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Sample records for actively regulated barrier

  1. Acute Modulations in Permeability Barrier Function Regulate Epidermal Cornification : Role of Caspase-14 and the Protease-Activated Receptor Type 2

    Demerjian, Marianne; Hachem, Jean-Pierre; Tschachler, Erwin; Denecker, Geertrui; Declercq, Wim; Vandenabeele, Peter; Mauro, Theodora; Hupe, Melanie; Crumrine, Debra; Roelandt, Truus; Houben, Evi; Elias, Peter M.; Feingold, Kenneth R.

    2008-01-01

    Stratum corneum comprises corneocytes, derived from outer stratum granulosum during terminal differentiation, embedded in a lipid-enriched extracellular matrix, secreted from epidermal lamellar bodies. Permeability barrier insults stimulate rapid secretion of preformed lamellar bodies from the outer stratum granulosum, regulated through modulations in ionic gradients and serine protease (SP)/protease-activated receptor type 2 (PAR2) signaling. Because corneocytes are also required for barrier...

  2. Barriers for recess physical activity

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

    2014-01-01

    ) with in total 111 children (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 rank the children's perceived barriers......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...... 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 (at 17 different schools...

  3. Dietary choline regulates antibacterial activity, inflammatory response and barrier function in the gills of grass carp (Ctenopharyngodon idella).

    Zhao, Hua-Fu; Jiang, Wei-Dan; Liu, Yang; Jiang, Jun; Wu, Pei; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu; Feng, Lin

    2016-05-01

    An 8-week feeding trial was conducted to determine the effects of graded levels of choline (197-1795 mg/kg) on antibacterial properties, inflammatory status and barrier function in the gills of grass carp. The results showed that optimal dietary choline supplementation significantly improved lysozyme and acid phosphatase activities, complement component 3 (C3) content, and the liver expressed antimicrobial peptide 2 and Hepcidin mRNA levels in the gills of fish (P C3 content and AHR activity, the dietary choline requirements for young grass carp (266.5-787.1 g) were estimated to be 1191.0 and 1555.0 mg/kg diet, respectively. PMID:26988287

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

    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

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

    Lee Na-Young; Kang Young-Sook

    2010-01-01

    Abstract 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 af...

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

    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-clam...

  7. Barriers to Physical Activity Among Gay Men.

    Cary, Miranda A; Brittain, Danielle R; Dinger, Mary K; Ford, Melissa L; Cain, Meagan; Sharp, Teresa A

    2016-09-01

    Gay men may not be physically active at recommended levels to achieve health benefits. Thus, a need exists to identify general (i.e., common across populations) and population-specific barriers that hinder or stop gay men from participating in physical activity (PA). Salient barriers may be identified through the extent each barrier limits PA (i.e., barrier limitation) and the level of one's confidence to overcome barriers and engage in PA (i.e., self-regulatory efficacy). The purposes of this study were to (1) provide a description of general and population-specific barriers to PA among sufficiently and insufficiently active gay men, (2) identify barrier limitation and self-regulatory efficacy for the reported barriers, and (3) examine the associations between meeting the current PA recommendation, barrier limitation, and self-regulatory efficacy. Participants were 108 self-identified gay males aged 21 to 64 years who completed a web-based survey. A total of 35 general barriers and no population-specific barriers were identified by the sufficiently and insufficiently active groups. The sufficiently active group reported higher self-regulatory efficacy and lower barrier limitation for nearly all reported barriers. A binary logistic regression used to examine the associations between PA, barrier limitation, and self-regulatory efficacy was statistically significant, χ(2)(2, N = 108) = 19.26, p < .0001, R(2) = .16. Only barrier limitation significantly contributed to the model. Future research should continue to examine barriers to PA among gay men to determine whether an intervention needs to be designed specifically for gay men or whether a one-size-fits-all intervention would be effective in helping all men overcome common barriers to engaging in PA. PMID:25643585

  8. TRPM2 channel regulates endothelial barrier function.

    Hecquet, Claudie M; Ahmmed, Gias U; Malik, Asrar B

    2010-01-01

    Oxidative [Au1]stress, through the production of oxygen metabolites such as hydrogen peroxide[Au2] (H(2)O(2)), increases vascular endothelial permeability and plays a crucial role in several lung diseases. The transient receptor potential (melastatin) 2 (TRPM2) is an oxidant-sensitive, nonselective cation channel that is widely expressed in mammalian tissues, including the vascular endothelium. We have demonstrated the involvement of TRPM2 in mediating oxidant-induced calcium entry and endothelial hyperpermeability in cultured pulmonary artery endothelial cells. Here, we provide evidence that neutrophil activation-dependent increase in endothelial permeability and neutrophil extravasation requires TRPM2 in cultured endothelial cells. In addition, protein kinase Calpha (PKCalpha) that rapidly colocalizes with the short (nonconducting) TRPM2 isoform after exposure to hydrogen peroxide positively regulates calcium entry through the functional TRPM2 channel. Thus, increase in lung microvessel permeability and neutrophil sequestration depends on the activation of endothelial TRPM2 by neutrophilic oxidants and on PKCalpha regulation of TRPM2 channel activity. Manipulating TRPM2 function in the endothelium may represent a novel strategy aimed to prevent oxidative stress-related vascular dysfunction. PMID:20204729

  9. Barriers to increased market-oriented activity

    Bisp, Søren

    1999-01-01

    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...

  10. Claudins, dietary milk proteins, and intestinal barrier regulation.

    Kotler, Belinda M; Kerstetter, Jane E; Insogna, Karl L

    2013-01-01

    The family of claudin proteins plays an important role in regulating the intestinal barrier by modulating the permeability of tight junctions. The impact of dietary protein on claudin biology has not been studied extensively. Whey proteins have been reported to improve intestinal barrier function, but their mechanism of action is not clear. Recent studies, however, have demonstrated increased intestinal claudin expression in response to milk protein components. Reviewed here are new findings suggesting that whey-protein-derived transforming growth factor β transcriptionally upregulates claudin-4 expression via a Smad-4-dependent pathway. These and other data, including limited clinical studies, are summarized below and, in the aggregate, suggest a therapeutic role for whey protein in diseases of intestinal barrier dysfunction, perhaps, in part, by regulating claudin expression. PMID:23282252

  11. Government regulation of business in a changing institutional barrier

    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.

  12. Barriers to Physical Activity Among Patients With Type 1 Diabetes

    Brazeau, Anne-Sophie; Rabasa-Lhoret, Rémi; Strychar, Irene; Mircescu, Hortensia

    2008-01-01

    OBJECTIVE—To determine, in an adult population with type 1 diabetes, barriers to regular physical activity using a diabetes-specific barriers measure (the Barriers to Physical Activity in Diabetes [type 1] [BAPAD1] scale) and factors associated with these barriers. RESEARCH DESIGN AND METHODS—One hundred adults with type 1 diabetes answered a questionnaire assessing perceived barriers to physical activity and related factors. A1C was obtained from the medical chart of each individual. RESULTS...

  13. Vinculin-dependent Cadherin mechanosensing regulates efficient epithelial barrier formation

    Floor Twiss

    2012-09-01

    Proper regulation of the formation and stabilization of epithelial cell–cell adhesion is crucial in embryonic morphogenesis and tissue repair processes. Defects in this process lead to organ malformation and defective epithelial barrier function. A combination of chemical and mechanical cues is used by cells to drive this process. We have investigated the role of the actomyosin cytoskeleton and its connection to cell–cell junction complexes in the formation of an epithelial barrier in MDCK cells. We find that the E-cadherin complex is sufficient to mediate a functional link between cell–cell contacts and the actomyosin cytoskeleton. This link involves the actin binding capacity of α-catenin and the recruitment of the mechanosensitive protein Vinculin to tensile, punctate cell–cell junctions that connect to radial F-actin bundles, which we name Focal Adherens Junctions (FAJ. When cell–cell adhesions mature, these FAJs disappear and linear junctions are formed that do not contain Vinculin. The rapid phase of barrier establishment (as measured by Trans Epithelial Electrical Resistance (TER correlates with the presence of FAJs. Moreover, the rate of barrier establishment is delayed when actomyosin contraction is blocked or when Vinculin recruitment to the Cadherin complex is prevented. Enhanced presence of Vinculin increases the rate of barrier formation. We conclude that E-cadherin-based FAJs connect forming cell–cell adhesions to the contractile actomyosin cytoskeleton. These specialized junctions are sites of Cadherin mechanosensing, which, through the recruitment of Vinculin, is a driving force in epithelial barrier formation.

  14. BARRIERS TO PHYSICAL ACTIVITY IN THE ELDERLY

    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.

  15. Circularly polarized antennas for active holographic imaging through barriers

    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.

  16. Human telomerase activity regulation

    Wojtyla, Aneta; Gladych, Marta; Rubis, Blazej

    2010-01-01

    Telomerase has been recognized as a relevant factor distinguishing cancer cells from normal cells. Thus, it has become a very promising target for anticancer therapy. The cell proliferative potential can be limited by replication end problem, due to telomeres shortening, which is overcome in cancer cells by telomerase activity or by alternative telomeres lengthening (ALT) mechanism. However, this multisubunit enzymatic complex can be regulated at various levels, including expression control b...

  17. Promoting Physical Activity: Addressing Barriers and Moving Forward

    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…

  18. Regulation of brain endothelial barrier function by microRNAs in health and neuroinflammation.

    Lopez-Ramirez, Miguel Alejandro; Reijerkerk, Arie; de Vries, Helga E; Romero, Ignacio Andres

    2016-08-01

    Brain endothelial cells constitute the major cellular element of the highly specialized blood-brain barrier (BBB) and thereby contribute to CNS homeostasis by restricting entry of circulating leukocytes and blood-borne molecules into the CNS. Therefore, compromised function of brain endothelial cells has serious consequences for BBB integrity. This has been associated with early events in the pathogenesis of several disorders that affect the CNS, such as multiple sclerosis, HIV-associated neurologic disorder, and stroke. Recent studies demonstrate that brain endothelial microRNAs play critical roles in the regulation of BBB function under normal and neuroinflammatory conditions. This review will focus on emerging evidence that indicates that brain endothelial microRNAs regulate barrier function and orchestrate various phases of the neuroinflammatory response, including endothelial activation in response to cytokines as well as restoration of inflamed endothelium into a quiescent state. In particular, we discuss novel microRNA regulatory mechanisms and their contribution to cellular interactions at the neurovascular unit that influence the overall function of the BBB in health and during neuroinflammation.-Lopez-Ramirez, M. A., Reijerkerk, A., de Vries, H. E., Romero, I. A. Regulation of brain endothelial barrier function by microRNAs in health and neuroinflammation. PMID:27118674

  19. Promoting Physical Activity in Primary Care: Overcoming the barriers

    Singer, Joel; Lindsay, Elizabeth A.; Wilson, Douglas M.C.

    1991-01-01

    The principle barriers preventing health care professionals from promoting physical activity include an incomplete understanding of the evidence linking physical activity and health, difficulty in translating research findings into a feasible and efficacious clinical intervention, resistance to adopting a preventive orientation, and concerns about the risks of physical activity. Low level activities likely provide benefit with little risk.

  20. Physical Activity and Youth with Disabilities: Barriers and Supports

    Block, Martin E.; Taliaferro, Andrea; Moran, Tom

    2013-01-01

    Physical activity and active use of leisure time is important for everyone but particularly important for youth with disabilities. Unfortunately, youth with disabilities often have a difficult time or are even excluded from participating in physical activity due to limited physical and cognitive skills, attitudinal barriers in the community, lack…

  1. Regulating prefrontal cortex activation

    Aznar, Susana; Klein, Anders Bue

    2013-01-01

    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 and the stria...

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

    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. PMID:27272074

  3. Physical activities in elderly: benefits and barriers

    Francis, Purity

    2014-01-01

    Abstract: Aim: To research and create awareness on how physical activities have promoted health in the life of the elderly. Research Questions: 1. What are the benefits of physical Activity for Elderly? 2. What obstacles inhibit elderly from physical activities? Method: The study was a Literature review with deductive content analysis method used for analyzing articles. The search engines used was EBSCO, SAGE and Google Scholar. The results are grouped in categories and sub catego...

  4. Physical activity barriers and facilitators among working mothers and fathers

    Mailey, Emily L.; Huberty, Jennifer; Dinkel, Danae; McAuley, Edward

    2014-01-01

    Background The transition to parenthood is consistently associated with declines in physical activity. In particular, working parents are at risk for inactivity, but research exploring physical activity barriers and facilitators in this population has been scarce. The purpose of this study was to qualitatively examine perceptions of physical activity among working parents. Methods Working mothers (n = 13) and fathers (n = 12) were recruited to participate in one of four focus group sessions a...

  5. Molecular regulation of osteoclast activity.

    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. PMID:16951988

  6. Barrier stabilizing mediators in regulation of microvascular endothelial permeability

    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.

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

    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.

  8. Photochemical activity in waters of the Great Barrier Reef

    Szymczak, R.; Waite, T. D.

    1991-12-01

    Photochemical activity in waters of the Great Barrier Reef was investigated through studies on the vertical, horizontal and temporal distribution of hydrogen peroxide and factors influencing its generation and decay processes. Surface hydrogen peroxide concentrations varied from 15 to 110 nM and generally decreased with depth, though a number of anomalies were detected. Photochemical activity decreased with increasing distance from the coast reflecting the positive influence of terrestrial inputs to the hydrogen peroxide generation and decay processes. Increases in photochemical activity were observed in the proximity of coral reefs. Hydrogen peroxide concentrations in the region were influenced by wind-induced mixing processes, atmospheric inputs, anthropogenic activity and seasonal light regimes.

  9. Barriers to competition in Croatia : the role of government regulation

    Rosa, Donato; Madzarevic-Sujster, Sanja; Boromisa, Ana-Maria; Sonje, Velimir

    2009-01-01

    This paper examines product market policies in Croatia by benchmarking them to OECD countries and highlighting how policies that are more conducive to competition would stimulate a more efficient allocation of resources and, in consequence, facilitate convergence to higher income levels. OECD indicators of overall regulation in product markets indicate that Croatias policies in 2007 were g...

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

    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

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

    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. PMID:27357921

  12. Neighborhood disadvantage, physical activity barriers, and physical activity among African American breast cancer survivors

    Antwan Jones

    2015-01-01

    Higher renter rates and individual barriers both contribute to lower levels of physical activity in African American breast cancer survivors. These data suggest that the potential for constant residential turnover (via rentership and perceived barriers may increase physical inactivity even where facilities may be available.

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

    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.

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

    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.

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

    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. Reproductive hormones regulate the selective permeability of the blood-brain barrier

    Wilson, Andrea C.; Clemente, Luca; Liu, Tianbing; Bowen, Richard L.; Meethal, Sivan Vadakkadath; Atwood, Craig S.

    2008-01-01

    Reproductive hormones regulate the selective permeability of the blood-brain barrier : Current address: Department of Biochemistry, Colorado State University, CO, USA. (Clemente, Luca) correspondence: Corresponding author. University of Wisconsin-Madison Medical School, Wm S. Middleton Memorial VA (GRECC 11G), 2500 Overlook Terrace, Madison, WI 53705, USA. Tel.: +1 608 256 1901x11664; fax: +1 608 280 7291. (Atw...

  17. Tax regulating carbon market in Brazil: barriers and perspectives

    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)

  18. Regulation of blood-testis barrier by actin binding proteins and protein kinases.

    Li, Nan; Tang, Elizabeth I; Cheng, C Yan

    2016-03-01

    The blood-testis barrier (BTB) is an important ultrastructure in the testis, since the onset of meiosis and spermiogenesis coincides with the establishment of a functional barrier in rodents and humans. It is also noted that a delay in the assembly of a functional BTB following treatment of neonatal rats with drugs such as diethylstilbestrol or adjudin also delays the first wave of spermiation. While the BTB is one of the tightest blood-tissue barriers, it undergoes extensive remodeling, in particular, at stage VIII of the epithelial cycle to facilitate the transport of preleptotene spermatocytes connected in clones across the immunological barrier. Without this timely transport of preleptotene spermatocytes derived from type B spermatogonia, meiosis will be arrested, causing aspermatogenesis. Yet the biology and regulation of the BTB remains largely unexplored since the morphological studies in the 1970s. Recent studies, however, have shed new light on the biology of the BTB. Herein, we critically evaluate some of these findings, illustrating that the Sertoli cell BTB is regulated by actin-binding proteins (ABPs), likely supported by non-receptor protein kinases, to modulate the organization of actin microfilament bundles at the site. Furthermore, microtubule-based cytoskeleton is also working in concert with the actin-based cytoskeleton to confer BTB dynamics. This timely review provides an update on the unique biology and regulation of the BTB based on the latest findings in the field, focusing on the role of ABPs and non-receptor protein kinases. PMID:26628556

  19. Proteinase activity regulation by glycosaminoglycans

    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.

  20. Regulation and repair of the alveolar-capillary barrier in acute lung injury.

    Bhattacharya, Jahar; Matthay, Michael A

    2013-01-01

    Considerable progress has been made in understanding the basic mechanisms that regulate fluid and protein exchange across the endothelial and epithelial barriers of the lung under both normal and pathological conditions. Clinically relevant lung injury occurs most commonly from severe viral and bacterial infections, aspiration syndromes, and severe shock. The mechanisms of lung injury have been identified in both experimental and clinical studies. Recovery from lung injury requires the reestablishment of an intact endothelial barrier and a functional alveolar epithelial barrier capable of secreting surfactant and removing alveolar edema fluid. Repair mechanisms include the participation of endogenous progenitor cells in strategically located niches in the lung. Novel treatment strategies include the possibility of cell-based therapy that may reduce the severity of lung injury and enhance lung repair. PMID:23398155

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

    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. PMID:27026634

  2. Neighborhood disadvantage, physical activity barriers, and physical activity among African American breast cancer survivors

    Antwan Jones; Paxton, Raheem J.

    2015-01-01

    In view of evidence that African American cancer survivors experience the greatest challenges in maintaining adequate levels of physical activity, this cross-sectional study was designed to determine whether individual and residential environment characteristics are associated with physical activity in this population. A total of 275 breast cancer survivors completed self-report items measuring sociodemographic variables, physical activity, and select barriers to physical activity in Spring o...

  3. Barriers to Leisure-Time Physical Activities in Individuals with Spinal Cord Injury.

    Hwang, Eric J; Groves, Mary D; Sanchez, Jacqueline N; Hudson, Cassandra E; Jao, Rachel G; Kroll, Meghan E

    2016-07-01

    This study investigated the personal, environmental, and activity barriers to leisure-time physical activities (LTPAs) among individuals with spinal cord injury (SCI). A survey instrument was administered to 85 participants with SCI. Personal barriers to LTPAs included issues involving motivation, pain, scheduling, and financial resources. Environmental barriers marked the issues regarding availability and accessibility to specialized programs, activities, and professional services. Activity barriers included limitations in equipment, training, and personal skills required by the selected activities. Significant negative correlations were found between these barriers and the levels of physical activity and satisfaction with physical activity. While working with clients with SCI, occupational therapists should identify those LTPA barriers and possible solutions in order to establish individualized action plans for enhancing participation in LTPAs. PMID:27218889

  4. Platelets actively sequester angiogenesis regulators

    Lakka Klement, Giannoula; Yip, Tai-Tung; Cassiola, Flavia; Kikuchi, Lena; Cervi, David; Podust, Vladimir; Italiano, Joseph E.; Wheatley, Erin; Abou-Slaybi, Abdo; Bender, Elise; Almog, Nava; Kieran, Mark W.; Folkman, Judah

    2009-01-01

    Clinical trials with antiangiogenic agents have not been able to validate plasma or serum levels of angiogenesis regulators as reliable markers of cancer presence or therapeutic response. We recently reported that platelets contain numerous proteins that regulate angiogenesis. We now show that accumulation of angiogenesis regulators in platelets of animals bearing malignant tumors exceeds significantly their concentration in plasma or serum, as well as their levels in platelets from non–tumor...

  5. Could one single dichotomous noise cause resonant activation for exit time over potential barrier?

    Li Jing-Hui

    2008-01-01

    This paper studies the mean first passage time (or exit time, or escape time) over the non-fluctuating potential barrier for a system driven only by a dichotomous noise. It finds that the dichotomous noise can make the particles escape over the potential barrier, in some circumstances; but in other circumstances, it can not. In the case that the particles escape over the potential barrier, a resonant activation phenomenon for the mean first passage time over the potential barrier is obtained.

  6. Bioluminescent imaging of ABCG2 efflux activity at the blood-placenta barrier

    Kumar, Jeyan S.; Bih-Rong Wei; Madigan, James P.; R Mark Simpson; Hall, Matthew D; Gottesman, Michael M.

    2016-01-01

    Physiologic barriers such as the blood placenta barrier (BPB) and the blood brain barrier protect the underlying parenchyma from pathogens and toxins. ATP-binding cassette (ABC) transporters are transmembrane proteins found at these barriers, and function to efflux xenobiotics and maintain chemical homeostasis. Despite the plethora of ex vivo and in vitro data showing the function and expression of ABC transporters, no imaging modality exists to study ABC transporter activity in vivo at the B...

  7. Regulation of nuclear and radiological activities

    The paper presents a review of the Moldovan regulatory framework regarding nuclear and radiological activities and of the competence of state regulatory authority - the National Agency for the Regulation of Nuclear and Radiological Activities.

  8. Barriers and Facilitators to Walking and Physical Activity Among American Indian Elders

    Craig N. Sawchuk, PhD; Russo, Joan E.; Andy Bogart, MA; Steve Charles; Jack Goldberg, PhD; Ralph Forquera; Peter Roy-Byrne, MD; Dedra Buchwald, MD

    2011-01-01

    Introduction Physical inactivity is common among older American Indians. Several barriers impede the establishment and maintenance of routine exercise. We examined personal and built-environment barriers and facilitators to walking and physical activity and their relationship with health-related quality of life in American Indian elders. Methods We used descriptive statistics to report barriers and facilitators to walking and physical activity among a sample of 75 American Indians aged 50 to ...

  9. Polarizability of the active site of cytochrome c reduces the activation barrier for electron transfer

    Dinpajooh, Mohammadhasan; Martin, Daniel R.; Matyushov, Dmitry V.

    2016-06-01

    Enzymes in biology’s energy chains operate with low energy input distributed through multiple electron transfer steps between protein active sites. The general challenge of biological design is how to lower the activation barrier without sacrificing a large negative reaction free energy. We show that this goal is achieved through a large polarizability of the active site. It is polarized by allowing a large number of excited states, which are populated quantum mechanically by electrostatic fluctuations of the protein and hydration water shells. This perspective is achieved by extensive mixed quantum mechanical/molecular dynamics simulations of the half reaction of reduction of cytochrome c. The barrier for electron transfer is consistently lowered by increasing the number of excited states included in the Hamiltonian of the active site diagonalized along the classical trajectory. We suggest that molecular polarizability, in addition to much studied electrostatics of permanent charges, is a key parameter to consider in order to understand how enzymes work.

  10. Polarizability of the active site of cytochrome c reduces the activation barrier for electron transfer

    Dinpajooh, Mohammadhasan; Martin, Daniel R.; Matyushov, Dmitry V.

    2016-01-01

    Enzymes in biology’s energy chains operate with low energy input distributed through multiple electron transfer steps between protein active sites. The general challenge of biological design is how to lower the activation barrier without sacrificing a large negative reaction free energy. We show that this goal is achieved through a large polarizability of the active site. It is polarized by allowing a large number of excited states, which are populated quantum mechanically by electrostatic fluctuations of the protein and hydration water shells. This perspective is achieved by extensive mixed quantum mechanical/molecular dynamics simulations of the half reaction of reduction of cytochrome c. The barrier for electron transfer is consistently lowered by increasing the number of excited states included in the Hamiltonian of the active site diagonalized along the classical trajectory. We suggest that molecular polarizability, in addition to much studied electrostatics of permanent charges, is a key parameter to consider in order to understand how enzymes work. PMID:27306204

  11. Barriers and Facilitators to Walking and Physical Activity Among American Indian Elders

    Craig N. Sawchuk, PhD

    2011-05-01

    Full Text Available IntroductionPhysical inactivity is common among older American Indians. Several barriers impede the establishment and maintenance of routine exercise. We examined personal and built-environment barriers and facilitators to walking and physical activity and their relationship with health-related quality of life in American Indian elders.MethodsWe used descriptive statistics to report barriers and facilitators to walking and physical activity among a sample of 75 American Indians aged 50 to 74 years. Pearson correlation coefficients were used to examine the relationship between health-related quality of life and barriers to walking and physical activity after adjusting for caloric expenditure and total frequency of all exercise activities.ResultsLack of willpower was the most commonly reported barrier. Elders were more likely to report personal as opposed to built-environment reasons for physical inactivity. Better health and being closer to interesting places were common walking facilitators. Health-related quality of life was inversely related to physical activity barriers, and poor mental health quality of life was more strongly associated with total barriers than poor physical health.ConclusionWe identified a variety of barriers and facilitators that may influence walking and physical activity among American Indian elders. More research is needed to determine if interventions to reduce barriers and promote facilitators can lead to objective, functional health outcomes.

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

    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

  13. Physical Activity Behavior, Barriers to Activity, and Opinions About a Smartphone-Based Physical Activity Intervention Among Rural Residents

    Kurti, Allison N; Logan, Henrietta; Manini, Todd; Dallery, Jesse

    2015-01-01

    Background: Rural Americans engage in less physical activity (PA) and experience higher rates of consequent health problems (i.e., obesity, cardiovascular disease) than urban Americans. Although geographic barriers have historically made this population hard to reach, rural individuals are increasingly gaining access to smartphones. Thus, the purpose of this study was to evaluate PA behavior and barriers to PA among rural residents and to gauge their receptiveness to a smartphone-based PA ...

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

    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…

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

    2007-01-01

    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 perm...

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

    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.

  17. Perceived benefits and barriers of physical activity: A social marketing formative study.

    Rundle-Thiele, Sharyn; Kubacki, Krzysztof; Gruneklee, Naomi

    2016-01-01

    The aim of this study was to gain formative research insights that can be used to design social marketing campaigns. One thousand four hundred fifty-nine people participated in an online survey. Factor analysis was undertaken to establish perceived benefits and barriers, and indexes were created for barriers, benefits, and healthy living knowledge. Four attitude groups were formed and analysis of variance was undertaken to explore group differences. Consumers with high perceived barriers report less physical activity than consumers with low perceived barriers to exercise. The current study provides evidence to suggest that exchange theory can offer important insights to inform social marketing intervention planning. PMID:27210584

  18. Regulation of ROCK Activity in Cancer

    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...

  19. An Electrokinetic Process Coupled Activated Carbon Barrier for Nickel Removal from Kaolinite

    Ahmad Jamshidi Zanjani

    2012-06-01

    Full Text Available Electrokinetic (EK remediation coupled with activated carbon barrier was evaluated to remove nickel (500 mg/kg from kaolinite. Laboratory experiments were performed by applying a constant voltage to create electric field strength of 1 or 1.25 V/cm for 3 days. Findings showed that the barrier filled with activated carbon could prevent the formation of reverse electro-osmotic flow, which had an adverse effect on the Ni(II removal. Application of activated carbon barrier into EK process resulted in an increase of Ni migration from 11 to 47%.

  20. An Electrokinetic Process Coupled Activated Carbon Barrier for Nickel Removal from Kaolinite

    Ahmad Jamshidi Zanjani; Mohsen Saeedi; Chih-Huang WENG

    2012-01-01

    Electrokinetic (EK) remediation coupled with activated carbon barrier was evaluated to remove nickel (500 mg/kg) from kaolinite. Laboratory experiments were performed by applying a constant voltage to create electric field strength of 1 or 1.25 V/cm for 3 days. Findings showed that the barrier filled with activated carbon could prevent the formation of reverse electro-osmotic flow, which had an adverse effect on the Ni(II) removal. Application of activated carbon barrier into EK process resul...

  1. Senescence-related functional nuclear barrier by down-regulation of nucleo-cytoplasmic trafficking gene expression

    One of the characteristic natures of senescent cells is the hypo- or irresponsiveness not only to growth factors but also to apoptotic stress. In the present study, we confirmed the inhibition of nuclear translocation of activated p-ERK1/2 and NF-kB p50 in response to growth stimuli or LPS in the senescent human diploid fibroblasts. In order to elucidate the underlying mechanism for the senescence-associated hypo-responsiveness, we carried out the comparison study for gene expression profiles through microarray analysis. In consequence, we observed the vast reduction in expression of nucleo-cytoplasmic trafficking genes in senescent cells, when compared with those in young cells. Expression levels of several nucleoporins, karyopherin α, karyopherin β, Ran, and Ran-regulating factors were confirmed to be down-regulated in senescent HDFs by using RT-PCR and Western blot methods. Taken together, these data suggest the operation of certain senescence-associated functional nuclear barriers by down-regulation of the nucleo-cytoplasmic trafficking genes in the senescent cells.

  2. Epicutaneous Allergic Sensitization by Cooperation between Allergen Protease Activity and Mechanical Skin Barrier Damage in Mice.

    Shimura, Sakiko; Takai, Toshiro; Iida, Hideo; Maruyama, Natsuko; Ochi, Hirono; Kamijo, Seiji; Nishioka, Izumi; Hara, Mutsuko; Matsuda, Akira; Saito, Hirohisa; Nakae, Susumu; Ogawa, Hideoki; Okumura, Ko; Ikeda, Shigaku

    2016-07-01

    Allergen sources such as mites, insects, fungi, and pollen contain proteases. Airway exposure to proteases induces allergic airway inflammation and IgE/IgG1 responses via IL-33-dependent mechanisms in mice. We examined the epicutaneous sensitization of mice to a model protease allergen, papain; the effects of tape stripping, which induces epidermal barrier dysfunction; and the atopic march upon a subsequent airway challenge. Papain painting on ear skin and tape stripping cooperatively promoted dermatitis, the skin gene expression of proinflammatory cytokines and growth factors, up-regulation of serum total IgE, and papain-specific IgE/IgG1 induction. Epicutaneous sensitization induced T helper (Th) 2 cells and Th17 differentiation in draining lymph nodes. Ovalbumin and protease inhibitor-treated papain induced no or weak responses, whereas the co-administration of ovalbumin and papain promoted ovalbumin-specific IgE/IgG1 induction. Wild-type and IL-33-deficient mice showed similar responses in the epicutaneous sensitization phase. The subsequent airway papain challenge induced airway eosinophilia and maintained high papain-specific IgE levels in an IL-33-dependent manner. These results suggest that allergen source-derived protease activity and mechanical barrier damage such as that caused by scratching cooperatively promote epicutaneous sensitization and skin inflammation and that IL-33 is dispensable for epicutaneous sensitization but is crucial in the atopic march upon a subsequent airway low-dose encounter with protease allergens. PMID:26987428

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

    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.

  4. Barriers and incentives to introducing new reactors in the de-regulated electricity market

    After a long period of stagnation, there is now a realistic prospect that a revival of nuclear power building is imminent in the USA and possibly also in the UK. New reactors will need to compete in electricity markets which are being progressively de-regulated. This is a very different situation from the one which prevailed when the existing reactors were built. There are strong incentives to pursue new reactors, but there are also difficult barriers to overcome. This paper considers these barriers and incentives in relation to both the evolutionary plants that are most likely to be built in the immediate future and also to more advanced plants that will hopefully follow. While those evolutionary designs currently positioned for new or replacement build have been developed specifically to address the needs of utilities, for many of the advanced concepts that will be presented at this workshop there is a large gulf separating the aspirations of the researchers and the needs of utilities. This gulf will have to be bridged if any such designs are eventually to be deployed commercially. (author)

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

    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

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

    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-lys3]-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

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

    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.

  8. Molecular regulation of telomerase activity in aging

    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.

  9. Rap1 spatially controls ArhGAP29 to inhibit Rho signaling during endothelial barrier regulation

    Post, A.; Pannekoek, W. J.; Ponsioen, B.; Vliem, M. J.; Bos, J. L.

    2015-01-01

    The small GTPase Rap1 controls the actin cytoskeleton by regulating Rho GTPase signaling. We recently established that the Rap1 effectors Radil and Rasip1, together with the Rho GTPase activating protein ArhGAP29, mediate Rap1-induced inhibition of Rho signaling in the processes of epithelial cell s

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

    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.

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

    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…

  12. Regulating the regulators: modulators of transcription factor activity.

    Everett, Logan; Hansen, Matthew; Hannenhalli, Sridhar

    2010-01-01

    Gene transcription is largely regulated by DNA-binding transcription factors (TFs). However, the TF activity itself is modulated via, among other things, post-translational modifications (PTMs) by specific modification enzymes in response to cellular stimuli. TF-PTMs thus serve as "molecular switchboards" that map upstream signaling events to the downstream transcriptional events. An important long-term goal is to obtain a genome-wide map of "regulatory triplets" consisting of a TF, target gene, and a modulator gene that specifically modulates the regulation of the target gene by the TF. A variety of genome-wide data sets can be exploited by computational methods to obtain a rough map of regulatory triplets, which can guide directed experiments. However, a prerequisite to developing such computational tools is a systematic catalog of known instances of regulatory triplets. We first describe PTM-Switchboard, a recent database that stores triplets of genes such that the ability of one gene (the TF) to regulate a target gene is dependent on one or more PTMs catalyzed by a third gene, the modifying enzyme. We also review current computational approaches to infer regulatory triplets from genome-wide data sets and conclude with a discussion of potential future research. PTM-Switchboard is accessible at http://cagr.pcbi.upenn.edu/PTMswitchboard / PMID:20827600

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

    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…

  14. Activation of toll like receptor-3 induces corneal epithelial barrier dysfunction.

    Wei, Jie; Jiang, Hua; Gao, Hongrui; Wang, Guangjie

    2015-06-01

    The epithelial barrier is critical in the maintenance of the homeostasis of the cornea. A number of eye disorders are associated with the corneal epithelial barrier dysfunction. Viral infection is one common eye disease type. This study aims to elucidate the mechanism by which the activation of toll like receptor 3 (TLR3) in the disruption of the corneal epithelial barrier. In this study, HCE cells (a human corneal epithelial cell line) were cultured into epithelial layers using as an in vitro model of the corneal epithelial barrier. PolyI:C was used as a ligand of TLR3. The transepithelial electric resistance (TER) and permeability of the HCE epithelial layer were assessed using as the parameters to evaluate the corneal epithelial barrier integrity. The results showed that exposure to PolyI:C markedly decreased the TER and increased the permeability of the HCE epithelial layers; the levels of cell junction protein, E-cadherin, were repressed by PolyI:C via increasing histone deacetylase-1 (HDAC1), the latter binding to the promoter of E-cadherin and repressed the transcription of E-cadherin. The addition of butyrate (an inhibitor of HDAC1) to the culture blocked the corneal epithelial barrier dysfunction caused by PolyI:C. In conclusion, activation of TLR3 can disrupt the corneal epithelial barrier, which can be blocked by the inhibitor of HDAC1. PMID:25912142

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

    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. PMID:25909603

  16. Urban particulate matter down-regulates filaggrin via COX2 expression/PGE2 production leading to skin barrier dysfunction.

    Lee, Chiang-Wen; Lin, Zih-Chan; Hu, Stephen Chu-Sung; Chiang, Yao-Chang; Hsu, Lee-Fen; Lin, Yu-Ching; Lee, I-Ta; Tsai, Ming-Horng; Fang, Jia-You

    2016-01-01

    We explored the regulation of filaggrin, cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) expression induced by urban particulate matter (PM) in human keratinocytes. In addition, we investigated the signaling pathways involved in PM-induced effects on COX2/PGE2 and filaggrin. PMs induced increases in COX2 expression and PGE2 production, and decreased filaggrin expression. These effects were attenuated by pretreatment with COX2 inhibitor and PGE2 receptor antagonist, or after transfection with siRNAs of the aryl hydrocarbon receptor (AhR), gp91phox and p47phox. Furthermore, PM-induced generation of reactive oxygen species (ROS) and NADPH oxidase activity was attenuated by pretreatment with an AhR antagonist (AhRI) or antioxidants. Moreover, Nox-dependent ROS generation led to phosphorylation of ERK1/2, p38, and JNK, which then activated the downstream molecules NF-κB and AP-1, respectively. In vivo studies in PMs-treated mice showed that AhRI and apocynin (a Nox2 inhibitor) had anti-inflammatory effects by decreasing COX2 and increasing filaggrin expression. Our results reveal for the first time that PMs-induced ROS generation is mediated through the AhR/p47 phox/NADPH oxidase pathway, which in turn activates ERK1/2, p38/NF-κB and JNK/AP-1, and which ultimately induces COX2 expression and filaggrin downregulation. Up-regulated expression of COX2 and production of PGE2 may lead to impairment of skin barrier function. PMID:27313009

  17. Commission of energy regulation. 2004 activity report

    The commission of energy regulation (CRE) is an independent administrative authority in charge of the control of the operation of gas and electricity markets. This document is the fifth activity report of CRE and covers the July 1, 2003 - June 30, 2004 period, which corresponds to the era of opening of energy markets as a consequence of the enforcement of the June 26, 2003 European directive. In the framework of the stakes made by energy markets liberalization, this document presents the situation of the gas and electricity markets during this period (European framework, regulation of both markets, public utility mission..) and describes CRE's means for the monitoring of these markets. (J.S.)

  18. VOCATIONAL ACTIVATION BARRIERS OF PEOPLE WITH DISABILITIES IN EMPLOYERS' VIEW FROM THE LUBUSKIE VOIVODESHIP

    Garbat, M.

    2013-01-01

    The article presents a diagnosis of employment and vocational activation barriers of people with disabilities. The diagnosis was made on the basis of quality research, on the strength of answers provided by employers from the Lubuskie Voivodeship. The research included employers representing numerous business branches, both those who employ people with disabilities and those who do not. The employers' opinions allow to advance a thesis that those barriers are heterogeneous and have many sourc...

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

    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.

  20. Thermal activation of current in an inhomogeneous Schottky diode with a Gaussian distribution of barrier height

    This paper investigates the thermal activation behaviour of current in an inhomogeneous Schottky diode with a Gaussian distribution of barrier height by numerical simulation. The analytical Gaussian distribution model predicted that the I-V-T curves may intersect with the possibility of the negative thermal activation of current, but may be contradictory to the thermionic emission mechanism in a Schottky diode. It shows that the cause of the unphysical phenomenon is related to the incorrect calculation of current across very low barriers. It proposes that junction voltage Vj, excluding the voltage drop across series resistance from the external bias, is a crucial parameter for correct calculation of the current across very low barriers. For correctly employing the thermionic emission model, Vj needs to be smaller than the barrier height ø. With proper scheme of series resistance connection where the condition of Vj > ø is guaranteed, I-V-T curves of an inhomogeneous Schottky diode with a Gaussian distribution of barrier height have been simulated, which demonstrate normal thermal activation. Although the calculated results exclude the intersecting possibility of I-V-T curves with an assumption of temperature-independent series resistance, it shows that the intersecting is possible when the series resistance has a positive temperature coefficient. Finally, the comparison of our numerical and analytical results indicates that the analytical Gaussian distribution model is valid and accurate in analysing I-V-T curves only for small barrier height inhomogeneity. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

  1. Anandamide rescues retinal barrier properties in Müller glia through nitric oxide regulation.

    Krishnan, G; Chatterjee, N

    2015-01-22

    The blood retinal barrier (BRB) can mitigate deleterious immune response. Dysfunction at the BRB can affect disease progression. Under inflammatory conditions Müller glia produce increased pro-inflammatory factors, like nitric oxide (NO). In this study we describe molecular events at the Müller glia during inflammation which could affect inner BRB properties. Griess assay and 4,5-diaminofluorescein diacetate (DAF-2DA) time-lapse fluorescence were used to measure NO production. Western blot was used to analyze the expression of inducible nitric oxide synthase (iNOS) and mitogen-activated protein kinases (MAPK) components. Lucifer Yellow was used to measure permeability. Griess assay and DAF-2DA time-lapse fluorescence images revealed that lipopolysaccharide (LPS) induced inflammation and increased NO production. In parallel, changes were observed in tight junction proteins, zona occludens 1 (ZO-1), connexin 43 (Cx43), and permeability. This was mediated through activation of iNOS and mitogen-activated protein kinase phosphatase-1 (MKP-1), implicated in immune response. Endocannabinoids can exert a protective and anti-inflammatory effect. Exogenous arachidonoyl ethanolamide (AEA) inhibited NO generation and also abolished LPS-induced increase in permeability. Our work suggests that subtle changes in Müller glia function, which act as part of the BRB, could contribute to retinal health. AEA which can reduce inflammatory cytotoxicity has potential as treatment in several ocular manifestations where the integrity of the BRB is crucial. PMID:25453774

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

    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.

  3. Src regulates the activity of SIRT2

    Choi, You Hee [College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju (Korea, Republic of); Kim, Hangun [College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon (Korea, Republic of); Lee, Sung Ho [College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju (Korea, Republic of); Jin, Yun-Hye, E-mail: jinyune@hanmail.net [College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju (Korea, Republic of); Lee, Kwang Youl, E-mail: kwanglee@chonnam.ac.kr [College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju (Korea, Republic of)

    2014-07-25

    Highlights: • Src decreases the protein levels of Sirt2. • Src inhibitor and knockdown of Src increase the protein levels of Sirt2. • Src interacts with and phosphorylates Sirt2. • Src regulate the activity of Sirt2. - Abstract: SIRT2 is a mammalian member of the Sirtuin family of NAD{sup +}-dependent protein deacetylases. The tyrosine kinase Src is involved in a variety of cellular signaling pathways, leading to the induction of DNA synthesis, cell proliferation, and cytoskeletal reorganization. The function of SIRT2 is modulated by post-translational modifications; however, the precise molecular signaling mechanism of SIRT2 through interactions with c-Src has not yet been established. In this study, we investigated the potential regulation of SIRT2 function by c-Src. We found that the protein levels of SIRT2 were decreased by c-Src, and subsequently rescued by the addition of a Src specific inhibitor, SU6656, or by siRNA-mediated knockdown of c-Src. The c-Src interacts with and phosphorylates SIRT2 at Tyr104. c-Src also showed the ability to regulate the deacetylation activity of SIRT2. Investigation on the phosphorylation of SIRT2 suggested that this was the method of c-Src-mediated SIRT2 regulation.

  4. Regulation of nuclear activity in Kazakhstan

    Major factors, by which the radiation situation in Kazakhstan is formed, are: enterprises of nuclear fuel cycle, including uranium mining and milling activity and geological exploration of uranium; nuclear power plant and research reactors; residues of atmospheric and underground nuclear explosions, which were conducted for military and peaceful purposes at the different test sites; mining and milling of commercial minerals accompanied by radioactive substances; using of radioactive sources in industry, medicine, agriculture and scientific research. Since 1991, after getting of sovereignty there was started creation of own legislative basis of the country for the field of atomic energy use. It includes laws, regulation and standards for nuclear and radiation safety of nuclear installations, personnel, involved in the activity with using of atomic energy, population and environment. Applicable system of state regulation in this area, including the regulatory body in the field of atomic energy use and various ministries, was created. As a result of these reforms, regulatory activities were improved in the country. This paper presents the current matters of nuclear and radiation safety regulation in Kazakhstan. (author)

  5. Activation of RhoA, but Not Rac1, Mediates Early Stages of S1P-Induced Endothelial Barrier Enhancement.

    Xun E Zhang

    Full Text Available Compromised endothelial barrier function is a hallmark of inflammation. Rho family GTPases are critical in regulating endothelial barrier function, yet their precise roles, particularly in sphingosine-1-phosphate (S1P-induced endothelial barrier enhancement, remain elusive. Confluent cultures of human umbilical vein endothelial cells (HUVEC or human dermal microvascular endothelial cells (HDMEC were used to model the endothelial barrier. Barrier function was assessed by determining the transendothelial electrical resistance (TER using an electrical cell-substrate impedance sensor (ECIS. The roles of Rac1 and RhoA were tested in S1P-induced barrier enhancement. The results show that pharmacologic inhibition of Rac1 with Z62954982 failed to block S1P-induced barrier enhancement. Likewise, expression of a dominant negative form of Rac1, or knockdown of native Rac1 with siRNA, failed to block S1P-induced elevations in TER. In contrast, blockade of RhoA with the combination of the inhibitors Rhosin and Y16 significantly reduced S1P-induced increases in TER. Assessment of RhoA activation in real time using a fluorescence resonance energy transfer (FRET biosensor showed that S1P increased RhoA activation primarily at the edges of cells, near junctions. This was complemented by myosin light chain-2 phosphorylation at cell edges, and increased F-actin and vinculin near intercellular junctions, which could all be blocked with pharmacologic inhibition of RhoA. The results suggest that S1P causes activation of RhoA at the cell periphery, stimulating local activation of the actin cytoskeleton and focal adhesions, and resulting in endothelial barrier enhancement. S1P-induced Rac1 activation, however, does not appear to have a significant role in this process.

