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Sample records for actively regulated barrier

  1. Checkpoint Kinase 1 Activation Enhances Intestinal Epithelial Barrier Function via Regulation of Claudin-5 Expression.

    Directory of Open Access Journals (Sweden)

    Akihiro Watari

    Full Text Available Several stressors are known to influence epithelial tight junction (TJ integrity, but the association between DNA damage and TJ integrity remains unclear. Here we examined the effects of daunorubicin and rebeccamycin, two anti-tumor chemicals that induce DNA damage, on TJ integrity in human intestinal epithelial cells. Daunorubicin and rebeccamycin dose-dependently enhanced transepithelial electrical resistance (TER and decreased flux of the 4 kDa FITC-dextran in Caco-2 cell monolayer. Daunorubicin- or rebeccamycin-induced enhancement of the TJ barrier function partly rescued attenuation of the barrier function by the inflammatory cytokines TNF-α and IFN-γ. Daunorubicin and rebeccamycin increased claudin-5 expression and the product was distributed in the actin cytoskeleton fraction, which was enriched with TJ proteins. Caffeine, which is an inhibitor of ataxia telangiectasia mutated protein (ATM and ataxia telangiectasia mutated and Rad3-related protein (ATR, and the Chk1 inhibitor inhibited the TER increases induced by daunorubicin and rebeccamycin, whereas a Chk2 inhibitor did not. Treatment with Chk1 siRNA also significantly inhibited the TER increases. Induction of claudin-5 expression was inhibited by Chk1 inhibitor and by siRNA treatment. Our results suggest that Chk1 activation by daunorubicin and rebeccamycin induced claudin-5 expression and enhanced TJ barrier function in Caco-2 cell monolayer, which suggests a link between DNA damage and TJ integrity in the human intestine.

  2. Checkpoint Kinase 1 Activation Enhances Intestinal Epithelial Barrier Function via Regulation of Claudin-5 Expression.

    Science.gov (United States)

    Watari, Akihiro; Hasegawa, Maki; Yagi, Kiyohito; Kondoh, Masuo

    2016-01-01

    Several stressors are known to influence epithelial tight junction (TJ) integrity, but the association between DNA damage and TJ integrity remains unclear. Here we examined the effects of daunorubicin and rebeccamycin, two anti-tumor chemicals that induce DNA damage, on TJ integrity in human intestinal epithelial cells. Daunorubicin and rebeccamycin dose-dependently enhanced transepithelial electrical resistance (TER) and decreased flux of the 4 kDa FITC-dextran in Caco-2 cell monolayer. Daunorubicin- or rebeccamycin-induced enhancement of the TJ barrier function partly rescued attenuation of the barrier function by the inflammatory cytokines TNF-α and IFN-γ. Daunorubicin and rebeccamycin increased claudin-5 expression and the product was distributed in the actin cytoskeleton fraction, which was enriched with TJ proteins. Caffeine, which is an inhibitor of ataxia telangiectasia mutated protein (ATM) and ataxia telangiectasia mutated and Rad3-related protein (ATR), and the Chk1 inhibitor inhibited the TER increases induced by daunorubicin and rebeccamycin, whereas a Chk2 inhibitor did not. Treatment with Chk1 siRNA also significantly inhibited the TER increases. Induction of claudin-5 expression was inhibited by Chk1 inhibitor and by siRNA treatment. Our results suggest that Chk1 activation by daunorubicin and rebeccamycin induced claudin-5 expression and enhanced TJ barrier function in Caco-2 cell monolayer, which suggests a link between DNA damage and TJ integrity in the human intestine.

  3. Arhgap17, a RhoGTPase activating protein, regulates mucosal and epithelial barrier function in the mouse colon

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    Lee, So-young; Kim, Hwain; Kim, Kyoungmi; Lee, Hyunji; Lee, Seungbok; Lee, Daekee

    2016-01-01

    Coordinated regulation of the actin cytoskeleton by the Rho GTPase family is required for the maintenance of polarity in epithelial cells as well as for their proliferation and migration. A RhoGTPase-activating protein 17 (Arhgap17) is known to be involved in multiple cellular processes in vitro, including the maintenance of tight junctions and vesicle trafficking. However, the function of Arhgap17 has not been studied in the physiological context. Here, we generated Arhgap17-deficient mice and examined the effect in the epithelial and mucosal barriers of the intestine. Reporter staining revealed that Arhgap17 expression is limited to the luminal epithelium of intestine. Arhgap17-deficient mice show an increased paracellular permeability and aberrant localization of the apical junction complex in the luminal epithelium, but do not develop spontaneous colitis. The inner mucus layer is impervious to the enteric bacteria irrespective of Tff3 downregulation in the Arhgap17-deficient mice. Interestingly however, treatment with dextran sulfate sodium (DSS) causes an increased accumulation of DSS and TNF production in intraluminal cells and rapid destruction of the inner mucus layer, resulting in increased severity of colitis in mutant mice. Overall, these data reveal that Arhgap17 has a novel function in regulating transcellular transport and maintaining integrity of intestinal barriers. PMID:27229483

  4. Arhgap17, a RhoGTPase activating protein, regulates mucosal and epithelial barrier function in the mouse colon.

    Science.gov (United States)

    Lee, So-Young; Kim, Hwain; Kim, Kyoungmi; Lee, Hyunji; Lee, Seungbok; Lee, Daekee

    2016-01-01

    Coordinated regulation of the actin cytoskeleton by the Rho GTPase family is required for the maintenance of polarity in epithelial cells as well as for their proliferation and migration. A RhoGTPase-activating protein 17 (Arhgap17) is known to be involved in multiple cellular processes in vitro, including the maintenance of tight junctions and vesicle trafficking. However, the function of Arhgap17 has not been studied in the physiological context. Here, we generated Arhgap17-deficient mice and examined the effect in the epithelial and mucosal barriers of the intestine. Reporter staining revealed that Arhgap17 expression is limited to the luminal epithelium of intestine. Arhgap17-deficient mice show an increased paracellular permeability and aberrant localization of the apical junction complex in the luminal epithelium, but do not develop spontaneous colitis. The inner mucus layer is impervious to the enteric bacteria irrespective of Tff3 downregulation in the Arhgap17-deficient mice. Interestingly however, treatment with dextran sulfate sodium (DSS) causes an increased accumulation of DSS and TNF production in intraluminal cells and rapid destruction of the inner mucus layer, resulting in increased severity of colitis in mutant mice. Overall, these data reveal that Arhgap17 has a novel function in regulating transcellular transport and maintaining integrity of intestinal barriers.

  5. Basic and clinical research on the regulation of the intestinal barrier by Lactobacillus and its active protein components: a review with experience of one center.

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    Liu, Zhi-Hua; Kang, Liang; Wang, Jian-Ping

    2014-12-01

    Probiotics got protective effects on the intestinal barrier. Our present study is to review the basic and clinical progress on the regulation of the intestinal barrier by Lactobacillus and its active protein components, combing the study of our center. Our study have isolated the active component of micro integral membrane protein (MIMP) within the media place of the integral membrane protein of Lactobacillus plantarum, which was verified about the protective effects against the intestinal epithelial dysfunction. On the other hand, we also found the effects of perioperative use of probiotics in the prevention and treatment of postoperative intestinal barrier dysfunction, and reduction of the postoperative infective complications. In this review, we would like to report the founding of our center, involving in the basic and clinical research progress of regulation of intestinal barrier by Lactobacillus and its active protein component MIMP. Furthermore, we may also promote our following studies about the MIMP and its clinical verification.

  6. Regulation of taurine transport at the blood-placental barrier by calcium ion, PKC activator and oxidative stress conditions

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    2010-01-01

    Background In the present study, we investigated the changes of uptake and efflux transport of taurine under various stress conditions using rat conditionally immortalized syncytiotrophoblast cell line (TR-TBT cells), as in vitro blood-placental barrier (BPB) model. Methods The transport of taurine in TR-TBT cells were characterized by cellular uptake study using radiolabeled taurine. The efflux of taurine was measured from the amount of radiolabeled taurine remaining in the cells after the uptake of radiolabeled taurine for 60 min. Results Taurine uptake was significantly decreased by phosphorylation of protein kinase C (PKC) activator in TR-TBT cells. Also, calcium ion (Ca2+) was involved in taurine transport in TR-TBT cells. Taurine uptake was inhibited and efflux was enhanced under calcium free conditions in the cells. In addition, oxidative stress induced the change of taurine transport in TR-TBT cells, but the changes were different depending on the types of oxidative stress inducing agents. Tumor necrosis factor-α (TNF-α), lipopolysaccharide (LPS) and diethyl maleate (DEM) significantly increased taurine uptake, but H2O2 and nitric oxide (NO) donor decreased taurine uptake in the cells. Taurine efflux was down-regulated by TNF-α in TR-TBT cells. Conclusion Taurine transport in TR-TBT cells were regulated diversely at extracellular Ca2+ level, PKC activator and oxidative stress conditions. It suggested that variable stresses affected the taurine supplies from maternal blood to fetus and taurine level of fetus. PMID:20804613

  7. JAM-A associates with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and regulate epithelial barrier function.

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    Monteiro, Ana C; Sumagin, Ronen; Rankin, Carl R; Leoni, Giovanna; Mina, Michael J; Reiter, Dirk M; Stehle, Thilo; Dermody, Terence S; Schaefer, Stacy A; Hall, Randy A; Nusrat, Asma; Parkos, Charles A

    2013-09-01

    Intestinal barrier function is regulated by epithelial tight junctions (TJs), structures that control paracellular permeability. Junctional adhesion molecule-A (JAM-A) is a TJ-associated protein that regulates barrier; however, mechanisms linking JAM-A to epithelial permeability are poorly understood. Here we report that JAM-A associates directly with ZO-2 and indirectly with afadin, and this complex, along with PDZ-GEF1, activates the small GTPase Rap2c. Supporting a functional link, small interfering RNA-mediated down-regulation of the foregoing regulatory proteins results in enhanced permeability similar to that observed after JAM-A loss. JAM-A-deficient mice and cultured epithelial cells demonstrate enhanced paracellular permeability to large molecules, revealing a potential role of JAM-A in controlling perijunctional actin cytoskeleton in addition to its previously reported role in regulating claudin proteins and small-molecule permeability. Further experiments suggest that JAM-A does not regulate actin turnover but modulates activity of RhoA and phosphorylation of nonmuscle myosin, both implicated in actomyosin contraction. These results suggest that JAM-A regulates epithelial permeability via association with ZO-2, afadin, and PDZ-GEF1 to activate Rap2c and control contraction of the apical cytoskeleton.

  8. Barriers for recess physical activity

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Tjørnhøj-Thomsen, Tine; Schipperijn, Jasper

    2014-01-01

    they would like to have more secluded areas added to the school playground, even in large schoolyards where lack of space was not a barrier. This aligned with girls' requests for more "hanging-out" facilities, whereas boys primarily wanted activity promoting facilities. CONCLUSION: Based on the results from......BACKGROUND: Many children, in particular girls, do not reach the recommended amount of daily physical activity. School recess provides an opportunity for both boys and girls to be physically active, but barriers to recess physical activity are not well understood. This study explores gender....... This was verified by a thematic analysis of transcripts from the open discussions and go-along interviews. RESULTS: The most frequently identified barriers for both boys and girls were weather, conflicts, lack of space, lack of play facilities and a newly-found barrier, use of electronic devices. While boys...

  9. Regulation to create environments conducive to physical activity: understanding the barriers and facilitators at the Australian state government level.

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    Jane Shill

    Full Text Available INTRODUCTION: Policy and regulatory interventions aimed at creating environments more conducive to physical activity (PA are an important component of strategies to improve population levels of PA. However, many potentially effective policies are not being broadly implemented. This study sought to identify potential policy/regulatory interventions targeting PA environments, and barriers/facilitators to their implementation at the Australian state/territory government level. METHODS: In-depth interviews were conducted with senior representatives from state/territory governments, statutory authorities and non-government organisations (n = 40 to examine participants': 1 suggestions for regulatory interventions to create environments more conducive to PA; 2 support for preselected regulatory interventions derived from a literature review. Thematic and constant comparative analyses were conducted. RESULTS: POLICY INTERVENTIONS MOST COMMONLY SUGGESTED BY PARTICIPANTS FELL INTO TWO AREAS: 1 urban planning and provision of infrastructure to promote active travel; 2 discouraging the use of private motorised vehicles. Of the eleven preselected interventions presented to participants, interventions relating to walkability/cycling and PA facilities received greatest support. Interventions involving subsidisation (of public transport, PA-equipment and the provision of more public transport infrastructure received least support. These were perceived as not economically viable or unlikely to increase PA levels. Dominant barriers were: the powerful 'road lobby', weaknesses in the planning system and the cost of potential interventions. Facilitators were: the provision of evidence, collaboration across sectors, and synergies with climate change/environment agendas. CONCLUSION: This study points to how difficult it will be to achieve policy change when there is a powerful 'road lobby' and government investment prioritises road infrastructure over PA

  10. Regulation of P-glycoprotein efflux activity by Z-guggulsterone of Commiphora mukul at the blood-brain barrier.

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    Xu, Hong-Bin; Yu, Jing; Xu, Lu-Zhong; Fu, Jun

    2016-04-15

    The present study was to investigate whether Z-guggulsterone had the regulatory effect on the activity and expression of P-glycoprotein in rat brain microvessel endothelial cells (rBMECs) and in rat brain. Inorganic phosphate liberation assay, high performance liquid chromatography, and western blot analysis were performed to assess the P-glycoprotein ATPase activity, the accumulation of NaF and rhodamine 123, and P-glycoprotein and MRP1 expression. The results showed that Z-guggulsterone (0-100 μM) significantly enhanced basal P-glycoprotein ATPase activity in a concentration-dependent manner. Tetrandrine (0.1, 0.3, 1 μM) or cyclosporine A (0.1, 0.3, 1 μM) had non-competitively inhibitory manner on Z-guggulsterone-stimulated P-glycoprotein ATPase activity, suggesting that Z-guggulsterone might have unique binding site or regulating site on P-glycoprotein. However, Z-guggulsterone (30, 100 μM) had almost no influence on MRP1 expression in rBMECs. Further results revealed that Z-guggulsterone (50mg/kg) significantly increased the accumulation of rhodamine 123 by down-regulating P-glycoprotein expression in rat brain, as compared with control (PZ-guggulsterone potentially inhibited the activity and expression of P-glycoprotein in rBMECs and in rat brain.

  11. NH4+ secretion in the avian colon. An actively regulated barrier to ammonium permeation of the colon mucosa

    DEFF Research Database (Denmark)

    Holtug, K.; Laverty, G.; Arnason, S.S.

    2009-01-01

    Experiments were designed to characterize an active, electrogenic transport of NH(4)(+) ions across the colonic epithelium of the domestic fowl (Gallus gallus). Colonic segments were isolated and stripped of underlying muscle. The mucosal epithelia were mounted in Ussing chambers and voltage......-clamped to measure the short-circuit currents (I(SC)) associated with transport. Bilateral addition of NH(4)(+) caused a dose-dependent outward current (negative I(SC)), with a Km of 34+/-8 mM and a maximal current response of 311+/-47 microA cm(-2) (12+/-2 microEq cm(-2) h(-1)). A similar effect was seen...... with unilateral addition of NH(4)(+) to the serosal (s) side, but not with mucosal (m) addition. Pre-treatment with 10(-4) M amiloride exposed a net outward (negative) I(SC), and serosal NH(4)(+) addition further increased this outward current with a Km of 53+/-24 mM. Decreasing the bath pH from 7.3 to 6.0 did...

  12. Barriers to physical activity among working mothers.

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    Dombrowski, Jill J

    2011-04-01

    Working mothers experience several barriers to physical activity. If these barriers can be identified by occupational health nurses and they can partner with working mothers to reduce these perceived barriers, the health of these workers can be improved and chronic disease risk prevented. The purpose of this study was to measure the effect of self-regulatory efficacy on physical activity among working mothers and to describe specific barriers to physical activity. The Barriers Specific Self-Efficacy Scale (BARSE) and the Kaiser Physical Activity Survey (KPAS) were used to measure the variables. Self-regulatory efficacy was found to be a strong predictor of physical activity in a diverse sample of working mothers who did not meet current recommendations for physical activity. Occupational health nurses can use these findings to design programs for groups and for counseling individuals.

  13. Understanding Motivators and Barriers to Physical Activity

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    Patay, Mary E.; Patton, Kevin; Parker, Melissa; Fahey, Kathleen; Sinclair, Christina

    2015-01-01

    The purpose of this study was to understand the factors that influence physical activity among year-round residents in an isolated summer resort community. Specifically, we explored the personal, environmental, social, and culture-specific perceived motivators and barriers to physical activity. Participants were formally interviewed about their…

  14. Understanding Motivators and Barriers to Physical Activity

    Science.gov (United States)

    Patay, Mary E.; Patton, Kevin; Parker, Melissa; Fahey, Kathleen; Sinclair, Christina

    2015-01-01

    The purpose of this study was to understand the factors that influence physical activity among year-round residents in an isolated summer resort community. Specifically, we explored the personal, environmental, social, and culture-specific perceived motivators and barriers to physical activity. Participants were formally interviewed about their…

  15. Hydrogen sulfide metabolism regulates endothelial solute barrier function

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    Shuai Yuan

    2016-10-01

    Full Text Available Hydrogen sulfide (H2S is an important gaseous signaling molecule in the cardiovascular system. In addition to free H2S, H2S can be oxidized to polysulfide which can be biologically active. Since the impact of H2S on endothelial solute barrier function is not known, we sought to determine whether H2S and its various metabolites affect endothelial permeability. In vitro permeability was evaluated using albumin flux and transendothelial electrical resistance. Different H2S donors were used to examine the effects of exogenous H2S. To evaluate the role of endogenous H2S, mouse aortic endothelial cells (MAECs were isolated from wild type mice and mice lacking cystathionine γ-lyase (CSE, a predominant source of H2S in endothelial cells. In vivo permeability was evaluated using the Miles assay. We observed that polysulfide donors induced rapid albumin flux across endothelium. Comparatively, free sulfide donors increased permeability only with higher concentrations and at later time points. Increased solute permeability was associated with disruption of endothelial junction proteins claudin 5 and VE-cadherin, along with enhanced actin stress fiber formation. Importantly, sulfide donors that increase permeability elicited a preferential increase in polysulfide levels within endothelium. Similarly, CSE deficient MAECs showed enhanced solute barrier function along with reduced endogenous bound sulfane sulfur. CSE siRNA knockdown also enhanced endothelial junction structures with increased claudin 5 protein expression. In vivo, CSE genetic deficiency significantly blunted VEGF induced hyperpermeability revealing an important role of the enzyme for barrier function. In summary, endothelial solute permeability is critically regulated via exogenous and endogenous sulfide bioavailability with a prominent role of polysulfides.

  16. Epithelial Barrier Regulation by Hypoxia-Inducible Factor.

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    Glover, Louise E; Colgan, Sean P

    2017-09-01

    Mucosal tissues represent surfaces that are exposed to the outside world and provide a conduit for internal and external communication. Tissues such as the intestine and the lung are lined by layer(s) of epithelial cells that, when organized in three dimensions, provide a critical barrier to the flux of luminal contents. This selective barrier is provided through the regulated expression of junctional proteins and mucins. Tissue oxygen metabolism is central to the maintenance of homeostasis in the mucosa. In some organs (e.g., the colon), low baseline Po2 determines tissue metabolism and results in basal expression of the transcription factor, hypoxia-inducible factor (HIF), which is enhanced after ischemia/inflammation. Recent studies have indicated that HIF contributes fundamentally to the expression of barrier-related genes and in the regulation of barrier-adaptive responses within the mucosa. Here, we briefly review recent literature on the topic of hypoxia and HIF regulation of barrier in mucosal health and during disease.

  17. Government regulation of business in a changing institutional barrier

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    Novikova I.

    2013-02-01

    Full Text Available The article examines the domestic experience in government regulation of business in a changing institutional barrier.Compared the degree of economic freedom in Ukraine. The emphasis is on the need to develop a national strategy of institutional development of domestic entrepreneurship.

  18. BARRIERS TO PHYSICAL ACTIVITY IN THE ELDERLY

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    Paulo Matias

    2015-04-01

    Full Text Available The population awareness of the physical exercise’s benefits is widely diffused. These benefits are particularly important in the elderly because, with increasing age, there is a decline of the musculoskeletal system and the maximum oxygen consumption which reduces the functional fitness of the elderly and can often lead to a significant decline in the quality of life. Despite this awareness, a large part of the population remains sedentary. It is important to know what the barriers are, so they can be circumvented in order to increase the engagement of the elderly population in existing physical activity programs.Objectives: This study aims to identify some of the personal, behavioral and environmental barriers that prevent older adults to be physically active.

  19. Barriers to increased market-oriented activity

    DEFF Research Database (Denmark)

    Bisp, Søren

    1999-01-01

    -oriented activity. A framework of six generic domains is suggested: Organizational structure, human resource management, market-oriented activity competence, psychological climate, managers' personality characteristics, and individually held beliefs. A model is suggested inter-relating the domains....... and related activities still seem to attract relatively few resources is not answered by supplying another checklist or package of facilitators. Based on published conceptual writings and empirical studies this article makes an account of what the intra-organizational barriers may be to increased market...

  20. Circularly polarized antennas for active holographic imaging through barriers

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    McMakin, Douglas L [Richland, WA; Severtsen, Ronald H [Richland, WA; Lechelt, Wayne M [West Richland, WA; Prince, James M [Kennewick, WA

    2011-07-26

    Circularly-polarized antennas and their methods of use for active holographic imaging through barriers. The antennas are dielectrically loaded to optimally match the dielectric constant of the barrier through which images are to be produced. The dielectric loading helps to remove barrier-front surface reflections and to couple electromagnetic energy into the barrier.

  1. Barriers to increased market-oriented activity

    DEFF Research Database (Denmark)

    Bisp, Søren

    1999-01-01

    Most research on market orientation has dealt with assessing how market orientation behaviour is related to business performance. This work has established an intense market-oriented activity as significantly and positively related to business performance under most circumstances. In a maturing...... and related activities still seem to attract relatively few resources is not answered by supplying another checklist or package of facilitators. Based on published conceptual writings and empirical studies this article makes an account of what the intra-organizational barriers may be to increased market...

  2. Karyopherins regulate nuclear pore complex barrier and transport function.

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    Kapinos, Larisa E; Huang, Binlu; Rencurel, Chantal; Lim, Roderick Y H

    2017-09-01

    Nucleocytoplasmic transport is sustained by karyopherins (Kaps) and a Ran guanosine triphosphate (RanGTP) gradient that imports nuclear localization signal (NLS)-specific cargoes (NLS-cargoes) into the nucleus. However, how nuclear pore complex (NPC) barrier selectivity, Kap traffic, and NLS-cargo release are systematically linked and simultaneously regulated remains incoherent. In this study, we show that Kapα facilitates Kapβ1 turnover and occupancy at the NPC in a RanGTP-dependent manner that is directly coupled to NLS-cargo release and NPC barrier function. This is underpinned by the binding affinity of Kapβ1 to phenylalanine-glycine nucleoporins (FG Nups), which is comparable with RanGTP·Kapβ1, but stronger for Kapα·Kapβ1. On this basis, RanGTP is ineffective at releasing standalone Kapβ1 from NPCs. Depleting Kapα·Kapβ1 by RanGTP further abrogates NPC barrier function, whereas adding back Kapβ1 rescues it while Kapβ1 turnover softens it. Therefore, the FG Nups are necessary but insufficient for NPC barrier function. We conclude that Kaps constitute integral constituents of the NPC whose barrier, transport, and cargo release functionalities establish a continuum under a mechanism of Kap-centric control. © 2017 Kapinos et al.

  3. Barriers to increasing market-oriented activity

    DEFF Research Database (Denmark)

    Bisp, Søren

    product development. Despite the increasing evidence of a positive relationship between above average business performance and a high level of market-oriented activity, normative recommendations on how to increase the level of market-oriented activity is sparse. The scientific contribution of the present...... research is to expand the understanding of what factors inhibit the increase of market-oriented activity and how these factors may interact. Identifying and describing the barriers is considered the first and necessary step in attempting to reach a higher level of market-oriented activity......Introduction: The Danish food processing industry faces a situation in which intensified competition in its primary markets and product categories forces several companies to rethink their relative focus in terms of marketing rather than production, or, in other words, in terms of value adding...

  4. Update on pulmonary edema: the role and regulation of endothelial barrier function.

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    Patterson, C E; Lum, H

    2001-01-01

    Discovery of the pathophysiologic mechanisms leading to pulmonary edema and identification of effective strategies for prevention remain significant clinical concerns. Endothelial barrier function is a key component for maintenance of the integrity of the vascular boundary in the lung, particularly since the gas exchange surface area of the alveolar-capillary membrane is large. This review is focused on new insights in the pulmonary endothelial response to injury and recovery, reversible activation by edemagenic agents, and the biochemical/structural basis for regulation of endothelial barrier function. This information is discussed in the context of fundamental concepts of lung fluid balance and pulmonary function.

  5. The Idefix enhancer-blocking insulator also harbors barrier activity.

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    Brasset, E; Hermant, C; Jensen, S; Vaury, C

    2010-01-15

    Chromatin insulators are cis-regulatory sequences participating in the regulation of gene expression. Their presence within the genome is associated with two main functions. One of them is an enhancer-blocking function that blocks enhancer-promoter communication when the insulator is located in between. The second is a boundary or barrier function that insulates independent units of transcription. This latter is observed when two insulators flanking a gene and its regulatory sequences block the regulatory influences of surrounding chromatin. Some years ago, we reported the presence of an insulator within the retrotransposon Idefix from Drosophila melanogaster. This insulator displays an enhancer-blocking activity toward an enhancer located within a second retrotransposon called ZAM. Here, we show that this insulator is not specific to the ZAM enhancer but has the capacity to interfere in the communication established between a broad range of cis-regulatory enhancer and a promoter. Furthermore, we show that, if it is placed on both sides of a transgene, this insulator acts as a barrier able to isolate the transgene from its repressive or enhancing environment. Thus, the Idefix insulator carries both an enhancer-blocking and a barrier activity. According to these properties, the Idefix insulator might prove to be a useful tool to isolate artificial transgenes from positive or negative influences from their integration sites.

  6. Rab5-mediated VE-cadherin internalization regulates the barrier function of the lung microvascular endothelium.

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    Yang, Junjun; Yao, Wei; Qian, Guisheng; Wei, Zhenghua; Wu, Guangyu; Wang, Guansong

    2015-12-01

    The small GTPase Rab5 has been well defined to control the vesicle-mediated plasma membrane protein transport to the endosomal compartment. However, its function in the internalization of vascular endothelial (VE)-cadherin, an important component of adherens junctions, and as a result regulating the endothelial cell polarity and barrier function remain unknown. Here, we demonstrated that lipopolysaccharide (LPS) simulation markedly enhanced the activation and expression of Rab5 in human pulmonary microvascular endothelial cells (HPMECs), which is accompanied by VE-cadherin internalization. In parallel, LPS challenge also induced abnormal cell polarity and dysfunction of the endothelial barrier in HPMECs. LPS stimulation promoted the translocation of VE-cadherin from the plasma membrane to intracellular compartments, and intracellularly expressed VE-cadherin was extensively colocalized with Rab5. Small interfering RNA (siRNA)-mediated depletion of Rab5a expression attenuated the disruption of LPS-induced internalization of VE-cadherin and the disorder of cell polarity. Furthermore, knockdown of Rab5 inhibited the vascular endothelial hyperpermeability and protected endothelial barrier function from LPS injury, both in vitro and in vivo. These results suggest that Rab5 is a critical mediator of LPS-induced endothelial barrier dysfunction, which is likely mediated through regulating VE-cadherin internalization. These findings provide evidence, implicating that Rab5a is a potential therapeutic target for preventing endothelial barrier disruption and vascular inflammation.

  7. Promoting Physical Activity: Addressing Barriers and Moving Forward

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    Beighle, Aaron; Morrow, James R.

    2014-01-01

    The barriers that keep individuals from adopting and maintaining active lifestyles are very complex. Strategies for overcoming these barriers and to incentivize and assist inactive individuals to benefit from physical activity are necessary. In addition, it is important to examine the impact of public policy on active living. As youth physical…

  8. Promoting Physical Activity: Addressing Barriers and Moving Forward

    Science.gov (United States)

    Beighle, Aaron; Morrow, James R.

    2014-01-01

    The barriers that keep individuals from adopting and maintaining active lifestyles are very complex. Strategies for overcoming these barriers and to incentivize and assist inactive individuals to benefit from physical activity are necessary. In addition, it is important to examine the impact of public policy on active living. As youth physical…

  9. Perceived barriers to physical activity in university students.

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    Arzu, Daskapan; Tuzun, Emine Handan; Eker, Levent

    2006-01-01

    Many studies which were published in other countries identified certain benefits and barriers to physical activity among young people. But there is no data about the subject pertaining to Turkish adolescents. This study tries to rectify this with a study of Turkish university students. Undergraduate university students (n = 303) were recruited to the study. Current exercise habits and perceived barriers to physical activity were assessed in the sample. Using a Likert Type scale, participants responded an instrument with 12 items representing barriers to physical activity. Mean scores were computed. External barriers were more important than internal barriers. "Lack of time due to busy lesson schedule", "My parents give academic success priority over exercise. "and "lack of time due to responsibilities related to the family and social environment "were most cited items for physical activity barriers. There is a need for future research, which will be carried out with larger sample groups to develop national standardized instrument. It will be helpful for accurately identify perceived barriers and then recommend changes to enhance physical activity among young people. Key PointsThe purpose of this study was to analyze perceived barriers to physical activity in the university students.The results showed that not having enough time was the most important barrier for not participating in physical activity among our samples.This study with relatively small sample must be considered as pilot study for related studies in the future.

  10. The Small GTPase Rap1 Is a Novel Regulator of RPE Cell Barrier Function

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    Wittchen, Erika S.

    2011-01-01

    Purpose. To determine whether the small GTPase Rap1 regulates the formation and maintenance of the retinal pigment epithelial (RPE) cell junctional barrier. Methods. An in vitro model was used to study RPE barrier properties. To dissect the role of Rap1, two techniques were used to inhibit Rap1 function: overexpression of RapGAP, which acts as a negative regulator of endogenous Rap1 activity, and treatment with engineered, adenovirally-transduced microRNAs to knockdown Rap1 protein expression. Transepithelial electrical resistance (TER) and real-time cellular analysis (RTCA) of impedance were used as readouts for barrier properties. Immunofluorescence microscopy was used to visualize localization of cadherins under steady state conditions and also during junctional reassembly after calcium switch. Finally, choroidal endothelial cell (CEC) migration across RPE monolayers was quantified under conditions of Rap1 inhibition in RPE. Results. Knockdown of Rap1 or inhibition of its activity in RPE reduces TER and electrical impedance of the RPE monolayers. The loss of barrier function is also reflected by the mislocalization of cadherins and formation of gaps within the monolayer. TER measurement and immunofluorescent staining of cadherins after a calcium switch indicate that junctional reassembly kinetics are also impaired. Furthermore, CEC transmigration is significantly higher in Rap1-knockdown RPE monolayers compared with control. Conclusions. Rap1 GTPase is an important regulator of RPE cell junctions, and is required for maintenance of barrier function. This observation that RPE monolayers lacking Rap1 allow greater transmigration of CECs suggests a possible role for potentiating choroidal neovascularization during the pathology of neovascular age-related macular degeneration. PMID:21873678

  11. Regulation of Thrombin-Induced Lung Endothelial Cell Barrier Disruption by Protein Kinase C Delta

    Science.gov (United States)

    Xie, Lishi; Chiang, Eddie T.; Kelly, Gabriel T.; Kanteti, Prasad; Singleton, Patrick A.; Camp, Sara M.; Zhou, Tingting; Dudek, Steven M.; Natarajan, Viswanathan; Wang, Ting; Black, Steven M.; Garcia, Joe G. N.; Jacobson, Jeffrey R.

    2016-01-01

    Protein Kinase C (PKC) plays a significant role in thrombin-induced loss of endothelial cell (EC) barrier integrity; however, the existence of more than 10 isozymes of PKC and tissue–specific isoform expression has limited our understanding of this important second messenger in vascular homeostasis. In this study, we show that PKCδ isoform promotes thrombin-induced loss of human pulmonary artery EC barrier integrity, findings substantiated by PKCδ inhibitory studies (rottlerin), dominant negative PKCδ construct and PKCδ silencing (siRNA). In addition, we identified PKCδ as a signaling mediator upstream of both thrombin-induced MLC phosphorylation and Rho GTPase activation affecting stress fiber formation, cell contraction and loss of EC barrier integrity. Our inhibitor-based studies indicate that thrombin-induced PKCδ activation exerts a positive feedback on Rho GTPase activation and contributes to Rac1 GTPase inhibition. Moreover, PKD (or PKCμ) and CPI-17, two known PKCδ targets, were found to be activated by PKCδ in EC and served as modulators of cytoskeleton rearrangement. These studies clarify the role of PKCδ in EC cytoskeleton regulation, and highlight PKCδ as a therapeutic target in inflammatory lung disorders, characterized by the loss of barrier integrity, such as acute lung injury and sepsis. PMID:27442243

  12. Regulation of Thrombin-Induced Lung Endothelial Cell Barrier Disruption by Protein Kinase C Delta.

    Directory of Open Access Journals (Sweden)

    Lishi Xie

    Full Text Available Protein Kinase C (PKC plays a significant role in thrombin-induced loss of endothelial cell (EC barrier integrity; however, the existence of more than 10 isozymes of PKC and tissue-specific isoform expression has limited our understanding of this important second messenger in vascular homeostasis. In this study, we show that PKCδ isoform promotes thrombin-induced loss of human pulmonary artery EC barrier integrity, findings substantiated by PKCδ inhibitory studies (rottlerin, dominant negative PKCδ construct and PKCδ silencing (siRNA. In addition, we identified PKCδ as a signaling mediator upstream of both thrombin-induced MLC phosphorylation and Rho GTPase activation affecting stress fiber formation, cell contraction and loss of EC barrier integrity. Our inhibitor-based studies indicate that thrombin-induced PKCδ activation exerts a positive feedback on Rho GTPase activation and contributes to Rac1 GTPase inhibition. Moreover, PKD (or PKCμ and CPI-17, two known PKCδ targets, were found to be activated by PKCδ in EC and served as modulators of cytoskeleton rearrangement. These studies clarify the role of PKCδ in EC cytoskeleton regulation, and highlight PKCδ as a therapeutic target in inflammatory lung disorders, characterized by the loss of barrier integrity, such as acute lung injury and sepsis.

  13. PERCEIVED BARRIERS TO PHYSICAL ACTIVITY IN UNIVERSITY STUDENTS

    Directory of Open Access Journals (Sweden)

    Arzu Daskapan

    2006-12-01

    Full Text Available Many studies which were published in other countries identified certain benefits and barriers to physical activity among young people. But there is no data about the subject pertaining to Turkish adolescents. This study tries to rectify this with a study of Turkish university students. Undergraduate university students (n = 303 were recruited to the study. Current exercise habits and perceived barriers to physical activity were assessed in the sample. Using a Likert Type scale, participants responded an instrument with 12 items representing barriers to physical activity. Mean scores were computed. External barriers were more important than internal barriers. "Lack of time due to busy lesson schedule", "My parents give academic success priority over exercise." and "lack of time due to responsibilities related to the family and social environment" were most cited items for physical activity barriers. There is a need for future research, which will be carried out with larger sample groups to develop national standardized instrument. It will be helpful for accurately identify perceived barriers and then recommend changes to enhance physical activity among young people.

  14. Irsogladine maleate regulates gap junctional intercellular communication-dependent epithelial barrier in human nasal epithelial cells.

    Science.gov (United States)

    Miyata, Ryo; Nomura, Kazuaki; Kakuki, Takuya; Takano, Ken-Ichi; Kohno, Takayuki; Konno, Takumi; Sawada, Norimasa; Himi, Tetsuo; Kojima, Takashi

    2015-04-01

    The airway epithelium of the human nasal mucosa acts as the first physical barrier that protects against inhaled substances and pathogens. Irsogladine maleate (IM) is an enhancer of gastric mucosal protective factors via upregulation of gap junctional intercellular communication (GJIC). GJIC is thought to participate in the formation of functional tight junctions. However, the effects of IM on GJIC and the epithelial barrier in human nasal epithelial cells (HNECs) remain unknown. To investigate the effects of IM on GJIC and the tight junctional barrier in HNECs, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were treated with IM and the GJIC inhibitors oleamide and 18β-GA. Some cells were pretreated with IM before treatment with TLR3 ligand poly(I:C) to examine whether IM prevented the changes via TLR3-mediated signal pathways. In hTERT-HNECs, GJIC blockers reduced the expression of tight junction molecules claudin-1, -4, -7, occludin, tricellulin, and JAM-A. IM induced GJIC activity and enhanced the expression of claudin-1, -4, and JAM-A at the protein and mRNA levels with an increase of barrier function. GJIC blockers prevented the increase of the tight junction proteins induced by IM. Furthermore, IM prevented the reduction of JAM-A but not induction of IL-8 and TNF-α induced by poly(I:C). In conclusion, IM can maintain the GJIC-dependent tight junctional barrier via regulation of GJIC in upper airway nasal epithelium. Therefore, it is possible that IM may be useful as a nasal spray to prevent the disruption of the epithelial barrier by viral infections and exposure to allergens in human nasal mucosa.

  15. International Collaboration Activities on Engineered Barrier Systems

    Energy Technology Data Exchange (ETDEWEB)

    Jove-Colon, Carlos F. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2016-08-31

    The Used Fuel Disposition Campaign (UFDC) within the DOE Fuel Cycle Technologies (FCT) program has been engaging in international collaborations between repository R&D programs for high-level waste (HLW) disposal to leverage on gathered knowledge and laboratory/field data of near- and far-field processes from experiments at underground research laboratories (URL). Heater test experiments at URLs provide a unique opportunity to mimetically study the thermal effects of heat-generating nuclear waste in subsurface repository environments. Various configurations of these experiments have been carried out at various URLs according to the disposal design concepts of the hosting country repository program. The FEBEX (Full-scale Engineered Barrier Experiment in Crystalline Host Rock) project is a large-scale heater test experiment originated by the Spanish radioactive waste management agency (Empresa Nacional de Residuos Radiactivos S.A. – ENRESA) at the Grimsel Test Site (GTS) URL in Switzerland. The project was subsequently managed by CIEMAT. FEBEX-DP is a concerted effort of various international partners working on the evaluation of sensor data and characterization of samples obtained during the course of this field test and subsequent dismantling. The main purpose of these field-scale experiments is to evaluate feasibility for creation of an engineered barrier system (EBS) with a horizontal configuration according to the Spanish concept of deep geological disposal of high-level radioactive waste in crystalline rock. Another key aspect of this project is to improve the knowledge of coupled processes such as thermal-hydro-mechanical (THM) and thermal-hydro-chemical (THC) operating in the near-field environment. The focus of these is on model development and validation of predictions through model implementation in computational tools to simulate coupled THM and THC processes.

  16. Colloidal Oatmeal (Avena Sativa) Improves Skin Barrier Through Multi-Therapy Activity.

    Science.gov (United States)

    Ilnytska, Olha; Kaur, Simarna; Chon, Suhyoun; Reynertson, Kurt A; Nebus, Judith; Garay, Michelle; Mahmood, Khalid; Southall, Michael D

    2016-06-01

    Oats (Avena sativa) are a centuries-old topical treatment for a variety of skin barrier conditions, including dry skin, skin rashes, and eczema; however, few studies have investigated the actual mechanism of action for the skin barrier strengthening activity of colloidal oatmeal. Four extracts of colloidal oatmeal were prepared with various solvents and tested in vitro for skin barrier related gene expression and activity. Extracts of colloidal oatmeal were found to induce the expression of genes related to epidermal differentiation, tight junctions and lipid regulation in skin, and provide pH-buffering capacity. Colloidal oatmeal boosted the expression of multiple target genes related to skin barrier, and resulted in recovery of barrier damage in an in vitro model of atopic dermatitis. In addition, an investigator-blinded study was performed with 50 healthy female subjects who exhibited bilateral moderate to severe dry skin on their lower legs. Subjects were treated with a colloidal oatmeal skin protectant lotion. Clinically, the colloidal oatmeal lotion showed significant clinical improvements in skin dryness, moisturization, and barrier. Taken together, these results demonstrate that colloidal oatmeal can provide clinically effective benefits for dry and compromised skin by strengthening skin barrier. J Drugs Dermatol. 2016;15(6):684-690.

  17. Attempting to be active: Self-efficacy and barrier limitation differentiate activity levels of working mothers.

    Science.gov (United States)

    Gierc, Madelaine; Locke, Sean; Jung, Mary; Brawley, Lawrence

    2016-07-01

    Working mothers are less physically active than working women without children and mothers who do not work. The purpose of this study was to examine concurrent self-regulatory efficacy and barriers to physical activity in a sample of working mothers. Women completed a mixed-methods survey which included measures of physical activity, concurrent self-regulatory efficacy, and barriers. Sufficiently active women experienced significantly greater concurrent self-regulatory efficacy and significantly less barrier limitation and frequency. No significant group differences were found for age, domestic duties performed, and children's extracurricular activities. Thematic analysis of barriers revealed six themes of common and unique factors, including limited time and family activities.

  18. Barrier role of actin filaments in regulated mucin secretion from airway goblet cells.

    Science.gov (United States)

    Ehre, Camille; Rossi, Andrea H; Abdullah, Lubna H; De Pestel, Kathleen; Hill, Sandra; Olsen, John C; Davis, C William

    2005-01-01

    Airway goblet cells secrete mucin onto mucosal surfaces under the regulation of an apical, phospholipase C/G(q)-coupled P2Y(2) receptor. We tested whether cortical actin filaments negatively regulate exocytosis in goblet cells by forming a barrier between secretory granules and plasma membrane docking sites as postulated for other secretory cells. Immunostaining of human lung tissues and SPOC1 cells (an epithelial, mucin-secreting cell line) revealed an apical distribution of beta- and gamma-actin in ciliated and goblet cells. In goblet cells, actin appeared as a prominent subplasmalemmal sheet lying between granules and the apical membrane, and it disappeared from SPOC1 cells activated by purinergic agonist. Disruption of actin filaments with latrunculin A stimulated SPOC1 cell mucin secretion under basal and agonist-activated conditions, whereas stabilization with jasplakinolide or overexpression of beta- or gamma-actin conjugated to yellow fluorescent protein (YFP) inhibited secretion. Myristoylated alanine-rich C kinase substrate, a PKC-activated actin-plasma membrane tethering protein, was phosphorylated after agonist stimulation, suggesting a translocation to the cytosol. Scinderin (or adseverin), a Ca(2+)-activated actin filament severing and capping protein was cloned from human airway and SPOC1 cells, and synthetic peptides corresponding to its actin-binding domains inhibited mucin secretion. We conclude that actin filaments negatively regulate mucin secretion basally in airway goblet cells and are dynamically remodeled in agonist-stimulated cells to promote exocytosis.

  19. Regulating prefrontal cortex activation

    DEFF Research Database (Denmark)

    Aznar, Susana; Klein, Anders Bue

    2013-01-01

    of emotion-based actions, such as addiction and other impulse-related behaviors. In this review, we give an overview of the 5-HT2A receptor distribution (neuronal, intracellular, and anatomical) along with its functional and physiological effect on PFC activation, and how that relates to more recent findings......The prefrontal cortex (PFC) is involved in mediating important higher-order cognitive processes such as decision making, prompting thereby our actions. At the same time, PFC activation is strongly influenced by emotional reactions through its functional interaction with the amygdala...... is highly expressed in the prefrontal cortex areas, playing an important role in modulating cortical activity and neural oscillations (brain waves). This makes it an interesting potential pharmacological target for the treatment of neuropsychiatric modes characterized by lack of inhibitory control...

  20. Protelytic Regulation of the Intestinal Epithelial Barrier: Mechanisms and Interventions

    Science.gov (United States)

    2015-09-01

    molecular mechanisms that mediate matriptase protection during DSS-induced experimental inflammatory colitis, 2) define molecular mechanisms by which...and protein levels by cytokines produced during inflammatory colitis. Further, matriptase acts downstream of prostasin to mediate barrier formation...6 TASK 2 To determine the molecular mechanisms that mediate matriptase protection during mucosal inflammation in experimental

  1. Nucleosome positioning and kinetics near transcription-start-site barriers are controlled by interplay between active remodeling and DNA sequence.

    Science.gov (United States)

    Parmar, Jyotsana J; Marko, John F; Padinhateeri, Ranjith

    2014-01-01

    We investigate how DNA sequence, ATP-dependent chromatin remodeling and nucleosome-depleted 'barriers' co-operate to determine the kinetics of nucleosome organization, in a stochastic model of nucleosome positioning and dynamics. We find that 'statistical' positioning of nucleosomes against 'barriers', hypothesized to control chromatin structure near transcription start sites, requires active remodeling and therefore cannot be described using equilibrium statistical mechanics. We show that, unlike steady-state occupancy, DNA site exposure kinetics near a barrier is dominated by DNA sequence rather than by proximity to the barrier itself. The timescale for formation of positioning patterns near barriers is proportional to the timescale for active nucleosome eviction. We also show that there are strong gene-to-gene variations in nucleosome positioning near barriers, which are eliminated by averaging over many genes. Our results suggest that measurement of nucleosome kinetics can reveal information about sequence-dependent regulation that is not apparent in steady-state nucleosome occupancy.

  2. TALE homeodomain proteins regulate site-specific terminal differentiation, LCE genes and epidermal barrier.

    Science.gov (United States)

    Jackson, Ben; Brown, Stuart J; Avilion, Ariel A; O'Shaughnessy, Ryan F L; Sully, Katherine; Akinduro, Olufolake; Murphy, Mark; Cleary, Michael L; Byrne, Carolyn

    2011-05-15

    The epidermal barrier varies over the body surface to accommodate regional environmental stresses. Regional skin barrier variation is produced by site-dependent epidermal differentiation from common keratinocyte precursors and often manifests as site-specific skin disease or irritation. There is strong evidence for body-site-dependent dermal programming of epidermal differentiation in which the epidermis responds by altering expression of key barrier proteins, but the underlying mechanisms have not been defined. The LCE multigene cluster encodes barrier proteins that are differentially expressed over the body surface, and perturbation of LCE cluster expression is linked to the common regional skin disease psoriasis. LCE subclusters comprise genes expressed variably in either external barrier-forming epithelia (e.g. skin) or in internal epithelia with less stringent barriers (e.g. tongue). We demonstrate here that a complex of TALE homeobox transcription factors PBX1, PBX2 and Pknox (homologues of Drosophila Extradenticle and Homothorax) preferentially regulate external rather than internal LCE gene expression, competitively binding with SP1 and SP3. Perturbation of TALE protein expression in stratified squamous epithelia in mice produces external but not internal barrier abnormalities. We conclude that epidermal barrier genes, such as the LCE multigene cluster, are regulated by TALE homeodomain transcription factors to produce regional epidermal barriers.

  3. Regulation of Copper Transport Crossing Brain Barrier Systems by Cu-ATPases: Effect of Manganese Exposure

    OpenAIRE

    Fu, Xue; Zhang, Yanshu; Jiang, Wendy; Monnot, Andrew Donald; Bates, Christopher Alexander; Zheng, Wei

    2014-01-01

    Regulation of cellular copper (Cu) homeostasis involves Cu-transporting ATPases (Cu-ATPases), i.e., ATP7A and ATP7B. The question as to how these Cu-ATPases in brain barrier systems transport Cu, i.e., toward brain parenchyma, cerebrospinal fluid (CSF), or blood, remained unanswered. This study was designed to characterize roles of Cu-ATPases in regulating Cu transport at the blood-brain barrier (BBB) and blood-CSF barrier (BCB) and to investigate how exposure to toxic manganese (Mn) altered ...

  4. Xenobiotic Receptor-Mediated Regulation of Intestinal Barrier Function and Innate Immunity

    Directory of Open Access Journals (Sweden)

    Harmit S. Ranhotra

    2016-07-01

    Full Text Available The molecular basis for the regulation of the intestinal barrier is a very fertile research area. A growing body of knowledge supports the targeting of various components of intestinal barrier function as means to treat a variety of diseases, including the inflammatory bowel diseases. Herein, we will summarize the current state of knowledge of key xenobiotic receptor regulators of barrier function, highlighting recent advances, such that the field and its future are succinctly reviewed. We posit that these receptors confer an additional dimension of host-microbe interaction in the gut, by sensing and responding to metabolites released from the symbiotic microbiota, in innate immunity and also in host drug metabolism. The scientific evidence for involvement of the receptors and its molecular basis for the control of barrier function and innate immunity regulation would serve as a rationale towards development of non-toxic probes and ligands as drugs.

  5. Barrier stabilizing mediators in regulation of microvascular endothelial permeability

    Institute of Scientific and Technical Information of China (English)

    HUANG Qiao-bing

    2012-01-01

    Increase of microvascular permeability is one of the most important pathological events in the pathogenesis of trauma and bum injury.Massive leakage of fluid from vascular space leads to lose of blood plasma and decrease of effective circulatory blood volume,resulting in formation of severe tissue edema,hypotension or even shock,especially in severe bum injury.Fluid resuscitation has been the only valid approach to sustain patient's blood volume for a long time,due to the lack of overall and profound understanding of the mechanisms of vascular hyperpenneability response.There is an emerging concept in recent years that some so-called barrier stabilizing mediators play a positive role in preventing the increase of vascular permeability.These mediators may be released in response to proinflammatory mediators and serve to restore endothelial barrier function.Some of these stabilizing mediators are important even in quiescent state because they preserve basal vascular permeability at low levels.This review introduces some of these mediators and reveals their underlying signaling mechanisms during endothelial barrier enhancing process.

  6. Influences and Barriers on Physical Activity in Pediatric Oncology Patients

    Directory of Open Access Journals (Sweden)

    Larrilyn Yelton

    2016-12-01

    Full Text Available Objectives: To determine the influence of family, peers, school, and physicians on exercise in pediatric oncology patients and evaluate the barriers to physical activity levels in this population. Methods: A search of PubMed and Google Scholar resulted in 12 related articles. The articles were assessed for the influence of school systems, family, peers, self-efficacy, and physicians on exercise. Additionally barriers and interventions to physical activity were also assessed. Limitations and research methodologies of each article were also evaluated. Results: Many school systems were unsure of expectations in regards to physical activity for their returning students with cancer. Most schools acknowledged willingness to increase exercise for these students; however, there is a communication gap between the medical field and the school system on what expectations should be. Family is associated with increased physical activity levels and healthier diets in this population with children preferring mothers as exercise partners more than fathers. While physician interventions have been shown to positively impact physical activity, it has been reported that physicians are not engaging in exercise counseling with their patients. Conclusion: Several issues and barriers related to physical activity in pediatric oncology population were identified. Studies have demonstrated it is feasible to increase physical activity and self-efficacy in this population. Further research is needed to better understand and quantify these issues as well as further test the interventions that have been suggested in this review and have been successful in other pediatric populations.

  7. Molecular regulation of osteoclast activity.

    Science.gov (United States)

    Bruzzaniti, Angela; Baron, Roland

    2006-06-01

    Osteoclasts are multinucleated cells derived from hematopoietic precursors that are primarily responsible for the degradation of mineralized bone during bone development, homeostasis and repair. In various skeletal disorders such as osteoporosis, hypercalcemia of malignancy, tumor metastases and Paget's disease, bone resorption by osteoclasts exceeds bone formation by osteoblasts leading to decreased bone mass, skeletal fragility and bone fracture. The overall rate of osteoclastic bone resorption is regulated either at the level of differentiation of osteoclasts from their monocytic/macrophage precursor pool or through the regulation of key functional proteins whose specific activities in the mature osteoclast control its attachment, migration and resorption. Thus, reducing osteoclast numbers and/or decreasing the bone resorbing activity of osteoclasts are two common therapeutic approaches for the treatment of hyper-resorptive skeletal diseases. In this review, several of the key functional players involved in the regulation of osteoclast activity will be discussed.

  8. Barriers associated with reduced physical activity in COPD patients

    Directory of Open Access Journals (Sweden)

    Priscila Batista Amorim

    2014-10-01

    Full Text Available OBJECTIVE: To evaluate the ability of COPD patients to perform activities of daily living (ADL; to identify barriers that prevent these individuals from performing ADL; and to correlate those barriers with dyspnea severity, six-minute walk test (6MWT, and an ADL limitation score. METHODS: In COPD patients and healthy, age-matched controls, the number of steps, the distance walked, and walking time were recorded with a triaxial accelerometer, for seven consecutive days. A questionnaire regarding perceived barriers and the London Chest Activity of Daily Living (LCADL scale were used in order to identify the factors that prevent the performance of ADL. The severity of dyspnea was assessed with two scales, whereas submaximal exercise capacity was determined on the basis of the 6MWT. RESULTS: We evaluated 40 COPD patients and 40 controls. In comparison with the control values, the mean walk time was significantly shorter for COPD patients (68.5 ± 25.8 min/day vs. 105.2 ± 49.4 min/day; p < 0.001, as was the distance walked (3.9 ± 1.9 km/day vs. 6.4 ± 3.2 km/day; p < 0.001. The COPD patients also walked fewer steps/day. The most common self-reported barriers to performing ADL were lack of infrastructure, social influences, and lack of willpower. The 6MWT distance correlated with the results obtained with the accelerometer but not with the LCADL scale results. CONCLUSIONS: Patients with COPD are less active than are healthy adults of a comparable age. Physical inactivity and the barriers to performing ADL have immediate implications for clinical practice, calling for early intervention measures.

  9. Butyrate Enhances the Intestinal Barrier by Facilitating Tight Junction Assembly via Activation of AMP-Activated Protein Kinase in Caco-2 Cell Monolayers12

    Science.gov (United States)

    Peng, Luying; Li, Zhong-Rong; Green, Robert S.; Holzman, Ian R.; Lin, Jing

    2009-01-01

    Butyrate, one of the SCFA, promotes the development of the intestinal barrier. However, the molecular mechanisms underlying the butyrate regulation of the intestinal barrier are unknown. To test the hypothesis that the effect of butyrate on the intestinal barrier is mediated by the regulation of the assembly of tight junctions involving the activation of the AMP-activated protein kinase (AMPK), we determined the effect of butyrate on the intestinal barrier by measuring the transepithelial electrical resistance (TER) and inulin permeability in a Caco-2 cell monolayer model. We further used a calcium switch assay to study the assembly of epithelial tight junctions and determined the effect of butyrate on the assembly of epithelial tight junctions and AMPK activity. We demonstrated that the butyrate treatment increased AMPK activity and accelerated the assembly of tight junctions as shown by the reorganization of tight junction proteins, as well as the development of TER. AMPK activity was also upregulated by butyrate during calcium switch-induced tight junction assembly. Compound C, a specific AMPK inhibitor, inhibited the butyrate-induced activation of AMPK. The facilitating effect of butyrate on the increases in TER in standard culture media, as well as after calcium switch, was abolished by compound C. We conclude that butyrate enhances the intestinal barrier by regulating the assembly of tight junctions. This dynamic process is mediated by the activation of AMPK. These results suggest an intriguing link between SCFA and the intracellular energy sensor for the development of the intestinal barrier. PMID:19625695

  10. Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers.

    Science.gov (United States)

    Peng, Luying; Li, Zhong-Rong; Green, Robert S; Holzman, Ian R; Lin, Jing

    2009-09-01

    Butyrate, one of the SCFA, promotes the development of the intestinal barrier. However, the molecular mechanisms underlying the butyrate regulation of the intestinal barrier are unknown. To test the hypothesis that the effect of butyrate on the intestinal barrier is mediated by the regulation of the assembly of tight junctions involving the activation of the AMP-activated protein kinase (AMPK), we determined the effect of butyrate on the intestinal barrier by measuring the transepithelial electrical resistance (TER) and inulin permeability in a Caco-2 cell monolayer model. We further used a calcium switch assay to study the assembly of epithelial tight junctions and determined the effect of butyrate on the assembly of epithelial tight junctions and AMPK activity. We demonstrated that the butyrate treatment increased AMPK activity and accelerated the assembly of tight junctions as shown by the reorganization of tight junction proteins, as well as the development of TER. AMPK activity was also upregulated by butyrate during calcium switch-induced tight junction assembly. Compound C, a specific AMPK inhibitor, inhibited the butyrate-induced activation of AMPK. The facilitating effect of butyrate on the increases in TER in standard culture media, as well as after calcium switch, was abolished by compound C. We conclude that butyrate enhances the intestinal barrier by regulating the assembly of tight junctions. This dynamic process is mediated by the activation of AMPK. These results suggest an intriguing link between SCFA and the intracellular energy sensor for the development of the intestinal barrier.

  11. Abl family kinases regulate endothelial barrier function in vitro and in mice.

    Directory of Open Access Journals (Sweden)

    Elizabeth M Chislock

    Full Text Available The maintenance of endothelial barrier function is essential for normal physiology, and increased vascular permeability is a feature of a wide variety of pathological conditions, leading to complications including edema and tissue damage. Use of the pharmacological inhibitor imatinib, which targets the Abl family of non-receptor tyrosine kinases (Abl and Arg, as well as other tyrosine kinases including the platelet-derived growth factor receptor (PDGFR, Kit, colony stimulating factor 1 receptor (CSF1R, and discoidin domain receptors, has shown protective effects in animal models of inflammation, sepsis, and other pathologies characterized by enhanced vascular permeability. However, the imatinib targets involved in modulation of vascular permeability have not been well-characterized, as imatinib inhibits multiple tyrosine kinases not only in endothelial cells and pericytes but also immune cells important for disorders associated with pathological inflammation and abnormal vascular permeability. In this work we employ endothelial Abl knockout mice to show for the first time a direct role for Abl in the regulation of vascular permeability in vivo. Using both Abl/Arg-specific pharmacological inhibition and endothelial Abl knockout mice, we demonstrate a requirement for Abl kinase activity in the induction of endothelial permeability by vascular endothelial growth factor both in vitro and in vivo. Notably, Abl kinase inhibition also impaired endothelial permeability in response to the inflammatory mediators thrombin and histamine. Mechanistically, we show that loss of Abl kinase activity was accompanied by activation of the barrier-stabilizing GTPases Rac1 and Rap1, as well as inhibition of agonist-induced Ca(2+ mobilization and generation of acto-myosin contractility. In all, these findings suggest that pharmacological targeting of the Abl kinases may be capable of inhibiting endothelial permeability induced by a broad range of agonists and that use

  12. High glucose induces dysfunction of airway epithelial barrier through down-regulation of connexin 43.

    Science.gov (United States)

    Yu, Hongmei; Yang, Juan; Zhou, Xiangdong; Xiao, Qian; Lü, Yang; Xia, Li

    2016-03-01

    The airway epithelium is a barrier to the inhaled antigens and pathogens. Connexin 43 (Cx43) has been found to play critical role in maintaining the function of airway epithelial barrier and be involved in the pathogenesis of the diabetic retinal vasculature, diabetes nephropathy and diabetes skin. Hyperglycemia has been shown to be an independent risk factor for respiratory infections. We hypothesize that the down-regulation of Cx43 induced by HG alters the expression of tight junctions (zonula occludens-1 (ZO-1) and occludin) and contributes to dysfunction of airway epithelial barrier, and Cx43 plays a critical role in the process in human airway epithelial cells (16 HBE). We show that high glucose (HG) decreased the expression of ZO-1 and occludin, disassociated interaction between Cx43 and tight junctions, and then increased airway epithelial transepithelial electrical resistance (TER) and permeability by down-regulation of Cx43 in human airway epithelial cells. These observations demonstrate an important role for Cx43 in regulating HG-induced dysfunction of airway epithelial barrier. These findings may bring new insights into the molecular pathogenesis of pulmonary infection related to diabetes mellitus and lead to novel therapeutic intervention for the dysfunction of airway epithelial barrier in chronic inflammatory airway diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Value-meaning Barriers in Research Activity of Junior Scientists

    Directory of Open Access Journals (Sweden)

    Shabalovskaya M.V.

    2017-08-01

    Full Text Available Contents of value-meaning barriers are covered that acquire certain specifics in research activity and influence formation of meaning-forming research motivation of junior scientists. Such barriers were assumed to be conditioned by dissonance between dominating values and degree of their realization in junior researchers. Sample of respondents included 88 beginners: postgraduate students (n=65 and masters (n=23 of Tomsk high schools aged between 21 and 35 years. As research methods the expanded version of technique by M. Rokeach (proposed by M.S. Yanitsky and A.V. Seryy, methods of statistical analysis of results (frequency analysis, Mann-Whitney test were used. Relevant value orientations of junior scientists are presented. Gender differences in value-meaning domain are revealed. Differences in values in postgraduate students and masters were found. Dissonance in degree of fulfillment of terminal and instrumental values has been established that indicates disturbances of value-meaning domain of the personality of junior scientists. Results add to scientific ideas about value-meaning barriers in research activity of junior scientists.

  14. Barriers, activities and participation: Incorporating ICF into service planning datasets.

    LENUS (Irish Health Repository)

    O'Donovan, MA

    2009-05-21

    Purpose. Guided by the World Health Organization\\'s International Classification of Functioning, Disability and Health (ICF), a measure of activity and participation (MAP) was developed and incorporated into the National Physical and Sensory Disability Database in Ireland. The aims of this article are to investigate and explore the relationship between the barriers, participation restriction and functioning levels experienced by people with disabilities. Method. Seven thousand five hundred and sixty-two personal interviews with people meeting specific eligibility criteria for registering onto the database were conducted across four health service executive regions in Ireland. Results. Overall, differences in barriers, participation restriction and activity limitations experienced by people with different types of disabilities were found to be significant. Furthermore, low functioning and experience of barriers were indicators of participation restriction. Conclusions. This article has shown that elements of the ICF have been successfully operationalised in a service planning tool through the development of the MAP. This provides a more holistic view of disability and will enable the impact of service interventions to be measured over time.

  15. Glycogen Synthase Kinase 3 (GSK-3) influences epithelial barrier function by regulating Occludin, Claudin-1 and E-cadherin expression

    Energy Technology Data Exchange (ETDEWEB)

    Severson, Eric A.; Kwon, Mike; Hilgarth, Roland S.; Parkos, Charles A. [Epithelial Pathobiology Research Unit, Dept. of Pathology, Emory University, Atlanta, GA 30322 (United States); Nusrat, Asma, E-mail: anusrat@emory.edu [Epithelial Pathobiology Research Unit, Dept. of Pathology, Emory University, Atlanta, GA 30322 (United States)

    2010-07-02

    The Apical Junctional Complex (AJC) encompassing the tight junction (TJ) and adherens junction (AJ) plays a pivotal role in regulating epithelial barrier function and epithelial cell proliferative processes through signaling events that remain poorly characterized. A potential regulator of AJC protein expression is Glycogen Synthase Kinase-3 (GSK-3). GSK-3 is a constitutively active kinase that is repressed during epithelial-mesenchymal transition (EMT). In the present study, we report that GSK-3 activity regulates the structure and function of the AJC in polarized model intestinal (SK-CO15) and kidney (Madin-Darby Canine Kidney (MDCK)) epithelial cells. Reduction of GSK-3 activity, either by small molecule inhibitors or siRNA targeting GSK-3 alpha and beta mRNA, resulted in increased permeability to both ions and bulk solutes. Immunofluorescence labeling and immunoblot analyses revealed that the barrier defects correlated with decreased protein expression of AJC transmembrane proteins Occludin, Claudin-1 and E-cadherin without influencing other TJ proteins, Zonula Occludens-1 (ZO-1) and Junctional Adhesion Molecule A (JAM-A). The decrease in Occludin and E-cadherin protein expression correlated with downregulation of the corresponding mRNA levels for these respective proteins following GSK-3 inhibition. These observations implicate an important role of GSK-3 in the regulation of the structure and function of the AJC that is mediated by differential modulation of mRNA transcription of key AJC proteins, Occludin, Claudin-1 and E-cadherin.

  16. VE-cadherin trans-interactions modulate Rac activation and enhancement of lung endothelial barrier by iloprost.

    Science.gov (United States)

    Birukova, Anna A; Tian, Yufeng; Dubrovskyi, Oleksii; Zebda, Noureddine; Sarich, Nicolene; Tian, Xinyong; Wang, Yingxiao; Birukov, Konstantin G

    2012-10-01

    Small GTPase Rac is important regulator of endothelial cell (EC) barrier enhancement by prostacyclin characterized by increased peripheral actin cytoskeleton and increased interactions between VE-cadherin and other adherens junction (AJ) proteins. This study utilized complementary approaches including siRNA knockdown, culturing in Ca(2+) -free medium, and VE-cadherin blocking antibody to alter VE-cadherin extracellular interactions to investigate the role of VE-cadherin outside-in signaling in modulation of Rac activation and EC barrier regulation by prostacyclin analog iloprost. Spatial analysis of Rac activation in pulmonary EC by FRET revealed additional spike in iloprost-induced Rac activity at the sites of newly formed cell-cell junctions. In contrast, disruption of VE-cadherin extracellular trans-interactions suppressed iloprost-activated Rac signaling and attenuated EC barrier enhancement and cytoskeletal remodeling. These inhibitory effects were associated with decreased membrane accumulation and activation of Rac-specific guanine nucleotide exchange factors (GEFs) Tiam1 and Vav2. Conversely, plating of pulmonary EC on surfaces coated with extracellular VE-cadherin domain further promoted iloprost-induced Rac signaling. In the model of thrombin-induced EC barrier recovery, blocking of VE-cadherin trans-interactions attenuated activation of Rac pathway during recovery phase and delayed suppression of Rho signaling and restoration of EC barrier properties. These results suggest that VE-cadherin outside-in signaling controls locally Rac activity stimulated by barrier protective agonists. This control is essential for maximal EC barrier enhancement and accelerated barrier recovery. Copyright © 2011 Wiley Periodicals, Inc.

  17. Proteolytic Regulation of the Intestinal Epithelial Barrier: Mechanisms and Interventions

    Science.gov (United States)

    2014-09-01

    Studies are planned to investigate T84 restitution in the absence and presence of IL-13 in the presence or absence of matriptase. To achieve this, we...position recorded relative to the base of the crypt. We plan to investigate other cell markers and in situ cell death by TUNEL assay and activated...promoter in both heterozygous and hypomorphic St14 mice. It was planned to focus on this task in Years 2 and 3 as proposed in the timeline. The

  18. Rap1 GTPase activation and barrier enhancement in rpe inhibits choroidal neovascularization in vivo.

    Directory of Open Access Journals (Sweden)

    Erika S Wittchen

    Full Text Available Loss of barrier integrity precedes the development of pathologies such as metastasis, inflammatory disorders, and blood-retinal barrier breakdown present in neovascular age-related macular degeneration. Rap1 GTPase is involved in regulating both endothelial and epithelial cell junctions; the specific role of Rap1A vs. Rap1B isoforms is less clear. Compromise of retinal pigment epithelium barrier function is a contributing factor to the development of AMD. We utilized shRNA of Rap1 isoforms in cultured human retinal pigment epithelial cells, along with knockout mouse models to test the role of Rap1 on promoting RPE barrier properties, with emphasis on the dynamic junctional regulation that is triggered when the adhesion between cells is challenged. In vitro, Rap1A shRNA reduced steady-state barrier integrity, whereas Rap1B shRNA affected dynamic junctional responses. In a laser-induced choroidal neovascularization (CNV model of macular degeneration, Rap1b(-/- mice exhibited larger CNV volumes compared to wild-type or Rap1a(-/- . In vivo, intravitreal injection of a cAMP analog (8CPT-2'-O-Me-cAMP that is a known Rap1 activator significantly reduced laser-induced CNV volume, which correlated with the inhibition of CEC transmigration across 8CPT-2'O-Me-cAMP-treated RPE monolayers in vitro. Rap1 activation by 8CPT-2'-O-Me-cAMP treatment increased recruitment of junctional proteins and F-actin to cell-cell contacts, increasing both the linearity of junctions in vitro and in cells surrounding laser-induced lesions in vivo. We conclude that in vitro, Rap1A may be important for steady state barrier integrity, while Rap1B is involved more in dynamic junctional responses such as resistance to junctional disassembly induced by EGTA and reassembly of cell junctions following disruption. Furthermore, activation of Rap1 in vivo inhibited development of choroidal neovascular lesions in a laser-injury model. Our data suggest that targeting Rap1 isoforms in vivo

  19. AKAP9, a Regulator of Microtubule Dynamics, Contributes to Blood-Testis Barrier Function.

    Science.gov (United States)

    Venkatesh, Deepak; Mruk, Dolores; Herter, Jan M; Cullere, Xavier; Chojnacka, Katarzyna; Cheng, C Yan; Mayadas, Tanya N

    2016-02-01

    The blood-testis barrier (BTB), formed between adjacent Sertoli cells, undergoes extensive remodeling to facilitate the transport of preleptotene spermatocytes across the barrier from the basal to apical compartments of the seminiferous tubules for further development and maturation into spermatozoa. The actin cytoskeleton serves unique structural and supporting roles in this process, but little is known about the role of microtubules and their regulators during BTB restructuring. The large isoform of the cAMP-responsive scaffold protein AKAP9 regulates microtubule dynamics and nucleation at the Golgi. We found that conditional deletion of Akap9 in mice after the initial formation of the BTB at puberty leads to infertility. Akap9 deletion results in marked alterations in the organization of microtubules in Sertoli cells and a loss of barrier integrity despite a relatively intact, albeit more apically localized F-actin and BTB tight junctional proteins. These changes are accompanied by a loss of haploid spermatids due to impeded meiosis. The barrier, however, progressively reseals in older Akap9 null mice, which correlates with a reduction in germ cell apoptosis and a greater incidence of meiosis. However, spermiogenesis remains defective, suggesting additional roles for AKAP9 in this process. Together, our data suggest that AKAP9 and, by inference, the regulation of the microtubule network are critical for BTB function and subsequent germ cell development during spermatogenesis.

  20. Active explosion barrier performance against methane and coal dust explosions

    Institute of Scientific and Technical Information of China (English)

    J J L du Plessis

    2015-01-01

    Preventing the propagation of methane or coal dust explosions through the use of active explosion-suppression systems remains one of the most underutilised explosion controls in underground coal mines. As part of the effort to develop better technologies to safeguard mines, the use of active barrier systems was investigated at Kloppersbos in South Africa. The system is designed to meet the requirements of the European Standard (EN 14591-4 2007) as well as the Mine Safety Standardisation in the Ministry of Coal Industry, Coal Industrial l Standard of the Peoples Republic of China (MT 694-1997). From the tests conducted, it can be concluded that the ExploSpot System was successful in stopping flame propagation for both methane and methane and coal dust hybrid explosions when ammonium phosphate powder was used as the suppression material. The use of this barrier will provide coal mine management with an additional explosion control close to the point of ignition and may find application within longwall faces further protecting mines against the risk of an explosion propagating throughout a mine.

  1. Intermittent hypoxia-induced endothelial barrier dysfunction requires ROS-dependent MAP kinase activation.

    Science.gov (United States)

    Makarenko, Vladislav V; Usatyuk, Peter V; Yuan, Guoxiang; Lee, May M; Nanduri, Jayasri; Natarajan, Viswanathan; Kumar, Ganesh K; Prabhakar, Nanduri R

    2014-04-15

    The objective of the present study was to determine the impact of simulated apnea with intermittent hypoxia (IH) on endothelial barrier function and assess the underlying mechanism(s). Experiments were performed on human lung microvascular endothelial cells exposed to IH-consisting alternating cycles of 1.5% O2 for 30s followed by 20% O2 for 5 min. IH decreased transendothelial electrical resistance (TEER) suggesting attenuated endothelial barrier function. The effect of IH on TEER was stimulus dependent and reversible after reoxygenation. IH-exposed cells exhibited stress fiber formation and redistribution of cortactin, vascular endothelial-cadherins, and zona occludens-1 junction proteins along with increased intercellular gaps at cell-cell boundaries. Extracellular signal-regulated kinase (ERK) and c-jun NH2-terminal kinase (JNK) were phosphorylated in IH-exposed cells. Inhibiting either ERK or JNK prevented the IH-induced decrease in TEER and the reorganization of the cytoskeleton and junction proteins. IH increased reactive oxygen species (ROS) levels, and manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride, a membrane-permeable antioxidant, prevented ERK and JNK phosphorylation as well as IH-induced changes in endothelial barrier function. These results demonstrate that IH via ROS-dependent activation of MAP kinases leads to reorganization of cytoskeleton and junction proteins resulting in endothelial barrier dysfunction.

