra; Landesman, Esther; Laklouk, Israa; Sarita-Reyes, Carmen; Gusenleitner, Daniel; Li, Amy; Monti, Stefano; Manteiga, Sara; Lee, Kyongbum

    2016-01-01

    The endogenous ligand-activated aryl hydrocarbon receptor (AHR) plays an important role in numerous biologic processes. As the known number of AHR-mediated processes grows, so too does the importance of determining what endogenous AHR ligands are produced, how their production is regulated, and what biologic consequences ensue. Consequently, our studies were designed primarily to determine whether ER−/PR−/Her2− breast cancer cells have the potential to produce endogenous AHR ligands and, if so, how production of these ligands is controlled. We postulated that: 1) malignant cells produce tryptophan-derived AHR ligand(s) through the kynurenine pathway; 2) these metabolites have the potential to drive AHR-dependent breast cancer migration; 3) the AHR controls expression of a rate-limiting kynurenine pathway enzyme(s) in a closed amplification loop; and 4) environmental AHR ligands mimic the effects of endogenous ligands. Data presented in this work indicate that primary human breast cancers, and their metastases, express high levels of AHR and tryptophan-2,3-dioxygenase (TDO); representative ER−/PR−/Her2− cell lines express TDO and produce sufficient intracellular kynurenine and xanthurenic acid concentrations to chronically activate the AHR. TDO overexpression, or excess kynurenine or xanthurenic acid, accelerates migration in an AHR-dependent fashion. Environmental AHR ligands 2,3,7,8-tetrachlorodibenzo[p]dioxin and benzo[a]pyrene mimic this effect. AHR knockdown or inhibition significantly reduces TDO2 expression. These studies identify, for the first time, a positive amplification loop in which AHR-dependent TDO2 expression contributes to endogenous AHR ligand production. The net biologic effect of AHR activation by endogenous ligands, which can be mimicked by environmental ligands, is an increase in tumor cell migration, a measure of tumor aggressiveness. PMID:27573671

  7. Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cells.

    PubMed

    Molina-Molina, M; Machahua-Huamani, C; Vicens-Zygmunt, V; Llatjós, R; Escobar, I; Sala-Llinas, E; Luburich-Hernaiz, P; Dorca, J; Montes-Worboys, A

    2018-04-27

    Pirfenidone, a pleiotropic anti-fibrotic treatment, has been shown to slow down disease progression of idiopathic pulmonary fibrosis (IPF), a fatal and devastating lung disease. Rapamycin, an inhibitor of fibroblast proliferation could be a potential anti-fibrotic drug to improve the effects of pirfenidone. Primary lung fibroblasts from IPF patients and human alveolar epithelial cells (A549) were treated in vitro with pirfenidone and rapamycin in the presence or absence of transforming growth factor β1 (TGF-β). Extracellular matrix protein and gene expression of markers involved in lung fibrosis (tenascin-c, fibronectin, collagen I [COL1A1], collagen III [COL3A1] and α-smooth muscle actin [α-SMA]) were analyzed. A cell migration assay in pirfenidone, rapamycin and TGF-β-containing media was performed. Gene and protein expression of tenascin-c and fibronectin of fibrotic fibroblasts were reduced by pirfenidone or rapamycin treatment. Pirfenidone-rapamycin treatment did not revert the epithelial to mesenchymal transition pathway activated by TGF-β. However, the drug combination significantly abrogated fibroblast to myofibroblast transition. The inhibitory effect of pirfenidone on fibroblast migration in the scratch-wound assay was potentiated by rapamycin combination. These findings indicate that the combination of pirfenidone and rapamycin widen the inhibition range of fibrogenic markers and prevents fibroblast migration. These results would open a new line of research for an anti-fibrotic combination therapeutic approach.

  8. Apatinib inhibits migration and invasion as well as PD-L1 expression in osteosarcoma by targeting STAT3.

    PubMed

    Zheng, Bingxin; Ren, Tingting; Huang, Yi; Guo, Wei

    2018-01-08

    The cure rate of osteosarcoma has not improved in the past 30 years. The new treatments and drugs is urgently needed, especially for metastatic osteosarcoma. Anti-angiogenesis therapy and immunotherapy has got promising anti-tumor effects in various tumors. It is hypothesised that combining checkpoint inhibitor immunotherapies with antiangiogenic treatment may have a synergistic effect and enhance the efficacy of both treatments. However, its underlying mechanism remain largely uninvestigated. To investigate the clinical significance of vascular endothelial growth factor receptor-2 (VEGFR2) and programmed death ligand-1 (PD-L1) in osteosarcoma, we analyzes their expression levels in 93 osteosarcoma specimens by immunohistochemistry. Meanwhile, we analyzes their correlation with the metastatic behavior and overall survival (OS). We also investigate the effects of Apatinib on migration and invasion of osteosarcoma cells and its underlying mechanism in vitro and in vivo. In our study, the positive rates of the VEGFR2 and PD-L1 expression are 64.5% (60/93) and 35.5% (33/93), respectively. A significant correlation is detected between VEGFR2 and PD-L1 expression (P = 0.009). Receiver-operating characteristic (ROC) curves analysis indicates the predictive value of the two markers in tumor metastasis, and both PD-L1 and VEGFR2 are negatively correlated with OS. Transwell assays reveals that VEGFR2 inhibition attenuates migration and invasion of osteosarcoma cells. Mechanistically, we demonstrate that Apatinib attenuates migration and invasion by suppressing epithelial-mesenchymal transition (EMT) and inactivating STAT3. Additionally, Apatinib reduces PD-L1 expression in osteosarcoma cells. Apatinib markedly weakens pulmonary metastatic potential of osteosarcoma in vivo. In conclusion, our study reveals a pro-metastatic functional mechanism for VEGFR2 in osteosarcoma. Furthermore, we demonstrate that Apatinib exerts anti-tumor effect not only through antiangiogenic effect, but also via suppressing immune escape, which may represent a potential therapeutic target for metastatic osteosarcoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Causal modeling in international migration research: a methodological prolegomenon.

    PubMed

    Papademetriou, D G; Hopple, G W

    1982-10-01

    The authors examine the value of using models to study the migration process. In particular, they demonstrate the potential utility of a partial least squares modeling approach to the causal analysis of international migration.

  10. Analytical tools for identification of non-intentionally added substances (NIAS) coming from polyurethane adhesives in multilayer packaging materials and their migration into food simulants.

    PubMed

    Félix, Juliana S; Isella, Francesca; Bosetti, Osvaldo; Nerín, Cristina

    2012-07-01

    Adhesives used in food packaging to glue different materials can provide several substances as potential migrants, and the identification of potential migrants and migration tests are required to assess safety in the use of adhesives. Solid-phase microextraction in headspace mode and gas chromatography coupled to mass spectrometry (HS-SPME-GC-MS) and ChemSpider and SciFinder databases were used as powerful tools to identify the potential migrants in the polyurethane (PU) adhesives and also in the individual plastic films (polyethylene terephthalate, polyamide, polypropylene, polyethylene, and polyethylene/ethyl vinyl alcohol). Migration tests were carried out by using Tenax(®) and isooctane as food simulants, and the migrants were analyzed by gas chromatography coupled to mass spectrometry. More than 63 volatile and semivolatile compounds considered as potential migrants were detected either in the adhesives or in the films. Migration tests showed two non-intentionally added substances (NIAS) coming from PU adhesives that migrated through the laminates into Tenax(®) and into isooctane. Identification of these NIAS was achieved through their mass spectra, and 1,6-dioxacyclododecane-7,12-dione and 1,4,7-trioxacyclotridecane-8,13-dione were confirmed. Caprolactam migrated into isooctane, and its origin was the external plastic film in the multilayer, demonstrating real diffusion through the multilayer structure. Comparison of the migration values between the simulants and conditions will be shown and discussed.

  11. Effects of atelocollagen on neural stem cell function and its migrating capacity into brain in psychiatric disease model.

    PubMed

    Yoshinaga, Toshihiro; Hashimoto, Eri; Ukai, Wataru; Ishii, Takao; Shirasaka, Tomohiro; Kigawa, Yoshiyasu; Tateno, Masaru; Kaneta, Hiroo; Watanabe, Kimihiko; Igarashi, Takeshi; Kobayashi, Seiju; Sohma, Hitoshi; Kato, Tadafumi; Saito, Toshikazu

    2013-10-01

    Stem cell therapy is well proposed as a potential method for the improvement of neurodegenerative damage in the brain. Among several different procedures to reach the cells into the injured lesion, the intravenous (IV) injection has benefit as a minimally invasive approach. However, for the brain disease, prompt development of the effective treatment way of cellular biodistribution of stem cells into the brain after IV injection is needed. Atelocollagen has been used as an adjunctive material in a gene, drug and cell delivery system because of its extremely low antigenicity and bioabsorbability to protect these transplants from intrabody environment. However, there is little work about the direct effect of atelocollagen on stem cells, we examined the functional change of survival, proliferation, migration and differentiation of cultured neural stem cells (NSCs) induced by atelocollagen in vitro. By 72-h treatment 0.01-0.05% atelocollagen showed no significant effects on survival, proliferation and migration of NSCs, while 0.03-0.05% atelocollagen induced significant reduction of neuronal differentiation and increase of astrocytic differentiation. Furthermore, IV treated NSCs complexed with atelocollagen (0.02%) could effectively migrate into the brain rather than NSC treated alone using chronic alcohol binge model rat. These experiments suggested that high dose of atelocollagen exerts direct influence on NSC function but under 0.03% of atelocollagen induces beneficial effect on regenerative approach of IV administration of NSCs for CNS disease.

  12. Atorvastatin Promotes Cytotoxicity and Reduces Migration and Proliferation of Human A172 Glioma Cells.

    PubMed

    Oliveira, Karen A; Dal-Cim, Tharine; Lopes, Flávia G; Ludka, Fabiana K; Nedel, Cláudia B; Tasca, Carla I

    2018-02-01

    Malignant gliomas have resistance mechanisms to chemotherapy that enable tumor invasiveness and aggressiveness. Alternative therapies in cancer treatment, as statins, have been suggested to decrease proliferation, inhibit cell migration, and induce cell death. The aim of this study was to evaluate the effect of atorvastatin (ATOR) on cell viability, migration, proliferation, apoptosis, and autophagy in A172 human glioma cells. Temozolomide (TMZ), a chemotherapic used to glioma treatment, was tested as a comparison to cytotoxic effects on gliomas. Cell viability was also assessed in primary culture of cortical astrocytes. ATOR treatment (0.1 to 20 μM) did not alter astrocytic viability. However, in glioma cells, ATOR showed cytotoxic effect at 10 and 20 μM concentrations. TMZ (500 μM) reduced cell viability similarly to ATOR, and drug association did not show additive effect on cell viability. ATOR, TMZ, and their association decreased cell migration. ATOR also decreased glioma cell proliferation. ATOR increased apoptosis, and TMZ association showed a potentiation effect, enhancing it. ATOR and TMZ treatment increased acidic vesicular organelle (AVO) presence in A172 cells, an indicative of autophagy. ATOR effect of reducing A172 cell viability did not alter glutamate transport and glutamine synthetase activity, but it was partially prevented through antagonism of ionotropic and metabotropic glutamate receptors. Our data shows a cytotoxic effect of ATOR on glioma cells, whereas no toxicity was observed to astrocytes. ATOR showed similar cytotoxic effect as TMZ to glioma cells, and it may be a safer drug, regarding side effect induction, than chemotherapic agents.

  13. The extra mile: Ungulate migration distance alters the use of seasonal range and exposure to anthropogenic risk

    USGS Publications Warehouse

    Sawyer, Hall; Middleton, Arthur D.; Hayes, Matthew M.; Kauffman, Matthew J.; Monteith, Kevin L.

    2016-01-01

    Partial migration occurs across a variety of taxa and has important ecological and evolutionary consequences. Among ungulates, studies of partially migratory populations have allowed researchers to compare and contrast performance metrics of migrants versus residents and examine how environmental factors influence the relative abundance of each. Such studies tend to characterize animals discretely as either migratory or resident, but we suggest that variable migration distances within migratory herds are an important and overlooked form of population structure, with potential consequences for animal fitness. We examined whether the variation in individual migration distances (20–264 km) within a single wintering population of mule deer (Odocoileus hemionus) was associated with several critical behavioral attributes of migration, including timing of migration, time allocation to seasonal ranges, and exposure to anthropogenic mortality risks. Both the timing of migration and the amount of time animals allocated to seasonal ranges varied with migration distance. Animals migrating long distances (150–250 km) initiated spring migration more than three weeks before than those migrating moderate (50–150 km) or short distances (<50 km). Across an entire year, long-distance migrants spent approximately 100 more days migrating compared to moderate- and short-distance migrants. Relatedly, winter residency of long-distance migrants was 71 d fewer than for animals migrating shorter distances. Exposure to anthropogenic mortality factors, including highways and fences, was high for long-distance migrants, whereas vulnerability to harvest was high for short- and moderate-distance migrants. By reducing the amount of time that animals spend on winter range, long-distance migration may alleviate intraspecific competition for limited forage and effectively increase carrying capacity. Clear differences in winter residency, migration duration, and risk of anthropogenic mortality among short-, moderate-, and long-distance migrants suggest fitness trade-offs may exist among migratory segments of the population. Future studies of partial migration may benefit from expanding comparisons of residents and migrants, to consider how variable migration distances of migrants may influence the costs and benefits of migration.

  14. Local application of periodontal ligament stromal cells promotes soft tissue regeneration.

    PubMed

    Baik, H S; Park, J; Lee, K J; Chung, C

    2014-09-01

    To test the potential stimulatory effect of local application of periodontal ligament (PDL) stromal cells on soft tissue regeneration. Fluorescently labeled PDL cells outgrown from extracted human premolars or phosphate-buffered saline were locally injected to the cutaneous wounds created on mice. Soft tissue regeneration was evaluated for 14 days using photographs and histomorphometry. PDL cell engraftment was tracked with confocal microscopy. To detect the paracrine effect of the PDL cells on soft tissue regeneration, PDL cell-conditioned medium (CM) was evaluated for the concentration of secretory factors, transforming growth factor-beta 1 (TGFβ1). The effect of PDL CM on the proliferation and migration of dermal fibroblast and keratinocyte was tested using MTT assay and migration assay. The application of PDL cells significantly promoted soft tissue regeneration compared with the application of PBS. Self-replicating PDL cells were engrafted into the hair follicles of the host tissue. Dermal fibroblast proliferation and keratinocyte migration were significantly enhanced by the treatment with PDL CM. Physiologically significant amount of TGFβ1 was secreted from PDL cells into the CM. Local injection of PDL cells promoted soft tissue regeneration in part by the enhancement of fibroblast proliferation and keratinocyte migration through a paracrine mechanism. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Migration and the Pursuit of Education in Southern Mexico

    ERIC Educational Resources Information Center

    Valentine, Jessa Lewis; Barham, Brad; Gitter, Seth; Nobles, Jenna

    2017-01-01

    Educational attainment in rural Mexico is increasingly structured by migration opportunities. The rise in adult US migration increases potential funding for adolescents to stay in school but may also decrease incentives for them to do so. Domestic migration flows can fund schooling locally, and may also support students' own movement for education…

  16. Modelling of wildlife migrations and its economic impacts

    NASA Astrophysics Data System (ADS)

    Myšková, Kateřina; Žák, Jaroslav

    2013-10-01

    Natural wildlife migrations are often disrupted by the construction of line structures, especially freeways. Various overpasses and underpasses (migration objects) are being designed to enable species to pass through line structures. The newly developed original procedure for the quantification of the utility of migration objects (migration potentials) and sections of line structures retrieves the deficiencies of the previous ones. The procedure has been developed under bulk information obtained by monitoring migrations using camera system and spy games. The log-normal distribution functions are used. The procedure for the evaluation of the probability of the permeability of the line structures sectors is also presented. The above mentioned procedures and algorithms can be used while planning, preparing, constructing or verifying the measures to assure the permeability of line structures for selected feral species. Using the procedures can significantly reduce financial costs and improve the permeability. When the migration potentials are correctly determined and the whole sector is taken into account for the migrations, some originally designed objects may be found to be redundant and not building them will bring financial savings.

  17. Cytotoxicity and mutagenicity studies on migration extracts from nanocomposites with potential use in food packaging.

    PubMed

    Maisanaba, Sara; Pichardo, Silvia; Jordá-Beneyto, María; Aucejo, Susana; Cameán, Ana M; Jos, Ángeles

    2014-04-01

    Clays are used in the food packaging industry to obtain nanocomposites. The use of these new materials is a concern, because they could reach consumers by oral exposure through possible migration, and potential toxic effects could be derived. In the present study, several in vitro basal cytotoxicity and mutagenicity tests on migration extracts obtained from a nanocomposite material with poly (lactic) acid (PLA) and two modified clays, Clay1 and Clay2, are shown. Migration extracts in distilled water showed values of 0.1 ± 0.2mg/dm(2) in all samples. Also, the content of characteristic metals of the clays structure (Al, Ca, Mg, Fe, Si) was studied and no statistical differences were observed. For the cytotoxicity assays, the human intestinal Caco-2 and human liver HepG2 cells were selected. Cells were exposed to concentrations between 2.5% and 100% extracts determining three different biomarkers of cellular viability. No significant differences were observed in the cytotoxicity assays. Finally, mutagenicity was evaluated by the Ames test and resulted in the absence of mutagenic response at all the concentrations assayed. Taking in account all above mentioned, these new materials show a good profile for their use in food packaging although further research is still needed. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2017-06-26

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

  19. 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.

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

    El-Badry, Kareem; Geha, Marla; Wetzel, Andrew

    We examine the effects of stellar feedback and bursty star formation on low-mass galaxies (M{sub star} = 2 × 10{sup 6} − 5 × 10{sup 10} M{sub ⊙}) using the Feedback in Realistic Environments (FIRE) simulations. While previous studies emphasized the impact of feedback on dark matter profiles, we investigate the impact on the stellar component: kinematics, radial migration, size evolution, and population gradients. Feedback-driven outflows/inflows drive significant radial stellar migration over both short and long timescales via two processes: (1) outflowing/infalling gas can remain star-forming, producing young stars that migrate ∼1 kpc within their first 100 Myr, and (2) gas outflows/inflows drive strong fluctuations in the globalmore » potential, transferring energy to all stars. These processes produce several dramatic effects. First, galaxies’ effective radii can fluctuate by factors of >2 over ∼200 Myr, and these rapid size fluctuations can account for much of the observed scatter in the radius at fixed M{sub star}. Second, the cumulative effects of many outflow/infall episodes steadily heat stellar orbits, causing old stars to migrate outward most strongly. This age-dependent radial migration mixes—and even inverts—intrinsic age and metallicity gradients. Thus, the galactic-archaeology approach of calculating radial star formation histories from stellar populations at z = 0 can be severely biased. These effects are strongest at M{sub star} ≈ 10{sup 7–9.6} M{sub ⊙}, the same regime where feedback most efficiently cores galaxies. Thus, detailed measurements of stellar kinematics in low-mass galaxies can strongly constrain feedback models and test baryonic solutions to small-scale problems in ΛCDM.« less

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Anitua, E; Pino, A; Orive, G

    2016-11-02

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

  4. Collective cell migration of thyroid carcinoma cells: a beneficial ability to override unfavourable substrates.

    PubMed

    Lobastova, Liudmila; Kraus, Dominik; Glassmann, Alexander; Khan, Dilaware; Steinhäuser, Christian; Wolff, Christina; Veit, Nadine; Winter, Jochen; Probstmeier, Rainer

    2017-02-01

    Tumor cell invasion and metastasis are life threatening events. Invasive tumor cells tend to migrate as collective sheets. In the present in vitro study we aimed to (i) assess whether collective tumor cells gain benefits in their migratory potential compared to single cells and (ii) to identify its putative underlying molecular mechanisms. The migratory potential of single and collective carcinoma cells was assessed using video time lapse microscopy and cell migration assays in the absence and presence of seven potential gap junction inhibitors or the Rac1 inhibitor Z62954982. The perturbation of gap junctions was assessed using a dye diffusion assay. In addition, LDH-based cytotoxicity and RT-PCR-based expression analyses were performed. Whereas single breast, cervix and thyroid carcinoma cells were virtually immobile on unfavourable plastic surfaces, we found that they gained pronounced migratory capacities as collectives under comparable conditions. Thyroid carcinoma cells, that were studied in more detail, were found to express specific subsets of connexins and to form active gap junctions as revealed by dye diffusion analysis. Although all potential gap junction blockers suppressed intercellular dye diffusion in at least one of the cell lines tested, only two of them were found to inhibit collective cell migration and none of them to inhibit single cell migration. In the presence of the Rac1 inhibitor Z62954982 collective migration, but not single cell migration, was found to be reduced up to 20 %. Our data indicate that collective migration enables tumor cells to cross otherwise unfavourable substrate areas. This capacity seems to be independent of intercellular communication via gap junctions, whereas Rac1-dependent intracellular signalling seems to be essential.

  5. A galvanotaxis assay for analysis of neural precursor cell migration kinetics in an externally applied direct current electric field.

    PubMed

    Babona-Pilipos, Robart; Popovic, Milos R; Morshead, Cindi M

    2012-10-13

    The discovery of neural stem and progenitor cells (collectively termed neural precursor cells) (NPCs) in the adult mammalian brain has led to a body of research aimed at utilizing the multipotent and proliferative properties of these cells for the development of neuroregenerative strategies. A critical step for the success of such strategies is the mobilization of NPCs toward a lesion site following exogenous transplantation or to enhance the response of the endogenous precursors that are found in the periventricular region of the CNS. Accordingly, it is essential to understand the mechanisms that promote, guide, and enhance NPC migration. Our work focuses on the utilization of direct current electric fields (dcEFs) to promote and direct NPC migration - a phenomenon known as galvanotaxis. Endogenous physiological electric fields function as critical cues for cell migration during normal development and wound repair. Pharmacological disruption of the trans-neural tube potential in axolotl embryos causes severe developmental malformations(1). In the context of wound healing, the rate of repair of wounded cornea is directly correlated with the magnitude of the epithelial wound potential that arises after injury, as shown by pharmacological enhancement or disruption of this dcEF(2-3). We have demonstrated that adult subependymal NPCs undergo rapid and directed cathodal migration in vitro when exposed to an externally applied dcEF. In this protocol we describe our lab's techniques for creating a simple and effective galvanotaxis assay for high-resolution, long-term observation of directed cell body translocation (migration) on a single-cell level. This assay would be suitable for investigating the mechanisms that regulate dcEF transduction into cellular motility through the use of transgenic or knockout mice, short interfering RNA, or specific receptor agonists/antagonists.

  6. Maternal and infant health of Mexican immigrants in the USA: the effects of acculturation, duration, and selective return migration.

    PubMed

    Ceballos, Miguel; Palloni, Alberto

    2010-08-01

    A significant body of research on minority health shows that while Hispanic immigrants experience unexpectedly favorable outcomes in maternal and infant health, their advantage deteriorates with increased time of residence in the USA. This is referred to as the 'acculturation paradox.' We assess the 'acculturation paradox' hypothesis that attributes this deterioration in birth and child health outcomes to negative effects of acculturation and behavioral adjustments made by immigrants while living in the USA, and investigate the potential for the existence of a selective return migration. We use a sample of Mexican immigrant women living in two Midwestern communities in the USA to analyze the effects of immigrant duration and acculturation on birth outcomes once controlling for social, behavioral, and environmental determinants of health status. These results are verified by conducting a similar analysis with a nationally representative sample of Mexican immigrants. We find duration of residence to have a significant and nonlinear relationship with birth outcomes and acculturation to not be statistically significant. The effect of mediators is minimal. The analyses of birth outcomes of Mexican immigrant women shows little evidence of an acculturation effect and indirectly suggest the existence of a selective return migration mechanism.

  7. Adenosine Stimulate Proliferation and Migration in Triple Negative Breast Cancer Cells

    PubMed Central

    Fernandez-Gallardo, Miriam; González-Ramírez, Ricardo; Sandoval, Alejandro; Monjaraz, Eduardo

    2016-01-01

    Emerging evidence suggests that the adenosine (Ado) receptors may play crucial roles in tumor progression. Here, we show that Ado increases proliferation and migration in a triple negative breast cancer model, the MDA-MB 231 cell line. The use of specific agonists and antagonists evidenced that these effects depend on the activation of the A2B receptor, which then triggers an intracellular response mediated by the adenylate cyclase/PKA/cAMP signaling pathway. Ado also increases the expression of NaV1.5 channels, a potential biomarker in breast cancer. Together, these data suggest important roles of the A2B receptors and NaV1.5 channels in the Ado-induced increase in proliferation and migration of the MDA-MB 231 cells. PMID:27911956

  8. Epidermal growth factor upregulates motility of Mat-LyLu rat prostate cancer cells partially via voltage-gated Na+ channel activity

    PubMed Central

    Ding, Yanning; Brackenbury, William J.; Onganer, Pinar U.; Montano, Ximena; Porter, Louise M.; Bates, Lucy F.; Djamgoz, Mustafa B. A.

    2014-01-01

    The main aim of this investigation was to determine whether a functional relationship existed between epidermal growth factor (EGF) and voltage-gated sodium channel (VGSC) upregulation, both associated with strongly metastatic prostate cancer cells. Incubation with EGF for 24 h more than doubled VGSC current density. Similar treatment with EGF significantly and dose-dependently enhanced the cells’ migration through Transwell filters. Both the patch clamp recordings and the migration assay suggested that endogenous EGF played a similar role. Importantly, co-application of EGF and tetrodotoxin, a highly selective VGSC blocker, abolished 65% of the potentiating effect of EGF. It is suggested that a significant portion of the EGF-induced enhancement of migration occurred via VGSC activity. PMID:17960590

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-05-01

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

  11. The effect of growth hormone on fibroblast proliferation and keratinocyte migration.

    PubMed

    Lee, Sang Woo; Kim, Suk Hwa; Kim, Ji Youn; Lee, Yoonho

    2010-04-01

    The beneficial effects of growth hormones (GHs) on wound healing have been reported. Although the mechanism of how GH promotes wound healing is unclear, there are reports showing that the principal factor lies in the GH-stimulated production of IGF-1 in topical wounds. In this study, a human primary cell model was devised to examine how the topical application of GHs affects fibroblast proliferation and keratinocyte migration, which play fundamental roles in wound healing. The fibroblasts were cultured in media with different concentrations of GH. The amount of fibroblast proliferation was assessed using a tetrazolium-based colourimetric assay (MTT assay). The amount of newly formed IGF-I mRNA was measured by reverse transcription and polymerase chain reaction (RT-PCR). Keratinocyte migration was compared using a migration assay. Fibroblast proliferation was significantly higher in the experimental group than in the control group (the absorbance of 2.5IU L(-1) GH applied group: 0.3954+/-0.056, control group: 0.2943+/-0.0554, P<0.05), and the promotion of IGF-I formation by fibroblasts was observed. There was more keratinocyte migration in the experimental group than in the control group (the remaining gap in the 2.5IU L(-1) GH applied group after keratinocyte migration: 46.57+/-2.22% of the primary gap, control group: 75.14+/-3.44%, P<0.05). GH enhances the local formation of IGF-1, which activates fibroblast proliferation and keratinocyte migration. These results highlight the potential of the topical application of GHs in the treatment of wounds. Copyright 2009 British Association of Plastic, Reconstructive and Aesthetic Surgeons. All rights reserved.

  12. Indomethacin inhibits eosinophil migration to prostaglandin D2 : therapeutic potential of CRTH2 desensitization for eosinophilic pustular folliculitis.

    PubMed

    Kataoka, Naoko; Satoh, Takahiro; Hirai, Aiko; Saeki, Kazumi; Yokozeki, Hiroo

    2013-09-01

    Indomethacin is a cyclo-oxygenase inhibitor, and shows therapeutic potential for various eosinophilic skin diseases, particularly eosinophilic pustular folliculitis. One of the unique characteristics of indomethacin is that, unlike other non-steroidal anti-inflammatory drugs, it is a potent agonist of chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2), a receptor for prostaglandin D2 (PGD2 ). This study investigated the pharmacological actions of indomethacin on eosinophil migration to clarify the actual mechanisms underlying the therapeutic effects of indomethacin on eosinophilic pustular folliculitis. Eosinophils exhibited chemokinetic and chemotactic responses to both PGD2 and indomethacin through CRTH2 receptors. Pre-treatment of eosinophils with indomethacin greatly inhibited eosinophil migration to PGD2 and, to a much lesser extent, to eotaxin (CCL11); these effects could be mediated by homologous and heterologous desensitization of eosinophil CRTH2 and CCR3, respectively, by agonistic effects of indomethacin on CRTH2. Indomethacin also cancelled a priming effect of Δ(12) -PGJ2 , a plasma metabolite of PGD2 , on eosinophil chemotaxis to eotaxin. Indomethacin down-modulated cell surface expression of both CRTH2 and CCR3. Hair follicle epithelium and epidermal keratinocytes around eosinophilic pustules together with the eccrine apparatus of palmoplantar lesions of eosinophilic pustular folliculitis were immunohistochemically positive for lipocalin-type PGD synthase. Indomethacin may exert therapeutic effects against eosinophilic skin diseases in which PGD2 -CRTH2 signals play major roles by reducing eosinophil responses to PGD2 . © 2013 John Wiley & Sons Ltd.

  13. Indomethacin inhibits eosinophil migration to prostaglandin D2: therapeutic potential of CRTH2 desensitization for eosinophilic pustular folliculitis

    PubMed Central

    Kataoka, Naoko; Satoh, Takahiro; Hirai, Aiko; Saeki, Kazumi; Yokozeki, Hiroo

    2013-01-01

    Summary Indomethacin is a cyclo-oxygenase inhibitor, and shows therapeutic potential for various eosinophilic skin diseases, particularly eosinophilic pustular folliculitis. One of the unique characteristics of indomethacin is that, unlike other non-steroidal anti-inflammatory drugs, it is a potent agonist of chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2), a receptor for prostaglandin D2 (PGD2). This study investigated the pharmacological actions of indomethacin on eosinophil migration to clarify the actual mechanisms underlying the therapeutic effects of indomethacin on eosinophilic pustular folliculitis. Eosinophils exhibited chemokinetic and chemotactic responses to both PGD2 and indomethacin through CRTH2 receptors. Pre-treatment of eosinophils with indomethacin greatly inhibited eosinophil migration to PGD2 and, to a much lesser extent, to eotaxin (CCL11); these effects could be mediated by homologous and heterologous desensitization of eosinophil CRTH2 and CCR3, respectively, by agonistic effects of indomethacin on CRTH2. Indomethacin also cancelled a priming effect of Δ12-PGJ2, a plasma metabolite of PGD2, on eosinophil chemotaxis to eotaxin. Indomethacin down-modulated cell surface expression of both CRTH2 and CCR3. Hair follicle epithelium and epidermal keratinocytes around eosinophilic pustules together with the eccrine apparatus of palmoplantar lesions of eosinophilic pustular folliculitis were immunohistochemically positive for lipocalin-type PGD synthase. Indomethacin may exert therapeutic effects against eosinophilic skin diseases in which PGD2-CRTH2 signals play major roles by reducing eosinophil responses to PGD2. PMID:23582181

  14. Cerium migration during PEM fuel cell assembly and operation

    DOE PAGES

    Baker, Andrew M.; Torraco, Dennis; Judge, Elizabeth J.; ...

    2015-09-14

    Cerium migration between PEM fuel cell components is influenced by potential-driven mobility, ionic diffusion, and gradients in water content. These factors were investigated in ex situ experiments and in operating fuel cells. Potential-induced migration was measured ex situ in hydrated window cells. Cerium-containing MEAs were also fabricated and tested under ASTs. MEA disassembly and subsequent XRF analysis were used to observe rapid cerium migration during cell assembly and operation. During MEA hot pressing, humidification, and low RH operation at OCV, ionic diffusion causes uniform migration from the membrane into the catalyst layers. During high RH operation at OCV, in-plane ceriummore » gradients arise due to variations in water content. These gradients may diminish the scavenging efficacy of cerium by reducing its proximity to generated radicals.« less

  15. Testing nano-silver food packaging to evaluate silver migration and food spoilage bacteria on chicken meat.

    PubMed

    Gallocchio, Federica; Cibin, Veronica; Biancotto, Giancarlo; Roccato, Anna; Muzzolon, Orietta; Carmen, Losasso; Simone, Belluco; Manodori, Laura; Fabrizi, Alberto; Patuzzi, Ilaria; Ricci, Antonia

    2016-06-01

    Migration of nanomaterials from food containers into food is a matter of concern because of the potential risk for exposed consumers. The aims of this study were to evaluate silver migration from a commercially available food packaging containing silver nanoparticles into a real food matrix (chicken meat) under plausible domestic storage conditions and to test the contribution of such packaging to limit food spoilage bacteria proliferation. Chemical analysis revealed the absence of silver in chicken meatballs under the experimental conditions in compliance with current European Union legislation, which establishes a maximum level of 0.010 mg kg(-1) for the migration of non-authorised substances through a functional barrier (Commission Regulation (EU) No. 10/2011). On the other hand, microbiological tests (total microbial count, Pseudomonas spp. and Enterobacteriaceae) showed no relevant difference in the tested bacteria levels between meatballs stored in silver-nanoparticle plastic bags or control bags. This study shows the importance of testing food packaging not only to verify potential silver migration as an indicator of potential nanoparticle migration, but also to evaluate the benefits in terms of food preservation so as to avoid unjustified usage of silver nanoparticles and possible negative impacts on the environment.

  16. [The breaking down of imaginary socio-cultural perceptions in the migration process].

    PubMed

    Aruj, R

    1998-01-01

    This is a general study of migration and of the reasons why people decide to migrate. The author develops a theoretical approach to the study of the causes of migration, which suggests that the decision to migrate is the result of a conflict which has taken place in the minds of potential migrants and their families in which traditional social and cultural values are questioned and found wanting. (ANNOTATION)

  17. Does Choice of Head Size and Neck Geometry Affect Stem Migration in Modular Large-Diameter Metal-on-Metal Total Hip Arthroplasty? A Preliminary Analysis

    PubMed Central

    Georgiou, CS; Evangelou, KG; Theodorou, EG; Provatidis, CG; Megas, PD

    2012-01-01

    Due to their theoretical advantages, hip systems combining modular necks and large diameter femoral heads have gradually gained popularity. However, among others, concerns regarding changes in the load transfer patterns were raised. Recent stress analyses have indeed shown that the use of modular necks and big femoral heads causes significant changes in the strain distribution along the femur. Our original hypothesis was that these changes may affect early distal migration of a modular stem. We examined the effect of head diameter and neck geometry on migration at two years of follow-up in a case series of 116 patients (125 hips), who have undergone primary Metal-on-Metal total hip arthroplasty with the modular grit-blasted Profemur®E stem combined with large-diameter heads (>36 mm). We found that choice of neck geometry and head diameter has no effect on stem migration. A multivariate regression analysis including the potential confounding variables of the body mass index, bone quality, canal fill and stem positioning revealed only a negative correlation between subsidence and canal fill in midstem area. Statistical analysis, despite its limitations, did not confirm our hypothesis that choice of neck geometry and/or head diameter affects early distal migration of a modular stem. However, the importance of correct stem sizing was revealed. PMID:23284597

  18. Does Choice of Head Size and Neck Geometry Affect Stem Migration in Modular Large-Diameter Metal-on-Metal Total Hip Arthroplasty? A Preliminary Analysis.

    PubMed

    Georgiou, Cs; Evangelou, Kg; Theodorou, Eg; Provatidis, Cg; Megas, Pd

    2012-01-01

    Due to their theoretical advantages, hip systems combining modular necks and large diameter femoral heads have gradually gained popularity. However, among others, concerns regarding changes in the load transfer patterns were raised. Recent stress analyses have indeed shown that the use of modular necks and big femoral heads causes significant changes in the strain distribution along the femur. Our original hypothesis was that these changes may affect early distal migration of a modular stem. We examined the effect of head diameter and neck geometry on migration at two years of follow-up in a case series of 116 patients (125 hips), who have undergone primary Metal-on-Metal total hip arthroplasty with the modular grit-blasted Profemur®E stem combined with large-diameter heads (>36 mm). We found that choice of neck geometry and head diameter has no effect on stem migration. A multivariate regression analysis including the potential confounding variables of the body mass index, bone quality, canal fill and stem positioning revealed only a negative correlation between subsidence and canal fill in midstem area. Statistical analysis, despite its limitations, did not confirm our hypothesis that choice of neck geometry and/or head diameter affects early distal migration of a modular stem. However, the importance of correct stem sizing was revealed.

  19. Modeling of thin-film GaAs growth

    NASA Technical Reports Server (NTRS)

    Heinbockel, J. H.

    1981-01-01

    A solid Monte Carlo model is constructed for the simulation of crystal growth. The model assumes thermally accommodated adatoms impinge upon the surface during a delta time interval. The surface adatoms are assigned a random energy from a Boltzmann distribution, and this energy determines whether the adatoms evaporate, migrate, or remain stationary during the delta time interval. For each addition or migration of an adatom, potential wells are adjusted to reflect the absorption, migration, or desorption potential changes.

  20. Numerical examination of the factors controlling DNAPL migration through a single fracture.

    PubMed

    Reynolds, D A; Kueper, B H

    2002-01-01

    The migration of five dense nonaqueous phase liquids (DNAPLs) through a single fracture in a clay aquitard was numerically simulated with the use of a compositional simulator. The effects of fracture aperture, fracture dip, matrix porosity, and matrix organic carbon content on the migration of chlorobenzene, 1,2-dichloroethylene, trichloroethylene, tetra-chloroethylene, and 1,2-dibromoethane were examined. Boundary conditions were chosen such that DNAPL entry into the system was allowed to vary according to the stresses applied. The aperture is the most important factor of those studied controlling the migration rate of DNAPL through a single fracture embedded in a clay matrix. Loss of mass to the matrix through diffusion does not significantly retard the migration rate of the DNAPL, particularly in larger aperture fractures (e.g., 50 microm). With time, the ratio of diffusive loss to the matrix to DNAPL flux into the fracture approaches an asymptotic value lower than unity. The implication is that matrix diffusion cannot arrest the migration of DNAPL in a single fracture. The complex relationships between density, viscosity, and solubility that, to some extent, govern the migration of DNAPL through these systems prevent accurate predictions without the use of numerical models. The contamination potential of the migrating DNAPL is significantly increased through the transfer of mass to the matrix. The occurrence of opposite concentration gradients within the matrix can cause dissolved phase contamination to exist in the system for more than 1000 years after the DNAPL has been completely removed from the fracture.

  1. 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.

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

    Fu Ping; Jiang Xiaohong; Arcasoy, Murat O.

    The role of erythropoietin receptor (EpoR) expression in tumor cells and the potential of EpoR-mediated signaling to contribute to cellular proliferation and invasiveness require further characterization. To determine whether EpoR expression and activation in tumor cells modulates intracellular signal transduction to promote cellular proliferation and migration, we employed a novel experimental model using human breast cancer cells engineered to stably express a constitutively active EpoR-R129C variant. EpoR-R129C expression resulted in increased cellular proliferation and migration of breast cancer cells and these effects were associated with significantly increased Epo-induced phosphorylation of ERK1/2, AKT and c-Jun-NH2-kinase (SAPK/JNK) proteins. Expression of the constitutivelymore » active EpoR-R129C receptor promoted the proliferation and migration of breast cancer cells via activation of ERK- and SAPK/JNK-dependent signaling pathways, respectively. These findings suggest that EpoR over-expression and activation in breast cancer cells has the potential to contribute to tumor progression by promoting the proliferation and invasiveness of the neoplastic cells.« less

  3. Swelling-induced chloride current in glioblastoma proliferation, migration, and invasion.

    PubMed

    Wong, Raymond; Chen, Wenliang; Zhong, Xiao; Rutka, James T; Feng, Zhong-Ping; Sun, Hong-Shuo

    2018-01-01

    Glioblastoma (GBM) remains as the most common and aggressive brain tumor. The survival of GBM has been linked to the aberrant activation of swelling-induced chloride current I Cl,swell . In this study, we investigated the effects of I Cl,swell on cell viability, proliferation, and migration in the human GBM cell lines, U251 and U87, using a combination of patch clamp electrophysiology, MTT, colony formation, wound healing assays and Western immunoblotting. First, we showed that the specific inhibitor of I Cl,swell , DCPIB, potently reduced the I Cl,swell in U87 cells. Next, in both U87 and U251 cells, we found that DCPIB reduced GBM viability, proliferation, colony formation, migration, and invasion. In addition, our Western immunoblot assay showed that DCPIB-treated U251 cells had a reduction in JAK2, STAT3, and Akt phosphorylation, thus, suggesting that DCPIB potentially suppresses GBM functions through inhibition of the JAK2/STAT3 and PI3K/Akt signaling pathways. Therefore, the I Cl,swell may be a potential drug target for GBM. © 2017 Wiley Periodicals, Inc.