  6. Activation of RhoA, but Not Rac1, Mediates Early Stages of S1P-Induced Endothelial Barrier Enhancement.

    Zhang, Xun E; Adderley, Shaquria P; Breslin, Jerome W

    2016-01-01

    Compromised endothelial barrier function is a hallmark of inflammation. Rho family GTPases are critical in regulating endothelial barrier function, yet their precise roles, particularly in sphingosine-1-phosphate (S1P)-induced endothelial barrier enhancement, remain elusive. Confluent cultures of human umbilical vein endothelial cells (HUVEC) or human dermal microvascular endothelial cells (HDMEC) were used to model the endothelial barrier. Barrier function was assessed by determining the transendothelial electrical resistance (TER) using an electrical cell-substrate impedance sensor (ECIS). The roles of Rac1 and RhoA were tested in S1P-induced barrier enhancement. The results show that pharmacologic inhibition of Rac1 with Z62954982 failed to block S1P-induced barrier enhancement. Likewise, expression of a dominant negative form of Rac1, or knockdown of native Rac1 with siRNA, failed to block S1P-induced elevations in TER. In contrast, blockade of RhoA with the combination of the inhibitors Rhosin and Y16 significantly reduced S1P-induced increases in TER. Assessment of RhoA activation in real time using a fluorescence resonance energy transfer (FRET) biosensor showed that S1P increased RhoA activation primarily at the edges of cells, near junctions. This was complemented by myosin light chain-2 phosphorylation at cell edges, and increased F-actin and vinculin near intercellular junctions, which could all be blocked with pharmacologic inhibition of RhoA. The results suggest that S1P causes activation of RhoA at the cell periphery, stimulating local activation of the actin cytoskeleton and focal adhesions, and resulting in endothelial barrier enhancement. S1P-induced Rac1 activation, however, does not appear to have a significant role in this process. PMID:27187066

  7. Midlife Women's Negotiations of Barriers to and Facilitators of Physical Activity: Implications for Counselors

    Hendry, Petra; Solmon, Melinda; Choate, Laura H.; Autrey, Pam; Landry, Joan B.

    2010-01-01

    The authors investigated barriers to exercise and facilitators that enable midlife women to engage in an active lifestyle. Findings provide counselors with insight into the meanings that women ascribe to physical activity so they can better assist clients in making choices that enhance their overall health and wellness.

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

    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…

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

    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…

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

    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. Motives for and barriers to physical activity among older adults with mobility limitations.

    Rasinaho, Minna; Hirvensalo, Mirja; Leinonen, Raija; Lintunen, Taru; Rantanen, Taina

    2007-01-01

    The purpose of this study was to investigate what older adults with severe, moderate, or no mobility limitation consider motives for and barriers to engaging in physical exercise. Community-dwelling adults (N=645) age 75-81 years completed a questionnaire about their motives for and barriers to physical exercise and answered interview questions on mobility limitation. Those with severely limited mobility more often reported poor health, fear and negative experiences, lack of company, and an unsuitable environment as barriers to exercise than did those with no mobility limitation. They also accentuated disease management as a motive for exercise, whereas those with no or moderate mobility limitation emphasized health promotion and positive experiences related to exercise. Information about differences in motives for and barriers to exercise among people with and without mobility limitation helps tailor support systems that support engagement in physical activity among older adults. PMID:17387231

  12. Breakdown of Epithelial Barrier Integrity and Overdrive Activation of Alveolar Epithelial Cells in the Pathogenesis of Acute Respiratory Distress Syndrome and Lung Fibrosis

    Shigehisa Yanagi

    2015-01-01

    Full Text Available Individual alveolar epithelial cells (AECs collaboratively form a tight barrier between atmosphere and fluid-filled tissue to enable normal gas exchange. The tight junctions of AECs provide intercellular sealing and are integral to the maintenance of the AEC barrier integrity. Disruption and failure of reconstitution of AEC barrier result in catastrophic consequences, leading to alveolar flooding and subsequent devastating fibrotic scarring. Recent evidences reveal that many of the fibrotic lung diseases involve AECs both as a frequent target of injury and as a driver of ongoing pathological processes. Aberrantly activated AECs express most of the growth factors and chemokines responsible for the proliferation, migration, and activation of fibroblasts. Current evidences suggest that AECs may acquire overdrive activation in the initial step of fibrosis by several mechanisms, including abnormal recapitulation of the developmental pathway, defects of the molecules essential for epithelial integrity, and acceleration of aging-related properties. Among these initial triggering events, epithelial Pten, a multiple phosphatase that negatively regulates the PI3K/Akt pathway and is crucial for lung development, is essential for the prevention of alveolar flooding and lung fibrosis through the regulation of AEC barrier integrity after injury. Reestablishment of AEC barrier integrity also involves the deployment of specialized stem/progenitor cells.

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

    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.

  14. Regulators of Slc4 bicarbonate transporter activity

    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.

  15. Diesel exhaust particles induce oxidative stress, proinflammatory signaling, and P-glycoprotein up-regulation at the blood-brain barrier

    Hartz, Anika M.S.; Bauer, Björn; Block, Michelle L.; Hong, Jau-Shyong; Miller, David S.

    2008-01-01

    Here, we report that diesel exhaust particles (DEPs), a major constituent of urban air pollution, affect blood-brain barrier function at the tissue, cellular, and molecular levels. Isolated rat brain capillaries exposed to DEPs showed increased expression and transport activity of the key drug efflux transporter, P-glycoprotein (6 h EC50 was ∼5 μg/ml). Up-regulation of P-glycoprotein was abolished by blocking transcription or protein synthesis. Inhibition of NADPH oxidase or pretreatment of c...

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

    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. PMID:26910962

  17. PATTERNS OF PHYSICAL ACTIVITY AMONG AMERICAN INDIAN CHILDREN: AN ASSESSMENT OF BARRIERS AND SUPPORT

    Thompson, Janice L.; Davis, Sally M.; Gittelsohn, Joel; Going, Scott; Becenti, Alberta; Metcalfe, Lauve; Stone, Elaine; Harnack, Lisa; Ring, Kim

    2016-01-01

    Estimates indicate that 10% to 50% of American Indian and non-Indian children in the U.S. are obese, defined as a body mass index ≥ 95th percentile of the NHANES II reference data. Pathways is a two-phase, multi-site study to develop and test a school-based obesity prevention program in American Indian schoolchildren in grades three through five. During Phase I feasibility prior to initiation of the Pathways trial, data were collected related to physical activity patterns, and the supports of, and barriers to, physical activity. Nine schools from communities representing six different tribal groups participated in this study. Multiple measures were used for data collection including direct observation, paired child interviews, and in-depth interviews and focus groups with adults. Students completed the self-administered Knowledge, Attitudes, and Behaviors (KAB) survey, and a Physical Activity Questionnaire (PAQ). Barriers to physical activity at schools included a lack of facilities, equipment, and trained staff persons for PE. Adults were not consistently active with their children, but they were highly supportive of their children’s activity level. Children reported a strong enjoyment of physical activity and strong peer support to be physically active. Weather conditions, safety concerns, and homework/chores were common barriers to physical activity reported by children and adult caregivers. The information was used to design culturally and age-appropriate, practical interventions including the five physical activity programs for schoolchildren in the Pathways study. PMID:11759094

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

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

    2014-06-01

    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 being active. Three hundred and forty surveys were returned out of 1,047 for a response rate of 32%. On school days, 41% of caregivers reported that their children spent more than 2 h watching television, playing video games, or spending time on the computer. While over half of respondents reported that their children get more than 2 h of physical activity on school days, 14% of children were reported to be physically active less than 1 h per day. Caregivers identified violence, cost of extracurricular activities, and lack of organized activities as barriers to their child's physical activity. The overwhelming majority of caregivers expressed interest in a program to make local playgrounds safer. In conclusion, children in Avondale are not participating in enough physical activity and are exposed to more screen time than is recommended by the AAP. Safety concerns were identified as a critical barrier to address in future advocacy efforts in this community. This project represents an important step toward increasing the physical activity of children in Avondale and engaging the local community. PMID:24306236

  19. Redox-active media for permeable reactive barriers

    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 (Fe3O4), 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

  20. Low activation barriers characterize intramolecular electron transfer in ascorbate oxidase

    Farver, O; Pecht, I

    1992-01-01

    Anaerobic reduction kinetics of the zucchini squash ascorbate oxidase (AO; L-ascorbate:oxygen oxidoreductase, EC 1.10.3.3) by pulse radiolytically produced CO2- radical ions were investigated. Changes in the absorption bands of type 1 [Cu(II)] (610 nm) and type 3 [Cu(II)] (330 nm) were monitored...... transfer to type 3 [Cu(II)]. The observed specific rates are similar to values reported for the limiting-rate constants of AO reduction by excess substrate, suggesting that internal electron transfer is the rate-determining step of AO activity. The temperature dependence of the intramolecular electron...... transfer rate constants was measured from 275 to 308 K at pH 5.5 and, from the Eyring plots, low activation enthalpies were calculated--namely, 9.1 +/- 1.1 and 6.8 +/- 1.0 kJ.mol-1 for the fastest and slowest phases, respectively. The activation entropies observed for these respective phases were -170...

  1. Breaking the HAC Barrier: Histone H3K9 acetyl/methyl balance regulates CENP-A assembly

    Ohzeki, J.-I.; M. Nakano; Masumoto, H; Kouprina, N.; Noskov, V. N.; Larionov, V; Bergmann, J H; Earnshaw, W C; Kimura, H.

    2012-01-01

    The kinetochore is responsible for accurate chromosome segregation. However, the mechanism by which kinetochores assemble and are maintained remains unclear. Here we report that de novo CENP-A assembly and kinetochore formation on human centromeric alphoid DNA arrays is regulated by a histone H3K9 acetyl/methyl balance. Tethering of histone acetyltransferases (HATs) to alphoid DNA arrays breaks a cell type-specific barrier for de novo stable CENP-A assembly and induces assembly of other kinet...

  2. Thermally activated resonant tunnelling in GaAs/AlGaAs triple barrier heterostructures

    We report the observation of a thermally activated resonant tunnelling feature in the current–voltage characteristics (I(V)) of triple barrier resonant tunnelling structures (TBRTS) due to the alignment of the n = 1 confined states of the two quantum wells within the active region. With great renewed interest in tunnelling structures for high frequency (THz) operation, the understanding of device transport and charge accumulation as a function of temperature is critical. With rising sample temperature, the tunnelling current of the observed low voltage resonant feature increases in magnitude showing a small negative differential resistance region which is discernible even at 293 K and is unique to multiple barrier devices. This behaviour is not observed in conventional double barrier resonant tunnelling structures where the transmission coefficient at the Fermi energy is predominantly controlled by an electric field, whereas in TBRTS it is strongly controlled by the 2D to 2D state alignment. (paper)

  3. Regulation of pokemon 1 activity by sumoylation.

    Roh, Hee-Eun; Lee, Min-Nyung; Jeon, Bu-Nam; Choi, Won-Il; Kim, Yoo-Jin; Yu, Mi-Young; Hur, Man-Wook

    2007-01-01

    Pokemon 1 is a proto-oncogenic transcriptional regulator that contains a POZ domain at the N-terminus and four Kruppel-like zinc fingers at the C-terminus. Pokemon 1 plays an important role in adipogenesis, osteogenesis, oncogenesis, and transcription of NF-kB responsive genes. Recent reports have shown that biological activities of transcription factors are regulated by sumolylation. We investigated whether Pokemon 1 is post-translationally modified by sumoylation and whether the modification affects Pokemon 1's transcriptional properties. We found that Pokemon 1 is sumoylated in vitro and in vivo. Upon careful analysis of the amino acid sequence of Pokemon 1, we found ten potential sumoylation sites located at lysines 61, 354, 371, 379, 383, 396, 486, 487, 536 and 539. We mutated each of these amino acids into arginine and tested whether the mutation could affect the transcriptional properties of Pokemon 1 on the Pokemon 1 responsive genes, such as ADH5/FDH and pG5-FRE-Luc. Wild-type Pokemon 1 potently represses transcription of ADH5/FDH. Most of the mutants, however, were weaker transcription repressors and repressed transcription 1.3-3.3 fold less effective. Although potential sumoylation sites were located close to the DNA binding domain or the nuclear localization sequence, the mutations did not alter nuclear localization or DNA binding activity. In addition, on the pG5-FRE-Luc test promoter construct, ectopic SUMO-1 repressed transcription in the presence of Pokemon 1. The sumoylation target lysine residue at amino acid 61, which is located in the middle of the POZ-domain, is important because K61R mutation resulted in a much weaker molecular interaction with corepressors. Our data suggest that Pokemon 1's activity as a transcription factor may involve sumoylation, and that sumoylation might be important in the regulation of transcription by Pokemon 1. PMID:17595526

  4. Regulation of polymorphonuclear cell activation by thrombopoietin.

    Brizzi, M F; Battaglia, E.; Rosso, A.; Strippoli, P; Montrucchio, G; Camussi, G.; Pegoraro, L

    1997-01-01

    Thrombopoietin (TPO) regulates early and late stages of platelet formation as well as platelet activation. TPO exerts its effects by binding to the receptor, encoded by the protooncogene c-mpl, that is expressed in a large number of cells of hematopoietic origin. In this study, we evaluated the expression of c-Mpl and the effects of TPO on human polymorphonuclear cells (PMN). We demonstrate that PMN express the TPO receptor c-Mpl and that TPO induces STAT1 tyrosine phosphorylation and the for...

  5. Vimentin regulates activation of the NLRP3 inflammasome

    Dos Santos, Gimena; Rogel, Micah R.; Baker, Margaret A.; Troken, James R.; Urich, Daniela; Morales-Nebreda, Luisa; Sennello, Joseph A.; Kutuzov, Mikhail A.; Sitikov, Albert; Davis, Jennifer M.; Lam, Anna P.; Cheresh, Paul; Kamp, David; Shumaker, Dale K.; Budinger, G. R. Scott; Ridge, Karen M.

    2015-03-01

    Activation of the NLRP3 inflammasome and subsequent maturation of IL-1β have been implicated in acute lung injury (ALI), resulting in inflammation and fibrosis. We investigated the role of vimentin, a type III intermediate filament, in this process using three well-characterized murine models of ALI known to require NLRP3 inflammasome activation. We demonstrate that central pathophysiologic events in ALI (inflammation, IL-1β levels, endothelial and alveolar epithelial barrier permeability, remodelling and fibrosis) are attenuated in the lungs of Vim-/- mice challenged with LPS, bleomycin and asbestos. Bone marrow chimeric mice lacking vimentin have reduced IL-1β levels and attenuated lung injury and fibrosis following bleomycin exposure. Furthermore, decreased active caspase-1 and IL-1β levels are observed in vitro in Vim-/- and vimentin-knockdown macrophages. Importantly, we show direct protein-protein interaction between NLRP3 and vimentin. This study provides insights into lung inflammation and fibrosis and suggests that vimentin may be a key regulator of the NLRP3 inflammasome.

  6. On the contribution of mucosal mast cells to the regulation of mouse intestinal barrier function

    Rychter, J.

    2010-01-01

    The primary functions of the small intestine are the digestion and transport of luminal content and the absorption of nutrients. During these processes the intestinal mucosa is exposed to various ingested and resident pathogens. The ability of the intestinal wall to prevent transmucosal passage of toxins or of harmful micro-organisms and their products is defined as the intestinal barrier function. Defective intestinal barrier function plays a role in a number of disorders such as inflammator...

  7. Similar barriers and facilitators to physical activity across different clinical groups experiencing lower limb spasticity.

    Hundza, Sandra; Quartly, Caroline; Kim, Jasmine M; Dunnett, James; Dobrinsky, Jill; Loots, Iris; Choy, Kim; Chow, Brayley; Hampshire, Alexis; Temple, Viviene A

    2016-07-01

    Purpose Given the importance of physical activity in maintaining health and wellness, an improved understanding of physical activity patterns across different clinical populations is required. This study examines the facilitators for, and barriers to, participation in physical activity across multiple contexts for three clinical groups with chronic lower limb spasticity (individuals with stroke, multiple sclerosis and incomplete spinal cord injury). Method This cross-sectional study employed quantitative measures for spasticity, ankle range of motion, pain, falls, cognition, mobility, and physical activity as well as qualitative semi-structured interviews. Results There were similar impairments in body functions and structures and limitations in activities across the clinical groups. These impairments and limitations negatively impacted participation in physical activity, which was low. Environmental and personal factors exacerbated or mitigated the limiting effects of body functions and structures and activities on physical activity in many areas of life. Conclusions In this population, participation in physical activity includes activities such as housework which are different than what is typically considered as physical activity. Further, the presence of similar barriers and facilitators across the groups suggests that support and services to promote valued forms of physical activity could be organised and delivered based on limitations in mobility and functioning rather than clinical diagnosis. Implications for rehabilitation Physical activity is of utmost importance in maintaining health and wellness in clinical populations. This research highlights the desired and actual physical activity for these populations can look different than what may traditionally be considered as physical activity (e.g. housework is not typically considered participation physical activity). Therefore, rehabilitation interventions need to be directly designed to enhance clients

  8. Regulation of Aicda expression and AID activity.

    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

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

    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…

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

    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…

  11. Phosphorylation regulates coilin activity and RNA association

    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.

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

    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

  13. Barrier properties of poly(vinyl alcohol) membranes containing carbon nanotubes or activated carbon.

    Surdo, Erin M; Khan, Iftheker A; Choudhury, Atif A; Saleh, Navid B; Arnold, William A

    2011-04-15

    Carbon nanotube addition has been shown to improve the mechanical properties of some polymers. Because of their unique adsorptive properties, carbon nanotubes may also improve the barrier performance of polymers used in contaminant containment. This study compares the barrier performance of poly(vinyl alcohol) (PVA) membranes containing single-walled carbon nanotubes (SWCNTs) to that for PVA containing powdered activated carbon (PAC). Raw and surface-functionalized versions of each sorbent were tested for their abilities to adsorb 1,2,4-trichlorobenzene and Cu(2+), representing the important hydrophobic organic and heavy metal contaminant classes, as they diffused across the PVA. In both cases, PAC (for 1,2,4-trichlorobenzene) and functionalized PAC (for Cu(2+)) outperformed SWCNTs on a per mass basis by trapping more of the contaminants within the barrier membrane. Kinetics of sorption are important in evaluating barrier properties, and poor performance of SWCNT-containing membranes as 1,2,4-TCB barriers is attributed to kinetic limitations. PMID:21349636

  14. Methane activation under dielectric barrier discharge plasma interacting with mesoporous material

    Kim, J; Park, D; Lee, C.(Institute of Physics, Academia Sinica, Taipei, Taiwan); Lee, D H; Kim, T.

    2015-01-01

    International audience Direct methane activation on a mesoporous material under dielectric barrier discharge (DBD) plasma was investigated in the present study. The specific surface area of the mesoporous material (SBA-15) was controlled by varying the hydrothermal reaction temperature to investigate the effect of the specific surface area on the methane activation. As a result, methane conversion increased as the specific surface area increased and the discharge frequency decreased. Energ...

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

    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 ...

  16. Blood-Brain Barrier Active Efflux Transporters: ATP-Binding Cassette Gene Family

    Löscher, Wolfgang; Potschka, Heidrun

    2005-01-01

    Summary: The blood-brain barrier (BBB) contributes to brain homeostasis by protecting the brain from potentially harmful endogenous and exogenous substances. BBB active drug efflux transporters of the ATP-binding cassette (ABC) gene family are increasingly recognized as important determinants of drug distribution to, and elimination from, the CNS. The ABC efflux transporter P-glycoprotein (Pgp) has been demonstrated as a key element of the BBB that can actively transport a huge variety of lip...

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

    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 (human activity, which currently is a global problem.

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

    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

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

    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

  20. Endoglin regulates cyclooxygenase-2 expression and activity.

    Jerkic, Mirjana; Rivas-Elena, Juan V; Santibanez, Juan F; Prieto, Marta; Rodríguez-Barbero, Alicia; Perez-Barriocanal, Fernando; Pericacho, Miguel; Arévalo, Miguel; Vary, Calvin P H; Letarte, Michelle; Bernabeu, Carmelo; López-Novoa, Jose M

    2006-08-01

    The endoglin heterozygous (Eng(+/-)) mouse, which serves as a model of hereditary hemorrhagic telangiectasia (HHT), was shown to express reduced levels of endothelial NO synthase (eNOS) with impaired activity. Because of intricate changes in vasomotor function in the Eng(+/-) mice and the potential interactions between the NO- and prostaglandin-producing pathways, we assessed the expression and function of cyclooxygenase (COX) isoforms. A specific upregulation of COX-2 in the vascular endothelium and increased urinary excretion of prostaglandin E(2) were observed in the Eng(+/-) mice. Specific COX-2 inhibition with parecoxib transiently increased arterial pressure in Eng(+/-) but not in Eng(+/+) mice. Transfection of endoglin in L6E9 myoblasts, shown previously to stimulate eNOS expression, led to downregulation of COX-2 with no change in COX-1. In addition, COX-2 promoter activity and protein levels were inversely correlated with endoglin levels, in doxycyclin-inducible endothelial cells. Chronic NO synthesis inhibition with N(omega)-nitro-l-arginine methyl ester induced a marked increase in COX-2 only in the normal Eng(+/+) mice. N(omega)-nitro-l-arginine methyl ester also increased COX-2 expression and promoter activity in doxycyclin-inducible endoglin expressing endothelial cells, but not in control cells. The level of COX-2 expression following transforming growth factor-beta1 treatment was less in endoglin than in mock transfected L6E9 myoblasts and was higher in human endothelial cells silenced for endoglin expression. Our results indicate that endoglin is involved in the regulation of COX-2 activity. Furthermore, reduced endoglin levels and associated impaired NO production may be responsible, at least in part, for augmented COX-2 expression and activity in the Eng(+/-) mice. PMID:16840721

  1. Structural Basis for Plexin Activation and Regulation.

    Kong, Youxin; Janssen, Bert J C; Malinauskas, Tomas; Vangoor, Vamshidhar R; Coles, Charlotte H; Kaufmann, Rainer; Ni, Tao; Gilbert, Robert J C; Padilla-Parra, Sergi; Pasterkamp, R Jeroen; Jones, E Yvonne

    2016-08-01

    Class A plexins (PlxnAs) act as semaphorin receptors and control diverse aspects of nervous system development and plasticity, ranging from axon guidance and neuron migration to synaptic organization. PlxnA signaling requires cytoplasmic domain dimerization, but extracellular regulation and activation mechanisms remain unclear. Here we present crystal structures of PlxnA (PlxnA1, PlxnA2, and PlxnA4) full ectodomains. Domains 1-9 form a ring-like conformation from which the C-terminal domain 10 points away. All our PlxnA ectodomain structures show autoinhibitory, intermolecular "head-to-stalk" (domain 1 to domain 4-5) interactions, which are confirmed by biophysical assays, live cell fluorescence microscopy, and cell-based and neuronal growth cone collapse assays. This work reveals a 2-fold role of the PlxnA ectodomains: imposing a pre-signaling autoinhibitory separation for the cytoplasmic domains via intermolecular head-to-stalk interactions and supporting dimerization-based PlxnA activation upon ligand binding. More generally, our data identify a novel molecular mechanism for preventing premature activation of axon guidance receptors. PMID:27397516

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

    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…

  3. Basic principles for regulating nuclear activities

    The AECB has developed as its mission statement: 'To ensure that the use of nuclear energy in Canada does not pose undue risk to health, safety, security and the environment'. This report proposes eleven qualitative principles for regulating nuclear activities whose achievement would satisfy the broad policy enunciated in the statement. They would further provide a basis for the specific regulatory requirements expressed by the AECB in its Regulations and other documents. They would thus represent a connecting link between the policy enunciated in the mission statement and the requirements. The proposed principles are largely concerned with how the allowable risk should be set for members of the public, for industry workers, for society as a whole, and for the environment. In making these recommendations the risks from normal operation of the licensed facility and those from a possible serious accident are considered separately. The distribution of risk between geographic communities and between generations is also addressed in the proposed principles. These are listed in the final section of the report. 23 refs

  4. Mechanisms and regulation of iron trafficking across the capillary endothelial cells of the blood-brain barrier

    Daniel J. Kosman

    2015-07-01

    Full Text Available The transcellular trafficking of iron from the blood into the brain interstitium depends on iron uptake proteins in the apical membrane of brain microvascular capillary endothelial cells and efflux proteins at the basolateral, abluminal membrane. In this review, we discuss the three mechanisms by which these cells take-up iron from the blood and the sole mechanism by which they efflux this iron into the abluminal space. We then focus on the regulation of this efflux pathway by exocrine factors that are released from neighboring astrocytes. Also discussed are the cytokines secreted by capillary cells that regulate the expression of these glial cell signals. Among the interstitial factors that regulate iron efflux into the brain is the amyloid precursor protein. The role of this amyliodogenic species in brain iron metabolism is discussed. Last, we speculate on the potential relationship between iron transport at the blood-brain barrier and neurological disorders associated with iron mismanagement.

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

    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.

  6. Activation barrier scaling for fluctuation induced switching in driven non-linear micromechanical oscillators

    We explore fluctuation induced switching in an underdamped micromechanical torsional oscillator driven far from equilibrium. Under a sufficiently strong periodic driving field, the oscillator possesses multiple stable dynamical states. Depending on whether the device is resonantly or parametrically driven, two different types of bifurcation occur. In the presence of noise, the oscillator is induced to switch from one dynamical state into the other. Near the bifurcation points, the activation barrier exhibits a power law dependence on the frequency detuning. The critical exponents are measured to be different for the two types of bifurcation. Both values are in agreement with theoretical predictions. Such scaling of the activation barrier close to the bifurcation point is expected to occur in all systems that are driven away from equilibrium

  7. Role of mast cells and probiotics in the regulation of intestinal barrier function

    Carlsson, Anders

    2013-01-01

    The intestinal mucosa is the largest contact area and one of the most important barriers to the outside environment. It is highly specialized in aiding us digest and absorb nutrients. It is daily exposed to several potentially dangerous substances and microorganisms, which if they were allowed to pass into the body, could give rise to diseases. Throughout the small intestine certain sites specialized in antigen sampling are found. These sites are named Peyer’s patches and are lymphoid follicl...

  8. Active control of internal transport barrier and confinement database in JT-60U reversed shear plasma

    Active control of internal transport barrier (ITB) and confinement properties of plasma with ITB have been studied in reversed shear plasmas. Modifications of the radial electric field (Er) profile by changing the combination of tangential neutral beams can control the ITB strength, where the contribution to Er from the toroidal rotation plays an important role. The ITB confinement database of reversed shear plasmas has been constructed. Stored energy is strongly correlated with poloidal magnetic field at the ITB foot. (author)

  9. Activation barrier scaling and crossover for noise-induced switching in a micromechanical parametric oscillator

    Chan, H. B.; Stambaugh, C.

    2006-01-01

    We explore fluctuation-induced switching in a parametrically-driven micromechanical torsional oscillator. The oscillator possesses 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, w...

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

    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

  11. 76 FR 12364 - Agency Information Collection Activities: Bonded Warehouse Regulations

    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:...

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

    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.

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

    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 inf

  14. Legislation on and regulation of nuclear activities

    This work is a compilation of legislative texts and regulations published by the Atomic Energy Commission's Legal Affairs Department (CEA). It provides a comprehensive source of knowledge and information on nuclear energy law. Legislative texts published over the last forty years, are collected and analytically indexed. The publication covers both French regulations and regulations of international organisations such as the International Atomic Energy Agency and Euratom. It is divided into eight different chapters, dealing with regulations relevant to international and national institutions, nuclear installations, third party liability, protection of persons and the environment, etc. A chronological table of the texts of international and national laws is also included in this work. (NEA)

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

    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

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

    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

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

    Wang, Kai; Jin, Xiaolu; Chen, Yifan; Song, Zehe; Jiang, Xiasen; Hu, Fuliang; 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 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. PMID:27164138

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

    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.

  19. Safety assessment of discharge chute isolation barrier preparation and installation activities. Revision 3

    Meichle, R.H.

    1994-11-08

    This revision adds a section addressing impacts of dropping surfacing tool and rack cutter on the basin floor, and corrects typographical errors. The safety assessment is made for the activities for the preparation and installation of the discharge chute isolation barriers. The safety assessment includes a hazard assessment and comparisons of potential accidents/events to those addressed by the current safety basis documentation. No significant hazards were identified. An evaluation against the USQ evaluation questions was made and the determination made that the activities do not represent a USQ. Hazard categorization techniques were used to provide a basis for readiness review classifications.

  20. Safety assessment of discharge chute isolation barrier preparation and installation activities. Revision 3

    This revision adds a section addressing impacts of dropping surfacing tool and rack cutter on the basin floor, and corrects typographical errors. The safety assessment is made for the activities for the preparation and installation of the discharge chute isolation barriers. The safety assessment includes a hazard assessment and comparisons of potential accidents/events to those addressed by the current safety basis documentation. No significant hazards were identified. An evaluation against the USQ evaluation questions was made and the determination made that the activities do not represent a USQ. Hazard categorization techniques were used to provide a basis for readiness review classifications

  1. Influence of sportive activity on skin barrier function: a quantitative evaluation of 60 athletes.

    Luebberding, Stefanie; Kolbe, Lea; Kerscher, Martina

    2013-06-01

    While sports-related diseases are well documented in the literature, no study regarding the physiology of athlete's skin has been published yet. However, some evidence is given for impairment of the skin barrier due to sportive activity accompanied by an increase in sweating. In this explorative study, we investigated the effect of sportive activity on skin physiology, namely stratum corneum hydration, skin surface pH, and sebum content. A total of 60 healthy Caucasian volunteers (35 females, 25 males; mean 27.35 ± 4.09) were enrolled in this study. Measurements were done before and after 45 minutes of endurance cardio training at forehead, chest, forearm, and armpits. Hydration level, sebum secretion, and pH value of hydrolipid acid film were measured with worldwide-acknowledged biophysical measuring methods. Stratum corneum hydration significantly increased after sportive activity. The increase was about 51.9% at the forearm and 31.9% at the chest. Sebum content at the forehead significantly decreased during exercising, from 87.36 μg/cm2 to 62.41 μg/cm2. At all investigated body sites, measured values for skin surface pH increased after sportive activity. Highest pH value was measured in armpits (pH 5.64-5.98) and lowest at forearm (pH 4.75-4.93). Sportive activity is accompanied by significant changes of skin physiology that could stress the barrier function of the skin. Higher skin surface pH and hyperhydration of the stratum corneum as well as increased lipid content on the skin surface are probably caused by an increased sweat production. The impaired skin barrier may also be the reason for some reported sports-related dermatoses. PMID:23488867

  2. Analgesic drug delivery via recombinant tissue plasminogen activator and microRNA-183-triggered opening of the blood-nerve barrier.

    Yang, Shaobing; Krug, Susanne M; Heitmann, Johanna; Hu, Liu; Reinhold, Ann Kristin; Sauer, Solange; Bosten, Judith; Sommer, Claudia; Fromm, Michael; Brack, Alexander; Rittner, Heike L

    2016-03-01

    The peripheral nerve contains three barriers which include the blood-nerve barrier consisting of endoneurial vessels and the perineurium as well as autotypic junctions in Schwann cells. The perineurium prevents diffusion of perineurally injected drugs that can be used for selective regional pain control. It is composed of a basal membrane and layers of perineurial cells sealed by tight junction proteins like claudin-1. Claudin-1 expression and barrier function are regulated via low-density lipoprotein receptor-related protein (LRP-1). Perisciatic application of recombinant tissue plasminogen activator (rtPA) or the catalytically inactive rtPAi - both agonists of LRP-1 - reduced claudin-1 mRNA and protein expression in the rat nerve. This facilitated an increase of nociceptive thresholds after local application of hydrophilic opioids or the voltage gated sodium channel blocker (NaV1.7) ProToxin-II without apparent nerve toxicity. RtPA-induced barrier opening was mediated by LRP-1 and intracellularly by Erk phosphorylation. In silico, microRNA (miR)-rno-29b-2-5p and rno-miR-183-5p were identified as potential regulators of claudin-1 transcription in the rat. RtPA application increased miR-183-5p in the sciatic nerve. MiR-183-5p mimics functionally opened the perineurium and downregulated claudin-1 expression in vivo. In vitro, hsa-miR-183-3p mimics reduced claudin-1 expression in human HT-29/B6 cells. Overall, rtPA regulates perineurial barrier tightness via LRP-1, Erk phosphorylation and miR-183-5p/3p. This mechanism might serve as a new principle to facilitate drug delivery to peripheral nerves in humans. PMID:26735170

  3. Activation and Regulation of Cellular Eicosanoid Biosynthesis

    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.

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

    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

  5. Regulation of myostatin activity and muscle growth

    Lee, Se-Jin; McPherron, Alexandra C.

    2001-01-01

    Myostatin is a transforming growth factor-β family member that acts as a negative regulator of skeletal muscle mass. To identify possible myostatin inhibitors that may have applications for promoting muscle growth, we investigated the regulation of myostatin signaling. Myostatin protein purified from mammalian cells consisted of a noncovalently held complex of the N-terminal propeptide and a disulfide-linked dimer of C-terminal fragments. The purified C-terminal myostatin dimer was capable of...

  6. Experiences of Barriers and Facilitators for Physical Activity from People with Mental Disorders who Participated in a Physical Activity Project : - An Interview Study

    Brandt, Katarina; Loelv, Sara

    2012-01-01

    Experiences of Barriers and Facilitators for Physical Activity from People with Mental Disorders who Participated in a Physical Activity Project - An Interview Study   Purpose: To explore the experiences regarding perceived barriers and facilitators for physical activity of three participants with mental disorders who took part in the Norwegian Physical Activity Mentor project. Design and methods: Descriptive qualitative design. Individual semi-structured interviews were used for data collec...

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

    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

  8. Methane activation using noble gases in a dielectric barrier discharge reactor

    The conversion of methane is measured in a planar-type dielectric barrier discharge reactor using three different noble gases—He, Ne, and Ar—as additives. The empirical results obtained clearly indicate that methane activation is considerably affected by thy type of noble gas used. Through 0-D calculations, the discharge parameters inside the reactor, i.e., electron temperature and electron density, are estimated using experiment results. A comparison of the discharge characteristics and experimental results shows that the electron temperature is an important factor in achieving high methane activation and the mixture with Ar gas shows the highest methane conversion. These results are constructed using the mechanisms of energy and charge transfer from excited and ionized noble gas atoms to methane molecules, considering the number density of active atoms of noble gases. Finally, electron temperatures obtained for gas mixtures having different reactant compositions and concentrations are analyzed to estimate methane activation

  9. Active conductivity of plane two-barrier resonance tunnel structure as operating element of quantum cascade laser or detector

    Ju.O. Set; M.V. Tkach; Matijek, V. O.; O.M. Voitsekhivska

    2011-01-01

    Within the model of rectangular potentials and different effective masses of electrons in different elements of plane two-barrier resonance tunnel structure there is developed a theory of spectral parameters of quasi-stationary states and active conductivity for the case of mono-energetic electronic current interacting with electromagnetic field. It is shown that the two-barrier resonance tunnel structure can be utilized as a separate or active element of quantum cascade laser or detector. Fo...

  10. Endothelium-Derived 5-Methoxytryptophan Protects Endothelial Barrier Function by Blocking p38 MAPK Activation

    Chu, Ling-Yun; Wang, Yi-Fu; Cheng, Huei-Hsuan; Kuo, Cheng-Chin; Wu, Kenneth K.

    2016-01-01

    The endothelial junction is tightly controlled to restrict the passage of blood cells and solutes. Disruption of endothelial barrier function by bacterial endotoxins, cytokines or growth factors results in inflammation and vascular damage leading to vascular diseases. We have identified 5-methoxytryptophan (5-MTP) as an anti-inflammatory factor by metabolomic analysis of conditioned medium of human fibroblasts. Here we postulated that endothelial cells release 5-MTP to protect the barrier function. Conditioned medium of human umbilical vein endothelial cells (HUVECs) prevented endothelial hyperpermeability and VE-cadherin downregulation induced by VEGF, LPS and cytokines. We analyzed the metabolomic profile of HUVEC conditioned medium and detected 5-MTP but not melatonin, serotonin or their catabolites, which was confirmed by enzyme-linked immunosorbent assay. Addition of synthetic pure 5-MTP preserved VE-cadherin and maintained barrier function despite challenge with pro-inflammatory mediators. Tryptophan hydroxylase-1, an enzyme required for 5-MTP biosynthesis, was downregulated in HUVECs by pro-inflammatory mediators and it was accompanied by reduction of 5-MTP. 5-MTP protected VE-cadherin and prevented endothelial hyperpermeability by blocking p38 MAPK activation. A chemical inhibitor of p38 MAPK, SB202190, exhibited a similar protective effect as 5-MTP. To determine whether 5-MTP prevents vascular hyperpermeability in vivo, we evaluated the effect of 5-MTP administration on LPS-induced murine microvascular permeability with Evans blue. 5-MTP significantly prevented Evans blue dye leakage. Our findings indicate that 5-MTP is a new class of endothelium-derived molecules which protects endothelial barrier function by blocking p38 MAPK. PMID:27002329

  11. Regulation of brain copper homeostasis by the brain barrier systems: Effects of Fe-overload and Fe-deficiency

    Monnot, Andrew D.; Behl, Mamta; Ho, Sanna; Zheng, Wei, E-mail: wzheng@purdue.edu

    2011-11-15

    Maintaining brain Cu homeostasis is vital for normal brain function. The role of systemic Fe deficiency (FeD) or overload (FeO) due to metabolic diseases or environmental insults in Cu homeostasis in the cerebrospinal fluid (CSF) and brain tissues remains unknown. This study was designed to investigate how blood-brain barrier (BBB) and blood-SCF barrier (BCB) regulated Cu transport and how FeO or FeD altered brain Cu homeostasis. Rats received an Fe-enriched or Fe-depleted diet for 4 weeks. FeD and FeO treatment resulted in a significant increase (+ 55%) and decrease (- 56%) in CSF Cu levels (p < 0.05), respectively; however, neither treatment had any effect on CSF Fe levels. The FeD, but not FeO, led to significant increases in Cu levels in brain parenchyma and the choroid plexus. In situ brain perfusion studies demonstrated that the rate of Cu transport into the brain parenchyma was significantly faster in FeD rats (+ 92%) and significantly slower (- 53%) in FeO rats than in controls. In vitro two chamber Transwell transepithelial transport studies using primary choroidal epithelial cells revealed a predominant efflux of Cu from the CSF to blood compartment by the BCB. Further ventriculo-cisternal perfusion studies showed that Cu clearance by the choroid plexus in FeD animals was significantly greater than control (p < 0.05). Taken together, our results demonstrate that both the BBB and BCB contribute to maintain a stable Cu homeostasis in the brain and CSF. Cu appears to enter the brain primarily via the BBB and is subsequently removed from the CSF by the BCB. FeD has a more profound effect on brain Cu levels than FeO. FeD increases Cu transport at the brain barriers and prompts Cu overload in the CNS. The BCB plays a key role in removing the excess Cu from the CSF.

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

    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.

  13. THE EUROPEAN MODEL OF STATE REGULATION OF TOURISM ACTIVITIES

    О. Davydova

    2013-01-01

    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, namel...

  14. Active control of internal transport barrier and confinement database in JT-60U reversed shear plasma

    Sakamoto, Yoshiteru; Takizuka, Tomonori; Shirai, Hiroshi; Fujita, Takaaki; Kamada, Yutaka; Ide, Shunsuke; Fukuda, Takeshi; Koide, Yoshihiko [Japan Atomic Energy Research Inst., Naka, Ibaraki (Japan). Naka Fusion Research Establishment

    2001-07-01

    Active control of internal transport barrier (ITB) and confinement properties of plasma with ITB have been studied in reversed shear plasmas. Modifications of the radial electric field (E{sub r}) profile by changing the combination of tangential neutral beams can control the ITB strength, where the contribution to E{sub r} from the toroidal rotation plays an important role. The ITB confinement database of reversed shear plasmas has been constructed. Stored energy is strongly correlated with poloidal magnetic field at the ITB foot. (author)

  15. Young adult males’ motivators and perceived barriers towards eating healthily and being active: a qualitative study

    Ashton, Lee M; Hutchesson, Melinda J.; Rollo, Megan E.; Morgan, Philip J; Thompson, Debbe I; Clare E. Collins

    2015-01-01

    Background 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 behaviours, and (2) explore any differences in responses by weight status categories. Methods Ten focus groups (32-63 minutes; 3-9 participants per group) were conducted with 61 young men (BMI: 25.3 ± 5.1 kg/m2, aged: 18-25 years) from the Hunter region, New South Wal...

  16. Mesenchymal Stem Cells Regulate Blood Brain Barrier Integrity in Traumatic Brain Injury Through Production of the Soluble Factor TIMP3

    Menge, Tyler; Zhao, Yuhai; Zhao, Jing; Wataha, Kathryn; Geber, Michael; Zhang, Jianhu; Letourneau, Phillip; Redell, John; Shen, Li; Wang, Jing; Peng, Zhalong; Xue, Hasen; Kozar, Rosemary; Cox, Charles S.; Khakoo, Aarif Y.; Holcomb, John B.; Dash, Pramod K.; Pati, Shibani

    2013-01-01

    Mesenchymal stem cells (MCSs) have been shown to have therapeutic potential in multiple disease states associated with vascular instability including traumatic brain injury (TBI). In the present study, Tissue Inhibitor of Matrix Metalloproteinase-3 (TIMP3) is identified as the soluble factor produced by MSCs that can recapitulate the beneficial effects of MSCs on endothelial function and blood brain barrier (BBB) compromise in TBI. Attenuation of TIMP3 expression in MSCs completely abrogates the effect of MSCs on BBB permeability and stability, while intravenous administration of rTIMP3 alone can inhibit BBB permeability in TBI. Our results demonstrate that MSCs increase circulating levels of soluble TIMP3, which inhibits VEGF-A induced breakdown of endothelial AJs in vitro and in vivo. These findings elucidate a clear molecular mechanism for the effects of MSCs on the BBB in TBI, and directly demonstrate a role for TIMP3 in regulation of BBB integrity. PMID:23175708

  17. Sex Hormones' Regulation of Rodent Physical Activity: A Review

    J. Timothy Lightfoot

    2008-01-01

    Full Text Available There is a large body of emerging literature suggesting that physical activity is regulated to a varying extent by biological factors. Available animal data strongly suggests that there is a differential regulation of physical activity by sex and that the majority of this differential regulation is mediated by estrogen/testosterone pathways with females in many animal species having higher daily activity levels than males. The purpose of this manuscript is to review the mechanisms by which estrogen and testosterone affect the regulation of daily activity. This review lays the foundation for future investigations in humans as well as discussions about relative disease risk mediated by differential biological regulation of physical activity by sex.