  2. Proteinase activity regulation by glycosaminoglycans

    Directory of Open Access Journals (Sweden)

    Tersariol I.L.S.

    2002-01-01

    Full Text Available There are few reports concerning the biological role and the mechanisms of interaction between proteinases and carbohydrates other than those involved in clotting. It has been shown that the interplay of enzymes and glycosaminoglycans is able to modulate the activity of different proteases and also to affect their structures. From the large number of proteases belonging to the well-known protease families and also the variety of carbohydrates described as widely distributed, only few events have been analyzed more deeply. The term "family" is used to describe a group of proteases in which every member shows an evolutionary relationship to at least one other protease. This relationship may be evident throughout the entire sequence, or at least in that part of the sequence responsible for catalytic activity. The majority of proteases belong to the serine, cysteine, aspartic or metalloprotease families. By considering the existing limited proteolysis process, in addition to the initial idea that the proteinases participate only in digestive processes, it is possible to conclude that the function of the enzymes is strictly limited to the cleavage of intended substrates since the destruction of functional proteins would result in normal tissue damage. In addition, the location as well as the eventual regulation of protease activity promoted by glycosaminoglycans can play an essential role in the development of several physiopathological conditions.

  3. Cyclosporin A induces hyperpermeability of the blood-brain barrier by inhibiting autocrine adrenomedullin-mediated up-regulation of endothelial barrier function.

    Science.gov (United States)

    Dohgu, Shinya; Sumi, Noriko; Nishioku, Tsuyoshi; Takata, Fuyuko; Watanabe, Takuya; Naito, Mikihiko; Shuto, Hideki; Yamauchi, Atsushi; Kataoka, Yasufumi

    2010-10-10

    Cyclosporin A, a potent immunosuppressant, can often produce neurotoxicity in patients, although its penetration into the brain is restricted by the blood-brain barrier (BBB). Brain pericytes and astrocytes, which are periendothelial accessory structures of the BBB, can be involved in cyclosporin A-induced BBB disruption. However, the mechanism by which cyclosporin A causes BBB dysfunction remains unknown. Here, we show that in rodent brain endothelial cells, cyclosporin A decreased transendothelial electrical resistance (TEER) by inhibiting intracellular signal transduction downstream of adrenomedullin, an autocrine regulator of BBB function. Cyclosporin A stimulated adrenomedullin release from brain endothelial cells, but did not affect binding of adrenomedullin to its receptors. This cyclosporin A-induced decrease in TEER was attenuated by exogenous addition of adrenomedullin. Cyclosporin A dose-dependently decreased the total cAMP concentration in brain endothelial cells. A combination of cyclosporin A (1microM) with an adenylyl cyclase inhibitor, 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22536; 10microM), or a protein kinase A (PKA) inhibitor, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H89; 1microM), markedly increased sodium fluorescein permeability in brain endothelial cells, whereas each drug alone had no effect. Thus, these data suggest that cyclosporin A inhibits the adenylyl cyclase/cyclic AMP/PKA signaling pathway activated by adrenomedullin, leading to impairment of brain endothelial barrier function. Copyright 2010. Published by Elsevier B.V.

  4. Physical Activity Pattern of Malaysian Preschoolers: Environment, Barriers, and Motivators for Active Play.

    Science.gov (United States)

    Lee, Shoo Thien; Wong, Jyh Eiin; Ong, Wei Wen; Ismail, Mohd Noor; Deurenberg, Paul; Poh, Bee Koon

    2016-07-01

    Children's physical activity has been correlated with child characteristics and social or physical environment. This study aimed to compare preschoolers' physical activity among various sociodemographic characteristics and to determine barriers, motivators, and environmental factors for active play. A total of 835 preschoolers were included in this analysis. Time spent on active play, quiet play, and screen time was reported by parents. Boys spent significantly more time on active play and screen time than girls. Time spent on quiet play was highest in East Coast Peninsular Malaysia and lowest in Sarawak. Some 40% of children achieved active play recommendation while 27% exceeded daily screen time recommendation. Most parents reported that their child played actively in the house area; and that the main barrier and motivator to active play were safety and child's enjoyment, respectively. These findings demonstrate that sociodemographic characteristics and environment should be considered in designing physical activity intervention programs.

  5. Barriers for recess physical activity: a gender specific qualitative focus group exploration

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Tjørnhøj-Thomsen, Tine; Schipperijn, Jasper

    barriers, there were both inter- and intra-gender differences in the children´s perceptions of these barriers. Weather was a barrier for all children, apart from the most active boys. Conflicts were perceived as a barrier particularly for those boys who played ballgames. Girls said they would like to have...... more secluded areas added to the school playground, even in large schoolyards where lack of space was not a barrier. This aligned with girls’ requests for more “hanging-out” facilities, whereas boys primarily wanted activity promoting facilities. Conclusion: Based on the results from this study, we......Background: Many children, in particular girls, do not reach the recommended amount of daily physical activity. School recess provides an opportunity for both boys and girls to be physically active, but barriers to recess physical activity are not well understood. This study explores gender...

  6. Self-regulation as a type of managerial activity.

    Directory of Open Access Journals (Sweden)

    Anna Algazina

    2017-01-01

    Full Text Available УДК 342.9The subject. In the context of the ongoing administrative reform in the Russian Federation the issue of self-regulation is becoming increasingly important.Introduction of Institute of self-regulation is intended to reduce the degree of state intervention in private spheres of professional activity, to eliminate excessive administrative barriers, reduce government expenditures on regulation and control in their respective areas of operation, which is especially important in the current economic conditions.However, in Russian legal science is no recognized definition of "self-regulation", but a unity of views on the question of the relationship between self-regulation and state regulation of business relations.In this regard, the author attempts to examine the concept of "self-regulation" through the prism of knowledge about public administration.The purpose of the article is to identify the essential features and to articulate the concept of self-regulation by comparing it with other varieties of regulation.Methodology. The methodological basis for the study: general scientific methods (analysis, synthesis, comparison, description; private and academic (interpretation, formal-legal.Results, scope. Based on the analysis allocated in the science of administrative law approaches to the system of public administration justifies the conclusion that the notion "regulation" is specific in relation to the generic concept of "management" and is a kind of management, consisting in the drafting of rules of conduct and sanctions for non-compliance or inadequate performance.In addition, the article highlights the problem of the genesis of self-regulation, building a system of principles of self-regulation, comparison of varieties of self-regulatory organizations among themselves.Conclusions. The comparison of self-regulation other types of regulation (such as state regulation and co-regulation highlighted the essential features of this phenomenon

  7. Peroxiredoxins in Regulation of MAPK Signalling Pathways; Sensors and Barriers to Signal Transduction

    Science.gov (United States)

    Latimer, Heather R.; Veal, Elizabeth A.

    2016-01-01

    Peroxiredoxins are highly conserved and abundant peroxidases. Although the thioredoxin peroxidase activity of peroxiredoxin (Prx) is important to maintain low levels of endogenous hydrogen peroxide, Prx have also been shown to promote hydrogen peroxide-mediated signalling. Mitogen activated protein kinase (MAPK) signalling pathways mediate cellular responses to a variety of stimuli, including reactive oxygen species (ROS). Here we review the evidence that Prx can act as both sensors and barriers to the activation of MAPK and discuss the underlying mechanisms involved, focusing in particular on the relationship with thioredoxin. PMID:26813660

  8. Cellular zinc is required for intestinal epithelial barrier maintenance via the regulation of claudin-3 and occludin expression.

    Science.gov (United States)

    Miyoshi, Yuka; Tanabe, Soichi; Suzuki, Takuya

    2016-07-01

    Intracellular zinc is required for a variety of cell functions, but its precise roles in the maintenance of the intestinal tight junction (TJ) barrier remain unclear. The present study investigated the essential roles of intracellular zinc in the preservation of intestinal TJ integrity and the underlying molecular mechanisms. Depletion of intracellular zinc in both intestinal Caco-2 cells and mouse colons through the application of a cell-permeable zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) induced a disruption of the TJ barrier, as indicated by increased FITC-labeled dextran flux and decreased transepithelial electrical resistance. The TPEN-induced TJ disruption is associated with downregulation of two TJ proteins, occludin and claudin-3. Biotinylation of cell surface proteins revealed that the zinc depletion induced the proteolysis of occludin but not claudin-3. Occludin proteolysis was sensitive to the inhibition of calpain activity, and increased calpain activity was observed in the zinc-depleted cells. Although quantitative PCR analysis and promoter reporter assay have demonstrated that the zinc depletion-induced claudin-3 downregulation occurred at transcriptional levels, a site-directed mutation in the egr1 binding site in the claudin-3 promoter sequence induced loss of both the basal promoter activity and the TPEN-induced decreases. Reduced egr1 expression by a specific siRNA also inhibited claudin-3 expression and transepithelial electrical resistance maintenance in cells. This study shows that intracellular zinc has an essential role in the maintenance of the intestinal epithelial TJ barrier through regulation of occludin proteolysis and claudin-3 transcription.

  9. Barriers Affecting Physical Activity in Rural Communities: Perceptions of Parents and Children

    Science.gov (United States)

    McWhinney, Sharon; McDonald, Andrea; Dawkins-Moultin, Lenna; Outley, Corliss; McKyer, E. Lisako; Thomas, Audrene

    2011-01-01

    A comprehensive understanding of the barriers inhibiting physical activity among children is critical in the fight against childhood obesity. This qualitative interview study examined parents' and children's perceptions of the barriers to physical activity in rural communities of low socioeconomic status. Parents and children concurred that the…

  10. Regulation of Copper Transport Crossing Brain Barrier Systems by Cu-ATPases: Effect of Manganese Exposure

    Science.gov (United States)

    Fu, Xue; Zhang, Yanshu; Jiang, Wendy; Monnot, Andrew Donald; Bates, Christopher Alexander; Zheng, Wei

    2014-01-01

    Regulation of cellular copper (Cu) homeostasis involves Cu-transporting ATPases (Cu-ATPases), i.e., ATP7A and ATP7B. The question as to how these Cu-ATPases in brain barrier systems transport Cu, i.e., toward brain parenchyma, cerebrospinal fluid (CSF), or blood, remained unanswered. This study was designed to characterize roles of Cu-ATPases in regulating Cu transport at the blood-brain barrier (BBB) and blood-CSF barrier (BCB) and to investigate how exposure to toxic manganese (Mn) altered the function of Cu-ATPases, thereby contributing to the etiology of Mn-induced parkinsonian disorder. Studies by quantitative real-time RT-PCR (qPCR), Western blot, and immunocytochemistry revealed that both Cu-ATPases expressed abundantly in BBB and BCB. Transport kinetic studies by in situ brain infusion and ventriculo-cisternal (VC) perfusion in Sprague Dawley rat suggested that the BBB was a major site for Cu entry into brain, whereas the BCB was a predominant route for Cu efflux from the CSF to blood. Confocal evidence showed that the presence of excess Cu or Mn in the choroid plexus cells led to ATP7A relocating toward the apical microvilli facing the CSF, but ATP7B toward the basolateral membrane facing blood. Mn exposure inhibited the production of both Cu-ATPases. Collectively, these data suggest that Cu is transported by the BBB from the blood to brain, which is mediated by ATP7A in brain capillary. By diffusion, Cu ions move from the interstitial fluid into the CSF, where they are taken up by the BCB. Within the choroidal epithelial cells, Cu ions are transported by ATP7B back to the blood. Mn exposure alters these processes, leading to Cu dyshomeostasis-associated neuronal injury. PMID:24614235

  11. Etk/Bmx activation modulates barrier function in epithelial cells.

    Science.gov (United States)

    Hamm-Alvarez, S F; Chang, A; Wang, Y; Jerdeva, G; Lin, H H; Kim, K J; Ann, D K

    2001-06-01

    Etk/Bmx is a member of the Tec family of cytoplasmic non-receptor tyrosine kinases known to express in epithelial cells. We demonstrate herein that Etk activation in stably Etk-transfected epithelial Pa-4 cells resulted in a consistently increased transepithelial resistance (TER). After 24 h of hypoxic (1% O(2)) exposure, the TER and equivalent active ion transport rate (I(eq)) were reduced to <5% of the normoxia control in Pa-4 cells, whereas both TER and I(eq) were maintained at comparable and 60% levels, respectively, relative to their normoxic controls in cells with Etk activation. Moreover, Pa-4 cells exhibited an abundant actin stress fiber network with a diffuse distribution of beta-catenin at the cell periphery. By contrast, Etk-activated cells displayed a redistribution of actin to an exclusively peripheral network, with a discrete band of beta-catenin also concentrated at the cell periphery, and an altered occludin distribution profile. On the basis of these findings, we propose that Etk may be a novel regulator of epithelial junctions during physiological and pathophysiological conditions.

  12. Barriers to involvement in physical activities of persons with mental illness.

    Science.gov (United States)

    Shor, Ron; Shalev, Anat

    2016-03-01

    Participating in physical activities could be essential for reducing the multiple risk factors for health problems that persons with severe mental illness (SMI) may suffer. However, people with SMI are significantly less active than the general population. To develop knowledge about factors related to the perceived barriers hindering this population's participation in physical activities and the benefits this participation would have, a study was conducted in Israel with 86 people with mental illness living in community mental health facilities prior to their participation in a health promotion program. A mixed method was implemented and included: a scale designed to measure participants' perceptions of the barriers to and benefits of involvement in physical activities; instruments focusing on bio-psycho-social factors that may affect the level of barriers experienced; and personal interviews. The findings revealed high ranking for accessibility barriers hindering the participation in physical activities. Bio-psycho-social factors stemming from the participants' mental health, such as level of depression, were correlated with higher ranking of accessibility barriers. Bio-psycho-social factors reflecting positive mental health and health, such as positive appraisal of body weight, were correlated with lower ranking of accessibility barriers. Other barriers may include organizational and broader systemic barriers in the mental health facilities where the participants reside. These findings illuminate the need to consider the unique challenges that persons with mental illness may face in any attempt to advance their involvement in physical activity.

  13. Is the perception of time pressure a barrier to healthy eating and physical activity among women?

    Science.gov (United States)

    Welch, Nicky; McNaughton, Sarah A; Hunter, Wendy; Hume, Clare; Crawford, David

    2009-07-01

    To describe the proportion of women reporting time is a barrier to healthy eating and physical activity, the characteristics of these women and the perceived causes of time pressure, and to examine associations between perceptions of time as a barrier and consumption of fruit, vegetables and fast food, and physical activity. A cross-sectional survey of food intake, physical activity and perceived causes of time pressure. A randomly selected community sample. A sample of 1580 women self-reported their food intake and their perceptions of the causes of time pressure in relation to healthy eating. An additional 1521 women self-reported their leisure-time physical activity and their perceptions of the causes of time pressure in relation to physical activity. Time pressure was reported as a barrier to healthy eating by 41% of the women and as a barrier to physical activity by 73%. Those who reported time pressure as a barrier to healthy eating were significantly less likely to meet fruit, vegetable and physical activity recommendations, and more likely to eat fast food more frequently. Women reporting time pressure as a barrier to healthy eating and physical activity are less likely to meet recommendations than are women who do not see time pressure as a barrier. Further research is required to understand the perception of time pressure issues among women and devise strategies to improve women's food and physical activity behaviours.

  14. Research on the application of active sound barriers for the transformer noise abatement

    Directory of Open Access Journals (Sweden)

    Hu Sheng

    2016-01-01

    Full Text Available Sound barriers are a type of measure most commonly used in the noise abatement of transformers. In the noise abatement project of substations, the design of sound barriers is restrained by the portal frames which are used to hold up outgoing lines from the main transformers, which impacts the noise reduction effect. If active sound barriers are utilized in these places, the noise diffraction of sound barriers can be effectively reduced. At a 110kV Substation, an experiment using a 15-channel active sound barrier has been carried out. The result of the experiment shows that the mean noise reduction value (MNRV of the noise measuring points at the substation boundary are 1.5 dB (A. The effect of the active noise control system is impacted by the layout of the active noise control system, the acoustic environment on site and the spectral characteristic of the target area.

  15. The potential benefits of herbicide regulation: a cautionary note for the Great Barrier Reef catchment area.

    Science.gov (United States)

    Davis, A M; Lewis, S E; Brodie, J E; Benson, Ash

    2014-08-15

    Industry transitions away from traditional photosystem II inhibiting (PSII) herbicides towards an 'alternative' herbicide suite are now widely advocated as a key component of improved environmental outcomes for Australia's Great Barrier Reef and improved environmental stewardship on the part of the Queensland sugar industry. A systematic desktop risk analysis found that based on current farming practices, traditional PSII herbicides can pose significant environmental risks. Several of the 'alternatives' that can directly fill a specific pre-emergent ('soil residual') weed control function similar to regulated PSII herbicides also, however, presented a similar environmental risk profile, regardless of farming systems and bio-climatic zones being considered. Several alternatives with a pre-emergent residual function as well as alternative post-emergent (contact or 'knockdown') herbicides were, predicted to pose lower environmental risks than the regulated PSII herbicides to most trophic levels, although environmental risks could still be present. While several herbicides may well be viable alternatives in terms of weed control, they can still present equal or possibly higher risks to the environment. Imposing additional regulations (or even de-registrations) on particular herbicides could result in marginal, and possibly perverse environmental impacts in the long term, if usage shifts to alternative herbicides with similar risk profiles. Regardless of any regulatory efforts, improved environmental sustainability outcomes in pesticide practices within the Great Barrier Reef catchment area will hinge primarily on the continuing adoption of integrated, strategic pest management systems and technologies applied to both traditional and 'alternative' herbicides. One of the emerging policy challenges is ensuring the requisite technical and extension support for cane growers to ensure effective adoption of rapidly evolving farming system technologies, in a very dynamic and

  16. MALT1 Protease Activation Triggers Acute Disruption of Endothelial Barrier Integrity via CYLD Cleavage.

    Science.gov (United States)

    Klei, Linda R; Hu, Dong; Panek, Robert; Alfano, Danielle N; Bridwell, Rachel E; Bailey, Kelly M; Oravecz-Wilson, Katherine I; Concel, Vincent J; Hess, Emily M; Van Beek, Matthew; Delekta, Phillip C; Gu, Shufang; Watkins, Simon C; Ting, Adrian T; Gough, Peter J; Foley, Kevin P; Bertin, John; McAllister-Lucas, Linda M; Lucas, Peter C

    2016-09-27

    Microvascular endothelial cells maintain a tight barrier to prevent passage of plasma and circulating immune cells into the extravascular tissue compartment, yet endothelial cells respond rapidly to vasoactive substances, including thrombin, allowing transient paracellular permeability. This response is a cornerstone of acute inflammation, but the mechanisms responsible are still incompletely understood. Here, we demonstrate that thrombin triggers MALT1 to proteolytically cleave cylindromatosis (CYLD). Fragmentation of CYLD results in microtubule disruption and a cascade of events leading to endothelial cell retraction and an acute permeability response. This finding reveals an unexpected role for the MALT1 protease, which previously has been viewed mostly as a driver of pro-inflammatory NF-κB signaling in lymphocytes. Thus, MALT1 not only promotes immune cell activation but also acutely regulates endothelial cell biology, actions that together facilitate tissue inflammation. Pharmacologic inhibition of MALT1 may therefore have synergistic impact by targeting multiple disparate steps in the overall inflammatory response.

  17. MALT1 Protease Activation Triggers Acute Disruption of Endothelial Barrier Integrity via CYLD Cleavage

    Directory of Open Access Journals (Sweden)

    Linda R. Klei

    2016-09-01

    Full Text Available Microvascular endothelial cells maintain a tight barrier to prevent passage of plasma and circulating immune cells into the extravascular tissue compartment, yet endothelial cells respond rapidly to vasoactive substances, including thrombin, allowing transient paracellular permeability. This response is a cornerstone of acute inflammation, but the mechanisms responsible are still incompletely understood. Here, we demonstrate that thrombin triggers MALT1 to proteolytically cleave cylindromatosis (CYLD. Fragmentation of CYLD results in microtubule disruption and a cascade of events leading to endothelial cell retraction and an acute permeability response. This finding reveals an unexpected role for the MALT1 protease, which previously has been viewed mostly as a driver of pro-inflammatory NF-κB signaling in lymphocytes. Thus, MALT1 not only promotes immune cell activation but also acutely regulates endothelial cell biology, actions that together facilitate tissue inflammation. Pharmacologic inhibition of MALT1 may therefore have synergistic impact by targeting multiple disparate steps in the overall inflammatory response.

  18. Glycosylation regulates prestin cellular activity.

    Science.gov (United States)

    Rajagopalan, Lavanya; Organ-Darling, Louise E; Liu, Haiying; Davidson, Amy L; Raphael, Robert M; Brownell, William E; Pereira, Fred A

    2010-03-01

    Glycosylation is a common post-translational modification of proteins and is implicated in a variety of cellular functions including protein folding, degradation, sorting and trafficking, and membrane protein recycling. The membrane protein prestin is an essential component of the membrane-based motor driving electromotility changes (electromotility) in the outer hair cell (OHC), a central process in auditory transduction. Prestin was earlier identified to possess two N-glycosylation sites (N163, N166) that, when mutated, marginally affect prestin nonlinear capacitance (NLC) function in cultured cells. Here, we show that the double mutant prestin(NN163/166AA) is not glycosylated and shows the expected NLC properties in the untreated and cholesterol-depleted HEK 293 cell model. In addition, unlike WT prestin that readily forms oligomers, prestin(NN163/166AA) is enriched as monomers and more mobile in the plasma membrane, suggesting that oligomerization of prestin is dependent on glycosylation but is not essential for the generation of NLC in HEK 293 cells. However, in the presence of increased membrane cholesterol, unlike the hyperpolarizing shift in NLC seen with WT prestin, cells expressing prestin(NN163/166AA) exhibit a linear capacitance function. In an attempt to explain this finding, we discovered that both WT prestin and prestin(NN163/166AA) participate in cholesterol-dependent cellular trafficking. In contrast to WT prestin, prestin(NN163/166AA) shows a significant cholesterol-dependent decrease in cell-surface expression, which may explain the loss of NLC function. Based on our observations, we conclude that glycosylation regulates self-association and cellular trafficking of prestin(NN163/166AA). These observations are the first to implicate a regulatory role for cellular trafficking and sorting in prestin function. We speculate that the cholesterol regulation of prestin occurs through localization to and internalization from membrane microdomains by

  19. Barriers and enablers of physical activity engagement for patients with COPD in primary care

    Directory of Open Access Journals (Sweden)

    Kosteli MC

    2017-03-01

    Full Text Available Maria-Christina Kosteli,1 Nicola R Heneghan,1 Carolyn Roskell,1 Sarah E Williams,1 Peymane Adab,2 Andrew P Dickens,2 Alexandra Enocson,2 David A Fitzmaurice,2 Kate Jolly,2 Rachel Jordan,2 Sheila Greenfield,2 Jennifer Cumming1 1School of Sport, Exercise and Rehabilitation Sciences, 2Institute of Applied Health Research, University of Birmingham, Edgbaston, Birmingham, UK Background: Given that physical activity (PA has a positive impact on COPD symptoms and prognosis, this study examined the factors that both encourage and limit participation in PA for individuals with COPD in a primary care setting from the perspective of social cognitive theory.Methods: A purposive sample of 26 individuals with a range of COPD severity (age range: 50–89 years; males =15 were recruited from primary care to participate in one of four focus groups. Thematic analysis was undertaken to identify key concepts related to their self-efficacy beliefs.Results: Several barriers and enablers closely related to self-efficacy beliefs and symptom severity were identified. The main barriers were health related (fatigue, mobility problems, breathing issues caused by the weather, psychological (embarrassment, fear, frustration/disappointment, attitudinal (feeling in control of their condition, PA perception, older age perception, and motivational. The main enabling factors were related to motivation (autonomous or controlled, attitudes, self-regulation, and performance accomplishments.Clinical implications: When designing interventions for individuals with COPD, it is important to understand the patient-specific social cognitive influences on PA participation. This information can then inform individually tailored management planning. Keywords: COPD, social cognitive theory, self-efficacy, barriers, enablers, primary care

  20. Barriers to physical activity in older adults in Germany: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Moschny Anna

    2011-11-01

    Full Text Available Abstract Background Data on barriers to physical activity in older adults in Germany are scarce. The aim of this study was to analyse barriers to physical activity in a cohort of older adults, allowing comparisons between men and women, and age groups. Methods 1,937 older adults with a median age of 77 (range 72-93 years (53.3% female took part in the 7-year follow-up telephone interviews of the getABI cohort. Participants who stated that they did not get enough physical activity were surveyed with respect to barriers to physical activity. Barriers were analysed for all respondents, as well as by sex and age group for cases with complete data. Multivariate logistic regression analysis was performed to evaluate differences between sexes and age groups. The level of significance (alpha Results 1,607 (83.0% participants stated that they were sufficiently physically active. 286 participants rated their physical activity as insufficient and responded to questions on barriers to physical activity completely. The three most frequently cited barriers were poor health (57.7%, lack of company (43.0%, and lack of interest (36.7%. Lack of opportunities for sports or leisure activities (30.3% vs. 15.6%, and lack of transport (29.0% vs. 7.1% were more frequently stated by female respondents than male respondents. These differences between men and women were significant (p = .003; p Conclusions The present study provides relevant data on barriers to physical activity in older adults. By revealing appreciable differences between men and women, and age groups, this study has implications for efforts to increase older adults' physical activity. Promotion and intervention strategies should consider the barriers and tailor measures to the specific needs of older adults in order to reduce their constraints to physical activity.

  1. Modeling, analysis, and validation of an active T-shaped noise barrier.

    Science.gov (United States)

    Fan, Rongping; Su, Zhongqing; Cheng, Li

    2013-09-01

    With ever-increasing land traffic, abatement of traffic noise using noise barriers remains significant, yet it is a challenging task due to spatial competition with other infrastructure. In this study, a deep insight into the diffraction characteristics of acoustic fields near noise barriers of various geometries and surface conditions was achieved using numerical simulations. A T-shaped passive noise barrier with acoustically soft upper surfaces was demonstrated to outperform other candidates in a middle- or high-frequency range. Based on attributes of the acoustic field diffracted by T-shaped barriers, an active control strategy was developed to revamp the T-shaped barrier, in which a filtered minimax algorithm was established to drive the secondary sound sources. This algorithm resulted in more uniformly distributed residual sound fields than a filtered-X least mean square algorithm. Performance of the actively controlled barrier was evaluated at different positions and spacings of secondary sound sources and error sensors, leading to a series of optimal criteria for the design of active noise barriers. A prototype was fabricated and validated experimentally, manifesting particular effectiveness in insulating low-frequency noise, supplementing well the capacity of a passive T-shaped barrier which is effective in the middle- or high-frequency range.

  2. Pregnane X Receptor Activation Attenuates Inflammation-Associated Intestinal Epithelial Barrier Dysfunction by Inhibiting Cytokine-Induced Myosin Light-Chain Kinase Expression and c-Jun N-Terminal Kinase 1/2 Activation.

    Science.gov (United States)

    Garg, Aditya; Zhao, Angela; Erickson, Sarah L; Mukherjee, Subhajit; Lau, Aik Jiang; Alston, Laurie; Chang, Thomas K H; Mani, Sridhar; Hirota, Simon A

    2016-10-01

    The inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with a complex etiology. IBD is thought to arise in genetically susceptible individuals in the context of aberrant interactions with the intestinal microbiota and other environmental risk factors. Recently, the pregnane X receptor (PXR) was identified as a sensor for microbial metabolites, whose activation can regulate the intestinal epithelial barrier. Mutations in NR1I2, the gene that encodes the PXR, have been linked to IBD, and in animal models, PXR deletion leads to barrier dysfunction. In the current study, we sought to assess the mechanism(s) through which the PXR regulates barrier function during inflammation. In Caco-2 intestinal epithelial cell monolayers, tumor necrosis factor-α/interferon-γ exposure disrupted the barrier and triggered zonula occludens-1 relocalization, increased expression of myosin light-chain kinase (MLCK), and activation of c-Jun N-terminal kinase 1/2 (JNK1/2). Activation of the PXR [rifaximin and [[3,5-Bis(1,1-dimethylethyl)-4-hydroxyphenyl]ethenylidene]bis-phosphonic acid tetraethyl ester (SR12813); 10 μM] protected the barrier, an effect that was associated with attenuated MLCK expression and JNK1/2 activation. In vivo, activation of the PXR [pregnenolone 16α-carbonitrile (PCN)] attenuated barrier disruption induced by toll-like receptor 4 activation in wild-type, but not Pxr-/-, mice. Furthermore, PCN treatment protected the barrier in the dextran-sulfate sodium model of experimental colitis, an effect that was associated with reduced expression of mucosal MLCK and phosphorylated JNK1/2. Together, our data suggest that the PXR regulates the intestinal epithelial barrier during inflammation by modulating cytokine-induced MLCK expression and JNK1/2 activation. Thus, targeting the PXR may prove beneficial for the treatment of inflammation-associated barrier disruption in the context of IBD.

  3. Regulation of p21ras activity

    DEFF Research Database (Denmark)

    Lowy, D R; Zhang, K; DeClue, J E

    1992-01-01

    The ras genes encode GTP/GDP-binding proteins that participate in mediating mitogenic signals from membrane tyrosine kinases to downstream targets. The activity of p21ras is determined by the concentration of GTP-p21ras, which is tightly regulated by a complex array of positive and negative control...... mechanisms. GAP and NF1 can negatively regulate p21ras activity by stimulating hydrolysis of GTP bound to p21ras. Other cellular factors can positively regulate p21ras by stimulating GDP/GTP exchange....

  4. Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Jian; Zhang, Lin [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Dai, Weiqi [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Mao, Yuqing [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Li, Sainan [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Wang, Jingjie; Li, Huanqing [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Guo, Chuanyong [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Fan, Xiaoming, E-mail: xiaomingfan57@sina.com [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China)

    2015-02-27

    Aim: This study aimed to investigate the effect and underlying mechanism of ghrelin on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. Methods and results: Acute colitis was induced in C57BL/6J mice by administering 2.5% DSS. Saline or 25, 125, 250 μg/kg ghrelin was administrated intraperitoneally (IP) to mice 1 day before colitis induction and on days 4, 5, and 6 after DSS administration. IP injection of a ghrelin receptor antagonist, [D-lys{sup 3}]-GHRP-6, was performed immediately prior to ghrelin injection. Ghrelin (125 or 250 μg/kg) could reduce the disease activity index, histological score, and myeloperoxidase activities in experimental colitis, and also prevented shortening of the colon. Ghrelin could prevent the reduction of transepithelial electrical resistance and tight junction expression, and bolstered tight junction structural integrity and regulated cytokine secretion. Ultimately, ghrelin inhibited nuclear factor kappa B (NF-κB), inhibitory κB-α, myosin light chain kinase, and phosphorylated myosin light chain 2 activation. Conclusions: Ghrelin prevented the breakdown of intestinal barrier function in DSS-induced colitis. The protective effects of ghrelin on intestinal barrier function were mediated by its receptor GHSR-1a. The inhibition of NF-κB activation might be part of the mechanism underlying the effects of ghrelin that protect against barrier dysfunction. - Highlights: • Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis. • The effect of ghrelin is mediated by GHSR-1a. • Inhibition of NF-κB activation.

  5. Barriers for recess physical activity: a gender specific qualitative focus group exploration

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Tjørnhøj-Thomsen, Tine; Schipperijn, Jasper

    (53 boys) from fourth grade, with a mean age of 10.4 years. The focus groups included an open group discussion, go-along group interviews, and a gender segregated post-it note activity. A content analysis of the post-it notes was used to prioritize the children´s perceived barriers. This was verified...... differences in children’s perceptions of barriers to recess physical activity. Based on the socio-ecological model four types of environmental barriers were distinguished: natural, social, physical and organizational environment Methods: Data were collected through 17 focus groups consisting of 111 children...... by a thematic analysis of data from the open discussions and go-along interviews. Results: The most frequently identified barriers for both boys and girls were weather, conflicts, lack of space, lack of facilities and a newly-found barrier, use of electronic devices. While boys and girls identifying the same...

  6. RNase L Interacts with Filamin A To Regulate Actin Dynamics and Barrier Function for Viral Entry

    Science.gov (United States)

    Siddiqui, Mohammad Adnan; Dayal, Shubham; Naji, Merna; Ezelle, Heather J.; Zeng, Chun; Zhou, Aimin; Hassel, Bret A.

    2014-01-01

    ABSTRACT The actin cytoskeleton and its network of associated proteins constitute a physical barrier that viruses must circumvent to gain entry into cells for productive infection. The mechanisms by which the physical signals of infection are sensed by the host to activate an innate immune response are not well understood. The antiviral endoribonuclease RNase L is ubiquitously expressed in a latent form and activated upon binding 2-5A, a unique oligoadenylate produced during viral infections. We provide evidence that RNase L in its inactive form interacts with the actin-binding protein Filamin A to modulate the actin cytoskeleton and inhibit virus entry. Cells lacking either RNase L or Filamin A displayed increased virus entry which was exacerbated in cells lacking both proteins. RNase L deletion mutants that reduced Filamin A interaction displayed a compromised ability to restrict virus entry, supporting the idea of an important role for the RNase L-Filamin A complex in barrier function. Remarkably, both the wild type and a catalytically inactive RNase L mutant were competent to reduce virus entry when transfected into RNase L-deficient cells, indicating that this novel function of RNase L is independent of its enzymatic activity. Virus infection and RNase L activation disrupt its association with Filamin A and release RNase L to mediate its canonical nuclease-dependent antiviral activities. The dual functions of RNase L as a constitutive component of the actin cytoskeleton and as an induced mediator of antiviral signaling and effector functions provide insights into its mechanisms of antiviral activity and opportunities for the development of novel antiviral agents. PMID:25352621

  7. [Molecular mechanisms regulating the activity of macrophages].

    Science.gov (United States)

    Onoprienko, L V

    2011-01-01

    This article reviews modern concepts of the most common types of macrophage activation: classical, alternative, and type II. Molecular mechanisms of induction and regulation of these three types of activation are discussed. Any population of macrophages was shown to change its properties depending on its microenvironment and concrete biological situation (the "functional plasticity of macrophages"). Many intermediate states of macrophages were described along with the most pronounced and well-known activation types (classical activation, alternative activation, and type II activation). These intermediate states are characterized by a variety of combinations of their biological properties, including elements of the three afore mentioned types of activation. Macrophage activity is regulated by a complex network of interrelated cascade mechanisms.

  8. Regulation of ROCK Activity in Cancer

    DEFF Research Database (Denmark)

    Morgan-Fisher, Marie; Wewer, Ulla M; Yoneda, Atsuko

    2013-01-01

    , these findings demonstrate additional modes to regulate ROCK activity. This review describes the molecular mechanisms of ROCK activity regulation in cancer, with emphasis on ROCK isoform-specific regulation and interaction partners, and discusses the potential of ROCKs as therapeutic targets in cancer.......Cancer-associated changes in cellular behavior, such as modified cell-cell contact, increased migratory potential, and generation of cellular force, all require alteration of the cytoskeleton. Two homologous mammalian serine/threonine kinases, Rho-associated protein kinases (ROCK I and II), are key...... regulators of the actin cytoskeleton acting downstream of the small GTPase Rho. ROCK is associated with cancer progression, and ROCK protein expression is elevated in several types of cancer. ROCKs exist in a closed, inactive conformation under quiescent conditions, which is changed to an open, active...

  9. Sirt1-Sirt3 axis regulates human blood-brain barrier permeability in response to ischemia.

    Science.gov (United States)

    Chen, Tao; Dai, Shu-Hui; Li, Xia; Luo, Peng; Zhu, Jie; Wang, Yu-Hai; Fei, Zhou; Jiang, Xiao-Fan

    2017-09-22

    Sirtuin1 (Sirt1) and Sirtuin3 (Sirt3) are two well-characterized members of the silent information regulator 2 (Sir2) family of proteins. Both Sirt1 and Sirt3 have been shown to play vital roles in resistance to cellular stress, but the interaction between these two sirtuins has not been fully determined. In this study, we investigated the role of Sirt1-Sirt3 axis in blood-brain barrier (BBB) permeability after ischemia in vitro. Human brain microvascular endothelial cells and astrocytes were co-cultured to model the BBB in vitro and oxygen and glucose deprivation (OGD) was performed to mimic ischemia. The results of transepithelial electrical resistance (TEER) showed that suppression of Sirt1 via siRNA or salermide significantly decreased BBB permeability, whereas Sirt3 knockdown increased BBB permeability. In addition, Sirt1 was shown to regulate Sirt3 expression after OGD through inhibiting the AMPK-PGC1 pathway. Application of the AMPK inhibitor compound C partially prevented the effects of Sirt1-Sirt3 axis on BBB permeability after OGD. The results of flow cytometry and cytochrome c release demonstrated that Sirt1 and Sirt3 exert opposite effects on OGD-induced apoptosis. Furthermore, suppression of Sirt1 was shown to attenuate mitochondrial reactive oxygen species (ROS) generation, which contribute to the Sirt1-Sirt3 axis-induced regulation of BBB permeability and cell damage. In summary, these findings demonstrate that the Sirt1-Sirt3 axis might act as an important modulator in BBB physiology, and could be a therapeutic target for ischemic stroke via regulating mitochondrial ROS generation. Copyright © 2017. Published by Elsevier B.V.

  10. Barriers to participation in physical activity and exercise among middle-aged and elderly individuals.

    Science.gov (United States)

    Justine, Maria; Azizan, Azliyana; Hassan, Vaharli; Salleh, Zoolfaiz; Manaf, Haidzir

    2013-10-01

    INTRODUCTION Although the benefits of physical activity and exercise are widely acknowledged, many middle-aged and elderly individuals remain sedentary. This cross-sectional study aimed to identify the external and internal barriers to physical activity and exercise participation among middle-aged and elderly individuals, as well as identify any differences in these barriers between the two groups. METHODS Recruited individuals were categorised into either the middle-aged (age 45-59 years, n = 60) or elderly (age ≥ 60 years, n = 60) group. Data on demographics, anthropometry, as well as external and internal barriers to participation in physical activity and exercise were collected. RESULTS Analysis showed no significant differences in the total scores of all internal barriers between the two groups (p > 0.05). The total scores for most external barriers between the two groups also showed no significant differences (p > 0.05); only 'cost' (p = 0.045) and 'exercise interferes with social/family activities' (p = 0.011) showed significant differences. The most common external barriers among the middle-aged and elderly respondents were 'not enough time' (46.7% vs. 48.4%), 'no one to exercise with' (40.0% vs. 28.3%) and 'lack of facilities' (33.4% vs. 35.0%). The most common internal barriers for middle-aged respondents were 'too tired' (48.3%), 'already active enough' (38.3%), 'do not know how to do it' (36.7%) and 'too lazy' (36.7%), while those for elderly respondents were 'too tired' (51.7%), 'lack of motivation' (38.4%) and 'already active enough' (38.4%). CONCLUSION Middle-aged and elderly respondents presented with similar external and internal barriers to physical activity and exercise participation. These factors should be taken into account when healthcare policies are being designed and when interventions such as the provision of facilities to promote physical activity and exercise among older people are being considered.

  11. Vasoinhibins regulate the inner and outer blood-retinal barrier and limit retinal oxidative stress

    Directory of Open Access Journals (Sweden)

    David eArredondo Zamarripa

    2014-10-01

    Full Text Available Vasoinhibins are prolactin fragments present in the retina, where they have been shown to prevent the hypervasopermeability associated with diabetes. Enhanced bradykinin (BK production contributes to the increased transport through the blood-retina barrier (BRB in diabetes. Here, we studied if vasoinhibins regulate BRB permeability by targeting the vascular endothelium and retinal pigment epithelium (RPE components of this barrier. Intravitreal injection of BK in male rats increased BRB permeability. Vasoinhibins prevented this effect, as did the B2 receptor antagonist Hoe-140. BK induced a transient decrease in mouse retinal and brain capillary endothelial monolayer resistance that was blocked by vasoinhibins. Both vasoinhibins and the nitric oxide (NO synthase inhibitor L-NAME, but not the antioxidant N-acetyl cysteine (NAC, blocked the transient decrease in bovine umbilical vein endothelial cell (BUVEC monolayer resistance induced by BK; this block was reversed by the NO donor DETANONOate. Vasoinhibins also prevented the BK-induced actin cytoskeleton redistribution, as did L-NAME. BK transiently decreased human RPE (ARPE-19 cell monolayer resistance, and this effect was blocked by vasoinhibins, L-NAME, and NAC. DETANONOate reverted the blocking effect of vasoinhibins. Similar to BK, the radical initiator Luperox induced a reduction in ARPE-19 cell monolayer resistance, which was prevented by vasoinhibins. These effects on RPE resistance coincided with actin cytoskeleton redistribution. Intravitreal injection of vasoinhibins reduced the levels of reactive oxygen species (ROS in retinas of streptozotocin-induced diabetic rats, particularly in the RPE and capillary-containing layers. Thus, vasoinhibins reduce BRB permeability by targeting both its main inner and outer components through NO- and ROS-dependent pathways, offering potential treatment strategies against diabetic retinopathies.

  12. Deubiquitylating enzyme USP9x regulates hippo pathway activity by controlling angiomotin protein turnover

    DEFF Research Database (Denmark)

    Nguyen, Thanh Hung; Andrejeva, Diana; Gupta, Rajat;

    2016-01-01

    The Hippo pathway has been identified as a key barrier for tumorigenesis, acting through downregulation of YAP/TAZ activity. Elevated YAP/TAZ activity has been documented in many human cancers. Ubiquitylation has been shown to play a key role in regulating YAP/TAZ activity through downregulation....../TAZ activity. We demonstrate that USPx regulates ubiquitin-mediated turnover of the YAP inhibitor, Angiomotin. USP9x acts to deubiquitylate Angiomotin at lysine 496, resulting in stabilization of Angiomotin and lower YAP/TAZ activity. USP9x mRNA levels were reduced in several cancers. Clinically, USP9x m...

  13. "What I Wish You Knew": Social Barriers toward Physical Activity in Youth with Congenital Heart Disease (CHD)

    Science.gov (United States)

    Moola, Fiona; Fusco, Caroline; Kirsh, Joel A.

    2011-01-01

    Despite the benefits of physical activity for youth with congenital heart disease (CHD), most patients are inactive. Although literature has addressed medical and psychological barriers to participation, little is known about the social barriers that youth encounter. This qualitative study explored sociocultural barriers to physical activity from…

  14. "What I Wish You Knew": Social Barriers toward Physical Activity in Youth with Congenital Heart Disease (CHD)

    Science.gov (United States)

    Moola, Fiona; Fusco, Caroline; Kirsh, Joel A.

    2011-01-01

    Despite the benefits of physical activity for youth with congenital heart disease (CHD), most patients are inactive. Although literature has addressed medical and psychological barriers to participation, little is known about the social barriers that youth encounter. This qualitative study explored sociocultural barriers to physical activity from…

  15. Barriers to Physical Activity Among African American Women: An Integrative Review of the Literature.

    Science.gov (United States)

    Joseph, Rodney P; Ainsworth, Barbara E; Keller, Colleen; Dodgson, Joan E

    2015-01-01

    A key aspect for researchers to consider when developing culturally appropriate physical activity (PA) interventions for African American (AA) women are the specific barriers AA women face that limit their participation in PA. Identification and critical examination of these barriers is the first step in developing comprehensive culturally relevant approaches to promote PA and help resolve PA-related health disparities in this underserved population. We conducted a systematic integrative literature review to identify barriers to PA among AA women. Five electronic databases were searched, and forty-two studies (twenty-seven qualitative, fourteen quantitative, one mixed method) published since 1990 (range 1998-2013) in English language journals met inclusion criteria for review. Barriers were classified as intrapersonal, interpersonal, or environment/community according to their respective level of influence within our social ecological framework. Intrapersonal barriers included lack of time, knowledge, and motivation; physical appearance concerns; health concerns; monetary cost of exercise facilities; and tiredness/fatigue. Interpersonal barriers included family/caregiving responsibilities; lack of social support; and lack of a PA partner. Environmental barriers included safety concerns; lack of facilities; weather concerns; lack of sidewalks; and lack of physically active AA role models. Results provide key leverage points for researchers to consider when developing culturally relevant PA interventions for AA women.

  16. A review of social and environmental barriers to physical activity for adults with intellectual disabilities.

    Science.gov (United States)

    Bodde, Amy E; Seo, Dong-Chul

    2009-04-01

    There is a higher prevalence of sedentary behavior among adults with intellectual disability (ID) compared to the general population. The majority of research on this topic has focused on assessing physical activity (PA) levels and there are relatively few studies addressing barriers to PA (including exercise) in this population. It is important to analyze the PA barriers faced by adults with ID in order to develop and implement intervention programs. A systematic research review was conducted to analyze the barriers to PA for adults with ID. Original research articles published after 1980 with primary intention of identifying PA determinants of age 18+ adults with ID were included. In total, 837 citations were returned, and after screening for repeated articles and inclusion criteria, 7 were included in the analysis. The primary barriers that reoccurred throughout the papers were transportation issues, financial limitations and lack of awareness of options. Other salient barriers included negative supports from caregivers and authority figures (e.g. teachers, coaches and parents) and lack of clear policies for engaging in regular activity in residential and day service programs. This study reveals clear barriers to PA to target. Of primary importance is the development of policies among agencies that serve individuals with ID that could help minimize transportation, financial, policy and educational barriers, which are more modifiable than negative supports.

  17. An Activity Theory Approach to Analyze Barriers to a Virtual Management Information Systems (MIS) Curriculum

    Science.gov (United States)

    Jaradat, Suhair; Qablan, Ahmad; Barham, Areej

    2011-01-01

    This paper explains how the activity theory is used as a framework to analyze the barriers to a virtual Management Information Stream (MIS) Curriculum in Jordanian schools, from both the sociocultural and pedagogical perspectives. Taking the activity system as a unit of analysis, this study documents the processes by which activities shape and are…

  18. Barriers and Facilitators of Breastfeeding for Primiparous Active Duty Military Mothers: A Qualitative Study

    Science.gov (United States)

    1999-05-11

    BARRIERS AND FACILITATORS OF BREASTFEEDING FOR PRIMIPAROUS ACTIVE DUTY MILITARY MOTHERS: A QUALITATIVE STUDY Kristine Markley Bristow APPROVED...BREASTFEEDING FOR PRIMIPAROUS ACTIVE DUTY MILITARY MOTHERS: A QUALITATIVE STUDY” beyond brief excerpts is with the permission of the copyright owner, and...breastfeeding for primiparous active duty military mothers, from their perspective, using a Husserlian phenomenological approach. A semi-structured

  19. The impact of peer victimization, parent distress and child depression on barrier formation and physical activity in overweight youth.

    Science.gov (United States)

    Gray, Wendy N; Janicke, David M; Ingerski, Lisa M; Silverstein, Janet H

    2008-02-01

    With the prevalence of childhood overweight reaching epidemic proportions, there is an increased need to identify factors which may aid in the development of successful weight intervention programs. Given that lower levels of physical activity are inversely correlated with weight status in children, research has focused on identifying and addressing reported barriers to physically activity. A relationship exists between the number of reported barriers and weight status such that children who are overweight report more barriers to being physically active. However, important demographic and psychosocial correlates of barriers have not been examined. This study investigates the relationship among parent distress, peer victimization, childhood depression, barriers to physical activity, and physical activity among a sample of 95 clinically overweight children and adolescents. Higher levels of parent distress, peer victimization, and childhood depression are predictive of a variety of barriers to physical activity, with peer victimization emerging as the strongest predictor of barriers. Barriers to physical activity mediate the relationships between peer victimization, parent distress, child depression and physical activity. These findings have significant implications for the development/design of weight intervention programs. Interventions targeting increases in physical activity should not only focus on the barriers children report, but should also include a psycho-emotional component to address factors such as parent distress, peer victimization and child mood that may contribute to barrier formation/maintenance. Future interventions may benefit from the identification of additional factors that impact barrier formation and physical activity levels among children.

  20. Molecular regulation of telomerase activity in aging

    Institute of Scientific and Technical Information of China (English)

    Craig Nicholls; He Li; Jian-Qiu Wang; Jun-Ping Liu

    2011-01-01

    The process of aging is mitigated by the maintenance and repair of chromosome ends (telomeres),resulting in extended lifespan.This review examines the molecular mechanisms underlying the actions and regulation of the enzyme telomerase reverse transcriptase (TERT),which functions as the primary mechanism of telomere maintenance and regulates cellular life expectancy.Underpinning increased cell proliferation,telomerase is also a key factor in facilitating cancer cell immortalization.The review focuses on aspects of hormonal regulations of telomerase,and the intraceilular pathways that converge to regulate telomerase activity with an emphasis on molecular interactions at protein and gene levels.In addition,the basic structure and function of two key telomerase enzyme components-the catalytic subunit TERT and the template RNA (TERC) are discussed briefly.

  1. Heat-Activated Effect of Exchange Coupling Between Two Ferromagnets Separated by an Amorphous Semiconducting Barrier

    Institute of Scientific and Technical Information of China (English)

    肖明文; 李正中; 许望

    2002-01-01

    We try to extend our previous zero-temperature tunnelling theory for the exchange coupling between two ferromagnets separated by an amorphous semiconducting barrier to the case of finite temperature. The result exhibits that the tunnelling electrons can absorb or emit phonons when they tunnel through the amorphous barrier at finite temperatures so that the interlayer exchange coupling is heat activated. This agrees with the experiments.

  2. Limited English proficient HMO enrollees remain vulnerable to communication barriers despite language assistance regulations.

    Science.gov (United States)

    Hadler, Max W; Chen, Xiao; Gonzalez, Erik; Roby, Dylan H

    2013-02-01

    HMO enrollees with limited English proficiency, and particularly those in poorer health, face communication barriers despite language assistance regulations. More than 1.3 million California HMO enrollees ages 18 to 64 do not speak English well enough to communicate with medical providers and may experience reduced access to high-quality health care if they do not receive appropriate language assistance services. Based on analysis of the 2007 and 2009 California Health Interview Surveys (CHIS), commercial HMO enrollees with limited English proficiency (LEP) in poorer health are more likely to have difficulty understanding their doctors, placing this already vulnerable population at even greater risk. The analysis also uses CHIS to examine the potential impact of health plan monitoring starting in 2009 (due to a 2003 amendment to the Knox-Keene Health Care Services Act) requiring health plans to provide free qualified interpretation and translation services to HMO enrollees. The authors recommend that California's health plans continue to incorporate trained interpreters into their contracted networks and delivery systems, paying special attention to enrollees in poorer health. The results may serve as a planning tool for health plans, providing a detailed snapshot of enrollee characteristics that will help design effective programs now and prepare for a likely increase in insured LEP populations in the future, as full implementation of the Affordable Care Act takes place over the next decade.

  3. Regulation of ROCK Activity in Cancer

    Science.gov (United States)

    Morgan-Fisher, Marie; Wewer, Ulla M.

    2013-01-01

    Cancer-associated changes in cellular behavior, such as modified cell-cell contact, increased migratory potential, and generation of cellular force, all require alteration of the cytoskeleton. Two homologous mammalian serine/threonine kinases, Rho-associated protein kinases (ROCK I and II), are key regulators of the actin cytoskeleton acting downstream of the small GTPase Rho. ROCK is associated with cancer progression, and ROCK protein expression is elevated in several types of cancer. ROCKs exist in a closed, inactive conformation under quiescent conditions, which is changed to an open, active conformation by the direct binding of guanosine triphosphate (GTP)–loaded Rho. In recent years, a number of ROCK isoform-specific binding partners have been found to modulate the kinase activity through direct interactions with the catalytic domain or via altered cellular localization of the kinases. Thus, these findings demonstrate additional modes to regulate ROCK activity. This review describes the molecular mechanisms of ROCK activity regulation in cancer, with emphasis on ROCK isoform-specific regulation and interaction partners, and discusses the potential of ROCKs as therapeutic targets in cancer. PMID:23204112

  4. Children's active play: self-reported motivators, barriers and facilitators

    Directory of Open Access Journals (Sweden)

    Rowan Brockman

    2011-06-01

    Full Text Available Physical activity has important benefits for children's physical health and mental wellbeing, but many children do not meet recommended levels. Research suggests that active play has the potential to make a valuable contribution to children's overall physical activity, whilst providing additional cognitive, social and emotional benefits. However, relatively little is known about the determinants of UK children's active play. Understanding these factors provides the critical first step in developing interventions to increase children's active play, and therefore overall physical activity. Eleven focus groups were conducted with 77, 10-11 year old children from four primary schools in Bristol, UK. Focus groups examined: (i factors which motivate children to take part in active play; (ii factors which limit children's active play and (iii factors which facilitate children's active play. All focus groups were audio-taped and transcribed verbatim. Data were analysed using a thematic approach. Children were motivated to engage in active play because they perceived it to be enjoyable, to prevent boredom, to have physical and mental health benefits and to provide freedom from adult control, rules and structure. However, children's active play was constrained by a number of factors, including rainy weather and fear of groups of teenagers in their play spaces. Some features of the physical environment facilitated children's active play, including the presence of green spaces and cul-de-sacs in the neighbourhood. Additionally, children's use of mobile phones when playing away from home was reported to help to alleviate parents' safety fears, and therefore assist children's active play. Children express a range of motivational and environmental factors that constrain and facilitate their active play. Consideration of these factors should improve effectiveness of interventions designed to increase active play.

  5. Is peripheral immunity regulated by blood-brain barrier permeability changes?

    Directory of Open Access Journals (Sweden)

    Erin Bargerstock

    Full Text Available S100B is a reporter of blood-brain barrier (BBB integrity which appears in blood when the BBB is breached. Circulating S100B derives from either extracranial sources or release into circulation by normal fluctuations in BBB integrity or pathologic BBB disruption (BBBD. Elevated S100B matches the clinical presence of indices of BBBD (gadolinium enhancement or albumin coefficient. After repeated sub-concussive episodes, serum S100B triggers an antigen-driven production of anti-S100B autoantibodies. We tested the hypothesis that the presence of S100B in extracranial tissue is due to peripheral cellular uptake of serum S100B by antigen presenting cells, which may induce the production of auto antibodies against S100B. To test this hypothesis, we used animal models of seizures, enrolled patients undergoing repeated BBBD, and collected serum samples from epileptic patients. We employed a broad array of techniques, including immunohistochemistry, RNA analysis, tracer injection and serum analysis. mRNA for S100B was segregated to barrier organs (testis, kidney and brain but S100B protein was detected in immunocompetent cells in spleen, thymus and lymph nodes, in resident immune cells (Langerhans, satellite cells in heart muscle, etc. and BBB endothelium. Uptake of labeled S100B by rat spleen CD4+ or CD8+ and CD86+ dendritic cells was exacerbated by pilocarpine-induced status epilepticus which is accompanied by BBBD. Clinical seizures were preceded by a surge of serum S100B. In patients undergoing repeated therapeutic BBBD, an autoimmune response against S100B was measured. In addition to its role in the central nervous system and its diagnostic value as a BBBD reporter, S100B may integrate blood-brain barrier disruption to the control of systemic immunity by a mechanism involving the activation of immune cells. We propose a scenario where extravasated S100B may trigger a pathologic autoimmune reaction linking systemic and CNS immune responses.

  6. Barrier-protective effects of activated protein C in human alveolar epithelial cells.

    Directory of Open Access Journals (Sweden)

    Ferranda Puig

    Full Text Available Acute lung injury (ALI is a clinical manifestation of respiratory failure, caused by lung inflammation and the disruption of the alveolar-capillary barrier. Preservation of the physical integrity of the alveolar epithelial monolayer is of critical importance to prevent alveolar edema. Barrier integrity depends largely on the balance between physical forces on cell-cell and cell-matrix contacts, and this balance might be affected by alterations in the coagulation cascade in patients with ALI. We aimed to study the effects of activated protein C (APC on mechanical tension and barrier integrity in human alveolar epithelial cells (A549 exposed to thrombin. Cells were pretreated for 3 h with APC (50 µg/ml or vehicle (control. Subsequently, thrombin (50 nM or medium was added to the cell culture. APC significantly reduced thrombin-induced cell monolayer permeability, cell stiffening, and cell contraction, measured by electrical impedance, optical magnetic twisting cytometry, and traction microscopy, respectively, suggesting a barrier-protective response. The dynamics of the barrier integrity was also assessed by western blotting and immunofluorescence analysis of the tight junction ZO-1. Thrombin resulted in more elongated ZO-1 aggregates at cell-cell interface areas and induced an increase in ZO-1 membrane protein content. APC attenuated the length of these ZO-1 aggregates and reduced the ZO-1 membrane protein levels induced by thrombin. In conclusion, pretreatment with APC reduced the disruption of barrier integrity induced by thrombin, thus contributing to alveolar epithelial barrier protection.

  7. A cluster expansion model for predicting activation barrier of atomic processes

    Energy Technology Data Exchange (ETDEWEB)

    Rehman, Tafizur; Jaipal, M. [Department of Chemical Engineering, Indian Institute of Technology Kanpur, Kanpur 208 016 (India); Chatterjee, Abhijit, E-mail: achatter@iitk.ac.in [Department of Chemical Engineering, Indian Institute of Technology Kanpur, Kanpur 208 016 (India); Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai 400 076 (India)

    2013-06-15

    We introduce a procedure based on cluster expansion models for predicting the activation barrier of atomic processes encountered while studying the dynamics of a material system using the kinetic Monte Carlo (KMC) method. Starting with an interatomic potential description, a mathematical derivation is presented to show that the local environment dependence of the activation barrier can be captured using cluster interaction models. Next, we develop a systematic procedure for training the cluster interaction model on-the-fly, which involves: (i) obtaining activation barriers for handful local environments using nudged elastic band (NEB) calculations, (ii) identifying the local environment by analyzing the NEB results, and (iii) estimating the cluster interaction model parameters from the activation barrier data. Once a cluster expansion model has been trained, it is used to predict activation barriers without requiring any additional NEB calculations. Numerical studies are performed to validate the cluster expansion model by studying hop processes in Ag/Ag(100). We show that the use of cluster expansion model with KMC enables efficient generation of an accurate process rate catalog.

  8. Epac Activation Regulates Human Mesenchymal Stem Cells Migration and Adhesion.

    Science.gov (United States)

    Yu, Jiao-Le; Deng, Ruixia; Chung, Sookja K; Chan, Godfrey Chi-Fung

    2016-04-01

    How to enhance the homing of human mesenchymal stem cells (hMSCs) to the target tissues remains a clinical challenge nowadays. To overcome this barrier, the mechanism responsible for the hMSCs migration and engraftment has to be defined. Currently, the exact mechanism involved in migration and adhesion of hMSCs remains unknown. Exchange protein directly activated by cAMP (Epac), a novel protein discovered in cAMP signaling pathway, may have a potential role in regulating cells adhesion and migration by triggering the downstream Rap family signaling cascades. However, the exact role of Epac in cells homing is elusive. Our study evaluated the role of Epac in the homing of hMSCs. We confirmed that hMSCs expressed functional Epac and its activation enhanced the migration and adhesion of hMSCs significantly. The Epac activation was further found to be contributed directly to the chemotactic responses induced by stromal cell derived factor-1 (SDF-1) which is a known chemokine in regulating hMSCs homing. These findings suggested Epac is connected to the SDF-1 signaling cascades. In conclusion, our study revealed that Epac plays a role in hMSCs homing by promoting adhesion and migration. Appropriate manipulation of Epac may enhance the homing of hMSCs and facilitate their future clinical applications.

  9. Do Perceived Cues, Benefits, and Barriers to Physical Activity Differ between Male and Female Adolescents?

    Science.gov (United States)

    Tergerson, Jennifer L.; King, Keith A.

    2002-01-01

    Surveyed adolescents at single-sex high schools to examine whether perceptions of physical activity differed by gender. The most helpful cue to physical activity for males and females was having a friend to exercise with. Parental encouragement and having a parent who exercised were also helpful. Wanting to do other things was a common barrier to…

  10. Identifying Facilitators and Barriers to Physical Activity for Adults with Down Syndrome

    Science.gov (United States)

    Mahy, J.; Shields, N.; Taylor, N. F.; Dodd, K. J.

    2010-01-01

    Background: Adults with Down syndrome are typically sedentary, and many do not participate in the recommended levels of physical activity per week. The aim of this study was to identify the facilitators and barriers to physical activity for this group. Method: Semi-structured interviews were conducted to elicit the views of adults with Down…

  11. Identifying the Barriers and Facilitators to Participation in Physical Activity for Children with Down Syndrome

    Science.gov (United States)

    Barr, M.; Shields, N.

    2011-01-01

    Background: Many children with Down syndrome do not undertake the recommended amount of daily physical activity. The aim of this study was to explore the barriers and facilitators to physical activity for this group. Methods: Eighteen in-depth interviews were conducted with 20 parents (16 mothers, 4 fathers) of children with Down syndrome aged…

  12. Identifying the Barriers and Facilitators to Participation in Physical Activity for Children with Down Syndrome

    Science.gov (United States)

    Barr, M.; Shields, N.

    2011-01-01

    Background: Many children with Down syndrome do not undertake the recommended amount of daily physical activity. The aim of this study was to explore the barriers and facilitators to physical activity for this group. Methods: Eighteen in-depth interviews were conducted with 20 parents (16 mothers, 4 fathers) of children with Down syndrome aged…

  13. Barriers to Physical Activity for People with Long-Term Neurological Conditions: A Review Study

    Science.gov (United States)

    Mulligan, Hilda F.; Hale, Leigh A.; Whitehead, Lisa; Baxter, G. David

    2012-01-01

    People with disability are insufficiently physically active for health. This study identified the volume, quality, and findings of research that exposes environmental and personal barriers of physical activity participation for people with neurological conditions. CINAHL, Sport Discus, EMBASE, Medline, and AMED were systematically searched between…

  14. Barriers in the implementation of a physical activity intervention in primary care settings: lessons learned.

    Science.gov (United States)

    Josyula, Lakshmi K; Lyle, Roseann M

    2013-01-01

    Barriers encountered in implementing a physical activity intervention in primary health care settings, and ways to address them, are described in this paper. A randomized comparison trial was designed to examine the impact of health care providers' written prescriptions for physical activity, with or without additional physical activity resources, to adult, nonpregnant patients on preventive care or chronic disease monitoring visits. Following abysmal recruitment outcomes, the research protocol was altered to make it more appealing to all the participants, i.e., health care providers, office personnel, and patients. Various barriers--financial, motivational, and executive--to the implementation of health promotion interventions in primary health care settings were experienced and identified. These barriers have been classified by the different participants in the research process, viz., healthcare providers, administrative personnel, researchers, and patients. Some of the barriers identified were lack of time and reimbursement for health promotion activities, and inadequate practice capacity, for health care providers; increased time and labor demands for administrative personnel; constrained access to participants, and limited funding, for researchers; and superseding commitments, and inaccurate comprehension of the research protocol, for patients. Solutions suggested to overcome these barriers include financial support, e.g., funding for researchers, remuneration for health care organization personnel, reimbursement for providers, payment for participants, and free or subsidized postage, and use of health facilities; motivational strategies such as inspirational leadership, and contests within health care organizations; and partnerships, with other expert technical and creative entities, to improve the quality, efficiency, and acceptability of health promotion interventions.

  15. Nuclear factor erythroid 2-related factor 2 (Nrf2 regulates airway epithelial barrier integrity

    Directory of Open Access Journals (Sweden)

    Yoshitaka Shintani

    2015-09-01

    Conclusions: Our results indicated that the Nrf2/AOX1 pathway was important for enhancing airway epithelial barrier integrity. Because the airway epithelium of asthmatics is susceptible to reduced barrier integrity, this pathway might be a new therapeutic target for asthma.

  16. Focal MMP-2 and MMP-9 Activity at the Blood-Brain Barrier Promotes Chemokine-Induced Leukocyte Migration

    Directory of Open Access Journals (Sweden)

    Jian Song

    2015-02-01

    Full Text Available Although chemokines are sufficient for chemotaxis of various cells, increasing evidence exists for their fine-tuning by selective proteolytic processing. Using a model of immune cell chemotaxis into the CNS (experimental autoimmune encephalomyelitis [EAE] that permits precise localization of immigrating leukocytes at the blood-brain barrier, we show that, whereas chemokines are required for leukocyte migration into the CNS, additional MMP-2/9 activities specifically at the border of the CNS parenchyma strongly enhance this transmigration process. Cytokines derived from infiltrating leukocytes regulate MMP-2/9 activity at the parenchymal border, which in turn promotes astrocyte secretion of chemokines and differentially modulates the activity of different chemokines at the CNS border, thereby promoting leukocyte migration out of the cuff. Hence, cytokines, chemokines, and cytokine-induced MMP-2/9 activity specifically at the inflammatory border collectively act to accelerate leukocyte chemotaxis across the parenchymal border.

  17. Active explosion barrier performance against methane and coal dust explosions

    National Research Council Canada - National Science Library

    J. J. L. du Plessis

    2015-01-01

    Preventing the propagation of methane or coal dust explosions through the use of active explosion-suppression systems remains one of the most underutilised explosion controls in underground coal mines...

  18. Removing the barrier to the calculation of activation energies

    Science.gov (United States)

    Mesele, Oluwaseun O.; Thompson, Ward H.

    2016-10-01

    Approaches for directly calculating the activation energy for a chemical reaction from a simulation at a single temperature are explored with applications to both classical and quantum systems. The activation energy is obtained from a time correlation function that can be evaluated from the same molecular dynamics trajectories or quantum dynamics used to evaluate the rate constant itself and thus requires essentially no extra computational work.

  19. AN ACTIVITY THEORY APPROACH TO STUDY BARRIERS OF FACULTY REGARDING TECHNOLOGY INTEGRATION IN HIGHER EDUCATION

    DEFF Research Database (Denmark)

    Castro Guzman, Willy

    2016-01-01

    Information and communication technologies are instruments for supporting new ways of teaching and learning. Nevertheless, its impact concerning scope has not reached the expected level. This strain between benefits and impact has been inquired from the perspective of barriers of teachers to use...... for a reconceptualization in the study of barriers arguing that the teaching process is a complex and dynamic activity that needs to be examined from a collective perspective. Cultural-Historical Activity Theory is the theoretical framework used in the study. It concludes with the necessity of overcoming the existing...

  20. Legal barriers to effective ecosystem management: exploring linkages between liability, regulations, and prescribed fire.

    Science.gov (United States)

    Wonkka, Carissa L; Rogers, William E; Kreuter, Urs P

    2015-12-01

    should consider the benefits of lower legal liability standards in conjunction with regulatory requirements that promote safety for those managing forests and rangelands with fire. Moreover, ecologists and land managers might be better prepared and motivated to educate stakeholder groups who influence prescribed fire policies if they are cognizant of the manner in which policy regulations and liability concerns create legal barriers that inhibit the implementation of effective ecosystem management strategies.

  1. Motivators and barriers for physical activity in the oldest old: a systematic review.

    Science.gov (United States)

    Baert, Veerle; Gorus, Ellen; Mets, Tony; Geerts, Christel; Bautmans, Ivan

    2011-09-01

    Worldwide, people engage insufficiently in physical activity, particularly subjects aged 80 years and over. For optimal life-style campaigns, knowledge of motivators and barriers for physical activity is mandatory. Given their specific needs, it is conceivable that these would be different for the oldest old compared to younger subjects. Pubmed, Web of Science and Psychinfo were systematically screened for articles reporting motivators and barriers for physical activity. Papers were excluded if data regarding elderly aged >79 years were absent. Forty-four relevant articles were included, involving a total of 28,583 subjects. Sixty one motivators and 59 barriers for physical activity in the elderly were identified, including those who are relevant for persons aged 80 years and over. Based on the results of our literature review, we recommend that when promoting physical activity in the oldest old, special attention is paid to the health benefits of physical activity, to the subject's fears, individual preferences and social support, and to constraints related to the physical environment. However, no studies were found exclusively describing people aged 80 years and over, and future research is necessary to differentiate the barriers or motivators that are specific for the oldest old from those of younger elderly.

  2. Physical activity in hypertrophic cardiomyopathy: prevalence of inactivity and perceived barriers

    Science.gov (United States)

    Sweeting, Joanna; Ingles, Jodie; Timperio, Anna; Patterson, Jillian; Ball, Kylie; Semsarian, Christopher

    2016-01-01

    Objectives This study aimed to determine the prevalence of physical inactivity and perceived barriers to physical activity among individuals with hypertrophic cardiomyopathy (HCM), and to determine potential demographic, clinical and health-related factors influencing likelihood of meeting physical activity guidelines. Methods This was a cross-sectional study of consecutive patients (n=198) with HCM attending a specialist HCM centre from July 2014 to November 2015. The primary outcome measure was physical activity (minutes per day), as measured by self-report (International Physical Activity Questionnaire (IPAQ)) and objective means (ActiGraph accelerometer). For both, participants were classified as meeting guidelines if they did at least 150 min per week of physical activity. Quality of life (Short Form-36 V.2, SF-36v2), barriers to exercise and clinical–demographic data were also collected. Results In total, 54.8% of participants did not meet physical activity recommendations based on IPAQ, and 12.7% did not meet guidelines based on accelerometer data. The most commonly identified barriers to exercise were ‘pain interferes with my exercise’ (33%) and ‘I have an injury/disability that stops me’ (29%). Independent factors associated with meeting guidelines included older age (OR 0.66, 95% CI 0.51 to 0.85, p=0.002), higher education level (OR 2.31, 95% CI 1.08 to 4.93, p=0.03), better physical quality of life (OR 1.05, 95% CI 1.0 to 1.09, p=0.05) and more reported barriers (OR 0.71, 95% CI 0.56 to 0.91, p=0.01). Conclusions More than half of the patients with HCM did not meet minimum physical activity recommendations. Several barriers to exercise among individuals with HCM exist, and provide the basis for targeted interventions to promote physical activity and improve overall health in patients with HCM. PMID:27547438

  3. Redox-active media for permeable reactive barriers

    Energy Technology Data Exchange (ETDEWEB)

    Sivavec, T.M. [General Electric Corp. Research and Development Center, Schenectady, NY (United States); Mackenzie, P.D.; Horney, D.P.; Baghel, S.S.

    1997-12-31

    In this paper, three classes of redox-active media are described and evaluated in terms of their long-term effectiveness in treating TCE-contaminated groundwater in permeable reactive zones. Zero-valent iron, in the form of recycled cast iron filings, the first class, has received considerable attention as a reactive media and has been used in about a dozen pilot- and full-scale subsurface wall installations. Criteria used in selecting commercial sources of granular iron, will be discussed. Two other classes of redox-active media that have not yet seen wide use in pilot- or full-scale installations will also be described: Fe(II) minerals and bimetallic systems. Fe(II) minerals, including magnetite (Fe{sub 3}O{sub 4}), and ferrous sulfide (troilite, FeS), are redox-active and afford TCE reduction rates and product distributions that suggest that they react via a reductive mechanism similar to that which operates in the FeO system. Fe(II) species within the passive oxide layer coating the iron metal may act as electron transfer mediators, with FeO serving as the bulk reductant. Bimetallic systems, the third class of redox-active media, are commonly prepared by plating a second metal onto zero-valent iron (e.g., Ni/Fe and Pd/Fe) and have been shown to accelerate solvent degradation rates relative to untreated iron metal. The long-term effectiveness of this approach, however, has not yet been determined in groundwater treatability tests. The results of a Ni-plated iron column study using site groundwater indicate that a change in reduction mechanism (to catalytic dehydrohalogenation/hydrogenation) accounts for the observed rate enhancement. A significant loss in media reactivity was observed over time, attributable to Ni catalyst deactivation or poisoning. Zero-valent iron systems have not shown similar losses in reactivity in long-term laboratory, pilot or field investigations.