  4. MiR-212 exerts suppressive effect on SKOV3 ovarian cancer cells through targeting HBEGF.

    PubMed

    Wei, Li-Qiang; Liang, Hui-Tao; Qin, Dong-Chun; Jin, Hui-Fang; Zhao, Yong; She, Ming-Cong

    2014-12-01

    MicroRNAs (miRNAs) play critical roles in the development and progression of ovarian cancer. We found that miR-212 was significantly downregulated in serum and tissues from epithelial ovarian cancer (EOC) patients. Overexpression of miR-212 in ovarian cancer cells inhibited cell proliferation, migration, and invasion. Luciferase reporter assay confirmed HBEGF as a direct target of miR-212. Overexpression of miR-212 decreased HBEGF expression at both the protein and messenger RNA (mRNA) levels. Knockdown of HBEGF expression in SKOV3 cell line significantly inhibited cell growth, migration, and invasion. HBEGF mRNA level was upregulated in EOC tissues and inversely correlated with miR-212 expression in tissues. Upregulation of HBEGF could attenuate the effect induced by miR-212. These findings indicate that miR-212 displays a tumor-suppressive effect in human ovarian cancer. And miR-212 suppresses cell proliferation, migration, and invasion by targeting the HBEGF transcript, highlighting the therapeutic potential of miR-212 and HBEGF in epithelial ovarian cancer treatment.

  5. 18β-glycyrrhetinic acid inhibits migration and invasion of human gastric cancer cells via the ROS/PKC-α/ERK pathway.

    PubMed

    Cai, Hongke; Chen, Xi; Zhang, Jianbo; Wang, Jijian

    2018-01-01

    18β-glycyrrhetinic acid (18β-GA) is a bioactive component of licorice root which exerts pharmacological activities including anti-inflammatory, antiviral, anti-oxidative and anti-cancer effects. The current study further investigated the molecular mechanisms associated with the inhibitory effects of 18β-GA on tumor metastasis in human gastric cancer cells. The results indicated that 18β-GA significantly reduced invasion and migration activities and suppressed MMP-2 and 9 activities on SGC-7901cells in a dose-dependent manner. Further study showed 18β-GA upregulated E-cadherin expression but downregulated vimentin expression. The results also showed that 18β-GA inhibited ROS formation, PKC-α expression and the phosphorylation of ERK in a dose-dependent manner. In conclusion, this study revealed that 18β-GA inhibits migration and invasion via the ROS/PKC-α/ERK signaling pathway in gastric cancer cells. This suggests that 18β-GA has the potential to be used as an effective chemopreventive agent for the prevention of gastric cancer metastasis.

  6. Natural disasters and population mobility in Bangladesh.

    PubMed

    Gray, Clark L; Mueller, Valerie

    2012-04-17

    The consequences of environmental change for human migration have gained increasing attention in the context of climate change and recent large-scale natural disasters, but as yet relatively few large-scale and quantitative studies have addressed this issue. We investigate the consequences of climate-related natural disasters for long-term population mobility in rural Bangladesh, a region particularly vulnerable to environmental change, using longitudinal survey data from 1,700 households spanning a 15-y period. Multivariate event history models are used to estimate the effects of flooding and crop failures on local population mobility and long-distance migration while controlling for a large set of potential confounders at various scales. The results indicate that flooding has modest effects on mobility that are most visible at moderate intensities and for women and the poor. However, crop failures unrelated to flooding have strong effects on mobility in which households that are not directly affected but live in severely affected areas are the most likely to move. These results point toward an alternate paradigm of disaster-induced mobility that recognizes the significant barriers to migration for vulnerable households as well their substantial local adaptive capacity.

  7. Comparing Habitat Suitability and Connectivity Modeling Methods for Conserving Pronghorn Migrations

    PubMed Central

    Poor, Erin E.; Loucks, Colby; Jakes, Andrew; Urban, Dean L.

    2012-01-01

    Terrestrial long-distance migrations are declining globally: in North America, nearly 75% have been lost. Yet there has been limited research comparing habitat suitability and connectivity models to identify migration corridors across increasingly fragmented landscapes. Here we use pronghorn (Antilocapra americana) migrations in prairie habitat to compare two types of models that identify habitat suitability: maximum entropy (Maxent) and expert-based (Analytic Hierarchy Process). We used distance to wells, distance to water, NDVI, land cover, distance to roads, terrain shape and fence presence to parameterize the models. We then used the output of these models as cost surfaces to compare two common connectivity models, least-cost modeling (LCM) and circuit theory. Using pronghorn movement data from spring and fall migrations, we identified potential migration corridors by combining each habitat suitability model with each connectivity model. The best performing model combination was Maxent with LCM corridors across both seasons. Maxent out-performed expert-based habitat suitability models for both spring and fall migrations. However, expert-based corridors can perform relatively well and are a cost-effective alternative if species location data are unavailable. Corridors created using LCM out-performed circuit theory, as measured by the number of pronghorn GPS locations present within the corridors. We suggest the use of a tiered approach using different corridor widths for prioritizing conservation and mitigation actions, such as fence removal or conservation easements. PMID:23166656

  8. Comparing habitat suitability and connectivity modeling methods for conserving pronghorn migrations.

    PubMed

    Poor, Erin E; Loucks, Colby; Jakes, Andrew; Urban, Dean L

    2012-01-01

    Terrestrial long-distance migrations are declining globally: in North America, nearly 75% have been lost. Yet there has been limited research comparing habitat suitability and connectivity models to identify migration corridors across increasingly fragmented landscapes. Here we use pronghorn (Antilocapra americana) migrations in prairie habitat to compare two types of models that identify habitat suitability: maximum entropy (Maxent) and expert-based (Analytic Hierarchy Process). We used distance to wells, distance to water, NDVI, land cover, distance to roads, terrain shape and fence presence to parameterize the models. We then used the output of these models as cost surfaces to compare two common connectivity models, least-cost modeling (LCM) and circuit theory. Using pronghorn movement data from spring and fall migrations, we identified potential migration corridors by combining each habitat suitability model with each connectivity model. The best performing model combination was Maxent with LCM corridors across both seasons. Maxent out-performed expert-based habitat suitability models for both spring and fall migrations. However, expert-based corridors can perform relatively well and are a cost-effective alternative if species location data are unavailable. Corridors created using LCM out-performed circuit theory, as measured by the number of pronghorn GPS locations present within the corridors. We suggest the use of a tiered approach using different corridor widths for prioritizing conservation and mitigation actions, such as fence removal or conservation easements.

  9. Carbon Ion Radiation Inhibits Glioma and Endothelial Cell Migration Induced by Secreted VEGF

    PubMed Central

    Liu, Yang; Liu, Yuanyuan; Sun, Chao; Gan, Lu; Zhang, Luwei; Mao, Aihong; Du, Yuting; Zhou, Rong; Zhang, Hong

    2014-01-01

    This study evaluated the effects of carbon ion and X-ray radiation and the tumor microenvironment on the migration of glioma and endothelial cells, a key process in tumorigenesis and angiogenesis during cancer progression. C6 glioma and human microvascular endothelial cells were treated with conditioned medium from cultures of glioma cells irradiated at a range of doses and the migration of both cell types, tube formation by endothelial cells, as well as the expression and secretion of migration-related proteins were evaluated. Exposure to X-ray radiation-conditioned medium induced dose-dependent increases in cell migration and tube formation, which were accompanied by an upregulation of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-2 and -9 expression. However, glioma cells treated with conditioned medium of cells irradiated at a carbon ion dose of 4.0 Gy showed a marked decrease in migratory potential and VEGF secretion relative to non-irradiated cells. The application of recombinant VEGF165 stimulated migration in glioma and endothelial cells, which was associated with increased FAK phosphorylation at Tyr861, suggesting that the suppression of cell migration by carbon ion radiation could be via VEGF-activated FAK signaling. Taken together, these findings indicate that carbon ion may be superior to X-ray radiation for inhibiting tumorigenesis and angiogenesis through modulation of VEGF level in the glioma microenvironment. PMID:24893038

  10. Torques Induced by Scattered Pebble-flow in Protoplanetary Disks

    NASA Astrophysics Data System (ADS)

    Benítez-Llambay, Pablo; Pessah, Martin E.

    2018-03-01

    Fast inward migration of planetary cores is a common problem in the current planet formation paradigm. Even though dust is ubiquitous in protoplanetary disks, its dynamical role in the migration history of planetary embryos has not been assessed. In this Letter, we show that the scattered pebble-flow induced by a low-mass planetary embryo leads to an asymmetric dust-density distribution that is able to exert a net torque. By analyzing a large suite of multifluid hydrodynamical simulations addressing the interaction between the disk and a low-mass planet on a fixed circular orbit, and neglecting dust feedback onto the gas, we identify two different regimes, gas- and gravity-dominated, where the scattered pebble-flow results in almost all cases in positive torques. We collect our measurements in a first torque map for dusty disks, which will enable the incorporation of the effect of dust dynamics on migration into population synthesis models. Depending on the dust drift speed, the dust-to-gas mass ratio/distribution, and the embryo mass, the dust-induced torque has the potential to halt inward migration or even induce fast outward migration of planetary cores. We thus anticipate that dust-driven migration could play a dominant role during the formation history of planets. Because dust torques scale with disk metallicity, we propose that dust-driven outward migration may enhance the occurrence of distant giant planets in higher-metallicity systems.

  11. Migration modelling from food-contact plastics into foodstuffs as a new tool for consumer exposure estimation.

    PubMed

    Franz, R

    2005-10-01

    One important aspect within the European Union's public healthcare is the exposure of consumers to undesirable chemicals in the diet. Food-contact materials (FCM) are one potential contamination source and therefore of particular interest for food exposure assessment. On the other hand, scientific investigations concerning the migration potential and behaviour of food-packaging materials have demonstrated that diffusion in and migration from FCM are foreseeable physical and, in principle, mathematically describable processes. Because of this situation and the current state-of-the-art in migration science, a research project was initiated within the 5th Framework Programme of the European Commission. This project, with the acronym 'FOODMIGROSURE' (European Union Contract No. 'QLK1-CT2002-2390') started on 1 March 2003, was due to last 3 years and had the participation of nine European project partners (see the project website: www.foodmigrosure.org). The aim of the project was to extend currently existing migration models (which have been demonstrated to be applicable for less complex matrices such as food simulants) to foodstuffs themselves. In this way, the project aims to provide a novel and economic tool for estimation of consumer exposure to chemicals migrating from food-contact plastic materials under any actual contact conditions. In addition, the project aims to increase knowledge of the mechanisms of diffusion of organic compounds in foodstuffs and provide data on the partitioning effects between FCM and foods. Today the latter aspect is increasingly regarded as a fundamental influence parameter for migration into foods. Based on the project achievements, a much better scientific basis is available to allow scientifically appropriate amendments of European Union Directive 85/572/EEC as well as to support further developments with the so-called Plastics Directive 2002/72/EC. The paper introduces the project and presents an overview of the project work progress.

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

    PubMed

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

    2016-09-01

    Coronary artery disease (CAD) accounts for over half of all cardiovascular disease-related deaths. Uncontrolled arterial smooth muscle (ASM) cell migration is a major component of CAD pathogenesis and efforts aimed at attenuating its progression are clinically essential. Cyclic nucleotide signaling has long been studied for its growth-mitigating properties in the setting of CAD and other vascular disorders. Heme-containing soluble guanylyl cyclase (sGC) synthesizes cyclic guanosine monophosphate (cGMP) and maintains vascular homeostasis predominantly through cGMP-dependent protein kinase (PKG) signaling. Considering that reactive oxygen species (ROS) can interfere with appropriate sGC signaling by oxidizing the cyclase heme moiety and so are associated with several CVD pathologies, the current study was designed to test the hypothesis that heme-independent sGC activation by BAY 60-2770 (BAY60) maintains cGMP levels despite heme oxidation and inhibits ASM cell migration through phosphorylation of the PKG target and actin-binding vasodilator-stimulated phosphoprotein (VASP). First, using the heme oxidant ODQ, cGMP content was potentiated in the presence of BAY60. Using a rat model of arterial growth, BAY60 significantly reduced neointima formation and luminal narrowing compared to vehicle (VEH)-treated controls. In rat ASM cells BAY60 significantly attenuated cell migration, reduced G:F actin, and increased PKG activity and VASP Ser239 phosphorylation (pVASP·S239) compared to VEH controls. Site-directed mutagenesis was then used to generate overexpressing full-length wild type VASP (FL-VASP/WT), VASP Ser239 phosphorylation-mimetic (FL-VASP/239D) and VASP Ser239 phosphorylation-resistant (FL-VASP/239A) ASM cell mutants. Surprisingly, FL-VASP/239D negated the inhibitory effects of FL-VASP/WT and FL-VASP/239A cells on migration. Furthermore, when FL-VASP mutants were treated with BAY60, only the FL-VASP/239D group showed reduced migration compared to its VEH controls. Intriguingly, FL-VASP/239D abrogated the stimulatory effects of FL-VASP/WT and FL-VASP/239A cells on PKG activity. In turn, pharmacologic blockade of PKG in the presence of BAY60 reversed the inhibitory effect of BAY60 on naïve ASM cell migration. Taken together, we demonstrate for the first time that BAY60 inhibits ASM cell migration through cGMP/PKG/VASP signaling yet through mechanisms independent of pVASP·S239 and that FL-VASP overexpression regulates PKG activity in rat ASM cells. These findings implicate BAY60 as a potential pharmacotherapeutic agent against aberrant ASM growth disorders such as CAD and also establish a unique mechanism through which VASP controls PKG activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. On the mobility of carbon-supported platinum nanoparticles towards unveiling cathode degradation in water electrolysis

    NASA Astrophysics Data System (ADS)

    Paciok, Paul; Schalenbach, Maximilian; Carmo, Marcelo; Stolten, Detlef

    2017-10-01

    This study investigates the influence of the hydrogen evolution reaction (HER) overpotential on the mobility of carbon-supported platinum particles. The migration of the platinum over the carbon support was analyzed by means of identical location transmission electron microscopy (IL-TEM). While at potentials of 0.1 and 0 V vs. reversible hydrogen electrode (RHE), no changes to the Pt/C material were observed. With a decrease of the overpotential to -0.1 V vs. RHE, an increase in the quantity of migrating platinum particles took place. At -0.2 V vs. RHE, a further rise in the particle migration was observed. The effect of the overpotential on the migration was explained by a higher hydrogen generation rate, the formation of a hydrogen monolayer on the platinum and the resulting changes of the platinum support distance. The mechanisms revealed in this study could describe a relevant source of degradation of PEM water electrolyzers.

  14. Controlling Oxygen Mobility in Ruddlesden–Popper Oxides

    PubMed Central

    Lee, Dongkyu; Lee, Ho Nyung

    2017-01-01

    Discovering new energy materials is a key step toward satisfying the needs for next-generation energy conversion and storage devices. Among the various types of oxides, Ruddlesden–Popper (RP) oxides (A2BO4) are promising candidates for electrochemical energy devices, such as solid oxide fuel cells, owing to their attractive physicochemical properties, including the anisotropic nature of oxygen migration and controllable stoichiometry from oxygen excess to oxygen deficiency. Thus, understanding and controlling the kinetics of oxygen transport are essential for designing optimized materials to use in electrochemical energy devices. In this review, we first discuss the basic mechanisms of oxygen migration in RP oxides depending on oxygen nonstoichiometry. We then focus on the effect of changes in the defect concentration, crystallographic orientation, and strain on the oxygen migration in RP oxides. We also briefly review their thermal and chemical stability. Finally, we conclude with a perspective on potential research directions for future investigation to facilitate controlling oxygen ion migration in RP oxides. PMID:28772732

  15. Antimetastatic effects of cordycepin mediated by the inhibition of mitochondrial activity and estrogen-related receptor α in human ovarian carcinoma cells

    PubMed Central

    Wang, Chia-Woei; Hsu, Wei-Hsuan; Tai, Chen-Jei

    2017-01-01

    Cordycepin (3′-deoxyadenosine) is a compound for antitumor, which has been found to exert antiangiogenic, antimetastatic, and antiproliferative effects, as well as inducing apoptosis. However, the association between cancer metastasis and mitochondrial activity in cordycepin-treated ovarian carcinoma cells remains unclear. The 50 and 100 μM of cordycepin inhibits mitochondrial fusion and induces mitochondrial fission, respectively. These suggested that cordycepin showed the down-regulation of mitochondrial function and limitation of energy production. Because of activation of mitochondria and generation of energy are needed in cancer cell migration/invasion. After 24 h treatment, cordycepin suppresses epithelial–mesenchymal transition and migration in ovarian carcinoma cells through inhibiting estrogen-related receptor (ERR)-α. The ERRα is a co-transcription factor for gene expressions associated with mitochondrial fusion. Our results indicate that cordycepin suppresses metastasis and migration of ovarian carcinoma cells via inhibiting mitochondrial activity in non-toxic concentrations, and cordycepin has potential benefits in ovarian cancer therapy. PMID:27966445

  16. Why fly the extra mile? Latitudinal trend in migratory fuel deposition rate as driver of trans-equatorial long-distance migration.

    PubMed

    Aharon-Rotman, Yaara; Gosbell, Ken; Minton, Clive; Klaassen, Marcel

    2016-09-01

    Trans-equatorial long-distance migrations of high-latitude breeding animals have been attributed to narrow ecological niche widths. We suggest an alternative hypothesis postulating that trans-equatorial migrations result from a possible increase in the rate at which body stores to fuel migration are deposited with absolute latitude; that is, longer, migrations away from the breeding grounds surpassing the equator may actually enhance fueling rates on the nonbreeding grounds and therewith the chance of a successful, speedy and timely migration back to the breeding grounds. To this end, we first sought to confirm the existence of a latitudinal trend in fuel deposition rate in a global data set of free-living migratory shorebirds and investigated the potential factors causing this trend. We next tested two predictions on how this trend is expected to impact the migratory itineraries on northward migration under the time-minimization hypothesis, using 56 tracks of high-latitude breeding shorebirds migrating along the East Asian-Australasian Flyway. We found a strong positive effect of latitude on fuel deposition rate, which most likely relates to latitudinal variations in primary productivity and available daily foraging time. We next confirmed the resulting predictions that (1) when flying from a stopover site toward the equator, migrants use long jumps that will take them to an equivalent or higher latitude at the opposite hemisphere; and (2) that from here onward, migrants will use small steps, basically fueling only enough to make it to the next suitable staging site. These findings may explain why migrants migrate "the extra mile" across the equator during the nonbreeding season in search of better fueling conditions, ultimately providing secure and fast return migrations to the breeding grounds in the opposite hemisphere.

  17. Risk factors for proximal migration of biliary tube stents

    PubMed Central

    Kawaguchi, Yoshiaki; Ogawa, Masami; Kawashima, Yohei; Mizukami, Hajime; Maruno, Atsuko; Ito, Hiroyuki; Mine, Tetsuya

    2014-01-01

    AIM: To analyze the risk factors for biliary stent migration in patients with benign and malignant strictures. METHODS: Endoscopic stent placement was performed in 396 patients with bile duct stenosis, at our institution, between June 2003 and March 2009. The indications for bile duct stent implantation included common bile duct stone in 190 patients, malignant lesions in 112, chronic pancreatitis in 62, autoimmune pancreatitis in 14, trauma in eight, surgical complications in six, and primary sclerosing cholangitis (PSC) in four. We retrospectively examined the frequency of stent migration, and analyzed the patient factors (disease, whether endoscopic sphincterotomy was performed, location of bile duct stenosis and diameter of the bile duct) and stent characteristics (duration of stent placement, stent type, diameter and length). Moreover, we investigated retrieval methods for migrated stents and their associated success rates. RESULTS: The frequency of tube stent migration in the total patient population was 3.5%. The cases in which tube stent migration occurred included those with common bile duct stones (3/190; 1.6%), malignant lesions (2/112; 1.8%), chronic pancreatitis (4/62; 6.5%), autoimmune pancreatitis (2/14; 14.3%), trauma (1/8; 12.5%), surgical complications (2/6; 33.3%), and PSC (0/4; 0%). The potential risk factors for migration included bile duct stenosis secondary to benign disease such as chronic pancreatitis and autoimmune pancreatitis (P = 0.030); stenosis of the lower bile duct (P = 0.031); bile duct diameter > 10 mm (P = 0.023); duration of stent placement > 1 mo (P = 0.007); use of straight-type stents (P < 0.001); and 10-Fr sized stents (P < 0.001). Retrieval of the migrated stents was successful in all cases. The grasping technique, using a basket or snare, was effective for pig-tailed or thin and straight stents, whereas the guidewire cannulation technique was effective for thick and straight stents. CONCLUSION: Migration of tube stents within the bile duct is rare but possible, and it is important to determine the risk factors involved in stent migration. PMID:24574806

  18. Gastrin regulates ABCG2 to promote the migration, invasion and side populations in pancreatic cancer cells via activation of NF-κB signaling

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

    Wang, Juan; Xin, Beibei; Wang, Hui

    Gastrin is absent in most normal adult pancreatic tissues but is highly expressed in pancreatic cancer tissues. Although Gastrin expression was reported to be associated with tumor proliferation in human pancreatic cancer, studies on the relationship between Gastrin and tumor metastasis in pancreatic cancer are rare. In this study, we performed an analysis to determine the effects of Gastrin on modulating the side populations, cell proportion and tumor cell metastatic potential and invasion activity and explored its mechanisms in pancreatic cancer. We indicated that Gastrin and ABCG2 were widely expressed in pancreatic cancer cell lines and overexpressed in cancer tissues.more » Gastrin induced ABCG2 expression, and this effect was mediated by NF-κB activation. Gastrin regulated the SP proportion of BxPC-3 cells via modulating ABCG2 expression. Through the regulation of the functions of NF-κB/ABCG2, Gastrin functionally promoted the migration and invasion in pancreatic cancer cell. The present study indicated that Gastrin induced ABCG2 expression by activating NF-κB and thereby modulated the SP proportion, tumor cell metastatic potential and invasion activity in pancreatic cancer. Gastrin could serve as an effective therapeutic target for the metastasis of pancreatic cancer. - Highlights: • Gastrin induces ABCG2 expression mediated by NF-κB activation. • Gastrin regulates NF-κB's function that binds to the ABCG2 promoter in BxPC-3 cells. • Gastrin promotes the SP proportion in BxPC-3 cells by modulating ABCG2 expression via activation of NF-κB molecule. • Gastrin induces an increase in migration and invasion potential in pancreatic cancer cell by regulating NF-κB/ABCG2 signaling.« less

  19. Effect of living cellular sheets on the angiogenic potential of human microvascular endothelial cells.

    PubMed

    Villar, Cristina C; Zhao, Xiang R; Livi, Carolina B; Cochran, David L

    2015-05-01

    A fundamental issue limiting the efficacy of surgical approaches designed to correct periodontal mucogingival defects is that new tissues rely on limited sources of blood supply from the adjacent recipient bed. Accordingly, therapies based on tissue engineering that leverage local self-healing potential may represent promising alternatives for the treatment of mucogingival defects by inducing local vascularization. The aim of this study is to evaluate the effect of commercially available living cellular sheets (LCS) on the angiogenic potential of neonatal dermal human microvascular endothelial cells (HMVEC-dNeo). The effect of LCS on HMVEC-dNeo proliferation, migration, capillary tube formation, gene expression, and production of angiogenic factors was evaluated over time. LCS positively influenced HMVEC-dNeo proliferation and migration. Moreover, HMVEC-dNeo incubated with LCS showed transcriptional profiles different from those of untreated cells. Whereas increased expression of angiogenic genes predominated early on in response to LCS, late-phase responses were characterized by up- and downregulation of angiostatic and angiogenic genes. However, this trend was not confirmed at the protein level, as LCS induced increased production of most of the angiogenic factors tested (i.e., epidermal growth factor [EGF], heparin-binding EGF-like growth factor, interleukin 6, angiopoietin, platelet-derived growth factor-BB, placental growth factor, and vascular endothelial growth factor) throughout the investigational period. Finally, although LCS induced HMVEC-dNeo proliferation, migration, and expression of angiogenic factors, additional factors and environmental pressures are likely to be required to promote the development of complex, mesh-like vascular structures. LCS favor initial mechanisms that govern angiogenesis but failed to enhance or accelerate HMVEC-dNeo morphologic transition to complex vascular structures.

  20. 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

  1. Reasons reported by African ophthalmologists for staying in Africa and for considering migrating.

    PubMed

    Nentwich, Martin M; Schaller, Ulrich C; Klauss, Volker

    2014-08-01

    In sub-Sahara Africa, the shortage of ophthalmologists is a major obstacle in the struggle of fighting preventable blindness. Migration of well-trained ophthalmologists has an additional negative effect on the low number of caregivers. However, to date, the reasons affecting migration of ophthalmologists have not been completely understood. The present study evaluates reasons reported by ophthalmologists for staying in their current work setting/country and potential reasons why they might consider migrating. In the years 2009-2011, after approval was obtained from the Institutional Review Board, a questionnaire evaluating reasons for and against migration of ophthalmologists was distributed to the participants of 2-week courses in Ethiopia, Cameroon and Kenya providing continuing medical education in the field of ophthalmology. A total of 84 ophthalmologists participated in this survey. The main reasons for staying in their current region/country were good working conditions, commitment to help, possibility of further training, familial ties and general feeling of satisfaction. Professional development elsewhere and better income abroad were named as the main reasons for considering migration. Almost half of the survey participants reported good infrastructure, equipment, and consumables, which is encouraging. Programs aimed at continuing medical education of ophthalmologists to enable professional development may have an appropriate role in the establishment of an ophthalmic infrastructure which can meet patients' needs.

  2. Migration of 18 trace elements from ceramic food contact material: influence of pigment, pH, nature of acid and temperature.

    PubMed

    Demont, M; Boutakhrit, K; Fekete, V; Bolle, F; Van Loco, J

    2012-03-01

    The effect of pH, nature of acid and temperature on trace element migration from ceramic ware treated with 18 commercially available glazes was studied. Besides of the well-studied lead and cadmium, migration of other toxic and non toxic elements such as aluminum, boron, barium, cobalt, chrome, copper, iron, lithium, magnesium, manganese, nickel, antimony, tin, strontium, titanium, vanadium, zinc and zirconium was investigated in order to evaluate their potential health hazards. Trace element concentrations were determined with Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). This study suggests that there is indeed a health risk concerning the possible migration of other elements than lead and cadmium. At low pH (2

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-08-05

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

  5. Sealing Penetrating Eye Injuries Using Photo-Activated Bonding

    DTIC Science & Technology

    2011-09-01

    called PTB ) with the potential to decrease vision loss and ocular complications in warfighters sustaining penetrating eye injuries. Scope: In year 2...not competitive with PTB for sealing is amnion over penetrating cornea injuries, determined that two potential adverse effects (inhibition of...epithelial cell migration and keratocyte phototoxicity) are not significant problems, demonstrated that PTB can be used to seal lacerations in thin (e.g

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

    PubMed

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

    2011-12-30

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

  7. Tyrosine Kinase Inhibitor, Vatalanib, Inhibits Proliferation and Migration of Human Pterygial Fibroblasts.

    PubMed

    Kim, Hong Kyu; Choi, Ji-Young; Park, Sang Min; Rho, Chang Rae; Cho, Kyong Jin; Jo, Sangmee Ahn

    2017-09-01

    Vatalanib is a small-molecule tyrosine kinase inhibitor. We investigated the effects of vatalanib on the proliferation and migration of cultured human pterygial fibroblasts (HPFs). Pterygium tissues were obtained after pterygium excision surgery and subjected to primary culture. HPFs were treated with vatalanib at various concentrations. Mitomycin C (MMC) was used as a positive control. Cell proliferation and migration assays were used to investigate the effects of vatalanib. Cell death was measured using flow cytometry analysis. Western blot analysis was performed to identify signaling molecules associated with the response to vatalanib. Vatalanib inhibited both proliferation and migration of HPFs in a dose-dependent manner. Cell proliferation was significantly suppressed by vatalanib (10 and 100 μM) and MMC (0.004% and 0.04%) treatments. Migration assays revealed significant HPF delay when treated with vatalanib (1, 10, and 100 μM) and MMC (0.004% and 0.04%) compared with that in a negative control. Cell death analysis showed that high concentrations of vatalanib (100 μM) and MMC (0.004% and 0.04%) decreased cell numbers. Western blot analysis of vatalanib-treated cells showed vascular endothelial growth factor and transforming growth factor-β significantly reduced, but there was no alteration in p53 protein levels in HPFs. These results indicate that vatalanib significantly suppressed the proliferation and migration of HPFs by decreasing vascular endothelial growth factor and transforming growth factor-β. Vatalanib showed less toxicity than that of MMC. Based on these results, vatalanib may potentially serve as a new adjuvant treatment after pterygium excision surgery.

  8. Characteristics of secondary migration driving force of tight oil and its geologic effect: a case study of Jurassic in Central Sichuan Basin

    NASA Astrophysics Data System (ADS)

    Pang, Zhenglian; Tao, Shizhen; Zhang, Bin; Wu, Songtao; Yang, Jiajing; Chen, Ruiyin

    2017-04-01

    As the rising of its production, tight oil is becoming more and more important. Much research has been done about it. Some articles mention that buoyancy is ineffective for tight oil secondary migration, and abnormal pressure is the alternative. Others believe that overpressure caused hydrocarbon generation is the very force. Though opinions have been given, there are two inadequacies. Firstly, the points are lack of sufficient evidences. Mostly, they are only one or two sentences in the papers. Secondly, geologic effect of the change of driving force hasn't been discussed. In this context, analog experiments, physical property testing, mercury injection, and oil/source comparison were utilized to study 3 issues: origin and value of tight oil secondary migration resistance, values and effectiveness of different potential driving forces, and geologic effect of tight oil secondary migration driving force. Firstly, resistance values of tight reservoir were detected by analog experiments. The value of tight limestone is 15.8MPa, while tight sandstone is 10.7MPa. Tiny size of pores and throats in tight reservoir is the main reason causing huge resistances. Over 90% of pores and throats in tight reservoir are smaller than 1μm. They form huge capillary force when oil migrating through them. Secondly, maximum of buoyancy in study area was confirmed, 0.09MPa, too small to overcome the resistances. Meanwhile, production data suggests that tight oil distribution pattern is not controlled by buoyancy. Conversely, analog experiment proves that overpressure caused by hydrocarbon generation can reach 38MPa, large enough to be the driving force. This idea is also supported by positive correlation between output and source rock formation pressure. Thirdly, is the geologic effect of tight oil secondary migration resistance and driving force. Tight oil can migrate only as non-darcy flow due to huge resistances according to percolation experiments. It needs to overcome the starting pressure gradient. As a result, it migrated a much shorter distance compared with conventional petroleum, coincident with the result of oil/source comparison. The effect of driving force is that boundary of tight oil profitable area is controlled by source rock. This boundary in the study area is the line of hydrocarbon generating strength of 40×104t/km2. By confirming controlling factors of tight oil formation and their evaluation index, it is of great significance during tight oil exploration.

  9. 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.

  10. In Vitro Effects of Pirfenidone on Cardiac Fibroblasts: Proliferation, Myofibroblast Differentiation, Migration and Cytokine Secretion

    PubMed Central

    Shi, Qiang; Liu, Xiaoyan; Bai, Yuanyuan; Cui, Chuanjue; Li, Jun; Li, Yishi; Hu, Shengshou; Wei, Yingjie

    2011-01-01

    Cardiac fibroblasts (CFs) are the primary cell type responsible for cardiac fibrosis during pathological myocardial remodeling. Several studies have illustrated that pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) attenuates cardiac fibrosis in different animal models. However, the effects of pirfenidone on cardiac fibroblast behavior have not been examined. In this study, we investigated whether pirfenidone directly modulates cardiac fibroblast behavior that is important in myocardial remodeling such as proliferation, myofibroblast differentiation, migration and cytokine secretion. Fibroblasts were isolated from neonatal rat hearts and bioassays were performed to determine the effects of pirfenidone on fibroblast function. We demonstrated that treatment of CFs with pirfenidone resulted in decreased proliferation, and attenuated fibroblast α-smooth muscle actin expression and collagen contractility. Boyden chamber assay illustrated that pirfenidone inhibited fibroblast migration ability, probably by decreasing the ratio of matrix metalloproteinase-9 to tissue inhibitor of metalloproteinase-1. Furthermore, pirfenidone attenuated the synthesis and secretion of transforming growth factor-β1 but elevated that of interleukin-10. These direct and pleiotropic effects of pirfenidone on cardiac fibroblasts point to its potential use in the treatment of adverse myocardial remodeling. PMID:22132230

  11. Time to Evolve? Potential Evolutionary Responses of Fraser River Sockeye Salmon to Climate Change and Effects on Persistence

    PubMed Central

    Reed, Thomas E.; Schindler, Daniel E.; Hague, Merran J.; Patterson, David A.; Meir, Eli; Waples, Robin S.; Hinch, Scott G.

    2011-01-01

    Evolutionary adaptation affects demographic resilience to climate change but few studies have attempted to project changes in selective pressures or quantify impacts of trait responses on population dynamics and extinction risk. We used a novel individual-based model to explore potential evolutionary changes in migration timing and the consequences for population persistence in sockeye salmon Oncorhynchus nerka in the Fraser River, Canada, under scenarios of future climate warming. Adult sockeye salmon are highly sensitive to increases in water temperature during their arduous upriver migration, raising concerns about the fate of these ecologically, culturally, and commercially important fish in a warmer future. Our results suggest that evolution of upriver migration timing could allow these salmon to avoid increasingly frequent stressful temperatures, with the odds of population persistence increasing in proportion to the trait heritability and phenotypic variance. With a simulated 2°C increase in average summer river temperatures by 2100, adult migration timing from the ocean to the river advanced by ∼10 days when the heritability was 0.5, while the risk of quasi-extinction was only 17% of that faced by populations with zero evolutionary potential (i.e., heritability fixed at zero). The rates of evolution required to maintain persistence under simulated scenarios of moderate to rapid warming are plausible based on estimated heritabilities and rates of microevolution of timing traits in salmon and related species, although further empirical work is required to assess potential genetic and ecophysiological constraints on phenological adaptation. These results highlight the benefits to salmon management of maintaining evolutionary potential within populations, in addition to conserving key habitats and minimizing additional stressors where possible, as a means to build resilience to ongoing climate change. More generally, they demonstrate the importance and feasibility of considering evolutionary processes, in addition to ecology and demography, when projecting population responses to environmental change. PMID:21738573

  12. 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.

  13. Juglone reduces growth and migration of U251 glioblastoma cells and disrupts angiogenesis.

    PubMed

    Wang, Jian; Liu, Ke; Wang, Xiao-Feng; Sun, Dian-Jun

    2017-10-01

    Accumulating data show that prolylisomerase (Pin1) is overexpressed in human glioblastoma multiforme (GBM) specimens. Therefore, Pin1 inhibitors should be investigated as a new chemotherapeutic drug that may enhance the clinical management of human gliomas. Recently, juglone, a Pin1 inhibitor, was shown to exhibit potent anticancer activity in various tumor cells, but its role in human glioma cells remains unknown. In the present study, we determined if juglone exerts antitumor effects in the U251 human glioma cell line and investigated its potential underlying molecular mechanisms. Cell survival, apoptosis, migration, angiogenesis and molecular targets were identified with multiple detection techniques including the MTT cell proliferation assay, dual acridine orange/ethidium bromide staining, electron microscopy, transwell migration assay, chick chorioallantoic membrane assay, quantitative real-time polymerase chain reaction and immunoblotting. The results showed that 5-20 µM juglone markedly suppressed cell proliferation, induced apoptosis, and enhanced caspase-3 activity in U251 cells in a dose- and time-dependent manner. Moreover, juglone inhibited cell migration and the formation of new blood vessels. At the molecular level, juglone markedly suppressed Pin1 levels in a time-dependent manner. TGF-β1/Smad signaling, a critical upstream regulator of miR-21, was also suppressed by juglone. Moreover, the transient overexpression of Pin1 reversed its antitumor effects in U251 cells and inhibited juglone-mediated changes to the TGF-β1/miR-21 signaling pathway. These findings suggest that juglone inhibits cell growth by causing apoptosis, thereby inhibiting the migration of U251 glioma cells and disrupting angiogenesis; and that Pin1 is a critical target for juglone's antitumor activity. The present study provides evidence that juglone has in vitro efficacy against glioma. Therefore, additional studies are warranted to examine the clinical potential of juglone in human gliomas.

  14. Electrical Signatures of Ethanol-Liquid Mixtures: Implications for Monitoring Biofuels Migration in the Subsurface

    EPA Science Inventory

    Ethanol (EtOH), an emerging contaminant with potential direct and indirect environmental effects, poses threats to water supplies when spilled in large volumes. A series of experiments was directed at understanding the electrical geophysical signatures arising from groundwater co...

  15. Proximal migration of transanastomotic pancreatic stent following pancreaticoduodenectomy and pancreaticojejunostomy.

    PubMed

    Ammori, B J; White, C M

    1999-06-01

    The use of catheters to stent the pancreaticojejunal anastomosis following pancreaticoduodenectomy is practiced by some surgeons. Their long-term effects in this setting, however, remain unknown. A 60-yr-old woman underwent a potentially curative pylorus preserving pancreaticoduodenectomy for Stage I ampullary carcinoma. Roux-en-Y pancreaticojejunostomy was constructed over a short stent. She presented 4 yr later with abdominal pain, steatorrhea, and weight loss. Computed tomography revealed a stent within the proximal pancreatic duct, with gross upstream ductal dilatation and parenchymal features of chronic pancreatitis. Laparotomy revealed no disease recurrence. The stent, removed through a jejunotomy, was occluded. On-table pancreatogram demonstrated a 3-cm proximal duct stricture. Drainage was achieved with a lateral pancreaticojejunostomy (modified Puestow procedure). Recovery was uneventful, with clinical recovery of pancreatic exocrine function at 6 mo follow-up. Proximal migration of transanastomotic pancreatic stent with subsequent development of chronic pancreatitis is a potential complication following pancreaticoduodenectomy. It can be managed effectively with stent removal and a lateral pancreaticojejunostomy.

  16. XCR1 promotes cell growth and migration and is correlated with bone metastasis in non-small cell lung cancer

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

    Wang, Ting; Han, Shuai; Wu, Zhipeng

    Bone metastasis occurs in approximately 30–40% patients with advanced non-small cell lung cancer (NSCLC), but the mechanism underlying this bone metastasis remains poorly understood. The chemokine super family is believed to play an important role in tumor metastasis in lung cancer. The chemokine receptor XCR1 has been identified to promote cell proliferation and migration in oral cancer and ovarian carcinoma, but the role of XCR1 in lung cancer has not been reported. In this study, we demonstrated for the first time that XCR1 was overexpressed in lung cancer bone metastasis as compared with that in patients with primary lung cancer.more » In addition, the XCR1 ligand XCL1 promoted the proliferation and migration of lung cancer cells markedly, and knockdown of XCR1 by siRNA abolished the effect of XCL1 in cell proliferation and migration. Furthermore, we identified JAK2/STAT3 as a novel downstream pathway of XCR1, while XCL1/XCR1 increased the mRNA level of the downstream of JAK2/STAT3 including PIM1, JunB, TTP, MMP2 and MMP9. These results indicate that XCR1 is a new potential therapeutic target for the treatment of lung cancer bone metastasis. - Highlights: • XCR1 is overexpressed in bone metastasis compared with primary NSCLC. • XCR1 activation by XCL1 promotes lung cancer cell proliferation and migration. • JAK2/STAT3 is a novel potential downstream pathway of XCR1.« less

  17. BioMig--A Method to Evaluate the Potential Release of Compounds from and the Formation of Biofilms on Polymeric Materials in Contact with Drinking Water.