  18. Aerobic Damage to [FeFe]-Hydrogenases: Activation Barriers for the Chemical Attachment of O2**

    Kubas, Adam; De Sancho, David; Best, Robert B; Blumberger, Jochen

    2014-01-01

    [FeFe]-hydrogenases are the best natural hydrogen-producing enzymes but their biotechnological exploitation is hampered by their extreme oxygen sensitivity. The free energy profile for the chemical attachment of O2 to the enzyme active site was investigated by using a range-separated density functional re-parametrized to reproduce high-level ab initio data. An activation free-energy barrier of 13 kcal mol−1 was obtained for chemical bond formation between the di-iron active site and O2, a value in good agreement with experimental inactivation rates. The oxygen binding can be viewed as an inner-sphere electron-transfer process that is strongly influenced by Coulombic interactions with the proximal cubane cluster and the protein environment. The implications of these results for future mutation studies with the aim of increasing the oxygen tolerance of this enzyme are discussed. PMID:24615978

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

    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. PMID:20364316

  20. Regulation of higher-activity NARM wastes by EPA

    The US Environmental Protection Agency (EPA) is currently developing standards for the disposal of low-level radioactive waste (LLW). As part of this Standard, EPA is including regulations for the disposal of naturally occurring and accelerator-produced radioactive material (NARM) wastes not covered under the Atomic Energy Act (AEA). The regulations will cover only higher-activity NARM wastes, defined as NARM waste with specific activity exceeding two nanocuries per gram. The proposed regulations will specify that NARM wastes exceeding the above limits, except for specific exempted items, must be disposed of in regulated radioactive waste disposal facilities. The proposed EPA regulations for NARM wastes will be discussed, as well as the costs and benefits of the regulation, how it will be implemented by EPA, and the rationale for covering only higher-activity NARM wastes exceeding two nanocuries per gram

  1. Aging, Physical Activity, and Energy Intake Regulation

    Van Walleghen, Emily Lynn

    2006-01-01

    More than seventy percent of Americans over the age of sixty are classified as overweight or obese, and the future incidence of these conditions is expected to rise. Although it is unclear why older adults are predisposed to weight gain, decreased total energy expenditure may contribute to positive energy balance. It is also possible that age-related impairments in energy intake regulation result in the inability to appropriately adjust food intake to meet energy requirements with advancing a...

  2. Understanding barriers and facilitators to healthy eating and active living in rural communities.

    Seguin, Rebecca; Connor, Leah; Nelson, Miriam; LaCroix, Andrea; Eldridge, Galen

    2014-01-01

    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. PMID:25574386

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

    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.

  4. [Measurement of active particles generated in a coaxial barrier discharge by spectral method].

    Li, Xue-Chen; Chang, Yuan-Yuan; Jia, Peng-Ying

    2013-05-01

    Coaxial dielectric barrier discharge has extensive application prospects. A dielectric barrier discharge device with water electrode was used to investigate the discharge properties and spectral intensity emitted from active particles in the air by optical method. Results indicate that the optical emission spectra consist of spectral lines from oxygen atoms (777.5 and 844.6 nm), which implies that oxygen atoms with high chemical activity were generated in the discharge plasma. Through spatially resolved measurements, spectral intensities from oxygen atoms were given as functions of the experimental parameters such as the value of the applied voltage, the gas flow rate and argon content. Results show that the spectral line intensity from oxygen atom increases with increasing the peak value of the applied voltage, increases with increasing the gas flow rate, reaches its maximum with a gas flow rate of 30 L x min(-1) and then decreases with further increasing the gas flow rate. Similarly, the spectral line intensity increases firstly and then decreases with increasing argon content (in a mixture of argon and air) and a maximum is reached when argon content is 16.7%. PMID:23905311

  5. Model of behavior of concrete barriers for the isolation of radioactive waste of low activity

    In most countries the final disposal of low level radioactive waste is performed in surface or near-surface disposal facilities, with an extended use of disposal designs in which concrete is the basic material of the isolation barriers. This thesis collects a good deal of the results of the research works on barriers behaviour performed in the frame of the different ENRESA R+D Plans in support of the enhancement of the safety assessment of the low activity radioactive was te disposal facility. In this work the functions of the different components of the disposal system are analysed together with their characteristics. Also there is a description of the evolution processes and the laws that control those processes, based on previous research works. The flow and content of water in low permeability porous media with particular regard to concrete is also developed for the expected environmental conditions after sealing the disposal vaults with an engineered cap and when they are exposed to non isothermal conditions having an influence in the behaviour of the system water content. A sum mary of the R+D work previously performed for ENRESA on the behaviour of low activity waste isolation barriers behaviour. Some enhancements on previous models and an integration scheme are also proposed. This work also contains the on going research tasks for the calibration of the models and the collection of experimental data that may al low a fruitful use of the models, beyond an academic exercise, and provide reference data for future development as well. The initial aim of this work was to propose a general model on the behaviour of the concrete barriers. Such general model still presents lack of experts consensus on basic aspects such as the CSH chemistry. It concludes that an approach based on the use of models representing separately the different processes, based on experimental work and expressed in phenomenological simple models is more rigorous at this point. Nevertheless

  6. "I Don't Have Time": Barriers and Facilitators to Physical Activity for Adults With Intellectual Disabilities.

    Taliaferro, Andrea R; Hammond, Lindsay

    2016-04-01

    Individuals with intellectual disabilities (ID) tend to have low rates of participation in voluntary or prescribed physical activity. The purpose of this study, therefore, was to identify the barriers, facilitators, and needs influencing physical activity participation of adults with ID within the framework of a social ecological model. A qualitative approach consisted of data collected from surveys and guided focus groups. Participants included adults with ID (n = 6) and their primary caregiver (n = 6). Barriers were categorized under three themes: organizational barriers, individual constraints, and external influences. Examples of subthemes included information dissemination, reliance on others, and caregiver considerations. Facilitators included primary caregivers as champions and camaraderie. Needs centered on family program involvement, improved programmatic structure, and programmatic support. Results indicate the need for community programs to examine barriers and facilitators applicable to their unique setting and population across all levels of a social ecological model. PMID:27078268

  7. Modern aspects of tax regulation of investment activity

    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.

  8. Detection of hydroxyl radicals during regeneration of granular activated carbon in dielectric barrier discharge plasma system

    To understand the reactions taking place in the dielectric barrier discharge (DBD) plasma system of activated carbon regeneration, the determination of active species is necessary. A method based on High Performance Liquid Chromatography with radical trapping by salicylic acid, has been developed to measure hydroxyl radical (.OH) in the DBD plasma reactor. The effects of applied voltage, treatment time, and gas flow rate and atmosphere were investigated. Experimental results indicated that increasing voltage, treatment time and air flow rate could enhance the formation of .OH. Oxygen atmosphere and a suitable GAC water content were contributed to .OH generation. The results give an insight into plasma chemical processes, and can be helpful to optimize the design and application for the plasma system.

  9. Activity Dependent Regulation of Inhibitory Circuitry

    Sharma, Nikhil

    2015-01-01

    Inhibition controls information flow through a neural circuit by modulating synaptic integration, restricting action potentials, and coordinating the activity of ensembles of neurons. These functions are mediated by a diverse array of inhibitory neuron subtypes that synapse on defined domains of a postsynaptic neuron. Activity-dependent transcription controls inhibitory synapse number and function, but how this transcription program affects the inhibitory inputs that form on di...

  10. Commission for energy regulation - 2012 Activity Report

    After a presentation of the organisation, role and missions of the French Commission for Energy Regulation (CRE), and of its relationship with other institutional actors, this report describes and comments the action of the CRE in the fields of dialogue and transparency. It presents and comments key figures regarding the electricity and gas retail markets. It reports and comments the European reaction to the cold peak of February 2012 (historical peak for consumption and prices, inquiry on the causes of these price peaks, need of a European market). The next part addresses the relationship between electricity grids and territories (solidarity between electricity grids as the basis of the Europe of energy, evolution of French grids to face new needs and to take regional and local dimensions into account). Another part addresses gas infrastructures which are considered as the cornerstone of a good operation for the French market and for the integration of the European energy market (gas world market in 2012, definition of a target model for the gas market by European regulators, evolution of the French market in compliance with the European target model, new tariffs for the use of natural gas transport networks). The report then addresses the development of renewable energies: actions of CRE (bidding, opinion of tariffs), influence of renewable energy development on electricity prices on gross markets, needed evolution of electricity grids. A last part addresses the issues of energy cost, demand management, and struggle against energy poverty

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

    Jørgensen, Sebastian Beck; Rose, Adam John

    2008-01-01

    AMPK is a metabolic "master" controller activated in skeletal muscle by exercise in a time and intensity dependent manner, and has been implicated in regulating metabolic pathways in muscle during physical exercise. AMPK signaling in skeletal muscle is regulated by several systemic...... and intracellular factors and the regulation of skeletal muscle AMPK in response to exercise is the focus of this review. Specifically, the role of LKB1 and phosphatase PP2C in nucleotide-dependent activation of AMPK, and ionized calcium in CaMKK-dependent activation of AMPK in working muscle is discussed. We also...

  12. Dietary methanol regulates human gene activity.

    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.

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

    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

  14. Characteristics of powdered activated carbon treated with dielectric barrier discharge for electric double-layer capacitors

    Highlights: ► The specific capacitance of the EDLCs could be improved by oxygen plasma treatment. ► 15 s treated EDLCs showed a 20% increase in capacitance relative to untreated EDLCs. ► The plasma treatment yields EDLCs that are suitable for high-energy applications. - Abstract: The electrochemical properties of electric double-layer capacitors (EDLCs) made with plasma-treated powdered activated carbon (treated using a dielectric barrier discharge) were examined using cyclic voltammetry (CV), Cole–Cole plots, and X-ray photoelectron spectroscopy (XPS). The dielectric barrier discharge method, which operates at atmospheric pressure, dramatically reduces the processing time and does not require vacuum equipment, making it a more practical alternative than low-pressure plasma treatment. The experimental data indicate that the specific capacitance of the EDLCs could be improved by oxygen plasma treatment. Capacitance of EDLCs made with activated carbon treated for 15 s showed 193.5 F/g that 20% increase in the specific capacitance relative to untreated EDLCs. This result indicates that the plasma treatment yields EDLCs that are suitable for high-energy applications. The enhancement of capacitance was mainly attributed to an increase in the BET surface area of the activated carbon and the creation of carboxyl groups on the surface of the carbon. The carboxyl groups induced oxidation–reduction reactions in the presence of O2 which was included in the operation gas. In addition, the carboxyl groups improved the penetration of the electrolyte solution into the carbon electrodes.

  15. Regulation of nuclear activities in Canada

    This review was initiated by the OECD Nuclear Energy Agency for its series of analytical studies on nuclear legislation. It looks at the historic background and general overview of the use and handling of nuclear energy; the governmental framework controlling nuclear activities; and the agencies involved in its research and industrial applications. The regulatory power and structure of the Atomic Energy Control Board are highlighted

  16. Hormonal Regulation of Hepatic Drug Metabolizing Enzyme Activity During Adolescence

    Kennedy, M J

    2008-01-01

    Activities of drug metabolizing enzymes (DME) are known to change throughout the course of physical and sexual maturation with the greatest variability noted during infancy and adolescence. The mechanisms responsible for developmental regulation of DME are currently unknown. However, the hormonal changes of puberty/adolescence provide a theoretical framework for understanding biochemical regulation of DME activity during growth and maturation. Important information regarding potential influen...

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

    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.

  18. Localized MHD activity near transport barriers in JT-60U and TFTR

    Localized MHD activity observed in JT-60U and TFTR near transport barriers with their associated large pressure gradients is investigated. Stability analysis of equilibria modeling the experiments supports an identification of this MHD as being due to an ideal MHD n = 1 instability. The appearance of the instability depends on the local pressure gradient, local shear in the q profile and the proximity of rational surfaces where q ∼ m/n and m and n are the poloidal and toroidal mode numbers respectively. The mode width is shown to depend on the local value of q, and is larger when q is smaller. In addition the role of the edge current density in coupling the internal mode to the plasma edge and of the energetic particles which can drive fishbone like modes is investigated. (author)

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

    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.

  20. Effects of ionizing radiation on the blood brain barrier permeability to pharmacologically active substances

    Trnovec, T.; Kallay, Z.; Bezek, S. (Institute of Experimental Pharmacology, Bratislava (Yugoslavia))

    1990-12-01

    Ionizing radiation can impair the integrity of the blood brain barrier (BBB). Data on early and late damage after brain irradiation are usually reported separately, yet a gradual transition between these two types has become evident. Signs appearing within 3 weeks after irradiation are considered to be early manifestations. The mechanism of radiation-effected integrity impairment of the BBB is discussed in relation to changes in morphological structures forming the BBB, the endothelium of intracerebral vessels, and in the surrounding astrocytes. Alterations in the function of the BBB are manifested in the endothelium by changes in the ultrastructural location of the activity of phosphatases and by the activation of pinocytotic vesicular transport, and in astrocyte cytoplasm by glycogen deposition. The changes in ultrastructure were critically surveyed with regard to increasing doses of radiation to the brain in the range of 5 Gy to 960 Gy. The qualitative as well as the semiquantitative and quantitative observations on the passage of substances across the damaged BBB were treated separately. Qualitative changes are based mainly on findings of extravasation of vital stains and of labelled proteins. The quantitative studies established differences in radiation-induced changes in the permeability of the BBB depending on the structure and physico-chemical properties of the barrier penetrating tracers. Indirect evaluation of radiation-induced BBB changes is based on studies of pharmacological effects of substances acting on the CNS. In conclusion, radiation impairs significantly the integrity of the BBB following single irradiation of the brain with a dose exceeding 10-15 Gy. The response of the BBB to ionizing radiation is dependent both on the dose to which the brain is exposed and on specific properties of the tracer. 68 references.

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

    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

  2. Active conductivity of plane two-barrier resonance tunnel structure as operating element of quantum cascade laser or detector

    Ju.O. Set

    2011-06-01

    Full Text Available Within the model of rectangular potentials and different effective masses of electrons in different elements of plane two-barrier resonance tunnel structure there is developed a theory of spectral parameters of quasi-stationary states and active conductivity for the case of mono-energetic electronic current interacting with electromagnetic field. It is shown that the two-barrier resonance tunnel structure can be utilized as a separate or active element of quantum cascade laser or detector. For the experimentally studied In0.53Ga0.47As/In0.52Al0.48As nano-system it is established that the two-barrier resonance tunnel structure, in detector and laser regimes, optimally operates (with the biggest conductivity at the smallest exciting current at the quantum transitions between the lowest quasi-stationary states.

  3. Developmental regulation of aromatase activity in the rat hypothalamus

    The brain of all mammalian species studied thus far contain an enzymatic activity (aromatase) that catalyzes the conversion of androgens to estrogens. The activity is highest during prenatal development and contributes to the establishment of sex differences which determine adult gonadotropin secretion patterns and reproductive behavior. The studies presented in this dissertation represent a systematic effort to elucidate the mechanism(s) that control the initiation of and contribute to maintaining rat hypothalamic aromatase activity during pre- and postnatal development. Aromatase enzyme activity was measured by the 3H2O release assay or by traditional estrogen product isolation. Brain aromatase mRNA was detected by hybridization to a cDNA encoding rat aromatase cytochrome P-450. In both males and females the time of puberty was associated with a decline in hypothalamic aromatase activity. This decline may represent a factor underlying the peri-pubertal decrease in the sensitivity to gonadal steroid feedback that accompanies completion of puberty. The results also indicate that androgens regulate brain aromatase levels during both the prepubertal and peri-pubertal stages of sexual development and that this regulation is transiently lost in young adults. Utilizing a hypothalamic organotypic culture system, aromatase activity in vitro was maintained for as long as two days. The results of studies of a variety of hormonal and metabolic regulators suggest that prenatal aromatase activity is regulated by factor(s) that function independently from the classical cyclic AMP and protein kinase C trans-membrane signaling pathways

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

    Vanraes, Patrick; Willems, Gert; Nikiforov, Anton; Surmont, Pieter; Lynen, Frederic; Vandamme, Jeroen; Van Durme, Jim; Verheust, Yannick P; Van Hulle, Stijn W H; Dumoulin, Ann; Leys, Christophe

    2015-12-15

    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. PMID:26282086

  5. Women bound to be active (years 3 and 4): can a book club help women overcome barriers to physical activity and improve self-worth?

    Huberty, Jennifer L; Vener, Jamie; Ransdell, Lynda; Schulte, Laura; Budd, Melissa A; Gao, Yong

    2010-01-01

    Little progress has been made toward increasing physical activity in women. This study aimed to determine if an 8-month theory-based book club intervention (Women Bound to Be Active) was effective in increasing: (a) self-worth, (b) benefits relative to barriers to physical activity, and (c) physical activity in women (n = 51). Findings suggested a book club was effective for improving: self-worth, the benefits relative to barriers to physical activity, and possibly participation in physical activity. This is an innovative model to help women become more active and learn skills that may enable them to be active on their own long after a physical activity program has ended. PMID:20349397

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

    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

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

    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.

  8. 北京市无障碍建设法规执行状况调研%Investigation on the Implementation of Barrier-free Regulations in Beijing

    安天义; 邓晓梅

    2011-01-01

    近年来我国的无障碍环境立法工作取得了瞩目的成绩,但也暴露出众多无障碍法规缺乏执行力的问题,限制了无障碍环境建设工作的落实和推广.本文关注于无障碍法规的执行力问题,以国内首部无障碍设施的地方性法规--为基准,对公共设施的无障碍建设情况开展实地调研.调研发现:以商业类设施和地铁类设施为代表的新建建筑比老建筑的无障碍建设情况要好;坡道、盲道、升降装置等设施的建设情况要明显好于警示标识、安全扶手、低位装置等设施;中的条款不够细致和全面,造成了在建设和验收环节没有明确的执行标准;而盲道被不合理占用等情况暴露出公众无障碍意识和知识缺乏的问题.本文的研究结果为无障碍法规的监督与执行提供了重要参考.%While the significant achievements have been obtained in respect of legislative work on barrier-free facilities, there are still problems with implementation of barrier-free regulations. This paper focuses on the implementation of Barrier-free regulations,and investigates the current situations of barrier-free environment of public buildings based on‘ The Regulation of Barrier-free Facilities Construction and Management in Beijing' , the first local regulation related to barrier-free in China. It is found that: ( 1 ) The barrierfree environment of new buildings, such as commercial buildings and subway facilities, is better than that of old buildings (2) Ramp way, blind walk way, barrier-free lift devices, and barrier-free lavatory are better built than warning sign, safety armrest, and lowposition devices; (3) The regulation is not comprehensive and explicit enough, which leads to no clear criteria to follow during construction and acceptance inspection; The misuse of blind walk way reveals that the public are lack of knowledge and awareness related to the barrier-free environment. The findings in this paper provide

  9. Post-translational regulation of Oct4 transcriptional activity.

    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.

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

    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.

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

    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

  12. Regulation of Mining and Mineral Processing Activities in South Africa

    In South Africa, the regulation of mining and mineral processing activities involving radioactive ores commenced in 1990. The paper provides an overview of the regulation of mining and mineral processing activities and the evolution of the authorization process from 1990 until recent times. Key developments in respect of controlling public exposure, occupational exposure, and environmental protection are provided. Future and present challenges are also identified with the resurgence of activities related to nuclear power generation linked to uranium mining. The centrality of nuclear and radiation safety requirements in the context of introducing improvements for effectively regulating mining are also cited and put forward. Reference is made to the role of the South African nuclear regulatory system and the impact of the nuclear safety and security regime. (author)

  13. REGULATION OF NITRATE REDUCTASE ACTIVITY IN RICE (ORYZA SATIVA L. BY GROWTH REGULATORS

    S HEMALATHA

    2002-12-01

    Full Text Available The effect of three growth regulators, namely kinetin, 6 benzyl adenine, 2 chloro ethyl trimethyl ammonium chloride at three concentrations (10-6 M, 5 x 10-5 M 10-4 M was studied on the catalytic activity of nitrate reductase in green and etiolated seedlings. A concentration of 5 x 10-5 M was optimal for all the growth regulators treatments. All the growth regulators stimulated nitrate reductase activity effectively at 5 x 10-5M concentration in both etiolated and green seedlings and had an additive effect when supplemented by NO-3 up to 140% to 160%. The 99.2% and 93.4% inhibition of nitrate reductase activity resulted in development of etiolated and green seedlings, respectively when treated with eukaryotic 80S ribosome protein synthesis inhibitor cycloheximide. Prokaryotic 70S inhibitor chloromphenicol did not have any effect on measured parameters. Actinomycin D, a RNA synthesis inhibitor also inhibited the enzyme activity as 80s inhibitors (Green 80%, etiolated 98%. One may suggest from this that both DNA and protein synthesis are involved in the induction of nitrate reductase activity. The differential effect of aminoacids was observed on enzyme activity in combination with growth regulators.

  14. Primary cilia regulate Gli/Hedgehog activation in pancreas

    Cervantes, Sara; Lau, Janet; Cano, David A.; Borromeo-Austin, Cecilia; Hebrok, Matthias

    2010-01-01

    Previous studies have suggested that defects in pancreatic epithelium caused by activation of the Hedgehog (Hh) signaling pathway are secondary to changes in the differentiation state of the surrounding mesenchyme. However, recent results describe a role of the pathway in pancreatic epithelium, both during development and in adult tissue during neoplastic transformation. To determine the consequences of epithelial Hh activation during pancreas development, we employed a transgenic mouse model in which an activated version of GLI2, a transcriptional mediator of the pathway, is overexpressed specifically in the pancreatic epithelium. Surprisingly, efficient Hh activation was not observed in these transgenic mice, indicating the presence of physiological mechanisms within pancreas epithelium that prevent full Hh activation. Additional studies revealed that primary cilia regulate the level of Hh activation, and that ablation of these cellular organelles is sufficient to cause significant up-regulation of the Hh pathway in pancreata of mice overexpressing GLI2. As a consequence of overt Hh activation, we observe profound morphological changes in both the exocrine and endocrine pancreas. Increased Hh activity also induced the expansion of an undifferentiated cell population expressing progenitor markers. Thus, our findings suggest that Hh signaling plays a critical role in regulating pancreatic epithelial plasticity. PMID:20479231

  15. Primary cilia regulate Gli/Hedgehog activation in pancreas.

    Cervantes, Sara; Lau, Janet; Cano, David A; Borromeo-Austin, Cecilia; Hebrok, Matthias

    2010-06-01

    Previous studies have suggested that defects in pancreatic epithelium caused by activation of the Hedgehog (Hh) signaling pathway are secondary to changes in the differentiation state of the surrounding mesenchyme. However, recent results describe a role of the pathway in pancreatic epithelium, both during development and in adult tissue during neoplastic transformation. To determine the consequences of epithelial Hh activation during pancreas development, we employed a transgenic mouse model in which an activated version of GLI2, a transcriptional mediator of the pathway, is overexpressed specifically in the pancreatic epithelium. Surprisingly, efficient Hh activation was not observed in these transgenic mice, indicating the presence of physiological mechanisms within pancreas epithelium that prevent full Hh activation. Additional studies revealed that primary cilia regulate the level of Hh activation, and that ablation of these cellular organelles is sufficient to cause significant up-regulation of the Hh pathway in pancreata of mice overexpressing GLI2. As a consequence of overt Hh activation, we observe profound morphological changes in both the exocrine and endocrine pancreas. Increased Hh activity also induced the expansion of an undifferentiated cell population expressing progenitor markers. Thus, our findings suggest that Hh signaling plays a critical role in regulating pancreatic epithelial plasticity. PMID:20479231

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

    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.

  17. Activation of ion transport systems during cell volume regulation

    This review discusses the activation of transport pathways during volume regulation, including their characteristics, the possible biochemical pathways that may mediate the activation of transport pathways, and the relations between volume regulation and transepithelial transport in renal cells. Many cells regulate their volume when exposed to an anisotonic medium. The changes in cell volume are caused by activation of ion transport pathways, plus the accompanying osmotically driven water movement such that cell volume returns toward normal levels. The swelling of hypertonically shrunken cells is termed regulatory volume increase (RVI) and involves an influx of NaCl into the cell via either activation of Na-Cl, Na-K-2Cl cotransport systems, or Na+-H+ and Cl--HCO3- exchangers. The reshrinking of hypotonically swollen cells is termed regulatory volume decrease (RVD) and involves an efflux of KCl and water from the cell by activation of either separate K+ and Cl- conductances, a K-Cl cotransport system, or parallel K+-H+ and Cl--HCO3- exchangers. The biochemical mechanisms involved in the activation of transport systems are largely unknown, however, the phosphoinositide pathway may be implicated in RVI; phorbol esters, cGMP, and Ca2+ affect the process of volume regulation. Renal tubular cells, as well as the blood cells that transverse the medulla, are subjected to increasing osmotic gradients from the corticomedullary junction to the papillary tip, as well as changing interstitial and tubule fluid osmolarity, depending on the diuretic state of the animal. Medullary cells from the loop of Henle and the papilla can volume regulate by activating Na-K-2Cl cotransport or Na+-H+ and Cl--HCO3- exchange systems

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

    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

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

    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.

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

    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.

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

    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

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

    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...

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

    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. PMID:26421625

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

    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

  5. Using community-based participatory research to identify potential interventions to overcome barriers to adolescents’ healthy eating and physical activity

    Goh, Ying-Ying; Bogart, Laura M.; Sipple-Asher, Bessie Ko; Uyeda, Kimberly; Hawes-Dawson, Jennifer; Olarita-Dhungana, Josephina; Ryan, Gery W.; Schuster, Mark A.

    2009-01-01

    Using a community-based participatory research approach, we explored adolescent, parent, and community stakeholder perspectives on barriers to healthy eating and physical activity, and intervention ideas to address adolescent obesity. We conducted 14 adolescent focus groups (n = 119), 8 parent focus groups (n = 63), and 28 interviews with community members (i.e., local experts knowledgeable about youth nutrition and physical activity). Participants described ecological and psychosocial barrie...

  6. Effect of Standardized Boesenbergia pandurata Extract and Its Active Compound Panduratin A on Skin Hydration and Barrier Function in Human Epidermal Keratinocytes

    Woo, Seon Wook; Rhim, Dong-Bin; Kim, Changhee; Hwang, Jae-Kwan

    2015-01-01

    The skin plays a key role in protecting the body from the environment and from water loss. Cornified envelope (CE) and natural moisturizing factor (NMF) are considered as the primary regulators of skin hydration and barrier function. The CE prevents loss of water from the body and is formed by cross-linking of several proteins. Among these proteins, filaggrin is an important protein because NMF is produced by the degradation of filaggrin. Proteases, including matriptase and prostasin, stimulate the generation of filaggrin from profilaggrin and caspase-14 plays a role in the degradation of filaggrin. This study elucidated the effects of an ethanol extract of Boesenbergia pandurata (Roxb.) Schltr., known as fingerroot, and its active compound panduratin A on CE formation and filaggrin processing in HaCaT, human epidermal keratinocytes. B. pandurata extract (BPE) and panduratin A significantly stimulated not only CE formation but also the expression of CE proteins, such as loricrin, involucrin, and transglutaminase, which were associated with PPARα expression. The mRNA and protein levels of filaggrin and filaggrin-related enzymes, such as matriptase, prostasin, and caspase-14 were also up-regulated by BPE and panduratin A treatment. These results suggest that BPE and panduratin A are potential nutraceuticals which can enhance skin hydration and barrier function based on their CE formation and filaggrin processing. PMID:25866745

  7. Energy Regulation Commission. Activity report. 1 July - 31 December 2008

    After a description of the scope of activities, organisation and operation of the CRE (Commission de Regulation de l'Energie, Energy regulation commission) and of the CorDIS (Comite de reglement des differents et des sanctions de la CRE, CRE's Committee for settlements of controversies and sanctions), this report outlines the importance of the grid manager independence and of the regulation reinforcement for the building up of a domestic energy market. It discusses the role of the regulation authority in the interconnection of European grids, their operation security and supply security, but also in pricing and in investments. It highlights the relationship between the reduction of carbon emission, energy demand management, strengthening of electric grids, financial incentives, and advanced metering systems. It describes how the CRE ensures a good operation of electricity and natural gas markets

  8. Active Inference, homeostatic regulation and adaptive behavioural control.

    Pezzulo, Giovanni; Rigoli, Francesco; Friston, Karl

    2015-11-01

    We review a theory of homeostatic regulation and adaptive behavioural control within the Active Inference framework. Our aim is to connect two research streams that are usually considered independently; namely, Active Inference and associative learning theories of animal behaviour. The former uses a probabilistic (Bayesian) formulation of perception and action, while the latter calls on multiple (Pavlovian, habitual, goal-directed) processes for homeostatic and behavioural control. We offer a synthesis these classical processes and cast them as successive hierarchical contextualisations of sensorimotor constructs, using the generative models that underpin Active Inference. This dissolves any apparent mechanistic distinction between the optimization processes that mediate classical control or learning. Furthermore, we generalize the scope of Active Inference by emphasizing interoceptive inference and homeostatic regulation. The ensuing homeostatic (or allostatic) perspective provides an intuitive explanation for how priors act as drives or goals to enslave action, and emphasises the embodied nature of inference. PMID:26365173

  9. THE EUROPEAN MODEL OF STATE REGULATION OF TOURISM ACTIVITIES

    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.

  10. The Immune System as a Regulator of Thyroid Hormone Activity

    Klein, John R.

    2006-01-01

    It has been known for decades that the neuroendocrine system can both directly and indirectly influence the developmental and functional activity of the immune system. In contrast, far less is known about the extent to which the immune system collaborates in the regulation of endocrine activity. This is particularly true for immune-endocrine interactions of the hypothalamus-pituitary-thyroid axis. Although thyroid stimulating hormone (TSH) can be produced by many types of extra-pituitary cell...

  11. Regulation of eNOS Enzyme Activity by Posttranslational Modification

    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, coo...

  12. Myostatin negatively regulates satellite cell activation and self-renewal

    McCroskery, Seumas; Thomas, Mark; Maxwell, Linda; Sharma, Mridula; Kambadur, Ravi

    2003-01-01

    Satellite cells are quiescent muscle stem cells that promote postnatal muscle growth and repair. Here we show that myostatin, a TGF-β member, signals satellite cell quiescence and also negatively regulates satellite cell self-renewal. BrdU labeling in vivo revealed that, among the Myostatin-deficient satellite cells, higher numbers of satellite cells are activated as compared with wild type. In contrast, addition of Myostatin to myofiber explant cultures inhibits satellite cell activation. Ce...

  13. Active Inference, homeostatic regulation and adaptive behavioural control

    Pezzulo, G; Rigoli, F.; Friston, K.

    2015-01-01

    We review a theory of homeostatic regulation and adaptive behavioural control within the Active Inference framework. Our aim is to connect two research streams that are usually considered independently; namely, Active Inference and associative learning theories of animal behaviour. The former uses a probabilistic (Bayesian) formulation of perception and action, while the latter calls on multiple (Pavlovian, habitual, goal-directed) processes for homeostatic and behavioural control. We offer a...

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

    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…

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

    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)...

  16. Regulation of Enzyme Activity through Interactions with Nanoparticles

    Bin Zhang; Bing Yan; Zhaochun Wu

    2009-01-01

    The structure and function of an enzyme can be altered by nanoparticles (NPs). The interaction between enzyme and NPs is governed by the key properties of NPs, such as structure, size, surface chemistry, charge and surface shape. Recent representative studies on the NP-enzyme interactions and the regulation of enzyme activity by NPs with different size, composition and surface modification are reviewed.

  17. 76 FR 28801 - Agency Information Collection Activities: Bonded Warehouse Regulations

    2011-05-18

    ... Federal Register (76 FR 11254) on March 1, 2011, allowing for a 60-day comment period. This notice allows... 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...

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

    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...... technology. Ertmer’s approach establishes first-order and second-orders barriers as hinderers for teacher’s adoption of technology. The study intends to answer what are the barriers existing in the socalled enthusiastic faculty teachers regarding technology integration in Education? Findings call for a...... dichotomies between enthusiastic-resistant teachers, the intrinsic-extrinsic barriers, and claims for passing from an individual to a collective approach to ICT integration in education...

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

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

    2013-01-01

    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...

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

    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.

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

    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

  2. METEORIN-LIKE is a cytokine associated with barrier tissues and alternatively activated macrophages

    Ushach, Irina; Burkhardt, Amanda M.; Martinez, Cynthia; Hevezi, Peter A.; Gerber, Peter Arne; Buhren, Bettina Alexandra; Schrumpf, Holger; Valle-Rios, Ricardo; Vazquez, Monica I.; Homey, Bernhard; Zlotnik, Albert

    2014-01-01

    Cytokines are involved in many functions of the immune system including initiating, amplifying and resolving immune responses. Through bioinformatics analyses of a comprehensive database of gene expression (BIGE: Body Index of Gene Expression) we observed that a small secreted protein encoded by a poorly characterized gene called meteorin-like (METRNL), is highly expressed in mucosal tissues, skin and activated macrophages. Further studies indicate that Metrnl is produced by Alternatively Activated Macrophages (AAM) and M-CSF cultured bone marrow macrophages (M2-like macrophages). In the skin, METRNL is expressed by resting fibroblasts and IFNγ-treated keratinocytes. A screen of human skin-associated diseases showed significant over-expression of METRNL in psoriasis, prurigo nodularis, actinic keratosis and atopic dermatitis. METRNL is also up-regulated in synovial membranes of human rheumatoid arthritis. Taken together, these results indicate that Metrnl represents a novel cytokine, which is likely involved in both innate and acquired immune responses. PMID:25486603

  3. Endothelium-Derived 5-Methoxytryptophan Protects Endothelial Barrier Function by Blocking p38 MAPK Activation

    Chu, Ling-Yun; Wang, Yi-Fu; Cheng, Huei-Hsuan; Kuo, Cheng-Chin; Wu, Kenneth K.

    2016-01-01

    The endothelial junction is tightly controlled to restrict the passage of blood cells and solutes. Disruption of endothelial barrier function by bacterial endotoxins, cytokines or growth factors results in inflammation and vascular damage leading to vascular diseases. We have identified 5-methoxytryptophan (5-MTP) as an anti-inflammatory factor by metabolomic analysis of conditioned medium of human fibroblasts. Here we postulated that endothelial cells release 5-MTP to protect the barrier fun...

  4. Commission for Energy regulation (CRE) - Activity report june 2008

    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 2008 activity report of CRE. Content: A - How CRE works: CRE regulatory authority and organisation: Powers, Organisation; Budget resources; Personnel; B - The Standing Committee for Dispute Settlement and Sanctions (CoRDiS) activity: Admissibility, Authority; C - Building a single European energy market: Overview; Organisation and coordination of the main European regulators (Work carried out collectively by European regulators, Regulator organisation and development, CRE's relations with European Community institutions, Development of CEER activities outside the European Union); CRE's European activities (The contribution of European regulators to the Third Energy Package, Integration of gas markets, Integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, Opening up markets to benefit consumers); European Community activities (The European Commission's proposals for the internal energy market: the Third Energy Package, The European Commission's proposals for fighting climate change: the Climate Package, Infringement

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

    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.

  6. Tetraspanin CD9 regulates osteoclastogenesis via regulation of p44/42 MAPK activity

    Tetraspanin CD9 has been shown to regulate cell-cell fusion in sperm-egg fusion and myotube formation. However, the role of CD9 in osteoclast, another multinucleated cell type, is not still clear. Therefore, we investigated the role of CD9 in osteoclast differentiation. CD9 was expressed in osteoclast lineage cells and its expression level increased during the progression of RANKL-induced osteoclastogenesis. KMC8, a neutralizing antibody specific to CD9, significantly suppressed RANKL-induced multinucleated osteoclast formation and the mRNA expression of osteoclast differentiation marker genes. To define CD9-regulated osteoclastogenic signaling pathway, MAPK pathways were examined. KMC8 induced long-term phosphorylation of p44/42 MAPK, but not of p38 MAPK. Constitutive activation of p44/42 MAPK by overexpressing constitutive-active mutant of MEK1 almost completely blocked osteoclast differentiation. Taken together, these results suggest that CD9 expressed on osteoclast lineage cells might positively regulate osteoclastogenesis via the regulation of p44/42 MAPK activity

  7. Skin Barrier Health: Regulation and Repair of the Stratum Corneum and the Role of Over-the-Counter Skin Care.

    Lee, Thomas; Friedman, Adam

    2016-09-01

    The epidermis functions as a physical barrier that separates the inner body from the outside environment. The outermost layer of the epidermis, the stratum corneum, plays a key role in maintaining this barrier. There are numerous biochemical changes that take place to and in the keratinocyte as it migrates from the bottom, or startum basale, to the top layer of the epidermis in order for this barrier to function appropriately. In addition, external and internal factors, such as irritants and underlying medical diseases, can also affect the stratum corneum, both of which can potentially lead to disruption of barrier function and ultimately skin pathology. In this article, we will review keratinocyte biology as it relates to the formation and function of the stratum corneum. We will also review stratum corneum structure, physiology, and the impact of chemical agents and defective stratum corneum components that can lead to skin disease. Finally, we will briefly discuss how moisturizers repair defects in the stratum corneum and restore barrier function. J Drugs Dermatol. 2016;15(9):1047-1051. PMID:27602965

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

    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

  9. NASA GSFC Science Communication Working Group: Addressing Barriers to Scientist and Engineer Participation in Education and Public Outreach Activities

    Bleacher, L.; Hsu, B. C.; Campbell, B. A.; Hess, M.

    2011-12-01

    The Science Communication Working Group (SCWG) at NASA Goddard Space Flight Center (GSFC) has been in existence since late 2007. The SCWG is comprised of education and public outreach (E/PO) professionals, public affairs specialists, scientists, and engineers. The goals of the SCWG are to identify barriers to scientist and engineer engagement in E/PO activities and to enable those scientists and engineers who wish to contribute to E/PO to be able to do so. SCWG members have held meetings with scientists and engineers across GSFC to determine barriers to their involvement in E/PO. During these meetings, SCWG members presented examples of successful, ongoing E/PO projects, encouraged active research scientists and engineers to talk about their own E/PO efforts and what worked for them, discussed the E/PO working environment, discussed opportunities for getting involved in E/PO (particularly in high-impact efforts that do not take much time), handed out booklets on effective E/PO, and asked scientists and engineers what they need to engage in E/PO. The identified barriers were consistent among scientists in GSFC's four science divisions (Earth science, planetary science, heliophysics, and astrophysics). Common barriers included 1) lack of time, 2) lack of funding support, 3) lack of value placed on doing E/PO by supervisors, 4) lack of training on doing appropriate/effective E/PO for different audiences, 5) lack of awareness and information about opportunities, 6) lack of understanding of what E/PO really is, and 7) level of effort required to do E/PO. Engineers reported similar issues, but the issues of time and funding support were more pronounced due to their highly structured work day and environment. Since the barriers were identified, the SCWG has taken a number of steps to address and rectify them. Steps have included holding various events to introduce scientists and engineers to E/PO staff and opportunities including an E/PO Open House, brown bag seminars on

  10. Heavy metal removal from MSWI fly ash by electrokinetic remediation coupled with a permeable activated charcoal reactive barrier

    Tao Huang; Dongwei Li; Liu Kexiang; Yuewei Zhang

    2015-01-01

    This paper presents the investigations into the feasibility of the application of a remediation system that couples electrokinetic remediation (EKR) with the permeable reactive barrier (PRB) concept for municipal solid waste incineration (MSWI) fly ash with activated charcoal as the PRB material. The experimental results of this study showed that the proposed combined method can effectively improve the remediation efficiency and that the addition of the oxalic acid to the PRB media before the...

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

    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

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

    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, Natural gas

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

    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

  14. Centromeric Transcription Regulates Aurora-B Localization and Activation

    Michael D. Blower

    2016-05-01

    Full Text Available Centromeric transcription is widely conserved; however, it is not clear what role centromere transcription plays during mitosis. Here, I find that centromeres are transcribed in Xenopus egg extracts into a long noncoding RNA (lncRNA; cen-RNA that localizes to mitotic centromeres, chromatin, and spindles. cen-RNAs bind to the chromosomal passenger complex (CPC in vitro and in vivo. Blocking transcription or antisense inhibition of cen-RNA leads to a reduction of CPC localization to the inner centromere and misregulation of CPC component Aurora-B activation independently of known centromere recruitment pathways. Additionally, transcription is required for normal bipolar attachment of kinetochores to the mitotic spindle, consistent with a role for cen-RNA in CPC regulation. This work demonstrates that cen-RNAs promote normal kinetochore function through regulation of the localization and activation of the CPC and confirm that lncRNAs are components of the centromere.

  15. Shape regulation generates elastic interaction between active force dipoles

    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...

  16. Regulation of burstiness by network-driven activation

    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.

  17. Activation and Regulation of DNA-Driven Immune Responses

    Paludan, Søren R

    2015-01-01

    The innate immune system provides early defense against infections and also plays a key role in monitoring alterations of homeostasis in the body. DNA is highly immunostimulatory, and recent advances in this field have led to the identification of the innate immune sensors responsible for the recognition of DNA as well as the downstream pathways that are activated. Moreover, information on how cells regulate DNA-driven immune responses to avoid excessive inflammation is now emerging. Finally,...

  18. Molecular regulation of vascular cambium identity and activity

    Kucukoglu, Melis

    2015-01-01

    In plants, secondary development and wood formation originates from the cell divisions within the vascular meristem, where the vascular stem cells are located. This thesis work presents my results on the molecular regulation of vascular cambium stem cell identity and activity. I have investigated the role of the receptor-like kinase PXC1 during vascular development in Arabidopsis thaliana. Mutant analysis revealed that in the absence of PXC1, plants display a pendant phenotype and reduced...

  19. Summary of regulation applicable to the gamma-graphy activities

    The regulations relative to the gamma radiography activities concerns in one hand the radioactive sources, and on the other hand the radiation protection of the workers. The necessity of having a person competent in radiation protection and the tasks he or she has to do are described. The training of operators, the medical surveillance, the dosimetry are such obligations. The maintenance of equipment is an other obligation. The last point concerns the transport of radioactive materials. (N.C.)

  20. Epigenetic regulation of satellite cell activation during muscle regeneration

    Dilworth, F Jeffrey; Blais, Alexandre

    2011-01-01

    Satellite cells are a population of adult muscle stem cells that play a key role in mediating muscle regeneration. Activation of these quiescent stem cells in response to muscle injury involves modulating expression of multiple developmentally regulated genes, including mediators of the muscle-specific transcription program: Pax7, Myf5, MyoD and myogenin. Here we present evidence suggesting an essential role for the antagonistic Polycomb group and Trithorax group proteins in the epigenetic ma...