  4. Regulators of Slc4 bicarbonate transporter activity

    Directory of Open Access Journals (Sweden)

    Ian M. Thornell

    2015-06-01

    Full Text Available The Slc4 family of transporters is comprised of anion exchangers (AE1-4, Na-coupled bicarbonate transporters (NCBTs including electrogenic Na/bicarbonate cotransporters (NBCe1 and NBCe2, electroneutral Na/bicarbonate cotransporters (NBCn1 and NBCn2, and the electroneutral Na-driven Cl-bicarbonate exchanger (NDCBE, as well as a borate transporter (BTR1. These transporters regulate intracellular pH (pHi and contribute to steady-state pHi, but are also involved in other physiological processes including CO2 carriage by red blood cells and solute secretion/reabsorption across epithelia. Acid-base transporters function as either acid extruders or acid loaders, with the Slc4 proteins moving HCO3– either into or out of cells. According to results from both molecular and functional studies, multiple Slc4 proteins and/or associated splice variants with similar expected effects on pHi are often found in the same tissue or cell. Such apparent redundancy is likely to be physiologically important. In addition to regulating pHi, a HCO3– transporter contributes to a cell’s ability to fine tune the intracellular regulation of the cotransported/exchanged ion(s (e.g., Na+ or Cl–. In addition, functionally similar transporters or splice variants with different regulatory profiles will optimize pH physiology and solute transport under various conditions or within subcellular domains. Such optimization will depend on activated signaling pathways and transporter expression profiles. In this review, we will summarize and discuss both classical and more recently identified regulators of the Slc4 proteins. Some of these regulators include traditional second messengers, lipids, binding proteins, autoregulatory domains, and less conventional regulators. The material presented will provide insight into the diversity and physiological significance of multiple members within the Slc4 gene family.

  5. Barriers, enjoyment, and preference for physical activity among adults with intellectual disability.

    Science.gov (United States)

    Temple, Viviene A

    2007-12-01

    Many adults with an intellectual disability exhibit low physical activity levels. The aim of this study was to examine the relationships between participation in physical activity/sedentary behaviour and factors consistent with behavioural choice theory: enjoyment, preference, and barriers. Examination of these relationships increases our understanding of physical activity behaviour among adults with an intellectual disability. A descriptive correlational design was used. Steps per day of adults with intellectual disability (n = 37) were measured using pedometers for 1 week and associations with barriers, enjoyment, and preference were computed from participant's survey responses. Average steps per day ranged from 1658 to 19 303 (M = 8100.5+/-3735.4). Linear regression showed that barriers to physical activity and preference for sedentary behaviour were significant predictors of steps per day R = 0.533 (P = 0.009); which accounted for 28.4% of the variance in steps per day. The factor that stands out from this study for the least active individuals was accessibility of physical activity options. Ensuring that the effort needed to engage in physical activity is manageable and perceived as achievable is important. In addition, the higher preference for sedentary activity among the least active individuals suggests that it will be valuable to examine what attracts adults with an intellectual disability to particular physical activities and what aspects of participation they find reinforcing.

  6. Predictors of physical activity and barriers to exercise in nursing and medical students

    OpenAIRE

    Blake, Holly; Stanulewicz, Natalia; McGill, Francesca

    2016-01-01

    Aims\\ud \\ud To investigate physical activity levels of nursing and medicine students; examine predictors of physical activity level; and examine the most influential benefits and barriers to exercise.\\ud Background\\ud \\ud Healthcare professionals have low levels of physical activity, which increases their health risk and may influence their health promotion practices with patients.\\ud Design\\ud \\ud We surveyed 361 nursing (n=193) and medicine (n=168) students studying at a UK medical school.\\...

  7. Predictors of physical activity and barriers to exercise in nursing and medical students

    OpenAIRE

    Blake, Holly; Stanulewicz, Natalia; McGill, Francesca

    2016-01-01

    Aims To investigate physical activity levels of nursing and medicine students; examine predictors of physical activity level; and examine the most influential benefits and barriers to exercise. Background Healthcare professionals have low levels of physical activity, which increases their health risk and may influence their health promotion practices with patients. Design We surveyed 361 nursing (n=193) and medicine (n=168) students studying at a UK medical school. Method...

  8. Activation of epithelial STAT3 regulates intestinal homeostasis.

    Science.gov (United States)

    Neufert, Clemens; Pickert, Geethanjali; Zheng, Yan; Wittkopf, Nadine; Warntjen, Moritz; Nikolaev, Alexei; Ouyang, Wenjun; Neurath, Markus F; Becker, Christoph

    2010-02-15

    The intestinal epithelium that lines the mucosal surface along the GI-tract is a key player for the intestinal homeostasis of the healthy individual. In case of a mucosal damage or a barrier defect as seen in patients with inflammatory bowel disease, the balance is disturbed, and translocation of intestinal microbes to the submucosa is facilitated. We recently demonstrated a pivotal role of STAT3 activation in intestinal epithelial cells (IEC) for the restoration of the balance at the mucosal surface of the gut in an experimental colitis model. STAT3 was rapidly induced in intestinal epithelial cells upon challenge of mice in both experimental colitis and intestinal wound healing models. STAT3 activation was found to be dispensable in the steady-state conditions but was important for efficient regeneration of the epithelium in response to injury. Here, we extend our previous findings by showing epithelial STAT3 activation in human patients suffering from IBD and provide additional insights how the activation of epithelial STAT3 by IL-22 regulates intestinal homeostasis and mucosal wound healing. We also demonstrate that antibody-mediated neutralization of IL-22 has little impact on the development of experimental colitis in mice, but significantly delays recovery from colitis. Thus, our data suggest that targeting the STAT3 signaling pathway in IEC is a promising therapeutic approach in situations when the intestinal homeostasis is disturbed, e.g., as seen in Crohn's disease or Ulcerative colitis.

  9. Perceived Reasons, Incentives, and Barriers to Physical Activity in Swedish Elderly Men

    Science.gov (United States)

    Bonn, Stephanie E; Trolle Lagerros, Ylva; Sjölander, Arvid; Bälter, Katarina

    2014-01-01

    Background Knowledge about factors influencing physical activity behavior is needed in order to tailor physical activity interventions to the individual. Objective The aim of this study was to explore and describe the perceived reasons, barriers, and incentives to increased physical activity, as well as preferable activities, among elderly men in Sweden. Methods In total, 150 men aged 50-86 years responded to a Web-based questionnaire. Men who reported that they exercised sometimes or often received questions about reasons for physical activity (n=104), while men who reported that they never or seldom exercised received questions about barriers (n=46). Results The most frequent perceived reason for being physically active was health (82%), followed by enjoyment (45%), and a desire to lose/maintain weight (27%). Lack of interest/motivation was identified as the primary perceived barrier (17%). Incentives for increasing the level of activity included becoming more motivated and having a training partner. Walking was the most preferred activity. Conclusions Enjoyment and maintaining a good health were important reasons for engaging in physical activity among Swedish elderly men. PMID:25488655

  10. Barriers, Motivations, and Preferences for Physical Activity Among Female African American Older Adults

    Directory of Open Access Journals (Sweden)

    Neha P. Gothe PhD

    2016-11-01

    Full Text Available According to the Centers for Disease Control and Prevention, less than 11% of adults more than the age of 65 meet the 2008 Physical Activity Guidelines for Americans. Among minority populations, only 5% of non-Hispanic Black older adults met the guidelines. Given our limited understanding of psychosocial and environmental factors that affect physical activity participation in these groups, the purpose of our focus groups was to investigate barriers, motivators, and preferences of physical activity for community-dwelling African American older adults. Three focus groups were conducted with female African American older adults (N = 20. Questions posed to each focus group targeted motivations and barriers toward physical activity as well as their preferences for physical activity. The motivations included perceived health benefits of physical activity, social support, and enjoyment associated with engagement in physical activity. Prominent barriers included time and physical limitations, peer pressure and family responsibilities, and weather and poor neighborhood conditions. Group activities involving a dance component and novel exercises such as tai-chi or yoga were preferred choices. These findings should be taken into consideration when designing and implementing research or community physical activity programs for female African American older adults.

  11. Ack1: activation and regulation by allostery.

    Directory of Open Access Journals (Sweden)

    Ketan S Gajiwala

    Full Text Available The non-receptor tyrosine kinase Ack1 belongs to a unique multi-domain protein kinase family, Ack. Ack is the only family of SH3 domain containing kinases to have an SH3 domain following the kinase domain; others have their SH3 domains preceding the kinase domain. Previous reports have suggested that Ack1 does not require phosphorylation for activation and the enzyme activity of the isolated kinase domain is low relative to other kinases. It has been shown to dimerize in the cellular environment, which augments its enzyme activity. The molecular mechanism of activation, however, remains unknown. Here we present structural and biochemical data on Ack1 kinase domain, and kinase domain+SH3 domain that suggest that Ack1 in its monomeric state is autoinhibited, like EGFR and CDK. The activation of the kinase domain may require N-lobe mediated symmetric dimerization, which may be facilitated by the N-terminal SAM domain. Results presented here show that SH3 domain, unlike in Src family tyrosine kinases, does not directly control the activation state of the enzyme. Instead we speculate that the SH3 domain may play a regulatory role by facilitating binding of the MIG6 homologous region to the kinase domain. We postulate that features of Ack1 activation and regulation parallel those of receptor tyrosine kinase EGFR with some interesting differences.

  12. A Comparison of Motivational Factors and Barriers to Physical Activity among Traditional versus Nontraditional College Students

    Science.gov (United States)

    Kulavic, Kimberly; Hultquist, Cherilyn N.; McLester, John R.

    2013-01-01

    Objective: To investigate the motivational factors and the barriers to physical activity (PA) in traditional college students (TS) and nontraditional college students (NTS) and determine if differences exist between these 2 groups. Participants: A total of 746 college students; 628 were TS (19.1 [plus-minus] 1.2 years), and 118 were NTS (31.2…

  13. Adolescents' Perspectives on the Barriers and Facilitators of Physical Activity: A Systematic Review of Qualitative Studies

    Science.gov (United States)

    Martins, João; Marques, Adilson; Sarmento, Hugo; Carreiro da Costa, Francisco

    2015-01-01

    This article examined qualitative studies of adolescents' perspectives about the facilitators and barriers of physical activity, published from 2007 to 2014. A systematic review of "Web of Science", "EBSCO", "Psychinfo" and "ERIC" databases was performed according to Preferred Reporting Items for Systematic…

  14. Confronting Physical Activity Programming Barriers for People with Disabilities: The Empowerment Model

    Science.gov (United States)

    Moran, Thomas Eugene; Taliaferro, Andrea R.; Pate, Joshua R.

    2014-01-01

    Community-based physical activity programs for people with disabilities have barriers that are unique to their program leader qualifications and the population they serve. Moran and Block (2010) argued that there is a need for practical strategies that are easy for communities to implement, maximize resources, and minimize the impact of barriers…

  15. Parent Support for Children's Physical Activity: A Qualitative Investigation of Barriers and Strategies

    Science.gov (United States)

    Bassett-Gunter, Rebecca; Rhodes, Ryan; Sweet, Shane; Tristani, Lauren; Soltani, Yasaman

    2017-01-01

    Purpose: Parents play an important role in supporting children's physical activity (PA) behavior. Parent PA support is a behavior unto itself that has been examined within the framework of an adapted theory of planned behavior (TPB). The primary purpose of this research was to identify key barriers to parent PA support to understand perceptions of…

  16. Young adult males' motivators and perceived barrier towards eating healthily and being active: A qualitative study

    Science.gov (United States)

    There is a lack of understanding of young men's perspectives in obesity-related research. This study aims to: (1) identify young men's perceived motivators and barriers in adopting healthy eating and physical activity behaviors, and (2) explore any differences in responses by weight status categorie...

  17. Adolescents' Perspectives on the Barriers and Facilitators of Physical Activity: A Systematic Review of Qualitative Studies

    Science.gov (United States)

    Martins, João; Marques, Adilson; Sarmento, Hugo; Carreiro da Costa, Francisco

    2015-01-01

    This article examined qualitative studies of adolescents' perspectives about the facilitators and barriers of physical activity, published from 2007 to 2014. A systematic review of "Web of Science", "EBSCO", "Psychinfo" and "ERIC" databases was performed according to Preferred Reporting Items for Systematic…

  18. A Qualitative Examination of Perceived Barriers and Facilitators of Physical Activity for Urban and Rural Youth

    Science.gov (United States)

    Moore, Justin B.; Jilcott, Stephanie B.; Shores, Kindal A.; Evenson, Kelly R.; Brownson, Ross C.; Novick, Lloyd F.

    2010-01-01

    Many adolescents, both rural and urban, are not meeting the recommended levels for physical activity (PA). This investigation was designed to elicit socioecologic barriers and facilitators for PA in rural and urban middle school youth and their parents. Thirteen focus groups were conducted with 41 youth and 50 parents from eastern North Carolina.…

  19. Isolation gowns in health care settings: Laboratory studies, regulations and standards, and potential barriers of gown selection and use

    Science.gov (United States)

    Kilinc Balci, F. Selcen

    2016-01-01

    Although they play an important role in infection prevention and control, textile materials and personal protective equipment (PPE) used in health care settings are known to be one of the sources of cross-infection. Gowns are recommended to prevent transmission of infectious diseases in certain settings; however, laboratory and field studies have produced mixed results of their efficacy. PPE used in health care is regulated as either class I (low risk) or class II (intermediate risk) devices in the United States. Many organizations have published guidelines for the use of PPE, including isolation gowns, in health care settings. In addition, the Association for the Advancement of Medical Instrumentation published a guidance document on the selection of gowns and a classification standard on liquid barrier performance for both surgical and isolation gowns. However, there is currently no existing standard specific to isolation gowns that considers not only the barrier resistance but also a wide array of end user desired attributes. As a result, infection preventionists and purchasing agents face several difficulties in the selection process, and end users have limited or no information on the levels of protection provided by isolation gowns. Lack of knowledge about the performance of protective clothing used in health care became more apparent during the 2014 Ebola epidemic. This article reviews laboratory studies, regulations, guidelines and standards pertaining to isolation gowns, characterization problems, and other potential barriers of isolation gown selection and use. PMID:26391468

  20. Physical activity in patients with heart failure: barriers and motivations with special focus on sex differences

    Directory of Open Access Journals (Sweden)

    Klompstra L

    2015-11-01

    Full Text Available Leonie Klompstra,1 Tiny Jaarsma,1 Anna Strömberg2,31Department of Social and Welfare Studies, Faculty of Health Sciences, 2Department of Medical and Health Sciences, Division of Nursing, 3Department of Cardiology, Linköping University, Linköping, SwedenBackground: Adherence to recommendations for physical activity is low in both male and female patients with heart failure (HF. Men are more physically active than women. In order to successfully promote physical activity, it is therefore essential to explore how much and why HF patients are physically active and if this is related to sex. The aim of this study was therefore to evaluate physical activity in HF patients, to describe the factors related to physical activity, and to examine potential barriers and motivations to physical activity with special focus on sex differences.Methods: The study had a cross-sectional survey design. HF patients living at home received a questionnaire during May–July 2014, with questions on physical activity (from the Short Form-International Physical Activity Questionnaire, and potential barriers and motivations to physical activity.Results: A total of 154 HF patients, 27% women, with a mean age of 70±10 were included. In total, 23% of the patients reported a high level of physical activity, 46% a moderate level, and 34% a low level. Higher education, self-efficacy, and motivation were significantly associated with a higher amount of physical activity. Symptoms or severity of the disease were not related to physical activity. All the potential barriers to exercise were reported to be of importance. Psychological motivations were most frequently rated as being the most important motivation (41% to be physically active. Physical motivations (33% and social motivations were rated as the least important ones (22%. Women had significantly higher total motivation to be physically active. These differences were found in social, physical, and psychological

  1. Assessment of active play, inactivity and perceived barriers in an inner city neighborhood

    OpenAIRE

    Kottyan, Gregg; Kottyan, Leah; Edwards, Nicholas M.; Unaka, Ndidi I.

    2014-01-01

    Avondale, a disadvantaged neighborhood in Cincinnati, lags behind on a number of indicators of child well-being. Childhood obesity has become increasingly prevalent, as one third of Avondale’s kindergarteners are obese or overweight. The study objective was to determine perceptions of the quantity of and obstacles to childhood physical activity in the Avondale community. Caregivers of children from two elementary schools were surveyed to assess their child’s physical activity and barriers to ...

  2. Regulation of Aicda expression and AID activity.

    Science.gov (United States)

    Zan, Hong; Casali, Paolo

    2013-03-01

    Activation-induced cytidine deaminase (AID) is expressed in a B cell differentiation stage-specific fashion and is essential for immunoglobulin (Ig) gene class switch DNA recombination (CSR) and somatic hypermutation (SHM). CSR and SHM play a central role in the maturation of antibody and autoantibody responses. AID displays a mutagenic activity by catalyzing targeted deamination of deoxycytidine (dC) residues in DNA resulting in dU:dG mismatches, which are processed into point-mutations in SHM or double-strand breaks (DSBs) in CSR. Although AID specifically targets the Ig gene loci (IgH, Igκ and Igλ), it can also home into a wide array of non-Ig genes in B-and non-B-cell backgrounds. Aberrant expression of AID is associated with multiple diseases such as allergy, inflammation, autoimmunity and cancer. In autoimmune systemic lupus erythematosus, dysregulated AID expression underpins increased CSR, SHM and autoantibody production. As a potent mutator, AID is under stringent transcriptional, post-transcriptional and post-translational regulation. AID is also regulated in its targeting and enzymatic function. In resting naïve or memory B cells, AID transcripts and protein are undetectable. These, however, are readily and significantly up-regulated in B cells induced to undergo CSR and/or SHM. Transcription factors, such as HoxC4 and NF-κB, which are up-regulated in a B cell lineage-and/or differentiation stage-specific manner, regulate the induction of AID. HoxC4 induces AID expression by directly binding to the AID gene promoter through an evolutionarily conserved 5'-ATTT-3' motif. HoxC4 is induced by the same stimuli that induce AID and CSR. It is further up-regulated by estrogen through three estrogen responsive elements in its promoter region. The targeting of AID to switch (S) regions is mediated by 14-3-3 adaptor proteins, which specifically bind to 5'-AGCT-3' repeats that are exist at high frequency in S region cores. Like HoxC4, 14-3-3 adaptors are induced

  3. Modelling Proteasome and Proteasome Regulator Activities

    Directory of Open Access Journals (Sweden)

    Juliane Liepe

    2014-06-01

    Full Text Available Proteasomes are key proteases involved in a variety of processes ranging from the clearance of damaged proteins to the presentation of antigens to CD8+ T-lymphocytes. Which cleavage sites are used within the target proteins and how fast these proteins are degraded have a profound impact on immune system function and many cellular metabolic processes. The regulation of proteasome activity involves different mechanisms, such as the substitution of the catalytic subunits, the binding of regulatory complexes to proteasome gates and the proteasome conformational modifications triggered by the target protein itself. Mathematical models are invaluable in the analysis; and potentially allow us to predict the complex interactions of proteasome regulatory mechanisms and the final outcomes of the protein degradation rate and MHC class I epitope generation. The pioneering attempts that have been made to mathematically model proteasome activity, cleavage preference variation and their modification by one of the regulatory mechanisms are reviewed here.

  4. Some methods to regulate low-bias negative differential resistance in σ barrier separating nanoscale molecular transport systems

    Science.gov (United States)

    Shen, Ji-Mei; Liu, Jing; Min, Yi; Zhou, Li-Ping

    2016-12-01

    Using the first-principles method which combines the nonequilibrium Green’s function (NEGF) with density functional theory (DFT), the role of defect, dopant, barrier length and geometric deformation for low-bias negative differential resistance (NDR) in two capped armchair carbon nanotubes (CNTs) sandwiching σ barrier are systematically analyzed. We found that this method can regulate the negative differential resistance (NDR) effects such as current peak and peak position. The adjusting mechanism may originate from orbital interaction and orbital reconstruction. Our calculations try to manipulate the transport characteristics in energy space by simply manipulating the structure in real space, which may promise the potential applications in nanomolecular-electronics in the future.

  5. Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation.

    Science.gov (United States)

    Sun, Yujia; Nien, Chung-Yi; Chen, Kai; Liu, Hsiao-Yun; Johnston, Jeff; Zeitlinger, Julia; Rushlow, Christine

    2015-11-01

    The Drosophila genome activator Vielfaltig (Vfl), also known as Zelda (Zld), is thought to prime enhancers for activation by patterning transcription factors (TFs). Such priming is accompanied by increased chromatin accessibility, but the mechanisms by which this occurs are poorly understood. Here, we analyze the effect of Zld on genome-wide nucleosome occupancy and binding of the patterning TF Dorsal (Dl). Our results show that early enhancers are characterized by an intrinsically high nucleosome barrier. Zld tackles this nucleosome barrier through local depletion of nucleosomes with the effect being dependent on the number and position of Zld motifs. Without Zld, Dl binding decreases at enhancers and redistributes to open regions devoid of enhancer activity. We propose that Zld primes enhancers by lowering the high nucleosome barrier just enough to assist TFs in accessing their binding motifs and promoting spatially controlled enhancer activation if the right patterning TFs are present. We envision that genome activators in general will utilize this mechanism to activate the zygotic genome in a robust and precise manner.

  6. Motivation and Barriers for Leisure-Time Physical Activity in Socioeconomically Disadvantaged Women.

    Science.gov (United States)

    Santos, Inês; Ball, Kylie; Crawford, David; Teixeira, Pedro J

    2016-01-01

    The aim of this study was to examine cross-sectional and longitudinal associations between motivation and barriers for physical activity, and physical activity behavior in women living in socioeconomic disadvantage. This study also examined whether weight control intentions moderate those associations. Data from 1664 women aged 18-46 years was collected at baseline and three-year follow-up as part of the Resilience for Eating and Activity Despite Inequality study. In mail-based surveys, women reported sociodemographic and neighborhood environmental characteristics, intrinsic motivation, goals and perceived family barriers to be active, weight control intentions and leisure-time physical activity (assessed through the IPAQ-L). Linear regression models assessed the association of intrinsic motivation, goals and barriers with physical activity at baseline and follow-up, adjusting for environmental characteristics and also physical activity at baseline (for longitudinal analyses), and the moderating effects of weight control intentions were examined. Intrinsic motivation and, to a lesser extent, appearance and relaxation goals for being physically active were consistently associated with leisure-time physical activity at baseline and follow-up. Perceived family barriers, health, fitness, weight and stress relief goals were associated with leisure-time physical activity only at baseline. Moderated regression analyses revealed that weight control intentions significantly moderated the association between weight goals and leisure-time physical activity at baseline (β = 0.538, 99% CI = 0.057, 0.990) and between intrinsic motivation and leisure-time physical activity at follow-up (β = 0.666, 99% CI = 0.188, 1.145). For women actively trying to control their weight, intrinsic motivation was significantly associated with leisure-time physical activity at follow-up (β = 0.184, 99% CI = 0.097, 0.313). Results suggest that, especially in women trying to control their weight

  7. Motivation and Barriers for Leisure-Time Physical Activity in Socioeconomically Disadvantaged Women.

    Directory of Open Access Journals (Sweden)

    Inês Santos

    Full Text Available The aim of this study was to examine cross-sectional and longitudinal associations between motivation and barriers for physical activity, and physical activity behavior in women living in socioeconomic disadvantage. This study also examined whether weight control intentions moderate those associations.Data from 1664 women aged 18-46 years was collected at baseline and three-year follow-up as part of the Resilience for Eating and Activity Despite Inequality study. In mail-based surveys, women reported sociodemographic and neighborhood environmental characteristics, intrinsic motivation, goals and perceived family barriers to be active, weight control intentions and leisure-time physical activity (assessed through the IPAQ-L. Linear regression models assessed the association of intrinsic motivation, goals and barriers with physical activity at baseline and follow-up, adjusting for environmental characteristics and also physical activity at baseline (for longitudinal analyses, and the moderating effects of weight control intentions were examined.Intrinsic motivation and, to a lesser extent, appearance and relaxation goals for being physically active were consistently associated with leisure-time physical activity at baseline and follow-up. Perceived family barriers, health, fitness, weight and stress relief goals were associated with leisure-time physical activity only at baseline. Moderated regression analyses revealed that weight control intentions significantly moderated the association between weight goals and leisure-time physical activity at baseline (β = 0.538, 99% CI = 0.057, 0.990 and between intrinsic motivation and leisure-time physical activity at follow-up (β = 0.666, 99% CI = 0.188, 1.145. For women actively trying to control their weight, intrinsic motivation was significantly associated with leisure-time physical activity at follow-up (β = 0.184, 99% CI = 0.097, 0.313.Results suggest that, especially in women trying to control

  8. Phosphorylation regulates coilin activity and RNA association

    Directory of Open Access Journals (Sweden)

    Hanna J. Broome

    2013-02-01

    The Cajal body (CB is a domain of concentrated components found within the nucleus of cells in an array of species that is functionally important for the biogenesis of telomerase and small nuclear ribonucleoproteins. The CB is a dynamic structure whose number and size change during the cell cycle and is associated with other nuclear structures and gene loci. Coilin, also known as the marker protein for the CB, is a phosphoprotein widely accepted for its role in maintaining CB integrity. Recent studies have been done to further elucidate functional activities of coilin apart from its structural role in the CB in an attempt to explore the rationale for coilin expression in cells that have few CBs or lack them altogether. Here we show that the RNA association profile of coilin changes in mitosis with respect to that during interphase. We provide evidence of transcriptional and/or processing dysregulation of several CB-related RNA transcripts as a result of ectopic expression of both wild-type and phosphomutant coilin proteins. We also show apparent changes in transcription and/or processing of these transcripts upon coilin knockdown in both transformed and primary cell lines. Additionally, we provide evidence of specific coilin RNase activity regulation, on both U2 and hTR transcripts, by phosphorylation of a single residue, serine 489. Collectively, these results point to additional functions for coilin that are regulated by phosphorylation.

  9. Motivators of and Barriers to Engaging in Physical Activity: Perspectives of Low-Income Culturally Diverse Adolescents and Adults

    Science.gov (United States)

    Bragg, Marie A.; Tucker, Carolyn M.; Kaye, Lily B.; Desmond, Frederic

    2009-01-01

    Background: Obesity rates are rising in the United States, especially among low-income and racial/ethnic minority individuals. Exploring motivators and barriers relative to engaging in physical activity is imperative. Purpose: The purpose of this study was to identify motivators and barriers relative to engagement in physical activity as reported…

  10. Activation of VEGF/Flk-1-ERK Pathway Induced Blood-Brain Barrier Injury After Microwave Exposure.

    Science.gov (United States)

    Wang, Li-Feng; Li, Xiang; Gao, Ya-Bing; Wang, Shui-Ming; Zhao, Li; Dong, Ji; Yao, Bin-Wei; Xu, Xin-Ping; Chang, Gong-Min; Zhou, Hong-Mei; Hu, Xiang-Jun; Peng, Rui-Yun

    2015-08-01

    Microwaves have been suggested to induce neuronal injury and increase permeability of the blood-brain barrier (BBB), but the mechanism remains unknown. The role of the vascular endothelial growth factor (VEGF)/Flk-1-Raf/MAPK kinase (MEK)/extracellular-regulated protein kinase (ERK) pathway in structural and functional injury of the blood-brain barrier (BBB) following microwave exposure was examined. An in vitro BBB model composed of the ECV304 cell line and primary rat cerebral astrocytes was exposed to microwave radiation (50 mW/cm(2), 5 min). The structure was observed by scanning electron microscopy (SEM) and the permeability was assessed by measuring transendothelial electrical resistance (TEER) and horseradish peroxidase (HRP) transmission. Activity and expression of VEGF/Flk-1-ERK pathway components and occludin also were examined. Our results showed that microwave radiation caused intercellular tight junctions to broaden and fracture with decreased TEER values and increased HRP permeability. After microwave exposure, activation of the VEGF/Flk-1-ERK pathway and Tyr phosphorylation of occludin were observed, along with down-regulated expression and interaction of occludin with zonula occludens-1 (ZO-1). After Flk-1 (SU5416) and MEK1/2 (U0126) inhibitors were used, the structure and function of the BBB were recovered. The increase in expression of ERK signal transduction molecules was muted, while the expression and the activity of occludin were accelerated, as well as the interactions of occludin with p-ERK and ZO-1 following microwave radiation. Thus, microwave radiation may induce BBB damage by activating the VEGF/Flk-1-ERK pathway, enhancing Tyr phosphorylation of occludin, while partially inhibiting expression and interaction of occludin with ZO-1.

  11. Lipid rafts regulate PCB153-induced disruption of occludin and brain endothelial barrier function through protein phosphatase 2A and matrix metalloproteinase-2.

    Science.gov (United States)

    Eum, Sung Yong; Jaraki, Dima; András, Ibolya E; Toborek, Michal

    2015-09-15

    Occludin is an essential integral transmembrane protein regulating tight junction (TJ) integrity in brain endothelial cells. Phosphorylation of occludin is associated with its localization to TJ sites and incorporation into intact TJ assembly. The present study is focused on the role of lipid rafts in polychlorinated biphenyl (PCB)-induced disruption of occludin and endothelial barrier function. Exposure of human brain endothelial cells to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) induced dephosphorylation of threonine residues of occludin and displacement of occludin from detergent-resistant membrane (DRM)/lipid raft fractions within 1h. Moreover, lipid rafts modulated the reduction of occludin level through activation of matrix metalloproteinase 2 (MMP-2) after 24h PCB153 treatment. Inhibition of protein phosphatase 2A (PP2A) activity by okadaic acid or fostriecin markedly protected against PCB153-induced displacement of occludin and increased permeability of endothelial cells. The implication of lipid rafts and PP2A signaling in these processes was further defined by co-immunoprecipitation of occludin with PP2A and caveolin-1, a marker protein of lipid rafts. Indeed, a significant MMP-2 activity was observed in lipid rafts and was increased by exposure to PCB153. The pretreatment of MMP-2 inhibitors protected against PCB153-induced loss of occludin and disruption of lipid raft structure prevented the increase of endothelial permeability. Overall, these results indicate that lipid raft-associated processes, such as PP2A and MMP-2 activation, participate in PCB153-induced disruption of occludin function in brain endothelial barrier. This study contributes to a better understanding of the mechanisms leading to brain endothelial barrier dysfunction in response to exposure to environmental pollutants, such as ortho-substituted PCBs.

  12. Lipid rafts regulate PCB153-induced disruption of occludin and brain endothelial barrier function through protein phosphatase 2A and matrix metalloproteinase-2

    Science.gov (United States)

    Eum, Sung Yong; Jaraki, Dima; András, Ibolya E.; Toborek, Michal

    2015-01-01

    Occludin is an essential integral transmembrane protein regulating tight junction (TJ) integrity in brain endothelial cells. Phosphorylation of occludin is associated with its localization to TJ sites and incorporation into intact TJ assembly. The present study is focused on the role of lipid rafts in polychlorinated biphenyl (PCB)-induced disruption of occludin and endothelial barrier function. Exposure of human brain endothelial cells to 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) induced dephosphorylation of threonine residues of occludin and displacement of occludin from detergent-resistant membrane (DRM)/lipid raft fractions within 1 h. Moreover, lipid rafts modulated the reduction of occludin level through activation of matrix metalloproteinase 2 (MMP-2) after 24 h h PCB153 treatment. Inhibition of protein phosphatase 2A (PP2A) activity by okadaic acid or fostriecin markedly protected against PCB153-induced displacement of occludin and increased permeability of endothelial cells. The implication of lipid rafts and PP2A signaling in these processes was further defined by co-immunoprecipitation of occludin with PP2A and caveolin-1, a marker protein of lipid rafts. Indeed, a significant MMP-2 activity was observed in lipid rafts and was increased by exposure to PCB153. The pretreatment of MMP-2 inhibitors protected against PCB153-induced loss of occludin and disruption of lipid raft structure prevented the increase of endothelial permeability. Overall, these results indicate that lipid raft-associated processes, such as PP2A and MMP-2 activation, participate in PCB153-induced disruption of occludin function in brain endothelial barrier. This study contributes to a better understanding of the mechanisms leading to brain endothelial barrier dysfunction in response to exposure to environmental pollutants, such as ortho-substituted PCBs. PMID:26080028

  13. Active barrier films of PET for solar cell application: Processing and characterization

    Energy Technology Data Exchange (ETDEWEB)

    Rossi, Gabriella; Scarfato, Paola; Incarnato, Loredana [Department of Industrial Engineering, University of Salerno, Via Giovanni Paolo II, 132 - 84084 Fisciano (Italy)

    2014-05-15

    A preliminary investigation was carried out on the possibility to improve the protective action offered by the standard multilayer structures used to encapsulate photovoltaic devices. With this aim, a commercial active barrier PET-based material, able to absorb oxygen when activated by liquid water, was used to produce flexible and transparent active barrier films, by means of a lab-scale film production plant. The obtained film, tested in terms of thermal, optical and oxygen absorption properties, shows a slow oxygen absorption kinetics, an acceptable transparency and an easy roll-to-roll processability, so proving itself as a good candidate for the development of protective coating for solar cells against the atmospheric degradation agents like the rain.

  14. Perceived barriers and facilitators to participation in physical activity for children with disability: a qualitative study.

    Science.gov (United States)

    Shields, Nora; Synnot, Anneliese

    2016-01-19

    Children with disability engage in less physical activity compared to their typically developing peers. Our aim was to explore the barriers and facilitators to participation in physical activity for this group. Ten focus groups, involving 63 participants (23 children with disability, 20 parents of children with disability and 20 sport and recreation staff), were held to explore factors perceived as barriers and facilitators to participation in physical activity by children with disability. Data were analysed thematically by two researchers. Four themes were identified: (1) similarities and differences, (2) people make the difference, (3) one size does not fit all, and (4) communication and connections. Key facilitators identified were the need for inclusive pathways that encourage ongoing participation as children grow or as their skills develop, and for better partnerships between key stakeholders from the disability, sport, education and government sectors. Children with disabilities' need for the early attainment of motor and social skills and the integral role of their families in supporting them were considered to influence their participation in physical activity. Children with disability were thought to face additional barriers to participation compared to children with typical development including a lack of instructor skills and unwillingness to be inclusive, negative societal attitudes towards disability, and a lack of local opportunities. The perspectives gathered in this study are relevant to the many stakeholders involved in the design and implementation of effective interventions, strategies and policies to promote participation in physical activity for children with disability. We outline ten strategies for facilitating participation.

  15. Perceived Barriers to Healthy Eating and Physical Activity among Adolescents in Seven Arab Countries: A Cross-Cultural Study

    Directory of Open Access Journals (Sweden)

    Abdulrahman O. Musaiger

    2013-01-01

    Full Text Available Objective. To highlight the perceived personal, social, and environmental barriers to healthy eating and physical activity among Arab adolescents. Method. A multistage stratified sampling method was used to select 4698 students aged 15–18 years (2240 males and 2458 females from public schools. Seven Arab counties were included in the study, namely, Algeria, Jordan, Kuwait, Libya, Palestine, Syria, and the United Arab Emirates. Self-reported questionnaire was used to list the barriers to healthy eating and physical activity facing these adolescents. Results. It was found that lack of information on healthy eating, lack of motivation to eat a healthy diet, and not having time to prepare or eat healthy food were the main barriers to healthy eating among both genders. For physical activity, the main barriers selected were lack of motivation to do physical activity, less support from teachers, and lack of time to do physical activity. In general, females faced more barriers to physical activity than males in all countries included. There were significant differences between males and females within each country and among countries for most barriers. Conclusion. Intervention programmes to combat obesity and other chronic noncommunicable diseases in the Arab world should include solutions to overcome the barriers to weight maintenance, particularly the sociocultural barriers to practising physical activity.

  16. Topical antihistamines display potent anti-inflammatory activity linked in part to enhanced permeability barrier function.

    Science.gov (United States)

    Lin, Tzu-Kai; Man, Mao-Qiang; Santiago, Juan-Luis; Park, Kyungho; Roelandt, Truus; Oda, Yuko; Hupe, Melanie; Crumrine, Debra; Lee, Hae-Jin; Gschwandtner, Maria; Thyssen, Jacob P; Trullas, Carles; Tschachler, Erwin; Feingold, Kenneth R; Elias, Peter M

    2013-02-01

    Systemic antagonists of the histamine type 1 and 2 receptors (H1/2r) are widely used as anti-pruritics and central sedatives, but demonstrate only modest anti-inflammatory activity. Because many inflammatory dermatoses result from defects in cutaneous barrier function, and because keratinocytes express both Hr1 and Hr2, we hypothesized that H1/2r antagonists might be more effective if they were used topically to treat inflammatory dermatoses. Topical H1/2r antagonists additively enhanced permeability barrier homeostasis in normal mouse skin by the following mechanisms: (i) stimulation of epidermal differentiation, leading to thickened cornified envelopes; and (ii) enhanced epidermal lipid synthesis and secretion. As barrier homeostasis was enhanced to a comparable extent in mast cell-deficient mice, with no further improvement following application of topical H1/2r antagonists, H1/2r antagonists likely oppose mast cell-derived histamines. In four immunologically diverse, murine disease models, characterized by either inflammation alone (acute irritant contact dermatitis, acute allergic contact dermatitis) or by prominent barrier abnormalities (subacute allergic contact dermatitis, atopic dermatitis), topical H1/2r agonists aggravated, whereas H1/2r antagonists improved, inflammation and/or barrier function. The apparent ability of topical H1r/2r antagonists to target epidermal H1/2r could translate into increased efficacy in the treatment of inflammatory dermatoses, likely due to decreased inflammation and enhanced barrier function. These results could shift current paradigms of antihistamine utilization from a predominantly systemic to a topical approach.

  17. A prospective examination of exercise and barrier self-efficacy to engage in leisure-time physical activity during pregnancy.

    Science.gov (United States)

    Cramp, Anita G; Bray, Steven R

    2009-06-01

    Pregnant women without medical contraindications should accumulate 30 min of moderate exercise on most days of the week, yet many pregnant women do not exercise at recommended levels. The purpose the study was to examine barriers to leisure-time physical activity (LTPA) and investigate barrier and exercise self-efficacy as predictors of self-reported LTPA during pregnancy. Pregnant women (n = 160) completed questionnaires eliciting barriers to LTPA, measures of exercise and barrier self-efficacy, and 6-week LTPA recall at gestational weeks 18, 24, 30, and 36. A total of 1,168 barriers were content-analyzed, yielding nine major themes including fatigue, time constraints, and physical limitations. Exercise self-efficacy predicted LTPA from gestational weeks 18 to 24 (beta = 0.32, R(2) = 0.26) and weeks 30 to 36 (beta = 0.41, R(2) = 0.37), while barrier self-efficacy predicted LTPA from weeks 24 to 30 (beta = 0.40, R(2) = 0.32). Pregnant women face numerous barriers to LTPA during pregnancy, the nature of which may change substantially over the course of pregnancy. Higher levels of self-efficacy to exercise and to overcome exercise barriers are associated with greater LTPA during pregnancy. Research and interventions to understand and promote LTPA during pregnancy should explore the dynamic nature of exercise barriers and foster women's confidence to overcome physical activity barriers.

  18. Cytokinins are central regulators of cambial activity.

    Science.gov (United States)

    Matsumoto-Kitano, Miho; Kusumoto, Takami; Tarkowski, Petr; Kinoshita-Tsujimura, Kaori; Václavíková, Katerina; Miyawaki, Kaori; Kakimoto, Tatsuo

    2008-12-16

    The roots and stems of dicotyledonous plants thicken by the cell proliferation in the cambium. Cambial proliferation changes in response to environmental factors; however, the molecular mechanisms that regulate cambial activity are largely unknown. The quadruple Arabidopsis thaliana mutant atipt1;3;5;7, in which 4 genes encoding cytokinin biosynthetic isopentenyltransferases are disrupted by T-DNA insertion, was unable to form cambium and showed reduced thickening of the root and stem. The atipt3 single mutant, which has moderately decreased levels of cytokinins, exhibited decreased root thickening without any other recognizable morphological changes. Addition of exogenously supplied cytokinins to atipt1;3;5;7 reactivated the cambium in a dose-dependent manner. When an atipt1;3;5;7 shoot scion was grafted onto WT root stock, both the root and shoot grew normally and trans-zeatin-type (tZ-type) cytokinins in the shoot were restored to WT levels, but isopentenyladenine-type cytokinins in the shoot remained unchanged. Conversely, when a WT shoot was grafted onto an atipt1;3;5;7 root, both the root and shoot grew normally and isopentenyladenine-type cytokinins in the root were restored to WT levels, but tZ-type cytokinins were only partially restored. Collectively, it can be concluded that cytokinins are important regulators of cambium development and that production of cytokinins in either the root or shoot is sufficient for normal development of both the root and shoot.

  19. Facilitators and barriers to physical activity as perceived by older adults with intellectual disability.

    Science.gov (United States)

    van Schijndel-Speet, Marieke; Evenhuis, Heleen M; van Wijck, Ruud; van Empelen, Pepijn; Echteld, Michael A

    2014-06-01

    Older people with intellectual disability (ID) are characterized by low physical activity (PA) levels. PA is important for reducing health risks and maintaining adequate fitness levels for performing activities of daily living. The aim of this study was to explore preferences of older adults with ID for specific physical activities, and to gain insight into facilitators and barriers to engaging into PA. Fourteen in-depth interviews and four focus groups were undertaken, with a total of 40 older adults with mild and moderate ID included in the analysis. NVivo software was used for analysing the transcribed verbatim interviews. In total, 30 codes for facilitators and barriers were identified. Themes concerning facilitators to PA were enjoyment, support from others, social contact and friendship, reward, familiarity, and routine of activities. Themes concerning barriers to PA were health and physiological factors, lack of self-confidence, lack of skills, lack of support, transportation problems, costs, and lack of appropriate PA options and materials. The results of the present study suggest that older adults with ID may benefit from specific PA programs, adapted to their individual needs and limitations. Results can be used for developing feasible health promotion programs for older adults with ID.

  20. Compromised epidermal barrier stimulates Harderian gland activity and hypertrophy in ACBP−/− mice[S

    Science.gov (United States)

    Bek, Signe; Neess, Ditte; Dixen, Karen; Bloksgaard, Maria; Marcher, Ann-Britt; Chemnitz, John; Færgeman, Nils J.; Mandrup, Susanne

    2015-01-01

    Acyl-CoA binding protein (ACBP) is a small, ubiquitously expressed intracellular protein that binds C14-C22 acyl-CoA esters with very high affinity and specificity. We have recently shown that targeted disruption of the Acbp gene leads to a compromised epidermal barrier and that this causes delayed adaptation to weaning, including the induction of the hepatic lipogenic and cholesterogenic gene programs. Here we show that ACBP is highly expressed in the Harderian gland, a gland that is located behind the eyeball of rodents and involved in the production of fur lipids and lipids used for lubrication of the eye lid. We show that disruption of the Acbp gene leads to a significant enlargement of this gland with hypertrophy of the acinar cells and increased de novo synthesis of monoalkyl diacylglycerol, the main lipid species produced by the gland. Mice with conditional targeting of the Acbp gene in the epidermis recapitulate this phenotype, whereas generation of an artificial epidermal barrier during gland development reverses the phenotype. Our findings indicate that the Harderian gland is activated by the compromised epidermal barrier as an adaptive and protective mechanism to overcome the barrier defect. PMID:26142722

  1. The benefits and barriers to physical activity and lifestyle interventions for osteoarthritis affecting the adult knee

    Directory of Open Access Journals (Sweden)

    Stevenson Jonathan

    2012-03-01

    Full Text Available Abstract Osteoarthritis prevalence is increasing, placing greater demands on healthcare and future socioeconomic costing models. Exercise and non-pharmacological methods should be employed to manage this common and disabling disease. Expectations at all stages of disease are increasing with a desire to remain active and independent. Three key areas have been reviewed; the evidence for physical activity, lifestyle changes and motivational techniques concerning knee osteoarthritis and the barriers to instituting such changes. Promotion of activity in primary care is discussed and evidence for compliance has been reviewed. This article reviews a subject that is integral to all professionals involved with osteoarthritis care.

  2. Activation barrier scaling and crossover for noise-induced switching in micromechanical parametric oscillators.

    Science.gov (United States)

    Chan, H B; Stambaugh, C

    2007-08-10

    We explore fluctuation-induced switching in parametrically driven micromechanical torsional oscillators. The oscillators possess one, two, or three stable attractors depending on the modulation frequency. Noise induces transitions between the coexisting attractors. Near the bifurcation points, the activation barriers are found to have a power law dependence on frequency detuning with critical exponents that are in agreement with predicted universal scaling relationships. At large detuning, we observe a crossover to a different power law dependence with an exponent that is device specific.

  3. Physical activity perceptions, context, barriers, and facilitators from a Hispanic child's perspective

    Science.gov (United States)

    Ross, Sharon E. Taverno; Francis, Lori A.

    2016-01-01

    Background In order to develop effective physical activity interventions and to address the burden of obesity in Hispanic children, qualitative studies are needed to build descriptive theory and expand the state of the science. The purpose of this study is to describe physical activity perceptions, context, facilitators, and barriers from the perspective of Hispanic immigrant-origin children. Method This in-depth, ethnographic study included 14, 6- to 11-year old, first- and second- generation Hispanic children recruited from an afterschool program in Southeastern Pennsylvania, USA. Methods included child observation, field notes, semi-structured interviews, and a PhotoVoice activity. Transcripts and field notes were coded and analyzed using the constant comparison method to identify overarching themes and patterns in the data. Results Data analysis yielded four overarching themes regarding children's perspectives on physical activity. Children engaged in a variety of physical activities and sedentary behaviors, which differed by physical (e.g., park, outside home, and afterschool programs) and social (e.g., parents, siblings, and friends) contexts. Children discussed specific benefits of physical activity. Children's negative attitudes toward physical activity were related to physical discomfort, low athletic competence, and safety concerns. Children perceived physical activity and play to be one in the same, and “fun” was identified as a primary driver of physical activity preferences. The facilitators and barriers to physical activity were related to specific parent/home, school, and neighborhood factors. Conclusion Findings from this study suggest that an emphasis on fun and active play, while taking into account family and neighborhood context, may be a desirable intervention approach in Hispanic immigrant-origin children. This study lays the groundwork for future studies to further explore some of the themes identified here to better understand children

  4. Physical activity perceptions, context, barriers, and facilitators from a Hispanic child's perspective

    Directory of Open Access Journals (Sweden)

    Sharon E. Taverno Ross

    2016-08-01

    Full Text Available Background: In order to develop effective physical activity interventions and to address the burden of obesity in Hispanic children, qualitative studies are needed to build descriptive theory and expand the state of the science. The purpose of this study is to describe physical activity perceptions, context, facilitators, and barriers from the perspective of Hispanic immigrant-origin children. Method: This in-depth, ethnographic study included 14, 6- to 11-year old, first- and second- generation Hispanic children recruited from an afterschool program in Southeastern Pennsylvania, USA. Methods included child observation, field notes, semi-structured interviews, and a PhotoVoice activity. Transcripts and field notes were coded and analyzed using the constant comparison method to identify overarching themes and patterns in the data. Results: Data analysis yielded four overarching themes regarding children's perspectives on physical activity. Children engaged in a variety of physical activities and sedentary behaviors, which differed by physical (e.g., park, outside home, and afterschool programs and social (e.g., parents, siblings, and friends contexts. Children discussed specific benefits of physical activity. Children's negative attitudes toward physical activity were related to physical discomfort, low athletic competence, and safety concerns. Children perceived physical activity and play to be one in the same, and “fun” was identified as a primary driver of physical activity preferences. The facilitators and barriers to physical activity were related to specific parent/home, school, and neighborhood factors. Conclusion: Findings from this study suggest that an emphasis on fun and active play, while taking into account family and neighborhood context, may be a desirable intervention approach in Hispanic immigrant-origin children. This study lays the groundwork for future studies to further explore some of the themes identified here to better

  5. Promoting physical activity participation among adolescents: The barriers and the suggestions

    Directory of Open Access Journals (Sweden)

    Niloofar Peykari

    2015-01-01

    Full Text Available Background: Physical activity is a complex behavior. To designing the effective intervention, qualitative researches may be allowed for greater understanding of the reasons behind the adolescences′ physical activity-related behaviors′. Methods: Using the grounded theory approach, including semi-structured focus group discussions (FGDs and in-depth interviews, we conducted a quantitative study to elicit the adolescents and key informants′ opinion regarding the satiation, needs, social and environmental barriers of adolescents′ physical activity. For FGDs, participants were selected from volunteered adolescent (aged 10-19 years of the populated western part of Tehran, which was selected as a research field. Key informants were invited from the health professionals and experts in the field of adolescents′ health. Results: According to findings, although the majority of participants agreed on the important role of physical activity, the lack of essential motivation and the pressure of educational assignments remove it from the daily program priorities. Lack of a safe environment for girls′ physical activity and high cost of professional sports were two first mentioned barriers. It was also suggested that future interventions should focus on improving more parents′ engagement and their direct participation in physical activities with their adolescents. Conclusions: We proposed the participatory strategies for adolescent′s physical activity promotion. Through which target groups participation during the designing, development, and implementation of health programs led to more effective interventions.

  6. Motivators and Barriers to Engaging in Healthy Eating and Physical Activity.

    Science.gov (United States)

    Ashton, Lee M; Hutchesson, Melinda J; Rollo, Megan E; Morgan, Philip J; Collins, Clare E

    2017-03-01

    Many Australian young men (18-25 years) fail to meet recommendations in national dietary or physical activity (PA) guidelines. However, there is a lack of understanding of their perspectives on PA and diet to inform intervention design. This study examined young men's motivators and barriers to healthy eating and PA, along with differences by demographic and behavioral factors. A cross-sectional online survey was completed by 282 men aged 18 to 25 years in Australia. Results identified the most common motivators for healthy eating included improving health (63.5%), body image (52.3%), and increasing energy (32.1%). Motivators for PA included improving body image (44.6%), fitness (44.2%), and health (41.0%). Common barriers to healthy eating were access to unhealthy foods (61.1%), time to cook/prepare healthy foods (55.0%), and motivation to cook healthy foods (50.7%). Barriers for PA included motivation (66.3%), time (57.8%), and cost of equipment/facilities (33.3%). Significant differences ( p healthy eating and/or PA were identified for BMI category, marital status, PA level, alcohol intake, and stress levels. Significant differences were identified for barriers to healthy eating and/or PA by BMI, PA level, stress, and fruit and vegetable intake, assessed using Pearson's chi-square test. Findings suggest that promotion of benefits related to health, appearance/body image, increased energy and fitness, and addressing key barriers including motivation, time, financial restraints, and accessibility of unhealthy foods, could engage young men in improving lifestyle behaviors. Differences by demographic and behavioral factors suggest development of tailored programs to address diversity among young men may be required.

  7. P-glycoprotein activity in the blood-brain barrier is affected by virus-induced neuroinflammation and antipsychotic treatment

    NARCIS (Netherlands)

    Doorduin, Janine; de Vries, Erik F. J.; Dierckx, Rudi A.; Klein, Hans C.

    2014-01-01

    A large percentage of schizophrenic patients respond poorly to antipsychotic treatment. This could be explained by inefficient drug transport across the blood-brain barrier due to P-glycoprotein mediated efflux. P-glycoprotein activity and expression in the blood-brain barrier can be affected by

  8. Lipid rafts regulate PCB153-induced disruption of occludin and brain endothelial barrier function through protein phosphatase 2A and matrix metalloproteinase-2

    Energy Technology Data Exchange (ETDEWEB)

    Eum, Sung Yong, E-mail: seum@miami.edu; Jaraki, Dima; András, Ibolya E.; Toborek, Michal

    2015-09-15

    Occludin is an essential integral transmembrane protein regulating tight junction (TJ) integrity in brain endothelial cells. Phosphorylation of occludin is associated with its localization to TJ sites and incorporation into intact TJ assembly. The present study is focused on the role of lipid rafts in polychlorinated biphenyl (PCB)-induced disruption of occludin and endothelial barrier function. Exposure of human brain endothelial cells to 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) induced dephosphorylation of threonine residues of occludin and displacement of occludin from detergent-resistant membrane (DRM)/lipid raft fractions within 1 h. Moreover, lipid rafts modulated the reduction of occludin level through activation of matrix metalloproteinase 2 (MMP-2) after 24 h PCB153 treatment. Inhibition of protein phosphatase 2A (PP2A) activity by okadaic acid or fostriecin markedly protected against PCB153-induced displacement of occludin and increased permeability of endothelial cells. The implication of lipid rafts and PP2A signaling in these processes was further defined by co-immunoprecipitation of occludin with PP2A and caveolin-1, a marker protein of lipid rafts. Indeed, a significant MMP-2 activity was observed in lipid rafts and was increased by exposure to PCB153. The pretreatment of MMP-2 inhibitors protected against PCB153-induced loss of occludin and disruption of lipid raft structure prevented the increase of endothelial permeability. Overall, these results indicate that lipid raft-associated processes, such as PP2A and MMP-2 activation, participate in PCB153-induced disruption of occludin function in brain endothelial barrier. This study contributes to a better understanding of the mechanisms leading to brain endothelial barrier dysfunction in response to exposure to environmental pollutants, such as ortho-substituted PCBs. - Highlights: • PCB153 disturbed human brain endothelial barrier through disruption of occludin. • Lipid raft-associated PP

  9. Ceramide 1-Phosphate Increases P-Glycoprotein Transport Activity at the Blood-Brain Barrier via Prostaglandin E2 Signaling.

    Science.gov (United States)

    Mesev, Emily V; Miller, David S; Cannon, Ronald E

    2017-04-01

    P-glycoprotein, an ATP-driven efflux pump, regulates permeability of the blood-brain barrier (BBB). Sphingolipids, endogenous to brain tissue, influence inflammatory responses and cell survival in vitro. Our laboratory has previously shown that sphingolipid signaling by sphingosine 1-phosphate decreases basal P-glycoprotein transport activity. Here, we investigated the potential for another sphingolipid, ceramide 1-phosphate (C1P), to modulate efflux pumps at the BBB. Using confocal microscopy and measuring luminal accumulation of fluorescent substrates, we assessed the transport activity of several efflux pumps in isolated rat brain capillaries. C1P treatment induced P-glycoprotein transport activity in brain capillaries rapidly and reversibly. In contrast, C1P did not affect transport activity of two other major efflux transporters, multidrug resistance protein 2 and breast cancer resistance protein. C1P induced P-glycoprotein transport activity without changing transporter protein expression. Inhibition of the key signaling components in the cyclooxygenase-2 (COX-2)/prostaglandin E2 signaling cascade (phospholipase A2, COX-2, multidrug resistance protein 4, and G-protein-coupled prostaglandin E2 receptors 1 and 2), abolished P-glycoprotein induction by C1P. We show that COX-2 and prostaglandin E2 are required for C1P-mediated increases in P-glycoprotein activity independent of transporter protein expression. This work describes how C1P activates a signaling cascade to dynamically regulate P-glycoprotein transport at the BBB and offers potential clinical targets to modulate neuroprotection and drug delivery to the CNS.

  10. Polyphenol-Rich Propolis Extracts Strengthen Intestinal Barrier Function by Activating AMPK and ERK Signaling

    Directory of Open Access Journals (Sweden)

    Kai Wang

    2016-05-01

    Full Text Available Propolis has abundant polyphenolic constituents and is used widely as a health/functional food. Here, we investigated the effects of polyphenol-rich propolis extracts (PPE on intestinal barrier function in human intestinal epithelial Caco-2 cells, as well as in rats. In Caco-2 cells, PPE increased transepithelial electrical resistance and decreased lucifer yellow flux. PPE-treated cells showed increased expression of the tight junction (TJ loci occludin and zona occludens (ZO-1. Confocal microscopy showed organized expressions in proteins related to TJ assembly, i.e., occludin and ZO-1, in response to PPE. Furthermore, PPE led to the activation of AMPK, ERK1/2, p38, and Akt. Using selective inhibitors, we found that the positive effects of PPE on barrier function were abolished in cells in which AMPK and ERK1/2 signaling were inhibited. Moreover, rats fed a diet supplemented with PPE (0.3% in the diet exhibited increased colonic epithelium ZO-1 expression. Overall, these data suggest that PPE strengthens intestinal barrier function by activating AMPK and ERK signaling and provide novel insights into the potential application of propolis for human gut health.

  11. Polyphenol-Rich Propolis Extracts Strengthen Intestinal Barrier Function by Activating AMPK and ERK Signaling.

    Science.gov (United States)

    Wang, Kai; Jin, Xiaolu; Chen, Yifan; Song, Zehe; Jiang, Xiasen; Hu, Fuliang; Conlon, Michael A; Topping, David L

    2016-05-07

    Propolis has abundant polyphenolic constituents and is used widely as a health/functional food. Here, we investigated the effects of polyphenol-rich propolis extracts (PPE) on intestinal barrier function in human intestinal epithelial Caco-2 cells, as well as in rats. In Caco-2 cells, PPE increased transepithelial electrical resistance and decreased lucifer yellow flux. PPE-treated cells showed increased expression of the tight junction (TJ) loci occludin and zona occludens (ZO)-1. Confocal microscopy showed organized expressions in proteins related to TJ assembly, i.e., occludin and ZO-1, in response to PPE. Furthermore, PPE led to the activation of AMPK, ERK1/2, p38, and Akt. Using selective inhibitors, we found that the positive effects of PPE on barrier function were abolished in cells in which AMPK and ERK1/2 signaling were inhibited. Moreover, rats fed a diet supplemented with PPE (0.3% in the diet) exhibited increased colonic epithelium ZO-1 expression. Overall, these data suggest that PPE strengthens intestinal barrier function by activating AMPK and ERK signaling and provide novel insights into the potential application of propolis for human gut health.

  12. Regulatory barriers for activating flexibility in the Nordic-Baltic electricity market

    DEFF Research Database (Denmark)

    Bergaentzlé, Claire; Skytte, Klaus; Soysal, Emilie Rosenlund

    2017-01-01

    The rapid growth of variable renewable energy (VRE) and the expected decrease of conventional generation capacities will generate more flexibility needs in power systems and require flexibility resources to be activated. Flexibility potentials do exist, whether they refer to installed generation......, load adjustment or to a greater coupling to other energy sectors. In this paper, we identify the framework conditions that influence the provision of VRE-friendly flexibility in the Nordic and Baltic electricity sector, i.e., the market and regulatory settings that act as drivers or barriers...... to flexibility. We find that the most restrictive barriers against flexibility are emitted by public authorities as part of broader policy strategies. Overall, we find that current regulatory and market framework conditions do not hinder flexibility. However, despite that, flexibility remains limited due...

  13. 76 FR 12364 - Agency Information Collection Activities: Bonded Warehouse Regulations

    Science.gov (United States)

    2011-03-07

    ... SECURITY U.S. Customs and Border Protection Agency Information Collection Activities: Bonded Warehouse... Bonded Warehouse Regulations. This request for comment is being made pursuant to the Paperwork Reduction... concerning the following information collection: Title: Bonded Warehouse Regulations. OMB Number:...

  14. Epigenetic regulation of the placental HSD11B2 barrier and its role as a critical regulator of fetal development

    OpenAIRE

    2014-01-01

    “Fetal programming” is a term used to describe how early-life experience influences fetal development and later disease risk. In humans, prenatal stress-induced fetal programming is associated with increased risk of preterm birth, and a heightened risk of metabolic and neurological diseases later in life. A critical determinant of this is the regulation of fetal exposure to glucocorticoids by the placenta. Glucocorticoids are the mediators through which maternal stress influences fetal develo...

  15. Barriers and Facilitators for Being Physically Active in Patients with Ankylosing Spondylitis: A Cross-sectional Comparative Study.

    Science.gov (United States)

    Fongen, Camilla; Sveaas, Silje Halvorsen; Dagfinrud, Hanne

    2015-06-01

    The aims of the present study were to explore the barriers and facilitators for being physically active and the perceived health benefits of physical activity in a group of patients with ankylosing spondylitis (AS), and to compare the findings with those in population controls. A total of 148 patients and 133 controls were included in a cross-sectional study. Barriers, facilitators and perceived health benefits were registered in a structured interview. Patients were significantly more likely to report barriers to being physically active compared with controls (78% versus 58%; p ≤ 0.001). The barriers most frequently reported by patients were pain (48%), stiffness (36%), fatigue (30%) and disability (21%). A similar proportion of patients (62%) and controls (61%) reported that they had the potential to become more physically active (p = 0.12). Time and motivation were the most frequently reported facilitators in both groups. Patients also reported stable disease (15%) and individually adapted physical activity (8%) as facilitators. An equal proportion of patients (96%) and controls (96%) reported that physical activity had a positive effect on their health (p = 0.94). Improved fitness and increased vitality were the most frequently reported health benefits in both groups. Patients also reported greater disease stability (37%) and reduced pain (33%) as benefits. A larger proportion of patients than controls reported barriers to being physically active. In addition to regular barriers, facilitators and health benefits, patients reported that disease-related factors influenced their participation in physical activity. Copyright © 2014 John Wiley & Sons, Ltd.

  16. Regulated competition in health care: Switching and barriers to switching in the Dutch health insurance system

    Directory of Open Access Journals (Sweden)

    Rijken Mieke

    2011-05-01

    Full Text Available Abstract Background In 2006, a number of changes in the Dutch health insurance system came into effect. In this new system mobility of insured is important. The idea is that insured switch insurers because they are not satisfied with quality of care and the premium of their insurance. As a result, insurers will in theory strive for a better balance between price and quality. The Dutch changes have caught the attention, internationally, of both policy makers and researchers. In our study we examined switching behaviour over three years (2007-2009. We tested if there are differences in the numbers of switchers between groups defined by socio-demographic and health characteristics and between the general population and people with chronic illness or disability. We also looked at reasons for (not-switching and at perceived barriers to switching. Methods Switching behaviour and reasons for (not-switching were measured over three years (2007-2009 by sending postal questionnaires to members of the Dutch Health Care Consumer Panel and of the National Panel of people with Chronic illness or Disability. Data were available for each year and for each panel for at least 1896 respondents - a response of between 71% and 88%. Results The percentages of switchers are low; 6% in 2007, 4% in 2008 and 3% in 2009. Younger and higher educated people switch more often than older and lower educated people and women switch more often than men. There is no difference in the percentage of switchers between the general population and people with chronic illness or disability. People with a bad self-perceived health, and chronically ill and disabled, perceive more barriers to switching than others. Conclusion The percentages of switchers are comparable to the old system. Switching is not based on quality of care and thus it can be questioned whether it will lead to a better balance between price and quality. Although there is no difference in the frequency of switching

  17. Perceived barriers to leisure-time physical activity during pregnancy: A literature review of quantitative and qualitative evidence.

    Science.gov (United States)

    Coll, Carolina V N; Domingues, Marlos R; Gonçalves, Helen; Bertoldi, Andréa D

    2017-01-01

    Identify perceived barriers to leisure-time physical activity during pregnancy to inform future interventions aimed at improving physical activity levels in pregnancy. PubMed/Medline and Web of Science databases were systematically searched using a reference period between 1986 and January/2016. A comprehensive search strategy was developed combining the following keywords: (barriers OR constraints OR perceptions OR attitudes) AND (physical activity OR exercise OR motor activity) AND (pregnancy OR pregnant women OR antenatal OR prenatal). Thematic synthesis was conducted to analyze the data. A socioecological model was used to categorize the reported barriers. Twelve quantitative studies and 14 qualitative studies were included. Barriers belonging to the intrapersonal level of the socioecological model were the most reported in the studies and were categorized in five themes as follows: (1) Pregnancy-related symptoms and limitations; (2) Time constraints; (3) Perceptions of already being active, (4) Lack of motivation and (5) Mother-child safety concerns. At the interpersonal level, barriers were coded into two descriptive themes: (1) Lack of advice and information and (2) Lack of social support. Two other themes were used to summarize Environmental, Organizational and Policy barriers: (1) Adverse weather and (2) Lack of resources. A range of relevant barriers to leisure-time physical-activity engagement during pregnancy were identified in this literature review. Pregnancy-related symptoms and limitations barriers were the most reported in studies, regardless of study design. Mother-child safety concerns, lack of advice/information and lack of social support were also important emphasized pregnancy-related barriers to be targeted in future interventions. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  18. Barriers, facilitators and attitudes influencing health promotion activities in general practice: an explorative pilot study

    Directory of Open Access Journals (Sweden)

    Geense Wytske W

    2013-02-01

    Full Text Available Abstract Background The number of chronically ill patients increases every year. This is partly due to an unhealthy lifestyle. However, the frequency and quality of (evidence-based health promotion activities conducted by Dutch general practitioners (GPs and practice nurses (PNs are limited. The aim of this pilot study was to explore which lifestyle interventions Dutch GPs and PNs carry out in primary care, which barriers and facilitators can be identified and what main topics are with respect to attitudes towards health promoting activities. These topic areas will be identified for a future, larger scale study. Method This qualitative study consisted of 25 semi-structured interviews with sixteen GPs and nine PNs. ATLAS.ti was used to analyse the transcripts of the interviews. Results All GPs and PNs said they discuss lifestyle with their patients. Next to this, GPs and PNs counsel patients, and/or refer them to other disciplines. Only few said they refer patients to specific lifestyle programs or interventions in their own practice or in the neighbourhood. Several barriers and facilitators were identified. The main topics as barriers are: a lack of patients’ motivation to make lifestyle changes, insufficient reimbursement, a lack of proven effectiveness of interventions and a lack of overview of health promoting programs in their neighbourhood. The most cited facilitators are availability of a PN, collaboration with other disciplines and availability of interventions in their own practice. With respect to attitudes, six different types of GPs were identified reflecting the main topics that relate to attitudes, varying from ‘ignorer’ to ‘nurturer’. The topics relating to PNs attitudes towards health promotion activities, were almost unanimously positive. Conclusion GPs and PNs all say they discuss lifestyle issues with their patients, but the health promotion activities that are organized in their practice vary. Main topics that hinder

  19. Activated barrier crossing dynamics in the non-radiative decay of NADH and NADPH

    Energy Technology Data Exchange (ETDEWEB)

    Blacker, Thomas S., E-mail: t.blacker@ucl.ac.uk [Centre for Mathematics and Physics in the Life Sciences and Experimental Biology (CoMPLEX), University College London, London WC1E 6BT (United Kingdom); Department of Physics and Astronomy, University College London, London WC1E 6BT (United Kingdom); Research Department of Cell and Developmental Biology, University College London, London WC1E 6BT (United Kingdom); Marsh, Richard J., E-mail: richard.marsh@ucl.ac.uk [Department of Physics and Astronomy, University College London, London WC1E 6BT (United Kingdom); Duchen, Michael R., E-mail: m.duchen@ucl.ac.uk [Research Department of Cell and Developmental Biology, University College London, London WC1E 6BT (United Kingdom); Bain, Angus J., E-mail: a.bain@ucl.ac.uk [Centre for Mathematics and Physics in the Life Sciences and Experimental Biology (CoMPLEX), University College London, London WC1E 6BT (United Kingdom); Department of Physics and Astronomy, University College London, London WC1E 6BT (United Kingdom)

    2013-08-30

    Highlights: ► NADH and NADPH have a high rate of non-radiative excited state decay. ► Conformational relaxation is shown to be a significant non-radiative pathway. ► The Kramers equation describes the barrier crossing dynamics of the relaxation. ► Conformational restriction upon enzyme binding will alter NAD(P)H lifetimes. - Abstract: In live tissue, alterations in metabolism induce changes in the fluorescence decay of the biological coenzyme NAD(P)H, the mechanism of which is not well understood. In this work, the fluorescence and anisotropy decay dynamics of NADH and NADPH were investigated as a function of viscosity in a range of water–glycerol solutions. The viscosity dependence of the non-radiative decay is well described by Kramers and Kramers–Hubbard models of activated barrier crossing over a wide viscosity range. Our combined lifetime and anisotropy analysis indicates common mechanisms of non-radiative relaxation in the two emitting states (conformations) of both molecules. The low frequencies associated with barrier crossing suggest that non-radiative decay is mediated by small scale motion (e.g. puckering) of the nicotinamide ring. Variations in the fluorescence lifetimes of NADH and NADPH when bound to different enzymes may therefore be attributed to differing levels of conformational restriction upon binding.

  20. Barriers, motivators, and facilitators of physical activity in dementia patients: A systematic review.

    Science.gov (United States)

    van Alphen, Helena J M; Hortobágyi, Tibor; van Heuvelen, Marieke J G

    2016-01-01

    Physical activity (PA) has the potential to slow the progression of dementia patients' cognitive and physical decline. A better understanding of the factors that facilitate or hamper dementia patients' PA participation will increase the success rate of implementing PA in dementia patients' daily care. We systematically screened the barriers, motivators, and facilitators of PA participation in dementia patients, complementing previous analyses of quantitative correlates of PA in community-dwelling dementia patients. Systematic searches yielded 78 potential studies of which seven met the eligibility criteria including 39 dementia patients and 36 caregivers (33 spouses and three daughters). We identified 35 barriers, 26 motivators, and 21 facilitators related to PA. We reduced these factors to six themes within the social-ecological model. Prominent barriers to PA were physical and mental limitations and difficulties with guidance and organization of PA by caregivers. Motivators included the motivation to maintain physical and mental health and participate in preferred PA options. Facilitators included strategies to avoid health problems, providing support and guidance for PA, and access to convenient and personalized PA options. The emerging picture suggests that dementia patients' PA participation will increase if service providers become familiar with the health benefits of PA, the characteristics of PA programs, methods of delivery, and the concepts of how such programs can be personalized to and synchronized with patients' individual needs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. ECONOMIC ACTIVITY REGULATION AND COMPETITION ASSESSMENT

    Directory of Open Access Journals (Sweden)

    Berinde Mihai

    2010-07-01

    Full Text Available In a broad sense, the term „competition” defines the relations between economic operators acting on the same market seeking attainment of certain interests in economic freedom conditions. The need for regulations in the area of competition stems from the nature of free, open market economy which is founded on the existence of fair competition between economic agents, competition which must be observed, maintained and protected by the law. Public authorities who issue various regulations should be cautious about how far this role is played in the economy and they way adopted regulations affect competition in the market. Hence, the need for prior assessment relating to the potential effect of a regulation on competition. It was proven in practice that some regulations may lead to measures that may affect competition directly or indirectly by: limiting the number or range of suppliers; limiting supplier capability to compete and reducing interests of suppliers to compete vigorously.

  2. Gi proteins regulate adenylyl cyclase activity independent of receptor activation.

    Science.gov (United States)

    Melsom, Caroline Bull; Ørstavik, Øivind; Osnes, Jan-Bjørn; Skomedal, Tor; Levy, Finn Olav; Krobert, Kurt Allen

    2014-01-01

    Despite the view that only β2- as opposed to β1-adrenoceptors (βARs) couple to G(i), some data indicate that the β1AR-evoked inotropic response is also influenced by the inhibition of Gi. Therefore, we wanted to determine if Gi exerts tonic receptor-independent inhibition upon basal adenylyl cyclase (AC) activity in cardiomyocytes. We used the Gs-selective (R,R)- and the Gs- and G(i)-activating (R,S)-fenoterol to selectively activate β2ARs (β1AR blockade present) in combination with Gi inactivation with pertussis toxin (PTX). We also determined the effect of PTX upon basal and forskolin-mediated responses. Contractility was measured ex vivo in left ventricular strips and cAMP accumulation was measured in isolated ventricular cardiomyocytes from adult Wistar rats. PTX amplified both the (R,R)- and (R,S)-fenoterol-evoked maximal inotropic response and concentration-dependent increases in cAMP accumulation. The EC50 values of fenoterol matched published binding affinities. The PTX enhancement of the Gs-selective (R,R)-fenoterol-mediated responses suggests that Gi regulates AC activity independent of receptor coupling to Gi protein. Consistent with this hypothesis, forskolin-evoked cAMP accumulation was increased and inotropic responses to forskolin were potentiated by PTX treatment. In non-PTX-treated tissue, phosphodiesterase (PDE) 3 and 4 inhibition or removal of either constitutive muscarinic receptor activation of Gi with atropine or removal of constitutive adenosine receptor activation with CGS 15943 had no effect upon contractility. However, in PTX-treated tissue, PDE3 and 4 inhibition alone increased basal levels of cAMP and accordingly evoked a large inotropic response. Together, these data indicate that Gi exerts intrinsic receptor-independent inhibitory activity upon AC. We propose that PTX treatment shifts the balance of intrinsic G(i) and Gs activity upon AC towards Gs, enhancing the effect of all cAMP-mediated inotropic agents.