    PubMed

    Wen, Gang; Kötzsch, Stefan; Vital, Marius; Egli, Thomas; Ma, Jun

    2015-10-06

    In contact with water, polymeric materials (plastics) release compounds that can support suspended microbial growth and/or biofilm formation. The different methods presently used in the European Union to test plastics take 7-16 weeks to obtain a result. In industry, this delays material and product development as well as quality testing. Therefore, we developed a method package (BioMig) that allows testing of plastic materials with high reproducibility in 2 weeks for their potential biofilm (or biomass) formation and release of carbonaceous migration products when in contact with water. BioMig consists of (i) an extended migration potential test (seven times for 24 h at 60 °C), based on the European norm EN 12873-1 and the German UBA (Umweltbundesamt) guideline, and (ii) a biomass formation potential (BFP) test (14 days at 30 °C), which is a modified version of the Dutch biofilm production potential test. In the migration potential test, the amount of carbon released into water by the specimen is quantified by monitoring total and assimilable organic carbon over time; furthermore, the modular design of the test also allows one to assess additional parameters such as pathogen growth potential on the migration water or toxic effects on microbial growth. Flow cytometry (FCM)-based total cell counting (TCC) is used to quantify microbial growth in suspension and on surfaces after removal with mild sonication without affecting cell integrity. The BFP test allows one to determine both the planktonic (pBFP) and the sessile (sBFP) cell fractions. The sBFP consists of surface-attached cells after removal (>90% efficiency). Results for four standard test materials (PE-Xa, PE-Xc, EPDM 2%, and EPDM 20%), plus positive (PVC-P) and negative (glass) controls are presented. FCM-based TCC demonstrates that the release of growth-supporting carbon and proliferation of surface-attached cells stops increasing and stabilizes after 14 days of incubation; this allows for faster assessment of growth-supporting properties of plastics with BioMig compared to established tests.

  18. Biological effects of plasma rich in growth factors (PRGF) on human endometrial fibroblasts.

    PubMed

    Anitua, Eduardo; de la Fuente, María; Ferrando, Marcos; Quintana, Fernando; Larreategui, Zaloa; Matorras, Roberto; Orive, Gorka

    2016-11-01

    To evaluate the biological outcomes of plasma rich in growth factors (PRGF) on human endometrial fibroblasts in culture. PRGF was obtained from three healthy donors and human endometrial fibroblasts (HEF) were isolated from endometrial specimens from five healthy women. The effects of PRGF on cell proliferation and migration, secretion of vascular endothelial growth factor (VEGF), procollagen type I and hyaluronic acid (HA) and contractility of isolated and cultured human endometrial fibroblasts (HEF) were analyzed. Statistical analysis was performed in order to compare the effects of PRGF with respect to control situation (T-test or Mann-Whitney U-test). We report a significantly elevated human endometrial fibroblast proliferation and migration after treatment with PRGF. In addition, stimulation of HEF with PRGF induced an increased expression of the angiogenic factor VEGF and favored the endometrial matrix remodeling by the secretion of procollagen type I and HA and endometrial regeneration by elevating the contractility of HEF. These results were obtained for all PRGF donors and each endometrial cell line. The myriad of growth factors contained in PRGF promoted HEF proliferation, migration and synthesis of paracrine molecules apart from increasing their contractility potential. These preliminary results suggest that PRGF improves the biological activity of HEF in vitro, enhancing the regulation of several cellular processes implied in endometrial regeneration. This innovative treatment deserves further investigation for its potential in "in vivo" endometrial development and especially in human embryo implantation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. 40 CFR 264.601 - Environmental performance standards.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... to migration of waste constituents in the ground water or subsurface environment, considering: (1... for migration through soil, liners, or other containing structures; (2) The hydrologic and geologic... users; (6) The patterns of land use in the -region; (7) The potential for deposition or migration of...

  20. Seasonal migration of marsupial megafauna in Pleistocene Sahul (Australia-New Guinea).

    PubMed

    Price, Gilbert J; Ferguson, Kyle J; Webb, Gregory E; Feng, Yue-Xing; Higgins, Pennilyn; Nguyen, Ai Duc; Zhao, Jian-Xin; Joannes-Boyau, Renaud; Louys, Julien

    2017-09-27

    Seasonal two-way migration is an ecological phenomenon observed in a wide range of large-bodied placental mammals, but is conspicuously absent in all modern marsupials. Most extant marsupials are typically smaller in body size in comparison to their migratory placental cousins, possibly limiting their potential to undertake long-distance seasonal migrations. But what about earlier, now-extinct giant marsupial megafauna? Here we present new geochemical analyses which show that the largest of the extinct marsupial herbivores, the enormous wombat-like Diprotodon optatum , undertook seasonal, two-way latitudinal migration in eastern Sahul (Pleistocene Australia-New Guinea). Our data infer that this giant marsupial had the potential to perform round-trip journeys of as much as 200 km annually, which is reminiscent of modern East African mammal migrations. These findings provide, to our knowledge, the first evidence for repetitive seasonal migration in any metatherian (including marsupials), living or extinct, and point to an ecological phenomenon absent from the continent since the Late Pleistocene. © 2017 The Author(s).

  1. Antiproliferative and Antiangiogenic Effects of Punica granatum Juice (PGJ) in Multiple Myeloma (MM)

    PubMed Central

    Tibullo, Daniele; Caporarello, Nunzia; Giallongo, Cesarina; Anfuso, Carmelina Daniela; Genovese, Claudia; Arlotta, Carmen; Puglisi, Fabrizio; Parrinello, Nunziatina L.; Bramanti, Vincenzo; Romano, Alessandra; Lupo, Gabriella; Toscano, Valeria; Avola, Roberto; Brundo, Maria Violetta; Di Raimondo, Francesco; Raccuia, Salvatore Antonio

    2016-01-01

    Multiple myeloma (MM) is a clonal B-cell malignancy characterized by an accumulation of clonal plasma cells (PC) in the bone marrow (BM) leading to bone destruction and BM failure. Despite recent advances in pharmacological therapy, MM remains a largely incurable pathology. Therefore, novel effective and less toxic agents are urgently necessary. In the last few years, pomegranate has been studied for its potential therapeutic properties including treatment and prevention of cancer. Pomegranate juice (PGJ) contains a number of potential active compounds including organic acids, vitamins, sugars, and phenolic components that are all responsible of the pro-apoptotic effects observed in tumor cell line. The aim of present investigation is to assess the antiproliferative and antiangiogenic potential of the PGJ in human multiple myeloma cell lines. Our data demonstrate the anti-proliferative potential of PGJ in MM cells; its ability to induce G0/G1 cell cycle block and its anti-angiogenic effects. Interestingly, sequential combination of bortezomib/PGJ improved the cytotoxic effect of the proteosome inhibitor. We investigated the effect of PGJ on angiogenesis and cell migration/invasion. Interestingly, we observed an inhibitory effect on the tube formation, microvessel outgrowth aorting ring and decreased cell migration and invasion as showed by wound-healing and transwell assays, respectively. Analysis of angiogenic genes expression in endothelial cells confirmed the anti-angiogenic properties of pomegranate. Therefore, PGJ administration could represent a good tool in order to identify novel therapeutic strategies for MM treatment, exploiting its anti-proliferative and anti-angiogenic effects. Finally, the present research supports the evidence that PGJ could play a key role of a future therapeutic approach for treatment of MM in order to optimize the pharmacological effect of bortezomib, especially as adjuvant after treatment. PMID:27706074

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

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

    Yu Yang; Gao Yu; Wang, Hong

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

  3. Pim-3 enhances melanoma cell migration and invasion by promoting STAT3 phosphorylation.

    PubMed

    Liu, Jing; Qu, Xinyu; Shao, Liwei; Hu, Yuan; Yu, Xin; Lan, Peixiang; Guo, Qie; Han, Qiuju; Zhang, Jian; Zhang, Cai

    2018-03-04

    Melanoma is the deadliest form of commonly encountered skin cancer, and has fast propagating and highly invasive characteristics. Pim-3, a highly expressed oncogene in melanoma, is a highly conserved serine/threonine kinase with various biological activities, such as proliferation-accelerating and anti-apoptosis effects on cancer progression. However, whether Pim-3 regulates melanoma metastasis has not been determined. Here, we constructed a Pim-3-silencing short hairpin RNA (sh-Pim-3), a TLR7-stimulating ssRNA and a dual-function vector containing a sh-Pim-3 and a ssRNA, and transfected them into the B16F10 melanoma cell line to investigate the effects of Pim-3 on migration and invasion in melanoma. We found that sh-Pim-3 inhibited B16F10 cell migration and invasion in vitro. In a tumor-bearing mouse model, sh-Pim-3 significantly downregulated pulmonary metastasis of B16F10 melanoma cell in vivo. Mechanistically, sh-Pim-3 inhibited metastasis by regulating the expression of genes related to epithelial-mesenchymal transition (EMT). Further study revealed that by promoting the phosphorylation of STAT3 (signal transducer and activator of transcription 3), Pim-3 induced the expression of Slug, Snail, and ZEB1, which enhanced EMT-related changes and induced melanoma migration and invasion. Our study suggests that Pim-3 is a potential effective target for melanoma therapy.

  4. Non-thermal plasma inhibits human cervical cancer HeLa cells invasiveness by suppressing the MAPK pathway and decreasing matrix metalloproteinase-9 expression

    NASA Astrophysics Data System (ADS)

    Li, Wei; Yu, K. N.; Bao, Lingzhi; Shen, Jie; Cheng, Cheng; Han, Wei

    2016-01-01

    Non-thermal plasma (NTP) has been proposed as a novel therapeutic method for anticancer treatment. However, the mechanism underlying its biological effects remains unclear. In this study, we investigated the inhibitory effect of NTP on the invasion of HeLa cells, and explored the possible mechanism. Our results showed that NTP exposure for 20 or 40 s significantly suppressed the migration and invasion of HeLa cells on the basis of matrigel invasion assay and wound healing assay, respectively. Moreover, NTP reduced the activity and protein expression of the matrix metalloproteinase (MMP)-9 enzyme. Western blot analysis indicated that NTP exposure effectively decreased phosphorylation level of both ERK1/2 and JNK, but not p38 MAPK. Furthermore, treatment with MAPK signal pathway inhibitors or NTP all exhibited significant depression of HeLa cells migration and MMP-9 expression. The result showed that NTP synergistically suppressed migration and MMP-9 expression in the presence of ERK1/2 inhibitor and JNK inhibitor, but not p38 MAPK inhibitor. Taken together, these findings suggested that NTP exposure inhibited the migration and invasion of HeLa cells via down-regulating MMP-9 expression in ERK1/2 and JNK signaling pathways dependent manner. These findings provide hints to the potential clinical research and therapy of NTP on cervical cancer metastasis.

  5. Low- and high-dose laser irradiation effects on cell migration and destruction

    NASA Astrophysics Data System (ADS)

    Layton, Elivia; Gallagher, Kyra A.; Zukerman, Sara; Stevens, Brianna; Zhou, Feifan; Liu, Hong; Chen, Wei R.

    2018-02-01

    Metastases are the cause of more than 90 percent of cancer-related deaths. Current treatment methods, including chemotherapy, radiation, and surgery, fail to target the metastases effectively. One potential treatment for metastatic cancer is laser immunotherapy (LIT). LIT combines the use of a photothermal laser with an immunoadjuvant, Glycated Chitosan (GC). GC combined with single-walled carbon nanotubes (SWNTs) has proven to be a viable alternative to traditional cancer treatment methods, when under irradiation of laser with appropriate wavelength. In this study, the effects of low dose and high dose laser irradiation on metastatic pancreatic cancer cell migration were observed. It was found that low dose irradiation increased the migration rate, but the high dose irradiation significantly decreased the migration rate of the cancer cells. When using LIT, the goal is to kill tumor cells and to prompt the correct immune response. If the tumor were irradiated with a low dose, it would promote metastasis. If the dose of irradiation were too high, it would destroy the entire tumor and the immune response would not recognize the tumor. Therefore, the laser dose plays an important role in LIT, particularly when using SWNT as light absorbing agent. Our results from this study will delineate the optimal laser irradiation dose for destroying tumor cells and at the same time preserve and release tumor antigens as a precursor of antitumor immune response.

  6. Mkit: A Cell Migration Assay Based on Microfluidic Device and Smartphone

    PubMed Central

    Yang, Ke; Wu, Jiandong; Peretz-Soroka, Hagit; Zhu, Ling; Li, Zhigang; Sang, Yaoshuo; Hipolito, Jolly; Zhang, Michael; Santos, Susy; Hillier, Craig; de Faria, Ricardo Lobato; Liu, Yong; Lin, Francis

    2017-01-01

    Mobile sensing based on the integration of microfluidic device and smartphone, so-called MS2 technology, has enabled many applications over recent years, and continues to stimulate growing interest in both research communities and industries. In particular, it has been envisioned that MS2 technology can be developed for various cell functional assays to enable basic research and clinical applications. Toward this direction, in this paper, we describe the development of a MS2-based cell functional assay for testing cell migration (the Mkit). The system is constructed as an integrated test kit, which includes microfluidic chips, a smartphone-based imaging platform, the phone apps for image capturing and data analysis, and a set of reagent and accessories for performing the cell migration assay. We demonstrated that the Mkit can effectively measure purified neutrophil and cancer cell chemotaxis. Furthermore, neutrophil chemotaxis can be tested from a drop of whole blood using the Mkit with red blood cell (RBC) lysis. The effects of chemoattractant dose and gradient profile on neutrophil chemotaxis were also tested using the Mkit. In addition to research applications, we demonstrated the effective use of the Mkit for on-site test at the hospital and for testing clinical samples from chronic obstructive pulmonary disease patient. Thus, this developed Mkit provides an easy and integrated experimental platform for cell migration related research and potential medical diagnostic applications. PMID:28772229

  7. The movement of people in Asia: internal, intra-regional and international migration.

    PubMed

    Lim, L L; Abella, M

    1994-01-01

    "The comprehensive overview of Asian-Pacific migration summarizes early population movements during the colonial period and describes the major types of contemporary Asian population movements: (1) environmental refugees, (2) political refugees, (3) internal population movements, (4) contract labor migration, (5) migration of permanent settlers, (6) business related movements and tourism. Projections of net international migration are given. Population growth, employment absorption and emigration pressures are likely to contribute to a large mobility potential for Asia, with significant implications for Australia." excerpt

  8. Migrants' dreams and planners' nightmares: international labour migration in the Arab world and the growth of two sets of cities.

    PubMed

    Findlay, A M

    1985-11-01

    "The author investigates how trends in international labour migration in the Arab world have been paralleled by new directions in migration research....[She] seeks to evaluate why the urban impact of international migration is so great and outlines the considerable potential which exists for pursuing research on this aspect of urban development." excerpt

  9. Pendulum migration and healthcare in border área.

    PubMed

    Zaslavsky, Ricardo; Goulart, Bárbara Niegia Garcia de

    2017-12-01

    This article aims to reflect about the importance and the potential impact of pendulum migration in the pursuance for healthcare, and, specifically, about the peculiarity of this kind of mobility in border areas. It describes the context in which the pendulum migration is inserted for the modification of the urban space in the 20th century, makes initial comments about legal aspects of the theme in health sector, and describes the reality of the Brazil-Argentina-Paraguay triple border as an important location of pendulum migration for the pursuance of healthcare as an illustrative fact. In this way, hypotheses are formulated about the causes of the pendulum migration impact on patient's health like the effect of the distance covered from home to healthcare facilities, and organizational aspects related to healthcare like the uncertainty about having or not health assistance due to international mobility. It concludes that this kind of mobility is very common in the pursuance of healthcare despite the traditional approach to the theme mentioning only work or study. Besides that, it is very important to study its impact on health and to include this theme on the cross border healthcare debate.

  10. Migration and speciation of heavy metal in salinized mine tailings affected by iron mining.

    PubMed

    Zhang, Xu; Yang, Huanhuan; Cui, Zhaojie

    2017-10-01

    The negative effects of heavy metals have aroused much attention due to their high toxicity to human beings. Migration and transformation trend of heavy metals have a close relationship with soil safety. Researching on migration and transformation of heavy metals in tailings can provide a reliable basis for pollution management and ecosystem restoration. Heavy metal speciation plays an important role in risk assessment. We chose Anshan tailings for our study, including field investigations and laboratory research. Four typical heavy metal elements of mine tailings {Fe (373.89 g/kg), Mn (2,303.80 mg/kg), Pb (40.99 mg/kg) and Cr (199.92 mg/kg)} were studied via Tessier test in vertical and horizontal direction. The main speciation of heavy metals in Anshan tailings was the residual. However, heavy metals have a strong ability for migration and transformation in vertical and horizontal directions. Its tendency to change from stable to unstable speciation results in increasing bioavailability and potential bioavailability. Fe, Mn, Pb and Cr showed different ability in the migration and transformation process (Mn > Pb > Fe > Cr) depending on the characteristics of heavy metals and physicochemical properties of the environment.

  11. Polarizability of Six-Helix Bundle and Triangle DNA Origami and Their Escape Characteristics from a Dielectrophoretic Trap.

    PubMed

    Gan, Lin; Camacho-Alanis, Fernanda; Ros, Alexandra

    2015-12-15

    DNA nanoassemblies, such as DNA origamis, hold promise in biosensing, drug delivery, nanoelectronic circuits, and biological computing, which require suitable methods for migration and precision positioning. Insulator-based dielectrophoresis (iDEP) has been demonstrated as a powerful migration and trapping tool for μm- and nm-sized colloids as well as DNA origamis. However, little is known about the polarizability of origami species, which is responsible for their dielectrophoretic migration. Here, we report the experimentally determined polarizabilities of the six-helix bundle origami (6HxB) and triangle origami by measuring the migration times through a potential landscape exhibiting dielectrophoretic barriers. The resulting migration times correlate to the depth of the dielectrophoretic potential barrier and the escape characteristics of the origami according to an adapted Kramer's rate model, allowing their polarizabilities to be determined. We found that the 6HxB polarizability is larger than that of the triangle origami, which correlates with the variations in charge density of both origamis. Further, we discuss the orientation of both origami species in the dielectrophoretic trap and discuss the influence of diffusion during the escape process. Our study provides detailed insight into the factors contributing to the migration through dielectrophoretic potential landscapes, which can be exploited for applications with DNA and other nanoassemblies based on dielectrophoresis.

  12. Elementary Mechanisms of Shear-Coupled Grain Boundary Migration

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

    A detailed theoretical study of the elementary mechanisms occurring during the shear-coupled grain boundary (GB) migration at low temperature is performed focusing on both the energetic and structural characteristics. The migration of a Σ13(320) GB in a copper bicrystal in response to external shear displacements is simulated using a semiempirical potential. The minimum energy path of the shear-coupled GB migration is computed using the nudge elastic band method. The GB migration occurs through the nucleation and motion of GB steps identified as disconnections. Energy barriers for the GB and disconnection migrations are evaluated.

  13. Vertically migrating swimmers generate aggregation-scale eddies in a stratified column.

    PubMed

    Houghton, Isabel A; Koseff, Jeffrey R; Monismith, Stephen G; Dabiri, John O

    2018-04-01

    Biologically generated turbulence has been proposed as an important contributor to nutrient transport and ocean mixing 1-3 . However, to produce non-negligible transport and mixing, such turbulence must produce eddies at scales comparable to the length scales of stratification in the ocean. It has previously been argued that biologically generated turbulence is limited to the scale of the individual animals involved 4 , which would make turbulence created by highly abundant centimetre-scale zooplankton such as krill irrelevant to ocean mixing. Their small size notwithstanding, zooplankton form dense aggregations tens of metres in vertical extent as they undergo diurnal vertical migration over hundreds of metres 3,5,6 . This behaviour potentially introduces additional length scales-such as the scale of the aggregation-that are of relevance to animal interactions with the surrounding water column. Here we show that the collective vertical migration of centimetre-scale swimmers-as represented by the brine shrimp Artemia salina-generates aggregation-scale eddies that mix a stable density stratification, resulting in an effective turbulent diffusivity up to three orders of magnitude larger than the molecular diffusivity of salt. These observed large-scale mixing eddies are the result of flow in the wakes of the individual organisms coalescing to form a large-scale downward jet during upward swimming, even in the presence of a strong density stratification relative to typical values observed in the ocean. The results illustrate the potential for marine zooplankton to considerably alter the physical and biogeochemical structure of the water column, with potentially widespread effects owing to their high abundance in climatically important regions of the ocean 7 .

  14. Ubenimex enhances Brd4 inhibition by suppressing HEXIM1 autophagic degradation and suppressing the Akt pathway in glioma cells.

    PubMed

    Han, Liping; Zhao, Qingwei; Liang, Xianhong; Wang, Xiaoqing; Zhang, Zhen; Ma, Zhiguo; Zhao, Miaoqing; Wang, Aihua; Liu, Shuai

    2017-07-11

    Inhibition of Brd4 by JQ1 treatment showed potential in the treatment of glioma, however, some cases showed low sensitivity of JQ1. In addition, the pre-clinical analysis showed its limitation by demonstrating that transient treatment with JQ1 leads to aggressive tumor development. Thus, an improved understanding of the mechanisms underlying JQ1 is urgently required to design strategies to improve its efficiency, as well as overcome its limitation. HEXIM1 has been confirmed to have an important role in regulating JQ1 sensitivity. In our study, ubenimex, a classical anti-cancer drug showed potential in regulating the JQ1 sensitivity of glioma cells using the WST-1 proliferation assay. Further studies demonstrated that ubenimex inhibited autophagy and downregulated the autophagic degradation of HEXIM1. The role of HEXIM1 in regulating JQ1 sensitivity was verified by the HEXIM1 knockdown. Since ubenimex was verified as an Akt inhibitor, we further studied the role of Akt inhibition in regulating JQ1 sensitivity and migration of glioma cells. Data showed that ubenimex improved the efficiency of JQ1 treatment and suppressed migration both in the in vitro and in vivo xenografts models. The Akt agonist attenuated these effects, pointing to the role of Akt inhibition in JQ1 sensitivity and suppressed migration. Our findings suggest the potential of ubenimex adjuvant treatment to enhance JQ1 efficiency and attenuate parts of its side effect (enhancing tumor aggressive) by regulating the autophagic degradation of HEXIM1 and Akt inhibition.

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

    PubMed Central

    2013-01-01

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

  16. Childbearing in crisis: war, migration and fertility in Angola.

    PubMed

    Avogo, Winfred; Agadjanian, Victor

    2008-09-01

    This study examines the short- and long-term effects of war-induced and war-unrelated migration on fertility outcomes using data from two peri-urban municipalities of Greater Luanda in Angola. In the short term, results from multi-level discrete-time logistic regression models indicate that net of other factors, war-unrelated migration is associated with a lower probability of birth than war-induced migration in a given year. Similar results are obtained when the effects of migration are lagged by a year. At the same time, the effects of war-triggered migration do not differ significantly from those of not migrating in a given year but are statistically significant when the effects of migration are lagged by a year. In the long term, the effects of migration experience on cumulative fertility are negligible and not statistically significant net of demographic and socioeconomic variables. Interpretations of the results are offered in the context of Angola and their broader implications are reflected on.

  17. Dike/Drift Interactions

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

    E. Gaffiney

    2004-11-23

    This report presents and documents the model components and analyses that represent potential processes associated with propagation of a magma-filled crack (dike) migrating upward toward the surface, intersection of the dike with repository drifts, flow of magma in the drifts, and post-magma emplacement effects on repository performance. The processes that describe upward migration of a dike and magma flow down the drift are referred to as the dike intrusion submodel. The post-magma emplacement processes are referred to as the post-intrusion submodel. Collectively, these submodels are referred to as a conceptual model for dike/drift interaction. The model components and analyses ofmore » the dike/drift interaction conceptual model provide the technical basis for assessing the potential impacts of an igneous intrusion on repository performance, including those features, events, and processes (FEPs) related to dike/drift interaction (Section 6.1).« less

  18. Wound healing potential of adipose tissue stem cell extract

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

    Na, You Kyung; Ban, Jae-Jun; Lee, Mijung

    Adipose tissue stem cells (ATSCs) are considered as a promising source in the field of cell therapy and regenerative medicine. In addition to direct cell replacement using stem cells, intercellular molecule exchange by stem cell secretory factors showed beneficial effects by reducing tissue damage and augmentation of endogenous repair. Delayed cutaneous wound healing is implicated in many conditions such as diabetes, aging, stress and alcohol consumption. However, the effects of cell-free extract of ATSCs (ATSC-Ex) containing secretome on wound healing process have not been investigated. In this study, ATSC-Ex was topically applied on the cutaneous wound and healing speed wasmore » examined. As a result, wound closure was much faster in the cell-free extract treated wound than control wound at 4, 6, 8 days after application of ATSC-Ex. Dermal fibroblast proliferation, migration and extracellular matrix (ECM) production are critical aspects of wound healing, and the effects of ATSC-Ex on human dermal fibroblast (HDF) was examined. ATSC-Ex augmented HDF proliferation in a dose-dependent manner and migration ability was enhanced by extract treatment. Representative ECM proteins, collagen type I and matrix metalloproteinase-1, are significantly up-regulated by treatment of ATSC-Ex. Our results suggest that the ATSC-Ex have improving effect of wound healing and can be the potential therapeutic candidate for cutaneous wound healing. - Highlights: • Topical application of ATSC-Ex results in faster wound closure than normal wound in vivo. • ATSC-Ex enhances dermal fibroblast proliferation, migration and extracellular matrix production. • This study suggests that ATSC-Ex is an effective source to augment wound healing.« less

  19. Anti-proliferative and anti-migratory effects of hyperforin in 2D and 3D artificial constructs of human dermal fibroblasts - A new option for hypertrophic scar treatment?

    PubMed

    Füller, J; Müller-Goymann, C C

    2018-05-01

    Hyperforin (HYP), one of the main bioactive compounds in extracts of Hypericum perforatum, is a potential drug candidate for the treatment of skin diseases. Since extracts have proven to support wound healing, in the present study effects of HYP on human dermal fibroblasts (HDF) were evaluated in 2D and 3D in vitro dermal constructs. Viability and cytotoxicity assays as well as a live-dead cell staining were performed to test at which concentration HYP reduces viability and/or shows cytotoxicity. Furthermore a differentiation between cytotoxic, anti-proliferative and anti-migratory effects was done. For the latter purpose a 2D migration assay was performed. HDF-induced contraction of a 3D artificial dermal (AD) construct was determined at given HYP concentration. Induction of apoptosis was examined by determination of caspase 3/7 activities. HYP reduced viability of HDF down to 70% at concentrations of 5-10µM. This decrease was not due to cytotoxicity but to a reduction in proliferation as shown from both the proliferation assay and the cytotoxicity assay as well as from live-dead cell staining. The 2D migration assay showed that HYP reduced migration activity of HDF cells at a concentration of 10µM. At this concentration HYP also reduced the HDF-induced contraction of collagen gels as 3D AD constructs. Apoptotic effects of HYP were excluded performing a caspase 3/7 activity detecting assay. The results show for the first time that HYP may be rather a potential candidate for treatment of hypertrophic scars than promoting effects which are understood as important in wound healing. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2016-10-01

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

  1. Sialic Acid Metabolic Engineering: A Potential Strategy for the Neuroblastoma Therapy

    PubMed Central

    Gnanapragassam, Vinayaga S.; Bork, Kaya; Galuska, Christina E.; Galuska, Sebastian P.; Glanz, Dagobert; Nagasundaram, Manimozhi; Bache, Matthias; Vordermark, Dirk; Kohla, Guido; Kannicht, Christoph; Schauer, Roland; Horstkorte, Rüdiger

    2014-01-01

    Background Sialic acids (Sia) represent negative-charged terminal sugars on most glycoproteins and glycolipids on the cell surface of vertebrates. Aberrant expression of tumor associated sialylated carbohydrate epitopes significantly increases during onset of cancer. Since Sia contribute towards cell migration ( =  metastasis) and to chemo- and radiation resistance. Modulation of cellular Sia concentration and composition poses a challenge especially for neuroblastoma therapy, due to the high heterogeneity and therapeutic resistance of these cells. Here we propose that Metabolic Sia Engineering (MSE) is an effective strategy to reduce neuroblastoma progression and metastasis. Methods Human neuroblastoma SH-SY5Y cells were treated with synthetic Sia precursors N-propanoyl mannosamine (ManNProp) or N-pentanoyl mannosamine (ManNPent). Total and Polysialic acids (PolySia) were investigated by high performance liquid chromatography. Cell surface polySia were examined by flow-cytometry. Sia precursors treated cells were examined for the migration, invasion and sensitivity towards anticancer drugs and radiation treatment. Results Treatment of SH-SY5Y cells with ManNProp or ManNPent (referred as MSE) reduced their cell surface sialylation significantly. We found complete absence of polysialylation after treatment of SH-SY5Y cells with ManNPent. Loss of polysialylation results in a reduction of migration and invasion ability of these cells. Furthermore, radiation of Sia-engineered cells completely abolished their migration. In addition, MSE increases the cytotoxicity of anti-cancer drugs, such as 5-fluorouracil or cisplatin. Conclusions Metabolic Sia Engineering (MSE) of neuroblastoma cells using modified Sia precursors reduces their sialylation, metastatic potential and increases their sensitivity towards radiation or chemotherapeutics. Therefore, MSE may serve as an effective method to treat neuroblastoma. PMID:25148252

  2. Antibacterial and Antimetastatic Potential of Diospyros lycioides Extract on Cervical Cancer Cells and Associated Pathogens

    PubMed Central

    Bagla, V. P.; Lubisi, V. Z.; Ndiitwani, T.; Mokgotho, M. P.; Mampuru, L.; Mbazima, V.

    2016-01-01

    Cervical cancer is among the most prevalent forms of cancer in women worldwide. Diospyros lycioides was extracted using hexane, ethyl acetate, acetone, and methanol and finger print profiles were determined. The leaf material was tested for the presence of flavonoids, tannins, saponins, terpenoids, and cardiac glycosides using standard chemical methods and the presence of flavonoids and phenolics using thin layer chromatography. The total phenolic content was determined using Folin-Ciocalteu procedure. The four extracts were tested for antibacterial activity using bioautography against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Escherichia coli. The acetone extract with the highest number of antibacterial and antioxidant compounds was assessed for its cytotoxicity on BUD-8 cells using the real-time xCELLigence system and its potential effects on metastatic cervical cancer (HeLa) cell migration and invasion were assessed using wound healing migration and invasion assays. The leaf extract tested positive for flavonoids, tannins, and terpenoids while the four different extracts tested in the antimicrobial assay contained constituents active against one or more of the organisms tested, except E. coli. The cytotoxicity of the acetone extract in real-time was concentration-dependent with potent ability to suppress the migration and invasion of HeLa cells. The finding demonstrates the acetone extract to contain constituents with antibacterial and antimetastatic effects on cervical cancer cells. PMID:27239210

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

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

    Bernhart, Eva; Damm, Sabine; Wintersperger, Andrea

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

  4. Microfluidic gradient device for studying mesothelial cell migration and the effect of chronic carbon nanotube exposure

    NASA Astrophysics Data System (ADS)

    Zhang, Hanyuan; Lohcharoenkal, Warangkana; Sun, Jianbo; Li, Xiang; Wang, Liying; Wu, Nianqiang; Rojanasakul, Yon; Liu, Yuxin

    2015-07-01

    Cell migration is one of the crucial steps in many physiological and pathological processes, including cancer development. Our recent studies have shown that carbon nanotubes (CNTs), similarly to asbestos, can induce accelerated cell growth and invasiveness that contribute to their mesothelioma pathogenicity. Malignant mesothelioma is a very aggressive tumor that develops from cells of the mesothelium, and is most commonly caused by exposure to asbestos. CNTs have a similar structure and mode of exposure to asbestos. This has raised a concern regarding the potential carcinogenicity of CNTs, especially in the pleural area which is a key target for asbestos-related diseases. In this paper, a static microfluidic gradient device was applied to study the migration of human pleural mesothelial cells which had been through a long-term exposure (4 months) to subcytotoxic concentration (0.02 µg cm-2) of single-walled CNTs (SWCNTs). Multiple migration signatures of these cells were investigated using the microfluidic gradient device for the first time. During the migration study, we observed that cell morphologies changed from flattened shapes to spindle shapes prior to their migration after their sensing of the chemical gradient. The migration of chronically SWCNT-exposed mesothelial cells was evaluated under different fetal bovine serum (FBS) concentration gradients, and the migration speeds and number of migrating cells were extracted and compared. The results showed that chronically SWCNT-exposed mesothelial cells are more sensitive to the gradient compared to non-SWCNT-exposed cells. The method described here allows simultaneous detection of cell morphology and migration under chemical gradient conditions, and also allows for real-time monitoring of cell motility that resembles in vivo cell migration. This platform would be much needed for supporting the development of more physiologically relevant cell models for better assessment and characterization of the mesothelioma hazard posed by nanomaterials.

  5. Wnt2 and WISP-1/CCN4 Induce Intimal Thickening via Promotion of Smooth Muscle Cell Migration.

    PubMed

    Williams, Helen; Mill, Carina A E; Monk, Bethan A; Hulin-Curtis, Sarah; Johnson, Jason L; George, Sarah J

    2016-07-01

    Increased vascular smooth muscle cell (VSMC) migration leads to intimal thickening which acts as a soil for atherosclersosis, as well as causing coronary artery restenosis after stenting and vein graft failure. Investigating factors involved in VSMC migration may enable us to reduce intimal thickening and improve patient outcomes. In this study, we determined whether Wnt proteins regulate VSMC migration and thereby intimal thickening. Wnt2 mRNA and protein expression were specifically increased in migrating mouse aortic VSMCs. Moreover, VSMC migration was induced by recombinant Wnt2 in vitro. Addition of recombinant Wnt2 protein increased Wnt1-inducible signaling pathway protein-1 (WISP-1) mRNA by ≈1.7-fold, via β-catenin/T-cell factor signaling, whereas silencing RNA knockdown of Wnt-2 reduced WISP-1 mRNA by ≈65%. Treatment with rWISP-1 significantly increased VSMC migration by ≈1.5-fold, whereas WISP-1 silencing RNA knockdown reduced migration by ≈40%. Wnt2 and WISP-1 effects were integrin-dependent and not additive, indicating that Wnt2 promoted VSMC migration via WISP-1. Additionally, Wnt2 and WISP-1 were significantly increased and colocated in human coronary arteries with intimal thickening. Reduced Wnt2 and WISP-1 levels in mouse carotid arteries from Wnt2(+/-) and WISP-1(-/-) mice, respectively, significantly suppressed intimal thickening in response to carotid artery ligation. In contrast, elevation of plasma WISP-1 via an adenovirus encoding WISP-1 significantly increased intimal thickening by ≈1.5-fold compared with mice receiving control virus. Upregulation of Wnt2 expression enhanced WISP-1 and promoted VSMC migration and thereby intimal thickening. As novel regulators of VSMC migration and intimal thickening, Wnt2 or WISP-1 may provide a potential therapy for restenosis and vein graft failure. © 2016 American Heart Association, Inc.

  6. Effect of Aqueous Extract of Giant Horsetail (Equisetum giganteum L.) in Antigen-Induced Arthritis.

    PubMed

    Farinon, Mirian; Lora, Priscila Schmidt; Francescato, Leandro Nicolodi; Bassani, Valquiria Linck; Henriques, Amélia Teresinha; Xavier, Ricardo Machado; de Oliveira, Patricia Gnieslaw

    2013-01-01

    Equisetum giganteum is a plant used in traditional medicine as diuretic. From our knowledge this is the first time this plant is tested in an in vivo model of acute inflammation. To evaluate the effect of aqueous extract of giant horsetail (AEGH) as immunomodulatory therapy, antigen-induced arthritis (AIA) was generated in mice with methylated bovine serum albumin (mBSA). Inflammation was evaluated by articular nociception, leukocytes migration and lymphocyte proliferation. AEGH reduced nociception at 3, 6 and 24 h (P < 0.01), decreased leukocyte migration (P < 0.015), and inhibited lymphocyte proliferation stimulated with Concanavalin A and Lipopolysaccharide (P < 0.05). In conclusion, AEGH has an anti-inflammatory potential in acute model of inflammation, as well as immunomodulatory effect on both B and T lymphocytes, with an action independent of cytotoxicity.

  7. Effect of Aqueous Extract of Giant Horsetail (Equisetum giganteum L.) in Antigen-Induced Arthritis

    PubMed Central

    Farinon, Mirian; Lora, Priscila Schmidt; Francescato, Leandro Nicolodi; Bassani, Valquiria Linck; Henriques, AmÉlia Teresinha; Xavier, Ricardo Machado; de Oliveira, Patricia Gnieslaw

    2013-01-01

    Equisetum giganteum is a plant used in traditional medicine as diuretic. From our knowledge this is the first time this plant is tested in an in vivo model of acute inflammation. To evaluate the effect of aqueous extract of giant horsetail (AEGH) as immunomodulatory therapy, antigen-induced arthritis (AIA) was generated in mice with methylated bovine serum albumin (mBSA). Inflammation was evaluated by articular nociception, leukocytes migration and lymphocyte proliferation. AEGH reduced nociception at 3, 6 and 24 h (P < 0.01), decreased leukocyte migration (P < 0.015), and inhibited lymphocyte proliferation stimulated with Concanavalin A and Lipopolysaccharide (P < 0.05). In conclusion, AEGH has an anti-inflammatory potential in acute model of inflammation, as well as immunomodulatory effect on both B and T lymphocytes, with an action independent of cytotoxicity. PMID:24494034

  8. 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.

  9. Surface coating for prevention of metallic seed migration in tissues

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

    Lee, Hyunseok; Park, Jong In; Lee, Won Seok

    Purpose: In radiotherapy, metallic implants often detach from their deposited sites and migrate to other locations. This undesirable migration could cause inadequate dose coverage for permanent brachytherapy and difficulties in image-guided radiation delivery for patients. To prevent migration of implanted seeds, the authors propose a potential strategy to use a biocompatible and tissue-adhesive material called polydopamine. Methods: In this study, nonradioactive dummy seeds that have the same geometry and composition as commercial I-125 seeds were coated in polydopamine. Using scanning electron microscopy and x-ray photoelectron spectroscopy, the surface of the polydopamine-coated and noncoated seeds was characterized. The detachment stress betweenmore » the two types of seeds and the tissue was measured. The efficacy of polydopamine-coated seed was investigated through in vitro migration tests by tracing the seed location after tissue implantation and shaking for given times. The cytotoxicity of the polydopamine coating was also evaluated. Results: The results of the coating characterization have shown that polydopamine was successfully coated on the surface of the seeds. In the adhesion test, the polydopamine-coated seeds had 2.1-fold greater detachment stress than noncoated seeds. From the in vitro test, it was determined that the polydopamine-coated seed migrated shorter distances than the noncoated seed. This difference was increased with a greater length of time after implantation. Conclusions: The authors suggest that polydopamine coating is an effective technique to prevent migration of implanted seeds, especially for permanent prostate brachytherapy.« less

  10. A model for migration and accumulation of hydrocarbons in the Thamama and Arab reservoirs in Abu Dhabi, U.A.E.

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

    Hawas, M.F.; Takezaki, H.