  1. Commission for Energy regulation (CRE) - Activity report June 2005

    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 2005 activity report of CRE. Content: A - The opening of the markets in France and in Europe: The opening of the markets one year after 1 July 2004 (An especially important step, Electricity and gas: a common framework with structural differences, The coexistence of market prices and regulated tariffs); The European texts of 26 June 2003 (Texts to give new impetus, Texts to harmonize the role and powers of national regulators, Texts to guarantee the independence of system operators, Texts to ensure transparent and non-discriminatory access to networks, Texts providing for strengthening of interconnections); The outlook for 2007, a fully open market (1 July 2007: a date set by the directives, Priority given to informing and protecting consumers); B - Regulation of the natural gas market: The gas market in the European context (Europe's dependency on imports is increasing, Gas prices increased considerably across the whole of Europe in 2004, The European gas scene continues to be dominated by a small number of players, Gas infrastructures need to be developed in Europe, The new European

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

    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

  3. Disorders of regulation of cognitive activity in autistic children.

    Adrien, J L; Martineau, J; Barthélémy, C; Bruneau, N; Garreau, B; Sauvage, D

    1995-06-01

    Infantile autism is a pervasive developmental disorder characterized by disturbances concerning not only the areas of socialization and communication ("aloneness") but also the ability to modify and change behavior ("need for sameness"). In most recent studies, various abnormal and deviant cognitive activities, such as the ability to regulate one's behavior, were considered as accounting for these signs. In this report, we examined the regulation of cognitive activity, from a developmental perspective in comparing autistic with mentally retarded children matched in a pairwise manner by global, verbal, and nonverbal developmental ages. All children were tested with tasks adapted from the Object Permanence Test which corresponds to Piaget's sensorimotor development Stages IV to VI. Results showed that autistic children had a pervasive difficulty in maintenance set, made more perseverative errors when the abstraction degree of task was higher, and were more variable in their behavioral strategies. Discussion is focused on the interests and limits of these tasks for the examination of regulation activity from diagnostic and developmental perspectives. Finally, interpretations about recent neuropsychological and neurophysiological works, and additional interdisciplinary studies are suggested. PMID:7559291

  4. p53 regulation and activity in mouse embryonic stem cells

    Solozobova, Valeriya

    2010-01-01

    P53 is a tumour development p53. The aim of this work was to study the regulation of p53 in embryonic stem cells and its activation in response to DNA damage. p53 was found that p53 becomes transcriptionally active in ES cells after DNA damage. Embryonic stem cells contain a relatively high amount of p53 protein and p53 RNA. After differentiation p53 level is rapidly downregulated. The high abundance of p53 in undifferentiated ES cells is a result of enhanced translation.

  5. After the Slippery Slope: Dutch Experiences on Regulating Active Euthanasia

    Boer, Th.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...

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

    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

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

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

    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

  9. Cooperative activation of transcription by autoimmune regulator AIRE and CBP

    Autoimmune regulator (AIRE) is a transcriptional regulator that is believed to control the expression of tissue-specific genes in the thymus. Mutated AIRE is responsible for onset of the hereditary autoimmune disease APECED. AIRE is able to form nuclear bodies (NBs) and interacts with the ubiquitous transcriptional coactivator CBP. In this paper, we show that CBP and AIRE synergistically activate transcription on different promoter reporters whereas AIRE gene mutation R257X, found in APECED patients, interferes with this coactivation effect. Furthermore, the overexpression of AIRE and CBP collaboratively enhance endogenous IFNβ mRNA expression. The immunohistochemical studies suggest that CBP, depending on the balance of nuclear proteins, is a component of AIRE NBs. We also show that AIRE NBs are devoid of active chromatin and, therefore, not sites of transcription. In addition, we demonstrate by 3D analyses that AIRE and CBP, when colocalizing, are located spatially differently within AIRE NBs. In conclusion, our data suggest that AIRE activates transcription of the target genes, i.e., autoantigens in collaboration with CBP and that this activation occurs outside of AIRE NBs

  10. The molecular regulation of Janus kinase (JAK) activation.

    Babon, Jeffrey J; Lucet, Isabelle S; Murphy, James M; Nicola, Nicos A; Varghese, Leila N

    2014-08-15

    The JAK (Janus kinase) family members serve essential roles as the intracellular signalling effectors of cytokine receptors. This family, comprising JAK1, JAK2, JAK3 and TYK2 (tyrosine kinase 2), was first described more than 20 years ago, but the complexities underlying their activation, regulation and pleiotropic signalling functions are still being explored. Here, we review the current knowledge of their physiological functions and the causative role of activating and inactivating JAK mutations in human diseases, including haemopoietic malignancies, immunodeficiency and inflammatory diseases. At the molecular level, recent studies have greatly advanced our knowledge of the structures and organization of the component FERM (4.1/ezrin/radixin/moesin)-SH2 (Src homology 2), pseudokinase and kinase domains within the JAKs, the mechanism of JAK activation and, in particular, the role of the pseudokinase domain as a suppressor of the adjacent tyrosine kinase domain's catalytic activity. We also review recent advances in our understanding of the mechanisms of negative regulation exerted by the SH2 domain-containing proteins, SOCS (suppressors of cytokine signalling) proteins and LNK. These recent studies highlight the diversity of regulatory mechanisms utilized by the JAK family to maintain signalling fidelity, and suggest alternative therapeutic strategies to complement existing ATP-competitive kinase inhibitors. PMID:25057888

  11. Calcium and cargoes as regulators of myosin 5a activity

    Myosin 5a is a two-headed actin-dependent motor that transports various cargoes in cells. Its enzymology and mechanochemistry have been extensively studied in vitro. It is a processive motor that takes multiple 36 nm steps on actin. The enzymatic activity of myosin 5 is regulated by an intramolecular folding mechanism whereby its lever arms fold back against the coiled-coil tail such that the motor domains directly bind the globular tail domains. We show that the structure seen in individual folded molecules is consistent with electron density map of two-dimensional crystals of the molecule. In this compact state, the actin-activated MgATPase activity of the molecule is markedly inhibited and the molecule cannot move processively on surface bound actin filaments. The actin-activated MgATPase activity of myosin 5a is activated by increasing the calcium concentration or by binding of a cargo-receptor molecule, melanophilin, in vitro. However, calcium binding to the calmodulin light chains results in dissociation of some of the calmodulin which disrupts the ability of myosin 5a to move on actin filaments in vitro. Thus we propose that the physiologically relevant activation pathway in vivo involves binding of cargo-receptor proteins

  12. MicroRNA-150 regulates blood-brain barrier permeability via Tie-2 after permanent middle cerebral artery occlusion in rats.

    Fang, Zhi; He, Quan-Wei; Li, Qian; Chen, Xiao-Lu; Baral, Suraj; Jin, Hui-Juan; Zhu, Yi-Yi; Li, Man; Xia, Yuan-Peng; Mao, Ling; Hu, Bo

    2016-06-01

    The mechanism of blood-brain barrier (BBB) disruption, involved in poststroke edema and hemorrhagic transformation, is important but elusive. We investigated microRNA-150 (miR-150)-mediated mechanism in the disruption of BBB after stroke in rats. We found that up-regulation of miR-150 increased permeability of BBB as detected by MRI after permanent middle cerebral artery occlusion in vivo as well as increased permeability of brain microvascular endothelial cells after oxygen-glucose deprivation in vitro. The expression of claudin-5, a key tight junction protein, was decreased in the ischemic boundary zone after up-regulation of miR-150. We found in brain microvascular endothelial cells that overexpression of miR-150 decreased not only cell survival rate but also the expression levels of claudin-5 after oxygen-glucose deprivation. With dual-luciferase assay, we confirmed that miR-150 could directly regulate the angiopoietin receptor Tie-2. Moreover, silencing Tie-2 with lentivirus-delivered small interfering RNA reversed the effect of miR-150 on endothelial permeability, cell survival, and claudin-5 expression. Furthermore, poststroke treatment with antagomir-150, a specific miR-150 antagonist, contributed to BBB protection, infarct volume reduction, and amelioration of neurologic deficits. Collectively, our findings suggested that miR-150 could regulate claudin-5 expression and endothelial cell survival by targeting Tie-2, thus affecting the permeability of BBB after permanent middle cerebral artery occlusion in rats, and that miR-150 might be a potential alternative target for the treatment of stroke.-Fang, Z., He, Q.-W., Li, Q., Chen, X.-L., Baral, S., Jin, H.-J., Zhu, Y.-Y., Li, M., Xia, Y.-P., Mao, L., Hu, B. MicroRNA-150 regulates blood-brain barrier permeability via Tie-2 after permanent middle cerebral artery occlusion in rats. PMID:26887441

  13. Commission for Energy regulation (CRE) - Activity report june 2006

    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 imports in gas

  14. Commission for Energy regulation (CRE) - Activity report june 2006

    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

  15. AMP-activated protein kinase (AMPK) activation regulates in vitro bone formation and bone mass

    Shah, M; Kola, B; Bataveljic, A.; Arnett, T. R.; Viollet, B.; Saxon, L.; Korbonits, M.; C. Chenu

    2010-01-01

    Adenosine 5′-monophosphate-activated protein kinase (AMPK), a regulator of energy homeostasis, has a central role in mediating the appetite-modulating and metabolic effects of many hormones and antidiabetic drugs metformin and glitazones. The objective of this study was to determine if AMPK can be activated in osteoblasts by known AMPK modulators and if AMPK activity is involved in osteoblast function in vitro and regulation of bone mass in vivo. ROS 17/2.8 rat osteoblast-like cells were cult...

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

    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. PMID:26495938

  17. Inhibitory neurotransmission regulates vagal efferent activity and gastric motility.

    McMenamin, Caitlin A; Travagli, R Alberto; Browning, Kirsteen N

    2016-06-01

    The gastrointestinal tract receives extrinsic innervation from both the sympathetic and parasympathetic nervous systems, which regulate and modulate the function of the intrinsic (enteric) nervous system. The stomach and upper gastrointestinal tract in particular are heavily influenced by the parasympathetic nervous system, supplied by the vagus nerve, and disruption of vagal sensory or motor functions results in disorganized motility patterns, disrupted receptive relaxation and accommodation, and delayed gastric emptying, amongst others. Studies from several laboratories have shown that the activity of vagal efferent motoneurons innervating the upper GI tract is inhibited tonically by GABAergic synaptic inputs from the adjacent nucleus tractus solitarius. Disruption of this influential central GABA input impacts vagal efferent output, hence gastric functions, significantly. The purpose of this review is to describe the development, physiology, and pathophysiology of this functionally dominant inhibitory synapse and its role in regulating vagally determined gastric functions. PMID:27302177

  18. [Polymethoxylated flavonoids activate cystic fibrosis transmembrane conductance regulator chloride channel].

    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. PMID:25896054

  19. Epidermal Growth Factor and Intestinal Barrier Function

    Liu, Hu; Yang, Shufen; Li, Zuohua; Zhong, Jinfeng

    2016-01-01

    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. PMID:27524860

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

    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

  1. Thermal activation at moderate-to-high and high damping: finite barrier effects and force spectroscopy.

    Mazo, J J; Fajardo, O Y; Zueco, D

    2013-03-14

    We study the thermal escape problem in the moderate-to-high and high damping regime of a system with a parabolic barrier. We present a formula that matches our numerical results accounting for finite barrier effects, and compare it with previous works. We also show results for the full damping range. We quantitatively study some aspects on the relation between mean first passage time and the definition of an escape rate. To finish, we apply our results and considerations in the framework of force spectroscopy problems. We study the differences on the predictions using the different theories and discuss the role of γF[over dot] as the relevant parameter at high damping. PMID:23514463

  2. Physical activity levels and perceived benefits and barriers to physical activity in HIV-infected women living in the deep south of the United States.

    Rehm, Kristina E; Konkle-Parker, Deborah

    2016-09-01

    Engaging in regular physical activity (PA) is important in maintaining health and increasing the overall quality of life of people living with HIV (PLWH). The deep south of the USA is known for its high rate of sedentary behavior although data on the activity levels and perceptions of the benefits and barriers to exercise in women living with HIV in the deep south are lacking. Understanding the perceived benefits and barriers to exercise can guide the development of PA interventions. We conducted a cross-sectional study to determine the PA levels and perceived benefits and barriers to exercise associated with both age and depression level in a group of HIV+ women living in the deep south. We recruited a total of 50 participants from a cohort site for the Women's Interagency HIV Study. Depression was assessed using the Center for Epidemiological Studies Depression Scale (CES-D) and benefits/barriers to exercise were measured using the Exercise Benefits and Barriers Scale (EBBS). We measured PA both subjectively and objectively using the International Physical Activity Questionnaire (IPAQ) and a Fitbit PA monitor, respectively. Our sample was predominantly African-American (96%) and the mean ±SD age, body mass index, and CES-D score were 42 ± 8.8 years, 36.6 ± 11.5 kg/m(2), and 15.6 ± 11.4, respectively. Both subjective and objective measures of PA indicated that our participants were sedentary. The greatest perceived benefit to exercise was physical performance and the greatest barrier to exercise was physical exertion. Higher overall perceived benefits were reported by women ≥43 years and women reporting higher levels of depression. There was no difference in overall barriers associated with age and depression level, but women with depression felt more fatigued by exercise. The results of this study can be helpful when designing and implementing PA interventions in women living with HIV in the deep south. PMID:27023306

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

    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.

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

    Cormier, Jean Marie; Aubry, Olivier; 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 dep...

  5. 10 Years-Activities at ONERA on Advanced Thermal Barrier Coatings

    Bacos, M. P; Dorvaux, J.M.; Landais, S.; Lavigne, O.; Mévrel, R.; M. Poulain; Rio, C; Vidal-Sétif, M.H.

    2011-01-01

    Developing thermal barrier coatings operating at higher temperature and/or for very long durations (commercial aircraft applications) is one of the technological and economical challenges for engine manufacturers. This includes the search for (i) low thermal conductivity, high thermal stability and CMAS resistant ceramic top coat, and (ii) alternative low cost bond coat with improved oxidation resistance and chemical compatibility with the substrate. This paper reviews the rationale sustainin...

  6. Recent development in safety regulation of nuclear fuel cycle activities

    Through the effort of deliberation and legislation over five years, Japanese government structure was reformed this January, with the aim of realizing simple, efficient and transparent administration. Under the reform, the Agency for Nuclear and Industrial Safety (ANIS) was founded in the Ministry of Economy, Trade and Industry (METI) to be responsible for safety regulation of energy-related nuclear activities, including nuclear fuel cycle activities, and industrial activities, including explosives, high-pressure gasses and mining. As one of the lessons learned from the JCO criticality accident of September 1999, it was pointed out that government's inspection function was not enough for fuel fabrication facilities. Accordingly, new statutory regulatory activities were introduced, namely, inspection of observance of safety rules and procedures for all kinds of nuclear operators and periodic inspection of fuel fabrication facilities. In addition, in order to cope with insufficient safety education and training of workers in nuclear facilities, licensees of nuclear facilities are required by law to specify safety education and training for their workers. ANIS is committed to enforce these new regulatory activities effectively and efficiently. In addition, it is going to be prepared for, in its capacity of safety regulatory authority, future development of Japanese fuel cycle activities, including commissioning of JNFL Rokkasho reprocessing plant and possible application for licenses for JNFL MOX fabrication plant and for spent fuel interim storage facilities. (author)

  7. Recent development in safety regulation of nuclear fuel cycle activities

    Through the effort of deliberation and legislation over five years, Japanese government structure was reformed this January, with the aim of realizing simple, efficient and transparent administration. Under the reform, the Agency for Nuclear and Industrial Safety (ANIS) was founded in the Ministry of Economy, Trade and Industry (METI) to be responsible for safety regulation of energy-related nuclear activities, including nuclear fuel cycle activities, and industrial activities, including explosives, high-pressure gasses and mining. As one of the lessons learned from the JCO criticality accident of September 1999, it was pointed out that the government's inspection function was not enough for fuel fabrication facilities. Accordingly, new statutory regulatory activities were introduced, namely, inspection of observance of safety rules and procedures for all kinds of nuclear operators and periodic inspection of fuel fabrication facilities. In addition, in order to cope with insufficient safety education and training of workers in nuclear facilities, licensees of nuclear facilities are required by law to specify safety education and training for their workers. ANIS is committed to enforce these new regulatory activities effectively and efficiently. In addition, it is going to be prepared, in its capacity as safety regulatory authority, for future development of Japanese fuel cycle activities, including commissioning of JNFL Rokkasho reprocessing plant and possible application for licenses for JNFL MOX fabrication plant and for spent fuel interim storage facilities. (author)

  8. A method to predict different mechanisms for blood-brain barrier permeability of CNS activity compounds in Chinese herbs using support vector machine.

    Jiang, Ludi; Chen, Jiahua; He, Yusu; Zhang, Yanling; Li, Gongyu

    2016-02-01

    The blood-brain barrier (BBB), a highly selective barrier between central nervous system (CNS) and the blood stream, restricts and regulates the penetration of compounds from the blood into the brain. Drugs that affect the CNS interact with the BBB prior to their target site, so the prediction research on BBB permeability is a fundamental and significant research direction in neuropharmacology. In this study, we combed through the available data and then with the help of support vector machine (SVM), we established an experiment process for discovering potential CNS compounds and investigating the mechanisms of BBB permeability of them to advance the research in this field four types of prediction models, referring to CNS activity, BBB permeability, passive diffusion and efflux transport, were obtained in the experiment process. The first two models were used to discover compounds which may have CNS activity and also cross the BBB at the same time; the latter two were used to elucidate the mechanism of BBB permeability of those compounds. Three optimization parameter methods, Grid Search, Genetic Algorithm (GA), and Particle Swarm Optimization (PSO), were used to optimize the SVM models. Then, four optimal models were selected with excellent evaluation indexes (the accuracy, sensitivity and specificity of each model were all above 85%). Furthermore, discrimination models were utilized to study the BBB properties of the known CNS activity compounds in Chinese herbs and this may guide the CNS drug development. With the relatively systematic and quick approach, the application rationality of traditional Chinese medicines for treating nervous system disease in the clinical practice will be improved. PMID:26632324

  9. How Phosphorylation and ATPase Activity Regulate Anion Flux though the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).

    Zwick, Matthias; Esposito, Cinzia; Hellstern, Manuel; Seelig, Anna

    2016-07-01

    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. PMID:27226582

  10. A preliminary analysis of barriers, intentions, and attitudes towards moderate physical activity in women who are overweight.

    Jewson, Elizabeth; Spittle, Michael; Casey, Meghan

    2008-11-01

    Physical activity is important for the health of all individuals, however, the determinants of physical activity behaviour for women who are overweight remain largely unexplored. The purpose of this investigation was to explore a range of factors that influence participation in physical activity for a group of women who are overweight. Participants were 30 women, aged 25-71 years, with a mean age of 46.8 years (+12.95) and an average BMI of 31.2kg/m(2) (+5.6). Self-reported level of physical activity, perceived barriers and facilitators of physical activity, attitudes, intentions and perceived behavioural control to physical activity were measured. Seventeen participants were generally active, with self-reported moderate physical activity of 218.53min (+/-113.82) in the last 7 days; whereas 13 participants were reportedly less active 43.46 (+/-42.98)min. Active participants were more likely to identify social reasons for participating in physical activity, while inactive participants perceived that their laziness prevented them from being physically active. There were no significant differences between active and inactive overweight women for attitude, intention or subjective norm for moderate-intensity physical activity. There was a significant difference between these women in perceived behavioural control (p=.014) for moderate-intensity physical activity, as women who felt more in control of their physical activity behaviour were more likely to engage in physical activity than inactive women. Future research should investigate interventions to increase behavioural control of moderate-intensity physical activity in women who are overweight. PMID:17884730

  11. Barriers, facilitators and preferences for the physical activity of school children. Rationale and methods of a mixed study

    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.

  12. Occludin controls HIV transcription in brain pericytes via regulation of SIRT-1 activation.

    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. PMID:26601824

  13. Active Use of the Natural Environment for Emotion Regulation

    Svein Åge Kjøs Johnsen

    2013-11-01

    Full Text Available Two studies on the use of nature for emotion regulation were conducted. Study 1 (N = 35 ran over two weeks and was an experimental investigation. Participants in the experimental condition were asked to use a picture of nature actively as environmental stimuli for emotion regulation in their everyday life, while two control groups simply looked at a picture of nature or a picture of balloons each evening. A significant effect of the manipulation was found on positive mood, but the effect was complex with an initial increase and then a decrease. There were no findings on negative mood. Study 2 (N = 473 explored the motivational tendency to seek out nature when the participants were happy or sad. A novel concept (expectancy construct was introduced to measure the perception of the emotion regulatory potential of different environments. The classical natural environment was rated highest on emotional potential of all environments tested here. Perceiving a higher emotional potential in nature was related to a higher intention to seek out nature when happy or sad. Personality and mood were also related to these concepts. Higher positive mood was related to the intention to seek out nature when happy. Conscientiousness was related to a more positive perception of nature. The studies support the notion that using nature may be an effective strategy for regulating one’s emotions.

  14. Erk1 positively regulates osteoclast differentiation and bone resorptive activity.

    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.

  15. Regulation of dopamine transporter activity by carboxypeptidase E

    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.

  16. Activity and regulation of the centrosome-associated proteasome.

    Fabunmi, R P; Wigley, W C; Thomas, P J; DeMartino, G N

    2000-01-01

    Regulated proteolysis is important for maintaining appropriate cellular levels of many proteins. The bulk of intracellular protein degradation is catalyzed by the proteasome. Recently, the centrosome was identified as a novel site for concentration of the proteasome and associated regulatory proteins (Wigley, W. C., Fabunmi, R. P., Lee, M. G., Marino, C. R., Muallem, S., DeMartino, G. N., and Thomas, P. J. (1999) J. Cell Biol. 145, 481-490). Here we provide evidence that centrosomes contain the active 26 S proteasome that degrades ubiquitinated-protein and proteasome-specific peptide substrates. Moreover, the centrosomes contain an ubiquitin isopeptidase activity. The proteolytic activity is ATP-dependent and is inhibited by proteasome inhibitors. Notably, treatment of cells with inhibitors of proteasome activity promotes redistribution of the proteasome and associated regulatory proteins to the centrosome independent of an intact microtubule system. These data provide biochemical evidence for active proteasomal complexes at the centrosome, highlighting a novel function for this organizing structure. PMID:10617632

  17. A role for VEGFR2 activation in endothelial responses caused by barrier disruptive OxPAPC concentrations.

    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

  18. Regulation of seasonal reproduction by hypothalamic activation of thyroid hormone

    TakashiYoshimura

    2014-02-01

    Full Text Available Organisms living outside the tropics measure the changes in the length of the day to adapt to seasonal changes in the environment. Animals that breed during spring and summer are called long-day breeders, while those that breed during fall are called short-day breeders. Although the influence of thyroid hormone in the regulation of seasonal reproduction has been known for several decades, its precise mechanism remained unknown. Recent studies revealed that the activation of thyroid hormone within the mediobasal hypothalamus (MBH plays a key role in this phenomenon. This localized activation of the thyroid hormone is controlled by thyrotropin (thyroid-stimulating hormone, TSH secreted from the pars tuberalis of the pituitary gland. Although seasonal reproduction is a rate-limiting factor in animal production, genes involved in photoperiodic signal transduction pathway could emerge as potential targets to facilitate domestication.

  19. The long noncoding RNA TUG1 regulates blood-tumor barrier permeability by targeting miR-144

    Cai, Heng; Xue, Yixue; Wang, Ping; WANG, ZHENHUA; Li, Zhen; Hu, Yi; Li, Zhiqing; Shang, Xiuli; Liu, Yunhui

    2015-01-01

    Blood-tumor barrier (BTB) limits the delivery of chemotherapeutic agent to brain tumor tissues. Long non-coding RNAs (lncRNAs) have been shown to play critical regulatory roles in various biologic processes of tumors. However, the role of lncRNAs in BTB permeability is unclear. LncRNA TUG1 (taurine upregulated gene 1) was highly expressed in glioma vascular endothelial cells from glioma tissues. It also upregulated in glioma co-cultured endothelial cells (GEC) from BTB model in vitro. Knockdo...

  20. Osteoblast differentiation and migration are regulated by dynamin GTPase activity.

    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. PMID:24387844

  1. Phosphatidylinositol-3-kinase regulates mast cell ion channel activity.

    Lam, Rebecca S; Shumilina, Ekaterina; Matzner, Nicole; Zemtsova, Irina M; Sobiesiak, Malgorzata; Lang, Camelia; Felder, Edward; Dietl, Paul; Huber, Stephan M; Lang, Florian

    2008-01-01

    Stimulation of the mast cell IgE-receptor (FcepsilonRI) by antigen leads to stimulation of Ca(2+) entry with subsequent mast cell degranulation and release of inflammatory mediators. Ca(2+) further activates Ca(2+)-activated K(+) channels, which in turn provide the electrical driving force for Ca(2+) entry. Since phosphatidylinositol (PI)-3-kinase has previously been shown to be required for mast cell activation and degranulation, we explored, whether mast cell Ca(2+) and Ca(2+)-activated K(+) channels may be sensitive to PI3-kinase activity. Whole-cell patch clamp experiments and Fura-2 fluorescence measurements for determination of cytosolic Ca(2+) concentration were performed in mouse bone marrow-derived mast cells either treated or untreated with the PI3-kinase inhibitors LY-294002 (10 muM) and wortmannin (100 nM). Antigen-stimulated Ca(2+) entry but not Ca(2+) release from the intracellular stores was dramatically reduced upon PI3-kinase inhibition. Ca(2+) entry was further inhibited by TRPV blocker ruthenium red (10 muM). Ca(2+) entry following readdition after Ca(+)-store depletion with thapsigargin was again decreased by LY-294002, pointing to inhibition of store-operated channels (SOCs). Moreover, inhibition of PI3-kinase abrogated IgE-stimulated, but not ionomycin-induced stimulation of Ca(2+)-activated K(+) channels. These observations disclose PI3-kinase-dependent regulation of Ca(2+) entry and Ca(2+)-activated K(+)-channels, which in turn participate in triggering mast cell degranulation. PMID:18769043

  2. SPATIAL HETEROGENEITY OF PHOTOSYNTHETIC ACTIVITY WITHIN DISEASED CORALS FROM THE GREAT BARRIER REEF

    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 of the...... associated 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....

  3. Validation and divergence of the activation energy barrier crossing transition at the AOT/lecithin reverse micellar interface.

    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. PMID:18281975

  4. TCEAL7 Inhibition of c-Myc Activity in Alternative Lengthening of Telomeres Regulates hTERT Expression

    Kyle Lafferty-Whyte

    2010-05-01

    Full Text Available Replicative senescence forms a major barrier to tumor progression. Cancer cells bypass this by using one of the two known telomere maintenance mechanisms: telomerase or the recombination-based alternative lengthening of telomeres (ALT mechanism. The molecular details of ALT are currently poorly understood. We have previously shown that telomerase is actively repressed through complex networks of kinase, gene expression, and chromatin regulation. In this study, we aimed to gain further understanding of the role of kinases in the regulation of telomerase expression in ALT cells. Using a whole human kinome small interfering RNA (siRNA screen, we highlighted 106 kinases whose expression is linked to human telomerase reverse transcriptase (hTERT promoter activity. Network modeling of transcriptional regulation implicated c-Myc as a key regulator of the 106 kinase hits. Given our previous observations of lower c-Myc activity in ALT cells, we further explored its potential to regulate telomerase expression in ALT. We found increased c-Myc binding at the hTERT promoter in telomerase-positive compared with ALT cells, although no expression differences in c-Myc, Mad, or Max were observed between ALT and telomerase-positive cells that could explain decreased c-Myc activity in ALT. Instead, we found increased expression of the c-Myc competitive inhibitor TCEAL7 in ALT cells and tumors and that alteration of TCEAL7 expression levels in ALT and telomerase-positive cells affects hTERT expression. Lower c-Myc activity in ALT may therefore be obtained through TCEAL7 regulation. Thus, TCEAL7 may present an interesting novel target for cancer therapy, which warrants further investigation.

  5. Histamine activates p38 MAP kinase and alters local lamellipodia dynamics, reducing endothelial barrier integrity and eliciting central movement of actin fibers.

    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. PMID:25948734

  6. DMPD: Receptor tyrosine kinases and the regulation of macrophage activation. [Dynamic Macrophage Pathway CSML Database

    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

  7. Regulation of TLR3 Activation by S100A9.

    Tsai, Su-Yu; Segovia, Jesus A; Chang, Te-Hung; Shil, Niraj K; Pokharel, Swechha M; Kannan, T R; Baseman, Joel B; Defrêne, Joan; Pagé, Nathalie; Cesaro, Annabelle; Tessier, Philippe A; Bose, Santanu

    2015-11-01

    Recognition of viral dsRNA by endosomal TLR3 activates innate immune response during virus infection. Trafficking of TLR3 to the endolysosomal compartment arising from fusion of late endosome (LE) with lysosome is required for recognition and detection of pathogen associated molecular patterns, which results in activation of the TLR3-dependent signaling cascade. Existing knowledge about the mechanism(s) and cellular factor(s) governing TLR3 trafficking is limited. In the current study, we identified intracellular S100A9 protein as a critical regulator of TLR3 trafficking. S100A9 was required for maturation of TLR3 containing early endosome (EE) into LE, the compartment that fuses with lysosome to form the endolysosomal compartment. A drastic reduction in cytokine production was observed in S100A9-knockout (KO) primary macrophages following RNA virus infection and treatment of cells with polyinosinic-polycytidylic acid (polyIC; a dsRNA mimetic that acts as a TLR3 agonist). Mechanistic studies revealed colocalization and interaction of S100A9 with TLR3 following polyIC treatment. S100A9-TLR3 interaction was critical for maturation of TLR3 containing EE into LE because TLR3 could not be detected in the LE of polyIC-treated S100A9-KO macrophages. Subsequently, TLR3 failed to colocalize with its agonist (i.e., biotin-labeled polyIC) in S100A9-deficient macrophages. The in vivo physiological role of S100A9 was evident from loss of cytokine production in polyIC-treated S100A9-KO mice. Thus, we identified intracellular S100A9 as a regulator of TLR3 signaling and demonstrated that S100A9 functions during pre-TLR3 activation stages by facilitating maturation of TLR3 containing EE into LE. PMID:26385519

  8. Perceived barriers and facilitators to increasing physical activity among people with musculoskeletal disorders: a qualitative investigation to inform intervention development

    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

  9. Substrate regulation of ascorbate transport activity in astrocytes

    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

  10. Transcriptional and nontranscriptional regulation of NIS activity and radioiodide transport

    Jung, Kyung Ho; Lee, Kyung Han [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2007-10-15

    Radioiodide transport has been extensively and successfully used in the evaluation and management of thyroid disease. The molecular characterization of the sodium/iodide symporter (NIS) and cloning of the NIS gene has led to the recent expansion of the use of radioiodide to cancers of the breast and other nonthyroidal tissues exogenously transduced with the NIS gene. More recently, discoveries regarding the functional analysis and regulatory processes of the NIS molecule are opening up exciting opportunities for new research and applications for NIS and radioiodide. The success of NIS based cancer therapy is dependent on achievement of maximal radioiodide transport sufficient to allow delivery of effective radiation doses. This in turn relies on high transcription rates of the NIS gene. However, newer discoveries indicate that nontranscriptional processes that regulate NIS trafficking to cell membrane are also critical determinants of radioiodide uptake. In this review, molecular mechanisms that underlie regulation of NIS transcription and stimuli that augment membrane trafficking and functional activation of NIS molecules will be discussed. A better understanding of how the expression and cell surface targeting of NIS proteins is controlled will hopefully aid in optimizing NIS gene based cancer treatment as well as NIS based reporter-gene imaging strategies.

  11. Parkin Regulates the Activity of Pyruvate Kinase M2.

    Liu, Kun; Li, Fanzhou; Han, Haichao; Chen, Yue; Mao, Zebin; Luo, Jianyuan; Zhao, Yingming; Zheng, Bin; Gu, Wei; Zhao, Wenhui

    2016-05-01

    Parkin, a ubiquitin E3 ligase, is mutated in most cases of autosomal recessive early onset Parkinson disease. It was discovered that Parkin is also mutated in glioblastoma and other human malignancies and that it inhibits tumor cell growth. Here, we identified pyruvate kinase M2 (PKM2) as a unique substrate for parkin through biochemical purification. We found that parkin interacts with PKM2 both in vitro and in vivo, and this interaction dramatically increases during glucose starvation. Ubiquitylation of PKM2 by parkin does not affect its stability but decreases its enzymatic activity. Parkin regulates the glycolysis pathway and affects the cell metabolism. Our studies revealed the novel important roles of parkin in tumor cell metabolism and provided new insight for therapy of Parkinson disease. PMID:26975375

  12. Suppression of PKC-α attenuates TNF-α-evoked cerebral barrier breakdown via regulations of MMP-2 and plasminogen-plasmin system.

    Abdullah, Zuraidah; Bayraktutan, Ulvi

    2016-07-01

    Ischaemic stroke, accompanied by neuroinflammation, impairs blood-brain barrier integrity through a complex mechanism involving both protein kinase C (PKC) and urokinase. Using an in vitro model of human blood-brain barrier (BBB) composed of brain microvascular endothelial cells (HBMEC) and astrocytes, this study assessed the putative roles of these elements in BBB damage evoked by enhanced availability of pro-inflammatory cytokine, TNF-α. Treatment of HBMEC with TNF-α significantly increased the mRNA and protein expressions of all plasminogen-plasmin system (PPS) components, namely tissue plasminogen activator, urokinase, urokinase plasminogen activator receptor and plasminogen activator inhibitor-1 and also the activities of urokinase, total PKC and extracellular MMP-2. Inhibition of urokinase by amiloride abated the effects of TNF-α on BBB integrity and MMP-2 activity without affecting that of total PKC. Conversely, pharmacological inhibition of conventional PKC isoforms dramatically suppressed TNF-α-induced overactivation of urokinase. Knockdown of PKC-α gene via specific siRNA in HBMEC suppressed the stimulatory effects of TNF-α on protein expression of all PPS components, MMP-2 activity, DNA fragmentation rates and pro-apoptotic caspase-3/7 activities. Establishment of co-cultures with BMEC transfected with PKC-α siRNA attenuated the disruptive effects of TNF-α on BBB integrity and function. This was partly due to elevations observed in expression of a tight junction protein, claudin-5 and partly to prevention of stress fibre formation. In conclusion, specific inhibition of PKC-α in cerebral conditions associated with exaggerated release of pro-inflammatory cytokines, notably TNF-α may be of considerable therapeutic value and help maintain endothelial cell viability, appropriate cytoskeletal structure and basement membrane. PMID:27094771

  13. Regulation of sucrose metabolism in higher plants: localization and regulation of activity of key enzymes

    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.

  14. The effect of interface phonons on operating electron states in three-barrier resonant tunneling structure as an active region of quantum cascade detector

    M.V. Tkach; Ju.O. Seti; Grynyshyn, Y. B.; O.M. Voitsekhivska

    2014-01-01

    The Hamiltonian of electrons interacting with interface phonons in three-barrier resonant tunneling structure is established using the first principles within the models of effective mass and polarization continuum. Using the Green's functions method, the temperature shifts and decay rates of operating electron states are calculated depending on geometric design of three-barrier nano-structure GaAs/AlxGa1-xAs which is an active region of quantum cascade detector. It is established that indepe...

  15. Regulation of ALF promoter activity in Xenopus oocytes.

    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.

  16. Protein kinase C-α signals P115RhoGEF phosphorylation and RhoA activation in TNF-α-induced mouse brain microvascular endothelial cell barrier dysfunction

    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

  17. Low Discretionary Time as a Barrier to Physical Activity and Intervention Uptake

    Wolin, Kathleen Y.; Bennett, Gary G.; McNeill, Lorna H.; Sorensen, Glorian; Emmons, Karen M.

    2008-01-01

    Objective: To determine whether self-reported discretionary time was associated with physical activity and uptake of a physical activity promotion intervention in a multi-ethnic urban sample. Methods: We examined the association of self-reported discretionary time with hours/week of leisure-time physical activity at baseline and physical activity…

  18. Perceived Barriers to Teaching Movement and Physical Activity to Kindergarteners in Ghana

    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…

  19. Enzymatic Regulation of Steroidogenesis and Nuclear Receptor Activation : Special Focus on Vitamin D and Sex Hormones

    LUNDQVIST, JOHAN

    2011-01-01

    Enzyme-catalyzed reactions are important to regulate steroidogenesis and nuclear receptor activation. The present investigation examines the role of steroid metabolism catalyzed by CYP7B1 for regulation of hormone receptor activation and the effects of vitamin D on enzymatic regulation of steroidogenesis. The study reports data indicating that CYP7B1 can regulate estrogenic signaling by converting estrogens into inactive or less active metabolites. Similar results were obtained for CYP7B1-med...

  20. Early activation of STAT3 regulates reactive astrogliosis induced by diverse forms of neurotoxicity.

    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

  1. RADIAL ANGULAR MOMENTUM TRANSFER AND MAGNETIC BARRIER FOR SHORT-TYPE GAMMA-RAY-BURST CENTRAL ENGINE ACTIVITY

    Soft extended emission (EE) following initial hard spikes up to 100 s was observed with Swift/BAT for about half of known short-type gamma-ray bursts (SGRBs). This challenges the conversional central engine models of SGRBs, i.e., compact star merger models. In the framework of black-hole-neutron-star merger models, we study the roles of radial angular momentum transfer in the disk and the magnetic barrier around the black hole in the activity of SGRB central engines. We show that radial angular momentum transfer may significantly prolong the lifetime of the accretion process, which may be divided into multiple episodes by the magnetic barrier. Our numerical calculations based on models of neutrino-dominated accretion flows suggest that disk mass is critical for producing the observed EE. In the case of the mass being ∼0.8 M ☉, our model can reproduce the observed timescale and luminosity of both the main and the EE episodes in a reasonable parameter set. The predicted luminosity of the EE component is lower than the observed EE within about one order of magnitude and the timescale is shorter than 20 s if the disk mass is ∼0.2 M ☉. Swift/BAT-like instruments may be not sensitive enough to detect the EE component in this case. We argue that the EE component could be a probe for the merger process and disk formation for compact star mergers.

  2. A coagulation-powdered activated carbon-ultrafiltration - Multiple barrier approach for removing toxins from two Australian cyanobacterial blooms

    Dixon, Mike B., E-mail: mike.dixon@sawater.com.au [Australian Water Quality Centre, SA Water Corporation, GPO Box 1751, Adelaide, SA, 5001 (Australia); School of Chemical Engineering, University of Adelaide, SA 5005 (Australia); Richard, Yann [School of Chemistry, Physics and Electronics, 48 Blvd du 11 Nov 1918, BP 2077-69616, Villeurbanne Cedex (France); Ho, Lionel [Australian Water Quality Centre, SA Water Corporation, GPO Box 1751, Adelaide, SA, 5001 (Australia); School of Earth and Environmental Sciences, University of Adelaide, SA 5005 (Australia); Chow, Christopher W.K. [Australian Water Quality Centre, SA Water Corporation, GPO Box 1751, Adelaide, SA, 5001 (Australia); O' Neill, Brian K. [School of Chemical Engineering, University of Adelaide, SA 5005 (Australia); Newcombe, Gayle [Australian Water Quality Centre, SA Water Corporation, GPO Box 1751, Adelaide, SA, 5001 (Australia)

    2011-02-28

    Cyanobacteria are a major problem for the world wide water industry as they can produce metabolites toxic to humans in addition to taste and odour compounds that make drinking water aesthetically displeasing. Removal of cyanobacterial toxins from drinking water is important to avoid serious illness in consumers. This objective can be confidently achieved through the application of the multiple barrier approach to drinking water quality and safety. In this study the use of a multiple barrier approach incorporating coagulation, powdered activated carbon (PAC) and ultrafiltration (UF) was investigated for the removal of intracellular and extracellular cyanobacterial toxins from two naturally occurring blooms in South Australia. Also investigated was the impact of these treatments on the UF flux. In this multibarrier approach, coagulation was used to remove the cells and thus the intracellular toxin while PAC was used for extracellular toxin adsorption and finally the UF was used for floc, PAC and cell removal. Cyanobacterial cells were completely removed using the UF membrane alone and when used in conjunction with coagulation. Extracellular toxins were removed to varying degrees by PAC addition. UF flux deteriorated dramatically during a trial with a very high cell concentration; however, the flux was improved by coagulation and PAC addition.

  3. Modeling the long-term durability of concrete barriers in the context of low-activity waste storage

    Protière, Y.; Samson, E.; Henocq, P.

    2013-07-01

    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.

  4. Modeling the long-term durability of concrete barriers in the context of low-activity waste storage

    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.

  5. Perceived Parental Barriers to and Strategies for Supporting Physical Activity and Healthy Eating among Head Start Children.

    Ling, Jiying; B Robbins, Lorraine; Hines-Martin, Vicki

    2016-06-01

    Despite the need for parents to support their children's healthy behaviors, knowledge of factors preventing parents from doing so is still rudimentary. This study primarily aimed to explore perceived parental barriers to and strategies for supporting physical activity and healthy eating among Head Start children. A semi-structured interview format was used with four focus groups conducted at two urban Head Start centers in the Midwestern U.S. A qualitative content analysis of audio-recorded sessions was facilitated using ATLAS.ti7. A convenience sample of 32 parents (Mage = 34.97 years) participated. Over half were female (78.1 %), African Americans (65.6 %), and single (65.6 %). About 61.3 % reported an annual family income garden. Many parents showed their preference for face-to-face meetings and a support group, but repulsion of counseling. To promote parental support in future interventions with Head Start children, their perceived intrapersonal, interpersonal, and environmental barriers should be considered as intervention targets. Involving parents through a support group and face-to-face meetings is recommended. PMID:26660100

  6. A coagulation-powdered activated carbon-ultrafiltration - Multiple barrier approach for removing toxins from two Australian cyanobacterial blooms

    Cyanobacteria are a major problem for the world wide water industry as they can produce metabolites toxic to humans in addition to taste and odour compounds that make drinking water aesthetically displeasing. Removal of cyanobacterial toxins from drinking water is important to avoid serious illness in consumers. This objective can be confidently achieved through the application of the multiple barrier approach to drinking water quality and safety. In this study the use of a multiple barrier approach incorporating coagulation, powdered activated carbon (PAC) and ultrafiltration (UF) was investigated for the removal of intracellular and extracellular cyanobacterial toxins from two naturally occurring blooms in South Australia. Also investigated was the impact of these treatments on the UF flux. In this multibarrier approach, coagulation was used to remove the cells and thus the intracellular toxin while PAC was used for extracellular toxin adsorption and finally the UF was used for floc, PAC and cell removal. Cyanobacterial cells were completely removed using the UF membrane alone and when used in conjunction with coagulation. Extracellular toxins were removed to varying degrees by PAC addition. UF flux deteriorated dramatically during a trial with a very high cell concentration; however, the flux was improved by coagulation and PAC addition.

  7. A coagulation-powdered activated carbon-ultrafiltration--multiple barrier approach for removing toxins from two Australian cyanobacterial blooms.

    Dixon, Mike B; Richard, Yann; Ho, Lionel; Chow, Christopher W K; O'Neill, Brian K; Newcombe, Gayle

    2011-02-28

    Cyanobacteria are a major problem for the world wide water industry as they can produce metabolites toxic to humans in addition to taste and odour compounds that make drinking water aesthetically displeasing. Removal of cyanobacterial toxins from drinking water is important to avoid serious illness in consumers. This objective can be confidently achieved through the application of the multiple barrier approach to drinking water quality and safety. In this study the use of a multiple barrier approach incorporating coagulation, powdered activated carbon (PAC) and ultrafiltration (UF) was investigated for the removal of intracellular and extracellular cyanobacterial toxins from two naturally occurring blooms in South Australia. Also investigated was the impact of these treatments on the UF flux. In this multibarrier approach, coagulation was used to remove the cells and thus the intracellular toxin while PAC was used for extracellular toxin adsorption and finally the UF was used for floc, PAC and cell removal. Cyanobacterial cells were completely removed using the UF membrane alone and when used in conjunction with coagulation. Extracellular toxins were removed to varying degrees by PAC addition. UF flux deteriorated dramatically during a trial with a very high cell concentration; however, the flux was improved by coagulation and PAC addition. PMID:21227576

  8. Notch1 regulated autophagy controls survival and suppressor activity of activated murine T-regulatory cells

    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

  9. Fear of Movement and Low Self-Efficacy Are Important Barriers in Physical Activity after Renal Transplantation.

    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.