  3. Barriers and motivators for physical activity among overweight and obese people with type 2 diabetes

    DEFF Research Database (Denmark)

    Lidegaard, Lærke; Schwennesen, Nete; Willaing, Ingrid

    2016-01-01

    and analysed thematically. Results We identified four main themes: 1) the body as a barrier to physical activity because of functional limitations; 2) logistical challenges, including lack of time and awareness of where to exercise in the local area; 3) being physically active with others, providing a sense...... with Type 2 diabetes aged 39–71 years. The facilitators used open-ended questions and probes such as images, statements and quotations about physical activity to foster active participation and interaction among participants. Focus groups were recorded on video and the discussions were transcribed...... is needed to investigate the effect of combining individually tailored exercise plans with the establishment of customized and locally based exercise communities that offer enjoyment and support. Additionally, it would be relevant to explore experiences of using self-tracking technologies to review short...

  4. Levels of physical activity, barriers, and stage of change in an urban population from a municipality in Colombia

    OpenAIRE

    Mónica María Arenas; Elkin Fernando Arango; Fredy Alonso Patiño; Mario Andrés Quintero

    2011-01-01

    Objective: To assess the levels of physical activity, barriers, and stage of change in an urban population 25 to 50 yearsof age from the Municipality of Santa Rosa de Osos, department of Antioquia.Materials and methods: A prevalence study was conducted, with a two-stage random sampling among 357 individualsnot suffering from any known cardiovascular disease. A pre-designed survey was conducted to assess the levels of physicalactivity, the stage of change, and physical activity barriers.Result...

  5. Na+/H+ Exchanger 9 Regulates Iron Mobilization at the Blood Brain Barrier in Response to Iron Starvation.

    Science.gov (United States)

    Beydoun, Rami; Hamood, Mohamed A; Gomez Zubeita, Daniela M; Kondapalli, Kalyan C

    2017-01-27

    Iron is essential for brain function, with loss of iron homeostasis in the brain linked to neurological diseases ranging from rare syndromes to more common disorders, such as Parkinson's and Alzheimer's diseases. Iron entry into the brain is regulated by the blood-brain barrier (BBB). Molecular mechanisms regulating this transport are poorly understood. Using an in vitro model of the BBB, we identify NHE9, an endosomal cation/proton exchanger, as a novel regulator of this system. Human brain microvascular endothelial cells (hBMVECs) that constitute the BBB receive brain-iron status information via paracrine signals from ensheathing astrocytes. In hBMVECs, we show that NHE9 expression is upregulated very early in a physiological response invoked by paracrine signals from iron-starved astrocytes. Ectopic expression of NHE9 in hBMVECs without external cues induced upregulation of the transferrin receptor (TfR) and downregulation of ferritin, leading to an increase in iron uptake. Mechanistically, we demonstrate that NHE9 localizes to recycling endosomes in hBMVECs where it raises the endosomal pH. The ensuing alkalization of the endosomal lumen increased translocation of TfRs to the hBMVEC membrane. TfRs on the membrane were previously shown to facilitate both recycling-dependent and independent iron uptake. We propose NHE9 regulates TfR-dependent, recycling-independent iron uptake in hBMVECs by fine-tuning the endosomal pH in response to paracrine signals and is therefore an important regulator in iron mobilization pathway at the BBB.

  6. Activation and Regulation of Cellular Eicosanoid Biosynthesis

    Directory of Open Access Journals (Sweden)

    Thomas G. Brock

    2007-01-01

    Full Text Available There is a growing appreciation for the wide variety of physiological responses that are regulated by lipid messengers. One particular group of lipid messengers, the eicosanoids, plays a central role in regulating immune and inflammatory responses in a receptor-mediated fashion. These mediators are related in that they are all derived from one polyunsaturated fatty acid, arachidonic acid. However, the various eicosanoids are synthesized by a wide variety of cell types by distinct enzymatic pathways, and have diverse roles in immunity and inflammation. In this review, the major pathways involved in the synthesis of eicosanoids, as well as key points of regulation, are presented.

  7. Barriers and Facilitators to Being Physically Active on a Rural U.S. Northern Plains American Indian Reservation

    Directory of Open Access Journals (Sweden)

    Lisa Jahns

    2014-11-01

    Full Text Available The objective of the present study was to identify barriers to and facilitators of physical activity among American Indian adults living on a rural, U.S. Northern Plains reservation using the nominal group technique (NGT. NGT is a method of data generation and interpretation that combines aspects of qualitative (free generation of responses and quantitative (systematic ranking of responses methodologies. Adults participated in one of two NGT sessions asking about either barriers to (n = 6, or facilitators of (n = 5, being physically active. Participants nominated and ranked 21 barriers and 18 facilitators. Barriers indicated lack of knowledge of how to fit physical activity into a daily schedule, work, caring for family members, and prioritizing sedentary pursuits. Other responses included environmental barriers such as lack of access and transportation to a gym, unsafe walking conditions, and inclement weather. Facilitators to following recommendations included knowledge of health benefits of physical activity and the perception of physical activity as enjoyable, including feeling good when working out. Environmental facilitators included being outdoors walking and biking as well as parks and exercise facilities. Responses provided direction for locally designed community-based programs to promote facilitators and decrease barriers to individual’s engagement in physical activity.

  8. Dissociation activation barrier and heat of chemisorption: A morse-type analytical approach

    Science.gov (United States)

    Shustorovich, Evgeny M.

    1985-02-01

    The activation barrier Δ E∗ABfor dissociation AB → A + B on transition-metal surfaces is analyzed within an additive Morse-type approach based on the bond-order conservation. It is shown that Δ E∗AB = DAB-( QA + QB + QAQB/( QA + QB) where DAB is the gas-phase dissociation energy and Q A(Q B) is the heat of atomic chemisorption. Estimates of Δ E∗ for H 2, N 2, O 2, and NO are shown to be in reasonable agreement with experiment. The two-dimensional potential diagram of the metal-AB interactions is defined analytically and discussed in some detail.

  9. Communications: Comparison of activation barriers for the Johari-Goldstein and alpha relaxations and its implications.

    Science.gov (United States)

    Goldstein, Martin

    2010-01-28

    The range of activation barrier heights for the Johari-Goldstein (JG) relaxation in glasses is shown to overlap the range for the main (alpha) relaxation, but to be on the average somewhat lower. This suggests the JG relaxation, like the alpha, involve transitions between megabasins in the energy landscape, and that the original conjecture by Johari and this author that the JG relaxation is an intrabasin one cannot be correct. A further possibility is that there is a closer connection of the JG relaxation to the phenomenon of dynamic heterogeneity in supercooled liquids than so far assumed.

  10. Theory of gelation, vitrification, and activated barrier hopping in mixtures of hard and sticky spheres.

    Science.gov (United States)

    Viehman, Douglas C; Schweizer, Kenneth S

    2008-02-28

    Naive mode coupling theory (NMCT) and the nonlinear stochastic Langevin equation theory of activated dynamics have been generalized to mixtures of spherical particles. Two types of ideal nonergodicity transitions are predicted corresponding to localization of both, or only one, species. The NMCT transition signals a dynamical crossover to activated barrier hopping dynamics. For binary mixtures of equal diameter hard and attractive spheres, a mixture composition sensitive "glass-melting" type of phenomenon is predicted at high total packing fractions and weak attractions. As the total packing fraction decreases, a transition to partial localization occurs corresponding to the coexistence of a tightly localized sticky species in a gel-like state with a fluid of hard spheres. Complex behavior of the localization lengths and shear moduli exist because of the competition between excluded volume caging forces and attraction-induced physical bond formation between sticky particles. Beyond the NMCT transition, a two-dimensional nonequilibrium free energy surface emerges, which quantifies cooperative activated motions. The barrier locations and heights are sensitive to the relative amplitude of the cooperative displacements of the different species.

  11. Bone morphogenetic protein receptor II regulates pulmonary artery endothelial cell barrier function.

    Science.gov (United States)

    Burton, Victoria J; Ciuclan, Loredana I; Holmes, Alan M; Rodman, David M; Walker, Christoph; Budd, David C

    2011-01-06

    Mutations in bone morphogenetic protein receptor II (BMPR-II) underlie most heritable cases of pulmonary arterial hypertension (PAH). However, less than half the individuals who harbor mutations develop the disease. Interestingly, heterozygous null BMPR-II mice fail to develop PAH unless an additional inflammatory insult is applied, suggesting that BMPR-II plays a fundamental role in dampening inflammatory signals in the pulmonary vasculature. Using static- and flow-based in vitro systems, we demonstrate that BMPR-II maintains the barrier function of the pulmonary artery endothelial monolayer suppressing leukocyte transmigration. Similar findings were also observed in vivo using a murine model with loss of endothelial BMPR-II expression. In vitro, the enhanced transmigration of leukocytes after tumor necrosis factor α or transforming growth factor β1 stimulation was CXCR2 dependent. Our data define how loss of BMPR-II in the endothelial layer of the pulmonary vasculature could lead to a heightened susceptibility to inflammation by promoting the extravasation of leukocytes into the pulmonary artery wall. We speculate that this may be a key mechanism involved in the initiation of the disease in heritable PAH that results from defects in BMPR-II expression.

  12. Survey of the Relationship Between Activity Energy Expenditure Metabolic Equivalents and Barrier Factors of Physical Activity in the Elderly in Kashan

    Science.gov (United States)

    Sadrollahi, Ali; Khalili, Zahra; Pour Nazari, Robab; Mohammadi, Majid; Ahmadi Khatir, Maryam; Mossadegh, Najima

    2016-01-01

    Background Physical activity in the elderly is influenced by aspects of aging that cause personal, mental, environmental, and social changes. Increases in factors that are barriers to activity cause physical energy expenditure to decrease. Objectives The aim of the present study was to survey the relationship between energy expenditure in metabolic equivalent units (MET) and factors that are barriers to physical activity in elderly people in Kashan, Iran Methods This is a descriptive analysis done in 2014. The study population was 400 people above 60 years old in medical facilities in Kashan. Multistage sampling was used in 10 clinics in 5 areas of Kashan. The sample size was varied according to gender and elderly population. Contributors were given questionnaires concerning energy expenditure levels in physical activity and factors that are barriers to being active. Results The average age among the study population was 67.6 ± 6.8 years median, and the interquartile range (IQR) of barriers to physical activity among Kashan’s elderly was (8.75) ± 33. Average energy expenditure was 326.21 ± 364.84 based on metabolic equivalent units (MET). In fact, 340 persons (85%) were practically without any active energy expenditure. The most common barrier was the lack of an appropriate place for doing physical activity; 298 (74%) of the participants cited this barrier. The results show the Spearman rank-order correlation is significant (P = 0.038, r = 0.104) between barriers to physical activity and activity energy expenditure in Kashan’s elderly. Conclusions Decreasing barriers to physical activity among the elderly causes physical activities to increase; therefore, energy expenditure is increased. Decreasing social and environmental problems for the elderly is effective in increasing physical activity and energy expenditure. PMID:28191341

  13. Monitoring seasonal bat activity on a coastal barrier island in Maryland, USA.

    Science.gov (United States)

    Johnson, Joshua B; Gates, J Edward; Zegre, Nicolas P

    2011-02-01

    Research on effects of wind turbines on bats has increased dramatically in recent years because of significant numbers of bats killed by rotating wind turbine blades. Whereas most research has focused on the Midwest and inland portions of eastern North America, bat activity and migration on the Atlantic Coast has largely been unexamined. We used three long-term acoustic monitoring stations to determine seasonal bat activity patterns on the Assateague Island National Seashore, a barrier island off the coast of Maryland, from 2005 to 2006. We recorded five species, including eastern red bats (Lasiurus borealis), big brown bats (Eptesicus fuscus), hoary bats (Lasiurus cinereus), tri-colored bats (Perimyotis subflavus), and silver-haired bats (Lasionycteris noctivagans). Seasonal bat activity (number of bat passes recorded) followed a cosine function and gradually increased beginning in April, peaked in August, and declined gradually until cessation in December. Based on autoregressive models, inter-night bat activity was autocorrelated for lags of seven nights or fewer but varied among acoustic monitoring stations. Higher nightly temperatures and lower wind speeds positively affected bat activity. When autoregressive model predictions were fitted to the observed nightly bat pass totals, model residuals>2 standard deviations from the mean existed only during migration periods, indicating that periodic increases in bat activity could not be accounted for by seasonal trends and weather variables alone. Rather, the additional bat passes were attributable to migrating bats. We conclude that bats, specifically eastern red, hoary, and silver-haired bats, use this barrier island during migration and that this phenomenon may have implications for the development of near and offshore wind energy.

  14. Alteration of intestinal barrier function during activity-based anorexia in mice.

    Science.gov (United States)

    Jésus, Pierre; Ouelaa, Wassila; François, Marie; Riachy, Lina; Guérin, Charlène; Aziz, Moutaz; Do Rego, Jean-Claude; Déchelotte, Pierre; Fetissov, Sergueï O; Coëffier, Moïse

    2014-12-01

    Anorexia nervosa is a severe eating disorder often leading to malnutrition and cachexia, but its pathophysiology is still poorly defined. Chronic food restriction during anorexia nervosa may induce gut barrier dysfunction, which may contribute to disease development and its complications. Here we have characterized intestinal barrier function in mice with activity-based anorexia (ABA), an animal model of anorexia nervosa. Male C57Bl/6 ABA or limited food access (LFA) mice were placed respectively in cages with or without activity wheel. After 5 days of acclimatization, both ABA and LFA mice had progressively limited access to food from 6 h/d at day 6 to 3 h/d at day 9 and until the end of experiment at day 17. A group of pair-fed mice (PF) was also compared to ABA. On day 17, food intake was lower in ABA than LFA mice (2.0 ± 0.18 g vs. 3.0 ± 0.14 g, p anorexia nervosa. The role of these alterations in the pathophysiology of anorexia nervosa should be further evaluated. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  15. [Current Status of Home Visit Programs: Activities and Barriers of Home Care Nursing Services].

    Science.gov (United States)

    Oh, Eui Geum; Lee, Hyun Joo; Kim, Yukyung; Sung, Ji Hyun; Park, Young Su; Yoo, Jae Yong; Woo, Soohee

    2015-10-01

    The purpose of this study was to examine the current status of home care nursing services provided by community health nurses and to identify barriers to the services. A cross-sectional survey was conducted with three types of community health care nurses. Participants were 257 nurses, 46 of whom were hospital based home care nurses, 176 were community based visiting nurses, and 35 were long term care insurance based visiting nurses. A structured questionnaire on 7 domains of home care nursing services with a 4-point Likert scale was used to measure activities and barriers to care. Data were analyzed using SPSS WIN 21.0 program. Hospital based home care nurses showed a high level of service performance activity in the domain of clinical laboratory tests, medications and injections, therapeutic nursing, and education. Community based visiting nurses had a high level of service performance in the reference domain. Long term care insurance based visiting nurses showed a high level of performance in the service domains of fundamental nursing and counseling. The results show that although health care service provided by the three types of community health nurse overlapped, the focus of the service is differentiated. Therefore, these results suggest that existing home care services will need to be utilized efficiently in the development of a new nursing care service for patients living in the community after hospital discharge.

  16. Understanding Barriers and Facilitators to Healthy Eating and Active Living in Rural Communities

    Directory of Open Access Journals (Sweden)

    Rebecca Seguin

    2014-01-01

    Full Text Available Objective. Studies demonstrate that people’s food and physical activity (PA environments influence behavior, yet research examining this in rural communities is limited. Methods. Focus groups of 8–15 women were conducted in rural communities in seven US states. Questions were designed to identify factors within residents’ food and PA environments they felt helped or hindered them from eating healthfully and being physically active. Results. Participants were aged 30–84 years; mean (SD = 61 (14 (N=95. On average, communities had fewer than 5,000 residents. Limited time, social norms, and distances from or lack of exercise facilities were common PA barriers. Facilitators for PA included social support, dog walking, and availability of affordable facilities. Healthy eating barriers included the perception that healthy foods were too expensive; calorically dense large portion sizes served at family meals; and frequency of eating foods away from home, which were perceived as generally unhealthy. Healthy eating supports included culture/value around local food gathering (e.g., hunting and gardening and preservation (e.g., canning and smoking. Friends and family were frequently identified as key influencers of eating and PA behavior. Conclusions. Targeting both social and built environment factors, particularly those unique to rural locales, may enhance support for healthy eating and PA behavior change interventions.

  17. Understanding barriers and facilitators to healthy eating and physical activity from patients either before and after knee arthroplasty.

    Science.gov (United States)

    Pellegrini, Christine A; Ledford, Gwendolyn; Chang, Rowland W; Cameron, Kenzie A

    2017-05-05

    We sought to identify patient-reported barriers and facilitators to healthy eating and physical activity among patients before or after knee arthroplasty. Twenty patients with knee osteoarthritis aged 40-79 years who had knee arthroplasty surgery scheduled or completed within 3 months were interviewed. Interview topics included perceived barriers and facilitators to healthy eating and activity before or after surgery. Interviews were coded and analyzed using constant comparative analysis. Interviews were completed with 11 pre-operative (67.1 ± 7.6 years, 45.5% female, BMI 31.2 ± 6.3) and nine post-operative patients (61.7 ± 11.7 years, 44.4% female, BMI 30.2 ± 4.7 kg/m(2)). The most commonly identified personal barriers to healthy eating identified were desire for high-fat/high-calorie foods, managing overconsumption and mood. Factors related to planning, portion control and motivation to improve health were identified as healthy eating facilitators. Identified personal barriers for activity included pain, physical limitations and lack of motivation, whereas facilitators included having motivation to improve knee symptoms/outcomes, personal commitment to activity and monitoring activity levels. Identifying specific eating and activity barriers and facilitators, such as mood and motivation to improve outcomes, provides critical insight from the patient perspective, which will aid in developing weight management programs during rehabilitation for knee arthroplasty patients. Implications for rehabilitation This study provides insight into the identified barriers and facilitators to healthy eating and physical activity in knee arthroplasty patients, both before and after surgery. Intrapersonal barriers that may hinder engagement in physical activity and rehabilitation include pain, physical limitations and lack of motivation; factors that may help to improve activity and the rehabilitation process include being motivated to improve knee outcomes

  18. Self-efficacy as a mediator of the relationship between perceived union barriers and women's participation in union activities.

    Science.gov (United States)

    Bulger, C A; Mellor, S

    1997-12-01

    This study investigated the influence of union self-efficacy (expectations of success in pursuit of union activities) as a mediator of the relationship between perceptions of barriers to union participation and women's participation in union activities (N = 89). Perceived barriers were defined in 4 domains (community, family, union, work), and self-efficacy was operationalized based on C. Lee and P. Bobko's (1994) analysis of self-efficacy measures (self-efficacy magnitude, self-efficacy strength). Union self-efficacy was found to mediate the relationship between the magnitude of perceived union barriers and the magnitude of union participation, although mediation was limited to women with weak union self-efficacy. Implications for designing training and intervention programs to enhance women's participation in the face of perceived barriers are discussed.

  19. 50 CFR 404.7 - Regulated activities.

    Science.gov (United States)

    2010-10-01

    ... vessel engine cooling water, weather deck runoff, and vessel engine exhaust; (f) Discharging or... effluent, cooling water, and engine exhaust; (g) Touching coral, living or dead; (h) Possessing fishing... Wildlife and Fisheries JOINT REGULATIONS (UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF...

  20. Pro-inflammatory cytokine regulation of P-glycoprotein in the developing blood-brain barrier.

    Directory of Open Access Journals (Sweden)

    Majid Iqbal

    Full Text Available Placental P-glycoprotein (P-gp acts to protect the developing fetus from exogenous compounds. This protection declines with advancing gestation leaving the fetus and fetal brain vulnerable to these compounds and potential teratogens in maternal circulation. This vulnerability may be more pronounced in pregnancies complicated by infection, which is common during pregnancy. Pro-inflammatory cytokines (released during infection have been shown to be potent inhibitors of P-gp, but nothing is known regarding their effects at the developing blood-brain barrier (BBB. We hypothesized that P-gp function and expression in endothelial cells of the developing BBB will be inhibited by pro-inflammatory cytokines. We have derived brain endothelial cell (BEC cultures from various stages of development of the guinea pig: gestational day (GD 50, 65 (term ~68 days and postnatal day (PND 14. Once these cultures reached confluence, BECs were treated with various doses (10(0-10(4 pg/mL of pro-inflammatory cytokines: interleukin-1β (IL-1β, interleukin-6 (IL-6 or tumor necrosis factor- α (TNF-α. P-gp function or abcb1 mRNA (encodes P-gp expression was assessed following treatment. Incubation of GD50 BECs with IL-1β, IL-6 or TNF-α resulted in no change in P-gp function. GD65 BECs displayed a dose-dependent decrease in function with all cytokines tested; maximal effects at 42%, 65% and 34% with IL-1β, IL-6 and TNF-α treatment, respectively (P<0.01. Inhibition of P-gp function by IL-1β, IL-6 and TNF-α was even greater in PND14 BECs; maximal effects at 36% (P<0.01, 84% (P<0.05 and 55% (P<0.01, respectively. Cytokine-induced reductions in P-gp function were associated with decreased abcb1 mRNA expression. These data suggest that BBB P-gp function is increasingly responsive to the inhibitory effects of pro-inflammatory cytokines, with increasing developmental age. Thus, women who experience infection and take prescription medication during pregnancy may expose the

  1. Counselling low-back-pain patients in secondary healthcare: a randomised trial addressing experienced workplace barriers and physical activity

    DEFF Research Database (Denmark)

    Jensen, Lone Donbæk; Maribo, Thomas; Schiøttz-Christensen, Berit;

    2012-01-01

    OBJECTIVE: To assess if counselling by an occupational physician (OP) addressing experienced workplace barriers and physical activity integrated as a part of low-back pain (LBP) outpatient treatment influences pain, function and sick leave. METHODS: Randomised controlled trial in the secondary...... addressing both workplace barriers and leisure-time physical activity. A workplace visit was performed if required. Pain, function and duration of sick leave due to LBP were primary outcomes. RESULTS: A reduction in bodily pain and improvement in physical function both measured by the 36-item short...... physical activity and maximum oxygen uptake, supported compliance and adherence to the part of the intervention focusing on enhanced physical activity. CONCLUSION: Two short counselling sessions by an OP combining advice on meeting workplace barriers and enhancing physical activity had a substantial effect...

  2. Expression profile of cornified envelope structural proteins and keratinocyte differentiation-regulating proteins during skin barrier repair.

    NARCIS (Netherlands)

    Koning, H.D. de; Bogaard, E.H.J. van den; Bergboer, J.G.M.; Kamsteeg, M.; Vlijmen-Willems, I.M.J.J. van; Hitomi, K.; Henry, J.; Simon, M.; Takashita, N.; Ishida-Yamamoto, A.; Schalkwijk, J.; Zeeuwen, P.L.J.M.

    2012-01-01

    BACKGROUND: Recent studies have emphasized the importance of heritable and acquired skin barrier abnormalities in common inflammatory diseases such as psoriasis and atopic dermatitis (AD). To date, no comprehensive studies on the effect of experimental barrier disruption on cornified envelope

  3. Outer Membrane Vesicles and Soluble Factors Released by Probiotic Escherichia coli Nissle 1917 and Commensal ECOR63 Enhance Barrier Function by Regulating Expression of Tight Junction Proteins in Intestinal Epithelial Cells

    Science.gov (United States)

    Alvarez, Carina-Shianya; Badia, Josefa; Bosch, Manel; Giménez, Rosa; Baldomà, Laura

    2016-01-01

    The gastrointestinal epithelial layer forms a physical and biochemical barrier that maintains the segregation between host and intestinal microbiota. The integrity of this barrier is critical in maintaining homeostasis in the body and its dysfunction is linked to a variety of illnesses, especially inflammatory bowel disease. Gut microbes, and particularly probiotic bacteria, modulate the barrier integrity by reducing gut permeability and reinforcing tight junctions. Probiotic Escherichia coli Nissle 1917 (EcN) is a good colonizer of the human gut with proven therapeutic efficacy in the remission of ulcerative colitis in humans. EcN positively modulates the intestinal epithelial barrier through upregulation and redistribution of the tight junction proteins ZO-1, ZO-2 and claudin-14. Upregulation of claudin-14 has been attributed to the secreted protein TcpC. Whether regulation of ZO-1 and ZO-2 is mediated by EcN secreted factors remains unknown. The aim of this study was to explore whether outer membrane vesicles (OMVs) released by EcN strengthen the epithelial barrier. This study includes other E. coli strains of human intestinal origin that contain the tcpC gene, such as ECOR63. Cell-free supernatants collected from the wild-type strains and from the derived tcpC mutants were fractionated into isolated OMVs and soluble secreted factors. The impact of these extracellular fractions on the epithelial barrier was evaluated by measuring transepithelial resistance and expression of several tight junction proteins in T-84 and Caco-2 polarized monolayers. Our results show that the strengthening activity of EcN and ECOR63 does not exclusively depend on TcpC. Both OMVs and soluble factors secreted by these strains promote upregulation of ZO-1 and claudin-14, and down-regulation of claudin-2. The OMVs-mediated effects are TcpC-independent. Soluble secreted TcpC contributes to the upregulation of ZO-1 and claudin-14, but this protein has no effect on the transcriptional

  4. [Construction and validation of a short scale of perception of barriers for the physical activity in adolescents].

    Science.gov (United States)

    Cabanas-Sánchez, Verónica; Tejero-González, Carlos M; Veiga, Oscar L

    2012-01-01

    One of the main problems of health in the first world is the increase of physical inactivity. In this respect, adolescence has been identified as a critic period with high decline of physical activity. Therefore, a relevant line of research is the understanding of this social phenomenon. The aim of this study was to design a scale to assess perceived barriers to physical activity on adolescents. A convenience sample of 160 Spanish adolescents (84 girls), between 12 and 18 years old, was recruited for this study. Firstly, there were designed 40 items whose pertinence was evaluated through content validation by experts. Later, the participants were divided in two randomized groups, and Exploratory Factor Analysis and Confirmatory Factor Analysis were performed to define a short scale of 12 items. Cronbach Alfa Coefficent was used to evaluate internal consistence of the instrument. The scale reports four dimensions: incompatibility barriers (2 items), self-concept barriers (4 items), amotivation barriers (4 items) and social barriers (2 items). The scale showed enough construct validity (χ2=60.78; d.f.=48; p=0.100; GFI=0.88; CFI=0.94; RMSEA=0.58) and high internal reliability (α=0.80). Moreover, the scale was able to explain 67% of the data variance. The Short Scale of Perceived Barriers to Physical Activity in Adolescents is a valid and reliable instrument.

  5. Trypanosome infection establishment in the tsetse fly gut is influenced by microbiome-regulated host immune barriers.

    Directory of Open Access Journals (Sweden)

    Brian L Weiss

    Full Text Available Tsetse flies (Glossina spp. vector pathogenic African trypanosomes, which cause sleeping sickness in humans and nagana in domesticated animals. Additionally, tsetse harbors 3 maternally transmitted endosymbiotic bacteria that modulate their host's physiology. Tsetse is highly resistant to infection with trypanosomes, and this phenotype depends on multiple physiological factors at the time of challenge. These factors include host age, density of maternally-derived trypanolytic effector molecules present in the gut, and symbiont status during development. In this study, we investigated the molecular mechanisms that result in tsetse's resistance to trypanosomes. We found that following parasite challenge, young susceptible tsetse present a highly attenuated immune response. In contrast, mature refractory flies express higher levels of genes associated with humoral (attacin and pgrp-lb and epithelial (inducible nitric oxide synthase and dual oxidase immunity. Additionally, we discovered that tsetse must harbor its endogenous microbiome during intrauterine larval development in order to present a parasite refractory phenotype during adulthood. Interestingly, mature aposymbiotic flies (Gmm(Apo present a strong immune response earlier in the infection process than do WT flies that harbor symbiotic bacteria throughout their entire lifecycle. However, this early response fails to confer significant resistance to trypanosomes. Gmm(Apo adults present a structurally compromised peritrophic matrix (PM, which lines the fly midgut and serves as a physical barrier that separates luminal contents from immune responsive epithelial cells. We propose that the early immune response we observe in Gmm(Apo flies following parasite challenge results from the premature exposure of gut epithelia to parasite-derived immunogens in the absence of a robust PM. Thus, tsetse's PM appears to regulate the timing of host immune induction following parasite challenge. Our results

  6. Sequential Notch activation regulates ventricular chamber development

    OpenAIRE

    D'Amato, Gaetano

    2016-01-01

    Tesis doctoral inédita, leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Bioquímica. Fecha de lectura: 15 de enero de 2016 Ventricular chamber morphogenesis is a beautiful example of tissue interactions orchestrating a precise gene regulatory network essential for tissue patterning, cellular proliferation and differentiation that ultimately lead to a fully compacted and functional adult ventricle. The Notch signaling pathway is a crucial regulator ...

  7. Active Power Regulation based on Droop for AC Microgrid

    DEFF Research Database (Denmark)

    Li, Chendan; Coelho, Ernane A. A.; Firoozabadi, Mehdi Savaghebi

    2015-01-01

    In this paper, two different control strategies are proposed to address the active power regulation issue in AC microgrids. The principle of power regulation in the droop controller is firstly introduced. Frequency scheduling and droop gain scheduling on top of droop control is proposed to succes......In this paper, two different control strategies are proposed to address the active power regulation issue in AC microgrids. The principle of power regulation in the droop controller is firstly introduced. Frequency scheduling and droop gain scheduling on top of droop control is proposed...

  8. Electron-phonon interaction in three-barrier nanosystems as active elements of quantum cascade detectors

    Energy Technology Data Exchange (ETDEWEB)

    Tkach, N. V., E-mail: ktf@chnu.edu.ua; Seti, Ju. A.; Grynyshyn, Yu. B. [Chernivtsy National University (Ukraine)

    2015-04-15

    The theory of electron tunneling through an open nanostructure as an active element of a quantum cascade detector is developed, which takes into account the interaction of electrons with confined and interface phonons. Using the method of finite-temperature Green’s functions and the electron-phonon Hamiltonian in the representation of second quantization over all system variables, the temperature shifts and electron-level widths are calculated and the contributions of different electron-phonon-interaction mechanisms to renormalization of the spectral parameters are analyzed depending on the geometrical configuration of the nanosystem. Due to weak electron-phonon coupling in a GaAs/Al{sub 0.34}Ga{sub 0.66}As-based resonant tunneling nanostructure, the temperature shift and rf field absorption peak width are not very sensitive to the electron-phonon interaction and result from a decrease in potential barrier heights caused by a difference in the temperature dependences of the well and barrier band gaps.

  9. Barriers to and Facilitators of Physical Activity Program Use Among Older Adults

    Science.gov (United States)

    Bethancourt, Hilary J.; Rosenberg, Dori E.; Beatty, Tara; Arterburn, David E.

    2014-01-01

    Objective Regular physical activity (PA) is important for maintaining long-term physical, cognitive, and emotional health. However, few older adults engage in routine PA, and even fewer take advantage of programs designed to enhance PA participation. Though most managed Medicare members have free access to the Silver Sneakers and EnhanceFitness PA programs, the vast majority of eligible seniors do not utilize these programs. The goal of this qualitative study was to better understand the barriers to and facilitators of PA and participation in PA programs among older adults. Design This was a qualitative study using focus group interviews. Setting Focus groups took place at three Group Health clinics in King County, Washington. Participants Fifty-two randomly selected Group Health Medicare members between the ages of 66 to 78 participated. Methods We conducted four focus groups with 13 participants each. Focus group discussions were audio-recorded, transcribed, and analyzed using an inductive thematic approach and a social-ecological framework. Results Men and women were nearly equally represented among the participants, and the sample was largely white (77%), well-educated (69% college graduates), and relatively physically active. Prominent barriers to PA and PA program participation were physical limitations due to health conditions or aging, lack of professional guidance, and inadequate distribution of information on available and appropriate PA options and programs. Facilitators included the motivation to maintain physical and mental health and access to affordable, convenient, and stimulating PA options. Conclusion Older adult populations may benefit from greater support and information from their providers and health care systems on how to safely and successfully improve or maintain PA levels through later adulthood. Efforts among health care systems to boost PA among older adults may need to consider patient-centered adjustments to current PA programs, as

  10. Perceived Benefits, Facilitators, Disadvantages, and Barriers for Physical Activity Amongst South Asian Adolescents in India and Canada.

    Science.gov (United States)

    Rajaraman, Divya; Correa, Natasha; Punthakee, Zubin; Lear, Scott A; Jayachitra, Krishnaswamy G; Vaz, Mario; Swaminathan, Sumathi

    2015-07-01

    The purpose of this study was to understand perceived benefits, facilitators, disadvantages, and barriers for physical activity among South Asian adolescents in India and Canada. Thirteen focus group discussions with South Asian (origin) adolescent boys and girls of different nutritional status and socioeconomic status in rural and urban India and urban Canada. Across the groups, fitness and 'energy' were perceived to be major benefits of physical activity. In India, better academic performance was highlighted, while health benefits were well detailed in Canadian groups. In all settings, friends, family, and teachers were perceived as facilitators of as well as barriers to physical activity. Lack of a safe space to play was a major concern for urban adolescents, while academic pressures and preference for other sedentary recreational activities were common barriers across all groups. Girls were less likely than boys to be interested in physical activity, with girls' participation in India further limited by societal restrictions. The study suggests key areas for promotion of physical activity among South Asian adolescents: balance between academic pressure and opportunities for physical activity, especially in India; urban planning for a built environment conducive to physical activity; and gender-sensitive programming to promote girls' activity which also addresses culture-specific barriers.

  11. Modern aspects of tax regulation of investment activity

    Directory of Open Access Journals (Sweden)

    E.S. Podakov

    2016-03-01

    Full Text Available The article investigates the tax regulation of investment activity in modern conditions. Scientists studied different views about the impact of tax regulations on the investment activity in the country. The author determines that the tax regulation of investment activity involves the use of state mechanisms taxation of certain measures to improve investment conditions. The subject is the state tax regulations, and the object is the investment activity of individual and institutional investors of any form of ownership including organizational and legal forms. Such regulation is performed by using complex special tools. The possible methods of tax stimulation of investment processes are described. The article deals with the current results of tax reform in Ukraine and predicts its possible consequences for agricultural producers. The rating positions of Ukraine according to international organizations are showed. The systematic analysis has been carried out and the impact of differential tax rates, tax exemption for a specified period, reducing the tax base, elimination of double taxation on investment activity in certain areas have been researched. The special instruments of investment activity tax regulation are considered. The options for improving investment activity by introducing effective tax regulation are determined.

  12. Perceived Barriers to and Facilitators of Physical Activity in Recipients of Solid Organ Transplantation, a Qualitative Study

    Science.gov (United States)

    van de Zande, Saskia C.; Dekker, Rienk; Verschuuren, Erik A. M.; Dijkstra, Pieter U.; van der Schans, Cees P.

    2016-01-01

    Background Sufficient physical activity is important for solid organ transplant recipients (heart, lung, liver, kidney). However, recipients do not meet the recommended amount or required type of physical activity. The perceived barriers to and facilitators of physical activity in this population are largely unknown. Methods Semi-structured in depth interviews were conducted with solid organ transplant recipients in order to explore experienced barriers and facilitators. Qualitative methodology with thematic line-by-line analysis was used for analysis, and derived themes were classified into personal and environmental factors. Results The most important indicated barriers were physical limitations, insufficient energy level, fear, and comorbidities. The most frequently mentioned facilitators included motivation, coping, consequences of (in)activity, routine/habit, goals/goal priority, and responsibility for the transplanted organ. Neutral factors acting as a barrier or facilitator were self-efficacy and expertise of personnel. A comparison of barriers and facilitators between transplant recipient groups yielded no overt differences. Conclusion Several personal and environmental factors were indicated that should be considered in intervention development to increase physical activity behavior in solid organ transplant recipients. PMID:27622291

  13. Allosteric regulation of deubiquitylase activity through ubiquitination

    Directory of Open Access Journals (Sweden)

    Serena eFaggiano

    2015-02-01

    Full Text Available Ataxin-3, the protein responsible for spinocerebellar ataxia type-3, is a cysteine protease that specifically cleaves poly-ubiquitin chains and participates in the ubiquitin proteasome pathway. The enzymatic activity resides in the N-terminal Josephin domain. An unusual feature of ataxin-3 is its low enzymatic activity especially for mono-ubiquitinated substrates and short ubiquitin chains. However, specific ubiquitination at lysine 117 in the Josephin domain activates ataxin-3 through an unknown mechanism. Here, we investigate the effects of K117 ubiquitination on the structure and enzymatic activity of the protein. We show that covalently linked ubiquitin rests on the Josephin domain, forming a compact globular moiety and occupying a ubiquitin binding site previously thought to be essential for substrate recognition. In doing so, ubiquitination enhances enzymatic activity by locking the enzyme in an activated state. Our results indicate that ubiquitin functions both as a substrate and as an allosteric regulatory factor. We provide a novel example in which a conformational switch controls the activity of an enzyme that mediates deubiquitination.

  14. 75 FR 9431 - Small and Medium-Sized Enterprises: U.S. and EU Export Activities, and Barriers and Opportunities...

    Science.gov (United States)

    2010-03-02

    ... From the Federal Register Online via the Government Publishing Office INTERNATIONAL TRADE COMMISSION Small and Medium-Sized Enterprises: U.S. and EU Export Activities, and Barriers and Opportunities... investigations, investigation No. 332-509, Small and Medium-Sized Enterprises: U.S. and EU Export Activities,...

  15. [Activating physiotherapy for chronic pain in elderly patients. Recommendations, barriers and resources].

    Science.gov (United States)

    Kuss, K; Laekeman, M

    2015-08-01

    Elderly patients with chronic pain are particularly at risk of functional limitations up to the loss of autonomy and social life. To facilitate autonomy, mobility and quality of life, physiotherapy plays an essential role in pain management. Nevertheless, programs that are specifically geared towards the needs of older patients are still uncommon. This article offers recommendations for structuring physiotherapy programs based on international guideline recommendations. First examples of pain management concepts for older adults demonstrate the positive results of activating therapy. Additionally, this article provides insights into barriers and resources of affected patients and all actors involved. However, physiotherapeutic treatment for aged chronic pain patients in Germany still shows considerable shortcomings but also offers an exciting challenge for the future.

  16. Degradation of Organic Compounds by Active Species Sprayed in a Dielectric Barrier Corona Discharge System

    Institute of Scientific and Technical Information of China (English)

    LI Jie; SONG Ling; LIU Qiang; QU Guangzhou; LI Guofeng; WU Yan

    2009-01-01

    Investigation was made into the degradation of organic compounds by a dielectric barrier corona discharge (DBCD) system. The DBCD, consisting of a quartz tube, a concentric high voltage electrode and a net wrapped to the external wall (used as ground electrode), was introduced to generate active species which were sprayed into the organic solution through an aerator fixed on the bottom of the tube. The effect of four factors-the discharge voltage, gas flow rate, solution conductivity, and pH of wastewater, on the degradation efficiency of phenol was assessed. The obtained results demonstrated that this process was an effective method for phenol degradation. The degradation rate was enhanced with the increase in power supplied. The degradation efficiency in alkaline conditions was higher than those in acid and neutral conditions.The optimal gas flow rate for phenol degradation in the system was 1.6 L/min, while the solution conductivity had little effect on the degradation.

  17. International Collaborations on Engineered Barrier Systems: Brief Overview of SKB-EBS Activities.

    Energy Technology Data Exchange (ETDEWEB)

    Jove-Colon, Carlos F. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-10-01

    Research collaborations with international partners on the behavior and performance of engineered barrier systems (EBS) are an important aspect of the DOE-NE Used Fuel Disposition Campaign strategy in the evaluation of disposal design concepts. These international partnerships are a cost-effective way of engaging in key R&D activities with common goals resulting in effective scientific knowledge exchanges thus enhancing existing and future research programs in the USA. This report provides a brief description of the activities covered by the Swedish Nuclear Fuel and Waste Management Company (SKB) EBS Task Force (TF) (referred hereafter as SKB EBS TF) and potential future directions for engagement of the DOE-NE UFDC program in relevant R&D activities. Emphasis is given to SKB EBS TF activities that are still ongoing and aligned to the UFDC R&D program. This include utilization of data collected in the bentonite rock interaction experiment (BRIE) and data sets from benchmark experiments produced by the chemistry or “C” part of the SKB EBS TF. Potential applications of information generated by this program include comparisons/tests between model and data (e.g., reactive diffusion), development and implementation of coupled-process models (e.g., HM), and code/model benchmarking.

  18. Dietary methanol regulates human gene activity.

    Directory of Open Access Journals (Sweden)

    Anastasia V Shindyapina

    Full Text Available Methanol (MeOH is considered to be a poison in humans because of the alcohol dehydrogenase (ADH-mediated conversion of MeOH to formaldehyde (FA, which is toxic. Our recent genome-wide analysis of the mouse brain demonstrated that an increase in endogenous MeOH after ADH inhibition led to a significant increase in the plasma MeOH concentration and a modification of mRNA synthesis. These findings suggest endogenous MeOH involvement in homeostasis regulation by controlling mRNA levels. Here, we demonstrate directly that study volunteers displayed increasing concentrations of MeOH and FA in their blood plasma when consuming citrus pectin, ethanol and red wine. A microarray analysis of white blood cells (WBC from volunteers after pectin intake showed various responses for 30 significantly differentially regulated mRNAs, most of which were somehow involved in the pathogenesis of Alzheimer's disease (AD. There was also a decreased synthesis of hemoglobin mRNA, HBA and HBB, the presence of which in WBC RNA was not a result of red blood cells contamination because erythrocyte-specific marker genes were not significantly expressed. A qRT-PCR analysis of volunteer WBCs after pectin and red wine intake confirmed the complicated relationship between the plasma MeOH content and the mRNA accumulation of both genes that were previously identified, namely, GAPDH and SNX27, and genes revealed in this study, including MME, SORL1, DDIT4, HBA and HBB. We hypothesized that human plasma MeOH has an impact on the WBC mRNA levels of genes involved in cell signaling.

  19. Endogenous methanol regulates mammalian gene activity.

    Directory of Open Access Journals (Sweden)

    Tatiana V Komarova

    Full Text Available We recently showed that methanol emitted by wounded plants might function as a signaling molecule for plant-to-plant and plant-to-animal communications. In mammals, methanol is considered a poison because the enzyme alcohol dehydrogenase (ADH converts methanol into toxic formaldehyde. However, the detection of methanol in the blood and exhaled air of healthy volunteers suggests that methanol may be a chemical with specific functions rather than a metabolic waste product. Using a genome-wide analysis of the mouse brain, we demonstrated that an increase in blood methanol concentration led to a change in the accumulation of mRNAs from genes primarily involved in detoxification processes and regulation of the alcohol/aldehyde dehydrogenases gene cluster. To test the role of ADH in the maintenance of low methanol concentration in the plasma, we used the specific ADH inhibitor 4-methylpyrazole (4-MP and showed that intraperitoneal administration of 4-MP resulted in a significant increase in the plasma methanol, ethanol and formaldehyde concentrations. Removal of the intestine significantly decreased the rate of methanol addition to the plasma and suggested that the gut flora may be involved in the endogenous production of methanol. ADH in the liver was identified as the main enzyme for metabolizing methanol because an increase in the methanol and ethanol contents in the liver homogenate was observed after 4-MP administration into the portal vein. Liver mRNA quantification showed changes in the accumulation of mRNAs from genes involved in cell signalling and detoxification processes. We hypothesized that endogenous methanol acts as a regulator of homeostasis by controlling the mRNA synthesis.

  20. Neuronal Activity Regulates Hippocampal miRNA Expression

    NARCIS (Netherlands)

    Eacker, Stephen M.; Keuss, Matthew J.; Berezikov, Eugene; Dawson, Valina L.; Dawson, Ted M.

    2011-01-01

    Neuronal activity regulates a broad range of processes in the hippocampus, including the precise regulation of translation. Disruptions in proper translational control in the nervous system are associated with a variety of disorders that fall in the autistic spectrum. MicroRNA (miRNA) represent a re

  1. The extracellular matrix protein laminin α2 regulates the maturation and function of the blood-brain barrier.

    Science.gov (United States)

    Menezes, Michael J; McClenahan, Freyja K; Leiton, Cindy V; Aranmolate, Azeez; Shan, Xiwei; Colognato, Holly

    2014-11-12

    Laminins are major constituents of the gliovascular basal lamina of the blood-brain barrier (BBB); however, the role of laminins in BBB development remains unclear. Here we report that Lama2(-/-) mice, lacking expression of the laminin α2 subunit of the laminin-211 heterotrimer expressed by astrocytes and pericytes, have a defective BBB in which systemically circulated tracer leaks into the brain parenchyma. The Lama2(-/-) vascular endothelium had significant abnormalities, including altered integrity and composition of the endothelial basal lamina, inappropriate expression of embryonic vascular endothelial protein MECA32, substantially reduced pericyte coverage, and tight junction abnormalities. Additionally, astrocytic endfeet were hypertrophic and lacked appropriately polarized aquaporin4 channels. Laminin-211 appears to mediate these effects at least in part by dystroglycan receptor interactions, as preventing dystroglycan expression in neural cells led to a similar set of BBB abnormalities and gliovascular disturbances, which additionally included perturbed vascular endothelial glucose transporter-1 localization. These findings provide insight into the cell and molecular changes that occur in congenital muscular dystrophies caused by Lama2 mutations or inappropriate dystroglycan post-translational modifications, which have accompanying brain abnormalities, including seizures. Our results indicate a novel role for laminin-dystroglycan interactions in the cooperative integration of astrocytes, endothelial cells, and pericytes in regulating the BBB.

  2. Insight into Nek2A activity regulation and its pharmacological ...

    African Journals Online (AJOL)

    Ambuj Kumar

    2012-11-28

    Nov 28, 2012 ... 3. Nek2A activity regulation and associated pathological outcomes . .... vide a detailed insight into how they coordinate the cell cycle .... the adenine subpocket creating steric hindrance in the plane of ... Three dimensional.

  3. Regulation of MDM2 Activity by Nucleolin

    Science.gov (United States)

    2007-06-01

    assistance with FACS analysis, Eric Rubin (UMDNJ) for providing the GST-nucleolin expression vectors, Cris- tina Cardoso for the pENeGFP RPA34 plasmid, and...formation, and functional char- acterization. J. Biol. Chem. 269:11121–11132. 25. Huang, W., and R. L. Erikson . 1994. Constitutive activation of Mek1

  4. Barriers to and enablers of physical activity in patients with COPD following a hospital admission: a qualitative study

    Directory of Open Access Journals (Sweden)

    Thorpe O

    2014-01-01

    Full Text Available Olivia Thorpe, Saravana Kumar, Kylie JohnstonInternational Centre for Allied Health Evidence, The Samson Institute for Health Research, School of Health Sciences, University of South Australia, Adelaide, SA, AustraliaBackground: Chronic obstructive pulmonary disease (COPD is characterized by a persistent blockage of airflow, prompting episodes of shortness of breath, commonly leading to hospitalization. Hospitalization may lead to a decline in physical activity following discharge. Physical activity has been shown to improve symptoms of COPD and reduce readmissions, and to decrease morbidity and mortality. This study aims to explore, from the perspectives of people with COPD, the barriers to and enablers of participation in physical activity following hospitalization for COPD.Methods: This study had a qualitative descriptive design and included semistructured interviews with 28 adult COPD patients who had been admitted to hospital with a primary diagnosis of exacerbation of COPD.Results: A plethora of barriers to but fewer enablers of participation in physical activity and pulmonary rehabilitation were identified for this cohort of people. The main barriers identified were health-related (comorbidities, COPD symptoms, and physical injury or illness environment-related (weather, transport, and finance, and self-related. The main enabling factors reported were access to health professionals and equipment, social support, routine and extracurricular activities, personal goals and motivation, and the effect of physical activity and "feeling better".Conclusion: This research provides a snapshot of the barriers to and enablers of physical activity and pulmonary rehabilitation in people with COPD. It is evident that there are significant barriers which hinder the ability of people with COPD to undertake and continue participation in physical activity and pulmonary rehabilitation. While there are some enablers that may counter these barriers, it is

  5. Physical Activity and Reported Barriers to Activity Among Type 2 Diabetic Patients in the United Arab Emirates

    Science.gov (United States)

    Al-Kaabi, Juma; Al-Maskari, Fatma; Afandi, Bachar; Parkar, Hasratali; Nagelkerke, Nicolaas

    2009-01-01

    OBJECTIVES: This study was designed to assess the physical activity practice among type 2 diabetic patients in the United Arab Emirates (UAE). METHODS: This is a cross-sectional study of type 2 diabetic patients who participated in the outpatient clinics in Al-Ain District, during 2006. The patients completed an interviewer-administered questionnaire, and measurements of blood pressure, body mass index, body fat, abdominal circumference, glycemic control (HbA1c), and fasting lipid profile. RESULTS: Of the 390 patients recruited, only 25% reported an increase in their physical activity levels following the diagnosis of diabetes, and only 3% reported physical activity levels that meet the recommended guidelines. More than half of the study subjects had uncontrolled hypertension (53%) and unacceptable lipid profiles; 71% had a high low-density lipoprotein (LDL), 73% had low high-density lipoprotein (HDL), and 59% had hypertriglyceridemia. Forty-four percent were obese and a further 34% were overweight. Abdominal obesity was also common (59%). Only 32% had an acceptable glycemic control. CONCLUSIONS: The physical activity practice of type 2 diabetic patients in the UAE is largely inadequate to meet the recommended level necessary to prevent or ameliorate diabetic complications. Interventions aiming at overcoming the barriers to physical activity are urgently needed. PMID:20043039

  6. Blood-brain barrier breakdown and myeloperoxidase activity in silver catfish experimentally infected with Pseudomonas aeruginosa.

    Science.gov (United States)

    Baldissera, M D; Souza, C F; Santos, R C V; Baldisserotto, B

    2017-08-24

    Central nervous system (CNS) infections continue to be an important cause of morbidity and mortality, and microbial invasion of the blood-brain barrier (BBB) is considered a prerequisite for CNS infections, which contribute to behavioural abnormalities and disease pathogenesis. Based on this information, the aim of this study was to evaluate whether Pseudomonas aeruginosa causes disruption of the BBB, and to investigate the involvement of cerebral myeloperoxidase (MPO) activity in this process in experimentally infected silver catfish. The permeability of the BBB to Evans blue dye increased in the infected animals on days three and six post-infection (PI) compared to the control group. Moreover, cerebral MPO activity and reactive oxygen species (ROS) levels also increased in the infected animals on days three and six PI compared to the control group. Based on this evidence, we concluded that P. aaeruginosa causes a disruption of the BBB, which may contribute to disease pathogenesis in the CNS. Moreover, the increase in cerebral MPO activity and ROS levels may be considered a pathway involved in BBB breakdown, allowing the passage of bacteria to the CNS. © 2017 John Wiley & Sons Ltd.

  7. Removal of atrazine in water by combination of activated carbon and dielectric barrier discharge

    Energy Technology Data Exchange (ETDEWEB)

    Vanraes, Patrick, E-mail: patrick.vanraes@ugent.be [Department of Applied Physics, Ghent University, Sint-Pietersnieuwstraat 41 B4, 9000 Gent (Belgium); Willems, Gert; Nikiforov, Anton [Department of Applied Physics, Ghent University, Sint-Pietersnieuwstraat 41 B4, 9000 Gent (Belgium); Surmont, Pieter; Lynen, Frederic [Separation Science Group, Department of Organic Chemistry, Ghent University, Krijgslaan 281 S4-bis, 9000 Gent (Belgium); Vandamme, Jeroen; Van Durme, Jim [Research Group Molecular Odor Chemistry, Department of Microbial and Molecular Systems (M2S), KU Leuven, Technology Campus, Gebroeders De Smetstraat 1, 9000 Gent (Belgium); Verheust, Yannick P.; Van Hulle, Stijn W.H.; Dumoulin, Ann [Department of Industrial Biological Sciences, Ghent University, Graaf Karel de Goedelaan 5, 8500 Kortrijk (Belgium); Leys, Christophe [Department of Applied Physics, Ghent University, Sint-Pietersnieuwstraat 41 B4, 9000 Gent (Belgium)

    2015-12-15

    Highlights: • Increasing input power with a factor 3.5 leads to deeper atrazine oxidation without significantly changing energy yield of atrazine removal. • Chlorine containing oxidation by-products of first and later generations are detected with HPLC–MS analysis, in agreement with literature. • Desorption analysis shows lower atrazine concentration and higher by-product concentration on activated carbon textile after plasma treatment. • Comparison with plasma reactors described in literature for atrazine decomposition confirms relatively high energy efficiency of our reactor. - Abstract: Efficiency of modern wastewater treatment plants to remove or decompose persistent contaminants in low concentration is often insufficient to meet the demands imposed by governmental laws. Novel, efficient and cheap methods are required to address this global issue. We developed a new type of plasma reactor, in which atrazine decomposition by atmospheric dielectric barrier discharge (DBD) in dry air is combined with micropollutant adsorption on activated carbon textile and with extra bubbling of generated ozone. Investigation of reaction kinetics and by-product analysis shows that increasing input power with a factor 3.5 leads to deeper atrazine oxidation without significantly changing energy yield of atrazine removal. By-products of first and later generations are detected with HPLC–MS analysis in water and adsorbed on the activated carbon textile. Our reactor is compared in energy efficiency with reactors described in literature, showing that combination of plasma discharge with pollutant adsorption and ozone recycling is attractive for future applications of water treatment.

  8. Fragile phagocytes: FMRP positively regulates engulfment activity.

    Science.gov (United States)

    Logan, Mary A

    2017-03-06

    Defective immune system function is implicated in autism spectrum disorders, including Fragile X syndrome. In this issue, O'Connor et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201607093) demonstrate that phagocytic activity of systemic immune cells is compromised in a Drosophila melanogaster model of Fragile X, highlighting intriguing new mechanistic connections between FMRP, innate immunity, and abnormal development.

  9. Regulation of APC/C activators in mitosis and meiosis.

    Science.gov (United States)

    Pesin, Jillian A; Orr-Weaver, Terry L

    2008-01-01

    The anaphase-promoting complex/cyclosome (APC/C) is a multisubunit E3 ubiquitin ligase that triggers the degradation of multiple substrates during mitosis. Cdc20/Fizzy and Cdh1/Fizzy-related activate the APC/C and confer substrate specificity through complex interactions with both the core APC/C and substrate proteins. The regulation of Cdc20 and Cdh1 is critical for proper APC/C activity and occurs in multiple ways: targeted protein degradation, phosphorylation, and direct binding of inhibitory proteins. During the specialized divisions of meiosis, the activity of the APC/C must be modified to achieve proper chromosome segregation. Recent studies show that one way in which APC/C activity is modified is through the use of meiosis-specific APC/C activators. Furthermore, regulation of the APC/C during meiosis is carried out by both mitotic regulators of the APC/C as well as meiosis-specific regulators. Here, we review the regulation of APC/C activators during mitosis and the role and regulation of the APC/C during female meiosis.

  10. Levels of physical activity, barriers, and stage of change in an urban population from a municipality in Colombia

    Directory of Open Access Journals (Sweden)

    Mónica María Arenas

    2011-09-01

    Full Text Available Objective: To assess the levels of physical activity, barriers, and stage of change in an urban population 25 to 50 yearsof age from the Municipality of Santa Rosa de Osos, department of Antioquia.Materials and methods: A prevalence study was conducted, with a two-stage random sampling among 357 individualsnot suffering from any known cardiovascular disease. A pre-designed survey was conducted to assess the levels of physicalactivity, the stage of change, and physical activity barriers.Results: The total low physical activity was 9%, and by domains: work 66.9%, transport 60.8%, household and garden(yard work 44.8%, and leisure-time 76.2%. The most important physical activity barriers were «lack of willpower» (70%and «lack of time» (46.2%. The most prevalent stages of change were «contemplation» (40.3% and «preparation» (17.1%.Conclusion: low physical activity levels were found in different domains of daily life, together with a high prevalenceof barriers and stages prior to physical activity practice, mainly among women and obese subjects.

  11. A Small Group Activity About Bacterial Regulation And Complementation

    Directory of Open Access Journals (Sweden)

    Susan M. Merkel

    2010-11-01

    Full Text Available As teachers, we well understand the need for activities that help develop critical-thinking skills in microbiology. In our experience, one concept that students have difficulty understanding is transcriptional regulation of bacterial genes. To help with this, we developed and evaluated a paper-based activity to help students understand and apply the concepts of bacterial transcriptional regulation. While we don't identify it as such, we use a complementation experiment to assess student understanding of how regulation changes when new DNA is introduced. In Part 1 of this activity, students complete an open book, take-home assignment that asks them to define common terminology related to regulation, and draw the regulatory components of different scenarios involving positive and negative regulation. In Part 2, students work in small groups of 3-4 to depict the regulatory components for a different scenario. They are asked to explain the results of a complementation experiment based on this scenario. They then predict the results of a slightly different experiment. Students who completed the Regulation Activity did significantly better on post-test questions related to regulation, compared to pre-test questions.

  12. Regulation and activity of a zinc uptake regulator, Zur, in Corynebacterium diphtheriae.

    Science.gov (United States)

    Smith, Kelsy F; Bibb, Lori A; Schmitt, Michael P; Oram, Diana M

    2009-03-01

    Regulation of metal ion homeostasis is essential to bacterial cell survival, and in most species it is controlled by metal-dependent transcriptional regulators. In this study, we describe a Corynebacterium diphtheriae ferric uptake regulator-family protein, Zur, that controls expression of genes involved in zinc uptake. By measuring promoter activities and mRNA levels, we demonstrate that Zur represses transcription of three genes (zrg, cmrA, and troA) in zinc-replete conditions. All three of these genes have similarity to genes involved in zinc uptake. Transcription of zrg and cmrA was also shown to be regulated in response to iron and manganese, respectively, by mechanisms that are independent of Zur. We demonstrate that the activity of the zur promoter is slightly decreased under low zinc conditions in a process that is dependent on Zur itself. This regulation of zur transcription is distinctive and has not yet been described for any other zur. An adjacent gene, predicted to encode a metal-dependent transcriptional regulator in the ArsR/SmtB family, is transcribed from a separate promoter whose activity is unaffected by Zur. A C. diphtheriae zur mutant was more sensitive to peroxide stress, which suggests that zur has a role in protecting the bacterium from oxidative damage. Our studies provide the first evidence of a zinc specific transcriptional regulator in C. diphtheriae and give new insights into the intricate regulatory network responsible for regulating metal ion concentrations in this toxigenic human pathogen.

  13. The Ubiquitin Ligase Siah2 Regulates PPARγ Activity in Adipocytes

    OpenAIRE

    Kilroy, Gail; Kirk-Ballard, Heather; Carter, Lauren E.; Floyd, Z. Elizabeth

    2012-01-01

    Moderate reductions in peroxisome proliferator-activated receptor (PPAR)γ levels control insulin sensitivity as effectively as activation of PPARγ in adipocytes by the thiazolidinediones. That observation suggests that PPARγ activity can be regulated by modulating the amount of PPARγ protein in adipocytes. Activation of PPARγ in adipocytes is linked to changes in PPARγ protein levels via increased degradation of PPARγ proteins by the ubiquitin proteasome system. Identification of the ubiquiti...

  14. CB2 Receptor Activation Inhibits Melanoma Cell Transmigration through the Blood-Brain Barrier

    Directory of Open Access Journals (Sweden)

    János Haskó

    2014-05-01

    Full Text Available During parenchymal brain metastasis formation tumor cells need to migrate through cerebral endothelial cells, which form the morphological basis of the blood-brain barrier (BBB. The mechanisms of extravasation of tumor cells are highly uncharacterized, but in some aspects recapitulate the diapedesis of leukocytes. Extravasation of leukocytes through the BBB is decreased by the activation of type 2 cannabinoid receptors (CB2; therefore, in the present study we sought to investigate the role of CB2 receptors in the interaction of melanoma cells with the brain endothelium. First, we identified the presence of CB1, CB2(A, GPR18 (transcriptional variant 1 and GPR55 receptors in brain endothelial cells, while melanoma cells expressed CB1, CB2(A, GPR18 (transcriptional variants 1 and 2, GPR55 and GPR119. We observed that activation of CB2 receptors with JWH-133 reduced the adhesion of melanoma cells to the layer of brain endothelial cells. JWH-133 decreased the transendothelial migration rate of melanoma cells as well. Our results suggest that changes induced in endothelial cells are critical in the mediation of the effect of CB2 agonists. Our data identify CB2 as a potential target in reducing the number of brain metastastes originating from melanoma.

  15. Surface alkaline phosphatase activities of macroalgae on coral reefs of the central Great Barrier Reef, Australia

    Science.gov (United States)

    Schaffelke, B.

    2001-05-01

    Inshore reefs of the Great Barrier Reef (GBR) are subject to episodic nutrient supply, mainly by flood events, whereas midshelf reefs have a more consistent low nutrient availability. Alkaline phosphatase activity (APA) enables macroalgae to increase their phosphorus (P) supply by using organic P. APA was high (~4.0 to 15.5 µmol PO4 3- g DW-1 h-1) in species colonising predominantly inshore reefs and low (study were much lower than data reported from other coral reef systems. In experiments with two Sargassum species tissue P levels were correlated negatively, and N:P ratios were positively correlated with APA. High APA can compensate for a relative P-limitation of macroalgae in coral reef systems that are subject to significant N-inputs, such as the GBR inshore reefs. APA and other mechanisms to acquire a range of nutrient species allow inshore species to thrive in habitats with episodic nutrient supply. These species also are likely to benefit from an increased nutrient supply caused by human activity, which currently is a global problem.

  16. CB2 Receptor Activation Inhibits Melanoma Cell Transmigration through the Blood-Brain Barrier

    Science.gov (United States)

    Haskó, János; Fazakas, Csilla; Molnár, Judit; Nyúl-Tóth, Ádám; Herman, Hildegard; Hermenean, Anca; Wilhelm, Imola; Persidsky, Yuri; Krizbai, István A.

    2014-01-01

    During parenchymal brain metastasis formation tumor cells need to migrate through cerebral endothelial cells, which form the morphological basis of the blood-brain barrier (BBB). The mechanisms of extravasation of tumor cells are highly uncharacterized, but in some aspects recapitulate the diapedesis of leukocytes. Extravasation of leukocytes through the BBB is decreased by the activation of type 2 cannabinoid receptors (CB2); therefore, in the present study we sought to investigate the role of CB2 receptors in the interaction of melanoma cells with the brain endothelium. First, we identified the presence of CB1, CB2(A), GPR18 (transcriptional variant 1) and GPR55 receptors in brain endothelial cells, while melanoma cells expressed CB1, CB2(A), GPR18 (transcriptional variants 1 and 2), GPR55 and GPR119. We observed that activation of CB2 receptors with JWH-133 reduced the adhesion of melanoma cells to the layer of brain endothelial cells. JWH-133 decreased the transendothelial migration rate of melanoma cells as well. Our results suggest that changes induced in endothelial cells are critical in the mediation of the effect of CB2 agonists. Our data identify CB2 as a potential target in reducing the number of brain metastastes originating from melanoma. PMID:24815068

  17. Employees with mental illness – Possibilities and barriers in professional activity

    Directory of Open Access Journals (Sweden)

    Anna Cybula-Fujiwara

    2015-02-01

    Full Text Available In Poland patients with psychiatric problems form a large group; in 2010 there were almost 1.5 million people for whom outpatient psychiatric care was provided, whereas approximately 200 thousand ill individuals were treated in 24-h psychiatric wards. Only 17% of the mentally disabled are professionally active. The results of many researches show that despite the detrimental influence of mental disorders on the employment (e.g., lower productivity, absenteeism, presenteism, increased risk of accidents at the workplace, professional activity can play a key role in the stabilization of the mental state, it can also help in disease recovery. People with mental disorders are a social group that is at the higher risk of exclusion from the job market. The opinion prevailing among employers is that mentally ill individuals have decreased ability to conduct professional activity, and social attitudes towards them tend to be based on marking and stigmatizing. This review tackles the advantages of working during the illness, barriers which people with mental disorders face on the job market when they want to either start or continue work, and professional functioning of people with diagnosed depression (e.g., affective disorders and schizophrenia (representing psychotic disorders. The analysis of existing data show that to improve the situation of mentally ill people present on the job market close cooperation between the representatives of various medical specializations is necessary, as well as their active participation in the process of social and professional rehabilitation of people affected by mental disorders. Med Pr 2015;66(1:57–69

  18. STUDY OF DESTRUCTION PROCESSES OF SYNTHETIC SURFACE-ACTIVE SUBSTENCES (SURFFACTANTS IN BARRIER DISCHARGE

    Directory of Open Access Journals (Sweden)

    V.I. Grinevich

    2012-06-01

    Full Text Available Kinetic data of degradation on aqueous solutions of surfactants in the plasma of barrier discharge are presented. The possible mechanism of proceeding processes is offered and considered. It is shown that the treatment in a barrier discharge results in decomposition efficiency of 95%. It is established that the main product of degradation are carboxylic acids.

  19. Disease activity in eosinophilic esophagitis is associated with impaired esophageal barrier integrity.

    Science.gov (United States)

    Warners, Marijn J; van Rhijn, Bram D; Verheij, Joanne; Smout, Andreas J P M; Bredenoord, Albert J

    2017-09-01

    In eosinophilic esophagitis (EoE), the esophageal barrier integrity is impaired. Integrity can be assessed with different techniques. To assess the correlations between esophageal eosinophilia and various measures of mucosal integrity and to evaluate whether endoscopic impedance measurements can predict disease activity, endoscopies and mucosal integrity measurements were performed in adult EoE patients with active disease (≥15 eosinophils/high-power field) at baseline (n = 32) and after fluticasone (n = 15) and elemental dietary treatment (n = 14) and in controls (n = 19). Mucosal integrity was evaluated during endoscopy using electrical tissue spectroscopy (ETIS) measuring mucosal impedance and transepithelial electrical resistance (TER) and transepithelial molecule-flux through biopsy specimens in Ussing chambers. We included 61 measurements; 32 of patients at baseline and 29 after treatment, 3 patients dropped out. After treatment, 20 patients were in remission (≤15 eosinophils/high-power field) and these measurements were compared with 41 measurements of patients with active disease (at baseline or after failed treatment). All four mucosal integrity measures showed significant impairment in active EoE compared with remission. Eosinophilia was negatively correlated with ETIS and TER and positively with transepithelial molecule flux (P ≤ 0.001). The optimal ETIS cutoff to predict disease activity was 6,000 Ω·m with a sensitivity of 79% [95% confidence interval (CI) 54-94%], specificity of 84% (95% CI 69-94%), positive predictive values of 89% (95% CI 77-95%) and negative predictive values of 71% (95% CI 54-84%). In EoE patients, markers of mucosal integrity correlate with esophageal eosinophilia. Additionally, endoscopic mucosal impedance measurements can predict disease activity.NEW & NOTEWORTHY In adult patients with eosinophilic esophagitis (EoE), the mucosal integrity, measured by making use of four different parameters, correlates strongly with

  20. Regulation of Activation Induced Deaminase (AID) by Estrogen.

    Science.gov (United States)

    Pauklin, Siim

    2016-01-01

    Regulation of Activation Induced Deaminase (AID) by the hormone estrogen has important implications for understanding adaptive immune responses as well as the involvement of AID in autoimmune diseases and tumorigenesis. This chapter describes the general laboratory techniques for analyzing AID expression and activity induced by estrogen, focusing on the isolation and preparation of cells for hormone treatment and the subsequent analysis of AID responsiveness to estrogen at the RNA level and for determining the regulation of AID activity via estrogen by analyzing Ig switch circle transcripts and mutations in switch region loci.

  1. Effects of single and repeated exposure to biocidal active substances on the barrier function of the skin in vitro

    NARCIS (Netherlands)

    Buist, H.E.; Sandt, J.J.M. van de; Burgsteden, J.A. van; Heer, C. de

    2005-01-01

    The dermal route of exposure is important in worker exposure to biocidal products. Many biocidal active substances which are used on a daily basis may decrease the barrier function of the skin to a larger extent than current risk assessment practice addresses, due to possible skin effects of repeate

  2. Correlates of daily leisure-time physical activity in a community sample: Narrow personality traits and practical barriers.

    Science.gov (United States)

    Gallagher, Patrick; Yancy, William S; Denissen, Jaap J A; Kühnel, Anja; Voils, Corrine I

    2013-12-01

    Previous studies examining correlates of leisure time physical activity (LTPA) have identified personality factors that are correlated with LTPA and practical factors that impede LTPA. The purpose of the present study was to test how several narrow traits predict daily reports of LTPA and to test whether traits that predict LTPA moderate the effects of practical barriers. 1192 participants completed baseline measures of personality, then reported their LTPA and several situational and environmental factors daily for 25 days. We used generalized estimating equations to measure how personality traits, practical barriers, and interactions between these factors affected (1) the odds of engaging in LTPA and (2) the duration of daily LTPA. Higher standing on Activity and Discipline and lower standing on Assertiveness predicted greater odds of engaging in LTPA and longer duration of LTPA, and higher standing on Aesthetics predicted shorter duration of LTPA. Poor weather conditions and less leisure time were associated with less LTPA, and effects of these barriers were generally greater among participants 30 and older. In participants older than 30, poor weather was associated with less LTPA among those with lower standing on Activity but was not associated with LTPA among those high in Activity. Despite Discipline's overall positive association with LTPA, less leisure time and less routineness were greater barriers for those high in Discipline. Assessing narrow personality traits could help target LTPA interventions to individual patients' needs and could help identify important new personality dynamics that affect LTPA.

  3. Barriers to and Suggestions for a Healthful, Active Lifestyle as Perceived by Rural and Urban Costa Rican Adolescents

    Science.gov (United States)

    Monge-Rojas, Rafael; Garita-Arce, Carlos; Sanchez-Lopez, Marta; Colon-Ramos, Uriyoan

    2009-01-01

    Objective: To assess the perceptions of rural and urban Costa Rican adolescents regarding which barriers and motivators affect their adoption of an active lifestyle. Design: Data were collected in focus group discussions. Participants: 108 male and female adolescents aged 12 to 18 from the 7th to 11th grades. Setting: Two urban and 1 rural high…

  4. Effects of single and repeated exposure to biocidal active substances on the barrier function of the skin in vitro

    NARCIS (Netherlands)

    Buist, H.E.; Sandt, J.J.M. van de; Burgsteden, J.A. van; Heer, C. de

    2005-01-01

    The dermal route of exposure is important in worker exposure to biocidal products. Many biocidal active substances which are used on a daily basis may decrease the barrier function of the skin to a larger extent than current risk assessment practice addresses, due to possible skin effects of repeate

  5. Facilitators and barriers to HIV activities in religious congregations: perspectives of clergy and lay leaders from a diverse urban sample.

    Science.gov (United States)

    Mendel, Peter; Derose, Kathryn Pitkin; Werber, Laura; Palar, Kartika; Kanouse, David E; Mata, Michael

    2014-10-01

    This paper examines facilitators and barriers to HIV activities within religious congregations, the relative internal or external sources of these influences, and suggestive differences across congregational types. Results are based on in-depth interviews with clergy and lay leaders (n = 57) from 14 congregations in Los Angeles County, California, purposively selected to reflect diversity in racial-ethnic composition, denomination, size, and HIV activity level. Many common facilitators and barriers were related to norms and attitudes, only a few of which appeared overtly associated with theological orientations. Clergy support was a facilitator particularly prevalent among congregations having higher HIV activity levels, indicating its importance in sustaining and expanding HIV programs. Resource issues were also prominent, with material resource barriers more frequently mentioned by smaller congregations and human resource barriers more among larger congregations. Organizational structure issues were mostly centered on external linkages with various social service, public health, and faith-based entities. Analysis of internal versus external sources highlights the roles of different stakeholders within and outside congregations in promoting HIV activities. Potential differences across congregational types represent fruitful areas for future research.

  6. Perceived barriers to and facilitators of physical activity in young adults with childhood-onset physical disabilities

    NARCIS (Netherlands)

    Buffart, L.M.; Westendorp, T.; Berg-Emons, van den R.J.; Stam, H.; Roebroeck, M.E.