    1995-08-01

    The distribution of hydrocarbons in the Lower Cretaceous Thamama Group and Upper Jurassic Arab Formation in Abu Dhabi is influenced by the development of the intervening Hith anhydrites. The geochemical analysis of Thamama and Arab hydrocarbons indicate that they were generated from a common source rock: the Upper Jurassic Diyab Formation. Studies carried out on the Miocene sabkha anhydrites in the coastal flat west of Abu Dhabi supported a model for vertical migration through the Hith anhydrites under certain conditions. The established model implies that the Diyab oil and gas had migrated essentially vertically and individually which means that themore » oil migrated prior to the gas and their distribution is controlled by the differential sealing potential of the anhydrites at each migration phase: a Hith anhydrite bed of more than 30 feet (ft.) thick was a perfect seal for hydrocarbon migration into the Arab reservoirs. In this case, oils could not break through to the overlying Thamama group. But where the anhydride bed thicknesses dropped below 30 ft. thick, this permitted oil migration through to the overlying Thamama reservoirs during the oil generation phase in the Turonian time. At a later stage, with additional depth of burial and progressive diagenesis anhydrite beds as thin as 8 ft. thick became effective seals. These controlled the distribution of the gas during the gas generation phase in the Eocene time.« less

  11. Rural–urban migration and mental and sexual health: a case study in Southwestern China

    PubMed Central

    Yang, Xiushi

    2014-01-01

    Massive rural–urban temporary migration has taken place amid China's rapid economic growth and development. Much has been written about the economic causes and consequences of this massive migration; less studied are the potential health and behavioral impacts of migration on migrants. Using data from a population-based sample survey conducted in southwestern China, this paper examines the potential impact of rural–urban migration and post-migration urban living on migrants' mental health and sexual risk behavior. The results suggest that regardless of places of origin and destination temporary migrants had on average poorer mental health and riskier sexual behavior than non-migrants. Compared to living in rural areas, living in urban areas does not make statistical difference in residents' mental health; it is only marginally associated with riskier sexual behavior. Rural–urban temporary migrants' mental health and health risk sexual behavior deserve more immediate research attention. Both selectivity of temporary migrants and migration-induced psycho-socio-behavioral changes may have contributed to migrants' poorer mental health and riskier sexual behavior. However, more theory-driven research with longitudinal design is needed before firm conclusions can be drawn about the underlying mechanisms that mediate or moderate the impact of temporary migration on migrants' mental health and sexual risk behavior. PMID:25932350

  12. Controls on drainage divide migration in the northern Sierras Pampeanas assessed through morphometric indicators

    NASA Astrophysics Data System (ADS)

    Seagren, E. G.; Schoenbohm, L. M.

    2017-12-01

    Drainage reorganization, primarily through progressive divide migration leading to discrete stream captures, is increasingly recognized as a common phenomenon during mountain-building events. This drainage rearrangement reflects complex interactions between tectonics, climate, and lithology, and can fundamentally change erosion and sedimentation patterns; therefore, determining the spatial extent and potential controls of divide migration is vital to understanding the topographic evolution of orogenic landscapes. Both geomorphic and morphometric evidence can be used to identify such drainage reorganization. The northern Sierras Pampeanas is an ideal location in which to study divide migration as limited glaciation and low out-of-channel erosion rates preserve evidence of reorganization. Additionally, several ranges in the region, such as Sierra de las Planchadas, exhibit geomorphic evidence of drainage rearrangement, including wind gaps and hairpin turns. Using ArcGIS, LSDTopoTools, and TopoToolbox, we conducted a systematic analysis of the spatial distribution of three morphometric indicators of divide migration: χ, Mx, and local headwater relief. Local `hotspots' undergoing drainage divide migration were identified using spatial autocorrelation and clustering methods - Gi* and Moran's I. Using spatial regression analysis, we assessed the potential controls of lithology, modern TRMM precipitation rates, and tectonics over divide migration. Preliminary results suggest broad westward migration of main drainage divides, following both the orographic precipitation gradient and regional slope.

  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. Evaluating predictors of local dabbling duck abundance during migration: Managing the spectrum of conditions faced by migrants

    USGS Publications Warehouse

    Aagaard, Kevin; Crimmins, Shawn M.; Thogmartin, Wayne E.; Tavernia, Brian G.; Lyons, James E.

    2015-01-01

    The development of robust modelling techniques to derive inferences from large-scale migratory bird monitoring data at appropriate scales has direct relevance to their management. The Integrated Waterbird Management and Monitoring programme (IWMM) represents one of the few attempts to monitor migrating waterbirds across entire flyways using targeted local surveys. This dataset included 13,208,785 waterfowl (eight Anas species) counted during 28,000 surveys at nearly 1,000 locations across the eastern United States between autumn 2010 and spring 2013 and was used to evaluate potential predictors of waterfowl abundance at the wetland scale. Mixed-effects, log-linear models of local abundance were built for the Atlantic and Mississippi flyways during spring and autumn migration to identify factors relating to habitat structure, forage availability, and migration timing that influence target dabbling duck species abundance. Results indicated that migrating dabbling ducks responded differently to environmental factors. While the factors identified demonstrated a high degree of importance, they were inconsistent across species, flyways and seasons. Furthermore, the direction and magnitude of the importance of each covariate group considered here varied across species. Given our results, actionable policy recommendations are likely to be most effective if they consider species-level variation within targeted taxonomic units and across management areas. The methods implemented here can easily be applied to other contexts, and serve as a novel investigation into local-level population patterns using data from broad-scale monitoring programmes.

  15. Quercetin Inhibits the Migration and Invasion of HCCLM3 Cells by Suppressing the Expression of p-Akt1, Matrix Metalloproteinase (MMP) MMP-2, and MMP-9.

    PubMed

    Lu, Jun; Wang, Zhiqiang; Li, Shuyan; Xin, Qi; Yuan, Miaomiao; Li, Huanping; Song, Xiaoxia; Gao, Haijun; Pervaiz, Nabeel; Sun, Xudong; Lv, Wei; Jing, Tao; Zhu, Yanmei

    2018-04-27

    BACKGROUND Quercetin is a natural bioactive flavonoid that is present in a wide variety of vegetables and fruits and exhibits a promising anti-metastasis property in various human cancer cells. However, the effect of quercetin on human HCCLM3 cells is unclear. MATERIAL AND METHODS In the current study, a wound-healing assay was performed using quercetin-treated HCCLM3 cells to further explore whether quercetin affects the motility of human HCCLM3 cells. Transwell assay was used to explore the potential effect of quercetin in HCCLM3 cells on cell migration and cell invasion. Western blotting analysis was used to explore the expression of p-Akt1, MMP-2, and MMP-9 in quercetin-treated HCCLM3 cells. RESULTS The wound-healing time was delayed in quercetin-treated HCCLM3 cells, and the ability to migrate and invade was inhibited in quercetin-treated human HCCLM3 cells. Moreover, the protein levels of p-Akt1, MMP-2, and MMP-9 were down-regulated in quercetin-treated HCCLM3 cells, as detected by Western blotting. CONCLUSIONS Our data show that quercetin attenuated cell migration and invasion by suppressing the protein levels of p-Akt1, MMP-2, and MMP-9 in HCCLM3 cells.

  16. Transforming Growth Factor β1 Promotes Migration and Invasion of Human Hepatocellular Carcinoma Cells Via Up-Regulation of Connective Tissue Growth Factor.

    PubMed

    Liu, Haizhou; Wang, Shaoyang; Ma, Weimin; Lu, Youguang

    2015-12-01

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a poor patient survival. Expression of TGF-β1 is up-regulated in HCC and is thought to play a crucial role in the occurrence and development of HCC. However, the mechanism of TGF-β1-mediated facilitation of malignant growth and invasion remains unclear, although some previous studies highlighted a potential involvement of the connective tissue growth factor (CTGF). Here we demonstrate that the in vitro migration of the HCC cell line SMMC-7721 is increased in the presence of recombinant TGF-β1, and that this effect is reversed by the specific inhibitor SB431542. Furthermore, TGF-β1 treatment up-regulated the expression of its own mRNA as well as the expression of CTGF mRNA. The TGF-β1-stimulated migration of SMMC-7721 cells was diminished by siRNA silencing of CTGF. These in vitro observations were validated in a murine xenograft model. In particular, silencing of CTFG diminished the TGF-β1-induced tumorigenesis in experimental animals. In conclusion, TGF-β1 plays a critical role in HCC migration and invasion, and this effect is dependent on CTGF.

  17. Effect of bottling and storage on the migration of plastic constituents in Spanish bottled waters.

    PubMed

    Guart, Albert; Bono-Blay, Francisco; Borrell, Antonio; Lacorte, Silvia

    2014-08-01

    Bottled water is packaged in either glass or, to a large extent, in plastic bottles with metallic or plastic caps of different material, shape and colour. Plastic materials are made of one or more monomers and several additives that can eventually migrate into water, either during bottle manufacturing, water filling or storage. The main objective of the present study was to carry out a comprehensive assessment of the quality of the Spanish bottled water market in terms of (i) migration of plastic components or additives during bottling and during storage and (ii) evaluation of the effect of the packaging material and bottle format on the migration potential. The compounds investigated were 5 phthalates, diethylhexyl adipate, alkylphenols and bisphenol A. A set of 362 bottled water samples corresponding to 131 natural mineral waters and spring waters sources and 3 treated waters of several commercial brands were analysed immediately after bottling and after one-year storage (a total of 724 samples). Target compounds were detected in 5.6% of the data values, with diethyl hexyl phthalate and bisphenol A being the most ubiquitous compounds detected. The total daily intake was estimated and a comparison with reference values was indicated. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Tramadol regulates proliferation, migration and invasion via PTEN/PI3K/AKT signaling in lung adenocarcinoma cells.

    PubMed

    Xia, M; Tong, J-H; Ji, N-N; Duan, M-L; Tan, Y-H; Xu, J-G

    2016-06-01

    Tramadol is used mainly for the treatment of moderate to severe chronic cancer pain. However, the effect of tramadol on lung cancer remains unclear. Therefore, it is important to explore the mechanism accounting for the function of tramadol on lung cancer. We investigated the effects of tramadol on the proliferation, migration and invasion in human lung adenocarcinoma cells in vitro by CCK-8 assay, wound healing assay and Transwell assay, respectively. We also explored the potential mechanism of tramadol on lung cancer cells by Western blotting. A549 and PC-9 cells were incubated with 2 µM tramadol for different time (0, 7, 14 and 28 d). The in vitro experiments showed that tramadol treatment significantly inhibited cell proliferation, migration and invasion in a time-dependent manner. Moreover, administration of tramadol suppressed tumor growth in vivo. The data also revealed that tramadol could up-regulate the protein expression level of PTEN and consistently inhibit the phosphorylation level of PI3K and Akt, whereas the total level of PI3K and Akt remain unchanged. These findings indicated that tramadol inhibited proliferation, migration and invasion of human lung adenocarcinoma cells through elevation of PTEN and inactivation of PI3K/Akt signaling.

  19. Attenuated migration by green tea extract (-)-epigallocatechin gallate (EGCG): involvement of 67 kDa laminin receptor internalization in macrophagic cells.

    PubMed

    Ren, Xuezhi; Guo, Xingzhi; Chen, Li; Guo, Minxia; Peng, Ning; Li, Rui

    2014-08-01

    Excessive activation of the microglia in the brain is involved in the development of several neurodegenerative diseases. Previous studies have indicated that (-)-epigallocatechin gallate (EGCG), a major active constituent of green tea, exhibits potent suppressive effects on the activation of microglia. As the 67 kDa laminin receptor (67LR) is a key element in cellular activation and migration, we investigated the effect of EGCG on cell migration and 67LR in lipopolysaccharide (LPS)-activated macrophagic RAW264.7 cells. The presence of EGCG (1-25 μM) markedly attenuated LPS-induced cell migration in a dose-dependent manner. However, the total amount of 67LR protein in the RAW264.7 cells was unaffected by EGCG, as revealed by Western blot analysis. In addition, confocal immunofluorescence microscopy indicated that EGCG caused a marked membrane translocation of 67LR from the membrane surface towards the cytoplasm. Cell-surface biotinylation analysis confirmed that EGCG induced a significant internalization of 67LR by 24-68% in a dose-dependent manner. This study helps to explain the pharmacological action of EGCG on 67LR, suggesting its potential use in the treatment of diseases associated with macrophage/microglia activation, such as neurodegenerative diseases and cancer.

  20. Investigation of particle inertial migration in high particle concentration suspension flow by multi-electrodes sensing and Eulerian-Lagrangian simulation in a square microchannel

    PubMed Central

    Zhao, Tong; Liu, Kai; Takei, Masahiro

    2016-01-01

    The inertial migration of neutrally buoyant spherical particles in high particle concentration (αpi > 3%) suspension flow in a square microchannel was investigated by means of the multi-electrodes sensing method which broke through the limitation of conventional optical measurement techniques in the high particle concentration suspensions due to interference from the large particle numbers. Based on the measured particle concentrations near the wall and at the corner of the square microchannel, particle cross-sectional migration ratios are calculated to quantitatively estimate the migration degree. As a result, particle migration to four stable equilibrium positions near the centre of each face of the square microchannel is found only in the cases of low initial particle concentration up to 5.0 v/v%, while the migration phenomenon becomes partial as the initial particle concentration achieves 10.0 v/v% and disappears in the cases of the initial particle concentration αpi ≥ 15%. In order to clarify the influential mechanism of particle-particle interaction on particle migration, an Eulerian-Lagrangian numerical model was proposed by employing the Lennard-Jones potential as the inter-particle potential, while the inertial lift coefficient is calculated by a pre-processed semi-analytical simulation. Moreover, based on the experimental and simulation results, a dimensionless number named migration index was proposed to evaluate the influence of the initial particle concentration on the particle migration phenomenon. The migration index less than 0.1 is found to denote obvious particle inertial migration, while a larger migration index denotes the absence of it. This index is helpful for estimation of the maximum initial particle concentration for the design of inertial microfluidic devices. PMID:27158288

  1. Determination of the Wound Healing Potentials of Medicinal Plants Historically Used in Ghana

    PubMed Central

    Freiesleben, Sara H.; Soelberg, Jens; Nyberg, Nils T.

    2017-01-01

    The present study was carried out to investigate the wound healing potentials of 17 medicinal plants historically used in Ghana for wound healing. Warm and cold water extracts were prepared from the 17 dried plant species and tested in vitro in the scratch assay with NIH 3T3 fibroblasts from mice. The wound healing scratch assay was used to evaluate the effect of the plants on cell proliferation and/or migration in vitro, as a test for potential wound healing properties. After 21 hours of incubation increased proliferation and/or migration of fibroblasts in the scratch assay was obtained for 5 out of the 17 plant species. HPLC separation of the most active plant extract, which was a warm water extract of Philenoptera cyanescens, revealed the wound healing activity to be attributed to rutin and a triglycoside of quercetin. The present study suggests that Allophylus spicatus, Philenoptera cyanescens, Melanthera scandens, Ocimum gratissimum, and Jasminum dichotomum have wound healing activity in vitro. PMID:28326125

  2. Habitat use by fishes of Lake Superior. II. Consequences of diel habitat use for habitat linkages and habitat coupling in nearshore and offshore waters

    USGS Publications Warehouse

    Gorman, Owen T.; Yule, Daniel L.; Stockwell, Jason D.

    2012-01-01

    Diel migration patterns of fishes in nearshore (15–80 m depth) and offshore (>80 m) waters of Lake Superior were examined to assess the potential for diel migration to link benthic and pelagic, and nearshore and offshore habitats. In our companion article, we described three types of diel migration: diel vertical migration (DVM), diel bank migration (DBM), and no diel migration. DVM was expressed by fishes migrating from benthopelagic to pelagic positions and DBM was expressed by fishes migrating horizontally from deep to shallow waters at night. Fishes not exhibiting diel migration typically showed increased activity by moving from benthic to benthopelagic positions within demersal habitat. The distribution and biomass of fishes in Lake Superior was characterized by examining 704 bottom trawl samples collected between 2001 and 2008 from four depth zones: ≤40, 41–80, 81–160, and >160 m. Diel migration behaviors of fishes described in our companion article were applied to estimates of areal biomass (kg ha−1) for each species by depth zone. The relative strength of diel migrations were assessed by applying lake area to areal biomass estimates for each species by depth zone to yield estimates of lake-wide biomass (metric tonnes). Overall, species expressing DVM accounted for 83%, DBM 6%, and non-migration 11% of the total lake-wide community biomass. In nearshore waters, species expressing DVM represented 74% of the biomass, DBM 25%, and non-migration 1%. In offshore waters, species expressing DVM represented 85%, DBM 1%, and non-migration 14% of the biomass. Of species expressing DVM, 83% of total biomass occurred in offshore waters. Similarly, 97% of biomass of non-migrators occurred in offshore waters while 83% of biomass of species expressing DBM occurred in nearshore waters. A high correlation (R2 = 0.996) between lake area and community biomass by depth zone resulted in 81% of the lake-wide biomass occurring in offshore waters. Accentuating this nearshore-offshore trend was one of increasing estimated total areal biomass of the fish community with depth zone, which ranged from 13.71 kg ha−1 at depths ≤40 m to 18.81 kg ha−1 at depths >160 m, emphasizing the importance of the offshore fish community to the lake ecosystem. The prevalence of diel migration expressed by Lake Superior fishes increases the potential of fish to link benthic and pelagic and shallow and deepwater habitats. These linkages enhance the potential for habitat coupling, a condition where habitats become interconnected and interdependent through transfers of energy and nutrients. Habitat coupling facilitates energy and nutrient flow through a lake ecosystem, thereby increasing productivity, especially in large lakes where benthic and pelagic, and nearshore and offshore habitats are often well separated. We propose that the application of biomass estimates to patterns of diel migration in fishes can serve as a useful metric for assessing the potential for habitat linkages and habitat coupling in lake ecosystems, and provide an important indicator of ecosystem health and function. The decline of native Lake Trout and ciscoes and recent declines in exotic Alewife and Rainbow Smelt populations in other Great Lakes have likely reduced the capacity for benthic-pelagic coupling in these systems compared to Lake Superior. We recommend comparing the levels and temporal changes in diel migration in other Great Lakes as a means to assess changes in the relative health and function of these ecosystems.

  3. Sodium phenylbutyrate antagonizes prostate cancer through the induction of apoptosis and attenuation of cell viability and migration.

    PubMed

    Xu, Yawen; Zheng, Shaobo; Chen, Binshen; Wen, Yong; Zhu, Shanwen

    2016-01-01

    Prostate cancer (PCa) is a leading cause of cancer-related death in men. Sodium phenylbutyrate (SPB) has shown its potential as an anticancer therapy in numerous cancer types. In the present study, we attempted to assess the effect of SPB against PCa and whether this treatment was associated with the regulation of survivin. Two human PCa cancer cell lines, DU145 and PC3, were used in the present study. Cell Counting Kit-8 (CCK-8) assay was conducted to measure the proliferation of PCa cells incubated with SPB. The effect of SPB on the cell apoptosis, cell colony formation ability, and cell morphological change was also assessed. Transwell experiment and Western blotting assay were performed to determine the effect of SPB on the migration and invasion ability of both cell types. Moreover, the expression pattern of survivin and MAPK members in both cell types after the treatment of SPB was also detected. Additionally, an in vivo tumor formation assay was performed to evaluate the treatment potential of SPB against PCa. We found that the viability of PCa cells was significantly inhibited by SPB treatment. As illustrated by flow cytometry, for DU145 cell line the average apoptotic rate of SPB-treated cells was significantly lower than that of the control group (P<0.05); similar results were also seen for PC3 (P<0.05). SPB administration also attenuated the colony formation and migration abilities in both cell lines. The expression level of survivin in SPB-treated cells was significantly downregulated, while the phosphorylation of p-38 and ERK was enhanced. Furthermore, in vivo tumor formation of both cell lines was suppressed by SPB as well. The above results confirmed the potential of SPB as an effective therapeutic agent for the prevention or treatment of PCa. This amelioration might be due to the blockade of the survivin pathway.

  4. MicroRNA-34a targets epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs) and inhibits breast cancer cell migration and invasion

    PubMed Central

    Fu, Shangyi; Yang, Luquan; Tania, Mousumi; Zhang, Xianqin; Xiao, Xiuli; Zhang, Xianning; Fu, Junjiang

    2017-01-01

    MicroRNA-34a (miR-34a) plays an essential role against tumorigenesis and progression of cancer metastasis. Here, we analyzed the expression, targets and functional effects of miR-34a on epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs), such as TWIST1, SLUG and ZEB1/2, and an EMT-inducing protein NOTCH1 in breast cancer (BC) cell migration and invasion and its correlation with tumorigenesis and clinical outcomes. Expression of miR-34a is downregulated in human metastatic breast cancers (MBC) compared to normal breast tissues and is negatively correlated with clinicopathological features of MBC patients. Ectopic expression of miR-34a in MBC cell-line BT-549 significantly inhibits cell migration and invasion, but exhibits no clear effect on BC cell growth. We found that miR-34a is able to inactivate EMT signaling pathway with mediatory of NOTCH1, TWIST1, and ZEB1 upon 3′-UTR activity in MBC cell lines, but has no inhibitory effects on SLUG and ZEB2. Furthermore, we investigated the synergistic effects of Thymoquinone (TQ) and miR-34a together on the expression of EMT-associated proteins. Results showed that co-delivery of miR-34a and TQ is able to inactivate EMT signaling pathway by directly targeting TWIST1 and ZEB1 in BT-549 cell line, indicating that they might be a promising therapeutic combination against breast cancer metastasis. Epigenetic inactivation of the EMT-TFs/miR-34a pathway can potentially alter the equilibrium of these regulations, facilitating EMT and metastasis in BC. Altogether, our findings suggest that miR-34a alone could serve as a potential therapeutic agent for MBC, and together with TQ, their therapeutic potential is synergistically enhanced. PMID:28423483

  5. MicroRNA-34a targets epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs) and inhibits breast cancer cell migration and invasion.

    PubMed

    Imani, Saber; Wei, Chunli; Cheng, Jingliang; Khan, Md Asaduzzaman; Fu, Shangyi; Yang, Luquan; Tania, Mousumi; Zhang, Xianqin; Xiao, Xiuli; Zhang, Xianning; Fu, Junjiang

    2017-03-28

    MicroRNA-34a (miR-34a) plays an essential role against tumorigenesis and progression of cancer metastasis. Here, we analyzed the expression, targets and functional effects of miR-34a on epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs), such as TWIST1, SLUG and ZEB1/2, and an EMT-inducing protein NOTCH1 in breast cancer (BC) cell migration and invasion and its correlation with tumorigenesis and clinical outcomes. Expression of miR-34a is downregulated in human metastatic breast cancers (MBC) compared to normal breast tissues and is negatively correlated with clinicopathological features of MBC patients. Ectopic expression of miR-34a in MBC cell-line BT-549 significantly inhibits cell migration and invasion, but exhibits no clear effect on BC cell growth. We found that miR-34a is able to inactivate EMT signaling pathway with mediatory of NOTCH1, TWIST1, and ZEB1 upon 3'-UTR activity in MBC cell lines, but has no inhibitory effects on SLUG and ZEB2. Furthermore, we investigated the synergistic effects of Thymoquinone (TQ) and miR-34a together on the expression of EMT-associated proteins. Results showed that co-delivery of miR-34a and TQ is able to inactivate EMT signaling pathway by directly targeting TWIST1 and ZEB1 in BT-549 cell line, indicating that they might be a promising therapeutic combination against breast cancer metastasis. Epigenetic inactivation of the EMT-TFs/miR-34a pathway can potentially alter the equilibrium of these regulations, facilitating EMT and metastasis in BC. Altogether, our findings suggest that miR-34a alone could serve as a potential therapeutic agent for MBC, and together with TQ, their therapeutic potential is synergistically enhanced.

  6. Rapamycin inhibits oxidative/nitrosative stress and enhances angiogenesis in high glucose-treated human umbilical vein endothelial cells: Role of autophagy.

    PubMed

    Rezabakhsh, Aysa; Ahmadi, Mahdi; Khaksar, Majid; Montaseri, Azadeh; Malekinejad, Hassan; Rahbarghazi, Reza; Garjani, Alireza

    2017-09-01

    Chronic hyperglycemia is a potent risk factor of abnormal angiogenesis with various tissue diseases. Autophagy, as an alternative cell response, is mostly generated by a vast array of insults. Applying autophagic response contributes to normal cell retrieval circumstance during various insults. We aimed to show whether stimulation/inhibition of autophagy could reduce or exacerbate oxidative status and angiogenic potential in endothelial cells after exposure to 30mM glucose. HUVECs were incubated with the combined regime of 100nM Rapamycin and 30mM glucose over a period of 72h. The effect of rapamycin on cell viability, malondialdehyde levels, and nitric oxide were monitored by convenient assays. Intracellular ROS level was measured by flow cytometric analysis and DCFDA. HUVECs migration and angiogenic properties were assessed using scratch test and tubulogenesis assay. The expression of autophagic modulators LC3, Becline-1 and P62 was measured by using western blotting. Data showed 30mM glucose reduced cell viability, migration and in vitro tubulogenesis and level of ROS and nitric oxide were found to increased (p<0.05). Rapamycin had potential to increase cell survival and significantly decreased the total levels of oxidative stress markers after cell exposure to 30mM glucose (p<0.05). Rapamycin potentially improved the detrimental effect of 30mM glucose on cell migration and tubulogenesis capacity (p<0.05). Effective autophagic response was stimulated by rapamycin by increasing beclin-1, and the LC3-II/I ratio and reducing intracellular P62 level (p<0.05), resulting in the improvement of cell health and function. Together, rapamycin protected HUVECs from damages caused by high glucose concentration. This effect was possibly mediated by autophagy-dependent pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Food resource effects on diel movements and body size of cisco in north-temperate lakes.

    PubMed

    Ahrenstorff, Tyler D; Hrabik, Thomas R; Jacobson, Peter C; Pereira, Donald L

    2013-12-01

    The movement patterns and body size of fishes are influenced by a host of physical and biological conditions, including temperature and oxygen, prey densities and foraging potential, growth optimization, and predation risk. Our objectives were to (1) investigate variability in vertical movement patterns of cisco (Coregonus artedi) in a variety of inland lakes using hydroacoustics, (2) explore the causal mechanisms influencing movements through the use of temperature/oxygen, foraging, growth, and predation risk models, and (3) examine factors that may contribute to variations in cisco body size by considering all available information. Our results show that cisco vertical movements vary substantially, with different populations performing normal diel vertical migrations (DVM), no DVM, and reverse DVM in lakes throughout Minnesota and northern Wisconsin, USA. Cisco populations with the smallest body size were found in lakes with lower zooplankton densities. These smaller fish showed movements to areas of highest foraging or growth potential during the day and night, despite moving out of preferred temperature and oxygen conditions and into areas of highest predation risk. In lakes with higher zooplankton densities, cisco grew larger and had movements more consistent with behavioral thermoregulation and predator avoidance, while remaining in areas with less than maximum foraging and growth potential. Furthermore, the composition of potential prey items present in each lake was also important. Cisco that performed reverse DVM consumed mostly copepods and cladocerans, while cisco that exhibited normal DVM or no migration consumed proportionally more macro-zooplankton species. Overall, our results show previously undocumented variation in migration patterns of a fish species, the mechanisms underlying those movements, and the potential impact on their growth potential.

  8. Modeling of point defects and rare gas incorporation in uranium mono-carbide

    NASA Astrophysics Data System (ADS)

    Chartier, A.; Van Brutzel, L.

    2007-02-01

    An embedded atom method (EAM) potential has been established for uranium mono-carbide. This EAM potential was fitted on structural properties of metallic uranium and uranium mono-carbide. The formation energies of point defects, as well as activation energies for self migration, have been evaluated in order to cross-check the suitability of the potential. Assuming that the carbon vacancies are the main defects in uranium mono-carbide compounds, the migration paths and energies are consistent with experimental data selected by Catlow[C.R.A. Catlow, J. Nucl. Mater. 60 (1976) 151]. The insertion and migration energies for He, Kr and Xe have also been evaluated with available inter-atomic potentials [H.H. Andersen, P. Sigmund, Nucl. Instr. and Meth. B 38 (1965) 238]. Results show that the most stable defect configuration for rare gases is within uranium vacancies. The migration energy of an interstitial Xe is 0.5 eV, in agreement with the experimental value of 0.5 eV [Hj. Matzke, Science of advanced LMFBR fuels, Solid State Physics, Chemistry and Technology of Carbides, Nitrides and Carbonitrides of Uranium and Plutonium, North-Holland, 1986].

  9. Device and methods for writing and erasing analog information in small memory units via voltage pulses

    DOEpatents

    El Gabaly Marquez, Farid; Talin, Albert Alec

    2018-04-17

    Devices and methods for non-volatile analog data storage are described herein. In an exemplary embodiment, an analog memory device comprises a potential-carrier source layer, a barrier layer deposited on the source layer, and at least two storage layers deposited on the barrier layer. The memory device can be prepared to write and read data via application of a biasing voltage between the source layer and the storage layers, wherein the biasing voltage causes potential-carriers to migrate into the storage layers. After initialization, data can be written to the memory device by application of a voltage pulse between two storage layers that causes potential-carriers to migrate from one storage layer to another. A difference in concentration of potential carriers caused by migration of potential-carriers between the storage layers results in a voltage that can be measured in order to read the written data.

  10. Immediate dietary effects on migrating Mormon cricket immunocompetence

    USDA-ARS?s Scientific Manuscript database

    Mormon crickets form bands and walk over rangeland in the western United States seeking salt and protein. Radio-tracking adult members of a Mormon cricket band in a high Sonoran desert of Utah, we investigated a potential trade-off between immunocompetence and migratory velocity. We asked: does acce...

  11. Evidence of sulfate-dependent anaerobic methane oxidation within an area impacted by coalbed methane-related gas migration

    EPA Science Inventory

    The rapid development of unconventional gas resources has been accompanied by an increase in public awareness regarding the potential effects of drilling operations on drinking water sources. Incidents have been reported involving blowouts (e.g., Converse County, WY; Lawrence Tow...

  12. State policies and internal migration in Asia.

    PubMed

    Oberai, A S

    1981-01-01

    The objective of this discussion is to identify policies and programs in Asia that are explicitly or implicitly designed to influence migration, to investigate why they were adopted and how far they have actually been implemented, and to assess their direct and indirect consequences. For study purposes, policies and programs are classified according to whether they prohibit or reverse migration, redirect or channel migration to specific rural or urban locations, reduce the total volume of migration, or encourage or discourage urban in-migration. Discussion of each type of policy is accompanied by a description of its rationale and implementation mechanism, examples of countries in Asia that have recourse to it, and its intended or actual effect on migration. Several countries in Asia have taken direct measures to reverse the flow of migration and to stop or discourage migration to urban areas. These measures have included administrative and legal controls, police registration, and direct "rustication" programs to remove urban inhabitants to the countryside. The availability of public land has prompted many Asian countries to adopt schemes that have been labeled resettlement, transmigration, colonization, or land development. These schemes have been designed to realize 1 or more of the following objectives: to provide land and income to the landless; increase agricultural production; correct spatial imbalances in the distribution of population; or exploit frontier lands for reasons of national security. 1 of the basic goals of decentralized industrialization and regional development policies has been the reduction of interregional disparities and the redirection of migrations from large metropolitan areas to smaller and medium sized towns. To encourage industry to move to small urban locations initial infrastructure investments, tax benefits, and other incentives have been offered. Policies to reduce the overall volume of migration have frequently included rural development programs, the primary purpose of which is to retain potential migrants in the rural areas, and preferential policies for natives with a view toward discouraging interregional migration. The explicit goal of rural development strategies is often to slow rural-urban migration. Slowly the attitude towards migrant squatters and slum dwellers is changing from punitive to more tolerant. Several measures have been taken to accommodate migrants in urban areas and to promote their welfare.

  13. Potential Effects of a Scenario Earthquake on the Economy of Southern California: Baseline County-Level Migration Characteristics and Trends 1995-2000 and 2001-2010

    USGS Publications Warehouse

    Sherrouse, Benson C.; Hester, David J.

    2008-01-01

    The Multi-Hazards Demonstration Project (MHDP) is a collaboration between the U.S. Geological Survey (USGS) and various partners from the public and private sectors and academia, meant to improve Southern California's resiliency to natural hazards. In support of the MHDP objectives, the ShakeOut Scenario was developed. It describes a magnitude 7.8 earthquake along the southernmost 300 kilometers (200 miles) of the San Andreas Fault, identified by geoscientists as a plausible event that will cause moderate to strong shaking over much of the eight-county (Imperial, Kern, Los Angeles, Orange, Riverside, San Bernardino, San Diego, and Ventura) Southern California region. This report uses historical, estimated, and projected population data from several Federal and State data sources to estimate baseline characteristics and trends of the region's population migration (that is, changes in a person's place of residence over time). The analysis characterizes migration by various demographic, economic, family, and household variables for the period 1995-2000. It also uses existing estimates (beginning in 2001) of the three components of population change - births, deaths, and migration - to extrapolate near-term projections of county-level migration trends through 2010. The 2010 date was chosen to provide baseline projections corresponding to a two-year recovery period following the November 2008 date that was selected for the occurrence of the ShakeOut Scenario earthquake. The baseline characteristics and projections shall assist with evaluating the effects of inflow and outflow migration trends for alternative futures in which the simulated M7.8 earthquake either does or does not occur and the impact of the event on housing and jobs, as well as community composition and regional economy changes based on dispersion of intellectual, physical, economic, and cultural capital.

  14. Physiological and hypoxic oxygen concentration differentially regulates human c-Kit+ cardiac stem cell proliferation and migration.

    PubMed

    Bellio, Michael A; Rodrigues, Claudia O; Landin, Ana Marie; Hatzistergos, Konstantinos E; Kuznetsov, Jeffim; Florea, Victoria; Valasaki, Krystalenia; Khan, Aisha; Hare, Joshua M; Schulman, Ivonne Hernandez

    2016-12-01

    Cardiac stem cells (CSCs) are being evaluated for their efficacy in the treatment of heart failure. However, numerous factors impair the exogenously delivered cells' regenerative capabilities. Hypoxia is one stress that contributes to inadequate tissue repair. Here, we tested the hypothesis that hypoxia impairs cell proliferation, survival, and migration of human CSCs relative to physiological and room air oxygen concentrations. Human endomyocardial biopsy-derived CSCs were isolated, selected for c-Kit expression, and expanded in vitro at room air (21% O 2 ). To assess the effect on proliferation, survival, and migration, CSCs were transferred to physiological (5%) or hypoxic (0.5%) O 2 concentrations. Physiological O 2 levels increased proliferation (P < 0.05) but did not affect survival of CSCs. Although similar growth rates were observed in room air and hypoxia, a significant reduction of β-galactosidase activity (-4,203 fluorescent units, P < 0.05), p16 protein expression (0.58-fold, P < 0.001), and mitochondrial content (0.18-fold, P < 0.001) in hypoxia suggests that transition from high (21%) to low (0.5%) O 2 reduces senescence and promotes quiescence. Furthermore, physiological O 2 levels increased migration (P < 0.05) compared with room air and hypoxia, and treatment with mesenchymal stem cell-conditioned media rescued CSC migration under hypoxia to levels comparable to physiological O 2 migration (2-fold, P < 0.05 relative to CSC media control). Our finding that physiological O 2 concentration is optimal for in vitro parameters of CSC biology suggests that standard room air may diminish cell regenerative potential. This study provides novel insights into the modulatory effects of O 2 concentration on CSC biology and has important implications for refining stem cell therapies. Copyright © 2016 the American Physiological Society.

  15. The regulatory effect of SC-236 (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-l] benzenesulfonamide) on stem cell factor induced migration of mast cells

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

    Kim, Su-Jin; College of Oriental Medicine, Kyung Hee University, 1 Hoegi-Dong, Dongdaemun-Gu, Seoul 130-701; Jeong, Hyun-Ja

    SC-236 (4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1-pyrazol-1-]benzenesulfonamide; C{sub 16}H{sub 11}ClF{sub 3}N{sub 3}O{sub 2}S), is a highly selective cyclooxygenase (COX)-2 inhibitor. Recently, there have been reports that SC-236 protects against cartilage damage in addition to reducing inflammation and pain in osteoarthritis. However, the mechanism involved in the inflammatory allergic reaction has not been examined. Mast cells accumulation can be related to inflammatory conditions, including allergic rhinitis, asthma, and rheumatoid arthritis. The aim of the present study is to investigate the effects of SC-236 on stem cell factor (SCF)-induced migration, morphological alteration, and cytokine production of rat peritoneal mast cells (RPMCs). We observed that SCF significantly inducedmore » the migration and morphological alteration. The ability of SCF to enhance migration and morphological alteration was abolished by treatment with SC-236. In addition, production of tumor necrosis factor (TNF)-{alpha}, interleukin (IL)-1{beta}, and vascular endothelial growth factor (VEGF) production induced by SCF was significantly inhibited by treatment with SC-236. Previous work has demonstrated that SCF-induced migration and cytokine production of mast cells require p38 MAPK activation. We also showed that SC-236 suppresses the SCF-induced p38 MAPK activation in RPMCs. These data suggest that SC-236 inhibits migration and cytokine production through suppression of p38 MAPK activation. These results provided new insight into the pharmacological actions of SC-236 and its potential therapeutic role in the treatment of inflammatory allergic diseases.« less

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

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

    You, Kun; Sun, Peisheng; Yue, Zhongyi

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

  17. 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.

  18. Limits to benthic feeding by eiders in a vital Arctic migration corridor due to localized prey and changing sea ice

    USGS Publications Warehouse

    Lovvorn, James R.; Rocha, Aariel R.; Jewett, Stephen C.; Dasher, Douglas; Oppel, Steffen; Powell, Abby

    2015-01-01

    Four species of threatened or declining eider ducks that nest in the Arctic migrate through the northeast Chukchi Sea, where anticipated industrial development may require prioritizing areas for conservation. In this nearshore corridor (10–40 m depth), the eiders’ access to benthic prey during the spring is restricted to variable areas of open water within sea ice. For the most abundant species, the king eider (Somateria spectabilis), stable isotopes in blood cells, muscle, and potential prey indicate that these eiders ate mainly bivalves when traversing this corridor. Bivalves there were much smaller than the same taxa in deeper areas of the northern Bering Sea, possibly due to higher mortality rates caused by ice scour in shallow water; future decrease in seasonal duration of fast ice may increase this effect. Computer simulations suggested that if these eiders forage for >15 h/day, they can feed profitably at bivalve densities >200 m−2 regardless of water depth or availability of ice for resting. Sampling in 2010–2012 showed that large areas of profitable prey densities occurred only in certain locations throughout the migration corridor. Satellite data in April–May over 13 years (2001–2013) indicated that access to major feeding areas through sea ice in different segments of the corridor can vary from 0% to 100% between months and years. In a warming and increasingly variable climate, unpredictability of access may be enhanced by greater effects of shifting winds on unconsolidated ice. Our results indicate the importance of having a range of potential feeding areas throughout the migration corridor to ensure prey availability in all years. Spatial planning of nearshore industrial development in the Arctic, including commercial shipping, pipeline construction, and the risk of released oil, should consider these effects of high environmental variability on the adequacy of habitats targeted for conservation.

  19. Impact of mesenchymal stem cells' secretome on glioblastoma pathophysiology.

    PubMed

    Vieira de Castro, Joana; Gomes, Eduardo D; Granja, Sara; Anjo, Sandra I; Baltazar, Fátima; Manadas, Bruno; Salgado, António J; Costa, Bruno M

    2017-10-02

    Glioblastoma (GBM) is a highly aggressive primary brain cancer, for which curative therapies are not available. An emerging therapeutic approach suggested to have potential to target malignant gliomas has been based on the use of multipotent mesenchymal stem cells (MSCs), either unmodified or engineered to deliver anticancer therapeutic agents, as these cells present an intrinsic capacity to migrate towards malignant tumors. Nevertheless, it is still controversial whether this innate tropism of MSCs towards the tumor area is associated with cancer promotion or suppression. Considering that one of the major mechanisms by which MSCs interact with and modulate tumor cells is via secreted factors, we studied how the secretome of MSCs modulates critical hallmark features of GBM cells. The effect of conditioned media (CM) from human umbilical cord perivascular cells (HUCPVCs, a MSC population present in the Wharton's jelly of the umbilical cord) on GBM cell viability, migration, proliferation and sensitivity to temozolomide treatment of U251 and SNB-19 GBM cells was evaluated. The in vivo chicken chorioallantoic membrane (CAM) assay was used to evaluate the effect of HUCPVCs CM on tumor growth and angiogenesis. The secretome of HUCPVCs was characterized by proteomic analyses. We found that both tested GBM cell lines exposed to HUCPVCs CM presented significantly higher cellular viability, proliferation and migration. In contrast, resistance of GBM cells to temozolomide chemotherapy was not significantly affected by HUCPVCs CM. In the in vivo CAM assay, CM from HUCPVCs promoted U251 and SNB-19 tumor cells growth. Proteomic analysis to characterize the secretome of HUCPVCs identified several proteins involved in promotion of cell survival, proliferation and migration, revealing novel putative molecular mediators for the effects observed in GBM cells exposed to HUCPVCs CM. These findings provide novel insights to better understand the interplay between GBM cells and MSCs, raising awareness to potential safety issues regarding the use of MSCs as stem-cell based therapies for GBM.