  10. Regulation of AMP-activated protein kinase by natural and synthetic activators.

    Grahame Hardie, David

    2016-01-01

    The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that is almost universally expressed in eukaryotic cells. While it appears to have evolved in single-celled eukaryotes to regulate energy balance in a cell-autonomous manner, during the evolution of multicellular animals its role has become adapted so that it also regulates energy balance at the whole body level, by responding to hormones that act primarily on the hypothalamus. AMPK monitors energy balance at the cellular level by sensing the ratios of AMP/ATP and ADP/ATP, and recent structural analyses of the AMPK heterotrimer that have provided insight into the complex mechanisms for these effects will be discussed. Given the central importance of energy balance in diseases that are major causes of morbidity or death in humans, such as type 2 diabetes, cancer and inflammatory disorders, there has been a major drive to develop pharmacological activators of AMPK. Many such activators have been described, and the various mechanisms by which these activate AMPK will be discussed. A particularly large class of AMPK activators are natural products of plants derived from traditional herbal medicines. While the mechanism by which most of these activate AMPK has not yet been addressed, I will argue that many of them may be defensive compounds produced by plants to deter infection by pathogens or grazing by insects or herbivores, and that many of them will turn out to be inhibitors of mitochondrial function. PMID:26904394

  11. Regulation of AMP-activated protein kinase by natural and synthetic activators

    David Grahame Hardie

    2016-01-01

    Full Text Available The AMP-activated protein kinase (AMPK is a sensor of cellular energy status that is almost universally expressed in eukaryotic cells. While it appears to have evolved in single-celled eukaryotes to regulate energy balance in a cell-autonomous manner, during the evolution of multicellular animals its role has become adapted so that it also regulates energy balance at the whole body level, by responding to hormones that act primarily on the hypothalamus. AMPK monitors energy balance at the cellular level by sensing the ratios of AMP/ATP and ADP/ATP, and recent structural analyses of the AMPK heterotrimer that have provided insight into the complex mechanisms for these effects will be discussed. Given the central importance of energy balance in diseases that are major causes of morbidity or death in humans, such as type 2 diabetes, cancer and inflammatory disorders, there has been a major drive to develop pharmacological activators of AMPK. Many such activators have been described, and the various mechanisms by which these activate AMPK will be discussed. A particularly large class of AMPK activators are natural products of plants derived from traditional herbal medicines. While the mechanism by which most of these activate AMPK has not yet been addressed, I will argue that many of them may be defensive compounds produced by plants to deter infection by pathogens or grazing by insects or herbivores, and that many of them will turn out to be inhibitors of mitochondrial function.

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

    Lidegaard, Lærke; Schwennesen, Nete; Willaing, Ingrid;

    2016-01-01

    mutual commitment and enjoyment; and 4) goal-setting and self-tracking, which was seen as an opportunity to track physical improvement over time. Conclusions The findings suggest that, once people are active, a high level of social interaction may help maintain their activity levels. Further research is......- and long-term goals....

  13. Facilitators and Barriers to Physical Activity as Perceived by Older Adults With Intellectual Disability

    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

  14. Identifying Barriers, Perceptions and Motivations Related to Healthy Eating and Physical Activity among 6th to 8th Grade, Rural, Limited-Resource Adolescents

    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…

  15. The effect of EU environmental regulation on international trade : restriction of hazardous substance as a trade barrier

    Honda, Keiichiro; 本田, 圭市郎

    2012-01-01

    In 2003 the Restriction of Hazardous Substances (RoHS) was established in the EU, which limited the trade of machinery, electrical and electronic equipment that have at least one of the substances considered hazardous under RoHS directive. Since countries trading with the EU must comply with this new regulation, it is expected a decrease in value of imports to the EU. In this paper, it is followed the procedures used in Heckman (1979), as well as the extended procedure suggested by Helpman, M...

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

    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...... 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......-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...

  17. Motivators and barriers to healthful eating and physical activity among low-income overweight and obese mothers.

    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. PMID:18502238

  18. Regulation of platelet activating factor receptor coupled phosphoinositide-specific phospholipase C activity

    Morrison, W.J.

    1988-01-01

    The major objectives of this study were two-fold. The first was to establish whether binding of platelet activating factor (PAF) to its receptor was integral to the stimulation of polyphosphoinositide-specific phospholipase C (PLC) in rabbit platelets. The second was to determine regulatory features of this receptor-coupled mechanism. ({sup 3}H)PAF binding demonstrated two binding sites, a high affinity site with a inhibitory constant (Ki) of 2.65 nM and a low affinity site with a Ki of 0.80 {mu}M. PAF receptor coupled activation of phosphoinositide-specific PLC was studied in platelets which were made refractory, by short term pretreatments, to either PAF or thrombin. Saponin-permeabilized rabbit platelets continue to regulate the mechanism(s) coupling PAF receptors to PLC stimulation. However, TRP{gamma}S and GDP{beta}S, which affect guanine nucleotide regulatory protein functions, were unable to modulate the PLC activity to any appreciable extent as compared to PAF. The possible involvement of protein kinase C (PKC) activation in regulating PAF-stimulated PLC activity was studied in rabbit platelets pretreated with staurosporine followed by pretreatments with PAF or phorbol 12-myristate 13-acetate (PMA).

  19. German National Galileo Public Regulated Service (PRS) Testing Activities

    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.

  20. Physical Activity in Adolescents — Barriers and Impact on Depressed Affect

    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...

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

    Rebecca Seguin; Leah Connor; Miriam Nelson; Andrea LaCroix; Galen Eldridge

    2014-01-01

    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 ...

  2. Multiple roles for keratin intermediate filaments in the regulation of epithelial barrier function and apico-basal polarity.

    Salas, Pedro J; Forteza, Radia; Mashukova, Anastasia

    2016-01-01

    As multicellular organisms evolved a family of cytoskeletal proteins, the keratins (types I and II) expressed in epithelial cells diversified in more than 20 genes in vertebrates. There is no question that keratin filaments confer mechanical stiffness to cells. However, such a number of genes can hardly be explained by evolutionary advantages in mechanical features. The use of transgenic mouse models has revealed unexpected functional relationships between keratin intermediate filaments and intracellular signaling. Accordingly, loss of keratins or mutations in keratins that cause or predispose to human diseases, result in increased sensitivity to apoptosis, regulation of innate immunity, permeabilization of tight junctions, and mistargeting of apical proteins in different epithelia. Precise mechanistic explanations for these phenomena are still lacking. However, immobilization of membrane or cytoplasmic proteins, including chaperones, on intermediate filaments ("scaffolding") appear as common molecular mechanisms and may explain the need for so many different keratin genes in vertebrates. PMID:27583190

  3. 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

    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.

  4. Collagen I-induced dendritic cells activation is regulated by TNF- production through down-regulation of IRF4

    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.

  5. Outdoor Built Environment Barriers and Facilitators to Activity among Midlife and Older Adults with Mobility Disabilities

    Rosenberg, Dori E.; Huang, Deborah L.; Simonovich, Shannon D.; Belza, Basia

    2013-01-01

    Purpose: To gain better understanding of how the built environment impacts neighborhood-based physical activity among midlife and older adults with mobility disabilities. Design and methods: We conducted in-depth interviews with 35 adults over age 50, which used an assistive device and lived in King County, Washington, U.S. In addition,…

  6. Motivators and barriers to engaging in healthy eating and physical activity in young adult men

    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...

  7. Adoption Activities on the Internet: A Call for Regulation

    Roby, Jini L.; White, Holly

    2010-01-01

    There is a growing practice of adoption services on the Internet with varying degrees of regulation, depending on whether it is domestic infant adoption, public foster care adoption, or international adoption. Regulation is particularly lacking in domestic infant adoptions, with Web sites connecting prospective birth and adoptive parents,…

  8. Tax regulating carbon market in Brazil: barriers and perspectives; Regulacao tributaria do mercado de carbono no Brasil: entraves e perspectivas

    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)

  9. Outdoor Built Environment Barriers and Facilitators to Activity among Midlife and Older Adults with Mobility Disabilities

    Rosenberg, Dori E.; Huang, Deborah L.; Simonovich, Shannon D.; Belza, Basia

    2012-01-01

    Purpose: To gain better understanding of how the built environment impacts neighborhood-based physical activity among midlife and older adults with mobility disabilities. Design and methods: We conducted in-depth interviews with 35 adults over age 50, which used an assistive device and lived in King County, Washington, U.S. In addition, participants wore Global Positioning Systems (GPS) devices for 3 days prior to the interview. The GPS maps were used as prompts during the interviews. Open co...

  10. Comparison of thermally activated overcoming of barriers in creep of aluminum and its solid solutions

    Dobeš, Ferdinand; Milička, Karel

    387ů389, - (2004), 595ů598. ISSN 0921-5093. [International Conference on the Strength of Materials /13./. Budapest, 25.08.2003-30.08.2003] R&D Projects: GA AV ČR IAA2041202; GA AV ČR IAA2041203 Institutional research plan: CEZ:AV0Z2041904 Keywords : creep * thermal activation * dislocation density Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.445, year: 2004

  11. Curcumin protects intestinal mucosal barrier function of rat enteritis via activation of MKP-1 and attenuation of p38 and NF-κB activation.

    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.

  12. Diffusion barriers in the kinetics of water vapor adsorption/desorption on activated carbons

    Harding, A.W.; Foley, N.J.; Thomas, K.M. [Univ. of Newcastle upon Tyne (United Kingdom); Norman, P.R.; Francis, D.C. [CBD, Salisbury (United Kingdom)

    1998-07-07

    The adsorption of water vapor on a highly microporous coconut-shell-derived carbon and a mesoporous wood-derived carbon was studied. These carbons were chosen as they had markedly different porous structures. The adsorption and desorption characteristics of water vapor on the activated carbons were investigated over the relative pressure range p/p{degree} = 0--0.9 for temperatures in the range 285--313 K in a static water vapor system. The adsorption isotherms were analyzed using the Dubinin-Serpinski equation, and this provided an assessment of the polarity of the carbons. The kinetics of water vapor adsorption and desorption were studied with different amounts of preadsorbed water for set changes in pressure relative to the saturated vapor pressure (p/p{degree}). The adsorption kinetics for each relative pressure step were compared and used to calculate the activation energies for the vapor pressure increments. The kinetic results are discussed in relation to their relative position on the equilibrium isotherm and the adsorption mechanism of water vapor on activated carbons.

  13. Cutaneous Human Papillomaviruses Down-regulate AKT1, whereas AKT2 Up-regulation and Activation Associates with Tumors

    O'Shaughnessy, Ryan F L; Akgũl, Baki; Storey, Alan; Pfister, Herbert; Harwood, Catherine A; Byrne, Carolyn

    2007-01-01

    Epithelial tumorigenesis has been linked to AKT up-regulation. Human papillomaviruses (HPV) cause anogenital cancers and anogenital HPV infection up-regulates AKT activity. Mounting evidence points to a role for cutaneous HPVs as etiologic factors in skin tumorigenesis. High-risk cutaneous β HPVs have been linked to carcinogenesis in immunosuppressed patients, and high-risk cutaneous HPV8 genes enhance tumorigenesis in transgenic mice. We find that, in contrast to anogenital HPVs, cutaneous H...

  14. AMP-activated protein kinase (AMPK) activation regulates in vitro bone formation and bone mass.

    Shah, M; Kola, B; Bataveljic, A; Arnett, T R; Viollet, B; Saxon, L; Korbonits, M; Chenu, C

    2010-08-01

    Adenosine 5'-monophosphate-activated protein kinase (AMPK), a regulator of energy homeostasis, has a central role in mediating the appetite-modulating and metabolic effects of many hormones and antidiabetic drugs metformin and glitazones. The objective of this study was to determine if AMPK can be activated in osteoblasts by known AMPK modulators and if AMPK activity is involved in osteoblast function in vitro and regulation of bone mass in vivo. ROS 17/2.8 rat osteoblast-like cells were cultured in the presence of AMPK activators (AICAR and metformin), AMPK inhibitor (compound C), the gastric peptide hormone ghrelin and the beta-adrenergic blocker propranolol. AMPK activity was measured in cell lysates by a functional kinase assay and AMPK protein phosphorylation was studied by Western Blotting using an antibody recognizing AMPK Thr-172 residue. We demonstrated that treatment of ROS 17/2.8 cells with AICAR and metformin stimulates Thr-172 phosphorylation of AMPK and dose-dependently increases its activity. In contrast, treatment of ROS 17/2.8 cells with compound C inhibited AMPK phosphorylation. Ghrelin and propranolol dose-dependently increased AMPK phosphorylation and activity. Cell proliferation and alkaline phosphatase activity were not affected by metformin treatment while AICAR significantly inhibited ROS 17/2.8 cell proliferation and alkaline phosphatase activity at high concentrations. To study the effect of AMPK activation on bone formation in vitro, primary osteoblasts obtained from rat calvaria were cultured for 14-17days in the presence of AICAR, metformin and compound C. Formation of 'trabecular-shaped' bone nodules was evaluated following alizarin red staining. We demonstrated that both AICAR and metformin dose-dependently increase trabecular bone nodule formation, while compound C inhibits bone formation. When primary osteoblasts were co-treated with AICAR and compound C, compound C suppressed the stimulatory effect of AICAR on bone nodule formation

  15. Effect of Standardized Boesenbergia pandurata Extract and Its Active Compound Panduratin A on Skin Hydration and Barrier Function in Human Epidermal Keratinocytes

    Woo, Seon Wook; Rhim, Dong-Bin; Kim, Changhee; Hwang, Jae-Kwan

    2015-01-01

    The skin plays a key role in protecting the body from the environment and from water loss. Cornified envelope (CE) and natural moisturizing factor (NMF) are considered as the primary regulators of skin hydration and barrier function. The CE prevents loss of water from the body and is formed by cross-linking of several proteins. Among these proteins, filaggrin is an important protein because NMF is produced by the degradation of filaggrin. Proteases, including matriptase and prostasin, stimula...

  16. A specific, transmembrane interface regulates fibroblast activation protein (FAP) homodimerization, trafficking and exopeptidase activity.

    Wonganu, Benjamaporn; Berger, Bryan W

    2016-08-01

    Fibroblast activation protein (FAP) is a cell-surface serine protease which promotes invasiveness of certain epithelial cancers and is therefore a potential target for cancer drug development and delivery. Unlike dipeptidyl peptidase IV (DPPIV), FAP exhibits prolyl endopeptidase activity and is active as a homodimer with specificity for type I collagen. The mechanism that regulates FAP homodimerization and its relation to prolyl endopeptidase activity is not completely understood. Here, we investigate key residues in the FAP TM domain that may be significant for FAP homodimerization. Mutations to predicted TM interfacial residues (G10L, S14L, and A18L) comprising a small-X3-small motif reduced FAP TM-CYTO dimerization relative to wild type as measured using the AraTM assay, whereas predicted off-interface residues showed no significant change from wild type. The results implied that the predicted small-X3-small dimer interface affect stabilization of FAP TM-CYTO homodimerization. Compared with FAPwild-type, the interfacial TM residue G10L significantly decreased FAP endopeptidase activity more than 25%, and also reduced cell-surface versus intracellular expression relative to other interfacial residues S14L and A18L. Thus, our results suggest FAP dimerization is important for both trafficking and protease activity, and is dependent on a specific TM interface. PMID:27155568

  17. Hepatitis C virus core protein regulates p300/CBP co-activation function. Possible role in the regulation of NF-AT1 transcriptional activity

    Hepatitis C virus (HCV) core is a viral structural protein; it also participates in some cellular processes, including transcriptional regulation. However, the mechanisms of core-mediated transcriptional regulation remain poorly understood. Oncogenic virus proteins often target p300/CBP, a known co-activator of a wide variety of transcription factors, to regulate the expression of cellular and viral genes. Here we demonstrate, for the first time, that HCV core protein interacts with p300/CBP and enhances both its acetyl-transferase and transcriptional activities. In addition, we demonstrate that nuclear core protein activates the NH2-terminal transcription activation domain (TAD) of NF-AT1 in a p300/CBP-dependent manner. We propose a model in which core protein regulates the co-activation function of p300/CBP and activates NF-AT1, and probably other p300/CBP-regulated transcription factors, by a novel mechanism involving the regulation of the acetylation state of histones and/or components of the transcriptional machinery

  18. Activated protein C: A regulator of human skin epidermal keratinocyte function

    Kelly; McKelvey; Christopher; John; Jackson; Meilang; Xue

    2014-01-01

    Activated protein C(APC) is a physiological anticoagulant, derived from its precursor protein C(PC). Independent of its anticoagulation, APC possesses strong anti-inflammatory, anti-apoptotic and barrier protective properties which appear to be protective in a number of disorders including chronic wound healing. The epidermis is the outermost skin layer and provides the first line of defence against the external environment. Keratinocytes are the most predominant cells in the epidermis and play a critical role in maintaining epidermal barrier function. PC/APC and its receptor, endothelial protein C receptor(EPCR), once thought to be restricted to the endothelium, are abundantly expressed by skin epidermal keratinocytes. These cells respond to APC by upregulating proliferation, migration and matrix metalloproteinase-2 activity and inhibiting apoptosis/inflammation leading to a wound healing phenotype. APC also increases barrier function of keratinocyte monolayers by promoting the expression of tight junction proteins and re-distributing them to cell-cell contacts. These cytoprotective properties of APC are mediated through EPCR, protease-activated receptors, epidermal growth factor receptor or Tie2. Future preventive and therapeutic uses of APC in skin disorders associated with disruption of barrier function and inflammation look promising. This review will focus on APC’s function in skin epidermis/keratinocytes and its therapeutical potential in skin inflammatory conditions.

  19. Arabidopsis PROTEASOME REGULATOR1 is required for auxin-mediated suppression of proteasome activity and regulates auxin signalling.

    Yang, Bao-Jun; Han, Xin-Xin; Yin, Lin-Lin; Xing, Mei-Qing; Xu, Zhi-Hong; Xue, Hong-Wei

    2016-01-01

    The plant hormone auxin is perceived by the nuclear F-box protein TIR1 receptor family and regulates gene expression through degradation of Aux/IAA transcriptional repressors. Several studies have revealed the importance of the proteasome in auxin signalling, but details on how the proteolytic machinery is regulated and how this relates to degradation of Aux/IAA proteins remains unclear. Here we show that an Arabidopsis homologue of the proteasome inhibitor PI31, which we name PROTEASOME REGULATOR1 (PTRE1), is a positive regulator of the 26S proteasome. Loss-of-function ptre1 mutants are insensitive to auxin-mediated suppression of proteasome activity, show diminished auxin-induced degradation of Aux/IAA proteins and display auxin-related phenotypes. We found that auxin alters the subcellular localization of PTRE1, suggesting this may be part of the mechanism by which it reduces proteasome activity. Based on these results, we propose that auxin regulates proteasome activity via PTRE1 to fine-tune the homoeostasis of Aux/IAA repressor proteins thus modifying auxin activity. PMID:27109828

  20. Permeable reactive barrier of surface hydrophobic granular activated carbon coupled with elemental iron for the removal of 2,4-dichlorophenol in water

    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 m2 g-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.

  1. Isotope dependent, temperature regulated, energy repartitioning in a low-barrier, short-strong hydrogen bonded cluster

    We investigate and analyze the vibrational properties, including hydrogen/deuterium isotope effects, in a fundamental organic hydrogen bonded system using multiple experimental (infrared multiple photon dissociation and argon-tagged action spectroscopy) and computational techniques. We note a qualitative difference between the two experimental results discussed here and employ ab initio molecular dynamics simulations to explain these results. A deeper understanding of the differences between the isotopically labeled systems arises from an analysis of the simulated cluster spectroscopy and leads to a system-bath coupling interpretation. Specifically, when a few active modes, involving the shared hydrogen/deuterium stretch, are identified and labeled as “system,” with all other molecular vibrational modes being identified as “bath” modes, we find critical differences in the coupling between the system modes for the shared proton and shared deuteron cases. These differences affect the energy repartitioning between these modes resulting in a complex spectral evolution as a function of temperature. Furthermore, intensity borrowing across modes that are widely distributed in the frequency domain plays an important role on the simulated spectra

  2. Mediating Effects of Self-Efficacy, Benefits and Barriers on the Association between Peer and Parental Factors and Physical Activity among Adolescent Girls with a Lower Educational Level.

    Maite Verloigne

    Full Text Available The prevalence of physical activity among lower educated adolescent girls is low, suggesting it is important to have insights into the complex processes that may underlie their physical activity levels. Therefore, this study aimed to examine the mediating effects of self-efficacy, perceived benefits and barriers on the associations between peer and parental variables and physical activity among lower educated adolescent girls.In total, 226 girls (mean age 16.0±1.0 years; 53% technical education; 47% vocational education from a convenience sample of 6 secondary schools in Flanders, Belgium, completed a questionnaire on their total physical activity level and related peer and parental variables (i.e. modeling of physical activity, co-participation in physical activities and encouragement to be active and personal variables (i.e. self-efficacy to be active, and specific perceived benefits of physical activity and specific barriers to be active. Mediating effects were tested using MacKinnon's product-of-coefficients test based on multilevel linear regression analyses.Higher peer and parental modeling, co-participation and encouragement were significantly related to a higher physical activity level among adolescent girls (p<0.05. Self-efficacy, the perceived benefits of having fun, being around friends or meeting new people, and not being bored and the perceived barrier of not liking physical activity mediated several associations between peer and parental variables and girls' physical activity, with some of the mediated proportions exceeding 60%.This study contributed to a better understanding of the complexity of how parental and peer factors work together with personal factors to influence the physical activity levels of adolescent girls with a lower educational level. Interventions should involve both peers and parents, as they may influence girls' physical activity both directly and indirectly through the internalisation of several personal

  3. Early Exercise Protects the Blood-Brain Barrier from Ischemic Brain Injury via the Regulation of MMP-9 and Occludin in Rats

    Yuling Zhang

    2013-05-01

    Full Text Available Early exercise within 24 h after stroke can reduce neurological deficits after ischemic brain injury. However, the mechanisms underlying this neuroprotection remain poorly understood. Ischemic brain injury disrupts the blood-brain barrier (BBB and then triggers a cascade of events, leading to secondary brain injury and poor long-term outcomes. This study verified the hypothesis that early exercise protected the BBB after ischemia. Adult rats were randomly assigned to sham, early exercise (EE or non-exercise (NE groups. The EE and NE groups were subjected to ischemia induced by middle cerebral artery occlusion (MCAO. The EE group ran on a treadmill beginning 24 h after ischemia, 30 min per day for three days. After three-days’ exercise, EB extravasation and electron microscopy were used to evaluate the integrity of the BBB. Neurological deficits, cerebral infarct volume and the expression of MMP-9, the tissue inhibitors of metalloproteinase-1 (TIMP-1, and occludin were determined. The data indicated that early exercise significantly inhibited the ischemia-induced reduction of occludin, and an increase in MMP-9 promoted TIMP-1 expression (p < 0.01, attenuated the BBB disruption (p < 0.05 and neurological deficits (p < 0.01 and diminished the infarct volume (p < 0.01. Our results suggest that the neuroprotection conferred by early exercise was likely achieved by improving the function of the BBB via the regulation of MMP-9 and occludin.

  4. International experience of administrative legal regulation of insurance in innovative and investment activity

    Шапенко, Людмила

    2016-01-01

    The author of the article analyzes and summarizes international experience of leading countries in the world regarding state regulation of insurance. Different approaches to administrative and legal regulation of insurance are investigated and the most appropriate model of regulation of the insurance market is defined. English abstract L. Shapenko International experience of administrative legal regulation of insurance in innovative and investment activity Ukraine that chose a direction of...

  5. Regulation of p53 Localization and Activity by Ubc13▿ †

    Laine, Aaron; Topisirovic, Ivan; Zhai, Dayong; John C Reed; Borden, Katherine L. B.; Ronai, Ze'ev

    2006-01-01

    The abundance and activity of p53 are regulated largely by ubiquitin ligases. Here we demonstrate a previously undisclosed regulation of p53 localization and activity by Ubc13, an E2 ubiquitin-conjugating enzyme. While increasing p53 stability, Ubc13 decreases p53 transcriptional activity and increases its localization to the cytoplasm, changes that require its ubiquitin-conjugating activity. Ubc13 elicits K63-dependent ubiquitination of p53, which attenuates Hdm2-induced polyubiquitination o...

  6. Alterations in blood-brain barrier ICAM-1 expression and brain microglial activation after λ-carrageenan-induced inflammatory pain

    Huber, J. D.; Campos, C. R.; Mark, K. S.; Davis, T. P.

    2014-01-01

    Previous studies showed that peripheral inflammatory pain increased blood-brain barrier (BBB) permeability and altered tight junction protein expression and the delivery of opioid analgesics to the brain. What remains unknown is which pathways and mediators during peripheral inflammation affect BBB function and structure. The current study investigated effects of λ-carrageenan-induced inflammatory pain (CIP) on BBB expression of ICAM-1. We also examined the systemic contribution of a number of proinflammatory cytokines and microglial activation in the brain to elucidate pathways involved in BBB disruption during CIP. We investigated ICAM-1 RNA and protein expression levels in isolated rat brain microvessels after CIP using RT-PCR and Western blot analyses, screened inflammatory cytokines during the time course of inflammation, assessed white blood cell counts, and probed for BBB and central nervous system stimulation and leukocyte transmigration using immunohistochemistry and flow cytometry. Results showed an early increase in ICAM-1 RNA and protein expression after CIP with no change in circulating levels of several proinflammatory cytokines. Changes in ICAM-1 protein expression were noted at 48 h. Immunohistochemistry showed that the induction of ICAM-1 was region specific with increased expression noted in the thalamus and frontal and parietal cortices, which directly correlated with increased expression of activated microglia. The findings of the present study were that CIP induces increased ICAM-1 mRNA and protein expression at the BBB and that systemic proinflammatory mediators play no apparent role in the early response (1–6 h); however, brain region-specific increases in micro-glial activation suggest a potential for a central-mediated response. PMID:16199477

  7. Regulating the reapers: activating metacaspases for programmed cell death.

    Lam, Eric; Zhang, Yi

    2012-08-01

    Research during the past two decades has revealed that specialized cysteine proteases act as conserved initiators or executioners for programmed cell death (PCD) in eukaryotes. Caspases were first identified as common regulators of PCD in metazoans, whereas the role of metacaspases (MCs) as regulators of cellular suicide in plants has only been shown genetically in the past several years. Together with recent biochemical and molecular characterizations of some of the representative MCs from different model systems, multiple mechanisms that can mediate the post-translational regulation of these proteases are beginning to emerge. Further elucidation of these regulatory pathways and definition of the downstream degradomes targeted by MCs should lead to a better understanding of cell death control in plants, protozoans, and fungi. PMID:22658651

  8. Physical Activity, Self-Regulation, and Early Academic Achievement in Preschool Children

    Becker, Derek R.; McClelland, Megan M.; Loprinzi, Paul; Trost, Stewart G.

    2014-01-01

    Research Findings: The present study investigated whether active play during recess was associated with self-regulation and academic achievement in a prekindergarten sample. A total of 51 children in classes containing approximately half Head Start children were assessed on self-regulation, active play, and early academic achievement. Path…

  9. Self-Regulated Learning and Perceived Health among University Students Participating in Physical Activity Classes

    McBride, Ron E.; Altunsöz, Irmak Hürmeriç; Su, Xiaoxia; Xiang, Ping; Demirhan, Giyasettin

    2016-01-01

    The purpose of this study was to explore motivational indicators of self-regulated learning (SRL) and the relationship between self-regulation (SR) and perceived health among university students enrolled in physical activity (PA) classes. One hundred thirty-one Turkish students participating in physical education activity classes at two…

  10. Active transport and diffusion barriers restrict Joubert Syndrome-associated ARL13B/ARL-13 to an Inv-like ciliary membrane subdomain.

    Sebiha Cevik

    Full Text Available Cilia are microtubule-based cell appendages, serving motility, chemo-/mechano-/photo- sensation, and developmental signaling functions. Cilia are comprised of distinct structural and functional subregions including the basal body, transition zone (TZ and inversin (Inv compartments, and defects in this organelle are associated with an expanding spectrum of inherited disorders including Bardet-Biedl syndrome (BBS, Meckel-Gruber Syndrome (MKS, Joubert Syndrome (JS and Nephronophthisis (NPHP. Despite major advances in understanding ciliary trafficking pathways such as intraflagellar transport (IFT, how proteins are transported to subciliary membranes remains poorly understood. Using Caenorhabditis elegans and mammalian cells, we investigated the transport mechanisms underlying compartmentalization of JS-associated ARL13B/ARL-13, which we previously found is restricted at proximal ciliary membranes. We now show evolutionary conservation of ARL13B/ARL-13 localisation to an Inv-like subciliary membrane compartment, excluding the TZ, in many C. elegans ciliated neurons and in a subset of mammalian ciliary subtypes. Compartmentalisation of C. elegans ARL-13 requires a C-terminal RVVP motif and membrane anchoring to prevent distal cilium and nuclear targeting, respectively. Quantitative imaging in more than 20 mutants revealed differential contributions for IFT and ciliopathy modules in defining the ARL-13 compartment; IFT-A/B, IFT-dynein and BBS genes prevent ARL-13 accumulation at periciliary membranes, whereas MKS/NPHP modules additionally inhibit ARL-13 association with TZ membranes. Furthermore, in vivo FRAP analyses revealed distinct roles for IFT and MKS/NPHP genes in regulating a TZ barrier to ARL-13 diffusion, and intraciliary ARL-13 diffusion. Finally, C. elegans ARL-13 undergoes IFT-like motility and quantitative protein complex analysis of human ARL13B identified functional associations with IFT-B complexes, mapped to IFT46 and IFT74

  11. Structural plasticity of GABAergic axons is regulated by network activity and GABAA receptor activation

    Anne eSchuemann

    2013-06-01

    Full Text Available Coordinated changes at excitatory and inhibitory synapses are essential for normal brain development and function. It is well established that excitatory neurons undergo structural changes, but our knowledge about inhibitory structural plasticity is rather scarce. Here we present a quantitative analysis of the dynamics of GABAergic boutons in the dendritic region of the hippocampal CA1 area using time-lapse two-photon imaging in organotypic hippocampal cultures from GAD65-GFP mice. We show that ~20% of inhibitory boutons are not stable. They are appearing, disappearing and reappearing at specific locations along the inhibitory axon and reflect immature or incomplete synapses. Furthermore, we observed that persistent boutons show large volume fluctuations over several hours, suggesting that presynaptic content of inhibitory synapses is not constant. Our data show that inhibitory boutons are highly dynamic structures and suggest that inhibitory axons are continuously probing potential locations for inhibitory synapse formation by redistributing presynaptic material along the axon.In addition, we found that neuronal activity affects the exploratory dynamics of inhibitory axons. Blocking network activity rapidly reduces the number of transient boutons, whereas enhancing activity reduces the number of persistent inhibitory boutons, possibly reflecting enhanced competition between boutons along the axon. The latter effect requires signaling through GABAA receptors. We propose that activity-dependent regulation of bouton dynamics contributes to inhibitory synaptic plasticity.

  12. Heavy metal removal from MSWI fly ash by electrokinetic remediation coupled with a permeable activated charcoal reactive barrier

    Huang, Tao; Li, Dongwei; Kexiang, Liu; Zhang, Yuewei

    2015-10-01

    This paper presents the investigations into the feasibility of the application of a remediation system that couples electrokinetic remediation (EKR) with the permeable reactive barrier (PRB) concept for municipal solid waste incineration (MSWI) fly ash with activated charcoal as the PRB material. The experimental results of this study showed that the proposed combined method can effectively improve the remediation efficiency and that the addition of the oxalic acid to the PRB media before the coupled system can further enhance the remediation process. In the optimization tests, the maximum removals of Zn, Pb, Cu and Cd were achieved under different experimental conditions. The voltage gradient and processing time were shown to have significant effects on the removal of Cu and Cd, whereas the addition of the oxalic acid had a more significant influence on the removal of Pb. Generally, the processing time is the most significant factor in changing the removal rates of HMs in the enhanced coupled system. In terms of the leaching toxicity, the specimen remediated by ENEKR + PRB showed the lowest leaching value for each HM in the S2 and S3 regions.

  13. Barriers and Facilitators for the Implementation of Primary Prevention and Health Promotion Activities in Primary Care: A Synthesis through Meta-Ethnography

    Maria Rubio-Valera; Mariona Pons-Vigués; María Martínez-Andrés; Patricia Moreno-Peral; Anna Berenguera; Ana Fernández

    2014-01-01

    BACKGROUND: Evidence supports the implementation of primary prevention and health promotion (PP&HP) activities but primary care (PC) professionals show resistance to implementing these activities. The aim was to synthesize the available qualitative research on barriers and facilitators identified by PC physicians and nurses in the implementation of PP&HP in adults. METHODS AND FINDINGS: A systematic search of three databases was conducted and supported by manual searches. The 35 articles incl...

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

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

    2015-01-01

    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...

  15. Physical activity among adolescents and barriers to delivering physical education in Cornwall and Lancashire, UK: A qualitative study of heads of PE and heads of schools

    Walters Stephen J; Jones Georgina L; Boyle Spencer

    2008-01-01

    Abstract Background Recent initiatives have been introduced by the UK government into secondary schools to increase pupils' access to physical activity (PA). Despite this, not enough is known about pupils' levels of physical activity or whether the delivery of these initiatives in schools facilitates or creates a barrier for pupils' PA. The aim of this study was to gain an understanding of adolescents PA levels from the perspective of those responsible for delivering physical education (PE) i...

  16. 15 CFR 922.82 - Prohibited or otherwise regulated activities.

    2010-01-01

    ... classification) that is approved in accordance with section 312 of the Federal Water Pollution Control Act, as... COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Gulf of the Farallones National... cooling water, clean vessel generator cooling water, clean bilge water, or anchor wash; or (iv)...

  17. 15 CFR 922.112 - Prohibited or otherwise regulated activities.

    2010-01-01

    ... with section 312 of the Federal Water Pollution Control Act, as amended, (FWPCA), 33 U.S.C. 1322... COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Cordell Bank National Marine... of untreated sewage; (C) Clean vessel deck wash down, clean vessel engine cooling water, clean...

  18. 15 CFR 922.122 - Prohibited or otherwise regulated activities.

    2010-01-01

    ... accordance with section 312 of the Federal Water Pollution Control Act, as amended, 33 U.S.C. 1322; (C) Water... section 312 of the Federal Water Pollution Control Act, as amended, 33 U.S.C. 1322) excluding oily wastes... COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Flower Garden Banks...

  19. 15 CFR 922.132 - Prohibited or otherwise regulated activities.

    2010-01-01

    ...) approved in accordance with section 312 of the Federal Water Pollution Control Act, as amended (FWPCA), 33... COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Monterey Bay National Marine... Director issue a National Marine Sanctuary permit under 15 CFR 922.48 and 922.133 or a Special Use...

  20. Phosphorylation networks regulating JNK activity in diverse genetic backgrounds

    Bakal, Chris; Linding, Rune; Llense, Flora;

    2008-01-01

    Cellular signaling networks have evolved to enable swift and accurate responses, even in the face of genetic or environmental perturbation. Thus, genetic screens may not identify all the genes that regulate different biological processes. Moreover, although classical screening approaches have suc...

  1. Polyphosphate - an ancient energy source and active metabolic regulator

    Achbergerová Lucia

    2011-08-01

    Full Text Available Abstract There are a several molecules on Earth that effectively store energy within their covalent bonds, and one of these energy-rich molecules is polyphosphate. In microbial cells, polyphosphate granules are synthesised for both energy and phosphate storage and are degraded to produce nucleotide triphosphate or phosphate. Energy released from these energetic carriers is used by the cell for production of all vital molecules such as amino acids, nucleobases, sugars and lipids. Polyphosphate chains directly regulate some processes in the cell and are used as phosphate donors in gene regulation. These two processes, energetic metabolism and regulation, are orchestrated by polyphosphate kinases. Polyphosphate kinases (PPKs can currently be categorized into three groups (PPK1, PPK2 and PPK3 according their functionality; they can also be divided into three groups according their homology (EcPPK1, PaPPK2 and ScVTC. This review discusses historical information, similarities and differences, biochemical characteristics, roles in stress response regulation and possible applications in the biotechnology industry of these enzymes. At the end of the review, a hypothesis is discussed in view of synthetic biology applications that states polyphosphate and calcium-rich organelles have endosymbiotic origins from ancient protocells that metabolized polyphosphate.

  2. Platelet activating factor-induced ceramide micro-domains drive endothelial NOS activation and contribute to barrier dysfunction.

    Sanda Predescu

    Full Text Available The spatial and functional relationship between platelet activating factor-receptor (PAF-R and nitric oxide synthase (eNOS in the lateral plane of the endothelial plasma membrane is poorly characterized. In this study, we used intact mouse pulmonary endothelial cells (ECs as well as endothelial plasma membrane patches and subcellular fractions to define a new microdomain of plasmalemma proper where the two proteins colocalize and to demonstrate how PAF-mediated nitric oxide (NO production fine-tunes ECs function as gatekeepers of vascular permeability. Using fluorescence microscopy and immunogold labeling electron microscopy (EM on membrane patches we demonstrate that PAF-R is organized as clusters and colocalizes with a subcellular pool of eNOS, outside recognizable vesicular profiles. Moreover, PAF-induced acid sphingomyelinase activation generates a ceramide-based microdomain on the external leaflet of plasma membrane, inside of which a signalosome containing eNOS shapes PAF-stimulated NO production. Real-time measurements of NO after PAF-R ligation indicated a rapid (5 to 15 min increase in NO production followed by a > 45 min period of reduction to basal levels. Moreover, at the level of this new microdomain, PAF induces a dynamic phosphorylation/dephosphorylation of Ser, Thr and Tyr residues of eNOS that correlates with NO production. Altogether, our findings establish the existence of a functional partnership PAF-R/eNOS on EC plasma membrane, at the level of PAF-induced ceramide plasma membrane microdomains, outside recognized vesicular profiles.

  3. Design of engineered sorbent barriers

    A sorbent barrier uses sorbent material such as activated carbon or natural zeolites to prevent the migration of radionuclides from a low-level waste site to the aquifer. The sorbent barrier retards the movement of radioactive contaminants, thereby providing time for the radionuclides to decay. Sorbent barriers can be a simple, effective, and inexpensive method for reducing the migration of radionuclides to the environment. Designing a sorbent barrier consists of using soil and sorbent material properties and site conditions as input to a model which will determine the necessary sorbent barrier thickness to meet contaminant limits. The paper covers the following areas: techniques for measuring sorption properties of barrier materials and underlying soils, use of a radionuclide transport model to determine the required barrier thickness and performance under a variety of site conditions, and cost estimates for applying the barrier

  4. Redox Regulation of the AMP-Activated Protein Kinase

    Yingying Han; Qilong Wang; Ping Song; Yi Zhu; Ming-Hui Zou

    2010-01-01

    Redox state is a critical determinant of cell function, and any major imbalances can cause severe damage or death. Objectives The aim of this study is to determine if AMP-activated protein kinase (AMPK), a cellular energy sensor, is activated by oxidants generated by Berberine in endothelial cells (EC). Methods Bovine aortic endothelial cells (BAEC) were exposed to Berberine. AMPK activity and reactive oxygen species were monitored after the incubation. Results In BAEC, Berberine caused a dos...

  5. Redox Regulation of Protein Tyrosine Phosphatase Activity by Hydroxyl Radical

    Meng, Fan-Guo; Zhang, Zhong-Yin

    2012-01-01

    Substantial evidence suggests that transient production of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) is an important signaling event triggered by the activation of various cell surface receptors. Major targets of H2O2 include protein tyrosine phosphatases (PTPs). Oxidation of the active site Cys by H2O2 abrogates PTP catalytic activity, thereby potentially furnishing a mechanism to ensure optimal tyrosine phosphorylation in response to a variety of physiological stimuli. ...

  6. Cyclin-Dependent Kinase 9 Activity Regulates Neutrophil Spontaneous Apoptosis

    Wang, K.; Hampson, P.; Hazeldine, J.; Kryštof, Vladimír; Strnad, Miroslav; Pechan, P.; Lord, J. M.

    2012-01-01

    Roč. 7, č. 1 (2012), "e30128". E-ISSN 1932-6203 R&D Projects: GA ČR GA301/08/1649 Grant ostatní: GA ČR(CZ) GA204/08/0511 Institutional research plan: CEZ:AV0Z50380511 Keywords : COLONY-STIMULATING FACTOR * PROGRAMMED CELL-DEATH * DOWN-REGULATION Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.730, year: 2012

  7. Nuclear translocation contributes to regulation of DNA excision repair activities

    Knudsen, Nina Østergaard; Andersen, Sofie Dabros; Lützen, Anne; Nielsen, Finn Cilius; Rasmussen, Lene Juel

    2009-01-01

    DNA mutations are circumvented by dedicated specialized excision repair systems, such as the base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR) pathways. Although the individual repair pathways have distinct roles in suppressing changes in the nuclear DNA, it is...... co-import appears to be a mechanism employed by the composite repair systems NER and MMR to enhance and regulate nuclear accumulation of repair proteins thereby ensuring faithful DNA repair....

  8. The Cytoskeletal Protein Ndel1 Regulates Dynamin 2 GTPase Activity

    Chansard, Mathieu; WANG, Jian; Tran, Hong Chi; Neumayer, Gernot; Shim, Su Yeon; Park, Young-Un; Belzil, Camille; Le, Hoa Thi; Park, Sang Ki; Nguyen, Minh Dang

    2011-01-01

    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 co...

  9. Exocyst Sec10 protects epithelial barrier integrity and enhances recovery following oxidative stress, by activation of the MAPK pathway

    Park, Kwon Moo; Fogelgren, Ben; Zuo, Xiaofeng; Kim, Jinu; Chung, Daniel C.; LIPSCHUTZ, Joshua H.

    2010-01-01

    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 r...

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

    Acheampong, Franklin; Anto, Berko Panyin

    2015-01-01

    Background 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 saf...