    2009-01-01

    OBJECTIVE: To explore the main barriers to and facilitators of physical activity in young adults with childhood-onset physical disabilities. DESIGN: Qualitative study using focus groups. PARTICIPANTS: Sixteen persons (12 men and 4 women) aged 22.4 (standard deviation 3.4) years, of whom 50% were

  7. Absence of canonical active chromatin marks in developmentally regulated genes

    Science.gov (United States)

    Ruiz-Romero, Marina; Corominas, Montserrat; Guigó, Roderic

    2015-01-01

    The interplay of active and repressive histone modifications is assumed to play a key role in the regulation of gene expression. In contrast to this generally accepted view, we show that transcription of genes temporally regulated during fly and worm development occurs in the absence of canonically active histone modifications. Conversely, strong chromatin marking is related to transcriptional and post-transcriptional stability, an association that we also observe in mammals. Our results support a model in which chromatin marking is associated to stable production of RNA, while unmarked chromatin would permit rapid gene activation and de-activation during development. In this case, regulation by transcription factors would play a comparatively more important regulatory role. PMID:26280901

  8. Calcium-activated potassium channels mediated blood-brain tumor barrier opening in a rat metastatic brain tumor model

    Directory of Open Access Journals (Sweden)

    Ong John M

    2007-03-01

    Full Text Available Abstract Background The blood-brain tumor barrier (BTB impedes the delivery of therapeutic agents to brain tumors. While adequate delivery of drugs occurs in systemic tumors, the BTB limits delivery of anti-tumor agents into brain metastases. Results In this study, we examined the function and regulation of calcium-activated potassium (KCa channels in a rat metastatic brain tumor model. We showed that intravenous infusion of NS1619, a KCa channel agonist, and bradykinin selectively enhanced BTB permeability in brain tumors, but not in normal brain. Iberiotoxin, a KCa channel antagonist, significantly attenuated NS1619-induced BTB permeability increase. We found KCa channels and bradykinin type 2 receptors (B2R expressed in cultured human metastatic brain tumor cells (CRL-5904, non-small cell lung cancer, metastasized to brain, human brain microvessel endothelial cells (HBMEC and human lung cancer brain metastasis tissues. Potentiometric assays demonstrated the activity of KCa channels in metastatic brain tumor cells and HBMEC. Furthermore, we detected higher expression of KCa channels in the metastatic brain tumor tissue and tumor capillary endothelia as compared to normal brain tissue. Co-culture of metastatic brain tumor cells and brain microvessel endothelial cells showed an upregulation of KCa channels, which may contribute to the overexpression of KCa channels in tumor microvessels and selectivity of BTB opening. Conclusion These findings suggest that KCa channels in metastatic brain tumors may serve as an effective target for biochemical modulation of BTB permeability to enhance selective delivery of chemotherapeutic drugs to metastatic brain tumors.

  9. Src tyrosine kinase regulates the stem cell factor–induced breakdown of the blood–retinal barrier

    Science.gov (United States)

    Im, Ji-Eun; Song, Sun-Hwa

    2016-01-01

    Purpose Stem cell factor (SCF) has been recently acknowledged as a novel endothelial permeability factor. However, the mechanisms by which SCF-induced activation of the SCF cognate receptor, cKit, enhances endothelial permeability have not been fully elucidated. This study aimed to investigate the role of Src in SCF-induced breakdown of the blood–retinal barrier (BRB). Methods In vitro endothelial permeability and in vivo retinal vascular permeability assays were performed to investigate the role of Src in SCF-induced breakdown of the BRB. Immunofluorescence staining experiments were performed to analyze the cellular distribution of phosphorylated Src and vascular endothelial (VE)-cadherin. Results SCF markedly reduced electric resistance across the human retinal vascular endothelial monolayer in vitro and enhanced extravasation of dyes in murine retinal vasculature in vivo. Inhibition of cKit activation using cKit mutant mice and chemical inhibitor substantially diminished the ability of SCF to increase endothelial permeability and retinal vascular leakage. In human retinal vascular endothelial cells, SCF induced strong phosphorylation of Src and distinct localization of phosphorylated Src in the plasma membrane. Inhibition of Src activation using chemical inhibitors abolished the SCF-induced hyperpermeability of human retinal vascular endothelial cells and retinal vascular leakage in mice. In addition, treatment with Src inhibitors restored junctional expression of VE-cadherin that disappeared in SCF-treated retinal endothelial cells and retinal vasculature. Conclusions These results showed the important role of Src in mediating SCF-induced breakdown of the BRB and retinal vascular leakage. Given that increased retinal vascular permeability is a common manifestation of various ocular diseases, the SCF/cKit/Src signaling pathway may be involved in the development of the hyperpermeable retinal vasculature in many ocular disorders.

  10. Rictor/mTORC2 regulates blood-testis barrier dynamics via its effects on gap junction communications and actin filament network.

    Science.gov (United States)

    Mok, Ka-Wai; Mruk, Dolores D; Lee, Will M; Cheng, C Yan

    2013-03-01

    In the mammalian testis, coexisting tight junctions (TJs), basal ectoplasmic specializations, and gap junctions (GJs), together with desmosomes near the basement membrane, constitute the blood-testis barrier (BTB). The most notable feature of the BTB, however, is the extensive network of actin filament bundles, which makes it one of the tightest blood-tissue barriers. The BTB undergoes restructuring to facilitate the transit of preleptotene spermatocytes at stage VIII-IX of the epithelial cycle. Thus, the F-actin network at the BTB undergoes cyclic reorganization via a yet-to-be explored mechanism. Rictor, the key component of mTORC2 that is known to regulate actin cytoskeleton, was shown to express stage-specifically at the BTB in the seminiferous epithelium. Its expression was down-regulated at the BTB in stage VIII-IX tubules, coinciding with BTB restructuring at these stages. Using an in vivo model, a down-regulation of rictor at the BTB was also detected during adjudin-induced BTB disruption, illustrating rictor expression is positively correlated with the status of the BTB integrity. Indeed, the knockdown of rictor by RNAi was found to perturb the Sertoli cell TJ-barrier function in vitro and the BTB integrity in vivo. This loss of barrier function was accompanied by changes in F-actin organization at the Sertoli cell BTB in vitro and in vivo, associated with a loss of interaction between actin and α-catenin or ZO-1. Rictor knockdown by RNAi was also found to impede Sertoli cell-cell GJ communication, disrupting protein distribution (e.g., occludin, ZO-1) at the BTB, illustrating that rictor is a crucial BTB regulator.

  11. Microbiota-host interactions in irritable bowel syndrome: epithelial barrier, immune regulation and brain-gut interactions.

    Science.gov (United States)

    Hyland, Niall P; Quigley, Eamonn M M; Brint, Elizabeth

    2014-07-21

    Irritable bowel syndrome (IBS) is a common, sometimes debilitating, gastrointestinal disorder worldwide. While altered gut motility and sensation, as well as aberrant brain perception of visceral events, are thought to contribute to the genesis of symptoms in IBS, a search for an underlying aetiology has, to date, proven unsuccessful. Recently, attention has been focused on the microbiota as a possible factor in the pathogenesis of IBS. Prompted by a number of clinical observations, such as the recognition of the de novo development of IBS following enteric infections, as well as descriptions of changes in colonic bacterial populations in IBS and supported by clinical responses to interventions, such as antibiotics and probiotics, that modify the microbiota, various approaches have been taken to investigating the microbiota-host response in IBS, as well as in animal models thereof. From such studies a considerable body of evidence has accumulated to indicate the activation or upregulation of both factors involved in bacterial engagement with the host as well host defence mechanisms against bacteria. Alterations in gut barrier function, occurring in response, or in parallel, to changes in the microbiota, have also been widely described and can be seen to play a pivotal role in generating and sustaining host immune responses both within and beyond the gut. In this manner a plausible hypothesis, based on an altered microbiota and/or an aberrant host response, for the pathogenesis, of at least some instances of IBS, can be generated.

  12. Dissipated power and induced velocity fields data of a micro single dielectric barrier discharge plasma actuator for active flow control☆

    Science.gov (United States)

    Pescini, E.; Martínez, D.S.; De Giorgi, M.G.; Francioso, L.; Ficarella, A.

    2015-01-01

    In recent years, single dielectric barrier discharge (SDBD) plasma actuators have gained great interest among all the active flow control devices typically employed in aerospace and turbomachinery applications [1,2]. Compared with the macro SDBDs, the micro single dielectric barrier discharge (MSDBD) actuators showed a higher efficiency in conversion of input electrical power to delivered mechanical power [3,4]. This article provides data regarding the performances of a MSDBD plasma actuator [5,6]. The power dissipation values [5] and the experimental and numerical induced velocity fields [6] are provided. The present data support and enrich the research article entitled “Optimization of micro single dielectric barrier discharge plasma actuator models based on experimental velocity and body force fields” by Pescini et al. [6]. PMID:26425667

  13. Post-translational regulation of Oct4 transcriptional activity.

    Directory of Open Access Journals (Sweden)

    Jonathan P Saxe

    Full Text Available Oct4 is a key component of the molecular circuitry which regulates embryonic stem cell proliferation and differentiation. It is essential for maintenance of undifferentiated, pluripotent cell populations, and accomplishes these tasks by binding DNA in multiple heterodimer and homodimer configurations. Very little is known about how formation of these complexes is regulated, or the mechanisms through which Oct4 proteins respond to complex extracellular stimuli which regulate pluripotency. Here, we provide evidence for a phosphorylation-based mechanism which regulates specific Oct4 homodimer conformations. Point mutations of a putative phosphorylation site can specifically abrogate transcriptional activity of a specific homodimer assembly, with little effect on other configurations. Moreover, we performed bioinformatic predictions to identify a subset of Oct4 target genes which may be regulated by this specific assembly, and show that altering Oct4 protein levels affects transcription of Oct4 target genes which are regulated by this assembly but not others. Finally, we identified several signaling pathways which may mediate this phosphorylation and act in combination to regulate Oct4 transcriptional activity and protein stability. These results provide a mechanism for rapid and reversible alteration of Oct4 transactivation potential in response to extracellular signals.

  14. Investigating Parental Beliefs Concerning Facilitators and Barriers to the Physical Activity in Down Syndrome and Typical Development

    Directory of Open Access Journals (Sweden)

    Marianna Alesi

    2017-01-01

    Full Text Available Family is a crucial factor to determine the amount, the duration, and the complexity of children’s sport activities. This study aims at comparing the beliefs concerning the involvement in sport activities among parents of children with Down syndrome (DS and parents of typically developing children (TDC. A phenomenological theoretical framework was adopted to realize semistructured interviews with the parents. The participants were 35 parents: 19 with children and adolescents with DS and 16 with TDC. The main facilitation/barrier themes identified by the parents of children with DS were the family and the expert at Adapted Physical Activity (APA instructors. Conversely, the parents of TDC identified social factors related to family as the only barrier. One of the issues that emerge from this study is the lack of home-based physical activity (PA intervention programs aimed at involving families and children.

  15. Degradation of organic compounds and production of activated species in Dielectric Barrier Discharges and Glidarc reactors

    CERN Document Server

    Cormier, Jean Marie; Khacef, Ahmed

    2008-01-01

    Major sterilization mechanisms are related to atoms and radicals, charged parti-cles, excited molecules, ozone, and UV radiation. The ROS (Reactive Oxygen Species) are well known as evildoers. These species are easily created in ambient air and water and they live long enough to reach the cell and attack the organic matter. Test molecules conversion in dry and wet air is studied using Dielectric Barrier Discharge (DBD) and Gliding Arc Reactors (GAR). The effects of tem-perature and energy deposition into the media on the active species production and then on the organic compounds degradation are presented for two non thermal plasma reactors: DBD and GAR. Main production species investigated are OH, O3, NOx, CO and CxHyOz by-products. It is shown from experiment analysis that the reactive species production is quite different from one reactor to another. GAR and pulsed DBD are two chemical processing ways in which the temperature of heavy species in ionized gas is determinant. By reviewing the species producti...

  16. Comparison Between Dielectric Barrier Discharge Plasma and Ozone Regenerations of Activated Carbon Exhausted with Pentachlorophenol

    Science.gov (United States)

    Qu, Guangzhou; Liang, Dongli; Qu, Dong; Huang, Yimei; Li, Jie

    2014-06-01

    In this study, two regeneration methods (dielectric barrier discharge (DBD) plasma and ozone (O3) regeneration) of saturated granular activated carbon (GAC) with pentachlorophenol (PCP) were compared. The results show that the two regeneration methods can eliminate contaminants from GAC and recover its adsorption properties to some extent. Comparing the DBD plasma with O3 regeneration, the adsorption rate and the capacity of the GAC samples after DBD plasma regeneration are greater than those after O3 regeneration. O3 regeneration decreases the specific surface area of GAC and increases the acidic surface oxygen groups on the surface of GAC, which causes a decrease in PCP on GAC uptake. With increasing regeneration cycles, the regeneration efficiencies of the two methods decrease, but the decrease in the regeneration efficiencies of GAC after O3 regeneration is very obvious compared with that after DBD plasma regeneration. Furthermore, the equilibrium data were fitted by the Freundlich and Langmuir models using the non-linear regression technique, and all the adsorption equilibrium isotherms fit the Langmuir model fairly well, which demonstrates that the DBD plasma and ozone regeneration processes do not appear to modify the adsorption process, but to shift the equilibrium towards lower adsorption concentrations. Analyses of the weight loss of GAC show that O3 regeneration has a lower weight loss than DBD plasma regeneration.

  17. Evaluation of the Antidepressant Activity, Hepatotoxicity and Blood Brain Barrier Permeability of Methyl Genipin

    Directory of Open Access Journals (Sweden)

    Xin Che

    2016-07-01

    Full Text Available Geniposide (GE is the main bioactive component of Gardeniae Fructus. The hepatotoxicity of geniposide limited clinical application. In order to get a new geniposide derivative that has less hepatotoxicity and still possesses the antidepressant activity, a new C-1 hydroxyl methylation derivative named methyl genipin (MG was synthesized from geniposide. In the present study, we demonstrated that MG did not increase the liver index, alanine aminotransferase (ALT and aspirate aminotransferase (AST. Histopathological examination suggested that no toxic damages were observed in rats treated orally with MG (0.72 mmol/kg. More importantly, a 7-day treatment with MG at 0.13, 0.26, and 0.52 mmol/kg/day could reduce the duration of immobility. It showed that the antidepressant-like effects of MG were similar to GE in the tail suspension test and the forced swim test. Furthermore, we found MG could be detected in the brain homogenate of mice treated orally with MG 0.52 mmol/kg/day for 1 day by HPLC. The area under the curve (AUC of MG in the brain homogenate was enhanced to 21.7 times that of GE. The brain amount and distribution speed of MG were improved significantly after oral administration. This study demonstrated that MG possessed the antidepressant effects and could cross the blood–brain barrier, but had less hepatotoxicity.

  18. Blood-brain barrier permeability mechanisms in view of quantitative structure-activity relationships (QSAR).

    Science.gov (United States)

    Bujak, Renata; Struck-Lewicka, Wiktoria; Kaliszan, Michał; Kaliszan, Roman; Markuszewski, Michał J

    2015-04-10

    The goal of the present paper was to develop a quantitative structure-activity relationship (QSAR) method using a simple statistical approach, such as multiple linear regression (MLR) for predicting the blood-brain barrier (BBB) permeability of chemical compounds. The "best" MLR models, comprised logP and either molecular mass (M) or isolated atomic energy (E(isol)), tested on a structurally diverse set of 66 compounds, is characterized the by correlation coefficients (R) around 0.8. The obtained models were validated using leave-one-out (LOO) cross-validation technique and the correlation coefficient of leave-one-out- R(LOO)(2) (Q(2)) was at least 0.6. Analysis of a case from legal medicine demonstrated informative value of our QSAR model. To best authors' knowledge the present study is a first application of the developed QSAR models of BBB permeability to case from the legal medicine. Our data indicate that molecular energy-related descriptors, in combination with the well-known descriptors of lipophilicity may have a supportive value in predicting blood-brain distribution, which is of utmost importance in drug development and toxicological studies.

  19. Degradation of triclosan in aqueous solution by dielectric barrier discharge plasma combined with activated carbon fibers.

    Science.gov (United States)

    Xin, Lu; Sun, Yabing; Feng, Jingwei; Wang, Jian; He, Dong

    2016-02-01

    The degradation of triclosan (TCS) in aqueous solution by dielectric barrier discharge (DBD) plasma with activated carbon fibers (ACFs) was investigated. In this study, ACFs and DBD plasma coexisted in a planar DBD plasma reactor, which could synchronously achieve degradation of TCS, modification and in situ regeneration of ACFs, enhancing the effect of recycling of ACFs. The properties of ACFs before and after modification by DBD plasma were characterized by BET and XPS. Various processing parameters affecting the synergetic degradation of TCS were also investigated. The results exhibited excellent synergetic effects in DBD plasma-ACFs system on TCS degradation. The degradation efficiency of 120 mL TCS with initial concentration of 10 mg L(-1) could reach 93% with 1 mm thick ACFs in 18 min at input power of 80 W, compared with 85% by single DBD plasma. Meanwhile, the removal rate of total organic carbon increased from 12% at pH 6.26-24% at pH 3.50. ACFs could ameliorate the degradation efficiency for planar DBD plasma when treating TCS solution at high flow rates or at low initial concentrations. A possible degradation pathway of TCS was investigated according to the detected intermediates, which were identified by liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) combined with theoretical calculation of Gaussian 09 program.

  20. Physiological roles of mitogen-activated-protein-kinase-activated p38-regulated/activated protein kinase

    Institute of Scientific and Technical Information of China (English)

    Sergiy; Kostenko; Gianina; Dumitriu; Kari; Jenssen; Lgreid; Ugo; Moens

    2011-01-01

    Mitogen-activated protein kinases(MAPKs)are a family of proteins that constitute signaling pathways involved in processes that control gene expression,cell division, cell survival,apoptosis,metabolism,differentiation and motility.The MAPK pathways can be divided into conventional and atypical MAPK pathways.The first group converts a signal into a cellular response through a relay of three consecutive phosphorylation events exerted by MAPK kinase kinases,MAPK kinase,and MAPK.Atypical MAPK pathways are not organized into this three-tiered cascade.MAPK that belongs to both conventional and atypical MAPK pathways can phosphorylate both non-protein kinase substrates and other protein kinases.The latter are referred to as MAPK-activated protein kinases.This review focuses on one such MAPK-activated protein kinase,MAPK-activated protein kinase 5(MK5)or p38-regulated/activated protein kinase(PRAK).This protein is highly conserved throughout the animal kingdom and seems to be the target of both conventional and atypical MAPK pathways.Recent findings on the regulation of the activity and subcellular localization,bona fide interaction partners and physiological roles of MK5/PRAK are discussed.

  1. Lack of facilities rather than sociocultural factors as the primary barrier to physical activity among female Saudi university students

    Directory of Open Access Journals (Sweden)

    Samara A

    2015-03-01

    Full Text Available Anastasia Samara,1 Anne Nistrup,1 Tamader Y AL-Rammah,2 Arja R Aro11Unit for Health Promotion and Research, University of Southern Denmark, Esbjerg, Denmark; 2Faculty of Rehabilitation and Health Sciences, Princess Nora Bint Abdul Rahman University, Riyadh, Kingdom of Saudi ArabiaPurpose: The Kingdom of Saudi Arabia is experiencing a dramatic increase in physical inactivity, with women having higher levels of inactivity than men among all age groups. It is assumed that factors such as dress codes, restrictions on going outdoors, and conservative norms are the main reasons for women’s low physical activity. Our aim was to explore the different parameters related to physical activity, including self-efficacy, as well as the perceived barriers to and benefits of physical activity in young Saudi females.Patients and methods: Ninety-four first-year female Saudi university students in Riyadh, Kingdom of Saudi Arabia, participated in the present study in 2014. The students were from eight bachelor’s programs in health and well-being, and each completed a questionnaire with questions divided into five parts as follows: 1 socioeconomic status, 2 physical activity, 3 self-efficacy 4 social factors, and 5 barriers and facilitators related to physical activity.Results: The students exercised at home and alone, and there was low self-efficacy for physical activity (mean score =42±14. Among social factors, attending university was the only factor that hindered physical activity (32%. Physical activity was positively perceived overall (mean score =131±10. Students showed awareness of the benefits of physical activity for health and well-being. The most important barrier was the lack of designated areas available for physical activity. Students disagreed that family or the Islamic community were barriers to physical activity.Conclusion: The lack of facilities and lack of encouragement from the university, but not a lack of knowledge (a high level of

  2. Role of Melatonin, Neuropeptide S and Short Chain Fatty Acids in Regulation of Duodenal Mucosal Barrier Function and Motility

    OpenAIRE

    Wan Saudi, Wan Salman

    2015-01-01

    The duodenal epithelium is regularly exposed to HCl, digestive enzymes, bacteria and toxins, and sometimes also to ethanol and drugs. The imbalance of aggressive factors in the intestinal lumen and mucosal barrier function increases the risk of tissue injury and inflammation. The key components of the duodenal barrier function include mucosal permeability, bicarbonate transport and the secretion or absorption of fluids. This thesis aims to elucidate the role of melatonin, neuropeptide S (NPS)...

  3. Motivations and barriers to prosthesis users participation in physical activity, exercise and sport: a review of the literature.

    Science.gov (United States)

    Deans, Sarah; Burns, David; McGarry, Anthony; Murray, Kevin; Mutrie, Nanette

    2012-09-01

    The UK will host the Paralympics in 2012 and the Commonwealth Games in 2014 showcasing the talents of elite athletes and aiming to inspire the population to become involved. However, low levels of physical activity are prevalent: only 40% of men and 28% of women meet the minimum UK physical activity recommendations. The population of people with limb absence is no exception. To determine if people with amputation are participating in physical activity and sport; whether post-amputation activity levels match pre-amputation levels; and if there are motivations and barriers to participation. Literature review. Five reviewers systematically searched all peer reviewed and gray literature in seven bibliographic databases and the Cochrane Library. Following rigorous elimination, 12 articles were finally included in the review and critically appraised. Four themes were identified: components; rehabilitation outcomes; body image; and motivations and barriers to participation. People with limb absence are not participating in physical activity conducive to health benefits, and only a minority participate in exercise and sports. Participation following amputation does not mirror that of pre-amputation levels, and more barriers than motivations exist to adopting or maintaining a physically active lifestyle.

  4. Epigenetic regulator Lid maintains germline stem cells through regulating JAK-STAT signaling pathway activity

    Directory of Open Access Journals (Sweden)

    Lama Tarayrah

    2015-11-01

    Full Text Available Signaling pathways and epigenetic mechanisms have both been shown to play essential roles in regulating stem cell activity. While the role of either mechanism in this regulation is well established in multiple stem cell lineages, how the two mechanisms interact to regulate stem cell activity is not as well understood. Here we report that in the Drosophila testis, an H3K4me3-specific histone demethylase encoded by little imaginal discs (lid maintains germline stem cell (GSC mitotic index and prevents GSC premature differentiation. Lid is required in germ cells for proper expression of the Stat92E transcription factor, the downstream effector of the Janus kinase signal transducer and activator of transcription (JAK-STAT signaling pathway. Our findings support a germ cell autonomous role for the JAK-STAT pathway in maintaining GSCs and place Lid as an upstream regulator of this pathway. Our study provides new insights into the biological functions of a histone demethylase in vivo and sheds light on the interaction between epigenetic mechanisms and signaling pathways in regulating stem cell activities.

  5. Parents' Perceived Barriers to Healthful Eating and Physical Activity for Low-Income Adolescents Who Are at Risk for Type 2 Diabetes

    Science.gov (United States)

    Peterson, Sharon L.; Bell, Toya Wilson; Hasin, Afroza

    2009-01-01

    Healthful eating and regular physical activity are vitally important for low-income adolescents who are at risk for developing type 2 diabetes (T2DM). To design a relevant, community-based intervention for these at risk adolescents, parent perceptions of barriers to healthful eating and physical activity should be assessed. Such barriers have been…

  6. Endophilin-1 regulates blood-brain barrier permeability by controlling ZO-1 and occludin expression via the EGFR-ERK1/2 pathway.

    Science.gov (United States)

    Liu, Wenjing; Wang, Ping; Shang, Chao; Chen, Lin; Cai, Heng; Ma, Jun; Yao, Yilong; Shang, Xiuli; Xue, Yixue

    2014-07-21

    The blood-brain barrier (BBB) plays a pivotal role in maintenance and regulation of the neural microenvironment. Brain endothelial cells (BECs), held together by tight junctions (TJs), have a primary role in restricting the permeability of the BBB. Endophilin-1 is a multifunctional protein that influences epithelial growth factor receptor (EGFR) endocytosis and degradation and plays an important role in regulating the glomerular filtration barrier in the kidney. Endophilin-1 likely plays a similar role in controlling BBB permeability. In this study, we therefore analyzed the expression and function of endophilin-1 in the human BEC line hCMEC/D3. Our results show that endophilin-1 over-expression reduced the expression of the TJ-associated proteins ZO-1 and occludin and increased the paracellular permeability of hCMEC/D3 cells, whereas silencing of endogenous endophilin-1 yielded the opposite results. Over-expression of ZO-1 and occludin prevented the increase in permeability induced by endophilin-1 over-expression, whereas down-regulation of ZO-1 and occludin prevented the reduction in permeability induced by endophilin-1 silencing. Co-localization and co-immunoprecipitation experiments suggested that endophilin-1 interacts with the EGFR. The levels of EGFR and its downstream effector phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) are significantly decreased when endophilin-1 is over-expressed. Conversely, endophilin-1 down-regulation led to markedly increased levels of these proteins. In addition, the reduced permeability induced by endophilin-1 down-regulation was blocked by AG1478 and PD98059, inhibitors of EGFR and ERK1/2, respectively. Up-regulation of ZO-1 and occludin was blocked by the EGFR and ERK1/2 inhibitors. These results suggest that endophilin-1 regulates BBB permeability by controlling ZO-1 and occludin expression via the EGFR-ERK1/2 pathway in BECs.

  7. c-Yes regulates cell adhesion at the blood-testis barrier and the apical ectoplasmic specialization in the seminiferous epithelium of rat testes.

    Science.gov (United States)

    Xiao, Xiang; Mruk, Dolores D; Lee, Will M; Cheng, C Yan

    2011-04-01

    During spermatogenesis, extensive junction restructuring takes place at the blood-testis barrier (BTB) and the Sertoli cell-spermatid interface known as the apical ectoplasmic specialization (apical ES, a testis-specific adherens junction) in the seminiferous epithelium. However, the mechanism(s) that regulates these critical events in the testis remains unknown. Based on the current concept in the field, changes in the phosphorylation status of integral membrane proteins at these sites can induce alterations in protein endocytosis and recycling, causing junction restructuring. Herein, c-Yes, a non-receptor protein tyrosine kinase, was found to express abundantly at the BTB and apical ES stage-specifically, coinciding with junction restructuring events at these sites during the seminiferous epithelial cycle of spermatogenesis. c-Yes also structurally associated with adhesion proteins at the BTB (e.g., occludin and N-cadherin) and the apical ES (e.g., β1-integrin, laminins β3 and γ3), possibly to regulate phosphorylation status of proteins at these sites. SU6656, a selective c-Yes inhibitor, was shown to perturb the Sertoli cell tight junction-permeability barrier in vitro, which is mediated by changes in the distribution of occludin and N-cadherin at the cell-cell interface, moving from cell surface to cytosol, thereby destabilizing the tight junction-barrier. However, this disruptive effect of SU6656 on the barrier was blocked by testosterone. Furthermore, c-Yes is crucial to maintain the actin filament network in Sertoli cells since a blockade of c-Yes by SU6656 induced actin filament disorganization. In summary, c-Yes regulates BTB and apical ES integrity by maintaining proper distribution of integral membrane proteins and actin filament organization at these sites.

  8. Counselling low-back-pain patients in secondary healthcare: a randomised trial addressing experienced workplace barriers and physical activity.

    Science.gov (United States)

    Jensen, Lone Donbæk; Maribo, Thomas; Schiøttz-Christensen, Berit; Madsen, Finn Hjorth; Gonge, Bigitte; Christensen, Michael; Frost, Poul

    2012-01-01

    To assess if counselling by an occupational physician (OP) addressing experienced workplace barriers and physical activity integrated as a part of low-back pain (LBP) outpatient treatment influences pain, function and sick leave. Randomised controlled trial in the secondary healthcare sector with 3 months' follow-up. The participants were LBP patients who, independently of sick-leave status, expressed concerns about the ability to maintain their current job. Patients referred for surgery were excluded. The intervention consisted of two counselling sessions conducted by an OP addressing both workplace barriers and leisure-time physical activity. A workplace visit was performed if required. Pain, function and duration of sick leave due to LBP were primary outcomes. A reduction in bodily pain and improvement in physical function both measured by the 36-item short-form health survey questionnaire in favour of the intervention group was found. The change in pain score was found to be clinically relevant. The risk of sick leave for at least 8 weeks due to LBP was significantly reduced in the intervention group. Two secondary outcomes, Fear Avoidance Beliefs about physical activity and maximum oxygen uptake, supported compliance and adherence to the part of the intervention focusing on enhanced physical activity. Two short counselling sessions by an OP combining advice on meeting workplace barriers and enhancing physical activity had a substantial effect on important prognostic factors for LBP patients with moderate to severe symptoms diagnosed in outpatient rheumatological clinics. Current Controlled Trials ISRCTN13071157.

  9. Extracellular Matrix Stiffness Regulates Osteogenic Differentiation through MAPK Activation.

    Directory of Open Access Journals (Sweden)

    Jun-Ha Hwang

    Full Text Available Mesenchymal stem cell (MSC differentiation is regulated by the extracellular matrix (ECM through activation of intracellular signaling mediators. The stiffness of the ECM was shown to be an important regulatory factor for MSC differentiation, and transcriptional coactivator with PDZ-binding motif (TAZ was identified as an effector protein for MSC differentiation. However, the detailed underlying mechanism regarding the role of ECM stiffness and TAZ in MSC differentiation is not yet fully understood. In this report, we showed that ECM stiffness regulates MSC fate through ERK or JNK activation. Specifically, a stiff hydrogel matrix stimulates osteogenic differentiation concomitant with increased nuclear localization of TAZ, but inhibits adipogenic differentiation. ERK and JNK activity was significantly increased in cells cultured on a stiff hydrogel. TAZ activation was induced by ERK or JNK activation on a stiff hydrogel because exposure to an ERK or JNK inhibitor significantly decreased the nuclear localization of TAZ, indicating that ECM stiffness-induced ERK or JNK activation is important for TAZ-driven osteogenic differentiation. Taken together, these results suggest that ECM stiffness regulates MSC differentiation through ERK or JNK activation.

  10. Extracellular Matrix Stiffness Regulates Osteogenic Differentiation through MAPK Activation.

    Science.gov (United States)

    Hwang, Jun-Ha; Byun, Mi Ran; Kim, A Rum; Kim, Kyung Min; Cho, Hang Jun; Lee, Yo Han; Kim, Juwon; Jeong, Mi Gyeong; Hwang, Eun Sook; Hong, Jeong-Ho

    2015-01-01

    Mesenchymal stem cell (MSC) differentiation is regulated by the extracellular matrix (ECM) through activation of intracellular signaling mediators. The stiffness of the ECM was shown to be an important regulatory factor for MSC differentiation, and transcriptional coactivator with PDZ-binding motif (TAZ) was identified as an effector protein for MSC differentiation. However, the detailed underlying mechanism regarding the role of ECM stiffness and TAZ in MSC differentiation is not yet fully understood. In this report, we showed that ECM stiffness regulates MSC fate through ERK or JNK activation. Specifically, a stiff hydrogel matrix stimulates osteogenic differentiation concomitant with increased nuclear localization of TAZ, but inhibits adipogenic differentiation. ERK and JNK activity was significantly increased in cells cultured on a stiff hydrogel. TAZ activation was induced by ERK or JNK activation on a stiff hydrogel because exposure to an ERK or JNK inhibitor significantly decreased the nuclear localization of TAZ, indicating that ECM stiffness-induced ERK or JNK activation is important for TAZ-driven osteogenic differentiation. Taken together, these results suggest that ECM stiffness regulates MSC differentiation through ERK or JNK activation.

  11. Perceived Barriers, Facilitators and Benefits for Regular Physical Activity and Exercise in Patients with Rheumatoid Arthritis: A Review of the Literature.

    Science.gov (United States)

    Veldhuijzen van Zanten, Jet J C S; Rouse, Peter C; Hale, Elizabeth D; Ntoumanis, Nikos; Metsios, George S; Duda, Joan L; Kitas, George D

    2015-10-01

    Rheumatoid arthritis (RA) is an autoimmune disease, which not only affects the joints but can also impact on general well-being and risk for cardiovascular disease. Regular physical activity and exercise in patients with RA have numerous health benefits. Nevertheless, the majority of patients with RA are physically inactive. This indicates that people with RA might experience additional or more severe barriers to physical activity or exercise than the general population. This narrative review provides an overview of perceived barriers, benefits and facilitators of physical activity and exercise in RA. Databases were searched for articles published until September 2014 using the terms 'rheumatoid arthritis', 'physical activity', 'exercise', 'barriers', 'facilitators', 'benefits', 'motivation', 'motivators' and 'enablers'. Similarities were found between disease-specific barriers and benefits of physical activity and exercise, e.g. pain and fatigue are frequently mentioned as barriers, but reductions in pain and fatigue are perceived benefits of physical activity and exercise. Even though exercise does not influence the existence of barriers, physically active patients appear to be more capable of overcoming them. Therefore, exercise programmes should enhance self-efficacy for exercise in order to achieve long-term physical activity and exercise behaviour. Encouragement from health professionals and friends/family are facilitators for physical activity and exercise. There is a need for interventions that support RA patients in overcoming barriers to physical activity and exercise and help sustain this important health behaviour.

  12. THE EUROPEAN MODEL OF STATE REGULATION OF TOURISM ACTIVITIES

    Directory of Open Access Journals (Sweden)

    О. Davydova

    2013-11-01

    Full Text Available In the article the existing model of state regulation of the development of tourism. Expediency of the European model of state regulation of tourism development in Ukraine. It is noted that the European model of state regulation of tourism activities based on the coordination of marketing activities and the development of cooperation between the public and private sectors. The basic forms of public-private partnerships and the advantages of using cluster model of development of tourism, namely, contracts, production sharing agreement, lease, joint venture. Promising areas of application of the PPP identified the transport sector, housing and utilities, energy and tourism sector. The features of cluster formations in the country and the prospects for tourism clusters.

  13. Pentraxins in the activation and regulation of innate immunity.

    Science.gov (United States)

    Daigo, Kenji; Inforzato, Antonio; Barajon, Isabella; Garlanda, Cecilia; Bottazzi, Barbara; Meri, Seppo; Mantovani, Alberto

    2016-11-01

    Humoral fluid phase pattern recognition molecules (PRMs) are a key component of the activation and regulation of innate immunity. Humoral PRMs are diverse. We focused on the long pentraxin PTX3 as a paradigmatic example of fluid phase PRMs. PTX3 acts as a functional ancestor of antibodies and plays a non-redundant role in resistance against selected microbes in mouse and man and in the regulation of inflammation. This molecule interacts with complement components, thus modulating complement activation. In particular, PTX3 regulates complement-driven macrophage-mediated tumor progression, acting as an extrinsic oncosuppressor in preclinical models and selected human tumors. Evidence collected over the years suggests that PTX3 is a biomarker and potential therapeutic agent in humans, and pave the way to translation of this molecule into the clinic. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Neural progenitor cells regulate microglia functions and activity.

    Science.gov (United States)

    Mosher, Kira I; Andres, Robert H; Fukuhara, Takeshi; Bieri, Gregor; Hasegawa-Moriyama, Maiko; He, Yingbo; Guzman, Raphael; Wyss-Coray, Tony

    2012-11-01

    We found mouse neural progenitor cells (NPCs) to have a secretory protein profile distinct from other brain cells and to modulate microglial activation, proliferation and phagocytosis. NPC-derived vascular endothelial growth factor was necessary and sufficient to exert at least some of these effects in mice. Thus, neural precursor cells may not only be shaped by microglia, but also regulate microglia functions and activity.

  15. Characterization of a dielectric barrier discharge in contact with liquid and producing a plasma activated water

    Science.gov (United States)

    Neretti, G.; Taglioli, M.; Colonna, G.; Borghi, C. A.

    2017-01-01

    In this work a low-temperature plasma source for the generation of plasma activated water (PAW) is developed and characterized. The plasma reactor was operated by means of an atmospheric-pressure air dielectric barrier discharge (DBD). The plasma generated is in contact with the water surface and is able to chemically activate the liquid medium. Electrodes were supplied by both sinusoidal and nanosecond-pulsed voltage waveforms. Treatment times were varied from 2 to 12 min to increase the energy dose released to the water by the DBD plasma. The physics of the discharge was studied by means of electrical, spectroscopic and imaging diagnostics. The interaction between the plasma and the liquid was investigated as well. Temperature and composition of the treated water were detected. Images of the discharges showed a filamentary behaviour in the sinusoidal case and a more homogeneous behaviour in the nanosecond-pulsed one. The images and the electrical measurements allowed to evaluate an average electron number density of about 4  ×  1019 and 6  ×  1017 m-3 for the sinusoidal and nanosecond-pulsed discharges respectively. Electron temperatures in the range of 2.1÷2.6 eV were measured by using spectroscopic diagnostics. Rotational temperatures in the range of 318-475 K were estimated by fitting synthetic spectra with the measured ones. Water temperature and pH level did not change significantly after the exposure to the DBD plasma. The production of ozone and hydrogen peroxide within the water was enhanced by increasing the plasma treatment time and the energy dose. Numerical simulations of the nanosecond-pulsed discharge were performed by using a self-consistent coupling of state-to-state kinetics of the air mixture with the Boltzmann equation of free electron kinetics. Temporal evolution of the electron energy distribution function shows departure from the Maxwellian distribution especially during the afterglow phase of the discharge. When

  16. Active galactic nuclei activity: self-regulation from backflow

    Science.gov (United States)

    Antonuccio-Delogu, V.; Silk, Joseph

    2010-06-01

    We study the internal circulation within the cocoon carved out by the relativistic jet emanating from an active galactic nucleus (AGN) within the interstellar medium (ISM) of its host galaxy. First, we develop a model for the origin of the internal flow, noticing that a significant increase of large-scale velocity circulation within the cocoon arises as significant gradients in the density and entropy are created near the hotspot (a consequence of Crocco's vorticity generation theorem). We find simple and accurate approximate solutions for the large-scale flow, showing that a backflow towards the few inner parsec region develops. We solve the appropriate fluid dynamic equations, and we use these solutions to predict the mass inflow rates towards the central regions. We then perform a series of 2D simulations of the propagation of jets using FLASH 2.5, in order to validate the predictions of our model. In these simulations, we vary the mechanical input power between 1043 and 1045 ergs-1, and assume a Navarro-Frenk-White (NFW) density profile for the dark matter halo, within which an isothermal diffuse ISM is embedded. The backflows which arise supply the central AGN region with very low angular-momentum gas, at average rates of the order of , the exact value seen to be strongly dependent on the central ISM density (for fixed input jet power). The time-scales of these inflows are apparently weakly dependent on the jet/ISM parameters, and are of the order of . We then argue that these backflows could (at least partially) feed the AGN, and provide a self-regulatory mechanism of AGN activity, that is not directly controlled by, but instead controls, the star formation rate within the central circumnuclear disc.

  17. Exploring physical activity engagement and barriers for asylum seekers in Australia coping with prolonged uncertainty and no right to work.

    Science.gov (United States)

    Hartley, Lisa; Fleay, Caroline; Tye, Marian E

    2017-05-01

    This paper explores the engagement in physical activity as a potential coping strategy for asylum seekers living in the Australian community without the right to work and with prolonged uncertainty, and benefits or barriers to undertaking such activity. Semi-structured in-depth interviews were held with 29 asylum seekers who had arrived to Australia by boat and were living in the community in the cities of Perth, Sydney or Melbourne in July-October 2013 after their release from immigration detention. The ratio of the numbers of men and women interviewed (23 men and 6 women) was comparable to the ratio of men and women who came by boat to Australia seeking asylum in 2012-2013. Nine participants reported that they participated in physical activity as a coping strategy. Seven other participants were so worried about their future and their families that they did not have the mental or physical energy to engage in physical activity. A further six wanted to participate in physical activity but faced a number of barriers to doing so. The seven remaining participants were either not asked about their physical activity engagement because they focused their discussion on other challenges or did not elaborate on why they were not engaging in physical activity. The findings suggest that physical activity, coupled with other coping strategies, are important for some asylum seekers in trying to manage the distress of being denied the right to work and living with prolonged uncertainty. In addition, these findings highlight the critical barrier that government policy plays in disabling engagement in physical activity, which further compounds social exclusion. This includes the lack of welfare support provided, which hinders people's financial ability to access activities and support in the community. © 2017 John Wiley & Sons Ltd.

  18. Signal integration by Ca2+ regulates intestinal stem cell activity

    Science.gov (United States)

    Deng, Hansong; Gerencser, Akos A.; Jasper, Heinrich

    2015-01-01

    Summary Somatic stem cells (SCs) maintain tissue homeostasis by dynamically adjusting proliferation and differentiation in response to stress and metabolic cues. Here, we identify Ca2+ signaling as a central regulator of intestinal SC (ISC) activity in Drosophila. We find that dietary L-glutamate stimulates ISC division and gut growth. The metabotropic glutamate receptor (mGluR) is required in ISCs for this response and for an associated modulation of cytosolic Ca2+ oscillations that results in sustained high cytosolic Ca2+ concentrations. High cytosolic Ca2+ induces ISC proliferation by regulating Calcineurin and CREB - regulated transcriptional co-activator (CRTC). In response to a wide range of dietary and stress stimuli, ISCs reversibly transition between Ca2+ oscillation states that represent poised or activated modes of proliferation, respectively. We propose that the dynamic regulation of intracellular Ca2+ levels allows effective integration of diverse mitogenic signals in ISCs to tailor their proliferative activity to the needs of the tissue. PMID:26633624

  19. How is AMPK activity regulated in skeletal muscles during exercise?

    DEFF Research Database (Denmark)

    Jørgensen, Sebastian Beck; Rose, Adam John

    2008-01-01

    discuss the influence of reactive oxygen species produced within the muscle as well as muscle glycogen and TAK1 in regulating AMPK during exercise. Currently, during intensive contraction, activation of alpha2-AMPK seems mainly to rely on AMP accumulating from ATP-hydrolysis whereas calcium signaling may...

  20. Role of PDI in regulating tissue factor: FVIIa activity.

    Science.gov (United States)

    Popescu, Narcis I; Lupu, Cristina; Lupu, Florea

    2010-04-01

    Cell exposed tissue factor (TF) is generally in a low procoagulant ("cryptic") state, and requires an activation step (decryption) to exhibit its full procoagulant potential. Recent data suggest that TF decryption may be regulated by the redox environment through the oxidoreductase activity of protein disulfide isomerase (PDI). In this article we review PDI contribution to different models of TF decryption, namely the disulfide switch model and the phosphatidylserine dynamics, and hypothesize on PDI contribution to TF self-association and association with lipid domains. Experimental evidence debate the disulfide switch model of TF decryption and its regulation by PDI. More recently we showed that PDI oxidoreductase activity regulates the phosphatidylserine equilibrium at the plasma membrane. Interestingly, PDI reductase activity could maintain TF in the reduced monomeric form, while also maintaining low exposure of PS, both states correlated with low procoagulant function. In contrast, PDI inhibition or oxidants may promote the adverse effects with a net increase in coagulation. The relative contribution of disulfide isomerization and PS exposure needs to be further analyzed to understand the redox control of TF procoagulant function. For the moment however TF regulation remains cryptic.

  1. Neuronal Activity Regulates Hippocampal miRNA Expression

    Science.gov (United States)

    Eacker, Stephen M.; Keuss, Matthew J.; Berezikov, Eugene; Dawson, Valina L.; Dawson, Ted M.

    2011-01-01

    Neuronal activity regulates a broad range of processes in the hippocampus, including the precise regulation of translation. Disruptions in proper translational control in the nervous system are associated with a variety of disorders that fall in the autistic spectrum. MicroRNA (miRNA) represent a relatively recently discovered player in the regulation of translation in the nervous system. We have conducted an in depth analysis of how neuronal activity regulates miRNA expression in the hippocampus. Using deep sequencing we exhaustively identify all miRNAs, including 15 novel miRNAs, expressed in hippocampus of the adult mouse. We identified 119 miRNAs documented in miRBase but less than half of these miRNA were expressed at a level greater than 0.1% of total miRNA. Expression profiling following induction of neuronal activity by electroconvulsive shock demonstrates that most miRNA show a biphasic pattern of expression: rapid induction of specific mature miRNA expression followed by a decline in expression. These results have important implications into how miRNAs influence activity-dependent translational control. PMID:21984899

  2. Neuronal activity regulates hippocampal miRNA expression.

    Directory of Open Access Journals (Sweden)

    Stephen M Eacker

    Full Text Available Neuronal activity regulates a broad range of processes in the hippocampus, including the precise regulation of translation. Disruptions in proper translational control in the nervous system are associated with a variety of disorders that fall in the autistic spectrum. MicroRNA (miRNA represent a relatively recently discovered player in the regulation of translation in the nervous system. We have conducted an in depth analysis of how neuronal activity regulates miRNA expression in the hippocampus. Using deep sequencing we exhaustively identify all miRNAs, including 15 novel miRNAs, expressed in hippocampus of the adult mouse. We identified 119 miRNAs documented in miRBase but less than half of these miRNA were expressed at a level greater than 0.1% of total miRNA. Expression profiling following induction of neuronal activity by electroconvulsive shock demonstrates that most miRNA show a biphasic pattern of expression: rapid induction of specific mature miRNA expression followed by a decline in expression. These results have important implications into how miRNAs influence activity-dependent translational control.

  3. 76 FR 28801 - Agency Information Collection Activities: Bonded Warehouse Regulations

    Science.gov (United States)

    2011-05-18

    ... SECURITY U.S. Customs and Border Protection Agency Information Collection Activities: Bonded Warehouse... approval in accordance with the Paperwork Reduction Act: Bonded Warehouse Regulations. This is a proposed..., mechanical, or other technological techniques or other forms of information. Title: Bonded...

  4. Elastically Cooperative Activated Barrier Hopping Theory of Relaxation in Viscous Fluids. II. Thermal Liquids

    Energy Technology Data Exchange (ETDEWEB)

    Mirigian, Stephen [University of Illinois, Urbana-Champaign; Schweizer, Kenneth [University of Illinois

    2014-01-01

    Building on the elastically collective nonlinear Langevin equation theory developed for hard spheres in Paper I, we propose and implement a quasi-universal theory for the alpha relaxation of thermal liquids based on mapping them to an effective hard sphere fluid via the dimensionless compressibility. The result is a zero adjustable parameter theory that can quantitatively address in a unified manner the alpha relaxation time over 14 or more decades. The theory has no singularities above zero Kelvin, and relaxation in the equilibrium low temperature limit is predicted to be of a roughly Arrhenius form. The two-barrier (local cage and long range collective elastic) description results in a rich dynamic behavior including apparent Arrhenius, narrow crossover, and deeply supercooled regimes, and multiple characteristic or crossover times and temperatures of clear physical meaning. Application of the theory to nonpolar molecules, alcohols, rare gases, and liquids metals is carried out. Overall, the agreement with experiment is quite good for the temperature dependence of the alpha time, plateau shear modulus, and Boson-like peak frequency for van der Waals liquids, though less so for hydrogen-bonding molecules. The theory predicts multiple growing length scales upon cooling, which reflect distinct aspects of the coupled local hopping and cooperative elastic physics. Calculations of the growth with cooling of an activation volume, which is strongly correlated with a measure of dynamic cooperativity, agree quantitatively with experiment. Comparisons with elastic, entropy crisis, dynamic facilitation, and other approaches are performed, and a fundamental basis for empirically extracted crossover temperatures is established. The present work sets the stage for addressing distinctive glassy phenomena in polymer melts, and diverse liquids under strong confinement.

  5. Elastically cooperative activated barrier hopping theory of relaxation in viscous fluids. II. Thermal liquids

    Science.gov (United States)

    Mirigian, Stephen; Schweizer, Kenneth S.

    2014-05-01

    Building on the elastically collective nonlinear Langevin equation theory developed for hard spheres in Paper I, we propose and implement a quasi-universal theory for the alpha relaxation of thermal liquids based on mapping them to an effective hard sphere fluid via the dimensionless compressibility. The result is a zero adjustable parameter theory that can quantitatively address in a unified manner the alpha relaxation time over 14 or more decades. The theory has no singularities above zero Kelvin, and relaxation in the equilibrium low temperature limit is predicted to be of a roughly Arrhenius form. The two-barrier (local cage and long range collective elastic) description results in a rich dynamic behavior including apparent Arrhenius, narrow crossover, and deeply supercooled regimes, and multiple characteristic or crossover times and temperatures of clear physical meaning. Application of the theory to nonpolar molecules, alcohols, rare gases, and liquids metals is carried out. Overall, the agreement with experiment is quite good for the temperature dependence of the alpha time, plateau shear modulus, and Boson-like peak frequency for van der Waals liquids, though less so for hydrogen-bonding molecules. The theory predicts multiple growing length scales upon cooling, which reflect distinct aspects of the coupled local hopping and cooperative elastic physics. Calculations of the growth with cooling of an activation volume, which is strongly correlated with a measure of dynamic cooperativity, agree quantitatively with experiment. Comparisons with elastic, entropy crisis, dynamic facilitation, and other approaches are performed, and a fundamental basis for empirically extracted crossover temperatures is established. The present work sets the stage for addressing distinctive glassy phenomena in polymer melts, and diverse liquids under strong confinement.

  6. Peroxisome proliferator-activated receptors and Alzheimer's disease: hitting the blood-brain barrier.

    Science.gov (United States)

    Zolezzi, Juan M; Inestrosa, Nibaldo C

    2013-12-01

    The blood-brain barrier (BBB) is often affected in several neurodegenerative disorders, such as Alzheimer's disease (AD). Integrity and proper functionality of the neurovascular unit are recognized to be critical for maintenance of the BBB. Research has traditionally focused on structural integrity more than functionality, and BBB alteration has usually been explained more as a consequence than a cause. However, ongoing evidence suggests that at the early stages, the BBB of a diseased brain often shows distinct expression patterns of specific carriers such as members of the ATP-binding cassette (ABC) transport protein family, which alter BBB traffic. In AD, amyloid-β (Aβ) deposits are a pathological hallmark and, as recently highlighted by Cramer et al. (2012), Aβ clearance is quite fundamental and is a less studied approach. Current knowledge suggests that BBB traffic plays a more important role than previously believed and that pharmacological modulation of the BBB may offer new therapeutic alternatives for AD. Recent investigations carried out in our laboratory indicate that peroxisome proliferator-activated receptor (PPAR) agonists are able to prevent Aβ-induced neurotoxicity in hippocampal neurons and cognitive impairment in a double transgenic mouse model of AD. However, even when enough literature about PPAR agonists and neurodegenerative disorders is available, the problem of how they exert their functions and help to prevent and rescue Aβ-induced neurotoxicity is poorly understood. In this review, along with highlighting the main features of the BBB and its role in AD, we will discuss information regarding the modulation of BBB components, including the possible role of PPAR agonists as BBB traffic modulators.

  7. Commission for Energy regulation (CRE) - Activity report June 2004

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2004-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2004 activity report of CRE. Content: A - Opening of the gas and electricity markets for professional customers on 1 July 2004; B - Regulation of the gas market: Gas markets and players (The European environment, The French gas market); Regulation of the gas market (Implementing regulation, Works planned for the coming year; C - Regulation of the electricity market: The electricity markets and players (The European electricity markets, The French electricity market, Monitoring the electricity market); Regulation of the French electricity market (Access to public grid, Cross-border exchanges, Un-bundled accounting principles); The public electricity service in the regulated market (Content of the public service, Public service charges, Electricity production public service financing, Electricity sales tariffs) D - The working of CRE: How CRE exercises its jurisdiction, Tools; E - Appendices: Glossary, Units and conversions, Council of European Energy Regulators, Index of tables and figures.

  8. Localized Down-regulation of P-glycoprotein by Focused Ultrasound and Microbubbles induced Blood-Brain Barrier Disruption in Rat Brain

    Science.gov (United States)

    Cho, Hongseok; Lee, Hwa-Youn; Han, Mun; Choi, Jong-Ryul; Ahn, Sanghyun; Lee, Taekwan; Chang, Yongmin; Park, Juyoung

    2016-08-01

    Multi-drug resistant efflux transporters found in Blood-Brain Barrier (BBB) acts as a functional barrier, by pumping out most of the drugs into the blood. Previous studies showed focused ultrasound (FUS) induced microbubble oscillation can disrupt the BBB by loosening the tight junctions in the brain endothelial cells; however, no study was performed to investigate its impact on the functional barrier of the BBB. In this study, the BBB in rat brains were disrupted using the MRI guided FUS and microbubbles. The immunofluorescence study evaluated the expression of the P-glycoprotein (P-gp), the most dominant multi-drug resistant protein found in the BBB. Intensity of the P-gp expression at the BBB disruption (BBBD) regions was significantly reduced (63.2 ± 18.4%) compared to the control area. The magnitude of the BBBD and the level of the P-gp down-regulation were significantly correlated. Both the immunofluorescence and histologic analysis at the BBBD regions revealed no apparent damage in the brain endothelial cells. The results demonstrate that the FUS and microbubbles can induce a localized down-regulation of P-gp expression in rat brain. The study suggests a clinically translation of this method to treat neural diseases through targeted delivery of the wide ranges of brain disorder related drugs.

  9. Localized Down-regulation of P-glycoprotein by Focused Ultrasound and Microbubbles induced Blood-Brain Barrier Disruption in Rat Brain

    Science.gov (United States)

    Cho, HongSeok; Lee, Hwa-Youn; Han, Mun; Choi, Jong-ryul; Ahn, Sanghyun; Lee, Taekwan; Chang, Yongmin; Park, Juyoung

    2016-01-01

    Multi-drug resistant efflux transporters found in Blood-Brain Barrier (BBB) acts as a functional barrier, by pumping out most of the drugs into the blood. Previous studies showed focused ultrasound (FUS) induced microbubble oscillation can disrupt the BBB by loosening the tight junctions in the brain endothelial cells; however, no study was performed to investigate its impact on the functional barrier of the BBB. In this study, the BBB in rat brains were disrupted using the MRI guided FUS and microbubbles. The immunofluorescence study evaluated the expression of the P-glycoprotein (P-gp), the most dominant multi-drug resistant protein found in the BBB. Intensity of the P-gp expression at the BBB disruption (BBBD) regions was significantly reduced (63.2 ± 18.4%) compared to the control area. The magnitude of the BBBD and the level of the P-gp down-regulation were significantly correlated. Both the immunofluorescence and histologic analysis at the BBBD regions revealed no apparent damage in the brain endothelial cells. The results demonstrate that the FUS and microbubbles can induce a localized down-regulation of P-gp expression in rat brain. The study suggests a clinically translation of this method to treat neural diseases through targeted delivery of the wide ranges of brain disorder related drugs. PMID:27510760

  10. Flufenamic acid protects against intestinal fluid secretion and barrier leakage in a mouse model of Vibrio cholerae infection through NF-κB inhibition and AMPK activation.

    Science.gov (United States)

    Pongkorpsakol, Pawin; Satitsri, Saravut; Wongkrasant, Preedajit; Chittavanich, Pamorn; Kittayaruksakul, Suticha; Srimanote, Potjanee; Chatsudthipong, Varanuj; Muanprasat, Chatchai

    2017-03-05

    Nuclear factor kappa B (NF-κB)-mediated inflammatory responses play crucial roles in the pathogenesis of diarrhea caused by the Vibrio cholerae El Tor variant (EL), which is a major bacterial strain causing recent cholera outbreaks. Flufenamic acid (FFA) has previously been demonstrated to be a potent activator of AMP-activated protein kinase (AMPK), which is a negative regulator of NF-κB signaling. This study aimed to investigate the anti-diarrheal efficacy of FFA in a mouse model of EL infection and to investigate the mechanisms by which FFA activates AMPK in intestinal epithelial cells (IEC). In a mouse closed loop model of EL infection, FFA treatment (20mg/kg) significantly abrogated EL-induced intestinal fluid secretion and barrier disruption. In addition, FFA suppressed NF-κB nuclear translocation and expression of proinflammatory mediators and promoted AMPK phosphorylation in the EL-infected mouse intestine. In T84 cells, FFA induced AMPK activation. Furthermore, FFA promoted tight junction assembly and prevented interferon gamma (IFN-γ)-induced barrier disruption in an AMPK-dependent manner. Biochemical and molecular docking analyses indicated that FFA activates AMPK via a direct stimulation of calcium/calmodulin-dependent protein kinase kinase beta (CaMKKβ) activity. Collectively, our data indicate that FFA represents a class of existing drugs that may be of potential utility in the treatment of cholera caused by EL infection via AMPK-mediated suppression of NF-κB signaling in IEC. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. A comparison of professional-level faculty and student perceptions of active learning: its current use, effectiveness, and barriers

    Science.gov (United States)

    Metz, Michael J.

    2014-01-01

    Active learning is an instructional method in which students become engaged participants in the classroom through the use of in-class written exercises, games, problem sets, audience-response systems, debates, class discussions, etc. Despite evidence supporting the effectiveness of active learning strategies, minimal adoption of the technique has occurred in many professional programs. The goal of this study was to compare the perceptions of active learning between students who were exposed to active learning in the classroom (n = 116) and professional-level physiology faculty members (n = 9). Faculty members reported a heavy reliance on lectures and minimal use of educational games and activities, whereas students indicated that they learned best via the activities. A majority of faculty members (89%) had observed active learning in the classroom and predicted favorable effects of the method on student performance and motivation. The main reported barriers by faculty members to the adoption of active learning were a lack of necessary class time, a high comfort level with traditional lectures, and insufficient time to develop materials. Students hypothesized similar obstacles for faculty members but also associated many negative qualities with the traditional lecturers. Despite these barriers, a majority of faculty members (78%) were interested in learning more about the alternative teaching strategy. Both faculty members and students indicated that active learning should occupy portions (29% vs. 40%) of face-to-face class time. PMID:25179615

  12. Counselling low-back-pain patients in secondary healthcare: a randomised trial addressing experienced workplace barriers and physical activity

    DEFF Research Database (Denmark)

    Jensen, Lone Donbæk; Maribo, Thomas; Schiøttz-Christensen, Berit

    2012-01-01

    OBJECTIVE: To assess if counselling by an occupational physician (OP) addressing experienced workplace barriers and physical activity integrated as a part of low-back pain (LBP) outpatient treatment influences pain, function and sick leave. METHODS: Randomised controlled trial in the secondary...... addressing both workplace barriers and leisure-time physical activity. A workplace visit was performed if required. Pain, function and duration of sick leave due to LBP were primary outcomes. RESULTS: A reduction in bodily pain and improvement in physical function both measured by the 36-item short......-form health survey questionnaire in favour of the intervention group was found. The change in pain score was found to be clinically relevant. The risk of sick leave for at least 8 weeks due to LBP was significantly reduced in the intervention group. Two secondary outcomes, Fear Avoidance Beliefs about...

  13. Topical antihistamines display potent anti-inflammatory activity linked in part to enhanced permeability barrier function

    DEFF Research Database (Denmark)

    Lin, Tzu-Kai; Man, Mao-Qiang; Santiago, Juan-Luis

    2013-01-01

    express both Hr1 and Hr2, we hypothesized that H1/2r antagonists might be more effective if they were used topically to treat inflammatory dermatoses. Topical H1/2r antagonists additively enhanced permeability barrier homeostasis in normal mouse skin by the following mechanisms: (i) stimulation...... of epidermal differentiation, leading to thickened cornified envelopes; and (ii) enhanced epidermal lipid synthesis and secretion. As barrier homeostasis was enhanced to a comparable extent in mast cell-deficient mice, with no further improvement following application of topical H1/2r antagonists, H1/2r...... antagonists likely oppose mast cell-derived histamines. In four immunologically diverse, murine disease models, characterized by either inflammation alone (acute irritant contact dermatitis, acute allergic contact dermatitis) or by prominent barrier abnormalities (subacute allergic contact dermatitis, atopic...

  14. A cross-sectional study of barriers to physical activity among overweight and obese patients with type 2 diabetes in Iran.

    Science.gov (United States)

    Halali, Faranak; Mahdavi, Reza; Asghari Jafarabadi, Mohammad; Mobasseri, Majid; Namazi, Nazli

    2016-09-01

    The objective of this study was to identify common barriers to physical activity practice among overweight/obese patients with type 2 diabetes in Iran and their associations with physical activity level. In this cross-sectional study, 146 overweight/obese volunteers with type 2 diabetes were recruited from diabetes clinics in Tabriz, Iran, between July 2012 and March 2013. A Persian version of the long-format International Physical Activity Questionnaire was used to assess physical activity level. A 12-item structured questionnaire was designed to assess physical activity barriers. The validity and reliability of the latter scale were assessed by related measures. An exploratory factor analysis with the principal component analysis extraction method and varimax rotation was performed to extract the underlying factors. Multivariate regression analysis was used to assess the relationship between barriers and physical activity level. About 73% of patients had moderate physical activity. Factor analysis yielded four factors as barriers to physical activity including: (i) negative attitude towards physical activity, (ii) discouragement, (iii) physical problems and (iv) cost/environmental factors. These factors explained about 51% of the total variance. There was a negative relationship between the factor 'physical problems' and physical activity level (P = 0.024). Overall, there were some barriers to physical activity. Health counsellors should address these barriers to increase the patients' adherence to physical activity recommendations. Physical conditions of the patients must be taken into account.

  15. Complement system part I - molecular mechanisms of activation and regulation

    Directory of Open Access Journals (Sweden)

    Nicolas eMerle

    2015-06-01

    Full Text Available Complement is a complex innate immune surveillance system, playing a key role in defense against pathogens and in host homeostasis. The complement system is initiated by conformational changes in recognition molecular complexes upon sensing danger signals. The subsequent cascade of enzymatic reactions is tightly regulated to assure that complement is activated only at specific locations requiring defense against pathogens, thus avoiding host tissue damage. Here we discuss the recent advances describing the molecular and structural basis of activation and regulation of the complement pathways and their implication on physiology and pathology. This article will review the mechanisms of activation of alternative, classical and lectin pathways, the formation of C3 and C5 convertases, the action of anaphylatoxins and the membrane attack complex. We will also discuss the importance of structure-function relationships using the example of atypical hemolytic uremic syndrome. Lastly we will discuss the development and benefits of therapies using complement inhibitors.

  16. Focal MMP-2 and MMP-9 activity at the blood-brain barrier promotes chemokine-induced leukocyte migration

    OpenAIRE

    Jian Song; Chuan Wu; Eva Korpos; Xueli Zhang; Smriti M. Agrawal; Ying Wang; Cornelius Faber; Michael Schäfers; Heinrich Körner; Ghislain Opdenakker; Rupert Hallmann; Lydia Sorokin

    2015-01-01

    Although chemokines are sufficient for chemotaxis of various cells, increasing evidence exists for their fine-tuning by selective proteolytic processing. Using a model of immune cell chemotaxis into the CNS (experimental autoimmune encephalomyelitis [EAE]) that permits precise localization of immigrating leukocytes at the blood-brain barrier, we show that, whereas chemokines are required for leukocyte migration into the CNS, additional MMP-2/9 activities specifically at the border of the CNS ...

  17. An analysis of potential barriers and enablers to regulating the television marketing of unhealthy foods to children at the state government level in Australia

    Directory of Open Access Journals (Sweden)

    Chung Alexandra

    2012-12-01

    Full Text Available Abstract Background In Australia there have been many calls for government action to halt the effects of unhealthy food marketing on children's health, yet implementation has not occurred. The attitudes of those involved in the policy-making process towards regulatory intervention governing unhealthy food marketing are not well understood. The objective of this research was to understand the perceptions of senior representatives from Australian state and territory governments, statutory authorities and non-government organisations regarding the feasibility of state-level government regulation of television marketing of unhealthy food to children in Australia. Method Data from in-depth semi-structured interviews with senior representatives from state and territory government departments, statutory authorities and non-government organisations (n=22 were analysed to determine participants' views about regulation of television marketing of unhealthy food to children at the state government level. Data were analysed using content and thematic analyses. Results Regulation of television marketing of unhealthy food to children was supported as a strategy for obesity prevention. Barriers to implementing regulation at the state level were: the perception that regulation of television advertising is a Commonwealth, not state/territory, responsibility; the power of the food industry and; the need for clear evidence that demonstrates the effectiveness of regulation. Evidence of community support for regulation was also cited as an important factor in determining feasibility. Conclusions The regulation of unhealthy food marketing to children is perceived to be a feasible strategy for obesity prevention however barriers to implementation at the state level exist. Those involved in state-level policy making generally indicated a preference for Commonwealth-led regulation. This research suggests that implementation of regulation of the television marketing of

  18. An analysis of potential barriers and enablers to regulating the television marketing of unhealthy foods to children at the state government level in Australia.

    Science.gov (United States)

    Chung, Alexandra; Shill, Jane; Swinburn, Boyd; Mavoa, Helen; Lawrence, Mark; Loff, Bebe; Crammond, Bradley; Sacks, Gary; Allender, Steven; Peeters, Anna

    2012-12-28

    In Australia there have been many calls for government action to halt the effects of unhealthy food marketing on children's health, yet implementation has not occurred. The attitudes of those involved in the policy-making process towards regulatory intervention governing unhealthy food marketing are not well understood. The objective of this research was to understand the perceptions of senior representatives from Australian state and territory governments, statutory authorities and non-government organisations regarding the feasibility of state-level government regulation of television marketing of unhealthy food to children in Australia. Data from in-depth semi-structured interviews with senior representatives from state and territory government departments, statutory authorities and non-government organisations (n=22) were analysed to determine participants' views about regulation of television marketing of unhealthy food to children at the state government level. Data were analysed using content and thematic analyses. Regulation of television marketing of unhealthy food to children was supported as a strategy for obesity prevention. Barriers to implementing regulation at the state level were: the perception that regulation of television advertising is a Commonwealth, not state/territory, responsibility; the power of the food industry and; the need for clear evidence that demonstrates the effectiveness of regulation. Evidence of community support for regulation was also cited as an important factor in determining feasibility. The regulation of unhealthy food marketing to children is perceived to be a feasible strategy for obesity prevention however barriers to implementation at the state level exist. Those involved in state-level policy making generally indicated a preference for Commonwealth-led regulation. This research suggests that implementation of regulation of the television marketing of unhealthy food to children should ideally occur under the direction

  19. Staying physically active after spinal cord injury: a qualitative exploration of barriers and facilitators to exercise participation.

    Science.gov (United States)

    Kehn, Matthew; Kroll, Thilo

    2009-06-01

    While enhancing physical activity has been an essential goal of public health officials, people with physical impairments such as spinal cord injury (SCI) are more likely to live a sedentary lifestyle. Exercise has been shown to decrease the risk for many of the secondary conditions associated with SCI, including osteoporosis, cardiovascular disease, pressure ulcers, urinary tract infections, diabetes and arthritis, yet this population is rarely a target for health promotion efforts. This paper examines the self-reported exercise experiences of people with SCI using a qualitative-exploratory design. We enrolled 26 individuals with SCI (15 self-described 'exercisers' and 11 'non-exercisers') from a non-random pool of survey responders. Semi-structured phone interviews were conducted to record participants' experiences with exercise pre/post injury, barriers and facilitators to being active and perceived health impact. Regardless of exercise status, all participants reported physical activity prior to injury and expressed interest in becoming active or maintaining an active lifestyle. Participants identified a range of both motivational and socio-environmental factors that were either facilitating or constraining of such a lifestyle. Non-exercisers identified barriers to exercise, including a perceived low return on physical investment, lack of accessible facilities, unaffordable equipment, no personal assistance and fear of injury. Exercisers identified facilitators, including personal motivation, independence, availability of accessible facilities and personal assistants, fear of health complications, and weight management. Exercisers associated a greater range of specific health benefits with being active than non-exercisers. Despite motivation and interest in being exercise active, people with SCI face many obstacles. Removal of barriers coupled with promotion of facilitating factors, is vital for enhancing opportunities for physical activity and reducing the

  20. Staying physically active after spinal cord injury: a qualitative exploration of barriers and facilitators to exercise participation

    Directory of Open Access Journals (Sweden)

    Kroll Thilo

    2009-06-01

    Full Text Available Abstract Background While enhancing physical activity has been an essential goal of public health officials, people with physical impairments such as spinal cord injury (SCI are more likely to live a sedentary lifestyle. Exercise has been shown to decrease the risk for many of the secondary conditions associated with SCI, including osteoporosis, cardiovascular disease, pressure ulcers, urinary tract infections, diabetes and arthritis, yet this population is rarely a target for health promotion efforts. This paper examines the self-reported exercise experiences of people with SCI using a qualitative-exploratory design. Methods We enrolled 26 individuals with SCI (15 self-described 'exercisers' and 11 'non-exercisers' from a non-random pool of survey responders. Semi-structured phone interviews were conducted to record participants' experiences with exercise pre/post injury, barriers and facilitators to being active and perceived health impact. Results Regardless of exercise status, all participants reported physical activity prior to injury and expressed interest in becoming active or maintaining an active lifestyle. Participants identified a range of both motivational and socio-environmental factors that were either facilitating or constraining of such a lifestyle. Non-exercisers identified barriers to exercise, including a perceived low return on physical investment, lack of accessible facilities, unaffordable equipment, no personal assistance and fear of injury. Exercisers identified facilitators, including personal motivation, independence, availability of accessible facilities and personal assistants, fear of health complications, and weight management. Exercisers associated a greater range of specific health benefits with being active than non-exercisers. Conclusion Despite motivation and interest in being exercise active, people with SCI face many obstacles. Removal of barriers coupled with promotion of facilitating factors, is vital for

  1. Cyclin-dependent kinase 9 activity regulates neutrophil spontaneous apoptosis.

    Directory of Open Access Journals (Sweden)

    Keqing Wang

    Full Text Available Neutrophils are the most abundant leukocyte and play a central role in the immune defense against rapidly dividing bacteria. However, they are also the shortest lived cell in the blood with a lifespan in the circulation of 5.4 days. The mechanisms underlying their short lifespan and spontaneous entry into apoptosis are poorly understood. Recently, the broad range cyclin-dependent kinase (CDK inhibitor R-roscovitine was shown to increase neutrophil apoptosis, implicating CDKs in the regulation of neutrophil lifespan. To determine which CDKs were involved in regulating neutrophil lifespan we first examined CDK expression in human neutrophils and found that only three CDKs: CDK5, CDK7 and CDK9 were expressed in these cells. The use of CDK inhibitors with differing selectivity towards the various CDKs suggested that CDK9 activity regulates neutrophil lifespan. Furthermore CDK9 activity and the expression of its activating partner cyclin T1 both declined as neutrophils aged and entered apoptosis spontaneously. CDK9 is a component of the P-TEFb complex involved in transcriptional regulation and its inhibition will preferentially affect proteins with short half-lives. Treatment of neutrophils with flavopiridol, a potent CDK9 inhibitor, increased apoptosis and caused a rapid decline in the level of the anti-apoptotic protein Mcl-1, whilst Bcl2A was unaffected. We propose that CDK9 activity is a key regulator of neutrophil lifespan, preventing apoptosis by maintaining levels of short lived anti-apoptotic proteins such as Mcl-1. Furthermore, as inappropriate inhibition of neutrophil apoptosis contributes to chronic inflammatory diseases such as Rheumatoid Arthritis, CDK9 represents a novel therapeutic target in such diseases.

  2. Endothelial PI 3-kinase activity regulates lymphocyte diapedesis.

    Science.gov (United States)

    Nakhaei-Nejad, Maryam; Hussain, Amer M; Zhang, Qiu-Xia; Murray, Allan G

    2007-12-01

    Lymphocyte recruitment to sites of inflammation involves a bidirectional series of cues between the endothelial cell (EC) and the leukocyte that culminate in lymphocyte migration into the tissue. Remodeling of the EC F-actin cytoskeleton has been observed after leukocyte adhesion, but the signals to the EC remain poorly defined. We studied the dependence of peripheral blood lymphocyte transendothelial migration (TEM) through an EC monolayer in vitro on EC phosphatidylinositol 3-kinase (PI 3-kinase) activity. Lymphocytes were perfused over cytokine-activated EC using a parallel-plate laminar flow chamber. Inhibition of EC PI 3-kinase activity using LY-294002 or wortmannin decreased lymphocyte TEM (48 +/- 6 or 34 +/- 7%, respectively, vs. control; mean +/- SE; P structure" after intercellular adhesion molecule-1 ligation, whereas this was inhibited by jasplakinolide treatment. A similar fraction of lymphocytes migrated on control or LY-294002-treated EC and localized to interendothelial junctions. However, lymphocytes failed to extend processes below the level of vascular endothelial (VE)-cadherin on LY-294002-treated EC. Together these observations indicate that EC PI 3-kinase activity and F-actin remodeling are required during lymphocyte diapedesis and identify a PI 3-kinase-dependent step following initial separation of the VE-cadherin barrier.