  20. Limits to benthic feeding by eiders in a vital Arctic migration corridor due to localized prey and changing sea ice

    NASA Astrophysics Data System (ADS)

    Lovvorn, James R.; Rocha, Aariel R.; Jewett, Stephen C.; Dasher, Douglas; Oppel, Steffen; Powell, Abby N.

    2015-08-01

    Four species of threatened or declining eider ducks that nest in the Arctic migrate through the northeast Chukchi Sea, where anticipated industrial development may require prioritizing areas for conservation. In this nearshore corridor (10-40 m depth), the eiders' access to benthic prey during the spring is restricted to variable areas of open water within sea ice. For the most abundant species, the king eider (Somateria spectabilis), stable isotopes in blood cells, muscle, and potential prey indicate that these eiders ate mainly bivalves when traversing this corridor. Bivalves there were much smaller than the same taxa in deeper areas of the northern Bering Sea, possibly due to higher mortality rates caused by ice scour in shallow water; future decrease in seasonal duration of fast ice may increase this effect. Computer simulations suggested that if these eiders forage for >15 h/day, they can feed profitably at bivalve densities >200 m-2 regardless of water depth or availability of ice for resting. Sampling in 2010-2012 showed that large areas of profitable prey densities occurred only in certain locations throughout the migration corridor. Satellite data in April-May over 13 years (2001-2013) indicated that access to major feeding areas through sea ice in different segments of the corridor can vary from 0% to 100% between months and years. In a warming and increasingly variable climate, unpredictability of access may be enhanced by greater effects of shifting winds on unconsolidated ice. Our results indicate the importance of having a range of potential feeding areas throughout the migration corridor to ensure prey availability in all years. Spatial planning of nearshore industrial development in the Arctic, including commercial shipping, pipeline construction, and the risk of released oil, should consider these effects of high environmental variability on the adequacy of habitats targeted for conservation.

  1. Facilitators and constraints at each stage of the migration decision process.

    PubMed

    Kley, Stefanie

    2017-10-01

    Behavioural models of migration emphasize the importance of migration decision-making for the explanation of subsequent behaviour. But empirical migration research regularly finds considerable gaps between those who intend to migrate and those who actually realize their intention. This paper applies the Theory of Planned Behaviour, enriched by the Rubicon model, to test specific hypotheses about distinct effects of facilitators and constraints on specific stages of migration decision-making and behaviour. The data come from a tailor-made panel survey based on random samples of people drawn from two German cities in 2006-07. The results show that in conventional models the effects of facilitators and constraints on migration decision-making are likely to be underestimated. Splitting the process of migration decision-making into a pre-decisional and a pre-actional phase helps to avoid bias in the estimated effects of facilitators and constraints on both migration decision-making and migration behaviour.

  2. High level of reactive oxygen species impaired mesenchymal stem cell migration via overpolymerization of F-actin cytoskeleton in systemic lupus erythematosus.

    PubMed

    Shi, D; Li, X; Chen, H; Che, N; Zhou, S; Lu, Z; Shi, S; Sun, L

    2014-12-01

    Some lines of evidence have demonstrated abnormalities of bone marrow mesenchymal stem cells (MSCs) in systemic lupus erythematosus (SLE) patients, characterized by defective phenotype of MSCs and slower growth with enhanced apoptosis and senescence. However, whether SLE MSCs demonstrate aberrant migration capacity or abnormalities in cytoskeleton are issues that remain poorly understood. In this study, we found that MSCs from SLE patients did show impairment in migration capacity as well as abnormalities in F-actin cytoskeleton, accompanied by a high level of intracellular reactive oxygen species (ROS). When normal MSCs were treated in vitro with H2O2, which increases intracellular ROS level as an oxidant, both reorganization of F-actin cytoskeleton and impairment of migration capability were observed. On the other hand, treatment with N-acetylcysteine (NAC), as an exogenous antioxidant, made F-actin more orderly and increased migration ratio in SLE MSCs. In addition, oral administration of NAC markedly reduced serum autoantibody levels and ameliorated lupus nephritis (LN) in MRL/lpr mice, partially reversing the abnormalities of MSCs. These results indicate that overpolymerization of F-actin cytoskeleton, which may be associated with high levels of ROS, causes impairment in the migration capacity of SLE MSCs and that oral administration of NAC may have potential therapeutic effects on MRL/lpr mice. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

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

    PubMed Central

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

    2006-01-01

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

  4. Thymoquinone suppresses metastasis of melanoma cells by inhibition of NLRP3 inflammasome

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

    Ahmad, Israr; Muneer, Kashiff M.; Tamimi, Iman A.

    2013-07-01

    The inflammasome is a multi-protein complex which when activated regulates caspase-1 activation and IL-1β and IL-18 secretion. The NLRP3 (NACHT, LRR, and pyrin domain-containing protein 3) inflammasome is constitutively assembled and activated in human melanoma cells. We have examined the inhibitory effect of thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone), a major ingredient of black seed obtained from the plant Nigella sativa on metastatic human (A375) and mouse (B16F10) melanoma cell lines. We have assessed whether thymoquinone inhibits metastasis of melanoma cells by targeting NLRP3 subunit of inflammasomes. Using an in vitro cell migration assay, we found that thymoquinone inhibited the migration of both humanmore » and mouse melanoma cells. The inhibitory effect of thymoquinone on metastasis was also observed in vivo in B16F10 mouse melanoma model. The inhibition of migration of melanoma cells by thymoquinone was accompanied by a decrease in expression of NLRP3 inflammasome resulting in decrease in proteolytic cleavage of caspase-1. Inactivation of caspase-1 by thymoquinone resulted in inhibition of IL-1β and IL-18. Treatment of mouse melanoma cells with thymoquinone also inhibited NF-κB activity. Furthermore, inhibition of reactive oxygen species (ROS) by thymoquinone resulted in partial inactivation of NLRP3 inflammasome. Thus, thymoquinone exerts its inhibitory effect on migration of human and mouse melanoma cells by inhibition of NLRP3 inflammasome. Thus, our results indicate that thymoquinone can be a potential immunotherapeutic agent not only as an adjuvant therapy for melanoma, but also, in the control and prevention of metastatic melanoma. - Highlights: • Thymoquinone causes inhibition of migration of melanoma cells. • Thymoquinone causes inhibition of metastasis in vivo. • Thymoquinone causes inhibition of migration by activation of NLRP3 inflammasome.« less

  5. BAG3 promotes the phenotypic transformation of primary rat vascular smooth muscle cells via TRAIL.

    PubMed

    Fu, Yao; Chang, Ye; Chen, Shuang; Li, Yuan; Chen, Yintao; Sun, Guozhe; Yu, Shasha; Ye, Ning; Li, Chao; Sun, Yingxian

    2018-05-01

    Under normal physiological condition, the mature vascular smooth muscle cells (VSMCs) show differentiated phenotype. In response to various environmental stimuluses, VSMCs convert from the differentiated phenotype to dedifferentiated phenotype characterized by the increased ability of proliferation/migration and the reduction of contractile ability. The phenotypic transformation of VSMCs played an important role in atherosclerosis. Both Bcl-2-associated athanogene 3 (BAG3) and tumor necrosis factor-related apopt-osis inducing ligand (TRAIL) involved in apoptosis. The relationship between BAG3 and TRAIL and their effects the proliferation and migration in VSMCs are rarely reported. This study investigated the effects of BAG3 on the phenotypic modulation and the potential underlying mechanisms in primary rat VSMCs. Primary rat VSMCs were extracted and cultured in vitro. Cell proliferation was detected by cell counting, real-time cell analyzer (RTCA) and EdU incorporation. Cell migration was detected by wound healing, Transwell and RTCA. BAG3 and TRAIL were detected using real-time PCR and western blotting and the secreted proteins in the cultured media by dot blot. The expression of BAG3 increased with continued passages in cultured primary VSMCs. BAG3 promoted the proliferation and migration of primary rat VSMC in a time-dependent manner. BAG3 significantly increased the expression of TRAIL while had no effects on its receptors. TRAIL knockdown or blocking by neutralizing antibody inhibited the proliferation of VSMCs induced by BAG3. TRAIL knockdown exerted no obvious influence on the migration of VSMCs. Based on this study, we report for the first time that BAG3 was expressed in cultured primary rat VSMCs and the expression of BAG3 increased with continued passages. Furthermore, BAG3 promoted the proliferation of VSMCs via increasing the expression of TRAIL. In addition, we also demonstrated that BAG3 promoted the migration of VSMCs independent of TRAIL upregulation.

  6. HA-1077 inhibits cell migration/invasion of oral squamous cell carcinoma.

    PubMed

    Moreira Carboni, Simone de Sales Costa; Rodrigues Lima, Nathália Alves; Pinheiro, Nanci Mendes; Tavares-Murta, Beatriz Martins; Crema, Virgínia Oliveira

    2015-10-01

    Oral squamous cell carcinoma (OSCC) is the most malignant lesion occurring in the head and neck. The Rho-kinases (ROCKs), effectors of Rho proteins, are involved in actin cytoskeletal organization, cell migration, and maintenance cortex. The HA-1077 inhibits the ROCKs. This study aimed to evaluate the effect of treatment with HA-1077 on cell motility in SCC-4 cells, a cell line originating from human OSCC. F-actin of SCC-4 cells treated or not with HA-1077 (1, 50 and 100 μmol/l), and also HA-1077 50 μmol/l and/or inhibitors Y-27632 30 μmol/l was stained with rhodamine-conjugated phalloidin and analyzed by confocal microscopy. Approximately 1×10 cells/well, control and treated with HA-1077 (25, 50, and 100 μmol/l) were added to the migration plate assay. In addition, 1×10 cells/well, control and treated with HA-1077 50 μmol/l, were tested by invasion assays (plate coated with Matrigel). The inhibition of ROCKs with HA-1077 and/or Y-27632 leads to morphological changes, affecting the organization of the actin. The inhibitory effect of HA-1077 (P<0.0001) was dose dependent as the number of cells migrated at 100 μmol/l was statistically different: 25 μmol/l (P<0.0001) and 50 μmol/l (P<0.01). The number of cells treated with HA-1077 50 μmol/l decreased compared with control cells that invaded through Matrigel (P<0.0001). This study shows an inhibitory effect of HA-1077 on cell migration and invasion, suggesting that the use of HA-1077 can be a potential therapy for OSCC.

  7. 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

  8. Shaping Disk Galaxy Stellar Populations via Internal and External Processes

    NASA Astrophysics Data System (ADS)

    Roškar, Rok

    2015-03-01

    In recent years, effects such as the radial migration of stars in disks have been recognized as important drivers of the properties of stellar populations. Radial migration arises due to perturbative effects of disk structures such as bars and spiral arms, and can deposit stars formed in disks to regions far from their birthplaces. Migrant stars can significantly affect the demographics of their new locales, especially in low-density regions such as in the outer disks. However, in the cosmological environment, other effects such as mergers and filamentary gas accretion also influence the disk formation process. Understanding the relative importance of these processes on the detailed evolution of stellar population signatures is crucial for reconstructing the history of the Milky Way and other nearby galaxies. In the Milky Way disk in particular, the formation of the thickened component has recently attracted much attention due to its potential to serve as a diagnostic of the galaxy's early history. Some recent work suggests, however, that the vertical structure of Milky Way stellar populations is consistent with models that build up the thickened component through migration. I discuss these developments in the context of cosmological galaxy formation.

  9. Effect of the oxidation front penetration on in-clad hydrogen migration

    NASA Astrophysics Data System (ADS)

    Feria, F.; Herranz, L. E.

    2018-03-01

    In LWR fuel claddings the embrittlement due to hydrogen precipitates (i.e., hydrides) is a degrading mechanism that concerns in nuclear safety, particularly in dry storage. A relevant factor is the radial distribution of the hydrogen absorbed, especially the hydride rim formed. Thus, a reliable assessment of fuel performance should account for hydrogen migration. Based on the current state of modelling of hydrogen dynamics in the cladding, a 1D radial model has been derived and coupled with the FRAPCON code. The model includes the effect of the oxidation front progression on in-clad hydrogen migration, based on experimental observations found (i.e., dissolution/diffusion/re-precipitation of the hydrogen in the matrix ahead of the oxidation front). A remarkable quantitative impact of this new contribution has been shown by analyzing the hydrogen profile across the cladding of several high burnup fuel scenarios (>60 GW d/tU); other potential contributions like thermodiffusion and diffusion in the hydride phase hardly make any difference. Comparisons against PIE measurements allow concluding that the model accuracy notably increases when the effect of the oxidation front is accounted for in the hydride rim formation. In spite of the promising results, further validation would be needed.

  10. Natural disasters and population mobility in Bangladesh

    PubMed Central

    Gray, Clark L.; Mueller, Valerie

    2012-01-01

    The consequences of environmental change for human migration have gained increasing attention in the context of climate change and recent large-scale natural disasters, but as yet relatively few large-scale and quantitative studies have addressed this issue. We investigate the consequences of climate-related natural disasters for long-term population mobility in rural Bangladesh, a region particularly vulnerable to environmental change, using longitudinal survey data from 1,700 households spanning a 15-y period. Multivariate event history models are used to estimate the effects of flooding and crop failures on local population mobility and long-distance migration while controlling for a large set of potential confounders at various scales. The results indicate that flooding has modest effects on mobility that are most visible at moderate intensities and for women and the poor. However, crop failures unrelated to flooding have strong effects on mobility in which households that are not directly affected but live in severely affected areas are the most likely to move. These results point toward an alternate paradigm of disaster-induced mobility that recognizes the significant barriers to migration for vulnerable households as well their substantial local adaptive capacity. PMID:22474361

  11. microRNA-625 inhibits tumorigenicity by suppressing proliferation, migration and invasion in malignant melanoma.

    PubMed

    Fang, Wei; Fan, Yibin; Fa, Zhenzong; Xu, Jinhua; Yu, Hongyu; Li, Pu; Gu, Julin

    2017-02-21

    Dysregulated microRNA (miR)-625 expression has been observed in several kinds of cancer. MicroRNAs are important factors in the development and progression of malignant melanoma, though the clinical significance and function of miR-625 in human malignant melanoma remain unclear. Levels of miR-625 expression were therefore determined in 36 pairs of malignant melanoma and adjacent non-tumor tissue using qPCR. The effects of miR-625 dysregulation on malignant melanoma cell proliferation, wound healing, migration and invasion in vitro and tumorigenicity in vivo were investigated using CCK-8, transwell assays, and a nude mouse subcutaneous tumor model. Bioinformatics analysis and luciferase reporter system were used to predict and confirm the target gene of miR-625. miR-625 levels were frequently decreased in malignant melanoma. Ectopic expression of miR-625 suppressed proliferation, wound healing, migration, and tumorgenicity in malignant melanoma. Moreover, miR-625 acted, at least in part, by suppressing potential target SOX2. These results show that miR-625 is a tumor suppressor that inhibits the development and progression of malignant melanoma, which suggests miR-625 is potentially a new diagnostic marker and therapeutic target of malignant melanoma.

  12. Anabolic Properties of High Mobility Group Box Protein-1 in Human Periodontal Ligament Cells In Vitro

    PubMed Central

    Wolf, Michael; Lossdörfer, Stefan; Römer, Piero; Bastos Craveiro, Rogerio; Deschner, James; Jäger, Andreas

    2014-01-01

    High mobility group box protein-1 (HMGB1) is mainly recognized as a chemoattractant for macrophages in the initial phase of host response to pathogenic stimuli. However, recent findings provide evidence for anabolic properties in terms of enhanced proliferation, migration, and support of wound healing capacity of mesenchymal cells suggesting a dual role of the cytokine in the regulation of immune response and subsequent regenerative processes. Here, we examined potential anabolic effects of HMGB1 on human periodontal ligament (PDL) cells in the regulation of periodontal remodelling, for example, during orthodontic tooth movement. Preconfluent human PDL cells (hPDL) were exposed to HMGB1 protein and the influence on proliferation, migration, osteogenic differentiation, and biomineralization was determined by MTS assay, real time PCR, immunofluorescence cytochemistry, ELISA, and von Kossa staining. HMGB1 protein increased hPDL cell proliferation, migration, osteoblastic marker gene expression, and protein production as well as mineralized nodule formation significantly. The present findings support the dual character of HMGB1 with anabolic therapeutic potential that might support the reestablishment of the structural and functional integrity of the periodontium following periodontal trauma such as orthodontic tooth movement. PMID:25525297

  13. Evaluation of the in vitro and in vivo angiogenic effects of exendin-4

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

    Kang, Hye-Min; Kang, Yujung; Chun, Hyung J.

    2013-04-26

    Highlights: •We investigated the effects of exendin-4 on the angiogenic process. •Exendin-4 increased migration, sprouting, and tube formation by HUVECs in in vitro. •Exendin-4 increased sprouts in aortic rings and induced new vessels in Matrigel in in vivo. •Exendin-4 may be of potential use for the treatment of vascular complications of diabetes. -- Abstract: Exendin-4, an analog of glucagon-like peptide (GLP)-1, has beneficial effects on cardiovascular disease induced by diabetes mellitus (DM). Recently, exendin-4 was reported to induce the proliferation of endothelial cells. However, its angiogenic effect on endothelial cells has not been clearly evaluated. Therefore, we investigated the effectsmore » of exendin-4 on the angiogenic process with respect to migration, sprouting, and neovascularization using in vitro and in vivo assays. Treatment with exendin-4 increased the migration of human umbilical vein endothelial cells (HUVECs) in in vitro scratch wound assays, as well as the number of lumenized vessels sprouting from HUVECs in in vitro 3D bead assays. These responses were abolished by co-treatment with exendin (9–39), a GLP-1 receptor antagonist, which suggests that exendin-4 regulates endothelial cell migration and tube formation in a GLP-1 receptor-dependent manner. In an ex vivo assay, treatment of aortic rings with exendin-4 increased the sprouting of endothelial cells. Exendin-4 also significantly increased the number of new vessels and induced blood flow in Matrigel plugs in in vivo assays. Our results provide clear evidence for the angiogenic effect of exendin-4 in in vitro and in vivo assays and provide a mechanism underlying the cardioprotective effects of exendin-4.« less

  14. The effect of ferulic acid ethyl ester on leptin-induced proliferation and migration of aortic smooth muscle cells.

    PubMed

    Tsai, Yung-Chieh; Lee, Yen-Mei; Hsu, Chih-Hsiung; Leu, Sy-Ying; Chiang, Hsiao-Yen; Yen, Mao-Hsiung; Cheng, Pao-Yun

    2015-08-28

    Leptin is a peptide hormone, which has a central role in the regulation of body weight; it also exerts many potentially atherogenic effects. Ferulic acid ethyl ester (FAEE) has been approved for antioxidant properties. The aim of this study was to investigate whether FAEE can inhibit the atherogenic effects of leptin and the possible molecular mechanism of its action. Both of cell proliferation and migration were measured when the aortic smooth muscle cell (A10 cell) treated with leptin and/or FAEE. Phosphorylated p44/42MAPK, cell cycle-regulatory protein (for example, cyclin D1, p21, p27), β-catenin and matrix metalloproteinase-9 (MMP-9) proteins levels were also measured. Results demonstrated that leptin (10, 100 ng ml(-1)) significantly increased the proliferation of cells and the phosphorylation of p44/42MAPK in A10 cells. The proliferative effect of leptin was significantly reduced by the pretreatment of U0126 (0.5 μM), a MEK inhibitor, in A10 cells. Meanwhile, leptin significantly increased the protein expression of cyclin D1, p21, β-catenin and decreased the expression of p27 in A10 cells. In addition, leptin (10 ng ml(-1)) significantly increased the migration of A10 cells and the expression of MMP-9 protein. Above effects of leptin were significantly reduced by the pretreatment of FAEE (1 and 10 μM) in A10 cells. In conclusion, FAEE exerts multiple effects on leptin-induced cell proliferation and migration, including the inhibition of p44/42MAPK phosphorylation, cell cycle-regulatory proteins and MMP-9, thereby suggesting that FAEE may be a possible therapeutic approach to the inhibition of obese vascular disease.

  15. The effect of ferulic acid ethyl ester on leptin-induced proliferation and migration of aortic smooth muscle cells

    PubMed Central

    Tsai, Yung-Chieh; Lee, Yen-Mei; Hsu, Chih-Hsiung; Leu, Sy-Ying; Chiang, Hsiao-Yen; Yen, Mao-Hsiung; Cheng, Pao-Yun

    2015-01-01

    Leptin is a peptide hormone, which has a central role in the regulation of body weight; it also exerts many potentially atherogenic effects. Ferulic acid ethyl ester (FAEE) has been approved for antioxidant properties. The aim of this study was to investigate whether FAEE can inhibit the atherogenic effects of leptin and the possible molecular mechanism of its action. Both of cell proliferation and migration were measured when the aortic smooth muscle cell (A10 cell) treated with leptin and/or FAEE. Phosphorylated p44/42MAPK, cell cycle-regulatory protein (for example, cyclin D1, p21, p27), β-catenin and matrix metalloproteinase-9 (MMP-9) proteins levels were also measured. Results demonstrated that leptin (10, 100 ng ml−1) significantly increased the proliferation of cells and the phosphorylation of p44/42MAPK in A10 cells. The proliferative effect of leptin was significantly reduced by the pretreatment of U0126 (0.5 μM), a MEK inhibitor, in A10 cells. Meanwhile, leptin significantly increased the protein expression of cyclin D1, p21, β-catenin and decreased the expression of p27 in A10 cells. In addition, leptin (10 ng ml−1) significantly increased the migration of A10 cells and the expression of MMP-9 protein. Above effects of leptin were significantly reduced by the pretreatment of FAEE (1 and 10 μM) in A10 cells. In conclusion, FAEE exerts multiple effects on leptin-induced cell proliferation and migration, including the inhibition of p44/42MAPK phosphorylation, cell cycle-regulatory proteins and MMP-9, thereby suggesting that FAEE may be a possible therapeutic approach to the inhibition of obese vascular disease. PMID:26315599

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

    PubMed Central

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

    2014-01-01

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

  17. Targeting Metastasis with Snake Toxins: Molecular Mechanisms

    PubMed Central

    Urra, Félix A.

    2017-01-01

    Metastasis involves the migration of cancer cells from a primary tumor to invade and establish secondary tumors in distant organs, and it is the main cause for cancer-related deaths. Currently, the conventional cytostatic drugs target the proliferation of malignant cells, being ineffective in metastatic disease. This highlights the need to find new anti-metastatic drugs. Toxins isolated from snake venoms are a natural source of potentially useful molecular scaffolds to obtain agents with anti-migratory and anti-invasive effects in cancer cells. While there is greater evidence concerning the mechanisms of cell death induction of several snake toxin classes on cancer cells; only a reduced number of toxin classes have been reported (i.e., disintegrins/disintegrin-like proteins, C-type lectin-like proteins, C-type lectins, serinproteases, cardiotoxins, snake venom cystatins) as inhibitors of adhesion, migration, and invasion of cancer cells. Here, we discuss the anti-metastatic mechanisms of snake toxins, distinguishing three targets, which involve (1) inhibition of extracellular matrix components-dependent adhesion and migration, (2) inhibition of epithelial-mesenchymal transition, and (3) inhibition of migration by alterations in the actin/cytoskeleton network. PMID:29189742

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  20. 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

  1. 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.

  2. Interplay between long noncoding RNA ZEB1-AS1 and miR-101/ZEB1 axis regulates proliferation and migration of colorectal cancer cells.

    PubMed

    Xiong, Wan-Cheng; Han, Na; Wu, Nan; Zhao, Ke-Lei; Han, Chen; Wang, Hui-Xin; Ping, Guan-Fang; Zheng, Peng-Fei; Feng, Hailong; Qin, Lei; He, Peng

    2018-01-01

    Long noncoding RNAs (lncRNAs) are dysregulated in many diseases. MicroRNA-101 (miR-101) functions as a tumor suppressor by directly targeting ZEB1 in various cancers. However, the potential mechanism of lncRNA ZEB1-AS1 and miR-101/ZEB1 axis in CRC remains unknown. In this study, we further investigated the potential interplay between miR-101/ZEB1 axis and lncRNA ZEB1-AS1 in colorectal cancer (CRC). Results showed that ZEB1-AS1 was upregulated in CRC tissues and cells. MiR-101 was downregulated in CRC tissues and negatively correlated with ZEB1-AS1 and ZEB1 expression levels in CRC. Functional experiments showed that, consistent with ZEB1-AS1 depletion, miR-101 overexpression and ZEB1 depletion inhibited the proliferation and migration of CRC cells. Overexpression of miR-101 partially abolished the effects of ZEB1-AS1 on the proliferation and migration of these cells. Moreover, combined ZEB1-AS1 depletion and miR-101 overexpression significantly inhibited cell proliferation and migration of the CRC cells. Hence, ZEB1-AS1 functioned as a molecular sponge for miR-101 and relieved the inhibition of ZEB1 caused by miR-101. This study revealed a novel regulatory mechanism between ZEB1-AS1 and miR-101/ZEB1 axis. The interplay between ZEB1-AS1 and miR-101/ZEB1 axis contributed to the proliferation and migration of CRC cells, and targeting this interplay could be a promising strategy for CRC treatment.

  3. Effects of electric fields on human mesenchymal stem cell behaviour and morphology using a novel multichannel device.

    PubMed

    Banks, T A; Luckman, P S B; Frith, J E; Cooper-White, J J

    2015-06-01

    The intrinsic piezoelectric nature of collagenous-rich tissues, such as bone and cartilage, can result in the production of small, endogenous electric fields (EFs) during applied mechanical stresses. In vivo, these EFs may influence cell migration, a vital component of wound healing. As a result, the application of small external EFs to bone fractures and cutaneous wounds is actively practiced clinically. Due to the significant regenerative potential of stem cells in bone and cartilage healing, and their potential role in the observed improved healing in vivo post applied EFs, using a novel medium throughput device, we investigated the impacts of physiological and aphysiological EFs on human bone marrow-derived mesenchymal stem cells (hBM-MSCs) for up to 15 hours. The applied EFs had significant impacts on hBM-MSC morphology and migration; cells displayed varying degrees of conversion to a highly elongated phenotype dependent on the EF strength, consistent perpendicular alignment to the EF vector, and definitive cathodal migration in response to EF strengths ≥0.5 V cm(-1), with the fastest migration speeds observed at between 1.7 and 3 V cm(-1). We observed variability in hBM-MSC donor-to-donor responses and overall tolerances to applied EFs. This study thus confirms hBM-MSCs are responsive to applied EFs, and their rate of migration towards the cathode is controllable depending on the EF strength, providing new insight into the physiology of hBM-MSCs and possibly a significant opportunity for the utilisation of EFs in directed scaffold colonisation in vitro for tissue engineering applications or in vivo post implantation.

  4. A MAPK-Driven Feedback Loop Suppresses Rac Activity to Promote RhoA-Driven Cancer Cell Invasion

    PubMed Central

    Hetmanski, Joseph H. R.; Zindy, Egor; Schwartz, Jean-Marc; Caswell, Patrick T.

    2016-01-01

    Cell migration in 3D microenvironments is fundamental to development, homeostasis and the pathobiology of diseases such as cancer. Rab-coupling protein (RCP) dependent co-trafficking of α5β1 and EGFR1 promotes cancer cell invasion into fibronectin (FN) containing extracellular matrix (ECM), by potentiating EGFR1 signalling at the front of invasive cells. This promotes a switch in RhoGTPase signalling to inhibit Rac1 and activate a RhoA-ROCK-Formin homology domain-containing 3 (FHOD3) pathway and generate filopodial actin-spike protrusions which drive invasion. To further understand the signalling network that drives RCP-driven invasive migration, we generated a Boolean logical model based on existing network pathways/models, where each node can be interrogated by computational simulation. The model predicted an unanticipated feedback loop, whereby Raf/MEK/ERK signalling maintains suppression of Rac1 by inhibiting the Rac-activating Sos1-Eps8-Abi1 complex, allowing RhoA activity to predominate in invasive protrusions. MEK inhibition was sufficient to promote lamellipodia formation and oppose filopodial actin-spike formation, and led to activation of Rac and inactivation of RhoA at the leading edge of cells moving in 3D matrix. Furthermore, MEK inhibition abrogated RCP/α5β1/EGFR1-driven invasive migration. However, upon knockdown of Eps8 (to suppress the Sos1-Abi1-Eps8 complex), MEK inhibition had no effect on RhoGTPase activity and did not oppose invasive migration, suggesting that MEK-ERK signalling suppresses the Rac-activating Sos1-Abi1-Eps8 complex to maintain RhoA activity and promote filopodial actin-spike formation and invasive migration. Our study highlights the predictive potential of mathematical modelling approaches, and demonstrates that a simple intervention (MEK-inhibition) could be of therapeutic benefit in preventing invasive migration and metastasis. PMID:27138333

  5. Sea louse infection of juvenile sockeye salmon in relation to marine salmon farms on Canada's west coast.

    PubMed

    Price, Michael H H; Proboszcz, Stan L; Routledge, Rick D; Gottesfeld, Allen S; Orr, Craig; Reynolds, John D

    2011-02-09

    Pathogens are growing threats to wildlife. The rapid growth of marine salmon farms over the past two decades has increased host abundance for pathogenic sea lice in coastal waters, and wild juvenile salmon swimming past farms are frequently infected with lice. Here we report the first investigation of the potential role of salmon farms in transmitting sea lice to juvenile sockeye salmon (Oncorhynchus nerka). We used genetic analyses to determine the origin of sockeye from Canada's two most important salmon rivers, the Fraser and Skeena; Fraser sockeye migrate through a region with salmon farms, and Skeena sockeye do not. We compared lice levels between Fraser and Skeena juvenile sockeye, and within the salmon farm region we compared lice levels on wild fish either before or after migration past farms. We matched the latter data on wild juveniles with sea lice data concurrently gathered on farms. Fraser River sockeye migrating through a region with salmon farms hosted an order of magnitude more sea lice than Skeena River populations, where there are no farms. Lice abundances on juvenile sockeye in the salmon farm region were substantially higher downstream of farms than upstream of farms for the two common species of lice: Caligus clemensi and Lepeophtheirus salmonis, and changes in their proportions between two years matched changes on the fish farms. Mixed-effects models show that position relative to salmon farms best explained C. clemensi abundance on sockeye, while migration year combined with position relative to salmon farms and temperature was one of two top models to explain L. salmonis abundance. This is the first study to demonstrate a potential role of salmon farms in sea lice transmission to juvenile sockeye salmon during their critical early marine migration. Moreover, it demonstrates a major migration corridor past farms for sockeye that originated in the Fraser River, a complex of populations that are the subject of conservation concern.

  6. Sea Louse Infection of Juvenile Sockeye Salmon in Relation to Marine Salmon Farms on Canada's West Coast

    PubMed Central

    Price, Michael H. H.; Proboszcz, Stan L.; Routledge, Rick D.; Gottesfeld, Allen S.; Orr, Craig; Reynolds, John D.

    2011-01-01

    Background Pathogens are growing threats to wildlife. The rapid growth of marine salmon farms over the past two decades has increased host abundance for pathogenic sea lice in coastal waters, and wild juvenile salmon swimming past farms are frequently infected with lice. Here we report the first investigation of the potential role of salmon farms in transmitting sea lice to juvenile sockeye salmon (Oncorhynchus nerka). Methodology/Principal Findings We used genetic analyses to determine the origin of sockeye from Canada's two most important salmon rivers, the Fraser and Skeena; Fraser sockeye migrate through a region with salmon farms, and Skeena sockeye do not. We compared lice levels between Fraser and Skeena juvenile sockeye, and within the salmon farm region we compared lice levels on wild fish either before or after migration past farms. We matched the latter data on wild juveniles with sea lice data concurrently gathered on farms. Fraser River sockeye migrating through a region with salmon farms hosted an order of magnitude more sea lice than Skeena River populations, where there are no farms. Lice abundances on juvenile sockeye in the salmon farm region were substantially higher downstream of farms than upstream of farms for the two common species of lice: Caligus clemensi and Lepeophtheirus salmonis, and changes in their proportions between two years matched changes on the fish farms. Mixed-effects models show that position relative to salmon farms best explained C. clemensi abundance on sockeye, while migration year combined with position relative to salmon farms and temperature was one of two top models to explain L. salmonis abundance. Conclusions/Significance This is the first study to demonstrate a potential role of salmon farms in sea lice transmission to juvenile sockeye salmon during their critical early marine migration. Moreover, it demonstrates a major migration corridor past farms for sockeye that originated in the Fraser River, a complex of populations that are the subject of conservation concern. PMID:21347456

  7. Unripe Rubus coreanus Miquel suppresses migration and invasion of human prostate cancer cells by reducing matrix metalloproteinase expression.

    PubMed

    Kim, Yesl; Lee, Seung Min; Kim, Jung-Hyun

    2014-01-01

    Rubus coreanus Miquel (RCM) is used to promote prostate health and has been shown to have anti-oxidant and anti-carcinogenic activities. However, the effects and mechanisms of RCM on prostate cancer metastasis remain unclear. PC-3 and DU 145 cells were treated with ethanol or water extract of unripe or ripe RCM and examined for cell invasion, migration, and matrix metalloproteinases (MMPs) activity and expression. Phosphoinositide 3-kinase (PI3K) and Akt activities were examined. Unripe RCM extracts exerted significant inhibitory effects on cell migration, invasion, and MMPs activities. A significant reduction in MMPs activities by unripe RCM ethanol extract treatment (UE) was associated with reduction of MMPs expression and induction of tissue inhibitors of metalloproteinases (TIMPs) expression. Furthermore, PI3K/Akt activity was diminished by UE treatment. In this study, we demonstrated that UE decreased metastatic potential of prostate cancer cells by reducing MMPs expression through the suppression of PI3K/Akt phosphorylation, thereby decreasing MMP activity and enhancing TIMPs expression.

  8. Doxycycline reverses epithelial-to-mesenchymal transition and suppresses the proliferation and metastasis of lung cancer cells.

    PubMed

    Qin, Yuan; Zhang, Qiang; Lee, Shan; Zhong, Wei-Long; Liu, Yan-Rong; Liu, Hui-Juan; Zhao, Dong; Chen, Shuang; Xiao, Ting; Meng, Jing; Jing, Xue-Shuang; Wang, Jing; Sun, Bo; Dai, Ting-Ting; Yang, Cheng; Sun, Tao; Zhou, Hong-Gang

    2015-12-01

    The gelatinase inhibitor doxycycline is the prototypical antitumor antibiotic. We investigated the effects of doxycycline on the migration, invasion, and metastasis of human lung cancer cell lines and in a mouse model. We also measured the effect of doxycycline on the transcription of epithelial-mesenchymal transition (EMT) markers, and used immunohistochemistry to determine whether EMT reversal was associated with doxycycline inhibition. Doxycycline dose-dependently inhibited proliferation, migration, and invasion of NCI-H446 human small cell lung cancer cells. It also suppressed tumor growth from NCI-H446 and A549 lung cancer cell xenografts without altering body weight, inhibited Lewis lung carcinoma cell migration, and prolonged survival. The activities of the transcription factors Twist1/2, SNAI1/2, AP1, NF-κB, and Stat3 were suppressed by doxycycline, which reversed EMT and inhibited signal transduction, thereby suppressing tumor growth and metastasis. Our data demonstrate functional targeting of transcription factors by doxycycline to reverse EMT and suppress tumor proliferation and metastasis. Thus, doxycycline selectively targets malignant tumors and reduces its metastatic potential with less cytotoxicity in lung cancer patients.

  9. Angle-domain common imaging gather extraction via Kirchhoff prestack depth migration based on a traveltime table in transversely isotropic media

    NASA Astrophysics Data System (ADS)

    Liu, Shaoyong; Gu, Hanming; Tang, Yongjie; Bingkai, Han; Wang, Huazhong; Liu, Dingjin

    2018-04-01

    Angle-domain common image-point gathers (ADCIGs) can alleviate the limitations of common image-point gathers in an offset domain, and have been widely used for velocity inversion and amplitude variation with angle (AVA) analysis. We propose an effective algorithm for generating ADCIGs in transversely isotropic (TI) media based on the gradient of traveltime by Kirchhoff pre-stack depth migration (KPSDM), as the dynamic programming method for computing the traveltime in TI media would not suffer from the limitation of shadow zones and traveltime interpolation. Meanwhile, we present a specific implementation strategy for ADCIG extraction via KPSDM. Three major steps are included in the presented strategy: (1) traveltime computation using a dynamic programming approach in TI media; (2) slowness vector calculation by the gradient of a traveltime table calculated previously; (3) construction of illumination vectors and subsurface angles in the migration process. Numerical examples are included to demonstrate the effectiveness of our approach, which henceforce shows its potential application for subsequent tomographic velocity inversion and AVA.

  10. Long non-coding RNA HOTAIR and STAT3 synergistically regulate the cervical cancer cell migration and invasion.

    PubMed

    Zhang, Yan; Cheng, Xiaoling; Liang, Hua; Jin, Zhenzhen

    2018-04-25

    Homeobox (HOX) transcript antisense RNA (HOTAIR) is a long intergenic non-coding RNA (lncRNA) that has been reported to be highly upregulated in several types of cancers. However, the role of HOTAIR in human cervical cancer is still unclear. We therefore investigated the expression and probable function of HOTAIR in cervical cancer cells. The expression of HOTAIR was examined in (HeLa, CaSki, ME-180, HT-3) and Human Cervical Epithelial Cells (HCerEpiC) by qRT-PCR. Transfection of si-NC, si-HOTAIR or si-STAT3 was carried out with the help of Lipofectamine 2000. The cell viability was assessed by CCK-8 assay. The cell migration and invasion was examined by wound healing and Boyden chamber assays. Protein expression was determined by western blotting. Our results showed that expression of HOTAIR was significantly upregulated in cervical cancer cells and inhibition of the expression of HOTAIR in HeLa cervical cancer cells resulted in suppression of cell proliferation, migration and invasion. Further, analysis of the promoter of HOTAIR, revealed that STAT3 could potentially regulate the activity of the HOTAIR in cervical cancer cells and inhibition of STAT3 had similar effects on the proliferation, migration and invasion of the cervical cancer cells as that of HOTAIR. Further, the suppression of STAT3 expression was associated with concomitant downregulation of IncRNA HOTAIR as indicated by the qRT-PCR. To unveil if STAT3 and HOTAIR have synergistic effects on the cell migration and invasion, si-STAT3 and si-HOTAIR were co-transformed into cervical HeLa cancer cells and it was observed that STAT3 and HOTAIR could synergistically inhibit the proliferation, migration and invasion of the cervical cancer cells. Taken together we conclude that HOTAIR and STAT3 synergistically regulate the proliferation, migration and invasion of cervical cancer cells. Copyright © 2018. Published by Elsevier B.V.

