WorldWideScience

Sample records for play activities secret

  1. Mycobacterial secretion systems ESX-1 and ESX-5 play distinct roles in host cell death and inflammasome activation

    KAUST Repository

    Abdallah, Abdallah

    2011-09-28

    During infection of humans and animals, pathogenic mycobacteria manipulate the host cell causing severe diseases such as tuberculosis and leprosy. To understand the basis of mycobacterial pathogenicity, it is crucial to identify the molecular virulence mechanisms. In this study, we address the contribution of ESX-1 and ESX-5 - two homologous type VII secretion systems of mycobacteria that secrete distinct sets of immune modulators - during the macrophage infection cycle. Using wild-type, ESX-1- and ESX-5-deficient mycobacterial strains, we demonstrate that these secretion systems differentially affect subcellular localization and macrophage cell responses. We show that in contrast to ESX-1, the effector proteins secreted by ESX-5 are not required for the translocation of Mycobacterium tuberculosis or Mycobacterium marinum to the cytosol of host cells. However, the M. marinum ESX-5 mutant does not induce inflammasome activation and IL-1b activation. The ESX-5 system also induces a caspase-independent cell death after translocation has taken place. Importantly, by means of inhibitory agents and small interfering RNA experiments, we reveal that cathepsin B is involved in both the induction of cell death and inflammasome activation upon infection with wild-type mycobacteria. These results reveal distinct roles for two different type VII secretion systems during infection and shed light on how virulent mycobacteria manipulate the host cell in various ways to replicate and spread. Copyright © 2011 by The American Association of Immunologists, Inc.

  2. Mycobacterial secretion systems ESX-1 and ESX-5 play distinct roles in host cell death and inflammasome activation

    KAUST Repository

    Abdallah, Abdallah; Bestebroer, Jovanka; Savage, Nigel D L; De Punder, Karin; Van Zon, Maaike; Wilson, Louis D.; Korbee, Cees J.; Van Der Sar, Astrid M.; Ottenhoff, Tom Hm M; Van Der Wel, Nicole N.; Bitter, Wilbert M.; Peters, Peter J.

    2011-01-01

    for the translocation of Mycobacterium tuberculosis or Mycobacterium marinum to the cytosol of host cells. However, the M. marinum ESX-5 mutant does not induce inflammasome activation and IL-1b activation. The ESX-5 system also induces a caspase-independent cell death

  3. The Secret of Play: Birth to 12 Months

    Science.gov (United States)

    Murphy, Ann Pleshette

    2009-01-01

    This article is an excerpt from "The Secret of Play: How to Raise Smart, Healthy, Caring Kids From Birth to Age 12" (2008, DK Publishing) by parenting expert Ann Pleshette Murphy. The author draws on child development research to help parents understand how play helps children learn at each stage of development and offers practical suggestions for…

  4. The Activity of Play

    DEFF Research Database (Denmark)

    Pichlmair, Martin

    This paper presents Activity Theory as a framework for understanding the action of playing games with the intention of building a foundation for the creation of new game design tools and methods. Activity Theory, an epistemological framework rooted in Soviet psychology of the first half of the 20...

  5. Hydathode trichomes actively secreting water from leaves play a key role in the physiology and evolution of root-parasitic rhinanthoid Orobanchaceae

    Czech Academy of Sciences Publication Activity Database

    Světlíková, P.; Hájek, Tomáš; Těšitel, J.

    2015-01-01

    Roč. 116, č. 1 (2015), s. 61-68 ISSN 0305-7364 Institutional support: RVO:67985939 Keywords : active water transport * parasite * water regime Subject RIV: EH - Ecology, Behaviour Impact factor: 3.982, year: 2015

  6. Dietary gamma oryzanol plays a significant role in the anti-inflammatory activity of rice bran oil by decreasing pro-inflammatory mediators secreted by peritoneal macrophages of rats.