  3. Cbl negatively regulates JNK activation and cell death

    Institute of Scientific and Technical Information of China (English)

    Andrew A Sproul; Zhiheng Xu; Michael Wilhelm; Stephen Gire; Lloyd A Greene

    2009-01-01

    Here, we explore the role of Cbl proteins in regulation of neuronal apoptosis. In two paradigms of neuron apopto-sis--nerve growth factor (NGF) deprivation and DNA damage--cellular levels of c-Cbl and Cbl-b fell well before the onset of cell death. NGF deprivation also induced rapid loss of tyrosine phosphorylation (and most likely, activa-tion) of c-Cbl. Targeting e-Cbl and Cbl-b with siRNAs to mimic their loss/inactivation sensitized neuronal cells to death promoted by NGF deprivation or DNA damage. One potential mechanism by which Cbl proteins might affect neuronal death is by regulation of apoptotic c-Jun N-terminal kinase (JNK) signaling. We demonstrate that Cbl pro-teins interact with the JNK pathway components mixed lineage kinase (MLK) 3 and POSH and that knockdown of Cbl proteins is sufficient to increase JNK pathway activity. Furthermore, expression of c-Cbl blocks the ability of MLKs to signal to downstream components of the kinase cascade leading to JNK activation and protects neuronal cells from death induced by MLKs, but not from downstream JNK activators. On the basis of these findings, we propose that Cbls suppress cell death in healthy neurons at least in part by inhibiting the ability of MLKs to activate JNK signaling. Apoptotic stimuli lead to loss of Cbl protein/activity, thereby removing a critical brake on JNK acti-vation and on cell death.

  4. Osteoblast response (initial adhesion and alkaline phosphatase activity following exposure to a barrier membrane/enamel matrix derivative combination

    Directory of Open Access Journals (Sweden)

    Thangakumaran S

    2009-01-01

    Full Text Available Background and Objective: The enamel matrix derivative (EMD has been used in combination with barrier membranes to optimize regeneration in vertical osseous defects. However, the osteoblast response when exposed to the EMD/barrier membrane combination has not yet been evaluated. The osteoblast behavior when exposed to a combination of regenerative materials must be evaluated to fully understand their effect on bone regeneration. Therefore, the present study was undertaken to estimate the initial adhesion and alkaline phosphatase (ALP activity of an osteoblast cell line (SaOS-2 when exposed to four commercially available resorbable membranes and determine if the addition of EMD had any modulatory effect on osteoblast behavior. Materials and Methods: 5 x 104 SaOS-2 cells between passages 7-10 were cultured in two 24-well culture plates. Plate A was used for the adhesion assay and Plate B was used for the ALP assay. A MTT (3-[4, 5-dimethylthiazolyl-2]-2, 5-diphenyltetrazolium bromide assay was done after 24 hours to determine the adhesion of the osteoblastic cells to four barrier membranes: 1 a non cross-linked porcine Type I and III collagen membrane (BG, 2 a weakly cross-linked Type I collagen membrane (HG, 3 a glutaraldehyde cross-linked bovine Type I collagen (BM, and 4 a resorbable polymer membrane (CP. Osteoblast differentiation was studied using an ALP assay with p-nitro phenyl phosphate as the substrate at 24 hours, 72 hours, and 1 week. A total of 50 µg/ml of EMD dissolved in 10 mM acetic acid was added into each well and the entire experimental protocol outlined above was repeated. Results: The osteoblast adhesion to collagen barriers showed a statistically insignificant reduction following the addition of EMD. Adhesion to the polymer barrier, although significantly lower when compared with collagen barriers, was unaffected by the addition of EMD. ALP activity after 1 week among the various groups was as follows: EMD alone (75.59±2

  5. Perceived barriers to pharmacist engagement in adverse drug event prevention activities in Ghana using semi-structured interview.

    Science.gov (United States)

    Acheampong, Franklin; Anto, Berko Panyin

    2015-09-07

    Pharmacist involvement in the prevention of medication errors is well documented. One such method, the process by which hospital pharmacists undertake these clinical interventions needs to be described and documented. The perceived barriers to pharmacists succeeding in getting their recommendations accepted could inform future safety strategy development. This study was therefore to trace the typical process involved and explore the perceived barriers to pharmacists' medication safety efforts. This study involved a retrospective evaluation of routine clinical interventions collected at a tertiary hospital in Ghana over 23 months. A sample of pharmacists who had submitted these reports were then interviewed. The interventions made related to drug therapy changes (76.0%), monitoring (13.0%), communication (5.4%), counselling (5.0%) and adverse drug events (0.6%). More than 90% of interventions were accepted. The results also showed that undertaking clinical interventions by pharmacists followed a sequential order with two interlinked subprocesses: Problem Identification and Problem Handling. In identifying the problem, as much information needed to be gathered, clinical issues identified and then the problems prioritised. During the problem handling stage, detailed assessment was made which led to the development of a pharmaceutical plan. The plan was then implemented and monitored to ensure appropriateness of desired outcomes. The main barrier mentioned by pharmacist related to the discrepant attitudes of doctors/nurses. The other barriers encountered during these tasks related to workload, and inadequate clinical knowledge. The attitudes were characterised by conflicts and egos resulting from differences in status/authority, responsibilities, and training. Though the majority of recommendations from pharmacists were accepted, the main barrier to hospital pharmacist engagement in medication error prevention activities related to discrepant attitudes of doctors and

  6. St. John's Wort constituents modulate P-glycoprotein transport activity at the blood-brain barrier.

    NARCIS (Netherlands)

    Ott, M.; Huls, M.; Cornelius, M.G.; Fricker, G.

    2010-01-01

    PURPOSE: The purpose of this study was to investigate the short-term signaling effects of St. John's Wort (SJW) extract and selected SJW constituents on the blood-brain barrier transporter P-glycoprotein and to describe the role of PKC in the signaling. METHODS: Cultured porcine brain capillary endo

  7. Barriers to Application of E-Learning in Training Activities of SMEs

    Science.gov (United States)

    Anderson, Randy J.; Wielicki, Tomasz; Anderson, Lydia E.

    2010-01-01

    This paper reports on the on-going study of Small and Mid-Size Enterprises (SMEs) in the Central California concerning their use of Information and Communication Technology (ICT). This research project analyzed data from a sample of 161 SMEs. Specifically, this part of the study is investigating the major barriers to applications of e-learning…

  8. Cichorium intybus root extract: A "vitamin D-like" active ingredient to improve skin barrier function.

    Science.gov (United States)

    Maia Campos, P M B G; G Mercurio, D; O Melo, M; Closs-Gonthier, B

    2017-02-01

    During the aging process, the human skin suffers many alterations including dryness, skin barrier function damage. The skin barrier function is important to the prevention of skin alterations and maintenance of homeostasis. So, the objective of this study was to assess the clinical efficacy on skin barrier function of Cichorium intybus root extract in cosmetic formulations with or without UV filters. Fifty women, aged between 45 and 60 years, were divided into two groups. One group received vehicle formulations containing UV filters, and the other group received formulations without UV filters. Both groups received a formulation containing the extract and the vehicle. The formulations were applied twice daily to the upper arms after washing with sodium lauryl sulphate. Transepidermal water loss (TEWL) and skin microrelief were evaluated before and after a 14- and 28-day period of treatment. The control regions and regions where the vehicles were applied showed an increase in the TEWL. For the formulations containing the extract, decreased TEWL and improved microrelief were observed when compared to the vehicle and control areas after a 28-day period. In conclusion, Cichorium intybus root extract showed protective and restructuring effects on the skin and stands out as an innovative ingredient to improve skin barrier function.

  9. Measurement of Plasma Density Produced in Dielectric Barrier Discharge for Active Aerodynamic Control with Interferometer

    Institute of Scientific and Technical Information of China (English)

    LI Gang; ZHANG Yi; XU Yan-Ji; LIN Bin; LI Yu-Tong; ZHU Jun-Qiang

    2009-01-01

    We utilize an interferometer to investigate the changes of the refractive index caused by dielectric barrier discharge plasma.The electronic density of the plasma produced is measured and analyzed tentatively.The results show that density of the plasma increases linearly with exciting voltages.

  10. CYLD regulates RhoA activity by modulating LARG ubiquitination.

    Directory of Open Access Journals (Sweden)

    Yunfan Yang

    Full Text Available Rho family guanosine triphosphatases (GTPases, such as RhoA, Cdc42, and Rac1, play a fundamental role in various cellular processes. The activation of Rho proteins is catalyzed by guanine nucleotide-exchange factors (GEFs, which promote the exchange of GDP for GTP. The precise mechanisms regulating the activation of Rho proteins are not fully understood. Herein, we demonstrate that RhoA activity is regulated by cylindromatosis (CYLD, a deubiquitinase harboring multiple functions. In addition, we find that RhoA-mediated cytoskeletal rearrangement, chromosome separation, and cell polarization are altered in CYLD-depleted cells. Mechanistically, CYLD does not interact with RhoA; instead, it interacts with and deubiquitinates leukemia-associated RhoGEF (LARG. Our data further show that CYLD-mediated deubiquitination of LARG enhances its ability to stimulate the GDP/GTP exchange on RhoA. These data thus identify LARG as a new substrate of CYLD and provide novel insights into the regulation of RhoA activation. Our results also suggest that the LARG-RhoA signaling pathway may play a role in diverse CYLD-mediated cellular events.

  11. CYLD regulates RhoA activity by modulating LARG ubiquitination.

    Science.gov (United States)

    Yang, Yunfan; Sun, Lei; Tala; Gao, Jinmin; Li, Dengwen; Zhou, Jun; Liu, Min

    2013-01-01

    Rho family guanosine triphosphatases (GTPases), such as RhoA, Cdc42, and Rac1, play a fundamental role in various cellular processes. The activation of Rho proteins is catalyzed by guanine nucleotide-exchange factors (GEFs), which promote the exchange of GDP for GTP. The precise mechanisms regulating the activation of Rho proteins are not fully understood. Herein, we demonstrate that RhoA activity is regulated by cylindromatosis (CYLD), a deubiquitinase harboring multiple functions. In addition, we find that RhoA-mediated cytoskeletal rearrangement, chromosome separation, and cell polarization are altered in CYLD-depleted cells. Mechanistically, CYLD does not interact with RhoA; instead, it interacts with and deubiquitinates leukemia-associated RhoGEF (LARG). Our data further show that CYLD-mediated deubiquitination of LARG enhances its ability to stimulate the GDP/GTP exchange on RhoA. These data thus identify LARG as a new substrate of CYLD and provide novel insights into the regulation of RhoA activation. Our results also suggest that the LARG-RhoA signaling pathway may play a role in diverse CYLD-mediated cellular events.

  12. Optimization of the configuration of a symmetric three-barrier resonant-tunneling structure as an active element of a quantum cascade detector

    Energy Technology Data Exchange (ETDEWEB)

    Tkach, N. V., E-mail: ktf@chnu.edu.ua; Seti, Ju. A. [Fedkovich Chernivtsy National University (Ukraine)

    2011-03-15

    On the basis of a model of rectangular potentials and different electron effective masses in wells and barriers of an open resonant-tunneling structure with identical outer barriers, a theory has been developed and the dynamic conductance caused by the interaction of the electromagnetic field with electrons passing through the structure has been calculated. Using the example of the three-barrier resonant-tunneling structure with In{sub 0.53}Ga{sub 0.47}As wells and In{sub 0.52}Al{sub 0.48}As barriers, it is shown that, independently of the geometrical sizes of potential wells and barriers, there exist three geometrical configurations (positions of the inner barrier with respect to outer ones) at which the nanosystem, as an active element, provides optimum operating conditions of the quantum cascade detector.

  13. Lhx8 regulates primordial follicle activation and postnatal folliculogenesis.

    Science.gov (United States)

    Ren, Yu; Suzuki, Hitomi; Jagarlamudi, Krishna; Golnoski, Kayla; McGuire, Megan; Lopes, Rita; Pachnis, Vassilis; Rajkovic, Aleksandar

    2015-06-16

    The early stages of ovarian follicle formation-beginning with the breakdown of germ cell cysts and continuing with the formation of primordial follicles and transition to primary and secondary follicles-are critical in determining reproductive life span and fertility. Previously, we discovered that global knockouts of germ cell-specific transcriptional co-regulators Sohlh1, Sohlh2, Lhx8, and Nobox, cause rapid oocyte loss and ovarian failure. Also factors such as Nobox and Sohlh1 are associated with human premature ovarian failure. In this study, we developed a conditional knockout of Lhx8 to study oocyte-specific pathways in postnatal folliculogenesis. The conditional deficiency of Lhx8 in the oocytes of primordial follicles leads to massive primordial oocyte activation, in part, by indirectly interacting with the PI3K-AKT pathway, as shown by synergistic effects on FOXO3 nucleocytoplasmic translocation and rpS6 activation. However, LHX8 does not directly regulate members of the PI3K-AKT pathway; instead, we show that LHX8 represses Lin28a expression, a known regulator of mammalian metabolism and of the AKT/mTOR pathway. LHX8 can bind to the Lin28a promoter, and the depletion of Lin28a in Lhx8-deficient oocytes partially suppresses primordial oocyte activation. Moreover, unlike the PI3K-AKT pathway, LHX8 is critical beyond primordial follicle activation, and blocks the primary to secondary follicle transition. Our results indicate that the LHX8-LIN28A pathway is essential in the earliest stages of primordial follicle activation, and LHX8 is an important oocyte-specific transcription factor in the ovary for regulating postnatal folliculogenesis.

  14. Short and long-term lifestyle coaching approaches used to address diverse participant barriers to weight loss and physical activity adherence.

    Science.gov (United States)

    Venditti, Elizabeth M; Wylie-Rosett, Judith; Delahanty, Linda M; Mele, Lisa; Hoskin, Mary A; Edelstein, Sharon L

    2014-02-12

    Individual barriers to weight loss and physical activity goals in the Diabetes Prevention Program, a randomized trial with 3.2 years average treatment duration, have not been previously reported. Evaluating barriers and the lifestyle coaching approaches used to improve adherence in a large, diverse participant cohort can inform dissemination efforts. Lifestyle coaches documented barriers and approaches after each session (mean session attendance = 50.3 ± 21.8). Subjects were 1076 intensive lifestyle participants (mean age = 50.6 years; mean BMI = 33.9 kg/m²; 68% female, 48% non-Caucasian). Barriers and approaches used to improve adherence were ranked by the percentage of the cohort for whom they applied. Barrier groupings were also analyzed in relation to baseline demographic characteristics. Top weight loss barriers reported were problems with self-monitoring (58%); social cues (58%); holidays (54%); low activity (48%); and internal cues (thought/mood) (44%). Top activity barriers were holidays (51%); time management (50%); internal cues (30%); illness (29%), and motivation (26%). The percentage of the cohort having any type of barrier increased over the long-term intervention period. A majority of the weight loss barriers were significantly associated with younger age, greater obesity, and non-Caucasian race/ethnicity (p-values vary). Physical activity barriers, particularly thought and mood cues, social cues and time management, physical injury or illness and access/weather, were most significantly associated with being female and obese (p  90% long term) and regularly reviewed self-monitoring skills. More costly approaches were used infrequently during the first 16 sessions (≤10%) but increased over 3.2 years. Behavioral problem solving approaches have short and long term dissemination potential for many kinds of participant barriers. Given minimal resources, increased attention to training lifestyle coaches in the consistent use of these

  15. Regulation of Multidrug Resistance P-Glycoprotein in the Developing Blood-Brain Barrier: Interplay between Glucocorticoids and Cytokines.

    Science.gov (United States)

    Iqbal, M; Baello, S; Javam, M; Audette, M C; Gibb, W; Matthews, S G

    2016-03-01

    P-glycoprotein (P-gp) encoded by Abcb1 provides protection to the developing brain from xenobiotics. P-gp in brain endothelial cells (BECs) derived from the developing brain microvasculature is up-regulated by glucocorticoids and inhibited by pro-inflammatory cytokines in vitro. However, little is known about how prenatal maternal glucocorticoid treatment can affect Abcb1/P-gp function and subsequent cytokine regulation in foetal BECs. We hypothesised that glucocorticoid exposure increases Abcb1/P-gp in the foetal brain microvasculature and enhances the sensitivity of Abcb1/P-gp in BECs to the inhibitory effects of cytokines. BECs isolated from dexamethasone- or vehicle-exposed foetal guinea pigs were cultured and treated with interleukin-1β, interleukin-6 or tumour necrosis factor-α, and Abcb1/P-gp expression and function were assessed. Prenatal dexamethasone exposure significantly increased Abcb1/P-gp expression/activity and cytokine receptor levels in BECs of the foetal brain microvasculature. Foetal dexamethasone exposure in vivo also increased the subsequent responsiveness of BECs to pro-inflammatory cytokines in vitro. In conclusion, maternal treatment with synthetic glucocorticoids appears to prematurely mature P-gp mediated drug resistance at the foetal BBB in vivo and profoundly impact the subsequent responsiveness of P-gp to pro-inflammatory cytokines in the foetal BEC. The significance of these findings to foetal brain protection against xenobiotics and other P-gp substrates in vivo requires further elaboration. However, the results of the present study may have implications for human pregnancy and foetal brain protection, particularly in cases of preterm birth combined with infection.

  16. The prevalence of barriers for Colombian college students engaging in physical activity.

    Science.gov (United States)

    Ramírez-Vélez, Robinson; Tordecilla-Sanders, Alejandra; Laverde, David; Hernández-Novoa, Juan Gilberto; Ríos, Marcelo; Rubio, Fernando; Correa-Bautista, Jorge Enrique; Martinez-Torres, Javier

    2014-09-18

    Objetivo: El objetivo de este trabajo fue analizar la prevalencia de barreras y su asociación con la práctica de AF en universitarios de Colombia. Métodos: Estudio descriptivo de corte transversal, en 5.663 sujetos (3.348 hombres), de tres ciudades de Colombia. Las razones que podrían impedir realizar AF, se evaluaron con el cuestionario de “Percepción de barreras para la práctica de la actividad física” (en inglés, Barriers to Being Active Quiz-21 ítems). Un análisis de regresión logística para cada barrera ajustado por las variables de confusión (sexo, edad e IMC) fue usado para verificar la asociación. Resultados: En la población general, el “miedo a lastimarse” (89,5%) y la “falta de habilidades” (82,1%) eran, en este orden, las razones más frecuentes como barreras auto-percibidas de la práctica de AF. El grupo de mujeres mostró una asociación protectora en relación con las barreras “falta de tiempo” (OR = 0,53 IC95% 0,47-0,60), “influencia social” (OR = 0,67 IC95% 0,60-0,75), “falta de energía” (OR = 0,54 IC95% 0,49-0,61), “falta de voluntad” (OR = 0,57 IC95% 0,51-0,64), “falta de habilidades” (OR = 0,76 IC95% 0,66-0,87) y “falta de recursos” (OR = 0,79 IC95% 0,71-0,89). Esta observación también aparece en el grupo de edades comprendidas entre los 20 y 23 años en la barrera “influencia social” (OR = 0,83 IC95% 0,74-0,94), y en los mayores a 23 años (OR = 0,86 IC95% 0,74-0,99) en la barrera “falta de energía”. Conclusión: Se encontró una importante prevalencia en la percepción de las barreras para cesar la práctica de AF. Estos resultados pueden servir de referencia para las acciones específicas para promover la AF y la salud en universitarios de Colombia.

  17. Alexithymia influences brain activation during emotion perception but not regulation.

    Science.gov (United States)

    van der Velde, Jorien; Gromann, Paula M; Swart, Marte; Wiersma, Durk; de Haan, Lieuwe; Bruggeman, Richard; Krabbendam, Lydia; Aleman, André

    2015-02-01

    Alexithymia is a psychological construct that can be divided into a cognitive and affective dimension. The cognitive dimension is characterized by difficulties in identifying, verbalizing and analysing feelings. The affective dimension comprises reduced levels of emotional experience and imagination. Alexithymia is widely regarded to arise from an impairment of emotion regulation. This is the first functional magnetic resonance imaging (fMRI) study to critically evaluate this by investigating the neural correlates of emotion regulation as a function of alexithymia levels. The aim of the current study was to investigate the neural correlates underlying the two alexithymia dimensions during emotion perception and emotion regulation. Using fMRI, we scanned 51 healthy subjects while viewing, reappraising or suppressing negative emotional pictures. The results support the idea that cognitive alexithymia, but not affective alexithymia, is associated with lower activation in emotional attention and recognition networks during emotion perception. However, in contrast with several theories, no alexithymia-related differences were found during emotion regulation (neither reappraisal nor suppression). These findings suggest that alexithymia may result from an early emotion processing deficit rather than compromised frontal circuits subserving higher-order emotion regulation processes.

  18. Neuronal activity-induced regulation of Lingo-1.

    Science.gov (United States)

    Trifunovski, Alexandra; Josephson, Anna; Ringman, Andreas; Brené, Stefan; Spenger, Christian; Olson, Lars

    2004-10-25

    Axonal regeneration after injury can be limited in the adult CNS by the presence of inhibitory proteins such as Nogo. Nogo binds to a receptor complex that consists of Nogo receptor (NgR), p75NTR, and Lingo-1. Nogo binding activates RhoA, which inhibits axonal outgrowth. Here we assessed Lingo-1 and NgR mRNA levels after delivery of BDNF into the rat hippocampal formation, Lingo-1 mRNA levels in rats subjected to kainic acid (KA) and running in running wheels. Lingo-1 mRNA was not changed by running. However, we found that Lingo-1 mRNA was strongly up-regulated while NgR mRNA was down-regulated in the dentate gyrus in both the BDNF and the KA experiments. Our data demonstrate inverse regulation of NgR and Lingo-1 in these situations, suggesting that Lingo-1 up-regulation is one characteristic of activity-induced neural plasticity responses.

  19. Commission for Energy regulation (CRE) - Activity report June 2007

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2007 activity report of CRE. Content: A - Towards a single European energy market: Birth of a single European energy market (Origins of Europe of Energy, Emergence of a European energy policy); Main European Community guiding lines (European governance as regards energy, Guiding principles for the internal energy market); European Community activities (European Commission reports, Electricity and gas Regional Initiatives); Organisation and coordination of European regulators (Joint organisation of European regulators, CRE's relations with European Community institutions); CRE's European activities (Regional integration of gas markets, Regional integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, CRE's other European activities); B - CRE action at national level: Grids/networks and infrastructures (General information, Electricity grids, Regulation of gas networks and infrastructures); Markets (Changes in the regulatory and legislative contexts of electricity and natural gas markets, Electricity markets

  20. Anti-inflammatory and Intestinal Barrier-protective Activities of Commensal Lactobacilli and Bifidobacteria in Thoroughbreds: Role of Probiotics in Diarrhea Prevention in Neonatal Thoroughbreds.

    Science.gov (United States)

    Tanabe, Soichi; Suzuki, Takuya; Wasano, Yuichiro; Nakajima, Fumihiko; Kawasaki, Hiroshi; Tsuda, Tomonori; Nagamine, Natsuko; Tsurumachi, Takashi; Sugaya, Kiyoshi; Akita, Hiroaki; Takagi, Misako; Takagi, Kunihiko; Inoue, Yoshinobu; Asai, Yo; Morita, Hidetoshi

    2014-01-01

    We previously isolated the commensal bacteria lactobacilli and bifidobacteria from the Thoroughbred intestine and prepared the horse probiotics LacFi(TM), consisting of Lactobacillus ruminis KK14, L. equi KK 15, L. reuteri KK18, L. johnsonii KK21, and Bifidobacterium boum HU. Here, we found that the five LacFi(TM) constituent strains remarkably suppressed pro-inflammatory interleukin-17 production in mouse splenocytes stimulated with interleukin-6 and transforming growth factor-β. The protective effects of the probiotic on impaired intestinal barrier function were evaluated in Caco-2 cells treated with tumor necrosis factor-α. Evaluation of transepithelial resistance showed that all the strains exhibited intestinal barrier protective activity, with significant suppression of barrier impairment by L. reuteri KK18. The LacFi(TM) constituent strains were detected in neonatal LacFi(TM)-administered Thoroughbred feces using polymerase chain reaction denaturing gradient gel electrophoresis and culture methods. These five strains were found to be the predominant lactobacilli and bifidobacteria in the intestinal microbiota of LacFi(TM)-administered Thoroughbreds. Administration of LacFi(TM) to neonatal Thoroughbreds decreased diarrhea incidence from 75.9% in the control group (n=29 neonatal Thoroughbreds) to 30.7% in the LacFi(TM)-administered group (n=101 neonatal Thoroughbreds) immediately after birth to 20 weeks after birth. LacFi(TM) treatment also prevented diarrhea especially at and around 4 weeks and from 10 to 16 weeks. The duration of diarrhea was also shorter in the probiotics-administered group (7.4 ± 0.8 days) than in the control group (14.0 ± 3.2 days). These results indicate that the LacFi(TM) probiotics regulates intestinal function and contributes to diarrhea prevention.

  1. Regulation of burstiness by network-driven activation

    CERN Document Server

    García-Pérez, Guillermo; Serrano, M Ángeles

    2014-01-01

    We prove that complex networks of interactions have the capacity to regulate and buffer unpredictable fluctuations in production events. We show that non-bursty network-driven activation dynamics can effectively regulate the level of burstiness in the production of nodes, which can be enhanced or reduced. Burstiness can be induced even when the endogenous inter-event time distribution of nodes' production is non-bursty. We found that hubs tend to be less controllable than low degree nodes, which are more susceptible to the networked regulatory effects. Our results have important implications for the analysis and engineering of bursty activity in a range of systems, from telecommunication networks to transcription and translation of genes into proteins in cells.

  2. Shape regulation generates elastic interaction between active force dipoles

    CERN Document Server

    Golkov, Roman

    2016-01-01

    The organization of live cells to tissues is associated with the mechanical interaction between cells, which is mediated through their mechanical environment. We model live cells as spherical active force dipoles surrounded by an infinite elastic matrix, and analytically evaluate their elastic interaction energy for different scenarios of their regulatory behavior. For purely dilational eigenstrains the elastic interaction energy between any two bodies vanishes. We identify mechanical interactions between active cells applying non isotropic displacements with a regulation mechanism designed so that they will preserve their spherical shape. We express the resultant non-isotropic deformation field by a multipole expansion in terms of spherical harmonics. Mechanical self-regulation of live cells is not fully understood, and we compare homeostatic (set point) force applied by the cells on their environment versus homeostatic displacements on their surface. By including or excluding the first term of the expansion...

  3. Epidermal Growth Factor and Intestinal Barrier Function

    Directory of Open Access Journals (Sweden)

    Xiaopeng Tang

    2016-01-01

    Full Text Available Epidermal growth factor (EGF is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health.

  4. Activated dynamics in dense fluids of attractive nonspherical particles. II. Elasticity, barriers, relaxation, fragility, and self-diffusion.

    Science.gov (United States)

    Tripathy, Mukta; Schweizer, Kenneth S

    2011-04-01

    In paper II of this series we apply the center-of-mass version of Nonlinear Langevin Equation theory to study how short-range attractive interactions influence the elastic shear modulus, transient localization length, activated dynamics, and kinetic arrest of a variety of nonspherical particle dense fluids (and the spherical analog) as a function of volume fraction and attraction strength. The activation barrier (roughly the natural logarithm of the dimensionless relaxation time) is predicted to be a rich function of particle shape, volume fraction, and attraction strength, and the dynamic fragility varies significantly with particle shape. At fixed volume fraction, the barrier grows in a parabolic manner with inverse temperature nondimensionalized by an onset value, analogous to what has been established for thermal glass-forming liquids. Kinetic arrest boundaries lie at significantly higher volume fractions and attraction strengths relative to their dynamic crossover analogs, but their particle shape dependence remains the same. A limited universality of barrier heights is found based on the concept of an effective mean-square confining force. The mean hopping time and self-diffusion constant in the attractive glass region of the nonequilibrium phase diagram is predicted to vary nonmonotonically with attraction strength or inverse temperature, qualitatively consistent with recent computer simulations and colloid experiments.

  5. Historical changes in the Mississippi-Alabama barrier islands and the roles of extreme storms, sea level, and human activities

    Science.gov (United States)

    Morton, Robert A.

    2007-01-01

    westward sediment transport by alongshore currents, and Cat Island is being reshaped as it adjusts to post-formation changes in wave and current patterns associated with deposition of the St. Bernard lobe of the Mississippi delta. The principal causes of barrier island land loss are frequent intense storms, a relative rise in sea level, and a deficit in the sediment budget. The only factor that has a historical trend that coincides with the progressive increase in rates of land loss is the progressive reduction in sand supply associated with nearly simultaneous deepening of channels dredged across the outer bars of the three tidal inlets maintained for deep-draft shipping. Neither rates of relative sea level rise nor storm parameters have long-term historical rends that match the increased rates of land loss since the mid 1800s. The historical rates of relative sea level rise in the northern Gulf of Mexico have been relatively constant and storm frequencies and intensities occur in multidecal cycles. However, the most recent land loss accelerations likely related to the increased storm activity since 1995. Considering the predicted trends for storms and sea level related to global warming, it is clear that the barrier islands will continue to lose land area at a rapid rate without a reversal in trend of at least one of the causal factors. The reduction in sand supply related to disruption of the alongshore sediment transport system is the only factor contributing to land loss that can be managed directly. This can be accomplished by placing dredged material so that the adjacent barrier island shores revive it for island nourishment and rebuilding.

  6. A Rewriting Framework and Logic for Activities Subject to Regulations

    Science.gov (United States)

    2015-02-28

    Lincoln, N. Martı́-Oliet, J. Meseguer, and C. Talcott. All About Maude: A High-Performance Logical Framework. Springer , 2007. R. Corin, S. Etalle, P. H...Under consideration for publication in Math. Struct. in Comp. Science A Rewriting Framework and Logic for Activities Subject to Regulations M A X K A...whenever applied. We present a formal semantics of our model based on focused proofs of linear logic with definitions. We also determine the

  7. Harvester ants use interactions to regulate forager activation and availability.

    Science.gov (United States)

    Pinter-Wollman, Noa; Bala, Ashwin; Merrell, Andrew; Queirolo, Jovel; Stumpe, Martin C; Holmes, Susan; Gordon, Deborah M

    2013-07-01

    Social groups balance flexibility and robustness in their collective response to environmental changes using feedback between behavioural processes that operate at different timescales. Here we examine how behavioural processes operating at two timescales regulate the foraging activity of colonies of the harvester ant, Pogonomyrmex barbatus, allowing them to balance their response to food availability and predation. Previous work showed that the rate at which foragers return to the nest with food influences the rate at which foragers leave the nest. To investigate how interactions inside the nest link the rates of returning and outgoing foragers, we observed outgoing foragers inside the nest in field colonies using a novel observation method. We found that the interaction rate experienced by outgoing foragers inside the nest corresponded to forager return rate, and that the interactions of outgoing foragers were spatially clustered. Activation of a forager occurred on the timescale of seconds: a forager left the nest 3-8 s after a substantial increase in interactions with returning foragers. The availability of outgoing foragers to become activated was adjusted on the timescale of minutes: when forager return was interrupted for more than 4-5 min, available foragers waiting near the nest entrance went deeper into the nest. Thus, forager activation and forager availability both increased with the rate at which foragers returned to the nest. This process was checked by negative feedback between forager activation and forager availability. Regulation of foraging activation on the timescale of seconds provides flexibility in response to fluctuations in food abundance, whereas regulation of forager availability on the timescale of minutes provides robustness in response to sustained disturbance such as predation.

  8. PLAP-1/Asporin Positively Regulates FGF-2 Activity.

    Science.gov (United States)

    Awata, T; Yamada, S; Tsushima, K; Sakashita, H; Yamaba, S; Kajikawa, T; Yamashita, M; Takedachi, M; Yanagita, M; Kitamura, M; Murakami, S

    2015-10-01

    PLAP-1 is an extracellular matrix protein that is predominantly expressed in the periodontal ligament within periodontal tissue. It was previously revealed that PLAP-1 negatively regulates bone morphogenetic protein 2 and transforming growth factor β activity through direct interactions. However, the interaction between PLAP-1 and other growth factors has not been defined. Here, we revealed that PLAP-1 positively regulates the activity of fibroblast growth factor 2 (FGF-2), a critical growth factor in tissue homeostasis and repair. In this study, we isolated mouse embryonic fibroblasts (MEFs) from Plap-1(-/-) mice generated in our laboratory. Interestingly, Plap-1(-/-) MEFs exhibited enhanced responses to bone morphogenetic protein 2 but defective responses to FGF-2, and Plap-1 transfection into Plap-1(-/-) MEFs rescued these defective responses. In addition, binding assays revealed that PLAP-1 promotes FGF-2-FGF receptor 1 (FGFR1) complex formation by direct binding to FGF-2. Immunocytochemistry analyses revealed colocalization of PLAP-1 and FGF-2 in wild-type MEFs and reduced colocalization of FGF-2 and FGFR1 in Plap-1(-/-) MEFs compared with wild-type MEFs. Taken together, PLAP-1 positively regulates FGF-2 activity through a direct interaction. Extracellular matrix-growth factor interactions have considerable effects; thus, this approach may be useful in several regenerative medicine applications.

  9. Length regulation of active biopolymers by molecular motors.

    Science.gov (United States)

    Johann, Denis; Erlenkämper, Christoph; Kruse, Karsten

    2012-06-22

    For biopolymers like cytoskeletal actin filaments and microtubules, assembly and disassembly are inherently dissipative processes. Molecular motors can affect the rates of subunit removal at filament ends. We introduce a driven lattice-gas model to study the effects of motor-induced depolymerization on the length of active biopolymers and find that increasing motor activity sharpens unimodal steady-state length distributions. Furthermore, for sufficiently fast moving motors, the relative width of the length distribution is determined only by the attachment rate of motors. Our results show how established molecular processes can be used to robustly regulate the size of cytoskeletal structures like mitotic spindles.

  10. Regulation of eNOS enzyme activity by posttranslational modification.

    Science.gov (United States)

    Heiss, Elke H; Dirsch, Verena M

    2014-01-01

    The regulation of endothelial NO synthase (eNOS) employs multiple different cellular control mechanisms impinging on level and activity of the enzyme. This review aims at summarizing the current knowledge on the posttranslational modifications of eNOS, including acylation, nitrosylation, phosphorylation, acetylation, glycosylation and glutathionylation. Sites, mediators and impact on enzyme localization and activity of the single modifications will be discussed. Moreover, interdependence, cooperativity and competition between the different posttranslational modifications will be elaborated with special emphasis on the susceptibility of eNOS to metabolic cues.

  11. Raf activation is regulated by tyrosine 510 phosphorylation in Drosophila.

    Directory of Open Access Journals (Sweden)

    Fan Xia

    2008-05-01

    Full Text Available The proto-oncoprotein Raf is pivotal for mitogen-activated protein kinase (MAPK signaling, and its aberrant activation has been implicated in multiple human cancers. However, the precise molecular mechanism of Raf activation, especially for B-Raf, remains unresolved. By genetic and biochemical studies, we demonstrate that phosphorylation of tyrosine 510 is essential for activation of Drosophila Raf (Draf, which is an ortholog of mammalian B-Raf. Y510 of Draf is phosphorylated by the c-src homolog Src64B. Acidic substitution of Y510 promotes and phenylalanine substitution impairs Draf activation without affecting its enzymatic activity, suggesting that Y510 plays a purely regulatory role. We further show that Y510 regulates Draf activation by affecting the autoinhibitory interaction between the N- and C-terminal fragments of the protein. Finally, we show that Src64B is required for Draf activation in several developmental processes. Together, these results suggest a novel mechanism of Raf activation via Src-mediated tyrosine phosphorylation. Since Y510 is a conserved residue in the kinase domain of all Raf proteins, this mechanism is likely evolutionarily conserved.

  12. Self-regulation of turbulence in low rotation DIII-D QH-mode with an oscillating transport barrier

    Science.gov (United States)

    Barada, Kshitish; Rhodes, T. L.; Burrell, K. H.; Zeng, L.; Chen, Xi

    2016-10-01

    We present observations of turbulence and flow shear limit cycle oscillations (LCOs) in wide pedestal QH-mode DIII-D tokamak plasmas that are consistent with turbulence self-regulation. In this low input torque regime, both edge harmonic oscillations (EHOs) and ELMs are absent. LCOs of ExB velocity shear and ñ present predator-prey like behavior in these fully developed QH-mode plasmas. During these limit cycle oscillations, the ExB poloidal flows possess a long-range toroidal correlation consistent with turbulence generated zonal flow activity. Further, these limit cycle oscillations are observed in a broad range of edge parameters including ne, Te, floor Langmuir probe ion saturation current, and radial electric field Er. TRANSP calculations of transport indicate little change between the EHO and LCO wide pedestal phases. These observations are consistent with LCO driven transport that may play a role in maintaining the profiles below ELM threshold in the EHO-free steady state wide pedestal QH-mode regime. Work supported by the US DOE under DE-FG02-08ER54984 and DE-FC02-04ER54698.

  13. "My hair or my health:" Overcoming barriers to physical activity in African American women with a focus on hairstyle-related factors.

    Science.gov (United States)

    Huebschmann, Amy G; Campbell, Lucille Johnson; Brown, Candace S; Dunn, Andrea L

    2016-01-01

    Physical activity disparities among African American (AA) women may be related to sociocultural barriers, including difficulties with restyling hair after exercise. We sought to identify physical activity barriers and facilitators in AA women with a focus on sociocultural factors related to hairstyle maintenance. Participants (n = 51) were AA women aged 19-73 years who completed valid surveys and participated in structured focus groups, stratified by age and physical activity levels, from November 2012 to February 2013. The Constant Comparison method was used to develop qualitative themes for barriers and facilitators. The most frequently reported general physical activity barrier among exercisers was "lack of money" (27%) and among non-exercisers was "lack of self-discipline" (57%). A hairstyle-related barrier of "sweating out my hairstyle" was reported by 7% of exercisers and 29% of non-exercisers. This hairstyle-related barrier included the need for extra time and money to restyle hair due to perspiration. Hairstyle-related facilitators included: prioritizing health over hairstyle and high self-efficacy to restyle hair after perspiration. Participants were interested in resources to simplify hairstyle maintenance. AA women whose hairstyle is affected by perspiration may avoid physical activity due to time and financial burdens. Increasing self-efficacy to restyle hair after perspiration may help to overcome this barrier.

  14. ATPase activity of the cystic fibrosis transmembrane conductance regulator.

    Science.gov (United States)

    Li, C; Ramjeesingh, M; Wang, W; Garami, E; Hewryk, M; Lee, D; Rommens, J M; Galley, K; Bear, C E

    1996-11-08

    The gene mutated in cystic fibrosis codes for the cystic fibrosis transmembrane conductance regulator (CFTR), a cyclic AMP-activated chloride channel thought to be critical for salt and water transport by epithelial cells. Plausible models exist to describe a role for ATP hydrolysis in CFTR channel activity; however, biochemical evidence that CFTR possesses intrinsic ATPase activity is lacking. In this study, we report the first measurements of the rate of ATP hydrolysis by purified, reconstituted CFTR. The mutation CFTRG551D resides within a motif conserved in many nucleotidases and is known to cause severe human disease. Following reconstitution the mutant protein exhibited both defective ATP hydrolysis and channel gating, providing direct evidence that CFTR utilizes ATP to gate its channel activity.

  15. Implement Obligations Seriously, Enjoy Rights Fully Make Active Countermeasure to the Barrier of Foreign Technology Trade

    Institute of Scientific and Technical Information of China (English)

    Li Changjiang

    2007-01-01

    @@ December 11th, 2006 is the fifth anniversary of China's entry into WTO. Over the past five years, what AQSIQ has done in implementing the obligations and enjoying the rights as a member of WTO? How's the performance? Facing with the current complicated barrier of technology trade worldwide, how will China reply to it? For these questions, reporters have made a special interview with Li Changjiang, Minister of AQSIQ.

  16. Activism on rifapentine pricing: removing cost barriers to improve the uptake of tuberculosis research innovations

    OpenAIRE

    Deluca, A; Frick, M; Lessem, E; Kanouse, J.; Wegener, D.; Mingote, L. Ruiz

    2014-01-01

    As recent advances have been made in developing tools to fight tuberculosis (TB), there is also a trend towards increasing advocacy by the civil society for TB research and access. One recent successful effort to increase access to treatment options for TB involved a collaborative effort to identify the need for and barriers to the use of rifapentine (RPT) use in the United States. Survey responses confirmed the under-utilization of RPT: 82% of survey respondents selected cost as a significan...

  17. Polyphenol-Rich Propolis Extracts Strengthen Intestinal Barrier Function by Activating AMPK and ERK Signaling

    OpenAIRE

    Kai Wang; Xiaolu Jin; Yifan Chen; Zehe Song; Xiasen Jiang; Fuliang Hu; Conlon, Michael A.; Topping, David L.

    2016-01-01

    Propolis has abundant polyphenolic constituents and is used widely as a health/functional food. Here, we investigated the effects of polyphenol-rich propolis extracts (PPE) on intestinal barrier function in human intestinal epithelial Caco-2 cells, as well as in rats. In Caco-2 cells, PPE increased transepithelial electrical resistance and decreased lucifer yellow flux. PPE-treated cells showed increased expression of the tight junction (TJ) loci occludin and zona occludens (ZO)-1. Confocal m...

  18. Methamphetamine Regulation of Firing Activity of Dopamine Neurons.

    Science.gov (United States)

    Lin, Min; Sambo, Danielle; Khoshbouei, Habibeh

    2016-10-05

    Methamphetamine (METH) is a substrate for the dopamine transporter that increases extracellular dopamine levels by competing with dopamine uptake and increasing reverse transport of dopamine via the transporter. METH has also been shown to alter the excitability of dopamine neurons. The mechanism of METH regulation of the intrinsic firing behaviors of dopamine neurons is less understood. Here we identified an unexpected and unique property of METH on the regulation of firing activity of mouse dopamine neurons. METH produced a transient augmentation of spontaneous spike activity of midbrain dopamine neurons that was followed by a progressive reduction of spontaneous spike activity. Inspection of action potential morphology revealed that METH increased the half-width and produced larger coefficients of variation of the interspike interval, suggesting that METH exposure affected the activity of voltage-dependent potassium channels in these neurons. Since METH has been shown to affect Ca(2+) homeostasis, the unexpected findings that METH broadened the action potential and decreased the amplitude of afterhyperpolarization led us to ask whether METH alters the activity of Ca(2+)-activated potassium (BK) channels. First, we identified BK channels in dopamine neurons by their voltage dependence and their response to a BK channel blocker or opener. While METH suppressed the amplitude of BK channel-mediated unitary currents, the BK channel opener NS1619 attenuated the effects of METH on action potential broadening, afterhyperpolarization repression, and spontaneous spike activity reduction. Live-cell total internal reflection fluorescence microscopy, electrophysiology, and biochemical analysis suggest METH exposure decreased the activity of BK channels by decreasing BK-α subunit levels at the plasma membrane.

  19. Physical activity in patients with type 2 diabetes and hypertension – insights into motivations and barriers from the MOBILE study

    Directory of Open Access Journals (Sweden)

    Duclos M

    2015-06-01

    Full Text Available Martine Duclos,1,2 Sylvie Dejager,3,4 Nicolas Postel-Vinay,5 Sylvie di Nicola,6 Stéphane Quéré,7 Béatrice Fiquet4,5 1Department of Sport Medicine and Functional Explorations, University-Hospital (CHU, G Montpied Hospital; INRA, UNH, CRNH Auvergne, 2Nutrition Department, University of Auvergne, Clermont-Ferrand, Auvergne, 3Department of Endocrinology and Metabolism, La Pitié-Salpétrière Hospital, Paris, 4Clinical and Scientific Affairs, Novartis Pharma SAS, Rueil-Malmaison, 5Department of Hypertension, Georges Pompidou European Hospital, Paris, 6Biostatistics, Inferential, Paris, 7Biostatistics, Novartis Pharma SAS, Rueil-Malmaison, France Background: Although physical activity (PA is key in the management of type 2 diabetes (T2DM and hypertension, it is difficult to implement in practice. Methods: Cross-sectional, observational study. Participating physicians were asked to recruit two active and four inactive patients, screened with the Ricci-Gagnon (RG self-questionnaire (active if score ≥16. Patients subsequently completed the International Physical Activity Questionnaire. The objective was to assess the achievement of individualized glycated hemoglobin and blood pressure goals (<140/90 mmHg in the active vs inactive cohort, to explore the correlates for meeting both targets by multivariate analysis, and to examine the barriers and motivations to engage in PA. Results: About 1,766 patients were analyzed. Active (n=628 vs inactive (n=1,138 patients were more often male, younger, less obese, had shorter durations of diabetes, fewer complications and other health issues, such as osteoarticular disorders (P<0.001 for all. Their diabetes and hypertension control was better and obtained despite a lower treatment burden. The biggest difference in PA between the active vs inactive patients was the percentage who declared engaging in regular leisure-type PA (97.9% vs 9.6%, also reflected in the percentage with vigorous activities in

  20. A cross-sectional study on patterns, motivating factors and barriers for physical activity among undergraduate medical students

    Directory of Open Access Journals (Sweden)

    HN Harsha Kumar

    2014-10-01

    Full Text Available Introduction: There is little published information exploring the perceptions and physical activity patterns among undergraduate medical students in our country. So this study was conducted with the following objectives: 1. To assess the perceptions about knowledge regarding physical activities among undergraduate medical students; 2. To assess their self-reported physical activity practices. Materials and Methods: This cross sectional study was conducted in Kasturba Medical College, Mangalore from 12 th to 30 th April, 2012. A total number of 427 students were chosen at by using the formula for infinite population. Tools: 1. A semi-structured questionnaire to know perceptions, barriers, and practices about physical activity; 2. Physical activity was assessed using International Physical Activity Questionnaire (IPAQ. Analysis was done by using SPSS version 11. Significance of differences across various levels of physical activity between different age-groups and gender were made by chi square test. Results: 376 students participated. Majority of them had high physical activity (54.75%. Knowledge was poor about prevention of diabetes (68.9%, stroke (61.6%, and osteoporosis (33.8%. Majority (82.4% of them perceived health-related benefits of physical activity as motivating factors rather than prevention of chronic noncommunicable diseases. Most of them (72.3% have enrolled in life style modification activities like yoga, going to gymnasium, etc. Conclusion: Most of the students fall into moderate physical activity group. Health-related benefits were the driving force for doing physical activity.

  1. Down-regulation of pigment epithelium-derived factor in uveitic lesion associates with focal vascular endothelial growth factor expression and breakdown of the blood-retinal barrier.

    Science.gov (United States)

    Deeg, Cornelia A; Altmann, Frank; Hauck, Stefanie M; Schoeffmann, Stephanie; Amann, Barbara; Stangassinger, Manfred; Ueffing, Marius

    2007-05-01

    Spontaneous equine recurrent uveitis (ERU) is an incurable autoimmune disease affecting the eye. Identifying biological markers or pathways associated with this disease may allow the understanding of its pathogenesis at a molecular level. The vitreous is the body fluid closest to the disease-affected tissue and possibly also an effector of pathological processes relevant for ERU. Surgical removal of vitreous leads to cessation of relapses in spontaneous uveitis of both man and horse, therefore vitreous composites are likely to contribute to disease progression. Uveitic vitreous is likely to contain potential biomarkers in relatively undiluted quantities. With the goal to identify these markers, we systematically compared vitreous from healthy and disease-affected eyes by proteomic profiling. Nine differentially expressed proteins were identified, that are functionally related to immune response, inflammation, and maintenance of the blood-retinal barrier. One of these, pigment epithelium-derived factor, a protein involved in maintaining a proper blood-retina barrier as well as protecting from neoangiogenesis was additionally found to be down-regulated within uveitic retinal lesions whereas, conversely, vascular endothelial growth factor was found to be up-regulated at these sites. Together, these changes point to as of yet undiscovered biological pathways involved in the pathogenesis of this autoimmune disease.

  2. USP21 regulates Hippo pathway activity by mediating MARK protein turnover

    DEFF Research Database (Denmark)

    Nguyen, Thanh Hung; Kugler, Jan-Michael; Loya, Anand Chainsukh

    2017-01-01

    The Hippo pathway, which acts to repress the activity of YAP and TAZ trancriptional co-activators, serve as a barrier for oncogenic transformation. Unlike other oncoproteins, YAP and TAZ are rarely activated by mutations or amplified in cancer. However, elevated YAP/TAZ activity is frequently obs...

  3. Barriers, facilitators and preferences for the physical activity of school children. Rationale and methods of a mixed study

    Directory of Open Access Journals (Sweden)

    Martínez-Andrés María

    2012-09-01

    Full Text Available Abstract Background Physical activity interventions in schools environment seem to have shown some effectiveness in the control of the current obesity epidemic in children. However the complexity of behaviors and the diversity of influences related to this problem suggest that we urgently need new lines of insight about how to support comprehensive population strategies of intervention. The aim of this study was to know the perceptions of the children from Cuenca, about their environmental barriers, facilitators and preferences for physical activity. Methods/Design We used a mixed-method design by combining two qualitative methods (analysis of individual drawings and focus groups together with the quantitative measurement of physical activity through accelerometers, in a theoretical sample of 121 children aged 9 and 11 years of schools in the province of Cuenca, Spain. Conclusions Mixed-method study is an appropriate strategy to know the perceptions of children about barriers and facilitators for physical activity, using both qualitative methods for a deeply understanding of their points of view, and quantitative methods for triangulate the discourse of participants with empirical data. We consider that this is an innovative approach that could provide knowledges for the development of more effective interventions to prevent childhood overweight.

  4. Hsp90 regulation of fibroblast activation in pulmonary fibrosis

    Science.gov (United States)

    Sontake, Vishwaraj; Wang, Yunguan; Kasam, Rajesh K.; Sinner, Debora; Reddy, Geereddy B.; Naren, Anjaparavanda P.; McCormack, Francis X.; Jegga, Anil G.; Madala, Satish K.

    2017-01-01

    Idiopathic pulmonary fibrosis (IPF) is a severe fibrotic lung disease associated with fibroblast activation that includes excessive proliferation, tissue invasiveness, myofibroblast transformation, and extracellular matrix (ECM) production. To identify inhibitors that can attenuate fibroblast activation, we queried IPF gene signatures against a library of small-molecule-induced gene-expression profiles and identified Hsp90 inhibitors as potential therapeutic agents that can suppress fibroblast activation in IPF. Although Hsp90 is a molecular chaperone that regulates multiple processes involved in fibroblast activation, it has not been previously proposed as a molecular target in IPF. Here, we found elevated Hsp90 staining in lung biopsies of patients with IPF. Notably, fibroblasts isolated from fibrotic lesions showed heightened Hsp90 ATPase activity compared with normal fibroblasts. 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), a small-molecule inhibitor of Hsp90 ATPase activity, attenuated fibroblast activation and also TGF-β–driven effects on fibroblast to myofibroblast transformation. The loss of the Hsp90AB, but not the Hsp90AA isoform, resulted in reduced fibroblast proliferation, myofibroblast transformation, and ECM production. Finally, in vivo therapy with 17-AAG attenuated progression of established and ongoing fibrosis in a mouse model of pulmonary fibrosis, suggesting that targeting Hsp90 represents an effective strategy for the treatment of fibrotic lung disease. PMID:28239659

  5. Commission for Energy regulation (CRE) - Activity report june 2006

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2006 activity report of CRE. Content: A - Opening of the electricity and natural gas markets to household consumers on 1 July 2007: CRE at the service of eligible customers (Information for eligible customers, Improved knowledge of non-household customers); Monitoring of the non-discrimination, transparency and independence of system operators (Drafting and distribution of codes of good conduct for system operators, The necessary improvement of system operator independence); Preparing the practical methods of opening: GTE 2007 and GTG 2007 (The necessary simplification of relations between operators and customers, Achieving a greater level of consumer information and protection, The clearly defined stages of the 'customer pathway', Profiling and settlement mechanisms: turning experience feedback from 2004 to good account); Persisting uncertainties and hurdles (The need for a suitable regulatory and legislative platform, Hurdles to the opening of the household market); B - Regulation of the natural gas market: The gas market in the European context (Increasing weight of

  6. Understanding the complex interplay of barriers to physical activity amongst black and minority ethnic groups in the United Kingdom:a qualitative synthesis using meta-ethnography

    OpenAIRE

    Koshoedo, Sejlo A.; Paul-Ebhohimhen, Virginia A; Jepson, Ruth G.; Watson, Margaret C

    2015-01-01

    Background To conduct a meta-ethnographic analysis of qualitative studies to identify barriers to Black and Minority Ethnic (BME) individuals engaging in physical activity in the UK context. Methods A qualitative synthesis using meta-ethnographic methods to synthesis studies of barriers to engaging in physical activity among BME groups in the UK. A comprehensive search strategy of multiple databases was employed to identify qualitative research studies published up to October 2012. The eleven...

  7. Active pre-filters for dc/dc Boost regulators

    Directory of Open Access Journals (Sweden)

    Carlos Andrés Ramos-Paja

    2014-07-01

    Full Text Available This paper proposes an active pre-filter to mitigate the current harmonics generated by classical dc/dc Boost regulators, which generate current ripples proportional to the duty cycle. Therefore, high output voltage conditions, i.e., high voltage conversion ratios, produce high current harmonics that must be filtered to avoid damage or source losses. Traditionally, these current components are filtered using electrolytic capacitors, which introduce reliability problems because of their high failure rate. The solution introduced in this paper instead uses a dc/dc converter based on the parallel connection of the Boost canonical cells to filter the current ripples generated by the Boost regulator, improving the system reliability. This solution provides the additional benefits of improving the overall efficiency and the voltage conversion ratio. Finally, the solution is validated with simulations and experimental results.

  8. Epigenetic regulation of hepatic stellate cell activation and liver fibrosis.

    Science.gov (United States)

    El Taghdouini, Adil; van Grunsven, Leo A

    2016-12-01

    Chronic liver injury to hepatocytes or cholangiocytes, when left unmanaged, leads to the development of liver fibrosis, a condition characterized by the excessive intrahepatic deposition of extracellular matrix proteins. Activated hepatic stellate cells constitute the predominant source of extracellular matrix in fibrotic livers and their transition from a quiescent state during fibrogenesis is associated with important alterations in their transcriptional and epigenetic landscape. Areas covered: We briefly describe the processes involved in hepatic stellate cell activation and discuss our current understanding of alterations in the epigenetic landscape, i.e DNA methylation, histone modifications and the functional role of non-coding RNAs that accompany this key event in the development of chronic liver disease. Expert commentary: Although great progress has been made, our understanding of the epigenetic regulation of hepatic stellate cell activation is limited and, thus far, insufficient to allow the development of epigenetic drugs that can selectively interrupt liver fibrosis.

  9. Filaggrin and Skin Barrier Function.

    Science.gov (United States)

    Kezic, Sanja; Jakasa, Ivone

    2016-01-01

    The skin barrier function is greatly dependent on the structure and composition of the uppermost layer of the epidermis, the stratum corneum (SC), which is made up of flattened anucleated cells surrounded by highly organized and continuous lipid matrix. The interior of the corneocytes consists mainly of keratin filaments aggregated by filaggrin (FLG) protein. Next, together with several other proteins, FLG is cross-linked into a mechanically robust cornified cell envelope providing a scaffold for the extracellular lipid matrix. In addition to its role for the SC structural and mechanical integrity, FLG degradation products account in part for the water-holding capacity and maintenance of acidic pH of the SC, both crucial for the epidermal barrier homoeostasis by regulating activity of multiple enzymes that control desquamation, lipid synthesis and inflammation. The major determinant of FLG expression in the skin are loss-of-function mutations in FLG, the strongest genetic risk factor for atopic dermatitis (AD), an inflammatory skin disease characterized by a reduced skin barrier function. The prevalence of FLG mutations varies greatly among different populations and ranges from about 10% in Northern Europeans to less than 1% in the African populations. An impaired skin barrier facilitates absorption of potentially hazardous chemicals, which might cause adverse effects in the skin, such as contact dermatitis, or systemic toxicity after their passage into blood. In another direction, a leaky epidermal barrier will lead to enhanced loss of water from the skin. A recent study has shown that even subtle increase in epidermal water loss in newborns increases the risk for AD. Although there are multiple modes of action by which FLG might affect skin barrier it is still unclear whether and how FLG deficiency leads to the reduced skin barrier function. This chapter summarizes the current knowledge in this field obtained from clinical studies, and animal and in vitro models

  10. A role for VEGFR2 activation in endothelial responses caused by barrier disruptive OxPAPC concentrations.

    Directory of Open Access Journals (Sweden)

    Anna A Birukova

    Full Text Available Oxidation products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine (OxPAPC differentially modulate endothelial cell (EC barrier function in a dose-dependent fashion. Vascular endothelial growth factor receptor-2 (VEGFR2 is involved in the OxPAPC-induced EC inflammatory activation. This study examined a role of VEGFR2 in barrier dysfunction caused by high concentrations of OxPAPC and evaluated downstream signaling mechanisms resulting from the effect of OxPAPC in EC from pulmonary and systemic circulation.EC monolayer permeability in human pulmonary artery endothelial cells (HPAEC and human aortic endothelial cells (HAEC was monitored by changes in transendothelial electrical resistance (TER across EC monolayers. Actin cytoskeleton was examined by immunostaining with Texas Red labeled phalloidin. Phosphorylation of myosin light chains (MLC and VE-Cadherin was examined by Western blot and immunofluorescence techniques. The role of VEGFR2 in OxPAPC-induced permeability and cytoskeletal arrangement were determined using siRNA-induced VEGFR2 knockdown.Low OxPAPC concentrations (5-20 µg/ml induced a barrier protective response in both HPAEC and HAEC, while high OxPAPC concentrations (50-100 µg/ml caused a rapid increase in permeability; actin stress fiber formation and increased MLC phosphorylation were observed as early as 30 min after treatment. VEGFR2 knockdown dramatically decreased the amount of MLC phosphorylation and stress fiber formation caused by high OxPAPC concentrations with modest effects on the amount of VE-cadherin phosphorylation at Y(731. We present evidence that activation of Rho is involved in the OxPAPC/VEGFR2 mechanism of EC permeability induced by high OxPAPC concentrations. Knockdown of VEGFR2 did not rescue the early drop in TER but prevented further development of OxPAPC-induced barrier dysfunction.This study shows that VEGFR2 is involved in the delayed phase of EC barrier dysfunction caused by high Ox

  11. Barriers to Physical Activity in a Population-based Sample of Children and Adolescents in Isfahan, Iran

    Directory of Open Access Journals (Sweden)

    Roya Kelishadi

    2010-01-01

    Full Text Available Objectives: This study was conducted to explore the barriers to physical activity in a representative sample of Iranian children and adolescents.Methods: The studywas conducted in 2007 in urban and rural areas of Isfahan district in Iran. In the qualitative part,we used the grounded theory approach, including semi-structured focus group discussionsand in-depth interviews. The quantitative part comprised 600 randomly selected students.Results: The qualitative study included 34 school students (16 girls, 20 parents (11 mothers and 11 school staff. All students disclosed that studying was a priority.They pointed to lack of safe and easy-access place for physical activity and unsupportive family as the main barriers. Lack of self-confidence and low self-worth were the two other concepts developed in this context.Parents pointed to lack of safe and easy-access place for activity followed by the priority of studying. The concepts derived from interviews with school staff included unhealthy modeling of parents, priority of studying, and inadequate public know-ledge about how to integrate physical activity in routine daily life.The quantitative survey comprised 600 students including 286 (47.8% girls. Parents’ education level had inverse association with children’s physical activity level. Significant inverse associations of self-efficacy and physical activity levels were documented.Conclusions: Increasing the public knowledge about adopting physical activity habits in routinedaily life, informing the families and students about the benefits of physical activity to improvelearning, as well as providing safe places such as using the school facilities in non-school hoursshould be considered in planning effective preventive strategies and interventions.

  12. DUB3 Deubiquitylating Enzymes Regulate Hippo Pathway Activity by Regulating the Stability of ITCH, LATS and AMOT Proteins

    DEFF Research Database (Denmark)

    Nguyen, Thanh Hung; Kugler, Jan-Michael; Cohen, Stephen Michael

    2017-01-01

    /TAZ, is regulated by ubiquitin mediated protein turnover and several ubiquitin ligase complexes have been implicated in human cancer. However, little is known about the deubiquitylating enzymes that counteract these ubiquitin ligases in regulation of the Hippo pathway. Here we identify the DUB3 family...... deubiquitylating enzymes as regulators of Hippo pathway activity. We provide evidence that DUB3 proteins regulate YAP/TAZ activity by controlling the stability of the E3 ligase ITCH, the LATS kinases and the AMOT family proteins. As a novel Hippo pathway regulator, DUB3 has the potential to act a tumor suppressor...

  13. [Polymethoxylated flavonoids activate cystic fibrosis transmembrane conductance regulator chloride channel].

    Science.gov (United States)

    Cao, Huan-Huan; Fang, Fang; Yu, Bo; Luan, Jian; Jiang, Yu; Yang, Hong

    2015-04-25

    Cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent chloride channel, plays key roles in fluid secretion in serous epithelial cells. Previously, we identified two polymethoxylated flavonoids, 3',4',5,5',6,7-hexamethoxyflavone (HMF) and 5-hydroxy-6,7,3',4'-tetramethoxyflavone (HTF) which could potentiate CFTR chloride channel activities. The present study was aimed to investigate the potentiation effects of HMF and HTF on CFTR Cl(-) channel activities by using a cell-based fluorescence assay and the short circuit Ussing chamber assay. The results of cell-based fluorescence assay showed that both HMF and HTF could dose-dependently potentiate CFTR Cl(-) channel activities in rapid and reversible ways, and the activations could be reversed by the CFTR blocker CFTRinh-172. Notably, HMF showed the highest affinity (EC50 = 2 μmol/L) to CFTR protein among the flavonoid CFTR activators identified so far. The activation of CFTR by HMF or HTF was forskolin (FSK) dependent. Both compounds showed additive effect with FSK and 3-Isobutyl-1-methylx (IBMX) in the activation of CFTR, while had no additive effect with genistein (GEN). In ex vivo studies, HMF and HTF could stimulate transepithelial Cl(-) secretion in rat colonic mucosa and enhance fluid secretion in mouse trachea submucosal glands. These results suggest that HMF and HTF may potentiate CFTR Cl(-) channel activities through both elevation of cAMP level and binding to CFTR protein pathways. The results provide new clues in elucidating structure and activity relationship of flavonoid CFTR activators. HMF might be developed as a new drug in the therapy of CFTR-related diseases such as bronchiectasis and habitual constipation.

  14. SPATIAL HETEROGENEITY OF PHOTOSYNTHETIC ACTIVITY WITHIN DISEASED CORALS FROM THE GREAT BARRIER REEF

    DEFF Research Database (Denmark)

    Roff, George; Ulstrup, Karin Elizabeth; Fine, Maoz

    2008-01-01

    Morphological diagnosis and descriptions of seven disease-like syndromes affecting scleractinian corals were characterized from the southern Great Barrier Reef (GBR). Chl a fluorescence of PSII was measured using an Imaging-PAM (pulse amplitude modulated) fluorometer, enabling visualization...... with white patch syndrome appeared to impact primarily on the symbiotic dinoflagellates, as evidenced by declines in minimum fluorescence (F0) and maximum quantum yield (Fv/Fm), with no indication of degeneration in the host tissues. Our results suggest that for the majority of coral syndromes from the GBR......, pathogenesis occurs in the host tissue, while the impact on the zooxanthellae populations residing in affected corals is minimal....

  15. 75 FR 5100 - Agency Information Collection Activities: NAFTA Regulations and Certificate of Origin

    Science.gov (United States)

    2010-02-01

    ... SECURITY Customs and Border Protection Agency Information Collection Activities: NAFTA Regulations and... collection requirement concerning the NAFTA Regulations and Certificate of Origin. This request for comment... CBP is soliciting comments concerning the following information collection: Title: NAFTA Regulations...

  16. The cytoskeletal protein Ndel1 regulates dynamin 2 GTPase activity.

    Directory of Open Access Journals (Sweden)

    Mathieu Chansard

    Full Text Available Cytoskeleton dynamics, membranes trafficking and positioning are essential for the proper functioning of any mammalian cell. The identification of the molecules and mechanisms that allow these cellular processes to interface is vital for understanding cell behaviors. Ndel1, the mammalian homolog of the Aspergillus nidulans NudE, organizes the cytoskeleton and regulates molecular motors, thereby impacting on the positioning of membranes. Hypothetically, Ndel1 can act in concert with enzymes controlling membrane trafficking (vesicle-mediated transport per se, but this idea has never been investigated. We now report that a pool of Ndel1 associates directly with Dynamin 2 (Dyn2, a large cytosolic GTPase involved in the trafficking of the AMPA receptor subunit GluR1. In vitro, Ndel1 enhances Dyn2 GTPase activity in its unassembled and assembled forms, without promoting oligomerization of the enzyme. In cells, gain and loss of function of Ndel1 recapitulate the effects of overexpression of Dyn2 and Dyn2 dominant negative with reduced GTPase activity on the intracellular localization of GluR1, respectively, without affecting the stability of microtubules. Together, these results indicate that Ndel1 regulates Dyn2 GTPase activity and impacts GluR1-containing membranes distribution in a manner reminiscent of Dyn2.

  17. Fbxw7 controls angiogenesis by regulating endothelial Notch activity.

    Directory of Open Access Journals (Sweden)

    Nanae Izumi

    Full Text Available Notch signaling controls fundamental aspects of angiogenic blood vessel growth including the selection of sprouting tip cells, endothelial proliferation and arterial differentiation. The E3 ubiquitin ligase Fbxw7 is part of the SCF protein complex responsible for the polyubiquitination and thereby proteasomal degradation of substrates such as Notch, c-Myc and c-Jun. Here, we show that Fbxw7 is a critical regulator of angiogenesis in the mouse retina and the zebrafish embryonic trunk, which we attribute to its role in the degradation of active Notch. Growth of retinal blood vessel was impaired and the Notch ligand Dll4, which is also a Notch target, upregulated in inducible and endothelial cell-specific Fbxw7(iECKO mutant mice. The stability of the cleaved and active Notch intracellular domain was increased after siRNA knockdown of the E3 ligase in cultured human endothelial cells. Injection of fbxw7 morpholinos interfered with the sprouting of zebrafish intersegmental vessels (ISVs. Arguing strongly that Notch and not other Fbxw7 substrates are primarily responsible for these phenotypes, the genetic inactivation of Notch pathway components reversed the impaired ISV growth in the zebrafish embryo as well as sprouting and proliferation in the mouse retina. Our findings establish that Fbxw7 is a potent positive regulator of angiogenesis that limits the activity of Notch in the endothelium of the growing vasculature.

  18. Negative regulation of lymphocyte activation by the adaptor protein LAX.

    Science.gov (United States)

    Zhu, Minghua; Granillo, Olivia; Wen, Renren; Yang, Kaiyong; Dai, Xuezhi; Wang, Demin; Zhang, Weiguo

    2005-05-01

    The membrane-associated adaptor protein LAX is a linker for activation of T cells (LAT)-like molecule that is expressed in lymphoid tissues. Upon stimulation of T or B cells, it is phosphorylated and interacts with Grb2 and the p85 subunit of PI3K. LAX, however, is not capable of replacing LAT in the TCR signaling pathway. In this study we report that upon T or B cell activation, the LAX protein was up-regulated dramatically. Although disruption of the LAX gene by homologous recombination had no major impact on lymphocyte development, it caused a significant reduction in CD23 expression on mature B cells. Interestingly, naive LAX(-/-) mice had spontaneous germinal center formation. Compared with normal T and B cells, LAX(-/-) T and B cells were hyperresponsive and had enhanced calcium flux, protein tyrosine phosphorylation, MAPK and Akt activation, and cell survival upon engagement of the T or B AgRs. Our data demonstrate that LAX functions as a negative regulator in lymphocyte signaling.

  19. [Vascular endothelial Barrier Function].

    Science.gov (United States)

    Ivanov, A N; Puchinyan, D M; Norkin, I A

    2015-01-01

    Endothelium is an important regulator of selective permeability of the vascular wall for different molecules and cells. This review summarizes current data on endothelial barrier function. Endothelial glycocalyx structure, its function and role in the molecular transport and leukocytes migration across the endothelial barrier are discussed. The mechanisms of transcellular transport of macromolecules and cell migration through endothelial cells are reviewed. Special section of this article addresses the structure and function of tight and adherens endothelial junction, as well as their importance for the regulation of paracellular transport across the endothelial barrier. Particular attention is paid to the signaling mechanism of endothelial barrier function regulation and the factors that influence on the vascular permeability.

  20. Benefits and barriers to physical activity for individuals with disabilities: a social-relational model of disability perspective.

    Science.gov (United States)

    Martin, Jeffrey J

    2013-01-01

    To provide a qualitative overview of selected research on physical activity (PA) engagement by people with physical disabilities (1) from a social relational model perspective. Selected articles that exemplify some of the paradoxes, nuances, contrasting perspectives and complexities of the knowledge base in this area are discussed within a disability studies framework. PA is arguably more important for people with disabilities relative to people without disabilities although they are quite inactive. Individuals who are physically activity enjoy a range of benefits spanning physiological, emotional, cognitive and social categories. Unfortunately many people cannot enjoy the benefits of PA because of the many medical, psychological, social and environmental barriers they face making PA quite difficult. Rehabilitation professionals can provide a better standard of care to clients if they are aware of the benefits and barriers of PA. Rehabilitation professionals should understand behavior change strategies and their application to people with disabilities in order to help their clients initiate and maintain physical activity (PA). Rehabilitation professionals should be aware of how they might convey low PA expectations to their clients and simultaneously understand the unique challenges faced by their clients in attempting to incorporate PA into their lives on a regular basis. Rehabilitation professionals should be familiar with local disability friendly exercise facilities and adapted sport programs in order to steer their clients towards such opportunities.

  1. Validation and divergence of the activation energy barrier crossing transition at the AOT/lecithin reverse micellar interface.

    Science.gov (United States)

    Narayanan, S Shankara; Sinha, Sudarson Sekhar; Sarkar, Rupa; Pal, Samir Kumar

    2008-03-13

    In this report, the validity and divergence of the activation energy barrier crossing model for the bound to free type water transition at the interface of the AOT/lecithin mixed reverse micelle (RM) has been investigated for the first time in a wide range of temperatures by time-resolved solvation of fluorophores. Here, picosecond-resolved solvation dynamics of two fluorescent probes, ANS (1-anilino-8-naphthalenesulfonic acid, ammonium salt) and Coumarin 500 (C-500), in the mixed RM have been carefully examined at 293, 313, 328, and 343 K. Using the dynamic light scattering (DLS) technique, the size of the mixed RMs at different temperatures was found to have an insignificant change. The solvation process at the reverse micellar interface has been found to be the activation energy barrier crossing type, in which interface-bound type water molecules get converted into free type water molecules. The activation energies, Ea, calculated for ANS and C-500 are 7.4 and 3.9 kcal mol(-1), respectively, which are in good agreement with that obtained by molecular dynamics simulation studies. However, deviation from the regular Arrhenius type behavior was observed for ANS around 343 K, which has been attributed to the spatial heterogeneity of the probe environments. Time-resolved fluorescence anisotropy decay of the probes has indicated the existence of the dyes in a range of locations in RM. With the increase in temperature, the overall anisotropy decay becomes faster revealing the lability of the microenvironment at elevated temperatures.

  2. Histamine activates p38 MAP kinase and alters local lamellipodia dynamics, reducing endothelial barrier integrity and eliciting central movement of actin fibers.