  11. Prevalência de barreiras para a prática de atividade física em adolescentes Prevalence of barriers for physical activity in adolescents

    Mariana Silva Santos

    2010-03-01

    Full Text Available O objetivo deste estudo foi analisar a prevalência de barreiras e sua associação com a prática de atividades físicas em adolescentes. O presente estudo, transversal, avaliou uma amostra representativa de escolares do ensino médio da rede pública da cidade de Curitiba-PR, Brasil. Um total de 1.609 escolares (59,7% do gênero feminino entre 14 e 18 anos de idade reportou, por meio de um questionário, o nível de atividade física e as barreiras para a prática de atividades físicas. Para verificar a associação entre a prevalência de barreiras e a atividade física foi realizada uma análise de regressão logística para cada barreira investigada ajustando para variáveis de confusão (idade e nível socioeconômico. As análises foram realizadas separadamente para meninos e meninas. Apenas 22% dos meninos e 9% das meninas atingiram a atual recomendação para atividade física. Entre as 12 barreiras investigadas, apenas "não ter alguém para levar" não diferiu entre os gêneros. Para todas as outras, a percepção de barreiras foi maior entre as meninas (p The aim of this study was to analyze the prevalence and association of barriers to physical activity among adolescents. This cross-sectional study evaluated a representative sample of public high school students in Curitiba-PR, Brazil. A total of 1,609 school adolescents (59.7% male between 14 and 18 years of age answered a questionnaire on physical activity status and barriers to physical activity. Logistic regressions were conducted for each barrier investigated to verify the association between the prevalence of barriers and physical activity, adjusting for confounding variables (age and socioeconomic status. Analyses were done separately for boys and girls. Only 22% of boys and 9% of girls achieved the current physical activity recommendation. Among the 12 barriers investigated, only "there is nobody to take" did not differ between boys and girls. The perception of barriers was

  12. Stromal cells control the epithelial residence of DCs and memory T cells by regulated activation of TGF-β.

    Mohammed, Javed; Beura, Lalit K; Bobr, Aleh; Astry, Brian; Chicoine, Brian; Kashem, Sakeen W; Welty, Nathan E; Igyártó, Botond Z; Wijeyesinghe, Sathi; Thompson, Emily A; Matte, Catherine; Bartholin, Laurent; Kaplan, Alesia; Sheppard, Dean; Bridges, Alina G; Shlomchik, Warren D; Masopust, David; Kaplan, Daniel H

    2016-04-01

    Cells of the immune system that reside in barrier epithelia provide a first line of defense against pathogens. Langerhans cells (LCs) and CD8(+) tissue-resident memory T cells (TRM cells) require active transforming growth factor-β1 (TGF-β) for epidermal residence. Here we found that integrins αvβ6 and αvβ8 were expressed in non-overlapping patterns by keratinocytes (KCs) and maintained the epidermal residence of LCs and TRM cells by activating latent TGF-β. Similarly, the residence of dendritic cells and TRM cells in the small intestine epithelium also required αvβ6. Treatment of the skin with ultraviolet irradiation decreased integrin expression on KCs and reduced the availability of active TGF-β, which resulted in LC migration. Our data demonstrated that regulated activation of TGF-β by stromal cells was able to directly control epithelial residence of cells of the immune system through a novel mechanism of intercellular communication. PMID:26901152

  13. Examining "Active" Procrastination from a Self-Regulated Learning Perspective

    Cao, Li

    2012-01-01

    This study examined the notion that active procrastinators are a positive type of procrastinators who possess desirable characteristics similar to non-procrastinators, but different from the traditional passive procrastinators. A two-step procedure was followed to categorise university students (N = 125) as active procrastinators, passive…

  14. Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration

    Plikus, M. V.; Mayer, J. A.; de La Cruz, D.; Baker, Ruth E.; Maini, P.K.; Maxson, R.; Chuong, C M

    2008-01-01

    In the age of stem cell engineering it is critical to understand how stem cell activity is regulated during regeneration. Hairs are mini-organs that undergo cyclic regeneration throughout adult life1, and are an important model for organ regeneration. Hair stem cells located in the follicle bulge2 are regulated by the surrounding microenvironment, or niche3. The activation of such stem cells is cyclic, involving periodic -catenin activity4, 5, 6, 7. In the adult mouse, regeneration occurs in ...

  15. Regulation of pH in human skeletal muscle: adaptations to physical activity

    Juel, C

    2008-01-01

    Regulation of pH in skeletal muscle is the sum of mechanisms involved in maintaining intracellular pH within the normal range. Aspects of pH regulation in human skeletal muscle have been studied with various techniques from analysis of membrane proteins, microdialysis, and the nuclear magnetic...... describes the contribution of each transport system in pH regulation at rest and during muscle activity. It is reported that the mechanisms involved in pH regulation can undergo adaptational changes in association with physical activity and that these changes are of functional importance....

  16. Recent achievements in regulating nuclear power activities in taiwan

    Full text: The energy resources in Taiwan are very scarce with more than 98% of the fuel sources imported from foreign countries. The nuclear power became essential because of its stability and economy in price. There are six operating nuclear power units in Taiwan, and two more advanced boiling water reactor units under construction. As the country's nuclear power still plays an important role, the Atomic Energy Council (AEC) devotes its great efforts working on reactor safety regulation, radiation protection, nuclear security, nuclear emergency preparedness, nuclear waste management and environmental monitoring. Recent achievements of AEC on the above mentioned topics will be covered in this presentation

  17. A computational method for the systematic screening of reaction barriers in enzymes: searching for Bacillus circulans xylanase mutants with greater activity towards a synthetic substrate

    Martin R. Hediger

    2013-07-01

    Full Text Available We present a semi-empirical (PM6-based computational method for systematically estimating the effect of all possible single mutants, within a certain radius of the active site, on the barrier height of an enzymatic reaction. The intent of this method is not a quantitative prediction of the barrier heights, but rather to identify promising mutants for further computational or experimental study. The method is applied to identify promising single and double mutants of Bacillus circulans xylanase (BCX with increased hydrolytic activity for the artificial substrate ortho-nitrophenyl β-xylobioside (ONPX2. The estimated reaction barrier for wild-type (WT BCX is 18.5 kcal/mol, which is in good agreement with the experimental activation free energy value of 17.0 kcal/mol extracted from the observed kcat using transition state theory (Joshi et al., 2001. The PM6 reaction profiles for eight single point mutations are recomputed using FMO-MP2/PCM/6-31G(d single points. PM6 predicts an increase in barrier height for all eight mutants while FMO predicts an increase for six of the eight mutants. Both methods predict that the largest change in barrier occurs for N35F, where PM6 and FMO predict a 9.0 and 15.8 kcal/mol increase, respectively. We thus conclude that PM6 is sufficiently accurate to identify promising mutants for further study. We prepared a set of all theoretically possible (342 single mutants in which every amino acid of the active site (except for the catalytically active residues E78 and E172 was mutated to every other amino acid. Based on results from the single mutants we construct a set of 111 double mutants consisting of all possible pairs of single mutants with the lowest barrier for a particular position and compute their reaction profile. None of the mutants have, to our knowledge, been prepared experimentally and therefore present experimentally testable predictions.

  18. A benzoate-activated promoter from Aspergillus niger and regulation of its activity.

    Antunes, Mauricio S; Hodges, Thomas K; Carpita, Nicholas C

    2016-06-01

    The filamentous fungus Aspergillus niger is able to use benzoic acid as a sole carbon source by conversion to protocatechuic acid and subsequent metabolism. Synthesis of the first enzyme in this metabolic pathway, benzoate p-hydroxylase, is encoded by the bphA gene and positively regulated at the transcriptional level by benzoic acid. Methyl benzoate and para-aminobenzoate also act as inducers of the bphA gene. We show that bphA expression in A. niger in response to benzoate is confined to a 530-bp fragment from the bphA promoter region from -787 to -509 bp from the transcriptional start site. Electrophoretic mobility-shift assays show that a benzoate-response element, consisting of a single 6-bp sequence (5'-TAGTCA-3') within a 51-bp sequence in this region, is most likely to be involved in binding of one or more proteins that modulate the activity of the promoter in response to benzoic acid. We show through fusion of promoter fragments with the green fluorescent protein that the active sequences are located within a 200-bp sequence containing the TAGTCA benzoate-response element. Identification of the benzoate-response element in the bphA promoter region constitutes the first step in the development of a benzoate-inducible promoter system that could be used to control gene expression in fungi, and possibly in other organisms, such as plant and animal cells. PMID:26907094

  19. The possible roles of hyperpolarization-activated cyclic nucleotide channels in regulating pacemaker activity in colonic interstitial cells of Cajal

    Shahi, Pawan Kumar; Choi, Seok; Zuo, Dong Chuan; Kim, Man Yoo; Park, Chan Guk; Kim, Young Dae; Lee, Jun; Park, Kyu Joo; So, Insuk; Jun, Jae Yeoul

    2013-01-01

    Background Hyperpolarization-activated cyclic nucleotide (HCN) channels are pacemaker channels that regulate heart rate and neuronal rhythm in spontaneously active cardiac and neuronal cells. Interstitial cells of Cajal (ICCs) are also spontaneously active pacemaker cells in the gastrointestinal tract. Here, we investigated the existence of HCN channel and its role on pacemaker activity in colonic ICCs. Methods We performed whole-cell patch clamp, RT-PCR, and Ca2+-imaging in cultured ICCs fro...

  20. Overcoming barriers to Clean Development Mechanism projects

    Ellis, J. [OECD, Paris (France); Kamel, S. [UNEP Risoe Centre on Energy, Climate and Sustainable Development URC, Roskilde (Denmark)

    2007-05-15

    The market for Clean Development Mechanism (CDM) projects is continuing to grow rapidly, with the current portfolio expecting to deliver 2 billion tons of CO2-eq greenhouse gas (GHG) emission reductions by 2012, equivalent to 17% of Annex I Parties' base year GHG emissions. In total, governments and companies have earmarked over USD11 billion for CDM funding to 2012. This study analyses the various barriers to CDM market expansion in developing countries, and makes recommendations on how some of them can be removed or reduced. It also examines the distribution of CDM projects amongst regions and sectors. Different types of barriers can impede the development of CDM projects. These include: National-level barriers not related specifically to the CDM such as the policy or legislative framework within which a CDM project operates, e.g. electricity-related regulations that constrain generation by independent power producers; National-level CDM-related barriers such as institutional capability/effectiveness or lack of awareness about CDM potential. For example, delays in host country approval of CDM projects can dampen interest in CDM project development; Project-related issues including availability (or not) of underlying project finance, or other country or project-related risks that render the performance of the project uncertain; International-level barriers such as constraints on project eligibility (e.g. on land use and forestry projects), available guidance and decisions (e.g. with respect to the inclusion of carbon capture and storage projects), etc. Thus, barriers to CDM development can arise at different parts of the CDM project cycle. The relative importance of particular barriers varies between countries as well as over time. A combination of factors is needed to drive growth in a country's CDM activity. This includes the presence of attractive CDM opportunities, a positive investment climate, and an enabling policy and legislative framework (in

  1. Importance of sports during youth and exercise barriers in 20- to 29-year-old male nonathletes differently motivated for regular physical activities

    Leyk, Dieter; Witzki, Alexander; Sievert, Alexander;

    2012-01-01

    activity of the parents. The majority of nonathletes (72.8%) indicate their intention to exercise in the future. Their intention differed significantly in H (88.1%), L (76.1%), and A (59.1%). However, there are good reasons to doubt that most of those intending nonathletes will actually become physically......The number of sedentary young adults has dramatically increased in past decades, and sedentary lifestyles are adopted at an increasingly earlier age. Little is known about barriers or predictors to (re)initiate regular physical activity in this group. The purpose of the study is to (a) identify...... subgroups in nonathletes differing in their amenability to physical exercise, (b) to analyze them for differences in barriers and intention to exercise, and (c) compare importance of sports during youth in nonathletes to trained peers. Using a health and fitness questionnaire 589 nonathletes were queried in...

  2. Role of two-photon electronic transitions in the formation of active dynamic conductivity in a three-barrier resonance tunneling structure with an applied Dc electric field

    The theory of active dynamic conductivity in a three-barrier resonance tunneling structure subjected to the combined action of a weak electromagnetic field and a longitudinal dc electric field is developed with regard for the contribution of laser induced one- and two-photon electronic transitions with different frequencies. For this purpose, the full Schroedinger equation is solved in the effective mass approximation and with the use of the model of rectangular potential wells and barriers for an electron. The maximum contribution of two-photon transitions to the formation of the total active dynamic conductivity in laser-induced transitions is shown not to exceed 38%. Geometric configurations of the resonance tunneling structure, for which the laser radiation intensity increases due to laser induced two-photon electronic transitions, are determined

  3. Regulation of Proteolytic Enzyme Activity in Lactococcus lactis

    Meijer, W.; Marugg, J D; Hugenholtz, J

    1996-01-01

    Two different Lactococcus lactis host strains, L. lactis subsp. lactis MG1363 and L. lactis subsp. cremoris SK1128, both containing plasmid pNZ521, which encodes the extracellular serine proteinase (PrtP) from strain SK110, were used to study the medium and growth-rate-dependent activity of three different enzymes involved in the proteolytic system of lactococci. The activity levels of PrtP and both the intracellular aminopeptidase PepN and the X-prolyl-dipeptidyl aminopeptidase PepXP were st...

  4. Hormonal Regulation of chicken intestinal NHE and SGLT-1 activities

    Ilundáin Larrañeta, María Anunciación; De la Horra, Maria del Carmen; Cano Rodríguez, María Mercedes; Peral Rubio, María José; Calonge Castrillo, María Luisa

    2001-01-01

    The effects of aldosterone and arginine vasotocin (AVT) on intestinal Na/Hexchange (NHE) and Na-sugar cotransport (SGLT-1) activi-ties have been investigated using brush-border membrane ves-icles isolated from Hubbard chicken small and large intestines, and they were compared with those induced by either Nadepletion or dehydration. Na depletion was induced by feeding the chickens with either a low- or a high-Na diet for either 0.5, 1, 2, 4, or 8 days. Ileal and colonic NHE2 activity inc...

  5. The role of AMP-activated protein kinase in regulation of skeletal muscle metabolism

    Anna Dziewulska; Paweł Dobrzyń; Agnieszka Dobrzyń

    2010-01-01

    AMP-activated protein kinase (AMPK) is a conserved, ubiquitously expressed eukaryotic enzyme that is activated in response to increasing AMP level. Regulation of AMPK activity in skeletal muscle is coordinated by contraction and phosphorylation by upstream kinases and a growing number of hormones and cytokines. Once activated, AMPK turns on catabolic, ATP-generating pathways, and turns off ATP-consuming metabolic processes such as biosynthesis and proliferation. Activation of AMPK promotes gl...

  6. Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels in the regulation of midbrain dopamine systems

    Chu, Hong-Yuan; Zhen, Xuechu

    2010-01-01

    Hyperpolarization-activated, cyclic nucleotide-gated channels (HCN channels) are expressed widely in the brain and invovled in various neuronal activities, including the control of neuronal rhythmic activity, setting the resting membrane potential, as well as dendritic integration. HCN channels also participate in the regulation of spontaneous activity of midbrain dopamine (DA) neurons to some extent. In slice preparations of midbrain, a hyperpolarization-activated non-selective cation curren...

  7. Regulation of AMP-activated protein kinase by LKB1 and CaMKK in adipocytes

    Gormand, Amélie; Henriksson, Emma; Ström, Kristoffer;

    2011-01-01

    AMP-activated protein kinase (AMPK) is a serine/threonine kinase that regulates cellular and whole body energy homeostasis. In adipose tissue, activation of AMPK has been demonstrated in response to a variety of extracellular stimuli. However, the upstream kinase that activates AMPK in adipocytes...

  8. Prostaglandin E2 Regulation of Cystic Fibrosis Transmembrane Conductance Regulator Activity and Airway Surface Liquid Volume Requires Gap Junctional Communication

    Scheckenbach, K E Ludwig; Losa, Davide; Dudez, Tecla; Bacchetta, Marc; O'Grady, Scott; Crespin, Sophie; Chanson, Marc

    2010-01-01

    Stimulation of the cystic fibrosis transmembrane conductance regulator (CFTR) by protease-activated receptors (PARs) at the basolateral membranes and by adenosine receptors (ADO-Rs) at the apical membrane maintain airway surface liquid (ASL) volume, which is required to ensure hydrated and clearable mucus. Both pathways involve the release of prostaglandin E2 (PGE2) and the stimulation of their basolateral receptors (EP-Rs). We sought to determine whether gap junctions contribute to the coord...

  9. Prostaglandin E₂regulation of cystic fibrosis transmembrane conductance regulator activity and airway surface liquid volume requires gap junctional communication

    Scheckenbach, K E Ludwig; Losa, Davide; Dudez, Tecla; Bacchetta, Marc; O'Grady, Scott; Crespin, Sophie; Chanson, Marc

    2011-01-01

    Stimulation of the cystic fibrosis transmembrane conductance regulator (CFTR) by protease-activated receptors (PARs) at the basolateral membranes and by adenosine receptors (ADO-Rs) at the apical membrane maintain airway surface liquid (ASL) volume, which is required to ensure hydrated and clearable mucus. Both pathways involve the release of prostaglandin E₂ (PGE₂) and the stimulation of their basolateral receptors (EP-Rs). We sought to determine whether gap junctions contribute to the coord...

  10. Mechanisms regulating regional cerebral activation during dynamic handgrip in humans

    Williamson, James; Friedman, D B; Mitchell, J H; Secher, N H; Friberg, L

    1996-01-01

    type of afferent input required for this cerebral activation. The rCBF was measured at +5.0 and +9.0 cm above the orbitomeatal (OM) plane in 13 subjects during 1) rest; 2) dynamic left-hand contractions; 3) postcontraction ischemia (metaboreceptor afferents); and 4) biceps brachii tendon vibration...

  11. Molecular mechanisms of complement activation, regulation and evasion

    Wu, J.

    2012-01-01

    The complement system of our immune defense can rapidly recognize and eliminate pathogens in blood. Activation of complement depends on enzymatic complexes, known as C3 convertases, which are short lived and dissociate irreversibly. Staphylococcus aureus secretes a small protein (named SCIN) that su

  12. Mapping barriers and intervention activities to behaviour change theory for Mobilization of Vulnerable Elders in Ontario (MOVE ON), a multi-site implementation intervention in acute care hospitals

    Moore, Julia E.; Mascarenhas, Alekhya; Marquez, Christine; Almaawiy, Ummukulthum; Chan, Wai-Hin; D’Souza, Jennifer; Liu, Barbara; Straus, Sharon E; ,

    2014-01-01

    Background As evidence-informed implementation interventions spread, they need to be tailored to address the unique needs of each setting, and this process should be well documented to facilitate replication. To facilitate the spread of the Mobilization of Vulnerable Elders in Ontario (MOVE ON) intervention, the aim of the current study is to develop a mapping guide that links identified barriers and intervention activities to behaviour change theory. Methods Focus groups were conducted with ...

  13. [ACTIVITY OF ANTIMICROBIAL NANOSTRUCTURED BARRIER LAYERS BASED ON POLYETHYLENETEREPHTHALATE IN RELATION TO CLINICAL STRAINES OF MICROORGANISMS FOR SICK PERSONS OF GASTROENTEROLOGICAL PROFILE].

    Elinson, V M; Rusanova, E V; Vasilenko, I A; Lyamin, A N; Kostyuchenko, L N

    2015-01-01

    Homeostasis transgressions of enteral medium including disbiotic ones are often accompanying deseases of digestive tract. Espessially it touches upon sick persons connected with probe nourishing. One of the way for solving this problem is normalization of digestion microflore by means of wares with nanotechnological modifications of walls (probes, stomic tubes) which provide them antimicrobial properties and assist to normalization of digestive microbiotis and enteral homeostasis completely. The aim to study is research of antimicrobial activity of of nanostructured barrier layers based on polyethyleneterephthalate (PET) in relation to clinical straines of microorganisms. For barrier layer creation the approach on the base of methods of ion-plasma technology was used including ion-plasma treatment (nanostructuring) of the surface by ions noble and chemically active gases and following formation nanodimensional carbon films on the surface/ For the study of antimicrobial activity in relation to clinical straines of microorganisms we used the technique which allowed to establish the influence of parting degree of microorganisms suspension and time for samples exposing and microorganisms adsorbed on the surface. In experiment clinical straines obtained from different materials were used: Staphylococcus Hly+ and Calbicans--from pharyngeal mucosa, E. coli--from feces, K.pneumoniae--from urine. Sharing out and species identification of microorganisms were fulfilled according with legasy documents. In results of the study itwas obtained not only the presence of staticticaly confirmed antimicrobial activity of PET samples with nanostructured barrier layers in relation to different stimulators of nosocomical infections but also the influence of different factors connected with formation of nanostructured layers and consequently based with them physicochemical characteristics such as, in particular, surface energy, surface relief parameters, surface charg and others, as well

  14. Married men’s perceptions of barriers for HIV-positive pregnant women accessing highly active antiretroviral therapy in rural Uganda

    Duff, Putu; Rubaale, Tom; Kipp, Walter

    2012-01-01

    Background The aim of this study was to describe the perceptions of married men about barriers to accessing and accepting highly active antiretroviral therapy (HAART) by pregnant/postnatal women positive for human immunodeficiency virus (HIV) and registered in Kabarole District’s Program for the Prevention of HIV from Mother to Child (PMTCT-Plus). Materials and methods Our study was a qualitative descriptive exploratory study using thematic analysis. Four focus group discussions were held wit...

  15. Married men’s perceptions of barriers for HIV-positive pregnant women accessing highly active antiretroviral therapy in rural Uganda

    Duff P; Rubaale T; Kipp W.

    2012-01-01

    Putu Duff,1 Tom Rubaale,2 Walter Kipp1,21School of Public Health, University of Alberta, Edmonton, Canada; 2Community ARV Project, Fort Portal, UgandaBackground: The aim of this study was to describe the perceptions of married men about barriers to accessing and accepting highly active antiretroviral therapy (HAART) by pregnant/postnatal women positive for human immunodeficiency virus (HIV) and registered in Kabarole District’s Program for the Prevention of HIV from Mother to Child ...

  16. Redox regulation of the AMP-activated protein kinase.

    Yingying Han

    Full Text Available Redox state is a critical determinant of cell function, and any major imbalances can cause severe damage or death.The aim of this study is to determine if AMP-activated protein kinase (AMPK, a cellular energy sensor, is activated by oxidants generated by Berberine in endothelial cells (EC.Bovine aortic endothelial cells (BAEC were exposed to Berberine. AMPK activity and reactive oxygen species were monitored after the incubation.In BAEC, Berberine caused a dose- and time-dependent increase in the phosphorylation of AMPK at Thr172 and acetyl CoA carboxylase (ACC at Ser79, a well characterized downstream target of AMPK. Concomitantly, Berberine increased peroxynitrite, a potent oxidant formed by simultaneous generation of superoxide and nitric oxide. Pre-incubation of BAEC with anti-oxidants markedly attenuated Berberine-enhanced phosphorylation of both AMPK and ACC. Consistently, adenoviral expression of superoxide dismutase and pretreatment of L-N(G-Nitroarginine methyl ester (L-NAME; a non-selective NOS inhibitor blunted Berberine-induced phosphorylation of AMPK. Furthermore, mitochondria-targeted tempol (mito-tempol pretreatment or expression of uncoupling protein attenuated AMPK activation caused by Berberine. Depletion of mitochondria abolished the effects of Berberine on AMPK in EC. Finally, Berberine significantly increased the phosphorylation of LKB1 at Ser307 and gene silencing of LKB1 attenuated Berberine-enhanced AMPK Thr172 phosphorylation in BAEC.Our results suggest that mitochondria-derived superoxide anions and peroxynitrite are required for Berberine-induced AMPK activation in endothelial cells.

  17. Hemodynamic activation of β-catenin and TCF signaling in vascular endothelium regulates fibronectin expression

    Gelfand, Bradley D.; Meller, Julia; Pryor, Andrew W.; Kahn, Michael; Schoppee Bortz, Pamela D.; Wamhoff, Brian R.; Blackman, Brett R.

    2011-01-01

    β-catenin/TCF signaling regulates a varied set of cellular functions including development and remodeling. Fibronectin is a TCF-regulated gene that is highly expressed in arterial endothelium during atherosclerosis development and contributes to the pathophysiology of the disease. However, the activation of endothelial β-catenin/TCF signaling and its role in fibronectin expression in atherosclerosis are not currently known.

  18. Proposal for regulation of logging activities in oil wells using ionizing radiation sources

    It covers general aspects of nuclear energy and the suitable legal frame for its application related to oil industry. Besides, a regulation proposal to control logging activities in Ecuador using ionizing radiation sources in oil wells. It was prepared taking into account the Ecuadorian Atomic Energy Commission criteria and international regulations

  19. Study on the Model for Regulation of the Allosteric Enzyme Activity

    LI,Qian-Zhong(李前忠); LUO,Liao-Fu(罗辽复); ZHANG,Li-Rong(张利绒)

    2002-01-01

    The effects of activator molecule and repressive molecule on binding process between allosteric enzyme and substrate are disused by considering the heterotropic effect of the regulating molecule that binds to allosteric enzyme. A model of allosteric enzyme with heterotropic effect is presented. The cooperativity and anticooperativity in the regulation process are studied.

  20. 75 FR 69688 - Agency Information Collection Activities: Regulation on Agency Protests

    2010-11-15

    ... SECURITY Agency Information Collection Activities: Regulation on Agency Protests AGENCY: Office of Chief... protests submitted by contractors to federal ] agencies. This regulation provides detailed guidance for... implement the FAR. FAR Part 33.103, Protests, Disputes, and Appeals prescribe policies and procedures...

  1. 78 FR 76851 - Agency Information Collection Activities: BP Regulations Pertaining to Customs Brokers

    2013-12-19

    ... SECURITY U.S. Customs and Border Protection Agency Information Collection Activities: BP Regulations Pertaining to Customs Brokers AGENCY: U.S. Customs and Border Protection (CBP), Department of Homeland... requirement concerning the CBP Regulations Pertaining to Customs Brokers (19 CFR Part 111). This request...

  2. 75 FR 67094 - Agency Information Collection Activities: CBP Regulations Pertaining to Customs Brokers

    2010-11-01

    ... SECURITY Customs and Border Protection Agency Information Collection Activities: CBP Regulations Pertaining to Customs Brokers AGENCY: U.S. Customs and Border Protection, Department of Homeland Security... concerning the: CBP Regulations Pertaining to Customs Brokers (19 CFR Part 111). This request for comment...

  3. Stable siRNA-mediated silencing of antizyme inhibitor: regulation of ornithine decarboxylase activity

    Ornithine decarboxylase (ODC) is the rate-limiting enzyme involved in the biosynthesis of polyamines essential for cell growth and differentiation. Aberrant upregulation of ODC, however, is widely believed to be a contributing factor in tumorigenesis. Antizyme is a major regulator of ODC, inhibiting ODC activity through the formation of complexes and facilitating degradation of ODC by the 26S proteasome. Moreover, the antizyme inhibitor (AZI) serves as another factor in regulating ODC, by binding to antizyme and releasing ODC from ODC-antizyme complexes. In our previous report, we observed elevated AZI expression in tumor specimens. Therefore, to evaluate the role of AZI in regulating ODC activity in tumors, we successfully down-regulated AZI expression using RNA interference technology in A549 lung cancer cells expressing high levels of AZI. Two AZI siRNAs, which were capable to generate a hairpin dsRNA loop targeting AZI, could successively decrease the expression of AZI. Using biological assays, antizyme activity increased in AZI-siRNA-transfected cells, and ODC levels and activity were reduced as well. Moreover, silencing AZI expression decreased intracellular polyamine levels, reduced cell proliferation, and prolonged population doubling time. Our results directly demonstrate that downregulation of AZI regulates ODC activity, intracellular polyamine levels, and cell growth through regulating antizyme activity. This study also suggests that highly expressed AZI may be partly responsible for increased ODC activity and cellular transformation

  4. Aptamer and PNIPAAm co-conjugated nanoparticles regulate activity of enzyme with different temperature.

    Yu, Jiemiao; Yang, Liangrong; Liang, Xiangfeng; Dong, Tingting; Qu, Hongnan; Rong, Meng; Liu, Huizhou

    2016-10-01

    In this paper, we described a temperature responsive nano-system that can regulate activity of enzyme with different temperature. Temperature responsive polymer poly(N-isopropylacrylamide) (PNIPAAm), with low critical solution temperature of 32°C, was synthesized with thiol modification. PNIPAAm and thrombin aptamer were co-functionalized on the surface of gold nanoparticles for effective regulation of thrombin activity with different temperature. On the one hand, we studied the thermal responsive properties of this inhibitor via UV-visible spectroscopy. On the other hand, we investigated the regulation of thrombin activity by this platform with different temperature. The PNIPAAm chains could extend and shrink with different temperature, which suggested that PNIPAAm on the surface of gold nanoparticles could regulate interaction between thrombin and aptamer according to temperature changing. At 25°C, PNIPAAm was hydrophilic extended state, which blocked the interaction between thrombin and aptamer on the surface of gold nanoparticles, therefore thrombin activity had no change. On the contrary, at 37°C, PNIPAAm transformed from hydrophilic extended state to hydrophobic shrank state, allowing the aptamer to capture thrombin, inhibiting the activity of thrombin. More interestingly, this regulation was reverse to normal condition, where 37°C was always the optimum reaction temperature for most of human enzymes. This system we prepared was opposite, which was capable of inhibiting the thrombin activity at 37°C. Furthermore, this was the first report of regulation of thrombin activity using this temperature responsive platform. PMID:27474278

  5. A computational method for the systematic screening of reaction barriers in enzymes: Searching for Bacillus circulans xylanase mutants with greater activity towards a synthetic substrate

    Hediger, Martin R; De Vico, Luca; Jensen, Jan H

    2013-01-01

    We present a semi-empirical (PM6-based) computational method for systematically estimating the effect of all possible single mutants, within a certain radius of the active site, on the barrier height of an enzymatic reaction. The intent of this method is not a quantitative prediction of the barrier heights, but rather to identify promising mutants for further computational or experimental study. The method is applied to identify promising single and double mutants of Bacillus circulans xylanase (BCX) with increased hydrolytic activity for the artificial substrate ortho-nitrophenyl \\beta-xylobioside (ONPX$_2$). The estimated reaction barrier for wild-type (WT) BCX is 18.5 kcal/mol, which is in good agreement with the experimental activation free energy value of 17.0 kcal/mol extracted from the observed k$_\\text{cat}$ using transition state theory (Joshi et al., Biochemistry 2001, 40, 10115). The PM6 reaction profiles for eight single point mutations are recomputed using FMO-MP2/PCM/6-31G(d) single points. PM6 ...

  6. Health system barriers to implementation of collaborative TB and HIV activities including prevention of mother to child transmission in South Africa.

    Uwimana, J; Jackson, D; Hausler, H; Zarowsky, C

    2012-05-01

    In South Africa, the control of TB and HIV co-infection remains a major challenge despite the availability of international and national guidelines for integration of TB and HIV services. This study was undertaken in KwaZulu-Natal, one of the provinces most affected by both TB and HIV, to identify and understand managers' and community care workers' (CCWs) perceptions of health systems barriers related to the implementation of collaborative TB/HIV activities, including prevention of mother to child transmission of HIV (PMTCT). We conducted 29 in-depth interviews with health managers at provincial, district and facility level and with managers of NGOs involved in TB and HIV care, as well as six focus group discussions with CCWs. Thematic analysis of transcripts revealed a convergence of perspectives on the process and the level of the implementation of policy directives on collaborative TB and HIV activities across all categories of respondents (i.e. province-, district-, facility- and community-based organizations). The majority of participants felt that the implementation of the policy was insufficiently consultative and that leadership and political will were lacking. The predominant themes related to health systems barriers include challenges related to structure and organisational culture; management, planning and power issues; unequal financing; and human resource capacity and regulatory problems notably relating to scope of practice of nurses and CCWs. Accelerated implementation of collaborative TB/HIV activities including PMTCT will require political will and leadership to address these health systems barriers. PMID:22394016

  7. 77 FR 76292 - Agency Information Collection Activities; Comment Request; Regulations for Equity in Athletics...

    2012-12-27

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF EDUCATION Agency Information Collection Activities; Comment Request; Regulations for Equity in Athletics Disclosure Act (EADA) AGENCY: The Office of Postsecondary Education (OPE), Department of Education (ED)....

  8. Regulation of drugs affecting striatal cholinergic activity by corticostriatal projections

    Research demonstrates that the chronic degeneration of the corticostriatal excitatory pathway makes the cholinergic neurons of the striatum insensitive to the neuropharmacological action of a number of different drugs. Female rats were used; they were killed and after the i.v. infusion of tritium-choline precursor, choline acetyltransferase activity was measured. Striatal noradrenaline, dopamine and serotonin content was measured by electrochemical detection coupled with high pressure liquid chromatography. Uptake of tritium-glutamic acid was estimated. The data were analyzed statistically. It is shown that there is evidence that the effects of a number of drugs capable of depressing cholinergic activity through receptor-mediated responses are operative only if the corticostriatal pathway is integral. Neuropharmacological responses in the brain appear to be the result of an interaction between several major neurotransmitter systems

  9. Down-regulation of human neutrophil activity by natural polyphenols

    Drábiková, K.; Perečko, T.; Nosáľ, R.; Harmatha, Juraj; Šmidrkal, J.; Jančinová, V.

    Bratislava : Institute of Experimental Pharmacology & Toxicology SAS, 2012 - (Bauer, V.; Mach, M.; Navarová, J.; Sotníková, R.), s. 98-108 ISBN 978-80-971042-0-7. [Drugs: Their Action in Pharmacology and Toxicology. Bratislava (SK), 31.05.2012] Institutional research plan: CEZ:AV0Z40550506 Keywords : activity of neutrophils * reactive oxygen species * natural polyphenols Subject RIV: CC - Organic Chemistry

  10. Osteoblast differentiation and migration are regulated by Dynamin GTPase activity

    Pierre P. Eleniste; Huang, Su; Wayakanon, Kornchanok; Largura, Heather W.; Bruzzaniti, Angela

    2013-01-01

    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...

  11. Subcellular localization of PUMA regulates its pro-apoptotic activity in Burkitt's lymphoma B cells

    Ambroise, Gorbatchev; Portier, Alain; Roders, Nathalie; Arnoult, Damien; Vazquez, Aimé

    2015-01-01

    The BH3-only protein PUMA (p53-upregulated modulator of apoptosis) is a major regulator of apoptosis. It belongs to the Bcl-2 family of proteins responsible for maintaining mitochondrial outer membrane integrity by controlling the intrinsic (mitochondrial) apoptotic pathway. We describe here a new pathway regulating PUMA activation through the control of its subcellular distribution. Surprisingly, neither PUMA upregulation in normal activated human B lymphocytes nor high levels of PUMA in Bur...

  12. Application of the Positive International Experience of Tax Regulation of Investment and Innovation Activity in Ukraine

    Krisovatyy Ihor A.

    2013-01-01

    The goal of the article is to study the positive international experience in the sphere of tax regulation of investment and innovation activity and a possibility of its use in modern practice. It analyses application of basic instruments of stimulation of investment and innovation activity in foreign countries. Namely: change of the taxation base, tax rate, use of the innovation loan and investment oriented depreciation policy. Using the study of experience of tax regulation in foreign countr...

  13. Diacylglycerol kinase theta and zeta isoforms: regulation of activity, protein binding partners and physiological functions

    Los, Alrik Pieter

    2007-01-01

    Diacylglycerol kinases (DGKs) phosphorylate the second messenger diacylglycerol (DAG) yielding phosphatidic acid (PA). In this thesis, we investigated which structural domains of DGKtheta are required for DGK activity. Furthermore, we showed that DGKzeta binds to and is activated by the Retinoblastoma tumour suppressor protein (pRB) and the pRB-related proteins p107 and p130, key regulators of the cell-cycle, differentiation and apoptosis. The interaction between pRB and DGKzeta is regulated ...

  14. Evaluation on changes caused by volcanic activities in the groundwater environment as a natural barrier for the HLW disposal. Literature survey and groundwater observation conducted at Mt. Iwate

    It is very important in the site characterization for the HLW disposal to understand changes in geochemical performances caused by volcanic activities in the groundwater environment as the natural barrier. The various effects and its magnitude of changes were listed up and were filed from literature surveys of the correlation between volcanic activities and hydrological can geochemical changes (e.g. water temperature, water pressure, water level, dissolved gas concentration of He and Rn, isotopic ratio of He, and chloride concentration) in volcanic aquifer. However, it is difficult to evaluate the magnitude of impacts, which volcanic activities will give to the groundwater environment in the natural barrier, through only the literature surveys. We have started monitoring of groundwater level and changes in groundwater quality, since volcanic activities have enhanced at Mt. Iwate from June in 1998. Judging from variation of isotopic ratio of dissolved He in groundwater, a prompt and sharp signals indicating volcanic activities will easily be found in shallow groundwater and discharged ponds. On the other hands, geochemical conditions in deep groundwater surroundings from some 100 m to 1000 m deep will be very stable, if the area being more than 5 km apart from the volcanic active center. Consequently, our observed results suggest that the groundwater environment which is not directly disturbed by the underground magmatic activities spreads under the area that is connected to trench side of the volcanic front. (author)

  15. Information barriers

    An information barrier (IB) consists of procedures and technology that prevent the release of sensitive information during a joint inspection of a sensitive nuclear item, and provides confidence that the measurement system into which it has been integrated functions exactly as designed and constructed. Work in the U.S. on radiation detection system information barriers dates back at least to 1990, even though the term is more recent. In January 1999, an Information Barrier Working Group (IBWG) was formed in the United States to help coordinate technical efforts related to information barrier research and development (R and D). This paper presents an overview of the efforts of this group, by its present and former Chairs, as well as recommendations for further information barrier R and D. Progress on the demonstration of monitoring systems containing IBs is also provided. From the U.S. IBWG perspective, the top-level functional requirements for the information barrier portion of an integrated radiation signature-information barrier inspection system are twofold: The host must be assured that its classified information is protected from disclosure to the inspecting party; and The inspecting party must be confident that the integrated inspection system measures, processes, and presents the radiation-signature-based measurement conclusion in an accurate and reproducible manner. It is the position in the United States that in the absence of any agreement to share classified nuclear weapons design information while implementing an inspection regime, the need to protect host country classified warhead design information is paramount and overrules the need to provide confidence to the inspecting party regarding the accuracy and reproducibility of the measurements. The U.S. IBWG has reached a consensus on several critical design elements that define a general standard for radiation signature information barrier design. Technical specialists from cooperating parties must be

  16. GITR Activation Positively Regulates Immune Responses against Toxoplasma gondii

    Costa, Frederico R. C.; Mota, Caroline M.; Santiago, Fernanda M.; Silva, Murilo V.; Ferreira, Marcela D.; Fonseca, Denise M.; Silva, João S.; Mineo, José R.; Mineo, Tiago W. P.

    2016-01-01

    Toxoplasma gondii is a widespread parasite responsible for causing clinical diseases especially in pregnant and immunosuppressed individuals. Glucocorticoid-induced TNF receptor (GITR), which is also known as TNFRS18 and belongs to the TNF receptor superfamily, is found to be expressed in various cell types of the immune system and provides an important costimulatory signal for T cells and myeloid cells. However, the precise role of this receptor in the context of T. gondii infection remains elusive. Therefore, the current study investigated the role of GITR activation in the immunoregulation mechanisms induced during the experimental infection of mice with T. gondii. Our data show that T. gondii infection slightly upregulates GITR expression in Treg cells and B cells, but the most robust increment in expression was observed in macrophages and dendritic cells. Interestingly, mice infected and treated with an agonistic antibody anti-GITR (DTA-1) presented a robust increase in pro-inflammatory cytokine production at preferential sites of parasite replication, which was associated with the decrease in latent brain parasitism of mice under treatment with DTA-1. Several in vivo and in vitro analysis were performed to identify the cellular mechanisms involved in GITR activation upon infection, however no clear alterations were detected in the phenotype/function of macrophages, Tregs and B cells under treatment with DTA-1. Therefore, GITR appears as a potential target for intervention during infection by the parasite Toxoplasma gondii, even though further studies are still necessary to better characterize the immune response triggered by GITR activation during T. gondii infection. PMID:27027302

  17. “I don’t have the heart”: a qualitative study of barriers to and facilitators of physical activity for people with coronary heart disease and depressive symptoms

    Rogerson Michelle C

    2012-11-01

    Full Text Available Abstract Background Physical activity has been shown to reduce depression in people with coronary heart disease (CHD, however many people with CHD do not engage in sufficient levels of physical activity to reap its positive effects. People with depression and CHD are at particular risk of non-adherence to physical activity. Little is known about the barriers to and facilitators of physical activity for people with CHD and depressive symptoms. Using qualitative interviews, the aim of this study was to explore the barriers to and facilitators of physical activity for cardiac patients with depressive symptoms. Methods Fifteen participants with CHD and depressive symptoms (assessed using the Cardiac Depression Scale participated in in-depth semi-structured interviews. The interviews were focussed on investigating participants’ experiences of physical activity since their cardiac event. Interviews were content analysed to determine major themes. Results Participants identified a number of barriers to and facilitators of physical activity. Barriers included having negative perceptions towards health and life changes as a result of the cardiac event, having low mood and low motivation to exercise, feeling physically restricted towards or fearful of exercise, lacking knowledge regarding exercise and perceiving external barriers. Facilitators included having a reason for exercising, being able to identify the psychological benefits of exercise, having positive social support and using psychological strategies. ‘Inactive’ participants reported more barriers and fewer facilitators than did ‘active’ participants. Conclusions The barriers reported in this study were highly salient for a number of participants. Health professionals and researchers can use this information to assist people with CHD and depressive symptoms to identify and possibly overcome barriers to physical activity. Relevant barriers and facilitators could be taken into account to

  18. Activating transcription factor 4 regulates osteoclast differentiation in mice

    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

    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 ...

  19. Tonic activity of Gα-gustducin regulates taste cell responsivity

    Clapp, Tod R.; Trubey, Kristina R.; Vandenbeuch, Aurelie; Stone, Leslie M; Margolskee, Robert F.; Chaudhari, Nirupa; Kinnamon, Sue C.

    2008-01-01

    The taste-selective G protein, α-gustducin (α-gus) is homologous to α-transducin and activates phosphodiesterase in vitro. α-Gustducin-knockout mice are compromised to bitter, sweet and umami taste stimuli, suggesting a central role in taste transduction. Here, we suggest a different role for Gα-gustducin. In taste buds of α-gustducin knockout mice, basal (unstimulated) cAMP levels are high compared to those of wild-type mice. Further, H-89, a cAMP-dependent Protein Kinase inhibitor, dramatic...

  20. Barriers to Screening and Possibilities for Active Detection of Family Medicine Attendees Exposed to Intimate Partner Violence

    Kopčavar Guček Nena

    2016-03-01

    Full Text Available In 1996 the World Health Organization declared intimate partner violence (IPV the most important public health problem. Meta-analyses in 2013 showed every third female globally had been a victim of violence. Experts find screening controversial; family medicine is the preferred environment for identifying victims of violence, but barriers on both sides prevent patients from discussing it with doctors.

  1. Phagocytic activity of neuronal progenitors regulates adult neurogenesis.

    Lu, Zhenjie; Elliott, Michael R; Chen, Yubo; Walsh, James T; Klibanov, Alexander L; Ravichandran, Kodi S; Kipnis, Jonathan

    2011-09-01

    Whereas thousands of new neurons are generated daily during adult life, only a fraction of them survive and become part of neural circuits; the rest die, and their corpses are presumably cleared by resident phagocytes. How the dying neurons are removed and how such clearance influences neurogenesis are not well understood. Here, we identify an unexpected phagocytic role for the doublecortin (DCX)-positive neuronal progenitor cells during adult neurogenesis. Our in vivo and ex vivo studies demonstrate that DCX(+) cells comprise a significant phagocytic population within the neurogenic zones. Intracellular engulfment protein ELMO1, which promotes Rac activation downstream of phagocytic receptors, was required for phagocytosis by DCX(+) cells. Disruption of engulfment in vivo genetically (in Elmo1-null mice) or pharmacologically (in wild-type mice) led to reduced uptake by DCX(+) cells, accumulation of apoptotic nuclei in the neurogenic niches and impaired neurogenesis. Collectively, these findings indicate a paradigm wherein DCX(+) neuronal precursors also serve as phagocytes, and that their phagocytic activity critically contributes to neurogenesis in the adult brain. PMID:21804544

  2. Xanthine oxidase activity regulates human embryonic brain cells growth

    Kevorkian G. A.

    2011-10-01

    Full Text Available Aim. Involvement of Xanthine Oxidase (XO; EC1.1.3.22 in cellular proliferation and differentiation has been suggested by the numerous investigations. We have proposed that XO might have undoubtedly important role during the development, maturation as well as the death of human embryos brain cells. Methods. Human abortion material was utilized for the cultivation of brain cells (E90. XO activity was measured by the formation of uric acid in tissue. Cell death was detected by the utility of Trypan Blue dye. Results. Allopurinol suppressed the XO activity in the brain tissue (0.12 ± 0.02; 0.20 ± 0.03 resp., p < 0.05. On day 12th the number of cells in the culture treated with the Allopurinol at the early stage of development was higher in comparison with the Control (2350.1 ± 199.0 vs 2123 ± 96 and higher in comparison with the late period of treatment (1479.6 ± 103.8, p < < 0.05. In all groups, the number of the dead cells was less than in Control, indicating the protective nature of Allopurinol as an inhibitor of XO. Conclusions. Allopurinol initiates cells proliferation in case of the early treatment of the human brain derived cell culture whereas at the late stages it has an opposite effect.