  11. Netrin-1 induces the migration of Schwann cells via p38 MAPK and PI3K-Akt signaling pathway mediated by the UNC5B receptor

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

    Lv, Jianwei; Tianjin Institute of Orthopedics in Traditional Chinese and Western Medicine, No. 155, Munan Road, Tianjin 300050; Sun, Xiaolei

    2015-08-14

    Schwann cells (SCs) play an essentially supportive role in the regeneration of injured peripheral nerve system (PNS). As Netrin-1 is crucial for the normal development of nervous system (NS) and can direct the process of damaged PNS regeneration, our study was designed to determine the role of Netrin-1 in RSC96 Schwann cells (an immortalized rat Schwann cell line) proliferation and migration. Our studies demonstrated that Netrin-1 had no effect on RSC96 cells proliferation, while significantly promoted RSC96 cells migration. The Netrin-1-induced RSC96 cells migration was significantly attenuated by inhibition of p38 and PI3K through pretreatment with SB203580 and LY294002 respectively,more » but not inhibition of MEK1/2 and JNK by U0126-EtOH and SP600125 individually. Treatment with Netrin-1 enhanced the phosphorylation of p38 and Akt. QRT-PCR indicated that Netrin-1 and only its receptors Unc5a, Unc5b and Neogenin were expressed in RSC96 cells, among which Unc5b expressed the most. And UNC5B protein was significantly increased after stimulated by Netrin-1. In conclusion, we show here that Netrin-1-enhanced SCs migration is mediated by activating p38 MAPK and PI3K-Akt signal cascades via receptor UNC5B, which suggests that Netrin-1 could serve as a new therapeutic strategy and has potential application value for PNS regeneration. - Highlights: • Netrin-1 attracts RSC96 Schwann cells migration in a dose dependent manner. • Netrin-1 induced Schwann cells migration is p38 and PI3K-Akt signaling dependent. • UNC5B may be dominant receptor mediating Netrin-1′ effect on RSC96 cells motility. • Netrin-1 may promote peripheral nerve repair by enhancing Schwann cells motility.« less

  12. miR-132 suppresses the migration and invasion of lung cancer cells by blocking USP9X-induced epithelial-mesenchymal transition

    PubMed Central

    Guo, Huihui; Zhang, Xilin; Chen, Qiuqiang; Bao, Ying; Dong, Chaohui; Wang, Xiang

    2018-01-01

    miR-132, a microRNA, has been reported to be down-regulated in several human cancers and is related with tumor progression; however, its function in non-small cell lung cancer (NSCLC) progression remains unclear. This study aimed to investigate the putative role of miR-132 in the metastasis of NSCLC. We determined the function of miR-132 in the migration and invasion of a NSCLC cell line in vitro using a miR-132 inhibitor and mimic. Our results showed overexpression of miR-132 significantly inhibited the migration and invasion of NSCLC cells in vitro. We then identified USP9X as a potential target of miR-132, and demonstrated miR-132 could regulate the expression of USP9X at both the mRNA and protein level. miR-132 could directly bind to the 3’ untranslated region (3’-UTR) of USP9X. Inhibition of USP9X by its inhibitor WP1130 reduced the migration and invasion of NSCLC cells. Furthermore, USP9X inhibition also reversed the increased migration and invasion mediated by miR-132 inhibition. We found USP9X inhibition up-regulated expression of the epithelial-mesenchymal transition (EMT) marker E-cadherin, but down-regulated vimentin expression. A similar effect was seen with miR-132 overexpression, while the opposite effect occurred with miR-132 knockdown. USP9X inhibition reversed the miR-132 inhibitor-induced vimentin up-regulation and E-cadherin down-regulation. Taken together, these results indicate miR-132 prohibits the migration and invasion of NSCLC cells via targeting USP9X-induced EMT. Our data provides further evidence for the critical role of miR-132 and USP9X in regulating cell invasion and migration of NSCLC. PMID:29423007

  13. miR-132 suppresses the migration and invasion of lung cancer cells by blocking USP9X-induced epithelial-mesenchymal transition.

    PubMed

    Guo, Huihui; Zhang, Xilin; Chen, Qiuqiang; Bao, Ying; Dong, Chaohui; Wang, Xiang

    2018-01-01

    miR-132, a microRNA, has been reported to be down-regulated in several human cancers and is related with tumor progression; however, its function in non-small cell lung cancer (NSCLC) progression remains unclear. This study aimed to investigate the putative role of miR-132 in the metastasis of NSCLC. We determined the function of miR-132 in the migration and invasion of a NSCLC cell line in vitro using a miR-132 inhibitor and mimic. Our results showed overexpression of miR-132 significantly inhibited the migration and invasion of NSCLC cells in vitro . We then identified USP9X as a potential target of miR-132, and demonstrated miR-132 could regulate the expression of USP9X at both the mRNA and protein level. miR-132 could directly bind to the 3' untranslated region (3'-UTR) of USP9X. Inhibition of USP9X by its inhibitor WP1130 reduced the migration and invasion of NSCLC cells. Furthermore, USP9X inhibition also reversed the increased migration and invasion mediated by miR-132 inhibition. We found USP9X inhibition up-regulated expression of the epithelial-mesenchymal transition (EMT) marker E-cadherin, but down-regulated vimentin expression. A similar effect was seen with miR-132 overexpression, while the opposite effect occurred with miR-132 knockdown. USP9X inhibition reversed the miR-132 inhibitor-induced vimentin up-regulation and E-cadherin down-regulation. Taken together, these results indicate miR-132 prohibits the migration and invasion of NSCLC cells via targeting USP9X-induced EMT. Our data provides further evidence for the critical role of miR-132 and USP9X in regulating cell invasion and migration of NSCLC.

  14. Lipid raft-mediated miR-3908 inhibition of migration of breast cancer cell line MCF-7 by regulating the interactions between AdipoR1 and Flotillin-1.

    PubMed

    Li, Yuan; Shan, Fei; Chen, Jinglong

    2017-03-21

    The mechanisms of lipid raft regulation by microRNAs in breast cancer are not fully understood. This work focused on the evaluation and identification of miR-3908, which may be a potential biomarker related to the migration of breast cancer cells, and elucidates lipid-raft-regulating cell migration in breast cancer. To confirm the prediction that miR-3908 is matched with AdipoR1, we used 3'-UTR luciferase activity of AdipoR1 to assess this. Then, human breast cancer cell line MCF-7 was cultured in the absence or presence of the mimics or inhibitors of miR-3908, after which the biological functions of MCF-7 cells were analyzed. The protein expression of AdipoR1, AMPK, and SIRT-1 were examined. The interaction between AdipoR1 and Flotillin-1, or its effects on lipid rafts on regulating cell migration of MCF-7, was also investigated. AdipoR1 is a direct target of miR-3908. miR-3908 suppresses the expression of AdipoR1 and its downstream pathway genes, including AMPK, p-AMPK, and SIRT-1. miR-3908 enhances the process of breast cancer cell clonogenicity. miR-3908 exerts its effects on the proliferation and migration of MCF-7 cells, which are mediated by lipid rafts regulating AdipoR1's ability to bind Flotillin-1. miR-3908 is a crucial mediator of the migration process in breast cancer cells. Lipid rafts regulate the interactions between AdipoR1 and Flotillin-1 and then the migration process associated with miR-3908 in MCF-7 cells. Our findings suggest that targeting miR-3908 and the lipid raft, may be a promising strategy for the treatment and prevention of breast cancer.

  15. Rural development and urban migration: can we keep them down on the farm?

    PubMed

    Rhoda, R

    1983-01-01

    This study tests the hypothesis that rural development projects and programs reduce rural-urban migration. The author presents various factors in the social theories of migration, including those relating to origin and destination, intervening obstacles such as distance, and personal factors. 3 economic models of migration are the human capital or cost-benefit approach, the expected income model, and the intersectoral linkage model. Empirical studies of migration indicate that: 1) rural areas with high rates of out-migration tend to have high population densities or high ratios of labor to arable land, 2) distance inhibits migration, 3) rural-urban migration is positively correlated with family income level, and 4) selectivity differences in socioeconomic status between migrants and nonmigrants often are grouped into development packages which might include irrigation, new varieties of seed, subsidized credit, increased extension, and improved marketing arrangements. The migration impacts of some of these efforts are described: 1) land reform usually is expected to slow rural out-migration because it normally increases labor utilization in rural areas, but this is a limited effect, 2) migration effects of the Green Revolution technology are mainly in rural-rural migration, and 3) agricultural mechanization may stimulate rural-urban migration in the long run. Development of rural social services migh have various effects on rural-urban migration. Better rural education, which improves the chances of urban employment, will stimulate rural-urban migration, while successful rural family planning programs will have a negative effect in the long run as there will be reduced population pressure on arable land. Better rural health services might reduce the incentive for rural-urban migration as well. It is suggested that governments reconsider policies which rely on rural development to curb rural-urban migration and alleviate problems of urban poverty and underemployment.

  16. Increases in reactive oxygen species enhance vascular endothelial cell migration through a mechanism dependent on the transient receptor potential melastatin 4 ion channel.

    PubMed

    Sarmiento, Daniela; Montorfano, Ignacio; Cerda, Oscar; Cáceres, Mónica; Becerra, Alvaro; Cabello-Verrugio, Claudio; Elorza, Alvaro A; Riedel, Claudia; Tapia, Pablo; Velásquez, Luis A; Varela, Diego; Simon, Felipe

    2015-03-01

    A hallmark of severe inflammation is reactive oxygen species (ROS) overproduction induced by increased inflammatory mediators secretion. During systemic inflammation, inflammation mediators circulating in the bloodstream interact with endothelial cells (ECs) raising intracellular oxidative stress at the endothelial monolayer. Oxidative stress mediates several pathological functions, including an exacerbated EC migration. Because cell migration critically depends on calcium channel-mediated Ca(2+) influx, the molecular identification of the calcium channel involved in oxidative stress-modulated EC migration has been the subject of intense investigation. The transient receptor potential melastatin 4 (TRPM4) protein is a ROS-modulated non-selective cationic channel that performs several cell functions, including regulating intracellular Ca(2+) overload and Ca(2+) oscillation. This channel is expressed in multiple tissues, including ECs, and contributes to the migration of certain immune cells. However, whether the TRPM4 ion channel participates in oxidative stress-mediated EC migration is not known. Herein, we investigate whether oxidative stress initiates or enhances EC migration and study the role played by the ROS-modulated TRPM4 ion channel in oxidative stress-mediated EC migration. We demonstrate that oxidative stress enhances, but does not initiate, EC migration in a dose-dependent manner. Notably, we demonstrate that the TRPM4 ion channel is critical in promoting H2O2-enhanced EC migration. These results show that TRPM4 is a novel pharmacological target for the possible treatment of severe inflammation and other oxidative stress-mediated inflammatory diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Side to Side Supercharging Allograft

    DTIC Science & Technology

    Side-to-side grafting between the PNA and regional in situ nerve trunks may be able to increase the effective critical length of the PNA. Nerve tissue...and provides an effective scaffolding system but depends on in situ Schwann cell migration to support axon regeneration. Though this process appears...loss and retraction can result in segmental gaps requiring some form of grafting. Autologous nerve grafting is associated with potential donor

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

    PubMed

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

    2017-10-10

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

  19. Pedagogical Potential of a Web-Based GIS Application for Migration Data: A Preliminary Investigation in the Context of South Korea

    ERIC Educational Resources Information Center

    Kim, Minsung; Kim, Kamyoung; Lee, Sang-Il

    2013-01-01

    This article examines the pedagogical potential of a Web-based GIS application, Population Migration Web Service (PMWS), in which students can examine population geography in an interactive and exploratory manner. This article introduces PMWS, a tailored, unique Internet GIS application that provides functions for visualizing spatial interaction…

  20. Phoyunnanin E inhibits migration of non-small cell lung cancer cells via suppression of epithelial-to-mesenchymal transition and integrin αv and integrin β3.

    PubMed

    Petpiroon, Nareerat; Sritularak, Boonchoo; Chanvorachote, Pithi

    2017-12-29

    The conversion of the epithelial phenotype of cancer cells into cells with a mesenchymal phenotype-so-called epithelial-mesenchymal transition (EMT)-has been shown to enhance the capacity of the cells to disseminate throughout the body. EMT is therefore becoming a potential target for anti-cancer drug discovery. Here, we showed that phoyunnanin E, a compound isolated from Dendrobium venustum, possesses anti-migration activity and addressed its mechanism of action. The cytotoxic and proliferative effects of phoyunnanin E on human non-small cell lung cancer-derived H460, H292, and A549 cells and human keratinocyte HaCaT cells were investigated by MTT assay. The effect of phoyunnanin E on EMT was evaluated by determining the colony formation and EMT markers. The migration and invasion of H460, H292, A549 and HaCaT cells was evaluated by wound healing assay and transwell invasion assay, respectively. EMT markers, integrins and migration-associated proteins were examined by western blot analysis. Phoyunnanin E at the concentrations of 5 and 10 μM, which are non-toxic to H460, H292, A549 and HaCaT cells showed good potential to inhibit the migratory activity of three types of human lung cancer cells. The anti-migration effect of phoyunnanin E was shown to relate to the suppressed EMT phenotypes, including growth in anchorage-independent condition, cell motility, and EMT-specific protein markers (N-cadherin, vimentin, slug, and snail). In addition to EMT suppression, we found that phoyunnanin E treatment with 5 and 10 μM could decrease the cellular level of integrin αv and integrin β3, these integrins are frequently up-regulated in highly metastatic tumor cells. We further characterized the regulatory proteins in cell migration and found that the cells treated with phoyunnanin E exhibited a significantly lower level of phosphorylated focal adhesion kinase (p-FAK) and phosphorylated ATP-dependent tyrosine kinase (p-AKT), and their downstream effectors (including Ras-related C3 botulinum (Rac-GTP); Cell division cycle 42 (Cdc42); and Ras homolog gene family, member A (Rho-GTP)) in comparison to those of the non-treated control. We have determined for the first time that phoyunnanin E could inhibit the motility of lung cancer cells via the suppression of EMT and metastasis-related integrins. This new information could support further development of this compound for anti-metastasis approaches.

  1. Food safety concerns deriving from the use of silver based food packaging materials.

    PubMed

    Pezzuto, Alessandra; Losasso, Carmen; Mancin, Marzia; Gallocchio, Federica; Piovesana, Alessia; Binato, Giovanni; Gallina, Albino; Marangon, Alberto; Mioni, Renzo; Favretti, Michela; Ricci, Antonia

    2015-01-01

    The formulation of innovative packaging solutions, exerting a functional antimicrobial role in slowing down food spoilage, is expected to have a significant impact on the food industry, allowing both the maintenance of food safety criteria for longer periods and the reduction of food waste. Different materials are considered able to exert the required antimicrobial activity, among which are materials containing silver. However, challenges exist in the application of silver to food contact materials due to knowledge gaps in the production of ingredients, stability of delivery systems in food matrices and health risks caused by the same properties which also offer the benefits. Aims of the present study were to test the effectiveness and suitability of two packaging systems, one of which contained silver, for packaging and storing Stracchino cheese, a typical Italian fresh cheese, and to investigate if there was any potential for consumers to be exposed to silver, via migration from the packaging to the cheese. Results did not show any significant difference in the effectiveness of the packaging systems on packaged Stracchino cheese, excluding that the active packaging systems exerted an inhibitory effect on the growth of spoilage microorganisms. Moreover, silver migrated into the cheese matrix throughout the storage time (24 days). Silver levels in cheese finally exceeded the maximum established level for the migration of a non-authorised substance through a functional barrier (Commission of the European Communities, 2009). This result poses safety concerns and strongly suggests the need for more research aimed at better characterizing the new packaging materials in terms of their potential impacts on human health and the environment.

  2. Effects of heat-treatment on plasma rich in growth factors-derived autologous eye drop.

    PubMed

    Anitua, E; Muruzabal, F; De la Fuente, M; Merayo-Lloves, J; Orive, G

    2014-02-01

    We have developed and characterized a new type of plasma rich in growth factors (PRGF) derived eye-drop therapy for patients suffering from autoimmune diseases. To determine the concentration of several growth factors, proteins, immunoglobulins and complement activity of the heat-inactivated eye-drop and to study its biological effects on cell proliferation and migration of different ocular surface cells, blood from healthy donors was collected, centrifuged and PRGF was prepared avoiding the buffy coat. The half volume of the obtained plasma supernatant from each donor was heat-inactivated at 56 °C for 1 h (heat-inactivated PRGF). The concentration of several proteins involved on corneal wound healing, immunoglubolins G, M and E and functional integrity of the complement system assayed by CH50 test were determined. The proliferative and migratory potential of inactivated and non-inactivated PRGF eye drops were assayed on corneal epithelial cells (HCE), keratocytes (HK) and conjunctival fibroblasts (HConF). Heat-inactivated PRGF preserves the content of most of the proteins and morphogens involved in its wound healing effects while reduces drastically the content of IgE and complement activity. Heat-inactivated PRGF eye drops increased proliferation and migration potential of ocular surface cells with regard to PRGF showing significant differences on proliferation and migration rate of HCE and HConF respectively. In summary, heat-inactivation of PRGF eye drops completely reduced complement activity and deceased significantly the presence of IgE, maintaining the biological activity of PRGF on ocular surface cells. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. 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

  4. Spatial analysis of the regional variation of reproductive tract infections and spousal migration correlates in Nepal.

    PubMed

    Johnson, Derek C; Lhaki, Pema; Buehler Cherry, Charlotte; Kempf, Mirjam-Colette; Chamot, Eric; Vermund, Sten H; Shrestha, Sadeep

    2017-05-30

    Nepal has a diverse geographic landscape that could potentially create clustered subpopulations with regional socio-cultures that could result in differential health outcomes. With an alarming rise in married male populations migrating for work, it is possible that these migrants are engaged in risky sexual behaviour, putting their wives at risk for infectious disease outcomes, including reproductive tract infections (RTI), when they return home. The prevalence of male migration varies by geographic region in Nepal and this variation could potentially contribute to different RTI rates. Using a cross-sectional dataset (the 2011 Nepal Demographic and Health Survey) including 9607 married women, we investigated geospatial and socio-cultural factors associated with the symptoms of RTIs with a focus on the husbands' migration status. Choropleth maps were created to illustrate areas with high percentages of RTIs that correlated with migration patterns. Overall, 31.9% of the husbands were migrating for work. After adjusting for wealth, contraception use, age at first marriage, urban/rural status and husband's education, women whose husbands had been absent for a year or more in Nepal's Mid-West region (OR 1.93 95%, CI 1.02-3.67) or Far-West region (OR 2.89 95%, CI 1.24-6.73) were more likely to report RTI-like symptoms than others. Our results suggest a potential association between husbands' migration status and Nepali women reporting RTI symptoms by geographic regions. However, further research is needed to put this outcome on a stronger footing with respect to this under-studied population, specifically in the context of geographical variation.

  5. Climate change may alter breeding ground distributions of eastern migratory monarchs (Danaus plexippus) via range expansion of Asclepias host plants.

    PubMed

    Lemoine, Nathan P

    2015-01-01

    Climate change can profoundly alter species' distributions due to changes in temperature, precipitation, or seasonality. Migratory monarch butterflies (Danaus plexippus) may be particularly susceptible to climate-driven changes in host plant abundance or reduced overwintering habitat. For example, climate change may significantly reduce the availability of overwintering habitat by restricting the amount of area with suitable microclimate conditions. However, potential effects of climate change on monarch northward migrations remain largely unknown, particularly with respect to their milkweed (Asclepias spp.) host plants. Given that monarchs largely depend on the genus Asclepias as larval host plants, the effects of climate change on monarch northward migrations will most likely be mediated by climate change effects on Asclepias. Here, I used MaxEnt species distribution modeling to assess potential changes in Asclepias and monarch distributions under moderate and severe climate change scenarios. First, Asclepias distributions were projected to extend northward throughout much of Canada despite considerable variability in the environmental drivers of each individual species. Second, Asclepias distributions were an important predictor of current monarch distributions, indicating that monarchs may be constrained as much by the availability of Asclepias host plants as environmental variables per se. Accordingly, modeling future distributions of monarchs, and indeed any tightly coupled plant-insect system, should incorporate the effects of climate change on host plant distributions. Finally, MaxEnt predictions of Asclepias and monarch distributions were remarkably consistent among general circulation models. Nearly all models predicted that the current monarch summer breeding range will become slightly less suitable for Asclepias and monarchs in the future. Asclepias, and consequently monarchs, should therefore undergo expanded northern range limits in summer months while encountering reduced habitat suitability throughout the northern migration.

  6. Climate Change May Alter Breeding Ground Distributions of Eastern Migratory Monarchs (Danaus plexippus) via Range Expansion of Asclepias Host Plants

    PubMed Central

    Lemoine, Nathan P.

    2015-01-01

    Climate change can profoundly alter species’ distributions due to changes in temperature, precipitation, or seasonality. Migratory monarch butterflies (Danaus plexippus) may be particularly susceptible to climate-driven changes in host plant abundance or reduced overwintering habitat. For example, climate change may significantly reduce the availability of overwintering habitat by restricting the amount of area with suitable microclimate conditions. However, potential effects of climate change on monarch northward migrations remain largely unknown, particularly with respect to their milkweed (Asclepias spp.) host plants. Given that monarchs largely depend on the genus Asclepias as larval host plants, the effects of climate change on monarch northward migrations will most likely be mediated by climate change effects on Asclepias. Here, I used MaxEnt species distribution modeling to assess potential changes in Asclepias and monarch distributions under moderate and severe climate change scenarios. First, Asclepias distributions were projected to extend northward throughout much of Canada despite considerable variability in the environmental drivers of each individual species. Second, Asclepias distributions were an important predictor of current monarch distributions, indicating that monarchs may be constrained as much by the availability of Asclepias host plants as environmental variables per se. Accordingly, modeling future distributions of monarchs, and indeed any tightly coupled plant-insect system, should incorporate the effects of climate change on host plant distributions. Finally, MaxEnt predictions of Asclepias and monarch distributions were remarkably consistent among general circulation models. Nearly all models predicted that the current monarch summer breeding range will become slightly less suitable for Asclepias and monarchs in the future. Asclepias, and consequently monarchs, should therefore undergo expanded northern range limits in summer months while encountering reduced habitat suitability throughout the northern migration. PMID:25705876

  7. Mkit: A cell migration assay based on microfluidic device and smartphone.

    PubMed

    Yang, Ke; Wu, Jiandong; Peretz-Soroka, Hagit; Zhu, Ling; Li, Zhigang; Sang, Yaoshuo; Hipolito, Jolly; Zhang, Michael; Santos, Susy; Hillier, Craig; de Faria, Ricardo Lobato; Liu, Yong; Lin, Francis

    2018-01-15

    Mobile sensing based on the integration of microfluidic device and smartphone, so-called MS 2 technology, has enabled many applications over recent years, and continues to stimulate growing interest in both research communities and industries. In particular, it has been envisioned that MS 2 technology can be developed for various cell functional assays to enable basic research and clinical applications. Toward this direction, in this paper, we describe the development of a MS 2 -based cell functional assay for testing cell migration (the M kit ). The system is constructed as an integrated test kit, which includes microfluidic chips, a smartphone-based imaging platform, the phone apps for image capturing and data analysis, and a set of reagent and accessories for performing the cell migration assay. We demonstrated that the M kit can effectively measure purified neutrophil and cancer cell chemotaxis. Furthermore, neutrophil chemotaxis can be tested from a drop of whole blood using the M kit with red blood cell (RBC) lysis. The effects of chemoattractant dose and gradient profile on neutrophil chemotaxis were also tested using the M kit . In addition to research applications, we demonstrated the effective use of the M kit for on-site test at the hospital and for testing clinical samples from chronic obstructive pulmonary disease patient. Thus, this developed M kit provides an easy and integrated experimental platform for cell migration related research and potential medical diagnostic applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. The influence of social stigma and discriminatory experience on psychological distress and quality of life among rural-to-urban migrants in China.

    PubMed

    Wang, Bo; Li, Xiaoming; Stanton, Bonita; Fang, Xiaoyi

    2010-07-01

    The global literature has revealed a potential negative impact of social stigma on both physical and mental health among stigmatized individuals; however, the mechanisms through which social stigma affects the individual's quality of life and mental health are not well understood. This research simultaneously examines the relationships of several determinants and mediating factors of psychological distress and quality of life. Data were collected through a cross-sectional survey among 1006 adult (predominantly male) rural-to-urban migrants in 2004-2005 in Beijing, China. Participants reported on their perceived social stigma, discriminatory experiences in daily life, preparation for migration, discrepancy between expectation and reality, coping with stigma-related stress, psychological distress, and quality of life. Structural equation modeling was performed. We found that perceived social stigma and discriminatory experiences had direct negative effects on psychological distress and quality of life among rural-to-urban migrants. Expectation-reality discrepancy mediated the effects of perceived social stigma and discriminatory experiences on psychological distress and quality of life; coping mediated the effect of social stigma on quality of life. Psychological distress was associated with quality of life. Preparation prior to migration was positively related to coping skills, which were positively related to quality of life. We conclude that perceived social stigma and daily discriminatory experiences have a significant influence on psychological distress and quality of life among rural-to-urban migrants. Pre-migration training with a focus on establishment of effective coping skills and preparation of migration may be helpful to improve their quality of life and mental health.

  9. Modern contraceptive use among migrant and non-migrant women in Kenya.

    PubMed

    Ochako, Rhoune; Askew, Ian; Okal, Jerry; Oucho, John; Temmerman, Marleen

    2016-06-01

    Manifest socio-economic differences are a trigger for internal migration in many sub-Saharan settings including Kenya. An interplay of the social, political and economic factors often lead to internal migration. Internal migration potentially has significant consequences on an individual's economic growth and on access to health services, however, there has been little research on these dynamics. In Kenya, where regional differentials in population growth and poverty reduction continue to be priorities in the post MDG development agenda, understanding the relationships between contraceptive use and internal migration is highly relevant. Using data from the 2008-09 Kenya Demographic and Health Survey (DHS), we analyze data from 5,905 women aged 15-49 years who reported being sexually active in the last 12 months prior to the survey. Bivariate and multivariate logistic regressions are fitted to predict correlates of contraceptive use in the presence of migration streams among other explanatory variables. Modern contraceptive use was significantly higher among women in all migration streams (non-migrant urban (OR = 2.8, p < 0.001), urban-urban (OR = 2.0, p < 0.001), urban-rural (OR = 2.0, p < 0.001), rural-urban (OR = 2.6, p < 0.001), rural-rural (OR = 1.7, p < 0.001), than non-migrant rural women. Women who internally migrate within Kenya, whether from rural to urban or between urban centres, were more likely to use modern contraception than non-migrant rural women. This phenomenon appears to be due to selection, adaption and disruption effects which are likely to promote use of modern contraceptives. Programmatically, the differentials in modern contraceptive use by the different migration streams should be considered when designing family planning programmes among migrant and non-migrant women.

  10. Adipose-derived stem cell-derived microvesicle-released miR-210 promoted proliferation, migration and invasion of endothelial cells by regulating RUNX3.

    PubMed

    Zheng, Zeqi; Liu, Lijuan; Zhan, Yuliang; Yu, Songping; Kang, Ting

    2018-06-18

    To explore the potential mechanism of miRNA released from adipose-derived stem cell (ADSC)-derived micro vesicle (MV) on the modulation of proliferation, migration and invasion of endothelial cells. miR-210 level was detected by qT-PCR. Alix, VEGF and RUNX3 expressions were detected by Western blot. The proliferation, migration and invasion of human umbilical vein endothelial cells (HUVECs) were observed by MTT assay and Transwell assay. Luciferase reporter gene assay was conducted to validate the targeting activity of MVs-released miR-210 on RUNX3. Hypoxia significantly increased the expression of MVs-released miR-210. MVs released from ADSCs in hypoxic group significantly promoted the proliferation, migration and invasion of HUVECs. Overexpression of miR-210 significantly upregulated VEGF expression, and promoted the proliferation, migration and invasion of HUVECs. Besides, RUNX3 was identified as the direct of miR-210 in HUVECs. Overexpression of miR-210 decreased RUNX3 expression and promoted the proliferation, migration and invasion of HUVECs, while overexpression of RUNX3 inhibited these promotion effects. In vivo experiment showed that MVs derived from ADSCs under hypoxia increased miR-210 level and capillary density, and inhibition of miR-210 decreased capillary density. We also found MVs downregulated RUNX3 expression, and inhibition of miR-210 upregulated RUNX3 expression. miR-210 released from ADSCs-derived MVs promoted proliferation, migration and invasion of HUVECs by targeting RUNX3, which revealed one of the mechanisms of ADSCs-derived MVs on the promotion of proliferation, migration and invasion of HUVECs.

  11. Quantitative Analysis of Complex Glioma Cell Migration on Electrospun Polycaprolactone Using Time-Lapse Microscopy

    PubMed Central

    Johnson, Jed; Nowicki, M. Oskar; Lee, Carol H.; Chiocca, E. Antonio; Viapiano, Mariano S.; Lawler, Sean E.

    2009-01-01

    Malignant gliomas are the most common tumors originating within the central nervous system and account for over 15,000 deaths annually in the United States. The median survival for glioblastoma, the most common and aggressive of these tumors, is only 14 months. Therapeutic strategies targeting glioma cells migrating away from the tumor core are currently hampered by the difficulty of reproducing migration in the neural parenchyma in vitro. We utilized a tissue engineering approach to develop a physiologically relevant model of glioma cell migration. This revealed that glioma cells display dramatic differences in migration when challenged by random versus aligned electrospun poly-ɛ-caprolactone nanofibers. Cells on aligned fibers migrated at an effective velocity of 4.2 ± 0.39 μm/h compared to 0.8 ± 0.08 μm/h on random fibers, closely matching in vivo models and prior observations of glioma spread in white versus gray matter. Cells on random fibers exhibited extension along multiple fiber axes that prevented net motion; aligned fibers promoted a fusiform morphology better suited to infiltration. Time-lapse microscopy revealed that the motion of individual cells was complex and was influenced by cell cycle and local topography. Glioma stem cell–containing neurospheres seeded on random fibers did not show cell detachment and retained their original shape; on aligned fibers, cells detached and migrated in the fiber direction over a distance sixfold greater than the perpendicular direction. This chemically and physically flexible model allows time-lapse analysis of glioma cell migration while recapitulating in vivo cell morphology, potentially allowing identification of physiological mediators and pharmacological inhibitors of invasion. PMID:19199562

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

    PubMed

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

    2015-10-01

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

  13. Shorebird migration in the face of climate change: potential shifts in migration phenology and resource availability

    USGS Publications Warehouse

    Stutzman, Ryan J.; Fontaine, Joseph J

    2015-01-01

    Changes in temperature and seasonality resulting from climate change are heterogeneous, potentially altering important sources of natural selection acting on species phenology. Some species have apparently adapted to climate change but the ability of most species to adapt remains unknown. The life history strategies of migratory animals are dictated by seasonal factors, which makes these species particularly vulnerable to heterogeneous changes in climate and phenology. Here, we examine the phenology of migratory shorebirds, their habitats, and primary food resources, and we hypothesize how climate change may affect migrants through predicted changes in phenology. Daily abundance of shorebirds at stopover sites was correlated with local phenology and peaked immediately prior to peaks in invertebrate food resources. A close relationship between migrant and invertebrate phenology indicates that shorebirds may be vulnerable to changes in seasonality driven by climate change. It is possible that shifts in migrant and invertebrate phenology will be congruent in magnitude and direction, but because migration phenology is dependent on a suite of ecological factors, any response is likely to occur at a larger temporal scale and may lag behind the response of invertebrate food resources. The resulting lack of sufficient access to food at stopover habitats may cause migrants to extend migration and have cascading effects throughout their life cycle. If the heterogeneous nature of climate change results in uneven changes in phenology between migrants and their prey, it may threaten the long-term viability of migratory populations

  14. 18ß-glycyrrhetinic acid derivative promotes proliferation, migration and aquaporin-3 expression in human dermal fibroblasts.

    PubMed

    Hung, Chi-Feng; Hsiao, Chien-Yu; Hsieh, Wen-Hao; Li, Hsin-Ju; Tsai, Yi-Ju; Lin, Chun-Nan; Chang, Hsun-Hsien; Wu, Nan-Lin

    2017-01-01

    Licorice (Glycyrrhiza) species have been widely used as a traditional medicine and a natural sweetener in foods. The 18β-glycyrrhetinic acid (18β-GA) is a bioactive compound in licorice that exhibits potential anti-cancer, anti-inflammatory, and anti-microbial activities. Many synthesized derivatives of 18β-GA have been reported to be cytotoxic and suggested for the treatment of malignant diseases. In this study, we explored the possible pharmacological roles of an 18β-GA derivative in skin biology using primary human dermal fibroblasts and HaCaT keratinocytes as cell models. We found that this 18β-GA derivative did not cause cell death, but significantly enhanced the proliferation of dermal fibroblasts and HaCaT keratinocytes. A scratch wound healing assay revealed that the 18β-GA derivative promoted the migration of fibroblasts. Due to the important role of aquaporin-3 in cell migration and proliferation, we also investigated the expression of aquaporin-3 and found this compound up-regulated the expression of aquaporin-3 in dermal fibroblasts and HaCaT keratinocytes. In dermal fibroblasts, the 18β-GA derivative induced the phosphorylation of Akt, ERK, and p38. The inhibitor of Akt predominantly suppressed the 18β-GA derivative-induced expression of aquaporin-3. Collectively, this compound had a positive effect on the proliferation, migration, and aquaporin-3 expression of skin cells, implying its potential role in the treatment of skin diseases characterized by impaired wound healing or dermal defects.

  15. The consequences of migration to the United States for short-term changes in the health of Mexican immigrants.

    PubMed

    Goldman, Noreen; Pebley, Anne R; Creighton, Mathew J; Teruel, Graciela M; Rubalcava, Luis N; Chung, Chang

    2014-08-01

    Although many studies have attempted to examine the consequences of Mexico-U.S. migration for Mexican immigrants' health, few have had adequate data to generate the appropriate comparisons. In this article, we use data from two waves of the Mexican Family Life Survey (MxFLS) to compare the health of current migrants from Mexico with those of earlier migrants and nonmigrants. Because the longitudinal data permit us to examine short-term changes in health status subsequent to the baseline survey for current migrants and for Mexican residents, as well as to control for the potential health selectivity of migrants, the results provide a clearer picture of the consequences of immigration for Mexican migrant health than have previous studies. Our findings demonstrate that current migrants are more likely to experience recent changes in health status-both improvements and declines-than either earlier migrants or nonmigrants. The net effect, however, is a decline in health for current migrants: compared with never migrants, the health of current migrants is much more likely to have declined in the year or two since migration and not significantly more likely to have improved. Thus, it appears that the migration process itself and/or the experiences of the immediate post-migration period detrimentally affect Mexican immigrants' health.

  16. Bisdemethoxycurcumin inhibits PDGF-induced vascular smooth muscle cell motility and proliferation

    PubMed Central

    Hua, Yinan; Dolence, Julia; Ramanan, Shalini; Ren, Jun; Nair, Sreejayan

    2013-01-01

    Scope A key event in the development of plaque in the arteries is the migration and proliferation of smooth muscle cells (SMCs) from the media to the intima of the blood vessel. This study was conducted to evaluate the effects of bisdemethoxycurcumin, a naturally occurring structural analog of curcumin, on PDGF-stimulated migration and proliferation of SMCs. Methods and results Demethoxycurcumin were synthesized by condensing vanillin and 4-hydroxybenzaldehyde. SMCs isolated from adult rat aorta were stimulated with PDGF in the presence or absence of curcumin or bisdemethoxycurcumin following which cell migration and proliferation were assessed by monolayer wound healing assay and [3H]-thymidine incorporation respectively. PDGF-induced phosphorylation of PDGF-receptor-β and its downstream effector Akt were assessed by Western blotting. Intracellular reactive oxygen species (ROS) was assessed using the fluorescent dye DCFDA. Bisdemethoxycurcumin elicited a concentration-dependent inhibition of PDGF-stimulated phosphorylation of PDGFR-β, Akt and Erk as well as the PDGF-stimulated SMC migration and proliferation. Bisdemethoxycurcumin was more potent than curcumin in inhibiting migration and proliferation and suppressing PDGF-signaling in SMCs. Both compounds were equipotent in inhibiting PDGF-stimulated intracellular ROS-generation. Conclusion Bisdemethoxycurcumin may be of potential use in the prevention or treatment of vascular disease. PMID:23554078

  17. MicroRNA-146a promote cell migration and invasion in human colorectal cancer via carboxypeptidase M/src-FAK pathway

    PubMed Central

    Zhan, Cheng; Le-Meng, Zhang; Liu, Hongchun; Cai, Yu; Tu, Chuantao; Li, Xi; Zou, Yanting; Zhang, Shuncai

    2017-01-01

    Colorectal cancer (CRC) is one of the most common cancers worldwide, and microRNAs play important roles in CRC progression. This study aimed to investigate the roles of miR-146a-5p in human CRC and their molecular mechanisms. First, we found that miR-146a-5p was significantly upregulated in CRC tissues and promoted the migration of CRC cells. Then, we identified carboxypeptidase M (CPM) as a direct target of miR-146a-5p, and found that it inhibited the migration and invasion of CRC cells. Our results also showed that CPM expression was positively correlated with overall survival and negatively correlated with recurrence, lymph node invasion, and N stage. Furthermore, we demonstrated that both miR-146a-5p and CPM regulated Src and FAK expression, while the Src-FAK signaling pathway is widely known to be associated with the migration and invasion of multiple tumor cells. This study is the first to demonstrate the functional and mechanistic relationship of the miR-146a-5p/CPM/Src-FAK axis and its effect on the migration and invasion of CRC cells. Thus, miR-146a-5p represents potential targets for CRC diagnosis and therapy. PMID:28186967

  18. Northward migrating trees establish in treefall gaps at the northern limit of the temperate-boreal ecotone, Ontario, Canada.

    PubMed

    Leithead, Mark D; Anand, Madhur; Silva, Lucas C R

    2010-12-01

    Climate change is expected to promote migration of species. In ecotones, areas of ecological tension, disturbances may provide opportunities for some migrating species to establish in otherwise competitive environments. The size of and time since disturbance may determine the establishment ability of these species. We investigated gap dynamics of an old-growth red pine (Pinus resinosa Sol. ex Aiton) forest in the Great Lakes-St. Lawrence forest in northern Ontario, Canada, a transition zone between temperate and boreal forest. We investigated the effects of gaps of different sizes and ages on tree species abundance and basal area. Our results show that tree species from the temperate forest further south, such as red maple (Acer rubrum L.), red oak (Quercus rubra L.), and white pine (Pinus strobus L.), establish more often in large, old gaps; however, tree species that have more northern distributions, such as black spruce (Picea mariana Mill.), paper birch (Betula papyrifera Marsh.), and red pine show no difference in establishment ability with gap size or age. These differences in composition could not be attributed to autogenic succession. We conclude that treefall gaps in this forest facilitate the establishment of northward migrating species, potentially providing a pathway for future forest migration in response to recent changes in climate.

  19. The Consequences of Migration to the United States for Short-term Changes in the Health of Mexican Immigrants

    PubMed Central

    Goldman, Noreen; Pebley, Anne R.; Creighton, Mathew J.; Teruel, Graciela M.; Rubalcava, Luis N.; Chung, Chang

    2014-01-01

    Although many studies have attempted to examine the consequences of Mexico-U.S. migration for Mexican immigrants’ health, few have had adequate data to generate the appropriate comparisons. In this article, we use data from two waves of the Mexican Family Life Survey (MxFLS) to compare the health of current migrants from Mexico with those of earlier migrants and nonmigrants. Because the longitudinal data permit us to examine short-term changes in health status subsequent to the baseline survey for current migrants and for Mexican residents, as well as to control for the potential health selectivity of migrants, the results provide a clearer picture of the consequences of immigration for Mexican migrant health than have previous studies. Our findings demonstrate that current migrants are more likely to experience recent changes in health status—both improvements and declines—than either earlier migrants or nonmigrants. The net effect, however, is a decline in health for current migrants: compared with never migrants, the health of current migrants is much more likely to have declined in the year or two since migration and not significantly more likely to have improved. Thus, it appears that the migration process itself and/or the experiences of the immediate post-migration period detrimentally affect Mexican immigrants’ health. PMID:24788391

  20. Does parental migration really benefit left-behind children? Comparative evidence from Ethiopia, India, Peru and Vietnam.