    Science.gov (United States)

    Adderley, Shaquria P; Lawrence, Curtis; Madonia, Eyong; Olubadewo, Joseph O; Breslin, Jerome W

    2015-07-01

    The role of the actin cytoskeleton in endothelial barrier function has been debated for nearly four decades. Our previous investigation revealed spontaneous local lamellipodia in confluent endothelial monolayers that appear to increase overlap at intercellular junctions. We tested the hypothesis that the barrier-disrupting agent histamine would reduce local lamellipodia protrusions and investigated the potential involvement of p38 mitogen-activated protein (MAP) kinase activation and actin stress fiber formation. Confluent monolayers of human umbilical vein endothelial cells (HUVEC) expressing green fluorescent protein-actin were studied using time-lapse fluorescence microscopy. The protrusion and withdrawal characteristics of local lamellipodia were assessed before and after addition of histamine. Changes in barrier function were determined using electrical cell-substrate impedance sensing. Histamine initially decreased barrier function, lamellipodia protrusion frequency, and lamellipodia protrusion distance. A longer time for lamellipodia withdrawal and reduced withdrawal distance and velocity accompanied barrier recovery. After barrier recovery, a significant number of cortical fibers migrated centrally, eventually resembling actin stress fibers. The p38 MAP kinase inhibitor SB203580 attenuated the histamine-induced decreases in barrier function and lamellipodia protrusion frequency. SB203580 also inhibited the histamine-induced decreases in withdrawal distance and velocity, and the subsequent actin fiber migration. These data suggest that histamine can reduce local lamellipodia protrusion activity through activation of p38 MAP kinase. The findings also suggest that local lamellipodia have a role in maintaining endothelial barrier integrity. Furthermore, we provide evidence that actin stress fiber formation may be a reaction to, rather than a cause of, reduced endothelial barrier integrity.

  3. Dynamic regulation of Polycomb group activity during plant development.

    Science.gov (United States)

    Bemer, Marian; Grossniklaus, Ueli

    2012-11-01

    Polycomb group (PcG) complexes play important roles in phase transitions and cell fate determination in plants and animals, by epigenetically repressing sets of genes that promote either proliferation or differentiation. The continuous differentiation of new organs in plants, such as leaves or flowers, requires a highly dynamic PcG function, which can be induced, modulated, or repressed when necessary. In this review, we discuss the recent advance in understanding PcG function in plants and focus on the diverse molecular mechanisms that have been described to regulate and counteract PcG activity in Arabidopsis.

  4. How Phosphorylation and ATPase Activity Regulate Anion Flux though the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).

    Science.gov (United States)

    Zwick, Matthias; Esposito, Cinzia; Hellstern, Manuel; Seelig, Anna

    2016-07-08

    The cystic fibrosis transmembrane conductance regulator (CFTR, ABCC7), mutations of which cause cystic fibrosis, belongs to the ATP-binding cassette (ABC) transporter family and works as a channel for small anions, such as chloride and bicarbonate. Anion channel activity is known to depend on phosphorylation by cAMP-dependent protein kinase A (PKA) and CFTR-ATPase activity. Whereas anion channel activity has been extensively investigated, phosphorylation and CFTR-ATPase activity are still poorly understood. Here, we show that the two processes can be measured in a label-free and non-invasive manner in real time in live cells, stably transfected with CFTR. This study reveals three key findings. (i) The major contribution (≥90%) to the total CFTR-related ATP hydrolysis rate is due to phosphorylation by PKA and the minor contribution (≤10%) to CFTR-ATPase activity. (ii) The mutant CFTR-E1371S that is still conductive, but defective in ATP hydrolysis, is not phosphorylated, suggesting that phosphorylation requires a functional nucleotide binding domain and occurs in the post-hydrolysis transition state. (iii) CFTR-ATPase activity is inversely related to CFTR anion flux. The present data are consistent with a model in which CFTR is in a closed conformation with two ATPs bound. The open conformation is induced by ATP hydrolysis and corresponds to the post-hydrolysis transition state that is stabilized by phosphorylation and binding of chloride channel potentiators.

  5. Occludin controls HIV transcription in brain pericytes via regulation of SIRT-1 activation.

    Science.gov (United States)

    Castro, Victor; Bertrand, Luc; Luethen, Mareen; Dabrowski, Sebastian; Lombardi, Jorge; Morgan, Laura; Sharova, Natalia; Stevenson, Mario; Blasig, Ingolf E; Toborek, Michal

    2016-03-01

    HIV invades the brain early after infection; however, its interactions with the cells of the blood-brain barrier (BBB) remain poorly understood. Our goal was to evaluate the role of occludin, one of the tight junction proteins that regulate BBB functions in HIV infection of BBB pericytes. We provide evidence that occludin levels largely control the metabolic responses of human pericytes to HIV. Occludin in BBB pericytes decreased by 10% during the first 48 h after HIV infection, correlating with increased nuclear translocation of the gene repressor C-terminal-binding protein (CtBP)-1 and NFκB-p65 activation. These changes were associated with decreased expression and activation of the class III histone deacetylase sirtuin (SIRT)-1. Occludin levels recovered 96 h after infection, restoring SIRT-1 and reducing HIV transcription to 20% of its highest values. We characterized occludin biochemically as a novel NADH oxidase that controls the expression and activation of SIRT-1. The inverse correlation between occludin and HIV transcription was then replicated in human primary macrophages and differentiated monocytic U937 cells, in which occludin silencing resulted in 75 and 250% increased viral transcription, respectively. Our work shows that occludin has previously unsuspected metabolic properties and is a target of HIV infection, opening the possibility of designing novel pharmacological approaches to control HIV transcription.

  6. Calculating Transition Energy Barriers and Characterizing Activation States for Steps of Fusion.

    Science.gov (United States)

    Ryham, Rolf J; Klotz, Thomas S; Yao, Lihan; Cohen, Fredric S

    2016-03-08

    We use continuum mechanics to calculate an entire least energy pathway of membrane fusion, from stalk formation, to pore creation, and through fusion pore enlargement. The model assumes that each structure in the pathway is axially symmetric. The static continuum stalk structure agrees quantitatively with experimental stalk architecture. Calculations show that in a stalk, the distal monolayer is stretched and the stored stretching energy is significantly less than the tilt energy of an unstretched distal monolayer. The string method is used to determine the energy of the transition barriers that separate intermediate states and the dynamics of two bilayers as they pass through them. Hemifusion requires a small amount of energy independently of lipid composition, while direct transition from a stalk to a fusion pore without a hemifusion intermediate is highly improbable. Hemifusion diaphragm expansion is spontaneous for distal monolayers containing at least two lipid components, given sufficiently negative diaphragm spontaneous curvature. Conversely, diaphragms formed from single-component distal monolayers do not expand without the continual injection of energy. We identify a diaphragm radius, below which central pore expansion is spontaneous. For larger diaphragms, prior studies have shown that pore expansion is not axisymmetric, and here our calculations supply an upper bound for the energy of the barrier against pore formation. The major energy-requiring deformations in the steps of fusion are: widening of a hydrophobic fissure in bilayers for stalk formation, splay within the expanding hemifusion diaphragm, and fissure widening initiating pore formation in a hemifusion diaphragm.

  7. Activism on rifapentine pricing: removing cost barriers to improve the uptake of tuberculosis research innovations.

    Science.gov (United States)

    DeLuca, A; Frick, M; Lessem, E; Kanouse, J; Wegener, D; Mingote, L Ruiz

    2014-12-21

    As recent advances have been made in developing tools to fight tuberculosis (TB), there is also a trend towards increasing advocacy by the civil society for TB research and access. One recent successful effort to increase access to treatment options for TB involved a collaborative effort to identify the need for and barriers to the use of rifapentine (RPT) use in the United States. Survey responses confirmed the under-utilization of RPT: 82% of survey respondents selected cost as a significant or potential barrier to use. Survey results provided data to support a year-long advocacy campaign urging the drug company Sanofi to lower the price of RPT. This campaign was based on a common evidence base built in part by the stakeholders themselves. After multiple engagements with communities and providers, Sanofi US announced on 12 December 2013 that they would drop the price of RPT to US$32 per blister pack of 32 tablets for US public health programs. While further work remains to secure access to RPT in the United States and worldwide, the lowering of the price of RPT reflects the positive impact that collaborative advocacy can accomplish, and sets an example for other drug companies to follow.

  8. Regulation of dopamine transporter activity by carboxypeptidase E

    Directory of Open Access Journals (Sweden)

    Zhang Heping

    2009-05-01

    Full Text Available Abstract Background The dopamine transporter (DAT plays a critical role in terminating the action of dopamine by rapid reuptake into the presynaptic neuron. Previous studies have revealed that the DAT carboxyl terminus (DAT-CT can directly interact with other cellular proteins and regulate DAT function and trafficking. Results Here, we have identified that carboxypeptidase E (CPE, a prohormone processing exopeptidase and sorting receptor for the regulated secretory pathway, interacts with the DAT-CT and affects DAT function. Mammalian cell lines coexpressing CPE and DAT exhibited increased DAT-mediated dopamine uptake activity compared to cells expressing DAT alone. Moreover, coexpression of an interfering DAT-CT minigene inhibited the effects of CPE on DAT. Functional changes caused by CPE could be attributed to enhanced DAT expression and subsequent increase in DAT cell surface localization, due to decreased DAT degradation. In addition, CPE association could reduce the phosphorylation state of DAT on serine residues, potentially leading to reduced internalization, thus stabilizing plasmalemmal DAT localization. Conclusion Taken together, our results reveal a novel role for CPE in the regulation of DAT trafficking and DAT-mediated DA uptake, which may provide a novel target in the treatment of dopamine-governed diseases such as drug addiction and obesity.

  9. SUMOylation of Argonaute-2 regulates RNA interference activity

    Science.gov (United States)

    Josa-Prado, Fernando; Henley, Jeremy M.; Wilkinson, Kevin A.

    2015-01-01

    Post-translational modification of substrate proteins by small ubiquitin-like modifier (SUMO) regulates a vast array of cellular processes. SUMOylation occurs through three sequential enzymatic steps termed E1, E2 and E3. Substrate selection can be determined through interactions between the target protein and the SUMO E2 conjugating enzyme Ubc9 and specificity can be enhanced by substrate interactions with E3 ligase enzymes. We used the putative substrate recognition (PINIT) domain from the SUMO E3 PIAS3 as bait to identify potential SUMO substrates. One protein identified was Argonaute-2 (Ago2), which mediates RNA-induced gene silencing through binding small RNAs and promoting degradation of complimentary target mRNAs. We show that Ago2 can be SUMOylated in mammalian cells by both SUMO1 and SUMO2. SUMOylation occurs primarily at K402, and mutation of the SUMO consensus site surrounding this lysine reduces Ago2-mediated siRNA-induced silencing in a luciferase-based reporter assay. These results identify SUMOylation as a potential regulator of Ago2 activity and open new avenues for research into the mechanisms underlying the regulation of RNA-induced gene silencing. PMID:26188511

  10. Erk1 positively regulates osteoclast differentiation and bone resorptive activity.

    Directory of Open Access Journals (Sweden)

    Yongzheng He

    Full Text Available The extracellular signal-regulated kinases (ERK1 and 2 are widely-expressed and they modulate proliferation, survival, differentiation, and protein synthesis in multiple cell lineages. Altered ERK1/2 signaling is found in several genetic diseases with skeletal phenotypes, including Noonan syndrome, Neurofibromatosis type 1, and Cardio-facio-cutaneous syndrome, suggesting that MEK-ERK signals regulate human skeletal development. Here, we examine the consequence of Erk1 and Erk2 disruption in multiple functions of osteoclasts, specialized macrophage/monocyte lineage-derived cells that resorb bone. We demonstrate that Erk1 positively regulates osteoclast development and bone resorptive activity, as genetic disruption of Erk1 reduced osteoclast progenitor cell numbers, compromised pit formation, and diminished M-CSF-mediated adhesion and migration. Moreover, WT mice reconstituted long-term with Erk1(-/- bone marrow mononuclear cells (BMMNCs demonstrated increased bone mineral density as compared to recipients transplanted with WT and Erk2(-/- BMMNCs, implicating marrow autonomous, Erk1-dependent osteoclast function. These data demonstrate Erk1 plays an important role in osteoclast functions while providing rationale for the development of Erk1-specific inhibitors for experimental investigation and/or therapeutic modulation of aberrant osteoclast function.

  11. Expressions of peroxisome proliferator-activated receptors (PPARs) are directly influenced by permeability barrier abrogation and inflammatory cytokines and depressed PPARα modulates expressions of chemokines and epidermal differentiation-related molecules in keratinocytes.

    Science.gov (United States)

    Adachi, Yasuko; Hatano, Yutaka; Sakai, Takashi; Fujiwara, Sakuhei

    2013-09-01

    Previous studies have demonstrated that the activation of peroxisome proliferator-activated receptors (PPARs) not only has positive effects on permeability barrier homoeostasis but also has anti-inflammatory effects by an as yet unknown mechanism. Reduced expression of PPARα in lesion of human atopic dermatitis (AD) and in epidermis of murine AD-like dermatitis has been demonstrated. This study revealed that expression of PPARα alone among PPARs (α, β/δ and γ) was suppressed by both permeability barrier abrogation and additional existence of Th2 cytokine in cultured normal human keratinocytes. In addition, expressions of transglutaminase 1 and loricrin and those of thymus and activation-related chemokine and regulated on activation normal T-cell expressed in cultured human keratinocytes were reduced and enhanced, respectively, by transfection with siRNA for PPARα. In conclusion, depressed PPARα in keratinocytes might be involved in a relationship between permeability barrier abrogation and allergic inflammation and could be a therapeutic target which accounts for both the aspects in AD. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Herbal medicines that benefit epidermal permeability barrier function

    Directory of Open Access Journals (Sweden)

    Lizhi Hu

    2015-06-01

    Full Text Available Epidermal permeability barrier function plays a critical role in regulating cutaneous functions. Hence, researchers have been searching for effective and affordable regimens to enhance epidermal permeability barrier function. In addition to topical stratum corneum lipids, peroxisome proliferator-activated receptor, and liver X receptor ligands, herbal medicines have been proven to benefit epidermal permeability barrier function in both normal and diseased skin, including atopic dermatitis, glucocorticoid-induced skin damage, and UVB-damaged skin. The potential mechanisms by which herbal medicines improve the permeability barrier include stimulation of epidermal differentiation, lipid production, antimicrobial peptide expression, and antioxidation. Therefore, utilization of herbal medicines could be a valuable alternative approach to enhance epidermal permeability barrier function in order to prevent and/or treat skin disorders associated with permeability barrier abnormalities.

  13. Estrogen receptor β regulates endometriotic cell survival through serum and glucocorticoid-regulated kinase activation.

    Science.gov (United States)

    Monsivais, Diana; Dyson, Matthew T; Yin, Ping; Navarro, Antonia; Coon, John S; Pavone, Mary Ellen; Bulun, Serdar E

    2016-05-01

    To determine the expression and biological roles of serum and glucocorticoid-regulated kinase (SGK1) in tissues and cells from patients with endometriosis and from healthy control subjects. Case-control. University research setting. Premenopausal women. Endometriotic tissues were obtained from women with ovarian endometriosis, and normal endometrial tissues were obtained from women undergoing hysterectomy for benign conditions. Expression levels of SGK1, the role of SGK1 in endometriosis pathology, and regulation of SGK1 by estrogen receptor (ER) β. Transcript and protein levels of SGK1 were significantly higher in endometriotic tissues and cells compared with normal endometrium. SGK1 mRNA and protein levels were stimulated by E2, by the ERβ-selective agonist diarylpropionitrile, and by prostaglandin E2. SGK1 was transcriptionally regulated by ERβ based on small interfering RNA knockdown and chromatin immunoprecipitation of ERβ followed by quantitative polymerase chain reaction. SGK1 knockdown led to increased cleavage of poly(ADP-ribose) polymerase, and SGK1 activation was correlated with the phosphorylation of FOXO3a, a proapoptotic factor. ERβ leads to SGK1 overexpression in endometriosis, which contributes to the survival of endometriotic lesions through inhibition of apoptosis. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  14. Assessing Barriers and Motivators for Use of a Trail for Active Transportation in a College Town

    OpenAIRE

    FitzPatrick, Timothy Michael

    2017-01-01

    A high amount of the US population is not physically active, contributing to rates of heart disease and obesity. One strategy to increase physical activity is to use more active transportation, defined as walking or biking for transit. Besides increasing physical activity levels, active transportation can provide other benefits such as decreased air pollution from cars. College campuses provide opportunities for active transportation as most residences are close to campus. Therefore, we exami...

  15. Barriers and facilitators to participation in workplace health promotion (WHP) activities: results from a cross-sectional survey of public-sector employees in Tasmania, Australia.

    Science.gov (United States)

    Kilpatrick, Michelle; Blizzard, Leigh; Sanderson, Kristy; Teale, Brook; Jose, Kim; Venn, Alison

    2017-01-19

    Issue addressed: Workplaces are promising settings for health promotion, yet employee participation in workplace health promotion (WHP) activities is often low or variable. This study explored facilitating factors and barriers associated with participation in WHP activities that formed part of a comprehensive WHP initiative run within the Tasmanian State Service (TSS) between 2009 and 2013.Methods: TSS employee (n=3228) completed surveys in 2013. Data included sociodemographic characteristics, employee-perceived availability of WHP activities, employee-reported participation in WHP activities, and facilitators and barriers to participation. Ordinal log-link regression was used in cross-sectional analyses.Results: Significant associations were found for all facilitating factors and participation. Respondents who felt their organisation placed a high priority on WHP, who believed that management supported participation or that the activities could improve their health were more likely to participate. Time- and health-related barriers were associated with participation in fewer activities. All associations were independent of age, sex, work schedule and employee-perceived availability of programs. Part-time and shift-work patterns, and location of activities were additionally identified barriers.Conclusion: Facilitating factors relating to implementation, peer and environmental support, were associated with participation in more types of activities, time- and health-related barriers were associated with less participation.So what?: Large and diverse organisations should ensure WHP efforts have manager support and adopt flexible approaches to maximise employee engagement.

  16. ROMK1 channel activity is regulated by monoubiquitination.

    Science.gov (United States)

    Lin, Dao-Hong; Sterling, Hyacinth; Wang, Zhijian; Babilonia, Elisa; Yang, Baofeng; Dong, Ke; Hebert, Steven C; Giebisch, Gerhard; Wang, Wen-Hui

    2005-03-22

    The ubiquitination of proteins can signal their degradation, modify their activity or target them to specific membranes or cellular organelles. Here, we show that monoubiquitination regulates the plasma membrane abundance and function of the potassium channel, ROMK. Immunoprecipitation of proteins obtained from renal cortex and outer medulla with ROMK antibody revealed that this channel was monoubiquitinated. To determine the ubiquitin binding site on ROMK1, all intracellular lysine (Lys) residues of ROMK1 were individually mutated to arginine (Arg), and a two-electrode voltage clamp was used to measure the ROMK1 channel activity in Xenopus oocytes. ROMK1 channel activity increased from 8.1 to 27.2 microA only when Lys-22 was mutated to Arg. Furthermore, Western blotting failed to detect the ubiquitinated ROMK1 in oocytes injected with R1K22R. Patch-clamp experiments showed that biophysical properties of R1K22R were identical to those of wild-type ROMK1. Although total protein expression levels of GFP-ROMK1 and GFP-R1K22R in oocytes were similar, confocal microscopy showed that the surface fluorescence intensity in oocytes injected with GFP-R1K22R was higher than that of GFP-ROMK1. In addition, biotin labeling of ROMK1 and R1K22R proteins expressed in HEK293 cells showed increased surface expression of the Lys-22 mutant channel. Finally, expression of R1K22R in COS7 cells significantly stimulated the surface expression of ROMK1. We conclude that ROMK1 can be monoubiquitinated and that Lys-22 is an ubiquitin-binding site. Thus, monoubiquitination of ROMK1 regulates channel activity by reducing the surface expression of channel protein. This finding implicates the linking of a single ubiquitin molecule to channels as an important posttranslational regulatory signal.

  17. Perceived barriers and facilitators to increasing physical activity among people with musculoskeletal disorders: a qualitative investigation to inform intervention development

    Directory of Open Access Journals (Sweden)

    McPhail SM

    2014-12-01

    Full Text Available Steven M McPhail,1,2 Mandy Schippers,1,2 Alison L Marshall,1 Monique Waite,1,2 Pim Kuipers2,3 1Institute of Health and Biomedical Innovation and School of Public Health and Social Work, Queensland University of Technology, 2Centre for Functioning and Health Research, Metro South Health, 3Griffith Health Institute and School of Human Services and Social Work, Griffith University, Brisbane, QLD, Australia Purpose: Musculoskeletal conditions can impair people’s ability to undertake physical activity as they age. The purpose of this qualitative study was to investigate perceived barriers and facilitators to undertaking physical activity reported by patients accessing ambulatory hospital clinics for musculoskeletal disorders.Patients and methods: A questionnaire with open-ended items was administered to patients (n=217, 73.3% of 296 eligible from three clinics providing ambulatory services for nonsurgical treatment of musculoskeletal disorders. The survey included questions to capture the clinical and demographic characteristics of the sample. It also comprised two open-ended questions requiring qualitative responses. The first asked the participant to describe factors that made physical activity more difficult, and the second asked which factors made it easier for them to be physically active. Participants’ responses to the two open-ended questions were read, coded, and thematically analyzed independently by two researchers, with a third researcher available to arbitrate any unresolved disagreement. Results: The mean (standard deviation age of participants was 53 (15 years; n=113 (52.1% were male. A total of 112 (51.6% participants reported having three or more health conditions; n=140 (64.5% were classified as overweight or obese. Five overarching themes describing perceived barriers for undertaking physical activity were “health conditions”, “time restrictions”, “poor physical condition”, “emotional, social, and psychological

  18. The regulation of ant colony foraging activity without spatial information.

    Science.gov (United States)

    Prabhakar, Balaji; Dektar, Katherine N; Gordon, Deborah M

    2012-01-01

    Many dynamical networks, such as the ones that produce the collective behavior of social insects, operate without any central control, instead arising from local interactions among individuals. A well-studied example is the formation of recruitment trails in ant colonies, but many ant species do not use pheromone trails. We present a model of the regulation of foraging by harvester ant (Pogonomyrmex barbatus) colonies. This species forages for scattered seeds that one ant can retrieve on its own, so there is no need for spatial information such as pheromone trails that lead ants to specific locations. Previous work shows that colony foraging activity, the rate at which ants go out to search individually for seeds, is regulated in response to current food availability throughout the colony's foraging area. Ants use the rate of brief antennal contacts inside the nest between foragers returning with food and outgoing foragers available to leave the nest on the next foraging trip. Here we present a feedback-based algorithm that captures the main features of data from field experiments in which the rate of returning foragers was manipulated. The algorithm draws on our finding that the distribution of intervals between successive ants returning to the nest is a Poisson process. We fitted the parameter that estimates the effect of each returning forager on the rate at which outgoing foragers leave the nest. We found that correlations between observed rates of returning foragers and simulated rates of outgoing foragers, using our model, were similar to those in the data. Our simple stochastic model shows how the regulation of ant colony foraging can operate without spatial information, describing a process at the level of individual ants that predicts the overall foraging activity of the colony.

  19. Regulated O2 activation in flavin-dependent monooxygenases.

    Science.gov (United States)

    Frederick, Rosanne E; Mayfield, Jeffery A; DuBois, Jennifer L

    2011-08-17

    Flavin-dependent monooxygenases (FMOs) are involved in important biosynthetic pathways in diverse organisms, including production of the siderophores used for the import and storage of essential iron in serious pathogens. We have shown that the FMO from Aspergillus fumigatus, an ornithine monooxygenase (Af-OMO), is mechanistically similar to its well-studied distant homologues from mammalian liver. The latter are highly promiscuous in their choice of substrates, while Af-OMO is unusually specific. This presents a puzzle: how do Af-OMO and other FMOs of the biosynthetic classes achieve such specificity? We have discovered substantial enhancement in the rate of O(2) activation in Af-OMO in the presence of L-arginine, which acts as a small molecule regulator. Such protein-level regulation could help explain how this and related biosynthetic FMOs manage to couple O(2) activation and substrate hydroxylation to each other and to the appropriate cellular conditions. Given the essentiality of Fe to Af and the avirulence of the Af-OMO gene knock out, inhibitors of Af-OMO are likely to be drug targets against this medically intractable pathogen.

  20. Intrinsic activation barriers and coadsorption effects for reactions on metal surfaces: unified formalism within the UBI-QEP approach

    Science.gov (United States)

    Sellers, Harrell; Shustorovich, Evgeny

    2002-04-01

    We present a unified formulation of the unity bond index-quadratic exponential potential method (UBI-QEP, formerly known as the BOC-MP method) of determining metal surface reaction energetics. We give a unified treatment of enthalpies and intrinsic activation barriers for dissociation and recombination reactions as particular cases of disproportionation reactions. We discuss numerous examples of elementary reactions, which form a database for various reaction mechanisms. We start with the zero coverage limit and then focus on coadsorption effects on reaction energetics on monometallic and bimetallic (alloy) surfaces. We consider first the full treatment and then develop the “uniform scaling” approximation, with guidelines (and examples) where it may be efficiently used. We provide tables of numerical values covering most of practically important cases of coadsorption effects on fcc(1 1 1) and fcc(1 0 0) surfaces, which allow one to easily estimate coverage effects on activation barriers by simple interpolation. We also clarify the nature of basic UBI-QEP parameters and correlation between local and global adsorbate coverage. These developments, illustrated by various examples, make applications of the UBI-QEP method much easier for practitioners, particularly those who have no UBI-model computer program and make calculations by hand.

  1. The component content of active particles in a plasma-chemical reactor based on volume barrier discharge

    Science.gov (United States)

    Soloshenko, I. A.; Tsiolko, V. V.; Pogulay, S. S.; Terent'yeva, A. G.; Bazhenov, V. Yu; Shchedrin, A. I.; Ryabtsev, A. V.; Kuzmichev, A. I.

    2007-02-01

    In this paper the results of theoretical and experimental studies of the component content of active particles formed in a plasma-chemical reactor composed of a multiple-cell generator of active particles, based on volume barrier discharge, and a working chamber are presented. For calculation of the content of uncharged plasma components an approach is proposed which is based on averaging of the power introduced over the entire volume. Advantages of such an approach lie in an absence of fitting parameters, such as the dimensions of microdischarges, their surface density and rate of breakdown. The calculation and the experiment were accomplished with the use of dry air (20% relative humidity) as the plasma generating medium. Concentrations of O3, HNO3, HNO2, N2 O5 and NO3 were measured experimentally in the discharge volume and working chamber for the residence time of particles on a discharge of 0.3 s and more and discharge specific power of 1.5 W cm-3. It has been determined that the best agreement between the calculation and the experiment occurs at calculated gas medium temperatures in the discharge plasma of about 400-425 K, which correspond to the experimentally measured rotational temperature of nitrogen. In most cases the calculated concentrations of O3, HNO3, HNO2, N2O5 and NO3 for the barrier discharge and the working chamber are in fairly good agreement with the respective measured values.

  2. PAHs in the Great Barrier Reef Lagoon reach potentially toxic levels from coal port activities

    Science.gov (United States)

    Burns, Kathryn A.

    2014-05-01

    In view of the controversy over expanding the coastal coal ports bordering the Great Barrier Reef (GBR) Lagoon and the World Heritage Area, I re-evaluated the data published in Burns and Brinkman (2011). I used the US EPA procedures for the determination of Equilibrium Partitioning Sediment Benchmarks (ESBs) for the protection of benthic organisms (Hansen et al., 2003), and the new proposed ANZECC/ARMCANZ (2013) sediment quality guidelines (Simpson et al., 2013) and determined that the coastal sediments offshore from the Hay Point coal terminal and suspended sediments caught in sediment traps inshore and at the offshore coral reefs contained levels of PAHs that approach the estimates for toxicity to benthic and water column organisms. This result is discussed in relation to risks posed to the GBR ecosystem by the port practices and the imminent expansion of the Abbott Point, Hay Point and other coal terminals.

  3. Osteoblast differentiation and migration are regulated by dynamin GTPase activity.

    Science.gov (United States)

    Eleniste, Pierre P; Huang, Su; Wayakanon, Kornchanok; Largura, Heather W; Bruzzaniti, Angela

    2014-01-01

    Bone formation is controlled by osteoblasts, but the signaling proteins that control osteoblast differentiation and function are still unclear. We examined if the dynamin GTPase, which is associated with actin remodeling and migration in other cells, plays a role in osteoblast differentiation and migration. Dynamin mRNA was expressed in primary osteoblasts throughout differentiation (0-21 days). However, alkaline phosphatase (ALP) activity, a marker of osteoblast differentiation, was decreased in osteoblasts over-expressing dynamin. Conversely, ALP activity was increased following shRNA-mediated knockdown of dynamin and in osteoblasts treated with the dynamin inhibitor, dynasore. Dynasore also reduced c-fos and osterix expression, markers of early osteoblasts, suggesting a role for dynamin in pre-osteoblast to osteoblast differentiation. Since dynamin GTPase activity is regulated by tyrosine phosphorylation, we examined the mechanism of dynamin dephosphorylation in osteoblasts. Dynamin formed a protein complex with the tyrosine phosphatase PTP-PEST and inhibition of phosphatase activity increased the level of phosphorylated dynamin. Further, PTP-PEST blocked the Src-mediated increase in the phosphorylation and GTPase activity of wild-type dynamin but not the phosphorylation mutant dynY231F/Y597F. Although ALP activity was increased in osteoblasts expressing GTPase-defective dynK44A, and to a lesser extent dynY231F/Y597F, osteoblast migration was significantly inhibited by dynK44A and dynY231F/Y597F. These studies demonstrate a novel role for dynamin GTPase activity and phosphorylation in osteoblast differentiation and migration, which may be important for bone formation.

  4. Promoting Physical Activity for Students with Autism Spectrum Disorder: Barriers, Benefits, and Strategies for Success

    Science.gov (United States)

    Menear, Kristi S.; Neumeier, William H.

    2015-01-01

    Many students with autism spectrum disorder (ASD) fall short of the recommended physical activity levels and experience challenges in physical activity and physical education settings. This article reviews factors that can improve the physical activity statistics of students with ASD, outlines the researched benefits of physical activity for…

  5. Promoting Physical Activity for Students with Autism Spectrum Disorder: Barriers, Benefits, and Strategies for Success

    Science.gov (United States)

    Menear, Kristi S.; Neumeier, William H.

    2015-01-01

    Many students with autism spectrum disorder (ASD) fall short of the recommended physical activity levels and experience challenges in physical activity and physical education settings. This article reviews factors that can improve the physical activity statistics of students with ASD, outlines the researched benefits of physical activity for…

  6. Activating transcription factor 4 regulates osteoclast differentiation in mice

    Science.gov (United States)

    Cao, Huiling; Yu, Shibing; Yao, Zhi; Galson, Deborah L.; Jiang, Yu; Zhang, Xiaoyan; Fan, Jie; Lu, Binfeng; Guan, Youfei; Luo, Min; Lai, Yumei; Zhu, Yibei; Kurihara, Noriyoshi; Patrene, Kenneth; Roodman, G. David; Xiao, Guozhi

    2010-01-01

    Activating transcription factor 4 (ATF4) is a critical transcription factor for osteoblast (OBL) function and bone formation; however, a direct role in osteoclasts (OCLs) has not been established. Here, we targeted expression of ATF4 to the OCL lineage using the Trap promoter or through deletion of Atf4 in mice. OCL differentiation was drastically decreased in Atf4–/– bone marrow monocyte (BMM) cultures and bones. Coculture of Atf4–/– BMMs with WT OBLs or a high concentration of RANKL failed to restore the OCL differentiation defect. Conversely, Trap-Atf4-tg mice displayed severe osteopenia with dramatically increased osteoclastogenesis and bone resorption. We further showed that ATF4 was an upstream activator of the critical transcription factor Nfatc1 and was critical for RANKL activation of multiple MAPK pathways in OCL progenitors. Furthermore, ATF4 was crucial for M-CSF induction of RANK expression on BMMs, and lack of ATF4 caused a shift in OCL precursors to macrophages. Finally, ATF4 was largely modulated by M-CSF signaling and the PI3K/AKT pathways in BMMs. These results demonstrate that ATF4 plays a direct role in regulating OCL differentiation and suggest that it may be a therapeutic target for treating bone diseases associated with increased OCL activity. PMID:20628199

  7. GARP regulates the bioavailability and activation of TGFβ.

    Science.gov (United States)

    Wang, Rui; Zhu, Jianghai; Dong, Xianchi; Shi, Minlong; Lu, Chafen; Springer, Timothy A

    2012-03-01

    Glycoprotein-A repetitions predominant protein (GARP) associates with latent transforming growth factor-β (proTGFβ) on the surface of T regulatory cells and platelets; however, whether GARP functions in latent TGFβ activation and the structural basis of coassociation remain unknown. We find that Cys-192 and Cys-331 of GARP disulfide link to the TGFβ1 prodomain and that GARP with C192A and C331A mutations can also noncovalently associate with proTGFβ1. Noncovalent association is sufficiently strong for GARP to outcompete latent TGFβ-binding protein for binding to proTGFβ1. Association between GARP and proTGFβ1 prevents the secretion of TGFβ1. Integrin α(V)β(6) and to a lesser extent α(V)β(8) are able to activate TGFβ from the GARP-proTGFβ1 complex. Activation requires the RGD motif of latent TGFβ, disulfide linkage between GARP and latent TGFβ, and membrane association of GARP. Our results show that GARP is a latent TGFβ-binding protein that functions in regulating the bioavailability and activation of TGFβ.

  8. Physical Activity Plays an Important Role in Body Weight Regulation

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Chaput

    2011-01-01

    Full Text Available Emerging literature highlights the need to incorporate physical activity into every strategy intended to prevent weight gain as well as to maintain weight loss over time. Furthermore, physical activity should be part of any plan to lose weight. The stimulus of exercise provides valuable metabolic adaptations that improve energy and macronutrient balance regulation. A tight coupling between energy intake and energy expenditure has been documented at high levels of physical exercise, suggesting that exercise may improve appetite control. The regular practice of physical activity has also been reported to reduce the risk of stress-induced weight gain. A more personalized approach is recommended when planning exercise programs in a clinical weight loss setting in order to limit the compensatory changes associated to exercise-induced weight loss. With modern environment promoting overeating and sedentary behavior, there is an urgent need for a concerted action including legislative measures to promote healthy active living in order to curb the current epidemic of chronic diseases.

  9. Activating transcription factor 4 regulates osteoclast differentiation in mice.

    Science.gov (United States)

    Cao, Huiling; Yu, Shibing; Yao, Zhi; Galson, Deborah L; Jiang, Yu; Zhang, Xiaoyan; Fan, Jie; Lu, Binfeng; Guan, Youfei; Luo, Min; Lai, Yumei; Zhu, Yibei; Kurihara, Noriyoshi; Patrene, Kenneth; Roodman, G David; Xiao, Guozhi

    2010-08-01

    Activating transcription factor 4 (ATF4) is a critical transcription factor for osteoblast (OBL) function and bone formation; however, a direct role in osteoclasts (OCLs) has not been established. Here, we targeted expression of ATF4 to the OCL lineage using the Trap promoter or through deletion of Atf4 in mice. OCL differentiation was drastically decreased in Atf4-/- bone marrow monocyte (BMM) cultures and bones. Coculture of Atf4-/- BMMs with WT OBLs or a high concentration of RANKL failed to restore the OCL differentiation defect. Conversely, Trap-Atf4-tg mice displayed severe osteopenia with dramatically increased osteoclastogenesis and bone resorption. We further showed that ATF4 was an upstream activator of the critical transcription factor Nfatc1 and was critical for RANKL activation of multiple MAPK pathways in OCL progenitors. Furthermore, ATF4 was crucial for M-CSF induction of RANK expression on BMMs, and lack of ATF4 caused a shift in OCL precursors to macrophages. Finally, ATF4 was largely modulated by M-CSF signaling and the PI3K/AKT pathways in BMMs. These results demonstrate that ATF4 plays a direct role in regulating OCL differentiation and suggest that it may be a therapeutic target for treating bone diseases associated with increased OCL activity.

  10. Neuroligin-1 links neuronal activity to sleep-wake regulation

    Science.gov (United States)

    El Helou, Janine; Bélanger-Nelson, Erika; Freyburger, Marlène; Dorsaz, Stéphane; Curie, Thomas; La Spada, Francesco; Gaudreault, Pierre-Olivier; Beaumont, Éric; Pouliot, Philippe; Lesage, Frédéric; Frank, Marcos G.; Franken, Paul; Mongrain, Valérie

    2013-01-01

    Maintaining wakefulness is associated with a progressive increase in the need for sleep. This phenomenon has been linked to changes in synaptic function. The synaptic adhesion molecule Neuroligin-1 (NLG1) controls the activity and synaptic localization of N-methyl-d-aspartate receptors, which activity is impaired by prolonged wakefulness. We here highlight that this pathway may underlie both the adverse effects of sleep loss on cognition and the subsequent changes in cortical synchrony. We found that the expression of specific Nlg1 transcript variants is changed by sleep deprivation in three mouse strains. These observations were associated with strain-specific changes in synaptic NLG1 protein content. Importantly, we showed that Nlg1 knockout mice are not able to sustain wakefulness and spend more time in nonrapid eye movement sleep than wild-type mice. These changes occurred with modifications in waking quality as exemplified by low theta/alpha activity during wakefulness and poor preference for social novelty, as well as altered delta synchrony during sleep. Finally, we identified a transcriptional pathway that could underlie the sleep/wake-dependent changes in Nlg1 expression and that involves clock transcription factors. We thus suggest that NLG1 is an element that contributes to the coupling of neuronal activity to sleep/wake regulation. PMID:23716671

  11. Antitumorigenic effect of atmospheric-pressure dielectric barrier discharge on human colorectal cancer cells via regulation of Sp1 transcription factor

    Science.gov (United States)

    Han, Duksun; Cho, Jin Hyoung; Lee, Ra Ham; Bang, Woong; Park, Kyungho; Kim, Minseok S.; Shim, Jung-Hyun; Chae, Jung-Il; Moon, Se Youn

    2017-02-01

    Human colorectal cancer cell lines (HT29 and HCT116) were exposed to dielectric barrier discharge (DBD) plasma at atmospheric pressure to investigate the anticancer capacity of the plasma. The dose- and time-dependent effects of DBDP on cell viability, regulation of transcription factor Sp1, cell-cycle analysis, and colony formation were investigated by means of MTS assay, DAPI staining, propidium iodide staining, annexin V-FITC staining, Western blot analysis, RT-PCR analysis, fluorescence microscopy, and anchorage-independent cell transformation assay. By increasing the duration of plasma dose times, significant reductions in the levels of both Sp1 protein and Sp1 mRNA were observed in both cell lines. Also, expression of negative regulators related to the cell cycle (such as p53, p21, and p27) was increased and of the positive regulator cyclin D1 was decreased, indicating that the plasma treatment led to apoptosis and cell-cycle arrest. In addition, the sizes and quantities of colony formation were significantly suppressed even though two cancer promoters, such as TPA and epidermal growth factor, accompanied the plasma treatment. Thus, plasma treatment inhibited cell viability and colony formation by suppressing Sp1, which induced apoptosis and cell-cycle arrest in these two human colorectal cancer cell lines.

  12. Aryl hydrocarbon receptor-mediated up-regulation of ATP-driven xenobiotic efflux transporters at the blood-brain barrier.

    Science.gov (United States)

    Wang, Xueqian; Hawkins, Brian T; Miller, David S

    2011-02-01

    Many widespread and persistent organic pollutants, e.g., 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), activate the aryl hydrocarbon receptor (AhR), causing it to translocate to the cell nucleus, where it transactivates target genes. AhR's ability to target the blood-brain barrier is essentially unexplored. We show here that exposing isolated rat brain capillaries to 0.05-0.5 nM TCDD roughly doubled transport activity and protein expression of P-glycoprotein, an ATP-driven drug efflux pump and a critical determinant of drug entry into the CNS. These effects were abolished by actinomycin D or cycloheximide or by the AhR antagonists resveratrol and α-naphthoflavone. Brain capillaries from TCDD-dosed rats (1-5 μg/kg, i.p.) exhibited increased transport activity and protein expression of 3 xenobiotic efflux pumps, P-glycoprotein, multidrug resistance-associated protein 2, and breast cancer resistance polypeptide, as well as expression of Cyp1a1 and Cyp1b1, both AhR target genes. Consistent with increased P-glycoprotein expression in capillaries from TCDD-dosed rats, in situ brain perfusion indicated significantly reduced brain accumulation of verapamil, a P-glycoprotein substrate. These findings suggest a new paradigm for the field of environmental toxicology: toxicants acting through AhR to target xenobiotic efflux transporters at the blood-brain barrier and thus reduce brain accumulation of CNS-acting therapeutic drugs.

  13. Protein kinase C-associated kinase regulates NF-κB activation through inducing IKK activation.

    Science.gov (United States)

    Kim, Sang-Woo; Schifano, Matthew; Oleksyn, David; Jordan, Craig T; Ryan, Daniel; Insel, Richard; Zhao, Jiyong; Chen, Luojing

    2014-10-01

    Activation of the transcription factor NF-κB induced by extracellular stimuli requires IKKα and IKKβ kinase activity. How IKKα and IKKβ are activated by various upstream signaling molecules is not fully understood. We previously showed that protein kinase C-associated kinase (PKK, also known as DIK/RIP4), which belongs to the receptor-interacting protein (RIP) kinase family, mediates the B cell activating factor of the TNF family (BAFF)-induced NF-κB activation in diffuse large B cell lymphoma (DLBCL) cell lines. Here we have investigated the mechanism underlying NF-κB activation regulated by PKK. Our results suggest that PKK can activate both the classical and the alternative NF-κB activation pathways. PKK associates with IKKα and IKKβ in mammalian cells and induces activation of both IKKα and IKKβ via phosphorylation of their serine residues 176/180 and 177/181, respectively. Unlike other members of the RIP family that activate NF-κB through a kinase-independent pathway, PKK appears to activate IKK and NF-κB mainly in a kinase-dependent manner. Suppression of PKK expression by RNA interference inhibits phosphorylation of IKKα and IKKβ as well as activation of NF-κB in human cancer cell lines. Thus, PKK regulates NF-κB activation by modulating activation of IKKα and IKKβ in mammalian cells. We propose that PKK may provide a critical link between IKK activation and various upstream signaling cascades, and may represent a potential target for inhibiting abnormal NF-κB activation in human cancers.

  14. DMPD: Receptor tyrosine kinases and the regulation of macrophage activation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 14726496 Receptor tyrosine kinases and the regulation of macrophage activation. Cor...(.csml) Show Receptor tyrosine kinases and the regulation of macrophage activation. PubmedID 14726496 Title ...Receptor tyrosine kinases and the regulation of macrophage activation. Authors Co

  15. Protein kinase C-α signals P115RhoGEF phosphorylation and RhoA activation in TNF-α-induced mouse brain microvascular endothelial cell barrier dysfunction

    Directory of Open Access Journals (Sweden)

    Deng Xiaolu

    2011-04-01

    Full Text Available Abstract Background Tumor necrosis factor-α (TNF-α, a proinflammatory cytokine, is capable of activating the small GTPase RhoA, which in turn contributes to endothelial barrier dysfunction. However, the underlying signaling mechanisms remained undefined. Therefore, we aimed to determine the role of protein kinase C (PKC isozymes in the mechanism of RhoA activation and in signaling TNF-α-induced mouse brain microvascular endothelial cell (BMEC barrier dysfunction. Methods Bend.3 cells, an immortalized mouse brain endothelial cell line, were exposed to TNF-α (10 ng/mL. RhoA activity was assessed by pull down assay. PKC-α activity was measured using enzyme assasy. BMEC barrier function was measured by transendothelial electrical resistance (TER. p115RhoGEF phosphorylation was detected by autoradiography followed by western blotting. F-actin organization was observed by rhodamine-phalloidin staining. Both pharmacological inhibitors and knockdown approaches were employed to investigate the role of PKC and p115RhoGEF in TNF-α-induced RhoA activation and BMEC permeability. Results We observed that TNF-α induces a rapid phosphorylation of p115RhoGEF, activation of PKC and RhoA in BMECs. Inhibition of conventional PKC by Gö6976 mitigated the TNF-α-induced p115RhoGEF phosphorylation and RhoA activation. Subsequently, we found that these events are regulated by PKC-α rather than PKC-β by using shRNA. In addition, P115-shRNA and n19RhoA (dominant negative mutant of RhoA transfections had no effect on mediating TNF-α-induced PKC-α activation. These data suggest that PKC-α but not PKC-β acts as an upstream regulator of p115RhoGEF phosphorylation and RhoA activation in response to TNF-α. Moreover, depletion of PKC-α, of p115RhoGEF, and inhibition of RhoA activation also prevented TNF-α-induced stress fiber formation and a decrease in TER. Conclusions Taken together, our results show that PKC-α phosphorylation of p115RhoGEF mediates TNF

  16. P-glycoprotein activity in the blood-brain barrier is affected by virus-induced neuroinflammation and antipsychotic treatment.

    Science.gov (United States)

    Doorduin, Janine; de Vries, Erik F J; Dierckx, Rudi A; Klein, Hans C

    2014-10-01

    A large percentage of schizophrenic patients respond poorly to antipsychotic treatment. This could be explained by inefficient drug transport across the blood-brain barrier due to P-glycoprotein mediated efflux. P-glycoprotein activity and expression in the blood-brain barrier can be affected by inflammation and pharmacotherapy. We therefore investigated the effect of herpes simplex virus type-1 (HSV-1) induced neuroinflammation and antipsychotic treatment on P-glycoprotein activity. Rats were inoculated with HSV-1 or PBS (control) on day 0 and treated with saline, clozapine or risperidone from day 0 up until day 4 post-inoculation. Positron emission tomography with the P-glycoprotein substrate [11C]verapamil was used to assess P-glycoprotein activity at day 6 post-inoculation. Disease symptoms in HSV-1 inoculated rats increased over time and were not significantly affected by treatment. The volume of distribution (VT) of [11C]verapamil was significantly lower (10-22%) in HSV-1 inoculated rats than in control rats. In addition, antipsychotic treatment significantly affected the VT of [11C]verapamil in all brain regions, although this effect was drug dependent. In fact, VT of [11C]verapamil was significantly increased (22-39%) in risperidone treated rats in most brain regions when compared to clozapine treated rats and in midbrain when compared to saline treated rats. No interaction between HSV-1 inoculation and antipsychotic treatment on VT of [11C]verapamil was found. In this study we demonstrated that HSV-1 induced neuroinflammation increased and risperidone treatment decreased P-glycoprotein activity. This finding is of importance for the understanding of treatment resistance in schizophrenia, and warrants further investigation of the underlying mechanism and the importance in clinical practice.

  17. Perceived Barriers to Teaching Movement and Physical Activity to Kindergarteners in Ghana

    Science.gov (United States)

    Sofo, Seidu; Asola, Eugene F.

    2015-01-01

    Regular participation in physical activity can improve students' health and academic achievement. It is important to develop a positive attitude toward participation in regular physical activity early in life. Thus, an understanding of factors that affect the activity levels of young children is essential. Therefore, the purpose of the study was…

  18. Facilitators and Barriers to Physical Activity as Perceived by Older Adults with Intellectual Disability

    Science.gov (United States)

    van Schijndel-Speet, Marieke; Evenhuis, Heleen M.; van Wijck, Ruud; van Empelen, Pepijn; Echteld, Michael A.

    2014-01-01

    Older people with intellectual disability (ID) are characterized by low physical activity (PA) levels. PA is important for reducing health risks and maintaining adequate fitness levels for performing activities of daily living. The aim of this study was to explore preferences of older adults with ID for specific physical activities, and to gain…

  19. Spatial regulation and the rate of signal transduction activation.

    Directory of Open Access Journals (Sweden)

    Nizar N Batada

    2006-05-01

    Full Text Available Of the many important signaling events that take place on the surface of a mammalian cell, activation of signal transduction pathways via interactions of cell surface receptors is one of the most important. Evidence suggests that cell surface proteins are not as freely diffusible as implied by the classic fluid mosaic model and that their confinement to membrane domains is regulated. It is unknown whether these dynamic localization mechanisms function to enhance signal transduction activation rate or to minimize cross talk among pathways that share common intermediates. To determine which of these two possibilities is more likely, we derive an explicit equation for the rate at which cell surface membrane proteins interact based on a Brownian motion model in the presence of endocytosis and exocytosis. We find that in the absence of any diffusion constraints, cell surface protein interaction rate is extremely high relative to cytoplasmic protein interaction rate even in a large mammalian cell with a receptor abundance of a mere two hundred molecules. Since a larger number of downstream signaling events needs to take place, each occurring at a much slower rate than the initial activation via association of cell surface proteins, we conclude that the role of co-localization is most likely that of cross-talk reduction rather than coupling efficiency enhancement.

  20. Ribosomal Protein S14 Negatively Regulates c-Myc Activity*

    Science.gov (United States)

    Zhou, Xiang; Hao, Qian; Liao, Jun-ming; Liao, Peng; Lu, Hua

    2013-01-01

    The ribosomal gene RPS14 is associated with the cancer-prone 5q-syndrome, which is caused by an interstitial deletion of the long arm of human chromosome 5. Previously, we found that ribosomal protein S14 (RPS14) binds to and inactivates MDM2, consequently leading to p53-dependent cell-cycle arrest and growth inhibition. However, it remains elusive whether RPS14 regulates cell proliferation in a p53-independent manner. Here, we show that RPS14 interacts with the Myc homology box II (MBII) and the C-terminal basic helix-loop-helix leucine zipper (bHLH-LZ) domains of the oncoprotein c-Myc. Further, RPS14 inhibited c-Myc transcriptional activity by preventing the recruitment of c-Myc and its cofactor, TRRAP, to the target gene promoters, as thus suppressing c-Myc-induced cell proliferation. Also, siRNA-mediated RPS14 depletion elevated c-Myc transcriptional activity determined by its target gene, Nucleolin, expression. Interestingly, RPS14 depletion also resulted in the induction of c-Myc mRNA and subsequent protein levels. Consistent with this, RPS14 promoted c-Myc mRNA turnover through an Argonaute 2 (Ago2)- and microRNA-mediated pathway. Taken together, our study demonstrates that RPS14 negates c-Myc functions by directly inhibiting its transcriptional activity and mediating its mRNA degradation via miRNA. PMID:23775087

  1. Regulation of nucleus accumbens activity by the hypothalamic neuropeptide MCH

    Science.gov (United States)

    Sears, Robert M.; Liu, Rong-Jian; Narayanan, Nandakumar S.; Sharf, Ruth; Yeckel, Mark F.; Laubach, Mark; Aghajanian, George K.; DiLeone, Ralph J.

    2010-01-01

    The lateral hypothalamus (LH) and the nucleus accumbens shell (AcbSh) are brain regions important for food intake. The AcbSh contains high levels of receptor for melanin-concentrating hormone (MCH), a lateral hypothalamic peptide critical for feeding and metabolism. MCH receptor (MCHR1) activation in the AcbSh increases food intake while AcbSh MCHR1 blockade reduces feeding. Here biochemical and cellular mechanisms of MCH action in the rodent AcbSh are described. A reduction of phosphorylation of GluR1 at Serine 845 (pSer845) is shown to occur after both pharmacological and genetic manipulations of MCHR1 activity. These changes depend upon signaling through Gi/o, and result in decreased surface expression of GluR1-containing AMPA receptors (AMPARs). Electrophysiological analysis of medium spiny neurons (MSNs) in the AcbSh revealed decreased amplitude of AMPAR-mediated synaptic events (mEPSC) with MCH treatment. In addition, MCH suppressed action potential firing MSNs through K+ channel activation. Finally, in vivo recordings confirmed that MCH reduces neuronal cell firing in the AcbSh in freely moving animals. The ability of MCH to reduce cell firing in the AcbSh is consistent with a general model from other pharmacological and electrophysiological studies whereby reduced AcbSh neuronal firing leads to food intake. The current work integrates the hypothalamus into this model, providing biochemical and cellular mechanisms whereby metabolic and limbic signals converge to regulate food intake. PMID:20554878

  2. Substrate regulation of ascorbate transport activity in astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, J.X.; Jaworski, E.M.; Kulaga, A.; Dixon, S.J. (Univ. of Western Ontario, London (Canada))

    1990-10-01

    Astrocytes possess a concentrative L-ascorbate (vitamin C) uptake mechanism involving a Na(+)-dependent L-ascorbate transporter located in the plasma membrane. The present experiments examined the effects of deprivation and supplementation of extracellular L-ascorbate on the activity of this transport system. Initial rates of L-ascorbate uptake were measured by incubating primary cultures of rat astrocytes with L-(14C)ascorbate for 1 min at 37 degrees C. We observed that the apparent maximal rate of uptake (Vmax) increased rapidly (less than 1 h) when cultured cells were deprived of L-ascorbate. In contrast, there was no change in the apparent affinity of the transport system for L-(14C)ascorbate. The increase in Vmax was reversed by addition of L-ascorbate, but not D-isoascorbate, to the medium. The effects of external ascorbate on ascorbate transport activity were specific in that preincubation of cultures with L-ascorbate did not affect uptake of 2-deoxy-D-(3H(G))glucose. We conclude that the astroglial ascorbate transport system is modulated by changes in substrate availability. Regulation of transport activity may play a role in intracellular ascorbate homeostasis by compensating for regional differences and temporal fluctuations in external ascorbate levels.

  3. Plasma activated dissociation of CO2 studied in a dielectric barrier discharge

    Science.gov (United States)

    Engeln, Richard; Brehmer, Florian; Welzel, Stefan; Klarenaar, Bart; van de Sanden, Richard; Tu/E Collaboration; Afs Gmbh Collaboration; Differ Collaboration

    2014-10-01

    The ever-increasing emission of carbon dioxide into the atmosphere as well as the intermittency problem of electricity produced by renewable energy sources are challenges that urgently need to be addressed. An approach addressing both issues at the same time is converting CO2 to a fuel using plasma driven by electricity from renewable sources. We will present in this contribution the results of a study on the conversion of CO2 to CO in a dielectric barrier discharge in pure CO2 at pressures up to 1000 mbar: FTIR absorption and Raman spectroscopy were applied to measure CO number densities and gas temperatures as function of the specific injected energy. CO densities with a maximum at 1018 cm-3 (mixing ratio of 4.4%) at 46 kJ/sl, energy efficiencies in the range of a few percent and gas temperatures up to 550 K were detected. The CO production is directly linked with the total number of transferred charges q during the residence time tres of CO2 molecules. Also ozone has been detected with a maximum mixing ratio of 0.075%.

  4. Active species delivered by dielectric barrier discharge filaments to bacteria biofilms on the surface of apple

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, He; Liu, Xin; Lu, Xinpei [State Key Lab of Advanced Electromagnetic Engineering and Technology, Huazhong University of Science and Technology, WuHan, HuBei (China); IFSA Collaborative Innovation Center, Shanghai Jiao Tong University, Shanghai 200240 (China); Liu, Dawei, E-mail: ldw636@msn.com [State Key Lab of Advanced Electromagnetic Engineering and Technology, Huazhong University of Science and Technology, WuHan, HuBei (China); IFSA Collaborative Innovation Center, Shanghai Jiao Tong University, Shanghai 200240 (China); State Key Laboratory of Electrical Insulation and Power Equipment, Xi' an Jiaotong University, Xi' an (China)

    2016-07-15

    The atmospheric pressure non-equilibrium plasma has shown a significant potential as a novel food decontamination technology. In this paper, we report a computational study of the intersection of negative streamer produced by air dielectric barrier discharge with bacteria biofilm on an apple surface. The structure, conductivities, and permittivities of bacteria biofilm have been considered in the Poisson's equations and transportation equations of charge and neutral species to realize self-consistent transportation of plasma between electrode and charging surfaces of apple. We find that the ionization near the biofilm facilitates the propagation of negative streamer when the streamer head is 1 mm from the biofilm. The structure of the biofilm results in the non-uniform distribution of ROS and RNS captured by flux and time fluence of these reactive species. The mean free path of charged species in μm scale permitted the plasma penetrate into the cavity of the biofilm, therefore, although the density of ROS and RNS decrease by 6–7 order of magnitude, the diffusion results in the uniform distribution of ROS and RNS inside the cavity during the pulse off period.

  5. Active species delivered by dielectric barrier discharge filaments to bacteria biofilms on the surface of apple

    Science.gov (United States)

    Cheng, He; Liu, Xin; Lu, Xinpei; Liu, Dawei

    2016-07-01

    The atmospheric pressure non-equilibrium plasma has shown a significant potential as a novel food decontamination technology. In this paper, we report a computational study of the intersection of negative streamer produced by air dielectric barrier discharge with bacteria biofilm on an apple surface. The structure, conductivities, and permittivities of bacteria biofilm have been considered in the Poisson's equations and transportation equations of charge and neutral species to realize self-consistent transportation of plasma between electrode and charging surfaces of apple. We find that the ionization near the biofilm facilitates the propagation of negative streamer when the streamer head is 1 mm from the biofilm. The structure of the biofilm results in the non-uniform distribution of ROS and RNS captured by flux and time fluence of these reactive species. The mean free path of charged species in μm scale permitted the plasma penetrate into the cavity of the biofilm, therefore, although the density of ROS and RNS decrease by 6-7 order of magnitude, the diffusion results in the uniform distribution of ROS and RNS inside the cavity during the pulse off period.

  6. BAK1 Directly Regulates Brassinosteroid Perception and BRI1 Activation

    Institute of Scientific and Technical Information of China (English)

    Kai He; Shengbao Xu; Jia Li

    2013-01-01

    Plants utilize plasma membrane-localized receptor-like kinases (RLKs) to sense extracellular signals to coordinate growth, development, and innate immune responses. BAK1 regulates multiple signaling pathways acting as a co-receptor of several distinct ligand-binding RLKs. It has been debated whether BAK1 serves as an essential regulatory component or only a signal amplifier without pathway specificity. This issue has been clarified recently. Genetic and structural analyses indicated that BAK1 and its homologs play indispensible roles in mediating brassinosteroid (BR) signaling pathway by directly perceiving the ligand BR and activating the receptor of BR, BRI1. The mechanism revealed by these studies now serves as a paradigm for how a pair of RLKs can function together in ligand binding and subsequent initiation of signaling.

  7. Modeling the long-term durability of concrete barriers in the context of low-activity waste storage

    Directory of Open Access Journals (Sweden)

    Samson E.

    2013-07-01

    Full Text Available The paper investigates the long-term durability of concrete barriers in contact with a cementitious wasteform designed to immobilize low-activity nuclear waste. The high-pH pore solution of the wasteform contains high concentration level of sulfate, nitrate, nitrite and alkalis. The multilayer concrete/wasteform system was modeled using a multiionic reactive transport model accounting for coupling between species, dissolution/ precipitation reactions, and feedback effect. One of the primary objectives was to investigate the risk associated with the presence of sulfate in the wasteform on the durability of concrete. Simulation results showed that formation of expansive phases, such as gypsum and ettringite, into the concrete barrier was not extensive. Based on those results, it was not possible to conclude that concrete would be severely damaged, even after 5,000 years. Lab work was performed to provide data to validate the modeling results. Paste samples were immersed in sulfate contact solutions and analyzed to measure the impact of the aggressive environment on the material. The results obtained so far tend to confirm the numerical simulations.

  8. Fear of Movement and Low Self-Efficacy Are Important Barriers in Physical Activity after Renal Transplantation.

    Directory of Open Access Journals (Sweden)

    Dorien M Zelle

    Full Text Available Physical activity (PA and exercise are commonly used as preventive measures for cardiovascular disease in the general population, and could be effective in the management of post-transplantation cardiovascular risk. PA levels are low after renal transplantation and very few renal transplant recipients (RTR meet the PA guidelines. Identification of barriers to regular PA is important to identify targets for intervention to improve PA levels after renal transplantation. We investigated fear of movement and physical self-efficacy as barriers to PA in RTR.RTR were investigated between 2001-2003. The Tampa Score of Kinesiophobia-Dutch Version (TSK-11 was used to assess fear of movement. Physical self-efficacy was measured with the LIVAS-scale. PA was assessed using validated questionnaires (Tecumseh Occupational Activity Questionnaire and the Minnesota Leisure Time Physical Activity Questionnaire.A total of 487 RTR (age 51±12 years, 55% men were studied. Median score [interquartile range] on TSK-11 was 22 [17-26]. Low physical self-efficacy (Exp B:0.41[0.31-0.54], p<0.001 and history of myocardial infarction, transient ischemic attack and cerebrovascular accident (Exp B:1.30[1.03-1.63],p = 0.03 were independent determinants for fear of movement. Fear of movement was associated with lower daily PA, occupational, sports and leisure time PA. Mediation-analysis showed that a large part (73% of the effect of fear of movement on PA was explained by low physical self-efficacy.This study was the first to examine fear of movement and self-efficacy in relation to PA in RTR. Fear of movement was associated with a low PA level, and the larger part of this relation was mediated by low physical self-efficacy. Both fear of movement and physical self-efficacy level are important targets for intervention during rehabilitation after renal transplantation.

  9. Fear of Movement and Low Self-Efficacy Are Important Barriers in Physical Activity after Renal Transplantation

    Science.gov (United States)

    Zelle, Dorien M.; Corpeleijn, Eva; Klaassen, Gerald; Schutte, Elise; Navis, Gerjan; Bakker, Stephan J. L.

    2016-01-01

    Background Physical activity (PA) and exercise are commonly used as preventive measures for cardiovascular disease in the general population, and could be effective in the management of post-transplantation cardiovascular risk. PA levels are low after renal transplantation and very few renal transplant recipients (RTR) meet the PA guidelines. Identification of barriers to regular PA is important to identify targets for intervention to improve PA levels after renal transplantation. We investigated fear of movement and physical self-efficacy as barriers to PA in RTR. Methods RTR were investigated between 2001–2003. The Tampa Score of Kinesiophobia–Dutch Version (TSK-11) was used to assess fear of movement. Physical self-efficacy was measured with the LIVAS-scale. PA was assessed using validated questionnaires (Tecumseh Occupational Activity Questionnaire and the Minnesota Leisure Time Physical Activity Questionnaire). Results A total of 487 RTR (age 51±12 years, 55% men) were studied. Median score [interquartile range] on TSK-11 was 22 [17–26]. Low physical self-efficacy (Exp B:0.41[0.31–0.54], p<0.001) and history of myocardial infarction, transient ischemic attack and cerebrovascular accident (Exp B:1.30[1.03–1.63],p = 0.03) were independent determinants for fear of movement. Fear of movement was associated with lower daily PA, occupational, sports and leisure time PA. Mediation-analysis showed that a large part (73%) of the effect of fear of movement on PA was explained by low physical self-efficacy. Conclusions This study was the first to examine fear of movement and self-efficacy in relation to PA in RTR. Fear of movement was associated with a low PA level, and the larger part of this relation was mediated by low physical self-efficacy. Both fear of movement and physical self-efficacy level are important targets for intervention during rehabilitation after renal transplantation. PMID:26844883

  10. Regulation of sucrose metabolism in higher plants: localization and regulation of activity of key enzymes

    Science.gov (United States)

    Winter, H.; Huber, S. C.; Brown, C. S. (Principal Investigator)

    2000-01-01

    Sucrose (Suc) plays a central role in plant growth and development. It is a major end product of photosynthesis and functions as a primary transport sugar and in some cases as a direct or indirect regulator of gene expression. Research during the last 2 decades has identified the pathways involved and which enzymes contribute to the control of flux. Availability of metabolites for Suc synthesis and 'demand' for products of sucrose degradation are important factors, but this review specifically focuses on the biosynthetic enzyme sucrose-phosphate synthase (SPS), and the degradative enzymes, sucrose synthase (SuSy), and the invertases. Recent progress has included the cloning of genes encoding these enzymes and the elucidation of posttranslational regulatory mechanisms. Protein phosphorylation is emerging as an important mechanism controlling SPS activity in response to various environmental and endogenous signals. In terms of Suc degradation, invertase-catalyzed hydrolysis generally has been associated with cell expansion, whereas SuSy-catalyzed metabolism has been linked with biosynthetic processes (e.g., cell wall or storage products). Recent results indicate that SuSy may be localized in multiple cellular compartments: (1) as a soluble enzyme in the cytosol (as traditionally assumed); (2) associated with the plasma membrane; and (3) associated with the actin cytoskeleton. Phosphorylation of SuSy has been shown to occur and may be one of the factors controlling localization of the enzyme. The purpose of this review is to summarize some of the recent developments relating to regulation of activity and localization of key enzymes involved in sucrose metabolism in plants.

  11. [Barriers and facilitators for physical activity during pregnancy and postpartum in women living in poverty of Mexico].

    Science.gov (United States)

    Lozada-Tequeanes, Ana Lilia; Campero-Cuenca, María de Lourdes Eugenia; Hernández, Bernardo; Rubalcava-Peñafiel, Luis; Neufeld, Lynnette Marie

    2015-01-01

    To explore perceptions of healthcare providers and beneficiaries of Oportunidades program on physical activity during pregnancy and post-partum; and identify current reported practices related to counseling on physical activity in the primary healthcare services in Mexico. A mixed methods approach was used which is part of a nutrition intervention of the Oportunidades program. Qualitative information was collected through interviews (50=women; 34=providers) and quantitative information was collected by questionnaires (n=88 women; n=64 provider; n=111 observations during consultation). The main barriers were: a) individual (lack of time and social support to childcare); b) sociocultural (gender bias derived from peer groups or family and lack of instructors), and c) environmental (lack of safe and adequate physical places). Only 38% of beneficiary women reported having been counseled on physical activity vs 63.4% of providers who reported having counseled on physical activity (p=0.002). There is a need to train healthcare providers and to promote physical activity during pregnancy and post-partum for reducing associated biases.

  12. Effects of Online Self-Regulation Activities on Physical Activity Among Pregnant and Early Postpartum Women.

    Science.gov (United States)

    Kim, Hye Kyung; Niederdeppe, Jeff; Graham, Meredith; Olson, Christine; Gay, Geri

    2015-01-01

    Physical and psychological changes that occur during pregnancy present a unique challenge for women's physical activity. Using a theory-based prospective design, this study examines the effects of pregnant women's (a) physical activity cognitions (self-efficacy, outcome expectancy, and safety beliefs) and (b) online self-regulation activities (goal-setting and self-monitoring) on subsequent changes in their physical activity intentions and behavior during pregnancy and immediately postpartum. The authors used data from three panel surveys administered to pregnant women enrolled in a web-based intervention to promote healthy pregnancy and postpartum weight, as well as log data on their use of self-regulatory features on the intervention website. Perceived self-efficacy and perceived safety of physical activity in pregnancy enhanced subsequent intentions to be physically active. Repeated goal-setting and monitoring of those goals helped to maintain positive intentions during pregnancy, but only repeated self-monitoring transferred positive intentions into actual behavior. Theoretically, this study offers a better understanding of the roles of self-regulation activities in the processes of goal-striving. The authors also discuss practical implications for encouraging physical activity among pregnant and early postpartum women.

  13. Regulation of ALF promoter activity in Xenopus oocytes.

    Directory of Open Access Journals (Sweden)

    Dan Li

    Full Text Available BACKGROUND: In this report we evaluate the use of Xenopus laevis oocytes as a matched germ cell system for characterizing the organization and transcriptional activity of a germ cell-specific X. laevis promoter. PRINCIPAL FINDINGS: The promoter from the ALF transcription factor gene was cloned from X. laevis genomic DNA using a PCR-based genomic walking approach. The endogenous ALF gene was characterized by RACE and RT-PCR for transcription start site usage, and by sodium bisulfite sequencing to determine its methylation status in somatic and oocyte tissues. Homology between the X. laevis ALF promoter sequence and those from human, chimpanzee, macaque, mouse, rat, cow, pig, horse, dog, chicken and X. tropicalis was relatively low, making it difficult to use such comparisons to identify putative regulatory elements. However, microinjected promoter constructs were very active in oocytes and the minimal promoter could be narrowed by PCR-mediated deletion to a region as short as 63 base pairs. Additional experiments using a series of site-specific promoter mutants identified two cis-elements within the 63 base pair minimal promoter that were critical for activity. Both elements (A and B were specifically recognized by proteins present in crude oocyte extracts based on oligonucleotide competition assays. The activity of promoter constructs in oocytes and in transfected somatic Xenopus XLK-WG kidney epithelial cells was quite different, indicating that the two cell types are not functionally equivalent and are not interchangeable as assay systems. CONCLUSIONS: Overall the results provide the first detailed characterization of the organization of a germ cell-specific Xenopus promoter and demonstrate the feasibility of using immature frog oocytes as an assay system for dissecting the biochemistry of germ cell gene regulation.

  14. Facilitators and Barriers to Physical Activity as Perceived by Older Adults With Intellectual Disability

    NARCIS (Netherlands)

    van Schijndel-Speet, Marieke; Evenhuis, Heleen M.; van Wijck, Ruud; van Empelen, Pepijn; Echteld, Michael A.

    2014-01-01

    Older people with intellectual disability (ID) are characterized by low physical activity (PA) levels. PA is important for reducing health risks and maintaining adequate fitness levels for performing activities of daily living. The aim of this study was to explore preferences of older adults with ID

  15. Facilitators and barriers to physical activity as perceived by older adults with intellectual disability

    NARCIS (Netherlands)

    Schijndel-Speet, M. van; Evenhuis, H.M.; Wijck, R. van; Empelen, P. van; Echteld, M.A.

    2014-01-01

    Older people with intellectual disability (ID) are characterized by low physical activity (PA) levels. PA is important for reducing health risks and maintaining adequate fitness levels for performing activities of daily living. The aim of this study was to explore preferences of older adults with ID

  16. Facilitators and Barriers to Physical Activity as Perceived by Older Adults With Intellectual Disability

    NARCIS (Netherlands)

    van Schijndel-Speet, Marieke; Evenhuis, Heleen M.; van Wijck, Ruud; van Empelen, Pepijn; Echteld, Michael A.

    Older people with intellectual disability (ID) are characterized by low physical activity (PA) levels. PA is important for reducing health risks and maintaining adequate fitness levels for performing activities of daily living. The aim of this study was to explore preferences of older adults with ID

  17. Carry-over of self-regulation for physical activity to self-regulating eating in women with morbid obesity.

    Science.gov (United States)

    Annesi, James J; Porter, Kandice J; Johnson, Ping H

    2015-01-01

    Poor outcomes from behavioral treatments of severe obesity have led to a dependence on invasive medical interventions, including surgery for morbidly obese individuals. Improved methods to self-regulate eating will be required to reduce obesity. The use of self-regulation methods for completing physical activity may carry over to increased self-regulation for eating through improved feelings of competence (self-efficacy) and mood. The study recruited women (Meanage = 43 years) with morbid obesity (MeanBMI = 44 kg/m(2)) to participate in 26 weeks of cognitive-behavioral support of physical activity paired with either nutrition education (n = 51) or cognitive-behavioral nutrition (n = 51) methods. Data collected were from 2011 and 2012. Significant improvements in self-regulation for physical activity, self-regulation for eating, overall mood, and self-efficacy for eating, with greater improvement in self-regulation for eating, were observed in the cognitive-behavioral nutrition group. Changes in mood and self-efficacy for eating significantly mediated the relationship between changes in self-regulation for physical activity and self-regulation for eating. When subscales of overall mood and self-efficacy were entered into separate regression equations as mediators, the only significant mediators were vigor, and controlling eating when socially pressured and when increased cues to overeat were present.