  3. AMP-Activated Protein Kinase Regulates Oxidative Metabolism in Caenorhabditis elegans through the NHR-49 and MDT-15 Transcriptional Regulators

    Moreno-Arriola, Elizabeth; EL Hafidi, Mohammed; Ortega-Cuéllar, Daniel; Carvajal, Karla

    2016-01-01

    Cellular energy regulation relies on complex signaling pathways that respond to fuel availability and metabolic demands. Dysregulation of these networks is implicated in the development of human metabolic diseases such as obesity and metabolic syndrome. In Caenorhabditis elegans the AMP-activated protein kinase, AAK, has been associated with longevity and stress resistance; nevertheless its precise role in energy metabolism remains elusive. In the present study, we find an evolutionary conserved role of AAK in oxidative metabolism. Similar to mammals, AAK is activated by AICAR and metformin and leads to increased glycolytic and oxidative metabolic fluxes evidenced by an increase in lactate levels and mitochondrial oxygen consumption and a decrease in total fatty acids and lipid storage, whereas augmented glucose availability has the opposite effects. We found that these changes were largely dependent on the catalytic subunit AAK-2, since the aak-2 null strain lost the observed metabolic actions. Further results demonstrate that the effects due to AAK activation are associated to SBP-1 and NHR-49 transcriptional factors and MDT-15 transcriptional co-activator, suggesting a regulatory pathway that controls oxidative metabolism. Our findings establish C. elegans as a tractable model system to dissect the relationship between distinct molecules that play a critical role in the regulation of energy metabolism in human metabolic diseases. PMID:26824904

  4. State regulation issues of intermediary activity of customs brokers in Ukraine

    Onyshchenko Svitlana; Korobkova Olena

    2013-01-01

    Regulatory influence in the sphere of service provision of customs affairs’ business activity is reviewed in the article; the problem of structural change in customs authority, creation of conditions for foreign-economic activity and transfer of such activity’s control function to Ministry of revenues and duties of Ukraine aiming at public interest protection; state regulation of customs intermediary’s activity and enhancing control of intermediary activity in the customs affair branch, using...

  5. Legal Instruments of Regulation of Development of Banking Activity in Ukraine

    Senyshch Pavlo M.

    2014-03-01

    Full Text Available The article considers main approaches to identification of essence of legal instruments of regulation of development of the banking activity, identifies the mechanism of legal regulation of the banking activity and its elements and justifies the system and form of legal regulation of the banking activity in Ukraine. It describes subjects of legal regulation of the banking activity at the international level, which are the Basel Committee on Banking Supervision, European Central Bank, IMF, International Financial Reporting Standards Foundation and others. The article considers specific features of the regulatory requirements of Basel II and Basel III and specific features of their introduction into the banking activity. It describes anti-cyclic measures offered by the Basel Committee, which should facilitate formation of such conditions, under which the banking sector could have a lower level of leverage and stability with respect to influence of system risks. Significant attention is paid to international instruments of regulation of the banking activity, which include the following legal acts: Uniform Rules for Collections, Uniform Customs and Practice for Documentary Credits, and Unified Rules for Loan Guarantees. The article shows that the share of subordinate legal acts is significant in the Ukrainian system of banking regulatory and legal acts since the state cannot operatively react to the changing processes in banking at the legislative level and, that is why, basic provisions on carrying out banking activity should be fixed in law.

  6. NON-TARIFF TRADE BARRIERS IN AGRICULTURE

    Mattson, Jeremy W.; Koo, Won W.; Taylor, Richard D.

    2004-01-01

    As trade agreements lower tariff rates throughout the world, other barriers to trade emerge. These non-tariff barriers can be just as troublesome for exporting companies. Non-tariff barriers include technical measures, customs rules and procedures, transport regulations or costs, lack of knowledge of regional markets, and import policies. The objective of this study is to identify non-tariff barriers faced by U.S., and more specifically North Dakota, exporting businesses, especially those inv...

  7. Zinc oxide influences mitogen-activated protein kinase and TGF-β1 signaling pathways, and enhances intestinal barrier integrity in weaned pigs.

    Song, Ze He; Xiao, Kan; Ke, Ya Lu; Jiao, Le Fei; Hu, Cai Hong

    2015-05-01

    Weaning is the most significant event in the life of pigs and is always related with intestinal disruption. Although it is well known that zinc oxide (ZnO) exerts beneficial effects on the intestinal barrier, the mechanisms underlying these effects have not yet been fully elucidated. We examined whether ZnO protects the intestinal barrier via mitogen-activated protein kinases and TGF-β1 signaling pathways. Twelve barrows weaned at 21 d of age were randomly assigned to two treatments (0 verus 2200 mg Zn/kg from ZnO) for 1 wk. The results showed that supplementation with ZnO increased daily gain and feed intake, and decreased postweaning scour scores. ZnO improved intestinal morphology, as indicated by increased villus height and villus height:crypt depth ratio, and intestinal barrier function, indicated by increased transepithelial electrical resistance and decreased mucosal-to-serosal permeability to 4-ku FITC dextran. ZnO decreased the ratios of the phosphorylated to total JNK and p38 (p-JNK/JNK and p-p38/p38), while it increased the ratio of ERK (p-ERK/ERK). Supplementation with ZnO increased intestinal TGF-β1 expression. The results indicate that supplementation with ZnO activates ERK ½, and inhibits JNK and p38 signaling pathways, and increases intestinal TGF-β1 expression in weaned pigs. PMID:24917655

  8. Partial Oxidation of Methane with Sol-Gel Fe/Hf/YSZ Catalyst in Dielectric Barrier Discharge: Catalyst Activation by Plasma

    2006-01-01

    A 1% Fe-30% Hf over yttria-stabilized zirconia catalyst in combination with novel plasma-assisted activation techniques for a direct partial oxidation of methane to methanol was tested using dielectric barrier discharge plasma at ambient temperature and atmospheric pressure. However, instead of methanol, the reaction products were dominated by H2,CO, CO2, C2, and H2O. A catalytically activated plasma process increased the production of methanol compared with a noncatalytic plasma process. The maximum selectivity of methanol production was achieved using a catalyst that was treated at higher applied power.

  9. Reciprocal regulation of LXRα activity by ASXL1 and ASXL2 in lipogenesis

    Park, Ui-Hyun; Seong, Mi-ran [Department of Bioscience and Biotechnology, Institute of Bioscience, BK21 Graduate Program, Sejong University, Seoul 143-747 (Korea, Republic of); Kim, Eun-Joo; Hur, Wonhee; Kim, Sung Woo [Department of Molecular Biology, BK21 Graduate Program, Dankook University, Gyeonggi-do 448-701 (Korea, Republic of); Yoon, Seung Kew [The Catholic University Liver Research Center and WHO Collaborating Center of Viral Hepatitis, The Catholic University, College of Medicine, Seoul 137-701 (Korea, Republic of); Um, Soo-Jong, E-mail: umsj@sejong.ac.kr [Department of Bioscience and Biotechnology, Institute of Bioscience, BK21 Graduate Program, Sejong University, Seoul 143-747 (Korea, Republic of)

    2014-01-10

    Highlights: •ASXL1 and ASXL2 directly interact with ligand-bound LXRα. •Ligand-induced LXRα activity is repressed by ASXL1 and activated by ASXL2. •ASXL1 and ASXL2 bind to the LXRE of the LXRα target promoter. •ASXL1 and ASXL2 reciprocally regulate lipogenesis in liver cells. -- Abstract: Liver X receptor alpha (LXRα), a member of the nuclear receptor superfamily, plays a pivotal role in hepatic cholesterol and lipid metabolism, regulating the expression of genes associated with hepatic lipogenesis. The additional sex comb-like (ASXL) family was postulated to regulate chromatin function. Here, we investigate the roles of ASXL1 and ASXL2 in regulating LXRα activity. We found that ASXL1 suppressed ligand-induced LXRα transcriptional activity, whereas ASXL2 increased LXRα activity through direct interaction in the presence of the ligand. Chromatin immunoprecipitation (ChIP) assays showed ligand-dependent recruitment of ASXLs to ABCA1 promoters, like LXRα. Knockdown studies indicated that ASXL1 inhibits, while ASXL2 increases, lipid accumulation in H4IIE cells, similar to their roles in transcriptional regulation. We also found that ASXL1 expression increases under fasting conditions, and decreases in insulin-treated H4IIE cells and the livers of high-fat diet-fed mice. Overall, these results support the reciprocal role of the ASXL family in lipid homeostasis through the opposite regulation of LXRα.

  10. Mechanistic studies of anticancer aptamer AS1411 reveal a novel role for nucleolin in regulating Rac1 activation.

    Reyes-Reyes, E Merit; Šalipur, Francesca R; Shams, Mitra; Forsthoefel, Matthew K; Bates, Paula J

    2015-08-01

    AS1411 is a G-rich quadruplex-forming oligodeoxynucleotide that binds specifically to nucleolin, a protein found on the surface and in the cytoplasm of most malignant cells but absent from the surface/cytoplasm of most normal cells. AS1411 has shown promising clinical activity and is being widely used as a tumor-targeting agent, but its mechanism of action is not fully understood. Previously, we showed that AS1411 is taken up in cancer cells by macropinocytosis (fluid phase endocytosis) and subsequently stimulates further macropinocytosis by a nucleolin-dependent mechanism. In the current study, we have investigated the significance and molecular mechanisms of AS1411-induced macropinocytosis. Our results indicate that the antiproliferative activity of AS1411 in various cell lines correlated with its capacity to stimulate macropinocytosis. In DU145 prostate cancer cells, AS1411 induced activation of EGFR, Akt, p38, and Rac1. Activation of Akt and p38 were not critical for AS1411 activity because Akt activation was not observed in all AS1411-responsive cell lines and knockdown of p38 had no effect on AS1411's ability to inhibit proliferation. On the other hand, activation of EGFR and Rac1 appeared to play a role in AS1411 activity in all cancer cell lines examined (DU145, MDA-MB-468, A549, LNCaP) and their inhibition significantly reduced AS1411-mediated macropinocytosis and AS1411 antiproliferative activity. Interestingly, downregulation of nucleolin expression by siRNA also produced a substantial increase in activated Rac1, revealing a previously unknown role for nucleolin as a negative regulator of Rac1 activation. Our results are consistent with a model whereby AS1411 binding to nucleolin leads to sustained activation of Rac1 and causes methuosis, a novel type of nonapoptotic cell death characterized by hyperstimulation of macropinocytosis. We speculate that methuosis is a tumor/metastasis suppressor mechanism that opposes the malignant functions of Rac1 and that

  11. Skin barrier in rosacea.

    Addor, Flavia Alvim Sant'Anna

    2016-01-01

    Recent studies about the cutaneous barrier demonstrated consistent evidence that the stratum corneum is a metabolically active structure and also has adaptive functions, may play a regulatory role in the inflammatory response with activation of keratinocytes, angiogenesis and fibroplasia, whose intensity depends primarily on the intensity the stimulus. There are few studies investigating the abnormalities of the skin barrier in rosacea, but the existing data already show that there are changes resulting from inflammation, which can generate a vicious circle caused a prolongation of flare-ups and worsening of symptoms. This article aims to gather the most relevant literature data about the characteristics and effects of the state of the skin barrier in rosacea. PMID:26982780

  12. Regulation of antioxidant enzyme activities in male and female rat macrophages by sex steroids

    Azevedo R.B.

    2001-01-01

    Full Text Available Human and animal immune functions present sex dimorphism that seems to be mainly regulated by sex hormones. In the present study, the activities of the antioxidant enzymes total superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GSH-Px were measured in intraperitoneal resident macrophages from adult male and female rats. In addition to comparing males and females, we also examined the regulation of these enzyme activities in macrophages by sex steroids. GSH-Px activity did not differ between male and female macrophages. However, both total SOD and CAT activities were markedly higher in females than in males (83 and 180%. Removal of the gonads in both males and females (comparison between castrated groups increased the difference in SOD activity from 83 to 138% and reduced the difference in CAT activity from 180 to 86%. Castration and testosterone administration did not significantly modify the activities of the antioxidant enzymes in male macrophages. Ovariectomy did not affect SOD or GSH-Px activity but markedly reduced (48% CAT activity. This latter change was fully reversed by estrogen administration, whereas progesterone had a smaller effect. These results led us to conclude that differences in the SOD and CAT activities may partially explain some of the differences in immune function reported for males and females. Also, estrogen is a potent regulator of CAT in macrophages and therefore this enzyme activity in macrophages may vary considerably during the menstrual cycle.

  13. Emotion Regulation and Excess Weight: Impaired Affective Processing Characterized by Dysfunctional Insula Activation and Connectivity

    Mata, Fernanda; Martínez-Zalacaín, Ignacio; Cano, Marta; Contreras-Rodríguez, Oren; Fernández-Aranda, Fernando; Yucel, Murat; Soriano-Mas, Carles; Verdejo-García, Antonio

    2016-01-01

    Emotion-regulation strategies are understood to influence food intake. This study examined the neurophysiological underpinnings of negative emotion processing and emotion regulation in individuals with excess weight compared to normal-weight controls. Fifteen participants with excess-weight (body mass index >25) and sixteen normal-weight controls (body mass index 18–25) performed an emotion-regulation task during functional magnetic resonance imaging. Participants were exposed to 24 negative affective or neutral pictures that they were instructed to Observe (neutral pictures), Maintain (sustain the emotion elicited by negative pictures) or Regulate (down-regulate the emotion provoked by negative pictures through previously trained reappraisal techniques). When instructed to regulate negative emotions by means of cognitive reappraisal, participants with excess weight displayed persistently heightened activation in the right anterior insula. Decreased responsivity was also found in right anterior insula, the orbitofrontal cortex and cerebellum during negative emotion experience in participants with excess weight. Psycho-physiological interaction analyses showed that excess-weight participants had decreased negative functional coupling between the right anterior insula and the right dlPFC, and the bilateral dmPFC during cognitive reappraisal. Our findings support contentions that excess weight is linked to an abnormal pattern of neural activation and connectivity during the experience and regulation of negative emotions, with the insula playing a key role in these alterations. We posit that ineffective regulation of emotional states contributes to the acquisition and preservation of excess weight. PMID:27003840

  14. Comparing Models for Generating a System of Activation and Inhibition of Self-Regulated Learning

    Magno, Carlo

    2008-01-01

    The study investigated the effect of activation and negative affect on self-regulation. The activation factors are self-determination, disengagement, initiative, and persistence while negative affect is composed of worry, anxiety, thought suppression, and fear of negative evaluation. Separate measures were used for each factor and administered to…

  15. An activator of transcription regulates phage TP901-1 late gene expression

    Brøndsted, Lone; Pedersen, Margit; Hammer, Karin

    2001-01-01

    A promoter active in the late phase of the lytic cycle of lactococcal bacteriophage TP901-1 has been identified. The promoter is tightly regulated and requires the product of the phage TP901-1 orf29 for activity. A deletion analysis of the late promoter region showed that a fragment as small as 99...... activate transcription of the promoter. Several lactococcal bacteriophages encode ORF29 homologous proteins, indicating that late transcription may be controlled by a similar mechanism in these phages. With the identification of this novel regulator, our results suggest that within the P335 group of...

  16. Cyclic dermal BMP signaling regulates stem cell activation during hair regeneration

    Plikus, Maksim V; Mayer, Julie; de la Cruz, Damon; Baker, Ruth E.; Maini, Philip K.; Maxson, Robert; Chuong, Cheng-ming

    2008-01-01

    In the age of stem cell engineering, it is critical to understand how stem cell activity is regulated during regeneration. Hairs are mini-organs that undergo cyclic regeneration throughout adult life,1 and are an important model for organ regeneration. Hair stem cells located in the follicle bulge2 are regulated by the surrounding micro-environment, or niche3. The activation of such stem cells is cyclic, involving periodic β-catenin activity4–7. In adult mouse, regeneration occurs in waves in...

  17. Assessment, Problems and Ways of Improvement of Technical Regulation of Foreign Economic Activity (FEA in the World

    Steblyanko Maryna D.

    2013-12-01

    Full Text Available The article analyses the state of technical regulation of FEA in the world and Ukraine and identifies main problems and ways of increase of efficiency of certification. It considers the system of technical regulation of EU and provides examples of application of technical barriers by some countries for ensuring security of goods in the domestic market. The article offers to develop a strategy of development of the national system of information provision of technical regulation and suspend transition from the system of mandatory certification to the system of assessment of correspondence with requirements of technical orders of business.

  18. Characterization of Adapter Protein NRBP as a Negative Regulator of T Cell Activation

    WANG Hui; LIN Zhi-xin; WU Jun

    2008-01-01

    Adapter proteins can regulate the gene transcriptions in disparate signaling pathway by interacting with multiple signaling molecules, including T cell activation signaling. Nuclear receptor binding protein (NRBP), a novel adapter protein, represents a small family of evolutionarily conserved proteins with homologs in Caenorhabditis elegans (C. elegans), Drosophila melanogaster (D.melanogaster), mouse and human. Here, we demonstrated that overexpression of NRBP in Jurkat TAg cells specifically impairs T cell receptor (TCR) or phorbol myristate acetate (PMA)/ionomycin-mediated signaling leading to nuclear factor of activated T cells (NFAT) promoter activation. Furthermore, the N-terminal of NRBP is necessary for its regulation of NFAT activation. Finally, we showed that NRBP has minimal effect on both TCR- and PMA-induced CD69 up-regulation in Jurkat TAg cells, which suggests that NRBP may function downstream of protein kinase C (PKC)/Ras pathway.

  19. Post-translational Control of the Temporal Dynamics of Transcription Factor Activity Regulates Neurogenesis.

    Quan, Xiao-Jiang; Yuan, Liqun; Tiberi, Luca; Claeys, Annelies; De Geest, Natalie; Yan, Jiekun; van der Kant, Rob; Xie, Wei R; Klisch, Tiemo J; Shymkowitz, Joost; Rousseau, Frederic; Bollen, Mathieu; Beullens, Monique; Zoghbi, Huda Y; Vanderhaeghen, Pierre; Hassan, Bassem A

    2016-01-28

    Neurogenesis is initiated by the transient expression of the highly conserved proneural proteins, bHLH transcriptional regulators. Here, we discover a conserved post-translational switch governing the duration of proneural protein activity that is required for proper neuronal development. Phosphorylation of a single Serine at the same position in Scute and Atonal proneural proteins governs the transition from active to inactive forms by regulating DNA binding. The equivalent Neurogenin2 Threonine also regulates DNA binding and proneural activity in the developing mammalian neocortex. Using genome editing in Drosophila, we show that Atonal outlives its mRNA but is inactivated by phosphorylation. Inhibiting the phosphorylation of the conserved proneural Serine causes quantitative changes in expression dynamics and target gene expression resulting in neuronal number and fate defects. Strikingly, even a subtle change from Serine to Threonine appears to shift the duration of Atonal activity in vivo, resulting in neuronal fate defects. PMID:26824657

  20. Family Child Care Providers’ Compliance With State Physical Activity Regulations, Delaware Child Care Provider Survey, 2011

    Sarah Williams Leng, MA

    2013-07-01

    Full Text Available Introduction Delaware is one state that has implemented comprehensive child care regulations to foster healthy dietary and physical activity behaviors of young children. This study describes the Delaware family child care environment and providers’ knowledge of and compliance with physical activity regulations. We analyzed the data to determine characteristics associated with predictors of knowledge of and compliance with these regulations. Methods A random stratified sample of 663 licensed Delaware family child care providers was mailed a survey on family child care characteristics and providers’ awareness and practices of the child care regulations. Three logistic regression models were used to explore the association between provider characteristics and their knowledge of and compliance with the regulations. Results Ultimately, 313 of the 663 eligible family child care providers participated in the survey (47.2% response rate. Controlling for covariates, we found that family child care providers’ education level was significantly associated with knowledge of the physical activity regulation. Another model showed that family child care providers with larger amounts of outdoor space were more likely to report compliance with the recommendation for unstructured physical activity than those without this described space (odds ratio, 2.45. A third model showed a significant association between available indoor space for all activities including running and reported greater compliance with the recommendation for structured physical activity than was reported by caregivers with less indoor space (odds ratio, 11.2. Conclusion To provide the recommended levels of physical activity for children in child care, the available physical space environment is an important area of focus for advocates of physical activity recommendations within the family child care environment.

  1. Understanding contextual barriers, supports, and opportunities for physical activity among Mexican-origin children in Texas border colonias: A descriptive study

    Umstattd Meyer M Renée

    2013-01-01

    Full Text Available Abstract Background The increasing numbers of colonias along the U.S.-Mexico border are characterized by disproportionately poor families of Mexican-origin, limited access to resources and health services, and heightened risk for obesity and diabetes. Despite consistent evidence supporting physical activity (PA in prevention of chronic diseases, many individuals of Mexican-origin, including children, fail to meet PA recommendations. Environmental influences on PA, founded in ecological and social cognitive perspectives, have not been examined among children living in colonias. The purpose of this study was to identify and better understand (1 household and neighborhood environmental PA resources/supports, (2 perceived barriers to engaging in PA, and (3 PA offerings, locations, and transportation characteristics for Mexican-origin children living in colonias. Methods Data for this study were collected by promotora-researchers (indigenous community health workers trained in research methods using face-to-face interviews conducted in Spanish. The sample consists of 94 mother-child dyads from Texas border colonias in Hidalgo County. Interviews included questionnaire items addressing PA barriers, household and neighborhood environmental support assessments conducted with each dyad, and open-ended questions that were coded to identify availability and locations of PA opportunities and transportation options. Descriptive statistics were calculated and differences between genders, birth countries, and BMI categories of children were determined using chi-square tests. Results All children were of Mexican-origin. The most frequently reported barriers were unleashed dogs in the street, heat, bad weather, traffic, no streetlights, and no place like a park to exercise. Prominent locations for current PA included schools, home, and parks. Common PA options for children were exercise equipment, running, playing, and sports. Environmental assessments identified

  2. Structural mechanism of GAF-regulated σ(54) activators from Aquifex aeolicus.

    Batchelor, Joseph D; Lee, Peter S; Wang, Andrew C; Doucleff, Michaeleen; Wemmer, David E

    2013-01-01

    The σ subunits of bacterial RNA polymerase occur in many variant forms and confer promoter specificity to the holopolymerase. Members of the σ(54) family of σ subunits require the action of a 'transcriptional activator' protein to open the promoter and initiate transcription. The activator proteins undergo regulated assembly from inactive dimers to hexamers that are active ATPases. These contact σ(54) directly and, through ATP hydrolysis, drive a conformational change that enables promoter opening. σ(54) activators use several different kinds of regulatory domains to respond to a wide variety of intracellular signals. One common regulatory module, the GAF domain, is used by σ(54) activators to sense small-molecule ligands. The structural basis for GAF domain regulation in σ(54) activators has not previously been reported. Here, we present crystal structures of GAF regulatory domains for Aquifex aeolicus σ(54) activators NifA-like homolog (Nlh)2 and Nlh1 in three functional states-an 'open', ATPase-inactive state; a 'closed', ATPase-inactive state; and a 'closed', ligand-bound, ATPase-active state. We also present small-angle X-ray scattering data for Nlh2-linked GAF-ATPase domains in the inactive state. These GAF domain dimers regulate σ(54) activator proteins by holding the ATPase domains in an inactive dimer conformation. Ligand binding of Nlh1 dramatically remodels the GAF domain dimer interface, disrupting the contacts with the ATPase domains. This mechanism has strong parallels to the response to phosphorylation in some two-component regulated σ(54) activators. We describe a structural mechanism of GAF-mediated enzyme regulation that appears to be conserved among humans, plants, and bacteria. PMID:23123379

  3. LPA is a novel lipid regulator of mesangial cell hexokinase activity and HKII isoform expression.

    Coy, Platina E; Taneja, Navin; Lee, Iris; Hecquet, Claudie; Bryson, Jane M; Robey, R Brooks

    2002-08-01

    The prototypical extracellular phospholipid mediator, lysophosphatidic acid (LPA), exhibits growth factor-like properties and represents an important survival factor in serum. This potent mesangial cell mitogen is increased in conditions associated with glomerular injury. It is also a known activator of the classic mitogen-activated protein kinase (MAPK) pathway, which plays an important role in the regulation of mesangial cell hexokinase (HK) activity. To better understand the mechanisms coupling metabolism to injury, we examined the ability of LPA to regulate HK activity and expression in cultured murine mesangial cells. LPA increased total HK activity in a concentration- and time-dependent manner, with maximal increases of >50% observed within 12 h of exposure to LPA concentrations > or =25 microM (apparent ED(50) 2 microM). These effects were associated with increased extracellular signal-regulated kinase (ERK) activity and were prevented by the pharmacological inhibition of either MAPK/ERK kinase or protein kinase C (PKC). Increased HK activity was also associated with increased glucose (Glc) utilization and lactate accumulation, as well as selectively increased HKII isoform abundance. The ability of exogenous LPA to increase HK activity was both Ca2+ independent and pertussis toxin insensitive and was mimicked by LPA-generating phospholipase A2. We conclude that LPA constitutes a novel lipid regulator of mesangial cell HK activity and Glc metabolism. This regulation requires sequential activation of both Ca2+-independent PKC and the classic MAPK pathway and culminates in increased HKII abundance. These previously unrecognized metabolic consequences of LPA stimulation have both physiological and pathophysiological implications. They also suggest a novel mechanism whereby metabolism may be coupled to cellular injury via extracellular lipid mediators. PMID:12110510

  4. NLRP3 Activation Was Regulated by DNA Methylation Modification during Mycobacterium tuberculosis Infection

    Wei, Meili; Wang, Lu; Wu, Tao; Xi, Jun; Han, Yuze; Yang, Xingxiang; Zhang, Ding; Fang, Qiang

    2016-01-01

    Mycobacterium tuberculosis (Mtb) infection activates the NLRP3 inflammasome in macrophages and dendritic cells. Much attention has been paid to the mechanisms for regulation of NLRP3 against Mtb. However, whether epigenetic mechanisms participated in NLRP3 activation is still little known. Here we showed that NLRP3 activation was regulated by DNA methylation modification. Mtb infection promoted NLRP3 activation and inflammatory cytokines expression. NLRP3 promoter was cloned and subsequently identified by Dual-Luciferase Reporter System. The results showed that NLRP3 promoter activity was decreased after methylation by DNA methylase Sss I in vitro. Meanwhile, DNA methyltransferases inhibitor DAC could upregulate the expression of NLRP3. Furthermore, promoter region of NLRP3 gene was demethylated after Mtb H37Rv strain infection. These data revealed that DNA methylation was involved in NLRP3 inflammasome activation during Mtb infection and provided a new insight into the relationship between host and pathogens. PMID:27366746

  5. Control of antioxidative response by the tumor suppressor protein PML through regulating Nrf2 activity

    Guo, Shuang; Cheng, Xiwen; Lim, Jun-Hee; Liu, Yu; Kao, Hung-Ying

    2014-01-01

    Oxidative stress is a consequence of an imbalance between reactive oxygen species (ROS) production and the ability of the cytoprotective system to detoxify the reactive intermediates. The tumor suppressor promyelocytic leukemia protein (PML) functions as a stress sensor. Loss of PML results in impaired mitochondrial complex II activity, increased ROS, and subsequent activation of nuclear factor erythroid 2–related factor 2 (Nrf2) antioxidative pathway. We also demonstrate that sulforaphane (SFN), an antioxidant, regulates Nrf2 activity by controlling abundance and subcellular distribution of PML and that PML is essential for SFN-mediated ROS increase, Nrf2 activation, antiproliferation, antimigration, and antiangiogenesis. Taking the results together, we have uncovered a novel antioxidative mechanism by which PML regulates cellular oxidant homeostasis by controlling complex II integrity and Nrf2 activity and identified PML as an indispensable mediator of SFN activity. PMID:24943846

  6. Gut barrier in health and disease: focus on childhood.

    Viggiano, D; Ianiro, G; Vanella, G; Bibbò, S; Bruno, G; Simeone, G; Mele, G

    2015-01-01

    The gut barrier is a functional unit, organized as a multi-layer system, made up of two main components: a physical barrier surface, which prevents bacterial adhesion and regulates paracellular diffusion to the host tissues, and a deep functional barrier, that is able to discriminate between pathogens and commensal microorganisms, organizing the immune tolerance and the immune response to pathogens. Other mechanisms, such as gastric juice and pancreatic enzymes (which both have antibacterial properties) participate in the luminal integrity of the gut barrier. From the outer layer to the inner layer, the physical barrier is composed of gut microbiota (that competes with pathogens to gain space and energy resources, processes the molecules necessary to mucosal integrity and modulates the immunological activity of deep barrier), mucus (which separates the intraluminal content from more internal layers and contains antimicrobial products and secretory IgA), epithelial cells (which form a physical and immunological barrier) and the innate and adaptive immune cells forming the gut-associated lymphoid tissue (which is responsible for antigen sampling and immune responses). Disruption of the gut barrier has been associated with many gastrointestinal diseases, but also with extra-intestinal pathological condition, such as type 1 diabetes mellitus, allergic diseases or autism spectrum disorders. The maintenance of a healthy intestinal barrier is therefore of paramount importance in children, for both health and economic reasons. Many drugs or compounds used in the treatment of gastrointestinal disorders act through the restoration of a normal intestinal permeability. Several studies have highlighted the role of probiotics in the modulation and reduction of intestinal permeability, considering the strong influence of gut microbiota in the modulation of the function and structure of gut barrier, but also on the immune response of the host. To date, available weapons for the

  7. Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma

    Lissanu Deribe, Yonathan

    2016-03-01

    PREX2 (phosphatidylinositol-3,4,5-triphosphate-dependent Rac-exchange factor 2) is a PTEN (phosphatase and tensin homolog deleted on chromosome 10) binding protein that is significantly mutated in cutaneous melanoma and pancreatic ductal adenocarcinoma. Here, genetic and biochemical analyses were conducted to elucidate the nature and mechanistic basis of PREX2 mutation in melanoma development. By generating an inducible transgenic mouse model we showed an oncogenic role for a truncating PREX2 mutation (PREX2E824*) in vivo in the context of mutant NRAS. Using integrative cross-species gene expression analysis, we identified deregulated cell cycle and cytoskeleton organization as significantly perturbed biological pathways in PREX2 mutant tumors. Mechanistically, truncation of PREX2 activated its Rac1 guanine nucleotide exchange factor activity, abolished binding to PTEN and activated the PI3K (phosphatidyl inositol 3 kinase)/Akt signaling pathway. We further showed that PREX2 truncating mutations or PTEN deletion induces down-regulation of the tumor suppressor and cell cycle regulator CDKN1C (also known as p57KIP2). This down-regulation occurs, at least partially, through DNA hypomethylation of a differentially methylated region in chromosome 11 that is a known regulatory region for expression of the CDKN1C gene. Together, these findings identify PREX2 as a mediator of NRAS-mutant melanoma development that acts through the PI3K/PTEN/Akt pathway to regulate gene expression of a cell cycle regulator.

  8. Physical activity among adolescents and barriers to delivering physical education in Cornwall and Lancashire, UK: A qualitative study of heads of PE and heads of schools

    Walters Stephen J

    2008-08-01

    Full Text Available Abstract Background Recent initiatives have been introduced by the UK government into secondary schools to increase pupils' access to physical activity (PA. Despite this, not enough is known about pupils' levels of physical activity or whether the delivery of these initiatives in schools facilitates or creates a barrier for pupils' PA. The aim of this study was to gain an understanding of adolescents PA levels from the perspective of those responsible for delivering physical education (PE in schools; heads of PE (HOPE and heads of school (HS. Methods Seventeen semi-structured qualitative interviews were carried out with a snowball sample of HOPE and HS in schools in the Northwest and Southwest of England. Thematic data analysis using NVIVO was used to identify emergent themes. Results 17 core themes were generated, 12 of which confirmed the findings from similar research. However, five themes relating to 'ethos of performance/elitism', 'lower fitness leads to lower ability', 'undervaluing activities within PE dept' or school as a whole', 'role of the school' and 'PE department doing all it can' offer valuable new insight into the factors which may encourage or prevent PA inside or outside the curriculum. Conclusion Despite many positive perceptions of the delivery of PE in schools, it is evident that barriers still exist within that delivery which discourages physical activity. More research is needed to particularly address the complex issues of elitism and the ethos of PA in schools.

  9. Luminal trypsin may regulate enterocytes through proteinase-activated receptor 2

    Kong, Wuyi; McConalogue, Karen; Khitin, Lev M.; Hollenberg, Morley D; Payan, Donald G.; Böhm, Stephan K.; Nigel W. Bunnett

    1997-01-01

    Proteinase-activated receptor 2 (PAR-2) is a recently characterized G-protein coupled receptor that is cleaved and activated by pancreatic trypsin. Trypsin is usually considered a digestive enzyme in the intestinal lumen. We examined the hypothesis that trypsin, at concentrations normally present in the lumen of the small intestine, is also a signaling molecule that specifically regulates enterocytes by activating PAR-2. PAR-2 mRNA was highly expressed in the mucosa of the small intestine and...

  10. Rapid neural regulation of muscle urokinase-like plasminogen activator as defined by nerve crush.

    Hantaï, D; Rao, J. S.; Festoff, B W

    1990-01-01

    Muscle plasminogen activators (PAs), such as urokinase-like PA and, to a lesser extent, tissue PA, increase dramatically after denervation induced by axotomy. The PA/plasmin system has also been implicated in degradation of specific components of the muscle fiber basement membrane after local activation of plasminogen. These results suggest that neural regulation of muscle extracellular matrix metabolism accompanies or precedes regeneration after injury and is mediated by activation of PAs. I...

  11. Information barriers

    Full text: An information barrier (IB) consists of procedures and technology that prevent the release of sensitive information during a joint inspection of a sensitive nuclear item, and provides confidence that the measurement system into which it has been integrated functions exactly as designed and constructed. Work in the U.S. on radiation detection system information barriers dates back at least to 1990, even though the terminology is more recent. In January 1999 the Joint DoD-DOE Information Barrier Working Group was formed in the United States to help coordinate technical efforts related to information barrier R and D. This paper presents an overview of the efforts of this group, by its Chairs, as well as recommendations for further information barrier R and D. Progress on the demonstration of monitoring systems containing IBs is also provided. From the U.S. perspective, the basic, top-level functional requirements for the information barrier portion of an integrated radiation signature-information barrier inspection system are twofold: The host must be assured that his classified information is protected from disclosure to the inspecting party; and The inspecting party must be confident that the integrated inspection system measures, processes, and presents the radiation-signature-based measurement conclusion in an accurate and reproducible manner. It is the position of the United States that in the absence of any agreement to share classified nuclear weapons design information in the conduct of an inspection regime, the requirement to protect host country classified warhead design information is paramount and admits no tradeoff versus the confidence provided to the inspecting party in the accuracy and reproducibility of the measurements. The U.S. has reached an internal consensus on several critical design elements that define a general standard for radiation signature information barrier design. These criteria have stood the test of time under intense

  12. Regulation of cancer stem cell activities by tumor-associated macrophages

    Jinushi, Masahisa; Baghdadi, Muhammad; Chiba, Shigeki; Yoshiyama, Hironori

    2012-01-01

    Recent studies revealed that tumor-associated macrophages play a decisive role in the regulation of tumor progression by manipulating tumor oncogenesis, angiogenesis and immune functions within tumor microenvironments. However, the role of cancer stem cells in the tumorigenic activities of tumor-associated macrophages during the course of transformation and treatment remains largely unknown. Recent studies have clarified the functional aspects of tumor-associated macrophages in the regulation...

  13. TAM receptors affect adult brain neurogenesis by negative regulation of microglial cell activation1

    Ji, Rui; Tian, Shifu; Lu, Helen J.; LU, QINGJUN; Yan ZHENG; Wang, Xiaomin; Ding, Jixiang; Li, Qiutang; Lu, Qingxian

    2013-01-01

    TAM tyrosine kinases play multiple functional roles including regulation of the target genes important in homeostatic regulation of cytokine receptors or Toll-like receptor-mediated signal transduction pathways. Here, we show that TAM receptors affect adult hippocampal neurogenesis and loss of TAM receptors impair hippocampal neurogenesis, largely attributed to exaggerated inflammatory responses by microglia characterized by increased MAP kinase and NF-κB activation and elevated production of...

  14. Smooth muscle–endothelial cell communication activates Reelin signaling and regulates lymphatic vessel formation

    Lutter, Sophie; Xie, Sherry; Tatin, Florence; Makinen, Taija

    2012-01-01

    Active lymph transport relies on smooth muscle cell (SMC) contractions around collecting lymphatic vessels, yet regulation of lymphatic vessel wall assembly and lymphatic pumping are poorly understood. Here, we identify Reelin, an extracellular matrix glycoprotein previously implicated in central nervous system development, as an important regulator of lymphatic vascular development. Reelin-deficient mice showed abnormal collecting lymphatic vessels, characterized by a reduced number of SMCs,...

  15. Effects of Environmental Regulation on Economic Activity and Pollution in Commercial Agriculture

    Sneeringer, Stacy E.

    2009-01-01

    Research on environmental regulation’s effects on economic activity has largely focused on manufacturing, ignoring one of the major polluters in the U.S. – commercial agriculture. As livestock production has become increasingly mobile, regulation has become an important criterion in firm location. This article extends the literature on environmental regulation’s economic effects to commercial agriculture by exploiting a series of regulations adopted in North Carolina in the 1990s. During this...

  16. Flip flops, dress clothes, and no coat: clothing barriers to children's physical activity in child-care centers identified from a qualitative study

    Saelens Brian E

    2009-11-01

    Full Text Available Abstract Background Three-quarters of 3-6 year-old children in the U.S. spend time in childcare; many spend most of their waking hours in these settings. Daily physical activity offers numerous health benefits, but activity levels vary widely across centers. This study was undertaken to explore reasons why physical activity levels may vary. The purpose of this paper is to summarize an unexpected finding that child-care providers cited was a key barrier to children's physical activity. Methods Nine focus groups with 49 child-care providers (55% black from 34 centers (including inner-city, suburban, Head Start and Montessori were conducted in Cincinnati, OH. Three independent raters analyzed verbatim transcripts for themes. Several techniques were used to increase credibility of findings, including interviews with 13 caregivers. Results Two major themes about clothing were: 1 children's clothing was a barrier to children's physical activity in child-care, and 2 clothing choices were a significant source of conflict between parents and child-care providers. Inappropriate clothing items included: no coat/hat/gloves in the wintertime, flip flops or sandals, dress/expensive clothes, jewelry, and clothes that were either too loose or too tight. Child-care providers explained that unless there were enough extra coats at the center, a single child without a coat could prevent the entire class from going outside. Caregivers suggested several reasons why parents may dress their child inappropriately, including forgetfulness, a rushed morning routine, limited income to buy clothes, a child's preference for a favorite item, and parents not understanding the importance of outdoor play. Several child-care providers favored specific policies prohibiting inappropriate clothing, as many reported limited success with verbal or written reminders to bring appropriate clothing. Conclusion Inappropriate clothing may be an important barrier to children's physical

  17. Casein Kinase 2 Regulates the mRNA-destabilizing Activity of Tristetraprolin*

    Lee, Won Hyeok; Lee, Hyun Hee; Vo, Mai-Tram; Kim, Hyo Jeong; Ko, Myoung Seok; Im, Yeong-Cheol; Min, Young Joo; Lee, Byung Ju; Cho, Wha Ja; Park, Jeong Woo

    2011-01-01

    Tristetraprolin (TTP) is an AU-rich element-binding protein that regulates mRNA stability. We previously showed that TTP acts as a negative regulator of VEGF gene expression in colon cancer cells. The p38 MAPK pathway is known to suppress the TTP activity. However, until now the signaling pathway to enhance TTP function is not well known. Here, we show that casein kinase 2 (CK2) enhances the TTP function in the regulation of the VEGF expression in colon cancer cells. CK2 increased TTP protein...

  18. Quercetin attenuates renal ischemia/reperfusion injury via an activation of AMP-activated protein kinase-regulated autophagy pathway.

    Chen, Bo-Lin; Wang, Li-Ting; Huang, Kuo-How; Wang, Ching-Chia; Chiang, Chih-Kang; Liu, Shing-Hwa

    2014-11-01

    Renal ischemia/reperfusion (I/R) is a major cause of acute renal failure. Quercetin, a flavonoid antioxidant, presents in many kinds of food. The molecular mechanism of quercetin on renal protection during I/R is still unclear. Here, we investigated the role of AMP-activated protein kinase (AMPK)-regulated autophagy in renal protection by quercetin. To investigate whether quercetin protects renal cells from I/R-induced cell injury, an in vitro model of I/R and an in vivo I/R model were used. Cell apoptosis was determined by propidium iodide/annexin V staining. Western blotting and immunofluorescence were used to determine the autophagy. AMPK expression was inhibited with appropriate short hairpin RNA (shRNA). In cultured renal tubular cell I/R model, quercetin decreased the cell injury, up-regulated the AMPK phosphorylation, down-regulated the mammalian target of rapamycin (mTOR) phosphorylation and activated autophagy during I/R. Knockdown of AMPK by shRNA transfection decreased the quercetin-induced autophagy but did not affect the mTOR phosphorylation. In I/R mouse model, quercetin decreased the increased serum creatinine level and altered renal histological score. Quercetin also increased AMPK phosphorylation, inhibited the mTOR phosphorylation and activated autophagy in the kidneys of I/R mice. These results suggest that quercetin activates an AMPK-regulated autophagy signaling pathway, which offers a protective effect in renal I/R injury. PMID:25087994

  19. Effect of a behavioral intervention on dimensions of self-regulation and physical activity among overweight and obese adults with type 2 diabetes: a pilot study.

    Silfee, Valerie; Petosa, Rick; Laurent, Devin; Schaub, Timothy; Focht, Brian

    2016-09-01

    The purpose of this pilot study was to determine the preliminary effect of a behavioral intervention on the use of self-regulation strategies and moderate-to-vigorous physical activity (MVPA) in overweight and obese adults with type 2 diabetes. 23 individuals recruited from ResearchMatc.org and campus advertisements were randomized into an intervention (n = 12) and control (n = 11) group. The intervention group received a behavioral intervention that used goal setting, time management, and self-monitoring to target dimensions of self-regulation and MVPA. The control received information regarding their PA habits. MVPA was measured via BodyMedia Armbands at pre- and post-test. The use of self-regulatory strategies for MVPA was assessed at pretest and posttest using the Self-Regulation for Exercise Scale. Cohen's d effect sizes were calculated to determine the practical impact of the intervention. The intervention had a large effect on all dimensions of self-regulation across time: including total self-regulation (3.15), self-monitoring (4.63), goal setting (3.17), social support (1.29), self-reward (1.98), time management (4.41), and overcoming barriers (2.25). The intervention had no impact on dimensions of MVPA across time. This pilot study demonstrated the ability of a behavioral intervention to improve the use of self-regulation strategies for MVPA in a sample of adults with type 2 diabetes. These findings can further inform the development of health promotion programs to promote self-regulation. Future research should focus on determining ability of improvements in self-regulation to stimulate behavior change. PMID:26785605

  20. Knowledge, perception, practice and barriers of breast cancer health promotion activities among community pharmacists in two Districts of Selangor state, Malaysia.