    Science.gov (United States)

    Rao, Y Poorna Chandra; Sugasini, D; Lokesh, B R

    2016-10-28

    Ricebran oil (RBO) is promoted as heart friendly oil because of its ability to maintain serum lipids at desirable levels. Inflammation also plays an important role on cardiovascular health. The role of minor constituents present in unsaponifiable fraction (UF) of RBO on inflammatory markers is not well understood. To evaluate this, we have taken RBO with UF (RBO-N), RBO stripped of UF (RBO-MCR) and RBO-MCR supplemented with UF from RBO (UFRBO) or Gamma-Oryzanol (γ-ORY) were added in AIN-93 diets which was then fed to Wistar rats for a period of 60 days. Groundnut oil with UF (GNO-N), UF removed GNO (GNO-MCR) and GNO-MCR supplemented with UF from RBO or γ-ORY was also used for comparison. The peritoneal macrophages from the rats were activated and pro-inflammatory mediators such as Reactive Oxygen Species (ROS), eicosanoids, cytokines, hydrolytic enzymes of lysosomal origin were monitored. The results indicated that UF of RBO and γ-ORY supplemented in the dietary oils play a significant role in reducing the secretion of pro-inflammatory mediators by macrophages. Hence γ-ORY in RBO significantly contributed to the anti-inflammatory properties of RBO. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Secreted and Transmembrane Wnt Inhibitors and Activators

    Science.gov (United States)

    Cruciat, Cristina-Maria; Niehrs, Christof

    2013-01-01

    Signaling by the Wnt family of secreted glycoproteins plays important roles in embryonic development and adult homeostasis. Wnt signaling is modulated by a number of evolutionarily conserved inhibitors and activators. Wnt inhibitors belong to small protein families, including sFRP, Dkk, WIF, Wise/SOST, Cerberus, IGFBP, Shisa, Waif1, APCDD1, and Tiki1. Their common feature is to antagonize Wnt signaling by preventing ligand–receptor interactions or Wnt receptor maturation. Conversely, the Wnt activators, R-spondin and Norrin, promote Wnt signaling by binding to Wnt receptors or releasing a Wnt-inhibitory step. With few exceptions, these antagonists and agonists are not pure Wnt modulators, but also affect additional signaling pathways, such as TGF-β and FGF signaling. Here we discuss their interactions with Wnt ligands and Wnt receptors, their role in developmental processes, as well as their implication in disease. PMID:23085770

  8. Active Gaming: The Future of Play?

    Science.gov (United States)

    Witherspoon, Lisa; Manning, John P.

    2012-01-01

    The authors examine technology-driven games--especially active gaming--as an evolving form of children's play. They offer an overview of play and its developmental benefits, describe the literature on the emergence of technology-driven play, and reflect on the diminishment of physical play in contemporary culture. They suggest that active gaming,…

  9. Transition problems and play as transitory activity

    DEFF Research Database (Denmark)

    Broström, Stig

    2005-01-01

    Because too many children experience the transition to school as a culture shock, during the past decade teachers have implemented so-called transition activities in order to bridge the gap betwen pre-school and schoo. However, transition to school also calls for a development of higher mental...... functions, among others the development of children's learning motive. From the view of activity theori, transition to formal education entails crossing boundaries from the activity system play to the activity system of school learning. The transition can be facilitated by developing a 'transitory activity...... system', which mediates between the two systems, ensuring that the result of one system serves as a tool for the next. Advanced forms of play might make up a transitory activity system. The paper describes different forms of play crossing the boundaies of role play (frame-play, aesthetic theme play...

  10. Position Statement on Active Outdoor Play

    OpenAIRE

    Tremblay, Mark S.; Gray, Casey; Babcock, Shawna; Barnes, Joel; Costas Bradstreet, Christa; Carr, Dawn; Chabot, Guylaine; Choquette, Louise; Chorney, David; Collyer, Cam; Herrington, Susan; Janson, Katherine; Janssen, Ian; Larouche, Richard; Pickett, William

    2015-01-01

    A diverse, cross-sectorial group of partners, stakeholders and researchers, collaborated to develop an evidence-informed Position Statement on active outdoor play for children aged 3–12 years. The Position Statement was created in response to practitioner, academic, legal, insurance and public debate, dialogue and disagreement on the relative benefits and harms of active (including risky) outdoor play. The Position Statement development process was informed by two systematic reviews, a critic...