    PubMed

    Viet Nguyen, Cuong

    2016-03-01

    Millions of children are left behind when their parents migrate from home to another place. This study examines whether parental migration can affect health and cognitive ability of left-behind children aged at 5-8 years old in Ethiopia, India, Peru, and Vietnam. It uses data on 7725 children in the four countries collected from Young Lives surveys in 2007 and 2009. It finds that although parental migration helps families increase per capita consumption, it does not improve health and cognitive ability of children. The effect of parental migration varies across different countries and different types of migration. In Ethiopia, parental migration does not have a significant effect on children. However, parental migration reduces health outcomes of children in other three countries and decreases cognitive ability test scores in India and Vietnam. The negative effect on children tends to be higher for long-term parental migration than short-term parental migration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Insights into Wilson's Warbler migration from analyses of hydrogen stable-isotope ratios

    Treesearch

    Jeffrey F. Kelly; Viorel Atudorei; Zachary D. Sharp; Deborah M. Finch

    2002-01-01

    Our ability to link the breeding locations of individual passerines to migration stopover sites and wintering locations is limited. Stable isotopes of hydrogen contained in bird feathers have recently shown potential in this regard. We measured hydrogen stable-isotope ratios (deltaD) of feathers from breeding, migrating, and wintering Wilson's Warblers. Analyses...

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

    Treesearch

    Michael D. Means; Deborah M. Finch

    1999-01-01

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

  3. Effect of perineoplasm perinephric adipose tissues on migration of clear cell renal cell carcinoma cells: a potential role of WNT signaling.

    PubMed

    Zi, Xiaolin; Lusch, Achim; Blair, Christopher A; Okhunov, Zhamshid; Yokoyama, Noriko N; Liu, Shuman; Baker, Molly; Huynh, Victor; Landman, Jaime

    2016-08-16

    To investigate the cellular and molecular interactions between clear-cell renal cell carcinoma (ccRCC) and perinephric adipose tissue (PAT), perineoplasm PAT, PAT away from the neoplasm, renal sinus and subcutaneous adipose tissues were collected at the time of renal surgery for renal masses and conditioned medium (CM) was generated from 62 patients. Perineoplasm PAT CMs from 44 out of 62 (about 71%) of patients with ccRCC or benign renal diseases (e.g. oncocytomas, angiomyolipomas, multicystic kidney, interstitial fibrosis, etc.) enhanced the migration of CaKi-2 cells. Perineoplasm PAT CMs from ccRCC significantly increased migration of ACHN and CaKi-2 cells by ~8.2 and ~2.4 folds, respectively, relative to those from benign renal diseases, whereas there is no significant difference in migration between ccRCC and benign renal diseases in CMs collected from culturing PAT away from neoplasm, renal sinus and subcutaneous adipose tissues. High Fuhrman Grade was associated with increased migration of Caki-2 cells by perineoplasm PAT CMs. Perineoplasm PATs from pT3 RCCs overexpressed multiple WNTs and their CMs exhibited higher WNT/ß-catenin activity and increased the migration of Caki-2 cells compared to CMs from benign neoplasms. Addition of secreted WNT inhibitory factor-1 recombinant protein into perineoplasm PAT CMs completely blocked the cell migration. These results indicate that WNT related factors from perineoplasm PAT may promote progression of local ccRCC to locally advanced (pT3) disease by increasing ccRCC cell mobility.

  4. Brown planthopper Nilaparvata lugens was concentrated at the rear of the typhoon Soudelor in Eastern China in August 2015.

    PubMed

    Ma, Jian; Wang, Ye-Chen; Hu, Yan-Yue; Lu, Ming-Hong; Wan, Gui-Jun; Chen, Fa-Jun; Liu, Wan-Cai; Zhai, Bao-Ping; Hu, Gao

    2017-03-28

    Sometimes, extreme weather is vital for the population survival of migratory insects by causing sudden population collapse or outbreak. Several studies have shown that rice planthopper migration was significantly influenced by typhoons in eastern Asia. Most typhoons occur in the summer, especially in August. In August, brown planthopper Nilaparvata lugens (Stål) migrates northward or southward depending on wind direction, and thus typhoons can potentially influence its migration process and population distribution. However, this has not yet been studied. This paper reported a case study on the effects of Typhoon Soudelor on the summer migration of N. lugens in eastern China in 2015. The migration pathways of N. lugens were reconstructed for the period under the influence of a typhoon by calculating the trajectories and migration events in eight counties of the Yangtze River Valley region with ancillary information. Trajectory modelling showed that most migrants took short distance migrations (less than 200 km) under the influence of the Typhoon Soudelor. Numerous N. lugens migrants were concentrated and deposited at the rear of the typhoon during the last 5 days of Typhoon Soudelor on August 9-13 due to horizontal convergence, and this led to an outbreak population. These results indicated that the N. lugens population was redistributed by the typhoon in the summer and that the population dynamics at the rear of a typhoon should be kept under close surveillance. This study provided insight into migratory organisms adapting to atmospheric features. © 2017 Institute of Zoology, Chinese Academy of Sciences.

  5. Vaccinium angustifolium (lowbush blueberry) leaf extract increases extravillous trophoblast cell migration and invasion in vitro.

    PubMed

    Ly, Christina; Ferrier, Jonathan; Gaudet, Jeremiah; Yockell-Lelièvre, Julien; Arnason, John Thor; Gruslin, Andrée; Bainbridge, Shannon

    2018-04-01

    Perturbations to extravillous trophoblast (EVT) cell migration and invasion are associated with the development of placenta-mediated diseases. Phytochemicals found in the lowbush blueberry plant (Vaccinium angustifolium) have been shown to influence cell migration and invasion in models of tumorigenesis and noncancerous, healthy cells, however never in EVT cells. We hypothesized that the phenolic compounds present in V. angustifolium leaf extract promote trophoblast migration and invasion. Using the HTR-8/SVneo human EVT cell line and Boyden chamber assays, the influence of V. angustifolium leaf extract (0 to 2 × 10 4  ng/ml) on trophoblast cell migration (n = 4) and invasion (n = 4) was determined. Cellular proliferation and viability were assessed using immunoreactivity to Ki67 (n = 3) and trypan blue exclusion assays (n = 3), respectively. At 20 ng/ml, V. angustifolium leaf extract increased HTR-8/SVneo cell migration and invasion (p < .01) and did not affect cell proliferation or viability. Chlorogenic acid was identified as a major phenolic compound of the leaf extract and the most active compound. Evidence from Western blot analysis (n = 3) suggests that the effects of the leaf extract and chlorogenic acid on trophoblast migration and invasion are mediated through an adenosine monophosphate-activated protein (AMP) kinase-dependent mechanism. Further investigations examining the potential therapeutic applications of this natural health product extract and its major chemical compounds in the context of placenta-mediated diseases are warranted. Copyright © 2018 John Wiley & Sons, Ltd.

  6. Effects of direct current electric fields on lung cancer cell electrotaxis in a PMMA-based microfluidic device.

    PubMed

    Li, Yaping; Xu, Tao; Chen, Xiaomei; Lin, Shin; Cho, Michael; Sun, Dong; Yang, Mengsu

    2017-03-01

    Tumor metastasis is the primary cause of cancer death. Numerous studies have demonstrated the electrotactic responses of various cancer cell types, and suggested its potential implications in metastasis. In this study, we used a microfluidic device to emulate endogenous direct current electric field (dcEF) environment, and studied the electrotactic migration of non-small cell lung cancer cell lines (H460, HCC827, H1299, and H1975) and the underlying mechanisms. These cell lines exhibited greatly different response in applied dcEFs (2-6 V/cm). While H460 cells (large cell carcinoma) showed slight migration toward cathode, H1299 cells (large cell carcinoma) showed increased motility and dcEF-dependent anodal migration with cell reorientation. H1975 cells (adenocarcinoma) showed dcEF-dependent cathodal migration with increased motility, and HCC827 cells (adenocarcinoma) responded positively in migration speed and reorientation but minimally in migrating directions to dcEF. Activation of MAPK and PI3K signaling pathways was found to be associated with the realignment and directed migration of lung cancer cells. In addition, both Ca 2+ influx through activated stretch-activated calcium channels (SACCs) (but not voltage-gated calcium channels, VGCCs) and Ca 2+ release from intracellular storage were involved in lung cancer cell electrotactic responses. The results demonstrated that the microfluidic device provided a stable and controllable microenvironment for cell electrotaxis study, and revealed that the electrotactic responses of lung cancer cells were heterogeneous and cell-type dependent, and multiple signals contributed to lung cancer cells electrotaxis.

  7. Final Project Memorandum: Ecological implications of mangrove forest migration in the southeastern U.S.

    USGS Publications Warehouse

    Osland, Michael J.; Day, Richard H.; Krauss, Ken W.; From, Andrew S.; Larriviere, Jack C.; Hester, Mark W.; Yando, Erik S.; Willis, Jonathan A

    2014-01-01

    Winter climate change has the potential to have a large impact on coastal wetlands in the southeastern United States. Warmer winter temperatures and reductions in the intensity of freeze events would likely lead to mangrove forest range expansion and salt marsh displacement in parts of the U.S. Gulf of Mexico and Atlantic coast. The objective of this research was to better evaluate the ecological implications of mangrove forest migration and salt marsh displacement. The potential ecological impacts of mangrove migration are diverse ranging from important biotic impacts (e.g., coastal fisheries, land bird migration; colonial-nesting wading birds) to ecosystem stability (e.g., response to sea level rise and drought; habitat loss; coastal protection) to biogeochemical processes (e.g., carbon storage; water quality). This research specifically investigated the impact of mangrove forest migration on coastal wetland soil processes and the consequent implications for coastal wetland responses to sea level rise and carbon storage.

  8. Potential interactions between diadromous fishes of U.K. conservation importance and the electromagnetic fields and subsea noise from marine renewable energy developments.

    PubMed

    Gill, A B; Bartlett, M; Thomsen, F

    2012-07-01

    The considerable extent of construction and operation of marine renewable energy developments (MRED) within U.K. and adjacent waters will lead, among other things, to the emission of electromagnetic fields (EMF) and subsea sounds into the marine environment. Migratory fishes that respond to natural environmental cues, such as the Earth's geomagnetic field or underwater sounds, move through the same waters that the MRED occupy, thereby raising the question of whether there are any effects of MRED on migratory fishes. Diadromous species, such as the Salmonidae and Anguillidae, which undertake large-scale migrations through coastal and offshore waters, are already significantly affected by other human activities leading to national and international conservation efforts to manage any existing threats and to minimize future concerns, including the potential effect of MRED. Here, the current state of knowledge with regard to the potential for diadromous fishes of U.K. conservation importance to be affected by MRED is reviewed. The information on which to base the review was found to be limited with respect to all aspects of these fishes' migratory behaviour and activity, especially with regards to MRED deployment, making it difficult to establish cause and effect relationships. The main findings, however, were that diadromous species can use the Earth's magnetic field for orientation and direction finding during migrations. Juveniles of anadromous brown trout (sea trout) Salmo trutta and close relatives of S. trutta respond to both the Earth's magnetic field and artificial magnetic fields. Current knowledge suggests that EMFs from subsea cables may interact with migrating Anguilla sp. (and possibly other diadromous fishes) if their movement routes take them over the cables, particularly in shallow water (<20 m). The only known effect is a temporary change in swimming direction. Whether this will represent a biologically significant effect, for example delayed migration, cannot yet be determined. Diadromous fishes are likely to encounter EMFs from subsea cables either during the adult movement phases of life or their early life stages during migration within shallow, coastal waters adjacent to natal rivers. The underwater sound from MRED devices has not been fully characterized to determine its acoustic properties and propagation through the coastal waters. MRED that require pile driving during construction appear to be the most relevant to consider. In the absence of a clear understanding of their response to underwater sound, the specific effects on migratory species of conservation concern remain very difficult to determine in relation to MRED. Based on the studies reviewed, it is suggested that fishes that receive high intensity sound in close proximity to construction may be physiologically affected to some degree, whereas those at farther distances, potentially up to several km, may exhibit behaviour responses; the effect of which is unknown and will be dependent on the properties of the received sound and receptor characteristics and condition. Whether there are behavioural effects on the fishes during operation is unknown but any change to the environment and subsequent response by the fishes would need to be considered over the lifetime of the MRED. It is not yet possible to determine if effects relating to sound exposure are biologically significant. The current assumptions of limited effects are built on an incomplete understanding of how the species move around their environment and interact with natural and anthropogenic EMFs and subsea sound. A number of important knowledge gaps exist, principally whether migratory fish species on the whole respond to the EMF and the sound associated with MRED. Future research should address the principal gaps before assuming that any effect on diadromous species results in a biological effect. © 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

  9. Preconditioning of bone marrow-derived mesenchymal stromal cells by tetramethylpyrazine enhances cell migration and improves functional recovery after focal cerebral ischemia in rats.

    PubMed

    Li, Lin; Chu, Lisheng; Fang, Yan; Yang, Yan; Qu, Tiebing; Zhang, Jianping; Yin, Yuanjun; Gu, Jingjing

    2017-05-12

    Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) is one of the new therapeutic strategies for treating ischemic stroke. However, the relatively poor migratory capacity of BMSCs toward infarcted regions limited the therapeutic potential of this approach. Pharmacological preconditioning can increase the expression of CXC chemokine receptor 4 (CXCR4) in BMSCs and enhance cell migration toward the injury site. In the present study, we investigated whether tetramethylpyrazine (TMP) preconditioning could enhance BMSCs migration to the ischemic brain and improve functional recovery through upregulating CXCR4 expression. BMSCs were identified by flow cytometry analysis. BMSCs migration was evaluated in vitro by transwell migration assay, and CXCR4 expression was measured by quantitative reverse transcription-polymerase chain reaction and western blot analysis. In rats with focal cerebral ischemia, the neurological function was evaluated by the modified neurological severity score, the adhesive removal test and the corner test. The homing BMSCs and angiogenesis were detected by immunofluorescence, and expression of stromal cell-derived factor-1 (SDF-1) and CXCR4 was measured by western blot analysis. Flow cytometry analysis demonstrated that BMSCs expressed CD29 and CD90, but not CD34 and CD45. TMP pretreatment dose-dependently induced BMSCs migration and CXCR4 expression in vitro, which was significantly inhibited by AMD3100, a CXCR4 antagonist. In rat stroke models, we found more TMP-preconditioned BMSCs homing toward the infarcted regions than nonpreconditioned cells, leading to improved neurological performance and enhanced angiogenesis. Moreover, TMP-preconditioned BMSCs significantly upregulated the protein expression of SDF-1 and CXCR4 in the ischemic boundary regions. These beneficial effects of TMP preconditioning were blocked by AMD3100. TMP preconditioning enhances the migration and homing ability of BMSCs, increases CXCR4 expression, promotes angiogenesis, and improves neurological performance. Therefore, TMP preconditioning may be an effective strategy to improve the therapeutic potency of BMSCs for ischemic stroke due to enhanced BMSCs migration to ischemic regions.

  10. Zinc oxide nanoparticles induce migration and adhesion of monocytes to endothelial cells and accelerate foam cell formation

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

    Suzuki, Yuka; Tada-Oikawa, Saeko; Ichihara, Gaku

    Metal oxide nanoparticles are widely used in industry, cosmetics, and biomedicine. However, the effects of exposure to these nanoparticles on the cardiovascular system remain unknown. The present study investigated the effects of nanosized TiO{sub 2} and ZnO particles on the migration and adhesion of monocytes, which are essential processes in atherosclerogenesis, using an in vitro set-up of human umbilical vein endothelial cells (HUVECs) and human monocytic leukemia cells (THP-1). We also examined the effects of exposure to nanosized metal oxide particles on macrophage cholesterol uptake and foam cell formation. The 16-hour exposure to ZnO particles increased the level of monocytemore » chemotactic protein-1 (MCP-1) and induced the migration of THP-1 monocyte mediated by increased MCP-1. Exposure to ZnO particles also induced adhesion of THP-1 cells to HUVECs. Moreover, exposure to ZnO particles, but not TiO{sub 2} particles, upregulated the expression of membrane scavenger receptors of modified LDL and increased cholesterol uptake in THP-1 monocytes/macrophages. In the present study, we found that exposure to ZnO particles increased macrophage cholesterol uptake, which was mediated by an upregulation of membrane scavenger receptors of modified LDL. These results suggest that nanosized ZnO particles could potentially enhance atherosclerogenesis and accelerate foam cell formation. - Highlights: • Effects of metal oxide nanoparticles on foam cell formation were investigated. • Exposure to ZnO nanoparticles induced migration and adhesion of monocytes. • Exposure to ZnO nanoparticles increased macrophage cholesterol uptake. • Expression of membrane scavenger receptors of modified LDL was also increased. • These effects were not observed after exposure to TiO{sub 2} nanoparticles.« less

  11. Movement of Cations through Cuticles of Citrus aurantium and Acer saccharum1

    PubMed Central

    Tyree, Melvin T.; Tabor, Christopher A.; Wescott, Charles R.

    1990-01-01

    We examined some biophysical mechanisms of ion migration across leaf cuticles enzymatically isolated from Acer saccharum L. and Citrus aurantium L. leaves. Diffusion potential measurements were used to calculate the permeabilities of Cl-, Li+, Na+, and Cs+ ions all as a ratio with respect to the permeability of K+ in cuticles. In 2 millimolar ionic strength solutions the permeability sequence from high to low was K = Cs > Na > Li » Cl. When the outer and inner surfaces of cuticles were bathed in artificial precipitation and artificial apoplast, respectively, diffusion potentials ranging from −52 to −91 millivolts were measured (inside negative). The Goldman equation predicted that the measured potentials were enough to increase the driving force on the accumulation of heavy metals by a factor of 4 to 7. Other ions migrate with forces 3 to 10 times less than predicted by the Goldman equation for concentration differences alone. Our analysis showed that Ca2+, and perhaps Mg2+, might even be accumulated against concentration gradients under some circumstances. Their uptake was apparently driven by the diffusion potentials created by the outward migration of monovalent salts. We feel that future models predicting leaching of nutrients from trees during acid rain events must be modified to account for the probable influence of diffusion potentials on ion migration. PMID:16667677

  12. sGD software for estimating spatially explicit indices of genetic diversity

    Treesearch

    A. J. Shirk; Samuel Cushman

    2011-01-01

    Anthropogenic landscape changes have greatly reduced the population size, range and migration rates of many terrestrial species. The small local effective population size of remnant populations favours loss of genetic diversity leading to reduced fitness and adaptive potential, and thus ultimately greater extinction risk. Accurately quantifying genetic diversity is...

  13. Persistent leatherback turtle migrations present opportunities for conservation.

    PubMed

    Shillinger, George L; Palacios, Daniel M; Bailey, Helen; Bograd, Steven J; Swithenbank, Alan M; Gaspar, Philippe; Wallace, Bryan P; Spotila, James R; Paladino, Frank V; Piedra, Rotney; Eckert, Scott A; Block, Barbara A

    2008-07-15

    Effective transboundary conservation of highly migratory marine animals requires international management cooperation as well as clear scientific information about habitat use by these species. Populations of leatherback turtles (Dermochelys coriacea) in the eastern Pacific have declined by >90% during the past two decades, primarily due to unsustainable egg harvest and fisheries bycatch mortality. While research and conservation efforts on nesting beaches are ongoing, relatively little is known about this population of leatherbacks' oceanic habitat use and migration pathways. We present the largest multi-year (2004-2005, 2005-2006, and 2007) satellite tracking dataset (12,095 cumulative satellite tracking days) collected for leatherback turtles. Forty-six females were electronically tagged during three field seasons at Playa Grande, Costa Rica, the largest extant nesting colony in the eastern Pacific. After completing nesting, the turtles headed southward, traversing the dynamic equatorial currents with rapid, directed movements. In contrast to the highly varied dispersal patterns seen in many other sea turtle populations, leatherbacks from Playa Grande traveled within a persistent migration corridor from Costa Rica, past the equator, and into the South Pacific Gyre, a vast, low-energy, low-productivity region. We describe the predictable effects of ocean currents on a leatherback migration corridor and characterize long-distance movements by the turtles in the eastern South Pacific. These data from high seas habitats will also elucidate potential areas for mitigating fisheries bycatch interactions. These findings directly inform existing multinational conservation frameworks and provide immediate regions in the migration corridor where conservation can be implemented. We identify high seas locations for focusing future conservation efforts within the leatherback dispersal zone in the South Pacific Gyre.

  14. Effect of ITGA5 down-regulation on the migration capacity of human dental pulp stem cells

    PubMed Central

    Xu, Shuaimei; Cui, Li; Ma, Dandan; Sun, Wenjuan; Wu, Buling

    2015-01-01

    Background: The purpose of this study was to evaluate the role of integrin-α5 (ITGA5) in regulating the migration capacity of human dental pulp stem cells (hDPSCs), which might provide new evidence for understanding the repair and regeneration mechanisms of dental pulp tissues. Materials and methods: The enzyme digestion method was employed to isolate the hDPSCs from dental pulp tissues. The cell surface markers of hDPSCs were detected using flow cytometry analysis. Then the colony forming and multi-differentiation capacity of hDPSCs were evaluated. The lentivirus vector that carried the ITGA5 shRNA was constructed and real-time PCR was used to examine the effectiveness of ITGA5 shRNA lentivirus. Then transwell assay was performed to evaluate the impact of ITGA5 inhibition on the migration capability of hDPSCs. Results: Our results showed that the cells we isolated from the dental pulps were positive for mesenchymal stem cells biomarkers. In addition, the cells possessed both colony forming capacity and multi-differentiation potential. ITGA5 shRNA lentivirus could not only infect hDPSCs with high efficiency, but also down-regulate the expression level of ITGA5 mRNA significantly (P<0.01). The transwell assay revealed the number of cells that migrated to the lower chamber was significantly less in the ITGA5 shRNA group compared with that in the scrambled shRNA group (P=0.016). Conclusion: ITGA5 plays an important role in maintaining and regulating the normal migration capacity of hDPSCs. PMID:26823759

  15. Melt migration modeling in partially molten upper mantle

    NASA Astrophysics Data System (ADS)

    Ghods, Abdolreza

    The objective of this thesis is to investigate the importance of melt migration in shaping major characteristics of geological features associated with the partial melting of the upper mantle, such as sea-floor spreading, continental flood basalts and rifting. The partial melting produces permeable partially molten rocks and a buoyant low viscosity melt. Melt migrates through the partially molten rocks, and transfers mass and heat. Due to its much faster velocity and appreciable buoyancy, melt migration has the potential to modify dynamics of the upwelling partially molten plumes. I develop a 2-D, two-phase flow model and apply it to investigate effects of melt migration on the dynamics and melt generation of upwelling mantle plumes and focusing of melt migration beneath mid-ocean ridges. Melt migration changes distribution of the melt-retention buoyancy force and therefore affects the dynamics of the upwelling plume. This is investigated by modeling a plume with a constant initial melt of 10% where no further melting is considered. Melt migration polarizes melt-retention buoyancy force into high and low melt fraction regions at the top and bottom portions of the plume and therefore results in formation of a more slender and faster upwelling plume. Allowing the plume to melt as it ascends through the upper mantle also produces a slender and faster plume. It is shown that melt produced by decompressional melting of the plume migrates to the upper horizons of the plume, increases the upwelling velocity and thus, the volume of melt generated by the plume. Melt migration produces a plume which lacks the mushroom shape observed for the plume models without melt migration. Melt migration forms a high melt fraction layer beneath the sloping base of the impermeable oceanic lithosphere. Using realistic conditions of melting, freezing and melt extraction, I examine whether the high melt fraction layer is able to focus melt from a wide partial melting zone to a narrow region beneath the observed neo-volcanic zone. My models consist of three parts; lithosphere, asthenosphere and a melt extraction region. It is shown that melt migrates vertically within the asthenosphere, and forms a high melt fraction layer beneath the sloping base of the impermeable lithosphere. Within the sloping high melt fraction layer, melt migrates laterally towards the ridge. In order to simulate melt migration via crustal fractures and cracks, melt is extracted from a melt extraction region extending to the base of the crust. Performance of the melt focusing mechanism is not significantly sensitive to the size of melt extraction region, melt extraction threshold and spreading rate. In all of the models, about half of the total melt production freezes beneath the cooling base of the lithosphere, and the rest is effectively focused towards the ridge and forms the crust. To meet the computational demand for a precise tracing of the deforming upwelling plume and including the chemical buoyancy of the partially molten zone in my models, a new numerical method is developed to solve the related pure advection equations. The numerical method is based on Second Moment numerical method of Egan and Mahoney [1972] which is improved to maintain a high numerical accuracy in shear and rotational flow fields. In comparison with previous numerical methods, my numerical method is a cost-effective, non-diffusive and shape preserving method, and it can also be used to trace a deforming body in compressible flow fields.

  16. Comparing Past and Future Elevational vs. Latitudinal Migrations in Mountains of the Western U.S

    NASA Astrophysics Data System (ADS)

    Cole, K. L.; Ironside, K.; Cobb, N.

    2009-12-01

    During the early Holocene, plant species of the western United States responded to the warming post-glacial temperatures by migrating to higher elevations and to more northerly latitudes. Models of species response to warmer climates assume similar processes will occur in the future but the rates and extent of these future migrations are unknown. Hypothetically, the rates of elevational and latitudinal migrations should differ depending upon the importance of spatial distance in determining the resulting migration rate. The diverse topography of the western United States presents an ideal laboratory for comparing these past elevational vs. latitudinal species movements. Abundant fossil records allow comparisons between these rates following rapidly warming periods in the past such as occurred in the early Holocene. At that time, species often equilibrated to the new temperature regime rapidly where they were only required to migrate a short distance uphill. But the same species required many thousands of years to subsequently approach their northern latitudinal boundaries. Further, the upper limits and lower limits for a species often did not move synchronously, yielding additional information on the dynamics of response to rapid warming for that particular species. We calibrated the available temperature space for several dominant forest tree species of the mountains of the interior western U.S. and then calculated their early Holocene rates of migration relative to geographic space. Next we were able to compare these estimations to the observations of each species recent historical autecological response to disturbances. For many species their paleoecological rates of change were consistent with observations of their dynamics over the last century. A few species, such as the wind dispersed Populus tremuloides, re-populate disturbed areas so rapidly that they have no discernable migration delay. Other species, such as Pinus ponderosa, can expand rapidly at a rate approximating 250 to 500 m/year. But even at such a rapid rate, they would only be able to expand a total of 45 km by the end of this century. And, because of their maturation time, this could constitute only three generations. Lastly, many species of interior semi-arid regions, such as Pseudotsuga menziesii and Pinus edulis, expand at rates of less than 100 m/yr. Finally, we applied calculated migration rates to modeled areas of future potential climate for each species. We generated these areas of future potential distribution using a selection of AR4 GCMs that were applied to species-specific climate models developed from late Twentieth Century correlations between climate and species ranges. Our results demonstrate that the incorporation of these migration rates greatly change the distributions that could be expected over the next 500 years. The effect of such migration rates have not been considered in models of future carbon balance, yet their history suggests that their importance may outweigh many other variables. Models incorporating migration should be even more important in the projection of future distributions of boreal species across expansive Arctic regions.

  17. Resveratrol Regulates Colorectal Cancer Cell Invasion by Modulation of Focal Adhesion Molecules

    PubMed Central

    Buhrmann, Constanze; Shayan, Parviz; Goel, Ajay; Shakibaei, Mehdi

    2017-01-01

    Resveratrol, a safe and multi-targeted agent, has been associated with suppression of survival, proliferation and metastasis of cancer, however, the underlying mechanisms for its anti-cancer activity, particularly on cellular signaling during cancer cell migration still remain poorly understood. We investigated the invasion response of two human colorectal cancer (CRC) cells (HCT116 and SW480) to resveratrol and studied the effect of specific pharmacological inhibitors, cytochalasin D (CytD) and focal adhesion kinase-inhibitor (FAK-I) on FAK, cell viability and migration in CRC. We found that resveratrol altered cell phenotype of both CRC cells, reduced cell viability and the results were comparable to FAK-I and CytD. These effects of resveratrol were associated with marked Sirt1 up-regulation, FAK down-regulation, inhibition of focal adhesion and potentiation of effects by combinatorial treatment of resveratrol and inhibitors. Interestingly, inhibition of FAK with FAK-I or treatment with CytD suppressed resveratrol-induced Sirt1 up-regulation and markedly down-regulated FAK expression. Resveratrol or combination treatment with inhibitors significantly activated caspase-3 and potentiated apoptosis. Moreover, resveratrol suppressed invasion and colony forming capacity, cell proliferation, β1-Integrin expression and activation of FAK of cells in alginate tumor microenvironment, similar to FAK-I or CytD. Finally, we demonstrated that resveratrol, FAK-I or CytD inhibited activation of NF-κB, suppressed NF-κB-dependent gene end-products involved in invasion, metastasis, and apoptosis; and these effects of resveratrol were potentiated by combination treatment with FAK-I or CytD. Our data illustrated that the anti-invasion effect of resveratrol by inhibition of FAK activity has a potential beneficial role in disease prevention and therapeutic management of CRC. PMID:28953264

  18. Resveratrol Regulates Colorectal Cancer Cell Invasion by Modulation of Focal Adhesion Molecules.

    PubMed

    Buhrmann, Constanze; Shayan, Parviz; Goel, Ajay; Shakibaei, Mehdi

    2017-09-27

    Resveratrol, a safe and multi-targeted agent, has been associated with suppression of survival, proliferation and metastasis of cancer, however, the underlying mechanisms for its anti-cancer activity, particularly on cellular signaling during cancer cell migration still remain poorly understood. We investigated the invasion response of two human colorectal cancer (CRC) cells (HCT116 and SW480) to resveratrol and studied the effect of specific pharmacological inhibitors, cytochalasin D (CytD) and focal adhesion kinase-inhibitor (FAK-I) on FAK, cell viability and migration in CRC. We found that resveratrol altered cell phenotype of both CRC cells, reduced cell viability and the results were comparable to FAK-I and CytD. These effects of resveratrol were associated with marked Sirt1 up-regulation, FAK down-regulation, inhibition of focal adhesion and potentiation of effects by combinatorial treatment of resveratrol and inhibitors. Interestingly, inhibition of FAK with FAK-I or treatment with CytD suppressed resveratrol-induced Sirt1 up-regulation and markedly down-regulated FAK expression. Resveratrol or combination treatment with inhibitors significantly activated caspase-3 and potentiated apoptosis. Moreover, resveratrol suppressed invasion and colony forming capacity, cell proliferation, β1-Integrin expression and activation of FAK of cells in alginate tumor microenvironment, similar to FAK-I or CytD. Finally, we demonstrated that resveratrol, FAK-I or CytD inhibited activation of NF-κB, suppressed NF-κB-dependent gene end-products involved in invasion, metastasis, and apoptosis; and these effects of resveratrol were potentiated by combination treatment with FAK-I or CytD. Our data illustrated that the anti-invasion effect of resveratrol by inhibition of FAK activity has a potential beneficial role in disease prevention and therapeutic management of CRC.

  19. Magnolol suppresses the proliferation and invasion of cholangiocarcinoma cells via inhibiting the NF-κB signaling pathway.

    PubMed

    Zhang, Fu-Hui; Ren, Hong-Yue; Shen, Jin-Xing; Zhang, Xiao-Yun; Ye, Hui-Ming; Shen, Dong-Yan

    2017-10-01

    Magnolol has shown the potential anticancer properties against a variety of cancers. However, the role of magnolol in cholangiocarcinoma (CCA) cells is unknown. In this study, we assessed the effect of magnolol on the CCA cells. CCA cells were treated with magnolol in the absence or presence of TNFα, the activator for NF-κB. After co-incubation with magnolol, cell proliferation and growth were examined by MTT, colony formation and xenograft tumors; cell cycle was analyzed by flow cytometry; cell migration and invasion were detected by wound healing and transwell assays; the expression of PCNA, Ki67, CyclinD1, MMP-2, MMP-7 and MMP-9 and NF-κB pathway were evaluated by using Western blot. Magnolol inhibited the abilities of CCA cell growth, migration and invasion accompanying with a decreased expression of PCNA, Ki67, MMP-2, MMP-7 and MMP-9 (all P<0.05). with magnolol induced cell cycle arrest in G1 phase with a downregulation of cell cycle protein CyclinD1 (all P<0.05). In addition, magnolol suppressed the expression of p-IκBα and p-P65 and the effect of magnolol on CCA cells could be inhibited by TNFα. Magnolol could inhibit the growth, migration and invasion of CCA cells through regulation of NF-κB pathway, and these data indicate that magnolol is a potential candidate for treating of CCA. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  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. A combination of desmopressin and docetaxel inhibit cell proliferation and invasion mediated by urokinase-type plasminogen activator (uPA) in human prostate cancer cells

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

    Sasaki, Hiroshi; Klotz, Laurence H.; Sugar, Linda M.

    Background: This study was designed to assess the effectiveness of a combination treatment using both desmopressin and docetaxel in prostate cancer treatment. Desmopressin is a well-known synthetic analogue of the antidiuretic hormone vasopressin. It has recently been demonstrated to inhibit tumor progression and metastasis in in vivo models. Docetaxel is widely used for the treatment of castration resistant prostate cancer (CRPC) patients. However, durable responses have been uncommon to date. In this study, we investigated the anti-tumor effect of desmopressin in combination with docetaxel in vitro and in vivo. Methods: Two prostate cancer cells (PC3, LNCaP) were treated with different concentrations of desmopressinmore » alone, docetaxel alone, and a combination of desmopressin and docetaxel. Cell proliferation was determined by MTS assay. The anti-invasive and anti-migration potential of desmopressin and in combination with docetaxel were examined by wound healing assay, migration chamber assay, and matrigel invasion assay. Results: The combination of desmopressin and docetaxel resulted in a significant inhibition of PC3 and LNCaP cell proliferation (p < 0.01). Additionally, cell migration and invasion were also inhibited by the combination when compared to that of either treatment alone in PC3 cells (p < 0.01). The anti-tumor effect of this combination treatment was associated with down-regulation of both urokinase-type plasminogen activator (uPA) and matrix metalloproteinase (MMP-2 and MMP-9) in PC3 cells. Conclusions: We are the first to elucidate the anti-tumor and anti-metastatic potential of desmopressin in combination with docetaxel in a prostate cancer model via the uPA-MMP pathway. Our finding could potentially contribute to the therapeutic profile of desmopressin and enhance the efficacy of docetaxel based treatment for CRPC. - Highlights: • Desmopressin inhibits cell proliferation in prostate cancer cells. • The expression of cyclin A and CDK2 were reduced in the cells treated with desmopressin and docetaxel. • uPA-MMP pathway mediates the desmopressin-induced migration and invasion of PC3 cells. • Desmopressin in combination with docetaxel inhibits PC-3 cell growth in a xenograft model.« less

  2. Endothelin-1 exacerbates development of hypertension and atherosclerosis in modest insulin resistant syndrome

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

    Lin, Yan-Jie; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Juan, Chi-Chang

    Endothelin-1 (ET-1) is known as potent vasoconstrictor, by virtue of its mitogenic effects, and may deteriorate the process of hypertension and atherosclerosis by aggravating hyperplasia and migration in VSMCs. Our previous study demonstrated that insulin infusion caused sequential induction of hyperinsulinemia, hyperendothelinemia, insulin resistance, and then hypertension in rats. However, the underlying mechanism of ET-1 interfere insulin signaling in VSMCs remains unclear. To characterize insulin signaling during modest insulin resistant syndrome, we established and monitored rats by feeding high fructose-diet (HFD) until high blood pressure and modest insulin resistance occurred. To explore the role of ET-1/ET{sub A}R during insulin resistance,more » ET{sub A}R expression, ET-1 binding, and insulin signaling were investigated in the HFD-fed rats and cultured A-10 VSMCs. Results showed that high blood pressure, tunica medial wall thickening, plasma ET-1 and insulin, and accompanied with modest insulin resistance without overweight and hyperglycemia occurred in early-stage HFD-fed rats. In the endothelium-denuded aorta from HFD-fed rats, ET{sub A}R expression, but not ET{sub B}R, and ET-1 binding in aorta were increased. Moreover, decreasing of insulin-induced Akt phosphorylation and increasing of insulin-induced ERK phosphorylation were observed in aorta during modest insulin resistance. Interestingly, in ET-1 pretreated VSMCs, the increment of insulin-induced Akt phosphorylation was decreased whereas the increment of insulin-induced ERK phosphorylation was increased. In addition, insulin potentiated ET-1-induced VSMCs migration and proliferation due to increasing ET-1 binding. ETAR antagonist reversed effects of ET-1 on insulin-induced signaling and VSMCs migration and proliferation. In summary, modest insulin resistance syndrome accompanied with hyperinsulinemia leading to the potentiation on ET-1-induced actions in aortic VSMCs. ET-1 via ET{sub A}R pathway suppressed insulin-induced AKT activation, whereas remained insulin-induced ERK activation. ET-1 and insulin synergistically potentiated migration and proliferation mainly through ET{sub A}R/ERK dependent pathway, which is dominant in VSMCs during modest insulin resistance syndrome. Therefore, ET-1 and ET{sub A}R are potential targets responsible for the observed synergism effect in the hypertensive atherosclerotic process through enhancement of ET-1 binding, ET-1 binding, ET{sub A}R expression, and ET-1-induced mitogenic actions in aortic VSMCs. - Highlights: • ET-1/ET{sub A}R signaling and insulin-induced pERK were high in modest insulin resistance. • ET-1 via ET{sub A}R suppressed insulin-induced pAKT but remained intact pERK in VSMCs. • Insulin potentiated ET-1-induced VSMC mitogenic action was ET{sub A}R/ERK dependent.« less

  3. Increasing the realism of projected tree species ranges by incorporating migration potential: an eastern US case study

    NASA Astrophysics Data System (ADS)

    Rogers, B. M.; Jantz, P.; Goetz, S. J.

    2015-12-01

    Models of vegetation distributions are used for a wide variety of purposes, from global assessments of biome shifts and biogeochemical feedbacks to local management planning. Dynamic vegetation models, mostly mechanistic in origin, are valuable for regional to global studies but remain limited for more local-scale applications, especially those that require species-specific responses to climate change. Species distribution models (SDMs) are broadly used for such applications, but these too have several outstanding limitations, one of the most prominent being a lack of dispersal and migration. Several hybrid models have recently been developed, but these generally require detailed parameterization of species-level attributes that may not be known. Here we present an approach to couple migration potential with SDM output for a large number of species in order to more realistically project future range shifts. We focus on 40 tree species in the eastern US of potential management concern, either because of their canopy dominance, ecosystem functions, or potential for utilizing future climates. Future climates were taken from a CMIP5 model ensemble average using RCP 4.5 and 8.5 scenarios. We used Random Forests to characterize current and future environmental suitability, and modeled migration as a negative exponential kernel that is affected by forest fragmentation and the density of current seed sources. We present results in a vulnerability framework relevant for a number of ongoing management activities in the region. We find an overarching pattern of northward and eastward range shifts, with high-elevation and northern species being the most adversely impacted. Because of limitations to migration, many newly suitable areas could not be utilized without active intervention. Only a few areas exhibited consistently favorable conditions that could be utilized by the relevant species, including the central Appalachian foothills and the Florida panhandle. We suggest that a continued effort to include migration potential into vegetation models can lead to more realistic results and management-relevant products.

  4. Decoupling migration effects from income effects on reproduction in Central American migrant-sending households.

    PubMed

    Davis, Jason

    2011-01-01

    Contemporary data for three Central American countries (Costa Rica, Guatemala, and Nicaragua) surveyed by the Latin American Migration Project were analyzed to determine if migration length and remittance transfers had an influence on fertility. The analysis was structured to separate societal influences on fertility attributable to migration from the income effects associated with remittance transfers. At the couple level, the odds that a birth would occur were negatively associated with an increase in U.S. remittance receipts and an increase in a wife’s migration duration. However, no correlation was found between length of male migration and couple fertility.

  5. The migration mechanism of transition metal ions in LiNi 0.5 Mn 1.5O 4

    DOE PAGES

    Xu, Gui-Liang; Qin, Yan; Ren, Yang; ...