    Beshir, Semira A; Hanipah, Monalina A

    2012-01-01

    Breast cancer is the most common cancer and the leading cause of cancer death among women in Malaysia. Despite the campaigns undertaken to raise the awareness of the public regarding breast cancer, breast cancer screening rates are still low in the country. The community pharmacist, as one of the most accessible healthcare practitioners, could play a role in the provision of breast cancer health promotion services to the community. However, there are no documented data regarding the community pharmacists' involvement in breast cancer related health promotion activities. Hence, this study was conducted to examine self-reported knowledge, practice and perception of community pharmacists on provision of breast cancer health promotion services and to investigate the barriers that limit their involvement. This cross-sectional survey conducted between May to September 2010, included a sample of 35 community pharmacists working in the districts of Hulu Langat and Sepang in state of Selangor. A 22-item validated questionnaire that included both closed and Lickert scale questions was used to interview those pharmacists who gave their informed consent to participate in the study. The data was analysed using SPSS. Only 11.3% of the community pharmacists answered all the questions on the knowledge section correctly. The mean overall knowledge of the community pharmacists on risk factors of breast cancer and screening recommendations is 56%. None of the respondents was currently involved in breast cancer health promotion activities. Lack of time (80%), lack of breast cancer educational materials (77.1%) and lack of training (62.9%) were the top three mentioned barriers. Despite these barriers, 94.3% (33) of the community pharmacists agreed that they should be involved in breast cancer health promotion activities. Hence, there is need to equip community pharmacists with necessary training and knowledge to enable them to contribute their share towards prevention and screening of

  1. Regulation of Peroxisome Proliferator-Activated Receptors by E6-Associated Protein

    Lakshmi Gopinathan

    2008-01-01

    Full Text Available Peroxisome proliferator-activated receptors (PPARs are nuclear receptors (NRs that regulate genes involved in lipid and glucose metabolism. PPAR activity is regulated by interactions with cofactors and of interest are cofactors with ubiquitin ligase activity. The E6-associated protein (E6-AP is an E3 ubiquitin ligase that affects the activity of other NRs, although its effects on PPARs have not been examined. E6-AP inhibited the ligand-independent transcriptional activity of PPARα and PPARβ, with marginal effects on PPARγ, and decreased basal mRNA levels of PPARα target genes. Inhibition of PPARα activity required the ubiquitin ligase function of E6-AP, but occurred in a proteasome-independent manner. PPARα interacted with E6-AP, and in mice treated with PPARα agonist clofibrate, mRNA and protein levels of E6-AP were increased in wildtype, but not in PPARα null mice, indicating a PPARα-dependent regulation. These studies suggest coordinate regulation of E6-AP and PPARα, and contribute to our understanding of the role of PPARs in cellular metabolism.

  2. Summary of activities at the Engineered Barriers Test Facility, October 1, 1995 to January 31, 1997, and initial data

    Replicates of two engineered barrier designs (a thick soil barrier and a bio/capillary barrier) were constructed in the test plots of the facility. Prior to placement of any soil in the test plots, instruments were calibrated and attached to plot instrument towers, which were then installed in the test plots. Soil from Spreading Area B was installed in the test plots in lifts and compacted. Instruments attached to the instrument tower were placed in shallow trenches dug in the lifts and buried. Each instrument was checked to make sure it functioned prior to installation of the next lift. Soil samples were collected from each lift in one plot during construction for later determination of physical and hydraulic properties. After completion of the test plots, the data acquisition system was finalized, and data collection began. Appropriate instrument calibration equations and equation coefficients are presented, and data reduction techniques are described. Initial data show test plot soils drying throughout the summer and early fall. This corresponds to low rainfall during this period. Infiltration of water into the test plots was first detected around mid-November with several subsequent episodes in December. Infiltration was verified by corresponding measurements from several different instruments ime domain reflectometry (TDR), neutron probe, thermocouple psychrometers, and heat dissipation sensors Tensiometer data does not appear to corroborate data from the other instruments. Test plots were warmer on the side closest to the access trench indicating a temperature effect from the trench. This resulted in greater soil moisture freezing with less and shallower infiltration on the far side of the plots than on the side closest to the trench. At the end of this monitoring period, infiltration in all but two of the test plots has reached the 155-cm depth. Infiltration in test plots B2 and S3 has reached only the 140-cm depth. The monitored infiltration events have not

  3. Activated H-Ras regulates hematopoietic cell survival by modulating Survivin

    Survivin expression and Ras activation are regulated by hematopoietic growth factors. We investigated whether activated Ras could circumvent growth factor-regulated Survivin expression and if a Ras/Survivin axis mediates growth factor independent survival and proliferation in hematopoietic cells. Survivin expression is up-regulated by IL-3 in Ba/F3 and CD34+ cells and inhibited by the Ras inhibitor, farnesylthiosalicylic acid. Over-expression of constitutively activated H-Ras (CA-Ras) in Ba/F3 cells blocked down-modulation of Survivin expression, G0/G1 arrest, and apoptosis induced by IL-3 withdrawal, while dominant-negative (DN) H-Ras down-regulated Survivin. Survivin disruption by DN T34A Survivin blocked CA-Ras-induced IL-3-independent cell survival and proliferation; however, it did not affect CA-Ras-mediated enhancement of S-phase, indicating that the anti-apoptotic activity of CA-Ras is Survivin dependent while its S-phase enhancing effect is not. These results indicate that CA-Ras modulates Survivin expression independent of hematopoietic growth factors and that a CA-Ras/Survivin axis regulates survival and proliferation of transformed hematopoietic cells

  4. Why some do but most don't. Barriers and enablers to engaging low-income groups in physical activity programmes: a mixed methods study

    Fox Kenneth R

    2011-06-01

    Full Text Available Abstract Background The beneficial effect of physical activity for the prevention of a range of chronic diseases is widely acknowledged. These chronic conditions are most pronounced in economically disadvantaged groups where physical activity levels are consistently lower, yet this group is particularly difficult to recruit and retain in physical activity programmes. This study examined the perceptions of participants, non-participants, and exercise leaders in a low-income area regarding barriers, motives, and enabling factors for organised physical activity with a view to improving recruitment and retention. Methods A mixed methods research approach was adopted to guide data collection and analysis. A survey, incorporating the Motivation for Physical Activity Measure - Revised (MPAM-R, was used to assess the motivations of 152 physical activity session participants in a highly deprived suburban neighbourhood. The MPAM-R data were analysed using t tests, analyses of variance to estimate age, body mass index, and activity mode differences and Pearson's correlation coefficient to address associations. Semi-structured interviews were also conducted with 33 local residents who did not participate in activity sessions and with 14 activity session leaders. All interviews were audio-taped, transcribed verbatim and analyzed using an inductive thematic approach. Results Participants reported cost, childcare, lack of time and low awareness as barriers to joining activity classes. The need for support, confidence and competence in order to take up activity was widely expressed, particularly among women. Once people are active, high levels of social interaction, interest and enjoyment are associated with improved levels of retention, with different types of physical activity scoring differently on these factors. Conclusions This study suggests that some factors such as cost, the fear of 'walking in alone', accessibility of facilities, and appropriate

  5. Dialectical behavior therapy alters emotion regulation and amygdala activity in patients with borderline personality disorder

    Goodman, Marianne; Carpenter, David; Tang, Cheuk Y.; Goldstein, Kim E.; Avedon, Jennifer; Fernandez, Nicolas; Mascitelli, Kathryn A.; Blair, Nicholas J.; New, Antonia S.; Triebwasser, Joseph; Siever, Larry J.; Hazlett, Erin A.

    2014-01-01

    Objective Siever and Davis’ (1991) psychobiological framework of borderline personality disorder (BPD) identifies affective instability (AI) as a core dimension characterized by prolonged and intense emotional reactivity. Recently, deficient amygdala habituation, defined as a change in response to repeated relative to novel unpleasant pictures within a session, has emerged as a biological correlate of AI in BPD. Dialectical behavior therapy (DBT), an evidence-based treatment, targets AI by teaching emotion-regulation skills. This study tested the hypothesis that BPD patients would exhibit decreased amygdala activation and improved habituation, as well as improved emotion regulation with standard 12-month DBT. Methods Event-related fMRI was obtained pre- and post-12-months of standard-DBT in unmedicated BPD patients. Healthy controls (HCs) were studied as a benchmark for normal amygdala activity and change over time (n = 11 per diagnostic-group). During each scan, participants viewed an intermixed series of unpleasant, neutral and pleasant pictures presented twice (novel, repeat). Change in emotion regulation was measured with the Difficulty in Emotion Regulation (DERS) scale. Results fMRI results showed the predicted Group × Time interaction: compared with HCs, BPD patients exhibited decreased amygdala activation with treatment. This post-treatment amygdala reduction in BPD was observed for all three pictures types, but particularly marked in the left hemisphere and during repeated-emotional pictures. Emotion regulation measured with the DERS significantly improved with DBT in BPD patients. Improved amygdala habituation to repeated-unpleasant pictures in patients was associated with improved overall emotional regulation measured by the DERS (total score and emotion regulation strategy use subscale). Conclusion These findings have promising treatment implications and support the notion that DBT targets amygdala hyperactivity—part of the disturbed neural

  6. AMP-activated protein kinase-regulated activation of the PGC-1alpha promoter in skeletal muscle cells.

    Isabella Irrcher

    Full Text Available The mechanisms by which PGC-1alpha gene expression is controlled in skeletal muscle remains largely undefined. Thus, we sought to investigate the transcriptional regulation of PGC-1alpha using AICAR, an activator of AMPK, that is known to increase PGC-1alpha expression. A 2.2 kb fragment of the human PGC-1alpha promoter was cloned and sequence analysis revealed that this TATA-less sequence houses putative consensus sites including a GC-box, a CRE, several IRSs, a SRE, binding sites for GATA, MEF2, p 53, NF-kappaB, and EBox binding proteins. AMPK activation for 24 hours increased PGC-1alpha promoter activity with concomitant increases in mRNA expression. The effect of AICAR on transcriptional activation was mediated by an overlapping GATA/EBox binding site at -495 within the PGC-1alpha promoter based on gel shift analyses that revealed increases in GATA/EBox DNA binding. Mutation of the EBox within the GATA/EBox binding site in the promoter reduced basal promoter activity and completely abolished the AICAR effect. Supershift analyses identified USF-1 as a DNA binding transcription factor potentially involved in regulating PGC-1alpha promoter activity, which was confirmed in vivo by ChIP. Overexpression of either GATA-4 or USF-1 alone increased the p851 PGC-1alpha promoter activity by 1.7- and 2.0-fold respectively, while co-expression of GATA-4 and USF-1 led to an additive increase in PGC-1alpha promoter activity. The USF-1-mediated increase in PGC-1alpha promoter activation led to similar increases at the mRNA level. Our data identify a novel AMPK-mediated regulatory pathway that regulates PGC-1alpha gene expression. This could represent a potential therapeutic target to control PGC-1alpha expression in skeletal muscle.

  7. The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome Function

    Cai, Weili; Wei, Youheng; Jarnik, Michal; Reich, John; Lilly, Mary A.

    2016-01-01

    TORC1 is a master regulator of metabolism in eukaryotes that responds to multiple upstream signaling pathways. The GATOR complex is a newly defined upstream regulator of TORC1 that contains two sub-complexes, GATOR1, which inhibits TORC1 activity in response to amino acid starvation and GATOR2, which opposes the activity of GATOR1. While the GATOR1 complex has been implicated in a wide array of human pathologies including cancer and hereditary forms of epilepsy, the in vivo relevance of the GATOR2 complex remains poorly understood in metazoans. Here we define the in vivo role of the GATOR2 component Wdr24 in Drosophila. Using a combination of genetic, biochemical, and cell biological techniques we demonstrate that Wdr24 has both TORC1 dependent and independent functions in the regulation of cellular metabolism. Through the characterization of a null allele, we show that Wdr24 is a critical effector of the GATOR2 complex that promotes the robust activation of TORC1 and cellular growth in a broad array of Drosophila tissues. Additionally, epistasis analysis between wdr24 and genes that encode components of the GATOR1 complex revealed that Wdr24 has a second critical function, the TORC1 independent regulation of lysosome dynamics and autophagic flux. Notably, we find that two additional members of the GATOR2 complex, Mio and Seh1, also have a TORC1 independent role in the regulation of lysosome function. These findings represent a surprising and previously unrecognized function of GATOR2 complex components in the regulation of lysosomes. Consistent with our findings in Drosophila, through the characterization of a wdr24-/- knockout HeLa cell line we determined that Wdr24 promotes lysosome acidification and autophagic flux in mammalian cells. Taken together our data support the model that Wdr24 is a key effector of the GATOR2 complex, required for both TORC1 activation and the TORC1 independent regulation of lysosomes. PMID:27166823

  8. All-trans retinoic acid negatively regulates cytotoxic activities of nature killer cell line 92

    NK cells are key components of innate immune systems and their activities are regulated by cytokines and hormones. All-trans retinoic acid (ATRA), as a metabolite of vitamin A and an immunomodulatory hormone, plays an important role in regulating immune responses. In the present study, we investigated the effect of ATRA on human NK cell line NK92. We found that ATRA dose-dependently suppressed cytotoxic activities of NK92 cells without affecting their proliferation. To explore the mechanisms underlying the ATRA influence on NK92 cells, we examined the production of cytokines (TNF-α, IFN-γ), gene expression of cytotoxic-associated molecules (perforin, granzyme B, nature killer receptors (NCRs), and NKG2D), and the activation of NF-κB pathways related with immune response. Our results demonstrated that ATRA suppressed NF-κB activity and prevented IκBα degradation in a dose-dependent way, inhibited IFN-γ production and gene expression of granzyme B and NKp46. Our findings suggest that ATRA is a negative regulator of NK92 cell activation and may act as a potential regulator of anti-inflammatory functions in vivo

  9. The Activity Centres (Young Persons' Safety) Act 1995, the Adventure Activities Licensing Regulations 1996.

    Journal of Adventure Education and Outdoor Leadership, 1996

    1996-01-01

    Explains licensing regulations applicable in the United Kingdom to commercial providers of adventure education programs that offer caving, climbing, trekking, and water sports; provides information on license applications, including licensing standards related to risk assessment and safety management procedures; and addresses issues related to the…

  10. Pharmacological Characterization of the Spectrum of Antiviral Activity and Genetic Barrier to Drug Resistance of M2-S31N Channel Blockers.

    Ma, Chunlong; Zhang, Jiantao; Wang, Jun

    2016-09-01

    Adamantanes (amantadine and rimantadine) are one of the two classes of Food and Drug Administration-approved antiviral drugs used for the prevention and treatment of influenza A virus infections. They inhibit viral replication by blocking the wild-type (WT) M2 proton channel, thus preventing viral uncoating. However, their use was discontinued due to widespread drug resistance. Among a handful of drug-resistant mutants, M2-S31N is the predominant mutation and persists in more than 95% of currently circulating influenza A strains. We recently designed two classes of M2-S31N inhibitors, S31N-specific inhibitors and S31N/WT dual inhibitors, which are represented by N-[(5-cyclopropyl-1,2-oxazol-3-yl)methyl]adamantan-1-amine (WJ379) and N-[(5-bromothiophen-2-yl)methyl]adamantan-1-amine (BC035), respectively. However, their antiviral activities against currently circulating influenza A viruses and their genetic barrier to drug resistance are unknown. In this report, we evaluated the therapeutic potential of these two classes of M2-S31N inhibitors (WJ379 and BC035) by profiling their antiviral efficacy against multidrug-resistant influenza A viruses, in vitro drug resistance barrier, and synergistic effect with oseltamivir. We found that M2-S31N inhibitors were active against several influenza A viruses that are resistant to one or both classes of Food and Drug Administration-approved anti-influenza drugs. In addition, M2-S31N inhibitors display a higher in vitro genetic barrier to drug resistance than amantadine. The antiviral effect of WJ379 was also synergistic with oseltamivir carboxylate. Overall, these results reaffirm that M2-S31N inhibitors are promising antiviral drug candidates that warrant further development. PMID:27385729

  11. Activity-dependent BDNF release via endocytic pathways is regulated by synaptotagmin-6 and complexin.

    Wong, Yu-Hui; Lee, Chia-Ming; Xie, Wenjun; Cui, Bianxiao; Poo, Mu-ming

    2015-08-11

    Brain-derived neurotrophic factor (BDNF) is known to modulate synapse development and plasticity, but the source of synaptic BDNF and molecular mechanisms regulating BDNF release remain unclear. Using exogenous BDNF tagged with quantum dots (BDNF-QDs), we found that endocytosed BDNF-QDs were preferentially localized to postsynaptic sites in the dendrite of cultured hippocampal neurons. Repetitive neuronal spiking induced the release of BDNF-QDs at these sites, and this process required activation of glutamate receptors. Down-regulating complexin 1/2 (Cpx1/2) expression eliminated activity-induced BDNF-QD secretion, although the overall activity-independent secretion was elevated. Among eight synaptotagmin (Syt) isoforms examined, down-regulation of only Syt6 impaired activity-induced BDNF-QD secretion. In contrast, activity-induced release of endogenously synthesized BDNF did not depend on Syt6. Thus, neuronal activity could trigger the release of endosomal BDNF from postsynaptic dendrites in a Cpx- and Syt6-dependent manner, and endosomes containing BDNF may serve as a source of BDNF for activity-dependent synaptic modulation. PMID:26216953

  12. RhoB controls endothelial barrier recovery by inhibiting Rac1 trafficking to the cell border.

    Marcos-Ramiro, Beatriz; García-Weber, Diego; Barroso, Susana; Feito, Jorge; Ortega, María C; Cernuda-Morollón, Eva; Reglero-Real, Natalia; Fernández-Martín, Laura; Durán, Maria C; Alonso, Miguel A; Correas, Isabel; Cox, Susan; Ridley, Anne J; Millán, Jaime

    2016-05-01

    Endothelial barrier dysfunction underlies chronic inflammatory diseases. In searching for new proteins essential to the human endothelial inflammatory response, we have found that the endosomal GTPase RhoB is up-regulated in response to inflammatory cytokines and expressed in the endothelium of some chronically inflamed tissues. We show that although RhoB and the related RhoA and RhoC play additive and redundant roles in various aspects of endothelial barrier function, RhoB specifically inhibits barrier restoration after acute cell contraction by preventing plasma membrane extension. During barrier restoration, RhoB trafficking is induced between vesicles containing RhoB nanoclusters and plasma membrane protrusions. The Rho GTPase Rac1 controls membrane spreading and stabilizes endothelial barriers. We show that RhoB colocalizes with Rac1 in endosomes and inhibits Rac1 activity and trafficking to the cell border during barrier recovery. Inhibition of endosomal trafficking impairs barrier reformation, whereas induction of Rac1 translocation to the plasma membrane accelerates it. Therefore, RhoB-specific regulation of Rac1 trafficking controls endothelial barrier integrity during inflammation. PMID:27138256

  13. AMP-activated protein kinase regulates nicotinamide phosphoribosyl transferase expression in skeletal muscle

    Brandauer, Josef; Vienberg, Sara Gry; Andersen, Marianne Agerholm;

    2013-01-01

    -activated protein kinase (AMPK) increases sirtuin activity by elevating NAD levels. As NAM directly inhibits sirtuins, increased Nampt activation or expression could be a metabolic stress response. Evidence suggests that AMPK regulates Nampt mRNA content, but whether repeated AMPK activation is necessary for...... increasing Nampt protein levels is unknown. To this end, we assessed whether exercise training- or 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR)-mediated increases in skeletal muscle Nampt abundance are AMPK dependant. One-legged knee-extensor exercise training in humans increased Nampt protein...

  14. Swelling-activated ion channels: functional regulation in cell-swelling, proliferation and apoptosis

    Stutzin, A; Hoffmann, E K

    2006-01-01

    physiological control. Thus, cell volume is under a tight and dynamic control and abnormal cell volume regulation will ultimately lead to severe cellular dysfunction, including alterations in cell proliferation and cell death. This review describes the different swelling-activated ion channels that participate...... as key players in the maintenance of normal steady-state cell volume, with particular emphasis on the intracellular signalling pathways responsible for their regulation during hypotonic stress, cell proliferation and apoptosis.......Cell volume regulation is one of the most fundamental homeostatic mechanisms and essential for normal cellular function. At the same time, however, many physiological mechanisms are associated with regulatory changes in cell size meaning that the set point for cell volume regulation is under...

  15. Activity-dependent brain-derived neurotrophic factor expression regulates cortistatin-interneurons and sleep behavior

    Martinowich Keri

    2011-03-01

    Full Text Available Abstract Background Sleep homeostasis is characterized by a positive correlation between sleep length and intensity with the duration of the prior waking period. A causal role for brain-derived neurotrophic factor (BDNF in sleep homeostasis has been suggested, but the underlying mechanisms remain unclear. Cortistatin, a neuropeptide expressed primarily in a subset of cortical GABAergic interneurons, is another molecule implicated in sleep homeostasis. Results We confirmed that sleep deprivation leads to an increase in cortical cortistatin mRNA expression. Disruption of activity-dependent BDNF expression in a genetically modified mouse line impairs both baseline levels of cortistatin mRNA as well as its levels following sleep deprivation. Disruption of activity-dependent BDNF also leads to a decrease in sleep time during the active (dark phase. Conclusion Our studies suggest that regulation of cortistatin-expressing interneurons by activity-dependent BDNF expression may contribute to regulation of sleep behavior.

  16. CYLD Regulates Noscapine Activity in Acute Lymphoblastic Leukemia via a Microtubule-Dependent Mechanism

    Yang, Yunfan; Ran, Jie; Sun, Lei; Sun, Xiaodong; Luo, Youguang; Yan, Bing; Tala; Liu, Min; Li, Dengwen; Zhang, Lei; Bao, Gang; Zhou, Jun

    2015-01-01

    Noscapine is an orally administrable drug used worldwide for cough suppression and has recently been demonstrated to disrupt microtubule dynamics and possess anticancer activity. However, the molecular mechanisms regulating noscapine activity remain poorly defined. Here we demonstrate that cylindromatosis (CYLD), a microtubule-associated tumor suppressor protein, modulates the activity of noscapine both in cell lines and in primary cells of acute lymphoblastic leukemia (ALL). Flow cytometry and immunofluorescence microscopy reveal that CYLD increases the ability of noscapine to induce mitotic arrest and apoptosis. Examination of cellular microtubules as well as in vitro assembled microtubules shows that CYLD enhances the effect of noscapine on microtubule polymerization. Microtubule cosedimentation and fluorescence titration assays further reveal that CYLD interacts with microtubule outer surface and promotes noscapine binding to microtubules. These findings thus demonstrate CYLD as a critical regulator of noscapine activity and have important implications for ALL treatment. PMID:25897332

  17. Somatostatin modulates insulin-degrading-enzyme metabolism: implications for the regulation of microglia activity in AD.

    Grazia Tundo

    Full Text Available The deposition of β-amyloid (Aβ into senile plaques and the impairment of somatostatin-mediated neurotransmission are key pathological events in the onset of Alzheimer's disease (AD. Insulin-degrading-enzyme (IDE is one of the main extracellular protease targeting Aβ, and thus it represents an interesting pharmacological target for AD therapy. We show that the active form of somatostatin-14 regulates IDE activity by affecting its expression and secretion in microglia cells. A similar effect can also be observed when adding octreotide. Following a previous observation where somatostatin directly interacts with IDE, here we demonstrate that somatostatin regulates Aβ catabolism by modulating IDE proteolytic activity in IDE gene-silencing experiments. As a whole, these data indicate the relevant role played by somatostatin and, potentially, by analogue octreotide, in preventing Aβ accumulation by partially restoring IDE activity.

  18. Regulation of programmed cell death by plasminogen activator inhibitor type 1 (PAI-1)

    Lademann, Ulrik Axel; Rømer, Maria Unni Koefoed

    2008-01-01

    numbers of reports suggest that PAI-1 also can regulate programmed cell death (PCD) in cancer cells and normal cells. A number of reports suggest that PAI-1 can inhibit PCD through its pro-adhesive/anti-proteolytic property whereas other reports suggest that PAI-1 induces PCD through its anti......-adhesive property.Furthermore,it has been suggested that PAI-1 can either induce or inhibit PCD though activation of cell signalling pathways.This review will focus on the regulation of programmed cell death by PAI-1 in both normal cells and cancer cells.......Elevated levels of plasminogen activator inhibitor-1 (PAI-1) are associated with poor prognosis in cancer. An explanation to the elevated levels of PAI-1 could be a protective response to the increased proteolytic activity, caused by elevated levels of urokinase- type plasminogen activator (u...

  19. The Proteasome Activator PA28γ, a Negative Regulator of p53, Is Transcriptionally Up-Regulated by p53

    Zhen-Xing Wan

    2014-02-01

    Full Text Available PA28γ (also called REGγ, 11Sγ or PSME3 negatively regulates p53 activity by promoting its nuclear export and/or degradation. Here, using the RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE method, we identified the transcription start site of the PA28γ gene. Assessment with the luciferase assay demonstrated that the sequence −193 to +16 is the basal promoter. Three p53 binding sites were found within the PA28γ promoter utilizing a bioinformatics approach and were confirmed by chromatin immunoprecipitation and biotinylated DNA affinity precipitation experiments. The p53 protein promotes PA28γ transcription, and p53-stimulated transcription of PA28γ can be inhibited by PA28γ itself. Our results suggest that PA28γ and p53 form a negative feedback loop, which maintains the balance of p53 and PA28γ in cells.

  20. Regulation of Mutagenic DNA Polymerase V Activation in Space and Time

    Robinson, Andrew; McDonald, John P.; Caldas, Victor E. A.; Patel, Meghna; Wood, Elizabeth A.; Punter, Christiaan M.; Ghodke, Harshad; Cox, Michael M.; Woodgate, Roger; Goodman, Myron F.; van Oijen, Antoine M.

    2015-01-01

    Spatial regulation is often encountered as a component of multi-tiered regulatory systems in eukaryotes, where processes are readily segregated by organelle boundaries. Well-characterized examples of spatial regulation are less common in bacteria. Low-fidelity DNA polymerase V (UmuD′2C) is produced in Escherichia coli as part of the bacterial SOS response to DNA damage. Due to the mutagenic potential of this enzyme, pol V activity is controlled by means of an elaborate regulatory system at transcriptional and posttranslational levels. Using single-molecule fluorescence microscopy to visualize UmuC inside living cells in space and time, we now show that pol V is also subject to a novel form of spatial regulation. After an initial delay (~ 45 min) post UV irradiation, UmuC is synthesized, but is not immediately activated. Instead, it is sequestered at the inner cell membrane. The release of UmuC into the cytosol requires the RecA* nucleoprotein filament-mediated cleavage of UmuD→UmuD′. Classic SOS damage response mutants either block [umuD(K97A)] or constitutively stimulate [recA(E38K)] UmuC release from the membrane. Foci of mutagenically active pol V Mut (UmuD′2C-RecA-ATP) formed in the cytosol after UV irradiation do not co-localize with pol III replisomes, suggesting a capacity to promote translesion DNA synthesis at lesions skipped over by DNA polymerase III. In effect, at least three molecular mechanisms limit the amount of time that pol V has to access DNA: (1) transcriptional and posttranslational regulation that initially keep the intracellular levels of pol V to a minimum; (2) spatial regulation via transient sequestration of UmuC at the membrane, which further delays pol V activation; and (3) the hydrolytic activity of a recently discovered pol V Mut ATPase function that limits active polymerase time on the chromosomal template. PMID:26317348

  1. Regulation of Mutagenic DNA Polymerase V Activation in Space and Time.

    Andrew Robinson

    2015-08-01

    Full Text Available Spatial regulation is often encountered as a component of multi-tiered regulatory systems in eukaryotes, where processes are readily segregated by organelle boundaries. Well-characterized examples of spatial regulation are less common in bacteria. Low-fidelity DNA polymerase V (UmuD'2C is produced in Escherichia coli as part of the bacterial SOS response to DNA damage. Due to the mutagenic potential of this enzyme, pol V activity is controlled by means of an elaborate regulatory system at transcriptional and posttranslational levels. Using single-molecule fluorescence microscopy to visualize UmuC inside living cells in space and time, we now show that pol V is also subject to a novel form of spatial regulation. After an initial delay (~ 45 min post UV irradiation, UmuC is synthesized, but is not immediately activated. Instead, it is sequestered at the inner cell membrane. The release of UmuC into the cytosol requires the RecA* nucleoprotein filament-mediated cleavage of UmuD→UmuD'. Classic SOS damage response mutants either block [umuD(K97A] or constitutively stimulate [recA(E38K] UmuC release from the membrane. Foci of mutagenically active pol V Mut (UmuD'2C-RecA-ATP formed in the cytosol after UV irradiation do not co-localize with pol III replisomes, suggesting a capacity to promote translesion DNA synthesis at lesions skipped over by DNA polymerase III. In effect, at least three molecular mechanisms limit the amount of time that pol V has to access DNA: (1 transcriptional and posttranslational regulation that initially keep the intracellular levels of pol V to a minimum; (2 spatial regulation via transient sequestration of UmuC at the membrane, which further delays pol V activation; and (3 the hydrolytic activity of a recently discovered pol V Mut ATPase function that limits active polymerase time on the chromosomal template.

  2. PI3Kγ activation by CXCL12 regulates tumor cell adhesion and invasion

    Tumor dissemination is a complex process, in which certain steps resemble those in leukocyte homing. Specific chemokine/chemokine receptor pairs have important roles in both processes. CXCL12/CXCR4 is the most commonly expressed chemokine/chemokine receptor pair in human cancers, in which it regulates cell adhesion, extravasation, metastatic colonization, angiogenesis, and proliferation. All of these processes require activation of signaling pathways that include G proteins, phosphatidylinositol-3 kinase (PI3K), JAK kinases, Rho GTPases, and focal adhesion-associated proteins. We analyzed these pathways in a human melanoma cell line in response to CXCL12 stimulation, and found that PI3Kγ regulates tumor cell adhesion through mechanisms different from those involved in cell invasion. Our data indicate that, following CXCR4 activation after CXCL12 binding, the invasion and adhesion processes are regulated differently by distinct downstream events in these signaling cascades.

  3. Heat Shock Protein 90 Indirectly Regulates ERK Activity by Affecting Raf Protein Metabolism

    Fei DOU; Liu-Di YUAN; Jing-Jing ZHU

    2005-01-01

    Extracellular signal-regulated protein kinase (ERK) has been implicated in the pathogenesis of several nerve system diseases. As more and more kinases have been discovered to be the client proteins of the molecular chaperone Hsp90, the use of Hsp90 inhibitors to reduce abnormal kinase activity is a new treatment strategy for nerve system diseases. This study investigated the regulation of the ERK pathway by Hsp90. We showed that Hsp90 inhibitors reduce ERK phosphorylation without affecting the total ERK protein level. Further investigation showed that Raf, the upstream kinase in the Ras-Raf-MEK-ERK pathway,forms a complex with Hsp90 and Hsp70. Treating cells with Hsp90 inhibitors facilitates Raf degradation,thereby down-regulating the activity of ERK.

  4. Evaluation of In Vitro Anti-Inflammatory Activities and Protective Effect of Fermented Preparations of Rhizoma Atractylodis Macrocephalae on Intestinal Barrier Function against Lipopolysaccharide Insult

    Shambhunath Bose

    2013-01-01

    Full Text Available Lipopolysaccharide (LPS, a potent inducer of systemic inflammatory responses, is known to cause impairment of intestinal barrier function. Here, we evaluated the in vitro protective effect of an unfermented formulation of Rhizoma Atractylodis Macrocephalae (RAM, a traditional Chinese herbal medicine widely used in the treatment of many digestive and gastrointestinal disorders, and two fermented preparations of RAM, designated as FRAM-1 (prepared in Luria-Bertani broth and FRAM-2 (prepared in glucose, on intestinal epithelial cells (IECs against LPS insult. In general, fermented formulations, especially FRAM-2, but not unfermented RAM, exerted an appreciable protective effect on IECs against LPS-induced perturbation of membrane resistance and permeability. Both fermented formulations exhibited appreciable anti-inflammatory activities in terms of their ability to inhibit LPS-induced gene expression and induced production of a number of key inflammatory mediators and cytokines in RAW 264.7 macrophage cells. However, in most cases, FRAM-2 exhibited stronger anti-inflammatory effects than FRAM-1. Our findings also suggest that suppression of nuclear factor-κβ (NF-κβ activity might be one of the possible mechanisms by which the fermented RAM exerts its anti-inflammatory effects. Collectively, our results highlight the benefits of using fermented products of RAM to protect against LPS-induced inflammatory insult and impairment in intestinal barrier function.

  5. Licensing and safety regulation on units engaged in civilian nuclear pressure retaining component's activities

    The NNSA convened a meeting for granting the first batch of 25 units engaged in the activities of civilian nuclear pressure retaining components with 45 qualificatory licenses in 1995, and will conduct surveillance and inspection pursuant to requirements of regulations on the associated implementing activities by units that had obtained a qualificatory license. At present, the NNSA has prepared part of inspection procedures of nuclear pressure retaining components

  6. Structural mechanism of GAF-regulated σ54 activators from Aquifex aeolicus

    Batchelor, Joseph D.; Lee, Peter S.; Wang, Andrew C.; Doucleff, Michaeleen; Wemmer, David E.

    2012-01-01

    The σ subunits of bacterial RNA polymerase occur in many variant forms, and confer promoter specificity to the holopolymerase. Members of the σ54 family of σ subunits require the action of a ‘transcriptional activator’ protein to open the promoter and initiate transcription. The activator proteins undergo regulated assembly from inactive dimers to hexamers that are active ATPases. These contact σ54 directly and, through ATP hydrolysis, drive a conformational change that enables promoter openi...

  7. The role of class I histocompatibility antigens in the regulation of T-cell activation.

    Dasgupta, J D; Cemach, K; Dubey, D P; Yunis, E J; Amos, D. B.

    1987-01-01

    Class I major histocompatibility antigens in humans (HLA antigens) were found to participate in the regulation of T-cell activation and proliferation induced by phytohemagglutinin. W6/32, a monomorphic antibody directed against class I HLA-A,B,C antigens, significantly inhibited the phytohemagglutinin-induced cell proliferation of peripheral blood lymphocytes. Almost complete suppression of cell activation was achieved on a subfraction of peripheral blood lymphocytes enriched in Mo1+ monocyte...

  8. Regulation and supervision of the decommissioning of the Active Central Laboratory (ACL) in Studsvik, Sweden

    The paper aims at presenting the experiences made by the Swedish Radiation Protection Authority (SSI) during the decommissioning of the Active Central Laboratory (ACL) in Studsvik, Sweden. As a background, the facility and the decommissioning activities that have been performed are described. This is followed by a description of the regulation and supervision by the SSI. Finally, the main experiences are listed and conclusions are drawn. (author)

  9. Negative regulation of glial engulfment activity by Draper terminates glial responses to axon injury

    Logan, Mary A.; Hackett, Rachel; Doherty, Johnna; Sheehan, Amy; Speese, Sean D.; Freeman, Marc R

    2012-01-01

    Neuronal injury elicits potent cellular responses from glia, but molecular pathways modulating glial activation, phagocytic function, and termination of reactive responses remain poorly defined. Here we show that positive or negative regulation of glial reponses to axon injury are molecularly encoded by unique isoforms of the Drosophila engulfment receptor Draper. Draper-I promotes engulfment of axonal debris through an immunoreceptor tyrosine-based activation motif (ITAM). In contrast, Drape...

  10. Regulation and practices regarding the management of very low activity radioactive wastes. Report nr 309

    This document reports a study which aims at analysing the recommendations made by international bodies (IAEA, Euratom) and the regulations of several countries (Germany, United States, United Kingdom, Sweden, Spain, Canada, Slovakia, Belgium, Japan and France) regarding the management of low activity radioactive wastes, with a focus on practices in releasing and recycling very low activity materials and the French national program for radioactive waste management

  11. Identification of Caspase-6 as a New Regulator of Alternatively Activated Macrophages.

    Yao, Yongfang; Shi, Qian; Chen, Bing; Wang, Qingsong; Li, Xinda; Li, Long; Huang, Yahong; Ji, Jianguo; Shen, Pingping

    2016-08-12

    Alternatively activated macrophages (AAMs) play essential roles in the promotion of tissue remodeling, vasculogenesis, and tumor progression; however, the detailed mechanisms underlying the activation of AAMs remain largely unknown. Here, by using quantitative proteomic analysis, we identified 62 proteins that were up-regulated in IL-4-induced macrophages. Among these, Caspase-6 was increased significantly. Caspase-6 is important in the apoptotic signaling pathway; however, its role in non-apoptosis is also reported. Here, we first examined the non-apoptotic role of Caspase-6 in the alternative activation of macrophages after administration of IL-4, 4T1 tumor conditional medium, or co-culture with 4T1 cells. Both treatments promoted alternative activation of RAW264.7 cells and primary macrophages, whereas disruption of caspase-6 expression and activity could markedly suppress the biomarker levels of AAMs. Overexpression of Caspase-6 could significantly promote the activation of AAMs. Importantly, we further present evidence that caspase-6 could regulate breast cancer cell invasion by modulating MMP-2 and MMP-9 expression in 4T1 tumor-associated macrophages, as ablation of protein levels or activity of caspase-6 suppressed tumor cell invasion in vitro In conclusion, the observed results markedly expanded our views of the dynamic changes in protein composition during alternative activation of macrophages, and they revealed a critical new role of caspase-6 in regulating this cellular biological process, which suggested that caspase-6 might be a key nod molecule to regulate immunological steady-state and be a therapeutic candidate for tumor immunotherapy. PMID:27325699

  12. Sphingomyelin synthase 1 activity is regulated by the BCR-ABL oncogene[S

    Burns, Tara Ann; Subathra, Marimuthu; signorelli, Paola; Choi, Young; Yang, Xiaofeng; Wang, Yong; Villani, Maristella; Bhalla, Kapil; Zhou, Daohong; Luberto, Chiara

    2013-01-01

    Sphingomyelin synthase (SMS) produces sphingomyelin while consuming ceramide (a negative regulator of cell proliferation) and forming diacylglycerol (DAG) (a mitogenic factor). Therefore, enhanced SMS activity could favor cell proliferation. To examine if dysregulated SMS contributes to leukemogenesis, we measured SMS activity in several leukemic cell lines and found that it is highly elevated in K562 chronic myelogenous leukemia (CML) cells. The increased SMS in K562 cells was caused by the ...

  13. An endogenous ribonuclease inhibitor regulates the antimicrobial activity of ribonuclease 7 in the human urinary tract

    Spencer, John David; Schwaderer, Andrew L.; Eichler, Tad; Wang, Huanyu; Kline, Jennifer; Justice, Sheryl S.; Cohen, Daniel M.; Hains, David S.

    2013-01-01

    Recent studies stress the importance of antimicrobial peptides in protecting the urinary tract from infection. Previously, we have shown that ribonuclease 7 (RNase 7) is a potent antimicrobial peptide that has broad-spectrum antimicrobial activity against uropathogenic bacteria. The urothelium of the lower urinary tract and intercalated cells of the kidney produce RNase 7 but regulation of its antimicrobial activity has not been well defined. Here we characterize the expression of an endogeno...

  14. Energy Conservation Analysis and Control of Hybrid Active Semiactive Suspension with Three Regulating Damping Levels

    Long Chen; Dehua Shi; Ruochen Wang; Huawei Zhou

    2016-01-01

    Active suspension has not been popularized for high energy consumption. To address this issue, this paper introduces the concept of a new kind of suspension. The linear motor is considered to be integrated into an adjustable shock absorber to form the hybrid active semiactive suspension (HASAS). To realize the superiority of HASAS, its energy consumption and regeneration mechanisms are revealed. And the system controller which is composed of linear quadratic regulator (LQR) controller, mode d...

  15. Effects of ethanol feeding on the activity and regulation of hepatic carnitine palmitoyltransferase I

    Guzman, M.; Geelen, M.J.H.

    1988-01-01

    The effects of ethanol administration on activity and regulation of carnitine palmitoyltransferase I (CPT-I) were studied in hepatocytes isolated from rats fed a liquid, high-fat diet containing 36% of total calories as ethanol or an isocaloric amount of sucrose. Cells were isolated at several time points in the course of a 5-week experimental period. Ethanol consumption markedly decreased CPT-I activity and increased enzyme sensitivity to inhibition by exogenously added malonyl-CoA. Changes ...

  16. Temporal self-regulation theory: a neurobiologically informed model for physical activity behavior

    Peter eHall; Geoffrey eFong

    2015-01-01

    Dominant explanatory models for physical activity behavior are limited by the exclusion of several important components, including temporal dynamics, ecological forces, and neurobiological factors. The latter may be a critical omission, given the relevance of several aspects of cognitive function for the self-regulatory processes that are likely required for consistent implementation of physical activity behavior in everyday life. This narrative review introduces temporal self-regulation theo...

  17. Sds22 regulates aurora B activity and microtubule–kinetochore interactions at mitosis

    Posch, Markus; Khoudoli, Guennadi A.; Swift, Sam; King, Emma M.; DeLuca, Jennifer G.; Swedlow, Jason R.

    2010-01-01

    We have studied Sds22, a conserved regulator of protein phosphatase 1 (PP1) activity, and determined its role in modulating the activity of aurora B kinase and kinetochore–microtubule interactions. Sds22 is required for proper progression through mitosis and localization of PP1 to mitotic kinetochores. Depletion of Sds22 increases aurora B T-loop phosphorylation and the rate of recovery from monastrol arrest. Phospho–aurora B accumulates at kinetochores in Sds22-depleted cells juxtaposed to c...

  18. Active and Passive Fatigue in Simulated Driving: Discriminating Styles of Workload Regulation and Their Safety Impacts

    Saxby, Dyani J.; Matthews, Gerald; Warm, Joel S.; Hitchcock, Edward M.; Neubauer, Catherine

    2013-01-01

    Despite the known dangers of driver fatigue, it is a difficult construct to study empirically. Different forms of task-induced fatigue may differ in their effects on driver performance and safety. Desmond and Hancock (2001) defined active and passive fatigue states that reflect different styles of workload regulation. In 2 driving simulator studies we investigated the multidimensional subjective states and safety outcomes associated with active and passive fatigue. Wind gusts were used to ind...

  19. cAMP/PKA signaling balances respiratory activity with mitochondria dependent apoptosis via transcriptional regulation

    Gourlay Campbell W

    2010-11-01

    Full Text Available Abstract Background Appropriate control of mitochondrial function, morphology and biogenesis are crucial determinants of the general health of eukaryotic cells. It is therefore imperative that we understand the mechanisms that co-ordinate mitochondrial function with environmental signaling systems. The regulation of yeast mitochondrial function in response to nutritional change can be modulated by PKA activity. Unregulated PKA activity can lead to the production of mitochondria that are prone to the production of ROS, and an apoptotic form of cell death. Results We present evidence that mitochondria are sensitive to the level of cAMP/PKA signaling and can respond by modulating levels of respiratory activity or committing to self execution. The inappropriate activation of one of the yeast PKA catalytic subunits, Tpk3p, is sufficient to commit cells to an apoptotic death through transcriptional changes that promote the production of dysfunctional, ROS producing mitochondria. Our data implies that cAMP/PKA regulation of mitochondrial function that promotes apoptosis engages the function of multiple transcription factors, including HAP4, SOK2 and SCO1. Conclusions We propose that in yeast, as is the case in mammalian cells, mitochondrial function and biogenesis are controlled in response to environmental change by the concerted regulation of multiple transcription factors. The visualization of cAMP/TPK3 induced cell death within yeast colonies supports a model that PKA regulation plays a physiological role in coordinating respiratory function and cell death with nutritional status in budding yeast.

  20. 76 FR 10384 - Agency Information Collection Activities: Regulation on Agency Protests

    2011-02-24

    ... published this information collection request (ICR) in the Federal Register on November 15, 2010 at 75 FR... SECURITY Agency Information Collection Activities: Regulation on Agency Protests AGENCY: Office of Chief Procurement Officer, Acquisition Policy and Legislation Office, DHS. ACTION: 30-Day Notice and request...