  18. Early activation of STAT3 regulates reactive astrogliosis induced by diverse forms of neurotoxicity.

    Directory of Open Access Journals (Sweden)

    James P O'Callaghan

    Full Text Available Astrogliosis, a cellular response characterized by astrocytic hypertrophy and accumulation of GFAP, is a hallmark of all types of central nervous system (CNS injuries. Potential signaling mechanisms driving the conversion of astrocytes into "reactive" phenotypes differ with respect to the injury models employed and can be complicated by factors such as disruption of the blood-brain barrier (BBB. As denervation tools, neurotoxicants have the advantage of selective targeting of brain regions and cell types, often with sparing of the BBB. Previously, we found that neuroinflammation and activation of the JAK2-STAT3 pathway in astrocytes precedes up regulation of GFAP in the MPTP mouse model of dopaminergic neurotoxicity. Here we show that multiple mechanistically distinct mouse models of neurotoxicity (MPTP, AMP, METH, MDA, MDMA, KA, TMT engender the same neuroinflammatory and STAT3 activation responses in specific regions of the brain targeted by each neurotoxicant. The STAT3 effects seen for TMT in the mouse could be generalized to the rat, demonstrating cross-species validity for STAT3 activation. Pharmacological antagonists of the neurotoxic effects blocked neuroinflammatory responses, pSTAT3tyr705 and GFAP induction, indicating that damage to neuronal targets instigated astrogliosis. Selective deletion of STAT3 from astrocytes in STAT3 conditional knockout mice markedly attenuated MPTP-induced astrogliosis. Monitoring STAT3 translocation in GFAP-positive cells indicated that effects of MPTP, METH and KA on pSTAT3tyr705 were localized to astrocytes. These findings strongly implicate the STAT3 pathway in astrocytes as a broadly triggered signaling pathway for astrogliosis. We also observed, however, that the acute neuroinflammatory response to the known inflammogen, LPS, can activate STAT3 in CNS tissue without inducing classical signs of astrogliosis. Thus, acute phase neuroinflammatory responses and neurotoxicity-induced astrogliosis both

  19. Identifying Barriers, Perceptions and Motivations Related to Healthy Eating and Physical Activity among 6th to 8th Grade, Rural, Limited-Resource Adolescents

    Science.gov (United States)

    Kumar, Janavi; Adhikari, Koushik; Li, Yijing; Lindshield, Erika; Muturi, Nancy; Kidd, Tandalayo

    2016-01-01

    Purpose: The purpose of this paper is to enable community members to discuss their perceptions of eating habits and physical activity in relation to sixth, seventh, and eighth graders, and reveal facilitators and barriers to healthy eating behavior and physical activity engagement. Design/methodology/approach: Nine focus groups, which included six…

  20. Identifying Barriers, Perceptions and Motivations Related to Healthy Eating and Physical Activity among 6th to 8th Grade, Rural, Limited-Resource Adolescents

    Science.gov (United States)

    Kumar, Janavi; Adhikari, Koushik; Li, Yijing; Lindshield, Erika; Muturi, Nancy; Kidd, Tandalayo

    2016-01-01

    Purpose: The purpose of this paper is to enable community members to discuss their perceptions of eating habits and physical activity in relation to sixth, seventh, and eighth graders, and reveal facilitators and barriers to healthy eating behavior and physical activity engagement. Design/methodology/approach: Nine focus groups, which included six…

  1. After the slippery slope: Dutch experiences on regulating active euthanasia.

    Science.gov (United States)

    Boer, Theo A

    2003-01-01

    "When a country legalizes active euthanasia, it puts itself on a slippery slope from where it may well go further downward." If true, this is a forceful argument in the battle of those who try to prevent euthanasia from becoming legal. The force of any slippery slope argument, however, is by definition limited by its reference to future developments which cannot empirically be sustained. Experience in the Netherlands--where a law regulating active euthanasia was accepted in April 2001--may shed light on the strengths as well as the weaknesses of the slippery slope argument in the context of the euthanasia debate. This paper consists of three parts. First, it clarifies the Dutch legislation on euthanasia and explains the cultural context in which it originated. Second, it looks at the argument of the slippery slope. A logical and an empirical version are distinguished, and the latter, though philosophically less interesting, proves to be most relevant in the discussion on euthanasia. Thirdly, it addresses the question whether Dutch experiences in the process of legalizing euthanasia justify the fear of the slippery slope. The conclusion is that Dutch experiences justify some caution.

  2. Activated Type 2 Innate Lymphoid Cells regulate Beige Fat Biogenesis

    Science.gov (United States)

    Lee, Min-Woo; Odegaard, Justin I.; Mukundan, Lata; Qiu, Yifu; Molofsky, Ari B.; Nussbaum, Jesse C.; Yun, Karen; Locksley, Richard M.; Chawla, Ajay

    2014-01-01

    SUMMARY Type 2 innate lymphoid cells (ILC2s), an innate source of the type 2 cytokines interleukin (IL)-5 and -13, participate in the maintenance of tissue homeostasis. Although type 2 immunity is critically important for mediating metabolic adaptations to environmental cold, the functions of ILC2s in beige or brown fat development are poorly defined. We report here that activation of ILC2s by IL-33 is sufficient to promote the growth of functional beige fat in thermoneutral mice. Mechanistically, ILC2 activation results in the proliferation of bipotential adipocyte precursors (APs) and their subsequent commitment to the beige fat lineage. Loss- and gain-of-function studies reveal that ILC2-and eosinophil-derived type 2 cytokines stimulate signaling via the IL-4Rα in PDGFRα+ APs to promote beige fat biogenesis. Together, our results highlight a critical role for ILC2s and type 2 cytokines in the regulation of adipocyte precursor numbers and fate, and as a consequence, adipose tissue homeostasis. PMID:25543153

  3. Sucking pump activity in feeding behaviour regulation in carpenter ants.

    Science.gov (United States)

    Falibene, Agustina; Gontijo, Alberto de Figueiredo; Josens, Roxana

    2009-06-01

    Modulation of liquid feeding-rate would allow insects to ingest more food in the same time when this was required. Ants can vary nectar intake rate by increasing sucking pump frequency according to colony requirements. We analysed electrical signals generated by sucking pump activity of ants during drinking solutions of different sucrose concentrations and under different carbohydrate-deprivation levels. Our aim was to define parameters that characterize the recordings and analyse their relationship with feeding behaviour. Signals showed that the initial and final frequencies of sucking pump activity, as well as the difference between them were higher in sugar-deprived ants. However, these parameters were not influenced by sucrose solution concentration, which affected the number of pump contractions and the volume per contraction. Unexpectedly, we found two different responses in feeding behaviour of starved and non-starved ants depending on concentration. Starved ants drank dilute solutions for the same length of time as non-starved ants but ingested higher volumes. While drinking the concentrated solutions, starved ants drank the same volume, but did so in a shorter time than the non-starved ones. Despite these differences, for each analysed concentration the total number of pump contractions remained constant independently of sugar-deprivation level. These results are discussed in the frame of feeding regulation and decision making in ant foraging behaviour.

  4. Efficiency of active barriers attaching biofilm as sediment capping to eliminate the internal nitrogen in eutrophic lake and canal

    Institute of Scientific and Technical Information of China (English)

    Tinglin Huang; Jinlan Xu; Daojian Cai

    2011-01-01

    Three active barrier materials (zeolite, ceramicite and light porous media) were applied for preventing nitrogen (N) release from eutrophic lake sediments. Long term experiment of two different lake sediments were carried out and the effect of zeolite dose was evaluated. The results indicated that about 90%-100% of total N in overlying water was eliminated by using zeolite. While the N removal efficiency by ceramic was lower than that by zeolite, and light porous media present the lowest efficiency of 59%. Long term sediment incubation experiments indicated that two eutrophic sediments were both effective in preventing N release in spite of different release characteristics. Bio-zeolite capping technology was able to effectively inhibit the release of N from the sediment, and the zeolite dose was independently from N removal.

  5. Plasminogen activator inhibitor type 1 regulates microglial motility and phagocytic activity

    Directory of Open Access Journals (Sweden)

    Jeon Hyejin

    2012-06-01

    Full Text Available Abstract Background Plasminogen activator inhibitor type 1 (PAI-1 is the primary inhibitor of urokinase type plasminogen activators (uPA and tissue type plasminogen activators (tPA, which mediate fibrinolysis. PAI-1 is also involved in the innate immunity by regulating cell migration and phagocytosis. However, little is known about the role of PAI-1 in the central nervous system. Methods In this study, we identified PAI-1 in the culture medium of mouse mixed glial cells by liquid chromatography and tandem mass spectrometry. Secretion of PAI-1 from glial cultures was detected by ELISA and western blotting analysis. Cell migration was evaluated by in vitro scratch-wound healing assay or Boyden chamber assay and an in vivo stab wound injury model. Phagocytic activity was measured by uptake of zymosan particles. Results The levels of PAI-1 mRNA and protein expression were increased by lipopolysaccharide and interferon-γ stimulation in both microglia and astrocytes. PAI-1 promoted the migration of microglial cells in culture via the low-density lipoprotein receptor-related protein (LRP 1/Janus kinase (JAK/signal transducer and activator of transcription (STAT1 axis. PAI-1 also increased microglial migration in vivo when injected into mouse brain. PAI-1-mediated microglial migration was independent of protease inhibition, because an R346A mutant of PAI-1 with impaired PA inhibitory activity also promoted microglial migration. Moreover, PAI-1 was able to modulate microglial phagocytic activity. PAI-1 inhibited microglial engulfment of zymosan particles in a vitronectin- and Toll-like receptor 2/6-dependent manner. Conclusion Our results indicate that glia-derived PAI-1 may regulate microglial migration and phagocytosis in an autocrine or paracrine manner. This may have important implications in the regulation of brain microglial activities in health and disease.

  6. Peptide Regulation of Cofilin Activity in the CNS: A Novel Therapeutic Approach for Treatment of Multiple Neurological Disorders.

    Science.gov (United States)

    Shaw, Alisa E; Bamburg, James R

    2017-02-19

    Cofilin is a ubiquitous protein which cooperates with many other actin-binding proteins in regulating actin dynamics. Cofilin has essential functions in nervous system development including neuritogenesis, neurite elongation, growth cone pathfinding, dendritic spine formation, and the regulation of neurotransmission and spine function, components of synaptic plasticity essential for learning and memory. Cofilin's phosphoregulation is a downstream target of many transmembrane signaling processes, and its misregulation in neurons has been linked in rodent models to many different neurodegenerative and neurological disorders including Alzheimer disease (AD), aggression due to neonatal isolation, autism, manic/bipolar disorder, and sleep deprivation. Cognitive and behavioral deficits of these rodent models have been largely abrogated by modulation of cofilin activity using viral-mediated, genetic, and/or small molecule or peptide therapeutic approaches. Neuropathic pain in rats from sciatic nerve compression has also been reduced by modulating the cofilin pathway within neurons of the dorsal root ganglia. Neuroinflammation, which occurs following cerebral ischemia/reperfusion, but which also accompanies many other neurodegenerative syndromes, is markedly reduced by peptides targeting specific chemokine receptors, which also modulate cofilin activity. Thus, peptide therapeutics offer potential for cost-effective treatment of a wide variety of neurological disorders. Here we discuss some recent results from rodent models using therapeutic peptides with a surprising ability to cross the rodent blood brain barrier and alter cofilin activity in brain. We also offer suggestions as to how neuronal-specific cofilin regulation might be achieved.

  7. Exocyst Sec10 protects epithelial barrier integrity and enhances recovery following oxidative stress, by activation of the MAPK pathway.

    Science.gov (United States)

    Park, Kwon Moo; Fogelgren, Ben; Zuo, Xiaofeng; Kim, Jinu; Chung, Daniel C; Lipschutz, Joshua H

    2010-03-01

    Cell-cell contacts are essential for epithelial cell function, and disruption is associated with pathological conditions including ischemic kidney injury. We hypothesize that the exocyst, a highly-conserved eight-protein complex that targets secretory vesicles carrying membrane proteins, is involved in maintaining renal epithelial barrier integrity. Accordingly, increasing exocyst expression in renal tubule cells may protect barrier function from oxidative stress resulting from ischemia and reperfusion (I/R) injury. When cultured on plastic, Madin-Darby canine kidney (MDCK) cells overexpressing Sec10, a central exocyst component, formed domes showing increased resistance to hydrogen peroxide (H2O2). Transepithelial electric resistance (TER) of Sec10-overexpressing MDCK cells grown on Transwell filters was higher than in control MDCK cells, and the rate of TER decrease following H2O2 treatment was less in Sec10-overexpressing MDCK cells compared with control MDCK cells. After removal of H2O2, TER returned to normal more rapidly in Sec10-overexpressing compared with control MDCK cells. In collagen culture MDCK cells form cysts, and H2O2 treatment damaged Sec10-overexpressing MDCK cell cysts less than control MDCK cell cysts. The MAPK pathway has been shown to protect animals from I/R injury. Levels of active ERK, the final MAPK pathway step, were higher in Sec10-overexpressing compared with control MDCK cells. U0126 inhibited ERK activation, exacerbated the H2O2-induced decrease in TER and cyst disruption, and delayed recovery of TER following H2O2 removal. Finally, in mice with renal I/R injury, exocyst expression decreased early and returned to normal concomitant with functional recovery, suggesting that the exocyst may be involved in the recovery following I/R injury.

  8. Performance of iron filings and activated sludge as media for permeable reactive barriers to treat zinc contaminated groundwater

    Directory of Open Access Journals (Sweden)

    Chayapat Hassapak

    2015-02-01

    Full Text Available Zinc is one of the important contaminants in groundwater. Removal of zinc by iron filings, activated sludge and lateritic soil was studied with batch test. The lowest optimum pH for removal of zinc by iron filings, activated sludge and lateritic soil was 6. From isotherm studies iron filings and activated sludge were chosen as media for permeable reactive barrier (PRB. The PRB of 0.5-m thick was simulated in the unconfined aquifer with the distance of 21.5 m downgradient of the zinc contaminated site having constant concentration of 100 mg/l. The groundwater flow in the site was induced by the hydraulic gradient of 0.02. Simulation results indicated that the concentration of zinc of treated groundwater was less than 5 mg/l, which met Thai Groundwater Quality Standard for Drinking Purposes. The continuous PRBs using iron filings and activated sludge could treat zinc for 2,170 and 2,248 days, respectively

  9. Motivators and barriers to healthful eating and physical activity among low-income overweight and obese mothers.

    Science.gov (United States)

    Chang, Mei-Wei; Nitzke, Susan; Guilford, Eileen; Adair, Constance H; Hazard, Diana L

    2008-06-01

    Low-income women who are overweight and obese are at high risk for long-term retention of weight gain during pregnancy, in part because they may have poor diets and inadequate physical activity, both of which may be exacerbated by stressful situations. This study identified motivators and barriers to healthful eating and physical activity among low-income overweight and obese non-Hispanic black and non-Hispanic white mothers. Qualitative data were collected via eight focus group interviews. Eighty low-income overweight and obese non-Hispanic black (n=41) and non-Hispanic white (n=39) mothers, age 18 to 35 years, were recruited from the Special Supplemental Nutrition Program for Women, Infants, and Children sites in six counties in Michigan. Personal appearance, fit in clothes, inability to play with their children, and social support were motivating factors for healthful eating and physical activity. Stressful experiences triggered emotional eating and reduced participants' ability to practice these behaviors. Other factors-for example, wanting quick weight-loss results-made it difficult for these mothers to follow recommended healthful lifestyle practices. Nutrition educators can address these concerns by including information about ways to deal with stress and emotional eating and emphasizing the benefits of healthful eating and physical activity in their program plans.

  10. Effect of tannic acid-fish scale gelatin hydrolysate hybrid nanoparticles on intestinal barrier function and α-amylase activity.

    Science.gov (United States)

    Wu, Shao-Jung; Ho, Yi-Cheng; Jiang, Shun-Zhou; Mi, Fwu-Long

    2015-07-01

    Practical application of tannic acid is limited because it readily binds proteins to form insoluble aggregates. In this study, tannic acid was self-assembled with fish scale gelatin hydrolysates (FSGH) to form stable colloidal complex nanoparticles. The nanoparticles prepared from 4 mg ml(-1) tannic acid and 4 mg ml(-1) FSGH had a mean particle size of 260.8 ± 3.6 nm, and showed a positive zeta potential (20.4 ± 0.4 mV). The nanoparticles acted as effective nano-biochelators and free radical scavengers because they provided a large number of adsorption sites for interaction with heavy metal ions and scavenging free radicals. The maximum adsorption capacity for Cu(2+) ions was 123.5 mg g(-1) and EC50 of DPPH radical scavenging activity was 21.6 ± 1.2 μg ml(-1). Hydroxyl radical scavenging effects of the nanoparticles were investigated by electron spin resonance spectroscopy. The copper-chelating capacity and free radical scavenging activity of the nanoparticles were associated with their capacity to inhibit Cu(2+) ion-induced barrier impairment and hyperpermeability of Caco-2 intestinal epithelial tight junction (TJ). However, α-amylase inhibitory activity of the nanoparticles was significantly lower than that of free tannic acid. The results suggest that the nanoparticles can ameliorate Cu(2+) ion induced intestinal epithelial TJ dysfunction without severely inhibiting the activity of the digestive enzymes.

  11. CE: Original research: hospital system barriers to rapid response team activation: a cognitive work analysis.

    Science.gov (United States)

    Braaten, Jane Saucedo

    2015-02-01

    The goal of rapid response team (RRT) activation in acute care facilities is to decrease mortality from preventable complications, but such efforts have been only moderately successful. Although recent research has shown decreased mortality when RRTs are activated more often, many hospitals have low activation rates. This has been linked to various hospital, team, and nursing factors. Yet there is a dearth of research examining how hospital systems shape nurses' behavior with regard to RRT activation. Making systemic constraints visible and modifying them may be the key to improving RRT activation rates and saving more lives. The purpose of this study was to use cognitive work analysis to describe factors within the hospital system that shape medical-surgical nurses' RRT activation behavior. Cognitive work analysis offers a framework for the study of complex sociotechnical systems. This framework was used as the organizing element of the study. Qualitative descriptive design was used to obtain data to fill the framework's five domains: resources, tasks, strategies, social systems, and worker competency. Data were obtained from interviews with 12 medical-surgical nurses and document review. Directed content analysis was used to place the obtained data into the framework's predefined domains. Many system factors affected participants' decisions to activate or not activate an RRT. Systemic constraints, especially in cases of subtle or gradual clinical changes, included a lack of adequate information, the availability of multiple strategies, the need to justify RRT activation, a scarcity of human resources, and informal hierarchical norms in the hospital culture. The most profound constraint was the need to justify the call. Justification was based on the objective or subjective nature of clinical changes, whether the nurse expected to be able to "handle" these changes, the presence or absence of a physician, and whether there was an expectation of support from the RRT

  12. Physical activity in patients with heart failure: barriers and motivations with special focus on sex differences

    OpenAIRE

    Klompstra L; Jaarsma T; Strömberg A

    2015-01-01

    Leonie Klompstra,1 Tiny Jaarsma,1 Anna Strömberg2,31Department of Social and Welfare Studies, Faculty of Health Sciences, 2Department of Medical and Health Sciences, Division of Nursing, 3Department of Cardiology, Linköping University, Linköping, SwedenBackground: Adherence to recommendations for physical activity is low in both male and female patients with heart failure (HF). Men are more physically active than women. In order to successfully promote physical acti...

  13. Promoting Physical Activity Participation among Adolescents: The Barriers and the Suggestions

    OpenAIRE

    Niloofar Peykari; Monir Baradaran Eftekhari; Fahimeh Ramezani Tehrani; Hosein Malek Afzali; Farzaneh Hejazi; Mehrdad Kazemzadeh Atoofi; Mostafa Qorbani; Hamid Asayesh; Shirin Djalalinia

    2015-01-01

    Background: Physical activity is a complex behavior. To designing the effective intervention, qualitative researches may be allowed for greater understanding of the reasons behind the adolescences′ physical activity-related behaviors′. Methods: Using the grounded theory approach, including semi-structured focus group discussions (FGDs) and in-depth interviews, we conducted a quantitative study to elicit the adolescents and key informants′ opinion regarding the satiation, needs, social and...

  14. Physical Activity in Adolescents — Barriers and Impact on Depressed Affect

    OpenAIRE

    Langguth, Nadine

    2016-01-01

    Adolescence is a high-risk period for physical inactivity as well as depressed affect, both related to various short-, mid-, and long-term negative consequences for adolescents' physical and mental health. Therefore, this developmental period is ideally suited for studying the association between change processes of everyday physical activity and change processes of depressed affect within person by applying an intensive longitudinal design. Given that physical activity substantially decrease...

  15. Notch1 regulated autophagy controls survival and suppressor activity of activated murine T-regulatory cells

    Science.gov (United States)

    Marcel, Nimi; Sarin, Apurva

    2016-01-01

    Cell survival is one of several processes regulated by the Notch pathway in mammalian cells. Here we report functional outcomes of non-nuclear Notch signaling to activate autophagy, a conserved cellular response to nutrient stress, regulating survival in murine natural T-regulatory cells (Tregs), an immune subset controlling tolerance and inflammation. Induction of autophagy required ligand-dependent, Notch intracellular domain (NIC) activity, which controlled mitochondrial organization and survival of activated Tregs. Consistently, NIC immune-precipitated Beclin and Atg14, constituents of the autophagy initiation complex. Further, ectopic expression of an effector of autophagy (Atg3) or recombinant NIC tagged to a nuclear export signal (NIC-NES), restored autophagy and suppressor function in Notch1-/- Tregs. Furthermore, Notch1 deficiency in the Treg lineage resulted in immune hyperactivity, implicating Notch activity in Treg homeostasis. Notch1 integration with autophagy, revealed in these experiments, holds implications for Notch regulated cell-fate decisions governing differentiation. DOI: http://dx.doi.org/10.7554/eLife.14023.001 PMID:27267497

  16. Hyperphosphorylation regulates the activity of SREBP1 during mitosis.

    Science.gov (United States)

    Bengoechea-Alonso, Maria T; Punga, Tanel; Ericsson, Johan

    2005-08-16

    The sterol regulatory element-binding protein (SREBP) family of transcription factors controls the biosynthesis of cholesterol and other lipids, and lipid synthesis is critical for cell growth and proliferation. We were, therefore, interested in the expression and activity of SREBPs during the cell cycle. We found that the expression of a number of SREBP-responsive promoter-reporter genes were induced in a SREBP-dependent manner in cells arrested in G2/M. In addition, the mature forms of SREBP1a and SREBP1c were hyperphosphorylated in mitotic cells, giving rise to a phosphoepitope recognized by the mitotic protein monoclonal-2 (MPM-2) antibody. In contrast, SREBP2 was not hyperphosphorylated in mitotic cells and was not recognized by the MPM-2 antibody. The MPM-2 epitope was mapped to the C terminus of mature SREBP1, and the mitosis-specific hyperphosphorylation of SREBP1 depended on this domain of the protein. The transcriptional and DNA-binding activity of SREBP1 was enhanced in cells arrested in G2/M, and these effects depended on the C-terminal domain of the protein. In part, these effects could be explained by our observation that mature SREBP1 was stabilized in G2/M. In agreement with these observations, we found that the synthesis of cholesterol was increased in G2/M-arrested cells. Thus, our results demonstrate that the activity of mature SREBP1 is regulated by phosphorylation during the cell cycle, suggesting that SREBP1 may provide a link between lipid synthesis, proliferation, and cell growth.

  17. 22 CFR 143.2 - To what programs or activities do these regulations apply?

    Science.gov (United States)

    2010-04-01

    ... what programs or activities do these regulations apply? These regulations apply to each foreign affairs... 22 Foreign Relations 1 2010-04-01 2010-04-01 false To what programs or activities do these regulations apply? 143.2 Section 143.2 Foreign Relations DEPARTMENT OF STATE CIVIL RIGHTS NONDISCRIMINATION ON...

  18. Oxidation of limonene using activated carbon modified in dielectric barrier discharge plasma

    Science.gov (United States)

    Glonek, Karolina; Wróblewska, Agnieszka; Makuch, Edyta; Ulejczyk, Bogdan; Krawczyk, Krzysztof; Wróbel, Rafał. J.; Koren, Zvi C.; Michalkiewicz, Beata

    2017-10-01

    The waste from industrial fruits processing is utilized for the extraction of limonene, a renewable terpene biomass compound obtained from orange peels. This was followed by limonene oxidation, which produces highly useful oxygenated derivatives (carveol, and perillyl alcohol, 1,2-epoxylimonene and its diol). New catalysts were obtained by treating relatively inexpensive commercially available EuroPh and FPV activated carbons with plasma. These catalysts were characterized by the following instrumental methods XRD, sorption of N2 and CO2, SEM, EDS, TEM, XPS, and Raman spectroscopy. The activities of the plasma-treated catalysts were measured in the oxidation of limonene by means of either hydrogen peroxide or t-butyl hydroperoxide as the oxidizing agents. During the oxidation with hydrogen peroxide the new plasma-treated catalysts were more active than their untreated counterparts. This effect was noticeable in the considerable increase in the conversion of limonene. The mechanism explaining this property is proposed, and it takes into account the role of the appropriate functional groups on the surface of the catalysts. This work has shown for the first time that the commercial EuroPh and FPV activated carbons, after having been treated by plasma, are active catalysts for the selective limonene oxidation for the production of value-added industrial products.

  19. Interrelations between blood-brain barrier permeability and matrix metalloproteinases are differently affected by tissue plasminogen activator and hyperoxia in a rat model of embolic stroke

    Directory of Open Access Journals (Sweden)

    Michalski Dominik

    2012-01-01

    Full Text Available Abstract Background In ischemic stroke, blood-brain barrier (BBB regulations, typically involving matrix metalloproteinases (MMPs and inhibitors (TIMPs as mediators, became interesting since tissue plasminogen activator (tPA-related BBB breakdown with risk of secondary hemorrhage was considered to involve these mediators too. Despite high clinical relevance, detailed interactions are purely understood. After a pilot study addressing hyperoxia as potential neuroprotective co-treatment to tPA, we analyzed interrelations between BBB permeability (BBB-P, MMPs and TIMPs. Findings Rats underwent embolic middle cerebral artery occlusion (eMCAO and treatment with normobaric (NBO or hyperbaric oxygen (HBO, tPA, tPA+HBO, or no treatment. BBB-P was assessed by intravenously applied FITC-albumin at 4 or 24 hours. MMP-2/-9 and TIMP-1/-2 serum levels were determined at 5 or 25 hours. Time point-corrected partial correlations were used to explore interrelations of BBB-P in ischemic regions (extra-/intravasal FITC-albumin ratio and related serum markers. BBB-P correlated positively with MMP-2 and MMP-9 in controls, whereas hyperoxia led to an inverse association, most pronounced for HBO/MMP-9 (r = -0.606; P Conclusions HBO was found to reverse the positively directed interrelation of BBB-P and MMPs after eMCAO, but this effect failed to sustain in the expected amount when HBO and tPA were given simultaneously.

  20. Ablation of CD11c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood-brain barrier permeability and altering tight junction/adhesion molecules.

    Science.gov (United States)

    Kim, Jin Hyoung; Hossain, Ferdaus Mohd Altaf; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Park, Sang-Youel; Lee, John-Hwa; Kim, Bumseok; Kim, Koanhoi; Eo, Seong Kug

    2016-10-01

    Japanese encephalitis (JE), characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV), is becoming a leading cause of viral encephalitis due to rapid changes in climate and demography. The blood-brain barrier (BBB) plays an important role in restricting neuroinvasion of peripheral leukocytes and virus, thereby regulating the progression of viral encephalitis. In this study, we explored the role of CD11c(hi) dendritic cells (DCs) in regulating BBB integrity and JE progression using a conditional depletion model of CD11c(hi) DCs. Transient ablation of CD11c(hi) DCs resulted in markedly increased susceptibility to JE progression along with highly increased neuro-invasion of JEV. In addition, exacerbated JE progression in CD11c(hi) DC-ablated hosts was closely associated with increased expression of proinflammatory cytokines (IFN-β, IL-6, and TNF-α) and CC chemokines (CCL2, CCL3, CXCL2) in the brain. Moreover, our results revealed that the exacerbation of JE progression in CD11c(hi) DC-ablated hosts was correlated with enhanced BBB permeability and reduced expression of tight junction and adhesion molecules (claudin-5, ZO-1, occluding, JAMs). Ultimately, our data conclude that the ablation of CD11c(hi) DCs provided a subsidiary impact on BBB integrity and the expression of tight junction/adhesion molecules, thereby leading to exacerbated JE progression. These findings provide insight into the secondary role of CD11c(hi) DCs in JE progression through regulation of BBB integrity and the expression of tight junction/adhesion molecules.

  1. Claudin-5 regulates blood-brain barrier permeability by modifying brain microvascular endothelial cell proliferation, migration, and adhesion to prevent lung cancer metastasis.

    Science.gov (United States)

    Ma, Shun-Chang; Li, Qi; Peng, Jia-Yi; Zhouwen, Jian-Long; Diao, Jin-Fu; Niu, Jian-Xing; Wang, Xi; Guan, Xiu-Dong; Jia, Wang; Jiang, Wen-Guo

    2017-09-29

    To investigate the roles of Claudin-5 (CLDN5) in regulating the permeability of the blood-brain barrier (BBB) during lung cancer brain metastasis. By silencing and overexpressing the CLDN5 gene in human brain vascular endothelial (hCMEC/D3) cells, we demonstrated the attenuation of cell migration ability and CLDN5's significant positive role in cell proliferation in CLDN5-overexpressing hCMEC/D3 cells and observed the opposite result in the CLDN5 knockdown group. The reinforced CLDN5 expression reduced the paracellular permeability of hCMEC/D3 cells and decreased the invasion of lung adenocarcinoma A549 cells. Overall, 1685 genes were found to be differentially expressed between the CLDN5-overexpressing cells and the control cells using the Affymetrix Human Transcriptome Array 2.0 (HTA 2.0), and the function of these genes was determined by Gene Ontology and pathway analyses. The possible biological functions of the 1685 genes include cell proliferation, adhesion molecules, and the Jak-STAT, PI3K-Akt, Wnt, and Notch signaling pathways. The identified sets of mRNAs that were specific to CLDN5-overexpressing hCMEC/D3 cells were verified by a qRT-PCR experiment. CLDN5 regulates the permeability of BBB by regulating the proliferation, migration, and permeability of hCMEC/D3 cells, especially through the cell adhesion molecule signaling pathway, to enhance the function of the tight junctions, which was involved in reducing the formation of lung cancer brain metastasis. © 2017 John Wiley & Sons Ltd.

  2. Intestinal Mucosal Barrier Is Injured by BMP2/4 via Activation of NF-κB Signals after Ischemic Reperfusion

    Directory of Open Access Journals (Sweden)

    Kang Chen

    2014-01-01

    Full Text Available Intestinal ischemic reperfusion (I/R can cause dysfunction of the intestinal mucosal barrier; however, the mechanism of the intestinal mucosal barrier dysfunction caused by I/R remains unclear. In this study, using intestinal epithelial cells under anaerobic cultivation and an in vivo rat intestinal I/R model, we found that hypoxia and I/R increased the expression of BMP2/4 and upregulated BMP type Ia receptor and BMP type II receptor expression. We also found that exogenous BMP2/4 can activate the ERK and AKT signaling pathways in rat small intestine (IEC-6 cells, thereby activating NF-κB signaling, which leads to increased levels of inflammatory factors, such as TNF-α and IL-6. Furthermore, recombinant BMP2/4 decreased the expression of the tight junction protein occludin via the activation of the NF-κB pathway; these effects were abolished by treatment with the BMP-specific antagonist noggin or the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC. All these factors can destroy the intestinal mucosal barrier, thereby leading to weaker barrier function. On the basis of these data, we conclude that BMP2/4 may act as the pathogenic basis for intestinal mucosal barrier dysfunction when the intestines suffer an I/R injury. Our results provide background for the development pharmacologic interventions in the management of I/R injury.

  3. Tax regulating carbon market in Brazil: barriers and perspectives; Regulacao tributaria do mercado de carbono no Brasil: entraves e perspectivas

    Energy Technology Data Exchange (ETDEWEB)

    Marques, Fernando; Magalhaes, Gerusa [Madrona Hong Mazzuco Brandao - Sociedade de Advogados (MHM), Sao Paulo, SP (Brazil)], email: gerusa.magalhaes@mhmlaw.com.br; Parente, Virginia [Universidade de Sao Paulo (IEE/USP), SP (Brazil). Inst. de Eletrotecnica e Energia], email: vparente@iee.usp.br; Romeiro, Viviane [Universidade de Sao Paulo (USP), SP (Brazil)], email: viviromeiro@usp.br

    2010-07-01

    The world is moving towards a low carbon economy to fight global warming caused by increases in anthropogenic emissions of greenhouse gases (GHGs). The carbon market beckons as a promising opportunity for Brazil through Clean Development Mechanism (CDM) projects, which result in Certified Emission Reductions (CERs). Although Brazil is responsible for about 8% of all CDM projects in the world, there is still no specific tax regulation for CERs, thus hindering the development of carbon market in Brazil. It is essential that Brazil have a consistent internal framework which guarantees to potential investors a minimum security on the legal and fiscal operations of CERs. There are government institutions, considering the current law and that, given the number of bills being processed in Congress, are not definitive. Such bills have different understandings for the legal classification of CERs and the related tax treatment. This article supports an urgent need for a regulatory tax system for CERs, proposing a tax exemption on transactions involving CERs in order to encourage the effective development of carbon markets in Brazil in the context of the currently international legal system in which Kyoto Protocol is based. (author)

  4. Male Gender Role Strain as a Barrier to African American Men's Physical Activity

    Science.gov (United States)

    Griffith, Derek M.; Gunter, Katie; Allen, Julie Ober

    2011-01-01

    Despite the potential health consequences, African American men tend to treat their roles as providers, fathers, spouses, and community members as more important than engaging in health behaviors such as physical activity. We conducted 14 exploratory focus groups with 105 urban, middle-aged African American men from the Midwest to examine factors…

  5. Enhancing Tumor Drug Delivery by Laser-Activated Vascular Barrier Disruption

    Science.gov (United States)

    2009-12-01

    acting drugs enhance photo- sensitizer activity. FASEB J. 2003;17:1121–3. 130. James DA, Swamy N, Paz N, Hanson RN, Ray R. Synthesis and estrogen...Shoemaker, Wai Lau, Rebecca L. Shattuck, Ann P. Kwiatkowski, Paul E. Matrisian, Luis Guerra -Santos, Emily Wilson, Thomas J. Lukas, Linda J. Van Eldik, and

  6. Barriers to Increasing the Physical Activity of People with Intellectual Disabilities

    Science.gov (United States)

    Cartwright, Luke; Reid, Marie; Hammersley, Richard; Walley, Robert M.

    2017-01-01

    Background: The prevalence of obesity, inactivity and related morbidity and mortality is higher amongst people with intellectual disabilities than in the population in general, an issue of global concern. This research examined the perspectives of people with intellectual disabilities and their carers, on exercise and activity. Materials and…

  7. Barriers, motivators, and facilitators of physical activity in dementia patients : A systematic review

    NARCIS (Netherlands)

    van Alphen, Helena J. M.; Hortobagyi, Tibor; van Heuvelen, Marieke J. G.

    2016-01-01

    Purpose: Physical activity (PA) has the potential to slow the progression of dementia patients' cognitive and physical decline. A better understanding of the factors that facilitate or hamper dementia patients' PA participation will increase the success rate of implementing PA in dementia patients'

  8. Barriers, motivators, and facilitators of physical activity in dementia patients : A systematic review

    NARCIS (Netherlands)

    van Alphen, Helena J. M.; Hortobagyi, Tibor; van Heuvelen, Marieke J. G.

    2016-01-01

    Purpose: Physical activity (PA) has the potential to slow the progression of dementia patients' cognitive and physical decline. A better understanding of the factors that facilitate or hamper dementia patients' PA participation will increase the success rate of implementing PA in dementia patients'

  9. Understanding and Dismantling Barriers for Partnerships for Inclusive Education: A Cultural Historical Activity Theory Perspective

    Science.gov (United States)

    Waitoller, Federico R.; Kozleski, Elizabeth B.

    2013-01-01

    Increasingly, universities and school districts share responsibility for teacher and student learning. Sharing responsibility demands that both institutions work to develop closer relationships through ongoing engagement, dialogue and negotiation. Drawing from Cultural Historical Activity Theory (CHAT), we examined one school/university…

  10. Barriers to Increasing the Physical Activity of People with Intellectual Disabilities

    Science.gov (United States)

    Cartwright, Luke; Reid, Marie; Hammersley, Richard; Walley, Robert M.

    2017-01-01

    Background: The prevalence of obesity, inactivity and related morbidity and mortality is higher amongst people with intellectual disabilities than in the population in general, an issue of global concern. This research examined the perspectives of people with intellectual disabilities and their carers, on exercise and activity. Materials and…

  11. Motivators and barriers to engaging in healthy eating and physical activity in young adult men

    Science.gov (United States)

    Internationally, young men (aged 18-25 years) have a high prevalence of overweight and obesity and many fail to meet recommended levels of physical activity or dietary guidelines. There is a lack of engagement and understanding of young men's needs in health-related research. Therefore, this study a...

  12. Office-based physical activity and nutrition intervention: barriers, enablers, and preferred strategies for workplace obesity prevention, Perth, Western Australia, 2012.

    Science.gov (United States)

    Blackford, Krysten; Jancey, Jonine; Howat, Peter; Ledger, Melissa; Lee, Andy H

    2013-09-12

    Workplace health promotion programs to prevent overweight and obesity in office-based employees should be evidence-based and comprehensive and should consider behavioral, social, organizational, and environmental factors. The objective of this study was to identify barriers to and enablers of physical activity and nutrition as well as intervention strategies for health promotion in office-based workplaces in the Perth, Western Australia, metropolitan area in 2012. We conducted an online survey of 111 employees from 55 organizations. The online survey investigated demographics, individual and workplace characteristics, barriers and enablers, intervention-strategy preferences, and physical activity and nutrition behaviors. We used χ(2) and Mann-Whitney U statistics to test for differences between age and sex groups for barriers and enablers, intervention-strategy preferences, and physical activity and nutrition behaviors. Stepwise multiple regression analysis determined factors that affect physical activity and nutrition behaviors. We identified several factors that affected physical activity and nutrition behaviors, including the most common barriers ("too tired" and "access to unhealthy food") and enablers ("enjoy physical activity" and "nutrition knowledge"). Intervention-strategy preferences demonstrated employee support for health promotion in the workplace. The findings provide useful insights into employees' preferences for interventions; they can be used to develop comprehensive programs for evidence-based workplace health promotion that consider environmental and policy influences as well as the individual.

  13. Historical changes in the Mississippi-Alabama barrier-island chain and the roles of extreme storms, sea level, and human activities

    Science.gov (United States)

    Morton, R.A.

    2008-01-01

    Barrier-island chains worldwide are undergoing substantial changes, and their futures remain uncertain. An historical analysis of a barrier-island chain in the north-central Gulf of Mexico shows that the Mississippi barriers are undergoing rapid systematic land loss and translocation associated with: (1) unequal lateral transfer of sand related to greater updrift erosion compared to downdrift deposition; (2) barrier narrowing resulting from simultaneous erosion of shores along the Gulf and Mississippi Sound; and (3) barrier segmentation related to storm breaching. Dauphin Island, Alabama, is also losing land for some of the same reasons as it gradually migrates landward. The principal causes of land loss are frequent intense storms, a relative rise in sea level, and a sediment-budget deficit. Considering the predicted trends for storms and sea level related to global warming, it is certain that the Mississippi-Alabama (MS-AL) barrier islands will continue to lose land area at a rapid rate unless the trend of at least one causal factor reverses. Historical land-loss trends and engineering records show that progressive increases in land-loss rate correlate with nearly simultaneous deepening of channels dredged across the outer bars of the three tidal inlets maintained for deep-draft shipping. This correlation indicates that channel-maintenance activities along the MS-AL barriers have impacted the sediment budget by disrupting the alongshore sediment transport system and progressively reducing sand supply. Direct management of this causal factor can be accomplished by strategically placing dredged sediment where adjacent barrier-island shores will receive it for island nourishment and rebuilding.

  14. V-1 regulates capping protein activity in vivo.

    Science.gov (United States)

    Jung, Goeh; Alexander, Christopher J; Wu, Xufeng S; Piszczek, Grzegorz; Chen, Bi-Chang; Betzig, Eric; Hammer, John A

    2016-10-25

    Capping Protein (CP) plays a central role in the creation of the Arp2/3-generated branched actin networks comprising lamellipodia and pseudopodia by virtue of its ability to cap the actin filament barbed end, which promotes Arp2/3-dependent filament nucleation and optimal branching. The highly conserved protein V-1/Myotrophin binds CP tightly in vitro to render it incapable of binding the barbed end. Here we addressed the physiological significance of this CP antagonist in Dictyostelium, which expresses a V-1 homolog that we show is very similar biochemically to mouse V-1. Consistent with previous studies of CP knockdown, overexpression of V-1 in Dictyostelium reduced the size of pseudopodia and the cortical content of Arp2/3 and induced the formation of filopodia. Importantly, these effects scaled positively with the degree of V-1 overexpression and were not seen with a V-1 mutant that cannot bind CP. V-1 is present in molar excess over CP, suggesting that it suppresses CP activity in the cytoplasm at steady state. Consistently, cells devoid of V-1, like cells overexpressing CP described previously, exhibited a significant decrease in cellular F-actin content. Moreover, V-1-null cells exhibited pronounced defects in macropinocytosis and chemotactic aggregation that were rescued by V-1, but not by the V-1 mutant. Together, these observations demonstrate that V-1 exerts significant influence in vivo on major actin-based processes via its ability to sequester CP. Finally, we present evidence that V-1's ability to sequester CP is regulated by phosphorylation, suggesting that cells may manipulate the level of active CP to tune their "actin phenotype."

  15. Phosphorylation regulates NCC stability and transporter activity in vivo.

    Science.gov (United States)

    Yang, Sung-Sen; Fang, Yu-Wei; Tseng, Min-Hua; Chu, Pei-Yi; Yu, I-Shing; Wu, Han-Chung; Lin, Shu-Wha; Chau, Tom; Uchida, Shinichi; Sasaki, Sei; Lin, Yuh-Feng; Sytwu, Huey-Kang; Lin, Shih-Hua

    2013-10-01

    A T60M mutation in the thiazide-sensitive sodium chloride cotransporter (NCC) is common in patients with Gitelman's syndrome (GS). This mutation prevents Ste20-related proline and alanine-rich kinase (SPAK)/oxidative stress responsive kinase-1 (OSR1)-mediated phosphorylation of NCC and alters NCC transporter activity in vitro. Here, we examined the physiologic effects of NCC phosphorylation in vivo using a novel Ncc T58M (human T60M) knock-in mouse model. Ncc(T58M/T58M) mice exhibited typical features of GS with a blunted response to thiazide diuretics. Despite expressing normal levels of Ncc mRNA, these mice had lower levels of total Ncc and p-Ncc protein that did not change with a low-salt diet that increased p-Spak. In contrast to wild-type Ncc, which localized to the apical membrane of distal convoluted tubule cells, T58M Ncc localized primarily to the cytosolic region and caused an increase in late distal convoluted tubule volume. In MDCK cells, exogenous expression of phosphorylation-defective NCC mutants reduced total protein expression levels and membrane stability. Furthermore, our analysis found diminished total urine NCC excretion in a cohort of GS patients with homozygous NCC T60M mutations. When Wnk4(D561A/+) mice, a model of pseudohypoaldosteronism type II expressing an activated Spak/Osr1-Ncc, were crossed with Ncc(T58M/T58M) mice, total Ncc and p-Ncc protein levels decreased and the GS phenotype persisted over the hypertensive phenotype. Overall, these data suggest that SPAK-mediated phosphorylation of NCC at T60 regulates NCC stability and function, and defective phosphorylation at this residue corrects the phenotype of pseudohypoaldosteronism type II.

  16. Ubiquitin chain conformation regulates recognition and activity of interacting proteins.

    Science.gov (United States)

    Ye, Yu; Blaser, Georg; Horrocks, Mathew H; Ruedas-Rama, Maria J; Ibrahim, Shehu; Zhukov, Alexander A; Orte, Angel; Klenerman, David; Jackson, Sophie E; Komander, David

    2012-12-13

    Mechanisms of protein recognition have been extensively studied for single-domain proteins, but are less well characterized for dynamic multidomain systems. Ubiquitin chains represent a biologically important multidomain system that requires recognition by structurally diverse ubiquitin-interacting proteins. Ubiquitin chain conformations in isolation are often different from conformations observed in ubiquitin-interacting protein complexes, indicating either great dynamic flexibility or extensive chain remodelling upon binding. Using single-molecule fluorescence resonance energy transfer, we show that Lys 63-, Lys 48- and Met 1-linked diubiquitin exist in several distinct conformational states in solution. Lys 63- and Met 1-linked diubiquitin adopt extended 'open' and more compact 'closed' conformations, and ubiquitin-binding domains and deubiquitinases (DUBs) select pre-existing conformations. By contrast, Lys 48-linked diubiquitin adopts predominantly compact conformations. DUBs directly recognize existing conformations, but may also remodel ubiquitin chains to hydrolyse the isopeptide bond. Disruption of the Lys 48-diubiquitin interface changes conformational dynamics and affects DUB activity. Hence, conformational equilibria in ubiquitin chains provide an additional layer of regulation in the ubiquitin system, and distinct conformations observed in differently linked polyubiquitin may contribute to the specificity of ubiquitin-interacting proteins.

  17. German National Galileo Public Regulated Service (PRS) Testing Activities

    Science.gov (United States)

    Habrich, Heinz; Söhne, Wolfgang

    2013-04-01

    The European Global Navigation System (GNSS) Galileo is going to be established in the near future. Currently, four satellites are in place forming the In-Orbit-Testing (IOT) phase. Within the next years, the constellation will be filled. Full Operational Capability (FOC) will be reached 2019. Beside the Open Service (OS) which is comparable to other OS of existing GNSS, e.g., GPS C/A, there is a so-called Public Regulated Service (PRS) included in the IOT satellites already. The PRS will have improved robustness, i.e. robust signals which will be resistant against involuntary interferences, jamming and spoofing. The PRS signal is encrypted and there will be a restricted access to authorized users, e.g. safety and emergency services, authorities with security task, critical infrastructure organizations etc. The access to the PRS which will be controlled through a special key management will be managed and supervised within the European Union (EU) Member States (MS) by national authorities, the Competent PRS Authority (CPA). But a set of Common Minimum Standards (CMS) will define the minimum requirements applicable to each PRS participant. Nevertheless, each MS is responsible for its national key management. This presentation will inform about the testing activities for Galileo PRS in Germany. The coarse concept for the testing is explained, the schedule is outlined. Finally, the paper will formulate some expectations to the Galileo PRS, e.g. for international cooperation.

  18. AMP-activated protein kinase (AMPK) activity negatively regulates chondrogenic differentiation.

    Science.gov (United States)

    Bandow, Kenjiro; Kusuyama, Joji; Kakimoto, Kyoko; Ohnishi, Tomokazu; Matsuguchi, Tetsuya

    2015-05-01

    Chondrocytes are derived from mesenchymal stem cells, and play an important role in cartilage formation. Sex determining region Y box (Sox) family transcription factors are essential for chondrogenic differentiation, whereas the intracellular signal pathways of Sox activation have not been clearly elucidated. AMP-activated protein kinase (AMPK) is a serine-threonine kinase generally regarded as a key regulator of cellular energy homeostasis. It is known that the catalytic alpha subunit of AMPK is activated by upstream AMPK kinases (AMPKKs) including liver kinase B1 (LKB1). We have previously reported that AMPK is a negative regulator of osteoblastic differentiation. Here, we have explored the role of AMPK in chondrogenic differentiation using in vitro culture models. The phosphorylation level of the catalytic AMPK alpha subunit significantly decreased during chondrogenic differentiation of primary chondrocyte precursors as well as ATDC-5, a well-characterized chondrogenic cell line. Treatment with metformin, an activator of AMPK, significantly reduced cartilage matrix formation and inhibited gene expression of sox6, sox9, col2a1 and aggrecan core protein (acp). Thus, chondrocyte differentiation is functionally associated with decreased AMPK activity. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Curcumin protects intestinal mucosal barrier function of rat enteritis via activation of MKP-1 and attenuation of p38 and NF-κB activation.

    Directory of Open Access Journals (Sweden)

    Wei-Bing Song

    Full Text Available BACKGROUND: Intestinal mucosa barrier (IMB dysfunction results in many notorious diseases for which there are currently few effective treatments. We studied curcumin's protective effect on IMB and examined its mechanism by using methotrexate (MTX induced rat enteritis model and lipopolysaccharide (LPS treated cell death model. METHODOLOGY/PRINCIPAL FINDINGS: Curcumin was intragastrically administrated from the first day, models were made for 7 days. Cells were treated with curcumin for 30 min before exposure to LPS. Rat intestinal mucosa was collected for evaluation of pathological changes. We detected the activities of D-lactate and diamine oxidase (DAO according to previous research and measured the levels of myeloperoxidase (MPO and superoxide dismutase (SOD by colorimetric method. Intercellular adhesion molecule-1 (ICAM-1, tumor necrosis factor α (TNF-α and interleukin 1β (IL-1β were determined by RT-PCR and IL-10 production was determined by ELISA. We found Curcumin decreased the levels of D-lactate, DAO, MPO, ICAM-1, IL-1β and TNF-α, but increased the levels of IL-10 and SOD in rat models. We further confirmed mitogen-activated protein kinase phosphatase-1 (MKP-1 was activated but phospho-p38 was inhibited by curcumin by western blot assay. Finally, NF-κB translocation was monitored by immunofluorescent staining. We showed that curcumin repressed I-κB and interfered with the translocation of NF-κB into nucleus. CONCLUSIONS/SIGNIFICANCE: The effect of curcumin is mediated by the MKP-1-dependent inactivation of p38 and inhibition of NF-κB-mediated transcription. Curcumin, with anti-inflammatory and anti-oxidant activities may be used as an effective reagent for protecting intestinal mucosa barrier and other related intestinal diseases.

  20. Regulation of human cerebro-microvascular endothelial baso-lateral adhesion and barrier function by S1P through dual involvement of S1P1 and S1P2 receptors.

    Science.gov (United States)

    Wiltshire, Rachael; Nelson, Vicky; Kho, Dan Ting; Angel, Catherine E; O'Carroll, Simon J; Graham, E Scott

    2016-01-27

    Herein we show that S1P rapidly and acutely reduces the focal adhesion strength and barrier tightness of brain endothelial cells. xCELLigence biosensor technology was used to measure focal adhesion, which was reduced by S1P acutely and this response was mediated through both S1P1 and S1P2 receptors. S1P increased secretion of several pro-inflammatory mediators from brain endothelial cells. However, the magnitude of this response was small in comparison to that mediated by TNFα or IL-1β. Furthermore, S1P did not significantly increase cell-surface expression of any key cell adhesion molecules involved in leukocyte recruitment, included ICAM-1 and VCAM-1. Finally, we reveal that S1P acutely and dynamically regulates microvascular endothelial barrier tightness in a manner consistent with regulated rapid opening followed by closing and strengthening of the barrier. We hypothesise that the role of the S1P receptors in this process is not to cause barrier dysfunction, but is related to controlled opening of the endothelial junctions. This was revealed using real-time measurement of barrier integrity using ECIS ZΘ TEER technology and endothelial viability using xCELLigence technology. Finally, we show that these responses do not occur simply though the pharmacology of a single S1P receptor but involves coordinated action of S1P1 and S1P2 receptors.

  1. Cystatin F regulates proteinase activity in IL-2-activated natural killer cells.

    Science.gov (United States)

    Maher, Katarina; Konjar, Spela; Watts, Colin; Turk, Boris; Kopitar-Jerala, Natasa

    2014-01-01

    Cystatin F is a unique member of the cystatin family of cysteine protease inhibitors, which is synthesized as an inactive dimer and it is activated by N-terminal cleavage in the endolysosomes. It is expressed in the cells of the immune system: myeloid cells and the cells involved in target cell killing: natural killer (NK) cells and cytotoxic T cells (CTLs). Upon activation of the NK cells with interleukin 2 (IL-2), cystatin F was found upregulated and co-localized in cytotoxic granules with cathepsin C (CatC) and CatV. However, cystatin F inhibits the CatC in cells only when its N-terminal part is processed. Although cystatin F could inhibit both CatV and CatC, the IL-2 stimulation of the YT cells resulted in an increased CatV activity, while the CatC activity was unchanged. The incubation of IL-2 activated NK cells with a cysteine proteinase inhibitor E-64d increased the cystatin F dimer formation. Our results suggest that cystatin F not only inhibits CatV, but it is processed by the CatV in order to inhibit the CatC activity in cytotoxic granules. The regulation of the CatC activity in the cytotoxic granules of the NK cells by the cystatin F could be important for the processing and activation of granule-associated serine proteases - granzymes.

  2. Low-Dose Endothelial Monocyte-Activating Polypeptide-II Increases Blood-Tumor Barrier Permeability by Activating the RhoA/ROCK/PI3K Signaling Pathway.

    Science.gov (United States)

    Li, Zhen; Liu, Xiao-Bai; Liu, Yun-Hui; Xue, Yi-Xue; Liu, Jing; Teng, Hao; Xi, Zhuo; Yao, Yi-Long

    2016-06-01

    Previous studies have demonstrated that low-dose endothelial monocyte-activating polypeptide-II (EMAP-II) can increase blood-tumor barrier (BTB) permeability via both paracellular and transcellular pathways. In addition, we revealed that the RhoA/Rho kinase (ROCK) signaling pathway is involved in EMAP-II-induced BTB opening. This study further investigated the exact mechanisms by which the RhoA/ROCK signaling pathway affects EMAP-II-induced BTB hyperpermeability. In an in vitro BTB model, low-dose EMAP-II significantly activated phosphatidylinositol-3-kinase (PI3K) in rat brain microvascular endothelial cells (RBMECs) at 0.75 h. Pretreatment with RhoA inhibitor C3 exoenzyme or ROCK inhibitor Y-27632 completely blocked EMAP-II-induced activation of PI3K. PKC-α/β inhibitor GÖ6976 pretreatment caused no change in EMAP-II-induced activation of PI3K. Besides, pretreatment with LY294002, a specific inhibitor of PI3K, did not affect EMAP-II-induced activation of PKC-α/β. Furthermore, LY294002 pretreatment significantly diminished EMAP-II-induced changes in BTB permeability, phosphorylation of myosin light chain and cofilin, expression and distribution of tight junction-associated protein ZO-1, and actin cytoskeleton arrangement in RBMECs. In summary, this study demonstrates that low-dose EMAP-II can increase BTB permeability by activating the RhoA/ROCK/PI3K signaling pathway.

  3. Collagen I-induced dendritic cells activation is regulated by TNF- production through down-regulation of IRF4

    Indian Academy of Sciences (India)

    Barun Poudel; Hyeon-Hui Ki; Young-Mi Lee; Dae-Ki Kim

    2015-03-01

    Previously we have shown that collagen I enhances the maturation and function of dendritic cells (DCs). Inflammatory mediators such as tumour necrosis factor (TNF)-, interleukin (IL)-1 and lipopolysaccharide (LPS) are also known to activate DCs. Here we investigated the involvement of TNF- on the collagen I-induced DCs activation. TNF-a neutralization inhibited collagen I-induced IL-12 secretions by DCs. Additionally, we observed suppression of collagen I-induced costimulatory molecules expression along with down-regulation of genes involved in DCs activation pathway. Furthermore, TNF- inhibition upon collagen Istimulation up-regulated the expression of interferon regulatory transcription factor IRF4, when compared to collagen I only treated cells. Collectively, our data demonstrate that collagen I induce TNF- production, which is crucial for the activation and function of DCs, through down-regulation of IRF4, and implicates the importance in development of anti- TNF- therapeutics for several inflammatory diseases.

  4. The role of multidrug resistance protein (MRP-1) as an active efflux transporter on blood-brain barrier (BBB) permeability.

    Science.gov (United States)

    Lingineni, Karthik; Belekar, Vilas; Tangadpalliwar, Sujit R; Garg, Prabha

    2017-01-03

    Drugs acting on central nervous system (CNS) may take longer duration to reach the market as these compounds have a higher attrition rate in clinical trials due to the complexity of the brain, side effects, and poor blood-brain barrier (BBB) permeability compared to non-CNS-acting compounds. The roles of active efflux transporters with BBB are still unclear. The aim of the present work was to develop a predictive model for BBB permeability that includes the MRP-1 transporter, which is considered as an active efflux transporter. A support vector machine model was developed for the classification of MRP-1 substrates and non-substrates, which was validated with an external data set and Y-randomization method. An artificial neural network model has been developed to evaluate the role of MRP-1 on BBB permeation. A total of nine descriptors were selected, which included molecular weight, topological polar surface area, ClogP, number of hydrogen bond donors, number of hydrogen bond acceptors, number of rotatable bonds, P-gp, BCRP, and MRP-1 substrate probabilities for model development. We identified 5 molecules that fulfilled all criteria required for passive permeation of BBB, but they all have a low logBB value, which suggested that the molecules were effluxed by the MRP-1 transporter.

  5. Arabidopsis TTG2 regulates TRY expression through enhancement of activator complex-triggered activation.

    Science.gov (United States)

    Pesch, Martina; Dartan, Burcu; Birkenbihl, Rainer; Somssich, Imre E; Hülskamp, Martin

    2014-10-01

    Trichome patterning in Arabidopsis thaliana is regulated by a regulatory feedback loop of the trichome promoting factors TRANSPARENT TESTA GLABRA1 (TTG1), GLABRA3 (GL3)/ENHANCER OF GL3 (EGL3), and GL1 and a group of homologous R3MYB proteins that act as their inhibitors. Together, they regulate the temporal and spatial expression of GL2 and TTG2, which are considered to control trichome cell differentiation. In this work, we show that TTG2 is a specific activator of TRY (but not CPC or GL2). The WRKY protein TTG2 binds to W-boxes in a minimal promoter fragment of TRY, and these W-boxes are essential for rescue of the try mutant phenotype. We further show that TTG2 alone is not able to activate TRY expression, but rather drastically enhances the activation by TTG1 and GL3. As TTG2 physically interacts with TTG1 and because TTG2 can associate with GL3 through its interaction with TTG1, we propose that TTG2 enhances the activity of TTG1 and GL3 by forming a protein complex.

  6. NMDA receptor activation regulates sociability by its effect on mTOR signaling activity

    Science.gov (United States)

    Burket, Jessica A.; Benson, Andrew D.; Tang, Amy H.; Deutsch, Stephen I.

    2017-01-01

    Tuberous Sclerosis Complex is one example of a syndromic form of autism spectrum disorder associated with disinhibited activity of mTORCl in neurons (e.g., cerebellar Purkinje cells). mTORCl is a complex protein possessing serine/threonine kinase activity and a key downstream molecule in a signaling cascade beginning at the cell surface with the transduction of neurotransmitters (e.g., glutamate and acetylcholine) and nerve growth factors (e.g., Brain-Derived Neurotrophic Factor). Interestingly, the severity of the intellectual disability in Tuberous Sclerosis Complex may relate more to this metabolic disturbance (i.e., overactivity of mTOR signaling) than the density of cortical tubers. Several recent reports showed that rapamycin, an inhibitor of mTORCl, improved sociability and other symptoms in mouse models of Tuberous Sclerosis Complex and autism spectrum disorder, consistent with mTORCl overactivity playing an important pathogenic role. NMDA receptor activation may also dampen mTORCl activity by at least two possible mechanisms: regulating intraneuronal accumulation of arginine and the phosphorylation status of a specific extracellular signal regulating kinase (i.e., ERK1/2), both of which are “drivers” of mTORCl activity. Conceivably, the prosocial effects of targeting the NMDA receptor with agonists in mouse models of autism spectrum disorders result from their ability to dampen mTORC1 activity in neurons. Strategies for dampening mTORC1 overactivity by NMDA receptor activation may be preferred to its direct inhibition in chronic neurodevelopmental disorders, such as autism spectrum disorders. PMID:25703582

  7. NMDA receptor activation regulates sociability by its effect on mTOR signaling activity.

    Science.gov (United States)

    Burket, Jessica A; Benson, Andrew D; Tang, Amy H; Deutsch, Stephen I

    2015-07-01

    Tuberous Sclerosis Complex is one example of a syndromic form of autism spectrum disorder associated with disinhibited activity of mTORC1 in neurons (e.g., cerebellar Purkinje cells). mTORC1 is a complex protein possessing serine/threonine kinase activity and a key downstream molecule in a signaling cascade beginning at the cell surface with the transduction of neurotransmitters (e.g., glutamate and acetylcholine) and nerve growth factors (e.g., Brain-Derived Neurotrophic Factor). Interestingly, the severity of the intellectual disability in Tuberous Sclerosis Complex may relate more to this metabolic disturbance (i.e., overactivity of mTOR signaling) than the density of cortical tubers. Several recent reports showed that rapamycin, an inhibitor of mTORC1, improved sociability and other symptoms in mouse models of Tuberous Sclerosis Complex and autism spectrum disorder, consistent with mTORC1 overactivity playing an important pathogenic role. NMDA receptor activation may also dampen mTORC1 activity by at least two possible mechanisms: regulating intraneuronal accumulation of arginine and the phosphorylation status of a specific extracellular signal regulating kinase (i.e., ERK1/2), both of which are "drivers" of mTORC1 activity. Conceivably, the prosocial effects of targeting the NMDA receptor with agonists in mouse models of autism spectrum disorders result from their ability to dampen mTORC1 activity in neurons. Strategies for dampening mTORC1 overactivity by NMDA receptor activation may be preferred to its direct inhibition in chronic neurodevelopmental disorders, such as autism spectrum disorders.

  8. MRX protects fork integrity at protein–DNA barriers, and its absence causes checkpoint activation dependent on chromatin context

    DEFF Research Database (Denmark)

    Bentsen, Iben Bach; Nielsen, Ida; Lisby, Michael

    2013-01-01

    To address how eukaryotic replication forks respond to fork stalling caused by strong non-covalent protein–DNA barriers, we engineered the controllable Fob-block system in Saccharomyces cerevisiae. This system allows us to strongly induce and control replication fork barriers (RFB) at their natural...

  9. Permeable reactive barrier of surface hydrophobic granular activated carbon coupled with elemental iron for the removal of 2,4-dichlorophenol in water

    Energy Technology Data Exchange (ETDEWEB)

    Yang Ji, E-mail: yangji@ecust.edu.cn [School of Resources and Environmental Engineering, State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, East China University of Science and Technology, Shanghai 200237 (China); Cao Limei; Guo Rui; Jia Jinping [School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240 (China)

    2010-12-15

    Granular activated carbon was modified with dimethyl dichlorosilane to improve its surface hydrophobicity, and therefore to improve the performance of permeable reactive barrier constructed with the modified granular activated carbon and elemental iron. X-ray photoelectron spectroscopy shows that the surface silicon concentration of the modified granular activated carbon is higher than that of the original one, leading to the increased surface hydrophobicity. Although the specific surface area decreased from 895 to 835 m{sup 2} g{sup -1}, the modified granular activated carbon could adsorb 20% more 2,4-dichlorophenol than the original one did in water. It is also proven that the permeable reactive barrier with the modified granular activated carbon is more efficient at 2,4-dichlorophenol dechlorination, in which process 2,4-dichlorophenol is transformed to 2-chlorophenol or 4-chlorophenol then to phenol, or to phenol directly.

  10. Regulator of complement activation (RCA) gene cluster in Xenopus tropicalis.

    Science.gov (United States)

    Oshiumi, Hiroyuki; Suzuki, Yuzuru; Matsumoto, Misako; Seya, Tsukasa

    2009-05-01

    Genome and expressed sequence tag information of Xenopus tropicalis suggested that short-consensus repeat (SCR)-containing proteins are encoded by three genes that are mapped within a 300-kb downstream of PFKFB2, which is a marker gene for the regulator of complement activation (RCA) loci in human and chicken. Based on this observation, we cloned the three cDNAs of these proteins using 3'- or 5'-RACE technique. Since their primary structures and locations of the proximity to the PFKFB2 locus, we named them amphibian RCA protein (ARC) 1, 2, and 3. Expression in human HEK293 or CHO cells suggested that ARC1 is a soluble protein of Mr approximately 67 kDa, ARC2 is a membrane protein with Mr 44 kDa, and ARC3 a secretary protein with a putative transmembrane region. They were N-glycosylated during maturation. In human and chicken RCA clusters, the order in which genes for soluble, GPI-anchored, and membrane forms of SCR proteins are arranged is from the distant to proximity to the PFKFB2 gene. However, the amphibian ARC1, 2, and 3 resembled one another and did not reflect the same order found in human and chicken RCA genes. This may be due to self-duplication of ARCs to form a family, and it evolved after the amphibia separated from the ancestor of the amniotes, which possessed soluble, GPI-anchored, and membrane forms of SCR protein members. Taken together, frog possesses a RCA locus, but the constitution of the ARC proteins differs from that of the amniotes with a unique self-resemblance.

  11. Identity, regulation, and activity of inducible diterpenoid phytoalexins in maize.

    Science.gov (United States)

    Schmelz, Eric A; Kaplan, Fatma; Huffaker, Alisa; Dafoe, Nicole J; Vaughan, Martha M; Ni, Xinzhi; Rocca, James R; Alborn, Hans T; Teal, Peter E

    2011-03-29

    Phytoalexins constitute a broad category of pathogen- and insect-inducible biochemicals that locally protect plant tissues. Because of their agronomic significance, maize and rice have been extensively investigated for their terpenoid-based defenses, which include insect-inducible monoterpene and sesquiterpene volatiles. Rice also produces a complex array of pathogen-inducible diterpenoid phytoalexins. Despite the demonstration of fungal-induced ent-kaur-15-ene production in maize over 30 y ago, the identity of functionally analogous maize diterpenoid phytoalexins has remained elusive. In response to stem attack by the European corn borer (Ostrinia nubilalis) and fungi, we observed the induced accumulation of six ent-kaurane-related diterpenoids, collectively termed kauralexins. Isolation and identification of the predominant Rhizopus microsporus-induced metabolites revealed ent-kaur-19-al-17-oic acid and the unique analog ent-kaur-15-en-19-al-17-oic acid, assigned as kauralexins A3 and B3, respectively. Encoding an ent-copalyl diphosphate synthase, fungal-induced An2 transcript accumulation precedes highly localized kauralexin production, which can eventually exceed 100 μg · g(-1) fresh weight. Pharmacological applications of jasmonic acid and ethylene also synergize the induced accumulation of kauralexins. Occurring at elevated levels in the scutella of all inbred lines examined, kauralexins appear ubiquitous in maize. At concentrations as low as 10 μg · mL(-1), kauralexin B3 significantly inhibited the growth of the opportunistic necrotroph R. microsporus and the causal agent of anthracnose stalk rot, Colletotrichum graminicola. Kauralexins also exhibited significant O. nubilalis antifeedant activity. Our work establishes the presence of diterpenoid defenses in maize and enables a more detailed analysis of their biosynthetic pathways, regulation, and crop defense function.

  12. Relationship between functional regulation of enteric epithelial barrier and autoimmunity disease%肠上皮屏障功能的调节与自身免疫性疾病的关系

    Institute of Scientific and Technical Information of China (English)

    李兰

    2011-01-01

    Ever increasing research find many autoimmune diseases have close relation to intestinal epithelium barrier. This review will provide a progress on the barrier structure, regulation and relation to autoimmune disease.%近年来研究发现很多自身免疫性疾病与肠上皮屏障的功能密切相关,本文着重对肠上皮屏障的基本结构、调控及与自身免疫性疾病的关系作一综述.

  13. Termination of the Activating NK Cell Immunological Synapse Is an Active and Regulated Process.

    Science.gov (United States)

    Netter, Petra; Anft, Moritz; Watzl, Carsten

    2017-08-23

    Cellular cytotoxicity is essential for the elimination of virus-infected and cancerous cells by NK cells. It requires a direct cellular contact through the establishment of an immunological synapse (IS) between the NK cell and the target cell. In this article, we show that not only the establishment of the IS, but also its maintenance is a highly regulated process. Ongoing receptor-proximal signaling events from activating NK cell receptors and actin dynamics were necessary to maintain a stable contact in an energy-dependent fashion, even after the IS was formed successfully. More importantly, the initiation of a contact to a new susceptible target cell resulted in accelerated detachment from an old target cell. We propose that the maintenance of an existing IS is a dynamic and regulated process to allow for effective serial killing of NK cells. Copyright © 2017 by The American Association of Immunologists, Inc.

  14. Corrigendum to "PAHs in the Great Barrier Reef Lagoon reach potentially toxic levels from coal port activities" [Estuar. Coast. Shelf Sci. 144, 39-45

    Science.gov (United States)

    Burns, Kathryn A.

    2014-08-01

    Erratum with respect to the paper: Burns, K A, 2014 PAHs in the Great Barrier Reef Lagoon reach potentially toxic levels from coal port activities. Estuarine Coastal and Shelf Science 144, 39-45. DOI 10.1016/j.ecss.2014.04.001.

  15. Facilitators and barriers in the collaboration between the primary care and the sport sector in order to promote physical activity: A systematic literature review

    NARCIS (Netherlands)

    Leenaars, K.E.; Smit, E.; Wagemakers, A.; Molleman, G.R.; Koelen, M.A.

    2015-01-01

    INTRODUCTION: The aim of this review was to identify collaborative initiatives between the primary care and the sport sector in order to promote physical activity (PA), and barriers and facilitators in these initiatives. METHOD: Pubmed, SportDiscus, Web of Science, and SOCindex were systematically s

  16. Facilitators and barriers in the collaboration between the primary care and the sport sector in order to promote physical activity: A systematic literature review

    NARCIS (Netherlands)

    Leenaars, K.E.F.; Smit, E.; Wagemakers, A.; Molleman, G.R.M.; Koelen, M.A.

    2015-01-01

    Introduction The aim of this review was to identify collaborative initiatives between the primary care and the sport sector in order to promote physical activity (PA), and barriers and facilitators in these initiatives. Method Pubmed, SportDiscus, Web of Science, and SOCindex were systematically sea

  17. Facilitators and barriers in the collaboration between the primary care and the sport sector in order to promote physical activity: A systematic literature review

    NARCIS (Netherlands)

    Leenaars, K.E.; Smit, E.; Wagemakers, A.; Molleman, G.R.; Koelen, M.A.

    2015-01-01

    INTRODUCTION: The aim of this review was to identify collaborative initiatives between the primary care and the sport sector in order to promote physical activity (PA), and barriers and facilitators in these initiatives. METHOD: Pubmed, SportDiscus, Web of Science, and SOCindex were systematically

  18. Facilitators and barriers in the collaboration between the primary care and the sport sector in order to promote physical activity: A systematic literature review

    NARCIS (Netherlands)

    Leenaars, K.E.F.; Smit, E.; Wagemakers, A.; Molleman, G.R.M.; Koelen, M.A.

    2015-01-01

    Introduction The aim of this review was to identify collaborative initiatives between the primary care and the sport sector in order to promote physical activity (PA), and barriers and facilitators in these initiatives. Method Pubmed, SportDiscus, Web of Science, and SOCindex were systematically

  19. The APPLE Project: An Investigation of the Barriers and Promoters of Healthy Eating and Physical Activity in New Zealand Children Aged 5-12 Years

    Science.gov (United States)

    Williden, Micalla; Taylor, Rachael W; McAuley, Kirsten A; Simpson, Jean C; Oakley, Maggie; Mann, Jim I

    2006-01-01

    Objective: To use the Analysis Grid for Environments Linked to Obesity (ANGELO) framework to determine the barriers and promoters of healthy eating and physical activity in children aged 5-12 years, as a basis for the development of a pilot community-based programme for preventing obesity in children (APPLE project: A Pilot Programme for Lifestyle…

  20. ATP Induces Disruption of Tight Junction Proteins via IL-1 Beta-Dependent MMP-9 Activation of Human Blood-Brain Barrier In Vitro

    Directory of Open Access Journals (Sweden)

    Fuxing Yang

    2016-01-01

    Full Text Available Disruption of blood-brain barrier (BBB follows brain trauma or central nervous system (CNS stress. However, the mechanisms leading to this process or the underlying neural plasticity are not clearly known. We hypothesized that ATP/P2X7R signaling regulates the integrity of BBB. Activation of P2X7 receptor (P2X7R by ATP induces the release of interleukin-1β (IL-1β, which in turn enhances the activity of matrix metalloproteinase-9 (MMP-9. Degradation of tight junction proteins (TJPs such as ZO-1 and occludin occurs, which finally contributes to disruption of BBB. A contact coculture system using human astrocytes and hCMEC/D3, an immortalized human brain endothelial cell line, was used to mimic BBB in vitro. Permeability was used to evaluate changes in the integrity of TJPs. ELISA, Western blot, and immunofluorescent staining procedures were used. Our data demonstrated that exposure to the photoreactive ATP analog, 3′-O-(4-benzoylbenzoyl adenosine 5′-triphosphate (BzATP, induced a significant decrease in ZO-1 and occludin expression. Meanwhile, the decrease of ZO-1 and occludin was significantly attenuated by P2X7R inhibitors, as well as IL-1R and MMP antagonists. Further, the induction of IL-1β and MMP-9 was closely linked to ATP/P2X7R-associated BBB leakage. In conclusion, our study explored the mechanism of ATP/P2X7R signaling in the disruption of BBB following brain trauma/stress injury, especially focusing on the relationship with IL-1β and MMP-9.