    2015-05-12

    The migration of transition metal ions in the oxygen framework was recently proposed to be responsible for the continuous loss of average working potential of high energy density layered–layered composite cathodes for lithium-ion batteries. The potential migration pathway in a model material, LiNi 0.5 Mn 1.5O 4 spinel, was investigated using in situ high-energy X-ray diffraction and in situ neutron diffraction during the solid state synthesis process. It was found that the migration of transition metal ions among octahedral sites is possible by using tetrahedral vacancies as intermediate sites. It was also suggested that the number of electrons in 3dmore » orbitals has a significant impact on their mobility in the hosting oxygen framework.« less

  6. Overexpression of HIF-1α in mesenchymal stem cells contributes to repairing hypoxic-ischemic brain damage in rats.

    PubMed

    Lin, Deju; Zhou, Liping; Wang, Biao; Liu, Lizhen; Cong, Li; Hu, Chuanqin; Ge, Tingting; Yu, Qin

    2017-01-01

    Preclinical researches on mesenchymal stem cells (MSCs) transplantation, which is used to treat hypoxic-ischemic (HI) brain damage, have received inspiring achievements. However, the insufficient migration of active cells to damaged tissues has limited their potential therapeutic effects. There are some evidences that hypoxia inducible factor-1 alpha (HIF-1α) promotes the viability and migration of the cells. Here, we aim to investigate whether overexpression of HIF-1α in MSCs could improve the viability and migration capacity of cells, and its therapeutic efficiency on HI brain damage. In the study, MSCs with HIF-1α overexpression was achieved by recombinant lentiviral vector and transplanted to the rats subsequent to HI. Our data indicated that overexpression of HIF-1α promoted the viability and migration of MSCs, HIF-1α overexpressed MSCs also had a stronger therapeutic efficiency on HI brain damaged treatment by mitigating the injury on behavioral and histological changes evoked by HI insults, accompanied with more MSCs migrating to cerebral damaged area. This study demonstrated that HIF-1α overexpression could increase the MSCs' therapeutic efficiency in HI and the promotion of the cells' directional migration to cerebral HI area by overexpression may be responsible for it, which showed that transplantation of MSCs with HIF-1α overexpression is an attractive therapeutic option to treat HI-induced brain injury in the future. Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.

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

    PubMed

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

    2016-03-01

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

  8. Multicore Considerations for Legacy Flight Software Migration

    NASA Technical Reports Server (NTRS)

    Vines, Kenneth; Day, Len

    2013-01-01

    In this paper we will discuss potential benefits and pitfalls when considering a migration from an existing single core code base to a multicore processor implementation. The results of this study present options that should be considered before migrating fault managers, device handlers and tasks with time-constrained requirements to a multicore flight software environment. Possible future multicore test bed demonstrations are also discussed.

  9. Diet drives the collective migrations and affects the immunity of Mormon crickets and locusts: A comparison of these potential superspreaders of disease

    USDA-ARS?s Scientific Manuscript database

    The need for resources is a major driver of animal migration and yet migration itself is energetically demanding. Mormon crickets and nymphal locusts readily engage in cannibalistic attacks that result in aligned, coordinated movement of individuals in massive bands that march daily for weeks at a ...

  10. Reverse Migration: Western European Muslim Women’s Flights to ISIL Territory

    DTIC Science & Technology

    2015-09-01

    women’s involvement in previous terrorist movements and proposes five potential motivations for migration: grievances toward Western society...voluntarily migrating to ISIL territory to support Islamic extremism. It evaluates women’s involvement in previous terrorist movements and proposes five...connect Western citizens to the pain and suffering in the Middle East. Consequently, they developed remarkably successful recruitment and propaganda

  11. Potential migration of buoyant LNAPL from intermediate level waste (ILW) emplaced in a geological disposal facility (GDF) for U.K. radioactive waste.

    PubMed

    Benbow, Steven J; Rivett, Michael O; Chittenden, Neil; Herbert, Alan W; Watson, Sarah; Williams, Steve J; Norris, Simon

    2014-10-15

    A safety case for the disposal of Intermediate Level (radioactive) Waste (ILW) in a deep geological disposal facility (GDF) requires consideration of the potential for waste-derived light non-aqueous phase liquid (LNAPL) to migrate under positive buoyancy from disposed waste packages. Were entrainment of waste-derived radionuclides in LNAPL to occur, such migration could result in a shorter overall travel time to environmental or human receptors than radionuclide migration solely associated with the movement of groundwater. This paper provides a contribution to the assessment of this issue through multiphase-flow numerical modelling underpinned by a review of the UK's ILW inventory and literature to define the nature of the associated ILW LNAPL source term. Examination has been at the waste package-local GDF environment scale to determine whether proposed disposal of ILW would lead to significant likelihood of LNAPL migration, both from waste packages and from a GDF vault into the local host rock. Our review and numerical modelling support the proposition that the release of a discrete free phase LNAPL from ILW would not present a significant challenge to the safety case even with conservative approximations. 'As-disposed' LNAPL emplaced with the waste is not expected to pose a significant issue. 'Secondary LNAPL' generated in situ within the disposed ILW, arising from the decomposition of plastics, in particular PVC (polyvinyl chloride), could form the predominant LNAPL source term. Released high molecular weight phthalate plasticizers are judged to be the primary LNAPL potentially generated. These are expected to have low buoyancy-based mobility due to their very low density contrast with water and high viscosity. Due to the inherent uncertainties, significant conservatisms were adopted within the numerical modelling approach, including: the simulation of a deliberately high organic material--PVC content wastestream (2D03) within an annular grouted waste package vulnerable to LNAPL release; upper bound inventory estimates of LNAPLs; incorporating the lack of any hydraulic resistance of the package vent; the lack of any degradation of dissolved LNAPL; and, significantly, the small threshold displacement pressure assumed at which LNAPL is able to enter initially water-saturated pores. Initial scoping calculations on the latter suggested that the rate at which LNAPL is able to migrate from a waste package is likely to be very small and insignificant for likely representative displacement pressure data: this represents a key result. Adopting a conservative displacement pressure, however, allowed the effect of other features and processes in the system to be assessed. High LNAPL viscosity together with low density contrast with water reduces LNAPL migration potential. Migration to the host rock is less likely if waste package vent fluxes are small, solubility limits are high and path lengths through the backfill are short. The capacity of the system to dissolve all of the free LNAPL will, however, depend on groundwater availability. Even with the conservatisms invoked, the overall conclusion of model simulations of intact and compromised (cracked or corroded) waste packages, for a range of realistic ILW LNAPL scenarios, is that it is unlikely that significant LNAPL would be able to migrate from the waste packages and even more unlikely it would be sufficiently persistent to reach the host rock immediately beyond the GDF. Copyright © 2014. Published by Elsevier B.V.

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

    PubMed

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

    2010-01-01

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

  13. Diurnal feeding behavior of the American Eel Anguilla rostrata

    USGS Publications Warehouse

    Engman, Augustin C.; Fischer, Jesse R.; Kwak, Thomas J.; Walter, Michael J.

    2017-01-01

    Despite potential to structure ecosystem food webs through top-down effects, the trophic interactions of the American Eel Anguilla rostrata remain largely understudied. All previous research on the trophic ecology of American Eel in inland aquatic ecosystems has been conducted in temperate continental regions of the species' range. These studies have led to a paradigm that American Eel is a nocturnally active benthic predator, which most commonly consumes benthic invertebrates. Tropical island streams and rivers have habitats and communities that are distinct from temperate counterparts, but comprise a large portion of the adult habitat in the American Eel's range. We documented a previously undescribed diurnal feeding behavior by American Eel in a Caribbean river and demonstrate that this behavior, and a shift toward more frequent daytime feeding, is linked to periodic mass migrations of postlarvae of amphidromous fish taxa, including the Sicydiine goby Sicydiumspp. Our findings indicate that periodic mass migrations of amphidromous postlarvae could function as a potentially important food source for American Eel in tropical regions of its distribution, despite the intermittence of availability. Furthermore, this suggests that the American Eel plays an important role in the structure of tropical lotic food webs through top-down effects that are potentially augmented by instream barriers.

  14. The potential for climate-driven bathymetric range shifts: sustained temperature and pressure exposures on a marine ectotherm, Palaemonetes varians

    PubMed Central

    Morris, J. P.; Thatje, S.; Cottin, D.; Oliphant, A.; Brown, A.; Shillito, B.; Ravaux, J.; Hauton, C.

    2015-01-01

    Range shifts are of great importance as a response for species facing climate change. In the light of current ocean-surface warming, many studies have focused on the capacity of marine ectotherms to shift their ranges latitudinally. Bathymetric range shifts offer an important alternative, and may be the sole option for species already at high latitudes or those within enclosed seas; yet relevant data are scant. Hydrostatic pressure (HP) and temperature have wide ranging effects on physiology, importantly acting in synergy thermodynamically, and therefore represent key environmental constraints to bathymetric migration. We present data on transcriptional regulation in a shallow-water marine crustacean (Palaemonetes varians) at atmospheric and high HP following 168-h exposures at three temperatures across the organisms’ thermal scope, to establish the potential physiological limit to bathymetric migration by neritic fauna. We observe changes in gene expression indicative of cellular macromolecular damage, disturbances in metabolic pathways and a lack of acclimation after prolonged exposure to high HP. Importantly, these effects are ameliorated (less deleterious) at higher temperatures, and exacerbated at lower temperatures. These data, alongside previously published behavioural and heat-shock analyses, have important implications for our understanding of the potential for climate-driven bathymetric range shifts PMID:26716003

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

    PubMed Central

    Turner, Kathryn L.; Sontheimer, Harald

    2014-01-01

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

  16. Envisioning migration: Mathematics in both experimental analysis and modeling of cell behavior

    PubMed Central

    Zhang, Elizabeth R.; Wu, Lani F.; Altschuler, Steven J.

    2013-01-01

    The complex nature of cell migration highlights the power and challenges of applying mathematics to biological studies. Mathematics may be used to create model equations that recapitulate migration, which can predict phenomena not easily uncovered by experiments or intuition alone. Alternatively, mathematics may be applied to interpreting complex data sets with better resolution—potentially empowering scientists to discern subtle patterns amid the noise and heterogeneity typical of migrating cells. Iteration between these two methods is necessary in order to reveal connections within the cell migration signaling network, as well as to understand the behavior that arises from those connections. Here, we review recent quantitative analysis and mathematical modeling approaches to the cell migration problem. PMID:23660413

  17. Envisioning migration: mathematics in both experimental analysis and modeling of cell behavior.

    PubMed

    Zhang, Elizabeth R; Wu, Lani F; Altschuler, Steven J

    2013-10-01

    The complex nature of cell migration highlights the power and challenges of applying mathematics to biological studies. Mathematics may be used to create model equations that recapitulate migration, which can predict phenomena not easily uncovered by experiments or intuition alone. Alternatively, mathematics may be applied to interpreting complex data sets with better resolution--potentially empowering scientists to discern subtle patterns amid the noise and heterogeneity typical of migrating cells. Iteration between these two methods is necessary in order to reveal connections within the cell migration signaling network, as well as to understand the behavior that arises from those connections. Here, we review recent quantitative analysis and mathematical modeling approaches to the cell migration problem. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. An exploratory study of internal migration and substance use among an indigenous community in Southern Mexico

    PubMed Central

    Pinedo, Miguel; Sim, D. Eastern Kang; Giacinto, Rebeca Espinoza; Zúñiga, María Luisa

    2015-01-01

    The primary aim of this study was to explore the association between internal migration experience within Mexico and lifetime substance use among a sample of 442 indigenous persons from Yucatan, Mexico. Adjusting for potential confounding, correlates of lifetime substance use were assessed among participants with and without internal migration experience. Internal migration to a tourist destination was independently associated with higher odds (Adjusted Odds Ratio (AOR): 2.1; 95% Confidence Interval (CI): 1.3-3.4) of reporting lifetime substance use. Findings suggest that environmental contexts of internal migration may be of importance in shaping vulnerability to substance use. PMID:26605952

  19. The novel kinase inhibitor ponatinib is an effective anti-angiogenic agent against neuroblastoma.

    PubMed

    Whittle, Sarah B; Patel, Kalyani; Zhang, Linna; Woodfield, Sarah E; Du, Michael; Smith, Valeria; Zage, Peter E

    2016-12-01

    Background High-risk neuroblastoma has poor outcomes with high rates of relapse despite aggressive treatment, and novel therapies are needed to improve these outcomes. Ponatinib is a multi-tyrosine kinase inhibitor that targets many pathways implicated in neuroblastoma pathogenesis. We hypothesized that ponatinib would be effective against neuroblastoma in preclinical models. Methods We evaluated the effects of ponatinib on survival and migration of human neuroblastoma cells in vitro. Using orthotopic xenograft mouse models of human neuroblastoma, we analyzed tumors treated with ponatinib for growth, gross and histologic appearance, and vascularity. Results Ponatinib treatment of neuroblastoma cells resulted in decreased cell viability and migration in vitro. In mice with orthotopic xenograft neuroblastoma tumors, treatment with ponatinib resulted in decreased growth and vascularity. Conclusions Ponatinib reduces neuroblastoma cell viability in vitro and reduces tumor growth and vascularity in vivo. The antitumor effects of ponatinib suggest its potential as a novel therapeutic agent for neuroblastoma, and further preclinical testing is warranted.

  20. Inhibitory effect of D3 dopamine receptors on neuropeptide Y‑induced migration in vascular smooth muscle cells.

    PubMed

    Xia, Xue-Wei; Zhou, Yong-Qiao; Luo, Hao; Zeng, Chunyu

    2017-10-01

    Abnormal migration of vascular smooth muscle cells (VSMCs) serves an important role in hypertension, atherosclerosis and restenosis following angioplasty, which is regulated numerous hormonal and humoral factors, including neuropeptide Y (NPY) and dopamine. Dopamine and NPY are both sympathetic neurotransmitters, and a previous study reported that NPY increased VSMC proliferation, while dopamine receptor inhibited it. Therefore, the authors wondered whether or not there is an inhibitory effect of dopamine receptor on NPY‑mediated VSMC migration. The present study demonstrated that stimulation with NPY dose‑dependence (10‑10‑10‑7M, 24 h) increased VSMC migration, the stimulatory effect of NPY was via the Y1 receptor. This is because, in the presence of the Y1 receptor antagonist, BIBP3226 (10‑7 M), the stimulatory effect of NPY on VSMC migration was blocked. Activation of the D3 receptor by PD128907 dose‑dependence (10‑11‑10‑8 M) reduced the stimulatory effect of NPY on VSMC migration. The effect of PD128907 was via the D3 receptor, because the inhibitory effect of PD128907 on NPY‑mediated migration was blocked by the D3 receptor antagonist, U99194. The authors' further study suggested that the inhibitory effect of the D3 receptor was via the PKA signaling pathway, in the presence of the PKA inhibitor, 14‑22 (10‑6 M), the inhibitory effect of PD128907 on VSMC migration was blocked. Moreover, the inhibitory effect of PD128907 was imitated by PKA activator, Sp‑cAMP [S], in the presence of Sp‑cAMP [S], the NPY‑mediated stimulatory effect on VSMC migration was abolished. The present study indicated that activation of the D3 receptor inhibits NPY Y1‑mediated migration on VSMCs, PKA is involved in the signaling pathway.

  1. Migration in the context of vulnerability and adaptation to climate change: insights from analogues

    PubMed Central

    McLeman, Robert A.; Hunter, Lori M.

    2011-01-01

    Migration is one of the variety of ways by which human populations adapt to environmental changes. The study of migration in the context of anthropogenic climate change is often approached using the concept of vulnerability and its key functional elements: exposure, system sensitivity, and adaptive capacity. This article explores the interaction of climate change and vulnerability through review of case studies of dry-season migration in the West African Sahel, hurricane-related population displacements in the Caribbean basin, winter migration of ‘snowbirds’ to the US Sun-belt, and 1930s drought migration on the North American Great Plains. These examples are then used as analogues for identifying general causal, temporal, and spatial dimensions of climate migration, along with potential considerations for policy-making and future research needs. PMID:22022342

  2. Cigarette smoking hinders human periodontal ligament-derived stem cell proliferation, migration and differentiation potentials

    PubMed Central

    Ng, Tsz Kin; Huang, Li; Cao, Di; Yip, Yolanda Wong-Ying; Tsang, Wai Ming; Yam, Gary Hin-Fai; Pang, Chi Pui; Cheung, Herman S.

    2015-01-01

    Cigarette smoking contributes to the development of destructive periodontal diseases and delays its healing process. Our previous study demonstrated that nicotine, a major constituent in the cigarette smoke, inhibits the regenerative potentials of human periodontal ligament-derived stem cells (PDLSC) through microRNA (miRNA) regulation. In this study, we hypothesized that the delayed healing in cigarette smokers is caused by the afflicted regenerative potential of smoker PDLSC. We cultured PDLSC from teeth extracted from smokers and non-smokers. In smoker PDLSC, we found significantly reduced proliferation rate and retarded migration capabilities. Moreover, alkaline phosphatase activity, calcium deposition and acidic polysaccharide staining were reduced after BMP2-induced differentiation. In contrast, more lipid deposition was observed in adipogenic-induced smoker PDLSC. Furthermore, two nicotine-related miRNAs, hsa-miR-1305 (22.08 folds, p = 0.040) and hsa-miR-18b (15.56 folds, p = 0.018), were significantly upregulated in smoker PDLSC, suggesting these miRNAs might play an important role in the deteriorative effects on stem cells by cigarette smoke. Results of this study provide further evidences that cigarette smoking affects the regenerative potentials of human adult stem cells. PMID:25591783

  3. Cigarette smoking hinders human periodontal ligament-derived stem cell proliferation, migration and differentiation potentials.

    PubMed

    Ng, Tsz Kin; Huang, Li; Cao, Di; Yip, Yolanda Wong-Ying; Tsang, Wai Ming; Yam, Gary Hin-Fai; Pang, Chi Pui; Cheung, Herman S

    2015-01-16

    Cigarette smoking contributes to the development of destructive periodontal diseases and delays its healing process. Our previous study demonstrated that nicotine, a major constituent in the cigarette smoke, inhibits the regenerative potentials of human periodontal ligament-derived stem cells (PDLSC) through microRNA (miRNA) regulation. In this study, we hypothesized that the delayed healing in cigarette smokers is caused by the afflicted regenerative potential of smoker PDLSC. We cultured PDLSC from teeth extracted from smokers and non-smokers. In smoker PDLSC, we found significantly reduced proliferation rate and retarded migration capabilities. Moreover, alkaline phosphatase activity, calcium deposition and acidic polysaccharide staining were reduced after BMP2-induced differentiation. In contrast, more lipid deposition was observed in adipogenic-induced smoker PDLSC. Furthermore, two nicotine-related miRNAs, hsa-miR-1305 (22.08 folds, p = 0.040) and hsa-miR-18b (15.56 folds, p = 0.018), were significantly upregulated in smoker PDLSC, suggesting these miRNAs might play an important role in the deteriorative effects on stem cells by cigarette smoke. Results of this study provide further evidences that cigarette smoking affects the regenerative potentials of human adult stem cells.

  4. Coupling between oxygen redox and cation migration explains unusual electrochemistry in lithium-rich layered oxides

    DOE PAGES

    Gent, William E.; Lim, Kipil; Liang, Yufeng; ...

    2017-12-01

    © 2017 The Author(s). Lithium-rich layered transition metal oxide positive electrodes offer access to anion redox at high potentials, thereby promising high energy densities for lithium-ion batteries. However, anion redox is also associated with several unfavorable electrochemical properties, such as open-circuit voltage hysteresis. Here we reveal that in Li 1.17-x Ni 0.21 Co 0.08 Mn 0.54 O 2 , these properties arise from a strong coupling between anion redox and cation migration. We combine various X-ray spectroscopic, microscopic, and structural probes to show that partially reversible transition metal migration decreases the potential of the bulk oxygen redox couple by >more » 1 V, leading to a reordering in the anionic and cationic redox potentials during cycling. First principles calculations show that this is due to the drastic change in the local oxygen coordination environments associated with the transition metal migration. We propose that this mechanism is involved in stabilizing the oxygen redox couple, which we observe spectroscopically to persist for 500 charge/discharge cycles.« less

  5. Coupling between oxygen redox and cation migration explains unusual electrochemistry in lithium-rich layered oxides

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

    Gent, William E.; Lim, Kipil; Liang, Yufeng

    © 2017 The Author(s). Lithium-rich layered transition metal oxide positive electrodes offer access to anion redox at high potentials, thereby promising high energy densities for lithium-ion batteries. However, anion redox is also associated with several unfavorable electrochemical properties, such as open-circuit voltage hysteresis. Here we reveal that in Li 1.17-x Ni 0.21 Co 0.08 Mn 0.54 O 2 , these properties arise from a strong coupling between anion redox and cation migration. We combine various X-ray spectroscopic, microscopic, and structural probes to show that partially reversible transition metal migration decreases the potential of the bulk oxygen redox couple by >more » 1 V, leading to a reordering in the anionic and cationic redox potentials during cycling. First principles calculations show that this is due to the drastic change in the local oxygen coordination environments associated with the transition metal migration. We propose that this mechanism is involved in stabilizing the oxygen redox couple, which we observe spectroscopically to persist for 500 charge/discharge cycles.« less

  6. The extract from Punica granatum (pomegranate) peel induces apoptosis and impairs metastasis in prostate cancer cells.

    PubMed

    Deng, Yuanle; Li, Yali; Yang, Fangfang; Zeng, Anqi; Yang, Shuping; Luo, Yi; Zhang, Yiwen; Xie, Yongmei; Ye, Tinghong; Xia, Yong; Yin, Wenya

    2017-09-01

    Prostate cancer is a big threat to male for its poor prognosis and high mortality rate. Natural compounds are important resources of many anticancer drugs. Pomegranate is a kind of antioxidant-rich fruit and its peel and seed has potential anticancer activities. In this study, we aimed to investigate the effects of pomegranate peel extract (PoPx) on the apoptosis and metastasis of prostate cancer cells and the related mechanism. We found that PoPx showed growth inhibition on prostate cancer cells. Nuclei morphological and flow cytometer (FCM) analysis indicated that PoPx could induce prostate cancer apoptosis. Further investigation indicated that mitochondrial mediated intrinsic pathway is involved in the apoptosis. Exposure to PoPx led to loss of mitochondrial transmembrane potential (Δym), accumulation of reactive oxygen species (ROS). Western blot analysis showed that PoPx could increase the expression ratio of Bax/Bcl2 and activation of apoptosis executor caspase 3. Wound healing assay and transwell migration and invasion assay implied that PoPx has the potential to inhibit migration and invasion, two critical steps in prostate cancer metastasis. Downregulation of MMP2/MMP9 and upregulation of TIMP2 showed accordance with the inhibition of migration and invasion. In summary, the present data showed that PoPx could be a promising drug candidate to treat prostate cancer, showing us a better way to develop novel drugs from natural compounds. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Modification of smoke toxicant yields alters the effects of cigarette smoke extracts on endothelial migration: an in vitro study using a cardiovascular disease model.

    PubMed

    Fearon, Ian M; Acheampong, Daniel O; Bishop, Emma

    2012-01-01

    Endothelial damage plays a key role in atherosclerosis and this is impacted upon by numerous risk factors including cigarette smoking. A potential measure to reduce the cardiovascular burden associated with smoking is to reduce smoke toxicant exposure. In an in vitro endothelial damage repair assay, endothelial cell migration was inhibited by cigarette smoke particulate matter (PM) generated from several cigarette types. This inhibition was reduced when cells were exposed to PM from an experimental cigarette with reduced smoke toxicant levels. As a number of toxicants induce oxidative stress and since oxidative stress may link cigarette smoke and endothelial damage, we hypothesized that PM effects were dependent on elevated cellular oxidants. However, although PM-induced cellular oxidant production could be inhibited by ascorbic acid or n-acetylcysteine, both these antioxidants were without effect on migration responses to PM. Furthermore, reactive oxygen species production, as indicated by dihydroethidium fluorescence, was not different in cells exposed to smoke from cigarettes with different toxicant levels. In summary, our data demonstrate that a cardiovascular disease-related biological response may be modified when cells are exposed to smoke containing different levels of toxicants. This appeared independent of the induction of oxidative stress.

  8. A Foraging Cost of Migration for a Partially Migratory Cyprinid Fish

    PubMed Central

    Chapman, Ben B.; Eriksen, Anders; Baktoft, Henrik; Brodersen, Jakob; Nilsson, P. Anders; Hulthen, Kaj; Brönmark, Christer; Hansson, Lars-Anders; Grønkjær, Peter; Skov, Christian

    2013-01-01

    Migration has evolved as a strategy to maximise individual fitness in response to seasonally changing ecological and environmental conditions. However, migration can also incur costs, and quantifying these costs can provide important clues to the ultimate ecological forces that underpin migratory behaviour. A key emerging model to explain migration in many systems posits that migration is driven by seasonal changes to a predation/growth potential (p/g) trade-off that a wide range of animals face. In this study we assess a key assumption of this model for a common cyprinid partial migrant, the roach Rutilus rutilus, which migrates from shallow lakes to streams during winter. By sampling fish from stream and lake habitats in the autumn and spring and measuring their stomach fullness and diet composition, we tested if migrating roach pay a cost of reduced foraging when migrating. Resident fish had fuller stomachs containing more high quality prey items than migrant fish. Hence, we document a feeding cost to migration in roach, which adds additional support for the validity of the p/g model of migration in freshwater systems. PMID:23723967

  9. Determinants of Mexico-U.S. Outward and Return Migration Flows: A State-Level Panel Data Analysis.

    PubMed

    Chort, Isabelle; de la Rupelle, Maëlys

    2016-10-01

    Using a unique panel data set of state-to-state outward and return migration flows between Mexico and the United States from 1995 to 2012, this study is the first to analyze Mexico-U.S. migration at the state level and explore simultaneously the effect of economic, environmental, and social factors in Mexico over two decades. Pairing origin and destination states and controlling for a rich structure of fixed effects, we find that income positively impacts migration outflows, especially for Mexican states of origin with a recent migration history and for low-educated migrant flows, suggesting the existence of credit constraints. We find evidence that drought causes more out-migration, while other climatic shocks have no effect. Violence is found to increase out-migration flows from border states and to decrease migration from other Mexican states, especially where violence is directed at migrants. Last, return flows are larger when income growth at destination is lower, consistent with the accumulation of savings as a primary motivation of migrants. Exploring the impact of the crisis, we find evidence of significant changes in the geography of migration flows. Traditional flows are drying up, and new migration corridors are rising, with implications on the composition of the Mexican population in the United States. Although the effect of income on flows in both directions is unchanged by the crisis, the negative effect of violence on out-migration tends to reverse at the end of the period. Overall, this study emphasizes the interest of analyzing disaggregated flows at the infra-country level.

  10. Effects of topical budesonide on epithelial restitution in vivo in guinea pig trachea.

    PubMed Central

    Erjefält, J. S.; Erjefält, I.; Sundler, F.; Persson, C. G.

    1995-01-01

    BACKGROUND--Continuous epithelial shedding and restitution processes may characterise the airways in diseases such as asthma. Epithelial restitution involves several humoral and cellular mechanisms that may potentially be affected by inhaled anti-asthma drugs. The present study examines the effect of a topical steroid on epithelial restitution in vivo in the guinea pig. METHODS--The airway epithelium was mechanically removed from well defined areas of guinea pig trachea without surgery and without damage to the basement membrane or bleeding. An anti-inflammatory dose of budesonide (1 mg) was administered repeatedly to the tracheal surface by local superfusion 24 hours before, at (0 hours), and 24 hours after the denudation. Migration of epithelial cells, formation of a plasma exudation-derived gel, and appearance of luminal leucocytes were recorded by scanning electron microscopy. Cell proliferation was visualised by bromodeoxyuridine immunohistochemistry and tissue neutrophils and eosinophils by enzyme histochemistry. RESULTS--Immediately after creation of the denuded zone ciliated and secretory cells on its border dedifferentiated, flattened out, and migrated speedily (mean (SE) 2.3 (0.3) micron/min) over the basement membrane. After 48 hours the entire denuded zone (800 microns wide) was covered by a tightly sealed epithelium; at this time increased proliferation was observed in new and old epithelium and subepithelial cells. Budesonide had no detectable effect on epithelial dedifferentiation, migration, sealing, or proliferation. Immediately after denudation and continuously during the migration phase plasma was extravasated creating a fibrinous gel rich in leucocytes, particularly neutrophils, over the denuded area. Budesonide had no effect on either the gel or the leucocyte density. CONCLUSIONS--These observations suggest that topical glucocorticoids may not interfere with a fast and efficient restitution of the epithelium in the airways. Images PMID:7570417

  11. Sociocultural behavior, sex-biased admixture, and effective population sizes in Central African Pygmies and non-Pygmies.

    PubMed

    Verdu, Paul; Becker, Noémie S A; Froment, Alain; Georges, Myriam; Grugni, Viola; Quintana-Murci, Lluis; Hombert, Jean-Marie; Van der Veen, Lolke; Le Bomin, Sylvie; Bahuchet, Serge; Heyer, Evelyne; Austerlitz, Frédéric

    2013-04-01

    Sociocultural phenomena, such as exogamy or phylopatry, can largely determine human sex-specific demography. In Central Africa, diverging patterns of sex-specific genetic variation have been observed between mobile hunter-gatherer Pygmies and sedentary agricultural non-Pygmies. However, their sex-specific demography remains largely unknown. Using population genetics and approximate Bayesian computation approaches, we inferred male and female effective population sizes, sex-specific migration, and admixture rates in 23 Central African Pygmy and non-Pygmy populations, genotyped for autosomal, X-linked, Y-linked, and mitochondrial markers. We found much larger effective population sizes and migration rates among non-Pygmy populations than among Pygmies, in agreement with the recent expansions and migrations of non-Pygmies and, conversely, the isolation and stationary demography of Pygmy groups. We found larger effective sizes and migration rates for males than for females for Pygmies, and vice versa for non-Pygmies. Thus, although most Pygmy populations have patrilocal customs, their sex-specific genetic patterns resemble those of matrilocal populations. In fact, our results are consistent with a lower prevalence of polygyny and patrilocality in Pygmies compared with non-Pygmies and a potential female transmission of reproductive success in Pygmies. Finally, Pygmy populations showed variable admixture levels with the non-Pygmies, with often much larger introgression from male than from female lineages. Social discrimination against Pygmies triggering complex movements of spouses in intermarriages can explain these male-biased admixture patterns in a patrilocal context. We show how gender-related sociocultural phenomena can determine highly variable sex-specific demography among populations, and how population genetic approaches contrasting chromosomal types allow inferring detailed human sex-specific demographic history.

  12. Sociocultural Behavior, Sex-Biased Admixture, and Effective Population Sizes in Central African Pygmies and Non-Pygmies

    PubMed Central

    Verdu, Paul; Becker, Noémie S.A.; Froment, Alain; Georges, Myriam; Grugni, Viola; Quintana-Murci, Lluis; Hombert, Jean-Marie; Van der Veen, Lolke; Le Bomin, Sylvie; Bahuchet, Serge; Heyer, Evelyne; Austerlitz, Frédéric

    2013-01-01

    Sociocultural phenomena, such as exogamy or phylopatry, can largely determine human sex-specific demography. In Central Africa, diverging patterns of sex-specific genetic variation have been observed between mobile hunter–gatherer Pygmies and sedentary agricultural non-Pygmies. However, their sex-specific demography remains largely unknown. Using population genetics and approximate Bayesian computation approaches, we inferred male and female effective population sizes, sex-specific migration, and admixture rates in 23 Central African Pygmy and non-Pygmy populations, genotyped for autosomal, X-linked, Y-linked, and mitochondrial markers. We found much larger effective population sizes and migration rates among non-Pygmy populations than among Pygmies, in agreement with the recent expansions and migrations of non-Pygmies and, conversely, the isolation and stationary demography of Pygmy groups. We found larger effective sizes and migration rates for males than for females for Pygmies, and vice versa for non-Pygmies. Thus, although most Pygmy populations have patrilocal customs, their sex-specific genetic patterns resemble those of matrilocal populations. In fact, our results are consistent with a lower prevalence of polygyny and patrilocality in Pygmies compared with non-Pygmies and a potential female transmission of reproductive success in Pygmies. Finally, Pygmy populations showed variable admixture levels with the non-Pygmies, with often much larger introgression from male than from female lineages. Social discrimination against Pygmies triggering complex movements of spouses in intermarriages can explain these male-biased admixture patterns in a patrilocal context. We show how gender-related sociocultural phenomena can determine highly variable sex-specific demography among populations, and how population genetic approaches contrasting chromosomal types allow inferring detailed human sex-specific demographic history. PMID:23300254

  13. Formononetin inhibits migration and invasion of MDA-MB-231 and 4T1 breast cancer cells by suppressing MMP-2 and MMP-9 through PI3K/AKT signaling pathways.

    PubMed

    Zhou, R; Xu, L; Ye, M; Liao, M; Du, H; Chen, H

    2014-10-01

    Formononetin is a naturally existing isoflavone, which can be found in the roots of Astragalus membranaceus, Trifolium pratense, Glycyrrhiza glabra, and Pueraria lobata. It was found to be associated with inhibition of cell proliferation and cell cycle progression, as well as induction of apoptosis in various cancer cell lines. However, the effect of formononetin on breast cancer cell metastasis remains unclear. In this study, we examined the effect of formononetin on the migration and invasion of breast cancer cells MDA-MB-231 and 4T1 in vitro and in vivo. Our data demonstrated that formononetin did not effectively inhibit the cell viability of MDA-MB-231 and 4T1 in 24 h with the concentration lower than 160 μmol/l. When treated with nontoxic concentration of formononetin, the migration and invasion of MDA-MB-231 and 4T1 cells were markedly suppressed by wound healing assay, chamber invasion assay, and in vivo mouse metastasis model. In vitro, formononetin reduced the expression of matrix metalloproteinase-2 (MMP-2), MMP-9 and increased the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. Furthermore, the immunofluorescence and immunoblotting assays indicated that formononetin was very effective in suppressing the phosphorylation of Akt and PI3K. Collectively, these results suggest that formononetin inhibited breast cancer cell migration and invasion by reducing the expression of MMP-2 and MMP-9 through the PI3K/AKT signaling pathway. These findings demonstrate a potentially new therapeutic strategy of formononetin as anti-invasive agent for breast cancer. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Vertical Migration Potential of Metal Contaminants at Small Arms Firing Ranges, Camp Edwards Military Reservation, Massachusetts.

    DTIC Science & Technology

    1998-03-01

    halloysite on lead concentration in solution 57 Figure 41. Solubility of lead carbonate as a function of pH for a total activity aH2C03...Effects of adsorption by halloysite (a clay) on lead concentration in solution. Contours are equilibrium lead concentrations at different clay

  15. Arthropods and associated arthropod-borne diseases transmitted by migrating birds. The case of ticks and tick-borne pathogens.

    PubMed

    Sparagano, Olivier; George, David; Giangaspero, Annunziata; Špitalská, Eva

    2015-09-30

    Geographic spread of parasites and pathogens poses a constant risk to animal health and welfare, particularly given that climate change is expected to potentially expand appropriate ranges for many key species. The spread of deleterious organisms via trade routes and human travelling is relatively closely controlled, though represents only one possible means of parasite/pathogen distribution. The transmission via natural parasite/pathogen movement between geographic locales, is far harder to manage. Though the extent of such movement may be limited by the relative inability of many parasites and pathogens to actively migrate, passive movement over long distances may still occur via migratory hosts. This paper reviews the potential role of migrating birds in the transfer of ectoparasites and pathogens between geographic locales, focusing primarily on ticks. Bird-tick-pathogen relationships are considered, and evidence provided of long-range parasite/pathogen transfer from one location to another during bird migration events. As shown in this paper not only many different arthropod species are carried by migrating birds but consequently these pests carry many different pathogens species which can be transmitted to the migrating birds or to other animal species when those arthropods are dropping during these migrations. Data available from the literature are provided highlighting the need to understand better dissemination paths and disease epidemiology. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. 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.

  17. In vitro migration and proliferation ("wound healing") potential of mesenchymal stromal cells generated from human CD271(+) bone marrow mononuclear cells.

    PubMed

    Latifi-Pupovci, Hatixhe; Kuçi, Zyrafete; Wehner, Sibylle; Bönig, Halvard; Lieberz, Ralf; Klingebiel, Thomas; Bader, Peter; Kuçi, Selim

    2015-09-25

    Emerging evidence indicates that mesenchymal stromal cells (MSCs) isolated from different tissue sources may be used in vivo as tissue restorative agents. To date, there is no evidence, however, on migration and proliferation ("wound healing") potential of different subsets of MSCs. The main goal of this study was therefore to compare the in vitro "wound healing" capacity of MSCs generated from positively selected CD271(+) bone marrow mononuclear cells (CD271-MSCs) and MSCs generated by plastic adherence (PA-MSCs). The in vitro model of wound healing (CytoSelect™ 24-Well Wound Healing Assay) was used in order to compare the migration and proliferation potential of CD271-MSCs and PA-MSCs of passage 2 and 4 cultured in presence or absence of growth factors or cytokines. CD271-MSCs of both passages when compared to PA-MSCs demonstrated a significantly higher potential to close the wound 12 and 24 h after initiation of the wound healing assay (P < 0.003 and P < 0.002, respectively). Noteworthy, the migration capacity of PA-MSCs of second passage was significantly improved after stimulation with FGF-2 (P < 0.02), PDGF-BB (P < 0.006), MCP-1 (P < 0.002) and IL-6 (P < 0.03), whereas only TGF-β enhanced significantly migration process of PA-MSCs of P4 12 h after the treatment (P < 0.02). Interestingly, treatment of CD271-MSCs of both passages with growth factors or cytokines did not affect their migratory potential. Our in vitro data provide the first evidence that CD271-MSCs are significantly more potent in "wound healing" than their counterparts PA-MSCs.

  18. EDUCATION, GENDER, AND MIGRATION IN THE CONTEXT OF SOCIAL CHANGE

    PubMed Central

    Williams, Nathalie

    2012-01-01

    Although sociologists have identified education as likely determinant of migration, the ways in which education affects migration are unclear and empirical results are disparate. This paper addresses the relationship between educational attainment, enrolment, and migration, focusing on the role of gender and how it changes with evolving social contexts. Using empirical analyses based in Nepal, results indicate that educational attainment has positive effects and enrolment has negative effects on out-migration and including enrolment in the model increases the effect of attainment. In the case of women, with the changing role of gender, increased education and labor force participation, the affect of educational attainment changes drastically over time, from almost no effect, to a strong positive effect. Consideration of enrolment, and the role of gender in education, employment, and marriage may help to explain the disparate results in past research on education and migration. PMID:20645440

  19. The crude extract of Corni Fructus inhibits the migration and invasion of U-2 OS human osteosarcoma cells through the inhibition of matrix metalloproteinase-2/-9 by MAPK signaling.

    PubMed

    Liao, Ching-Lung; Lin, Ju-Hwa; Lien, Jin-Cherng; Hsu, Shu-Chun; Chueh, Fu-Shin; Yu, Chien-Chih; Wu, Ping-Ping; Huang, Yi-Ping; Lin, Jaung-Geng; Chung, Jing-Gung

    2015-01-01

    Osteosarcoma is the most common primary malignancy of the bone cancers. In the Chinese population, the crude extract of Corni Fructus (CECF) has been used as Traditional Chinese medicine to treat several different diseases for hundreds of years. In the present study, effects of CECF on inhibition of migration and invasion in U-2 OS human osteosarcoma cells were examined. CECF significantly inhibited migration and invasion of U-2 OS human osteosarcoma cells. We also found that CECF inhibited activities of matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9). CECF decreased protein levels of FAK, PKC, SOS1, MKK7, MEKK3, GRB2, NF-κB p65, COX-2, HIF-1α, PI3K, Rho A, ROCK-1, IRE-1α, p-JNK1/2, p-ERK1/2, p-p38, Ras, p-PERK, MMP-2, MMP-9, and VEGF in U-2 OS cells. Results of this study indicate that CECF may have potential as a novel anticancer agent for the treatment of osteosarcoma by inhibiting migration and invasion of cancer cells. © 2013 Wiley Periodicals, Inc.

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

    PubMed

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

    2015-05-01

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

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