  11. Position Statement on Active Outdoor Play

    Science.gov (United States)

    Tremblay, Mark S.; Gray, Casey; Babcock, Shawna; Barnes, Joel; Costas Bradstreet, Christa; Carr, Dawn; Chabot, Guylaine; Choquette, Louise; Chorney, David; Collyer, Cam; Herrington, Susan; Janson, Katherine; Janssen, Ian; Larouche, Richard; Pickett, William; Power, Marlene; Sandseter, Ellen Beate Hansen; Simon, Brenda; Brussoni, Mariana

    2015-01-01

    A diverse, cross-sectorial group of partners, stakeholders and researchers, collaborated to develop an evidence-informed Position Statement on active outdoor play for children aged 3–12 years. The Position Statement was created in response to practitioner, academic, legal, insurance and public debate, dialogue and disagreement on the relative benefits and harms of active (including risky) outdoor play. The Position Statement development process was informed by two systematic reviews, a critical appraisal of the current literature and existing position statements, engagement of research experts (N = 9) and cross-sectorial individuals/organizations (N = 17), and an extensive stakeholder consultation process (N = 1908). More than 95% of the stakeholders consulted strongly agreed or somewhat agreed with the Position Statement; 14/17 participating individuals/organizations endorsed it; and over 1000 additional individuals and organizations requested their name be listed as a supporter. The final Position Statement on Active Outdoor Play states: “Access to active play in nature and outdoors—with its risks— is essential for healthy child development. We recommend increasing children’s opportunities for self-directed play outdoors in all settings—at home, at school, in child care, the community and nature.” The full Position Statement provides context for the statement, evidence supporting it, and a series of recommendations to increase active outdoor play opportunities to promote healthy child development. PMID:26062040

  12. Position Statement on Active Outdoor Play.

    Science.gov (United States)

    Tremblay, Mark S; Gray, Casey; Babcock, Shawna; Barnes, Joel; Bradstreet, Christa Costas; Carr, Dawn; Chabot, Guylaine; Choquette, Louise; Chorney, David; Collyer, Cam; Herrington, Susan; Janson, Katherine; Janssen, Ian; Larouche, Richard; Pickett, William; Power, Marlene; Sandseter, Ellen Beate Hansen; Simon, Brenda; Brussoni, Mariana

    2015-06-08

    A diverse, cross-sectorial group of partners, stakeholders and researchers, collaborated to develop an evidence-informed Position Statement on active outdoor play for children aged 3-12 years. The Position Statement was created in response to practitioner, academic, legal, insurance and public debate, dialogue and disagreement on the relative benefits and harms of active (including risky) outdoor play. The Position Statement development process was informed by two systematic reviews, a critical appraisal of the current literature and existing position statements, engagement of research experts (N=9) and cross-sectorial individuals/organizations (N=17), and an extensive stakeholder consultation process (N=1908). More than 95% of the stakeholders consulted strongly agreed or somewhat agreed with the Position Statement; 14/17 participating individuals/organizations endorsed it; and over 1000 additional individuals and organizations requested their name be listed as a supporter. The final Position Statement on Active Outdoor Play states: "Access to active play in nature and outdoors--with its risks--is essential for healthy child development. We recommend increasing children's opportunities for self-directed play outdoors in all settings--at home, at school, in child care, the community and nature." The full Position Statement provides context for the statement, evidence supporting it, and a series of recommendations to increase active outdoor play opportunities to promote healthy child development.

  13. Position Statement on Active Outdoor Play

    Directory of Open Access Journals (Sweden)

    Mark S. Tremblay

    2015-06-01

    Full Text Available A diverse, cross-sectorial group of partners, stakeholders and researchers, collaborated to develop an evidence-informed Position Statement on active outdoor play for children aged 3–12 years. The Position Statement was created in response to practitioner, academic, legal, insurance and public debate, dialogue and disagreement on the relative benefits and harms of active (including risky outdoor play. The Position Statement development process was informed by two systematic reviews, a critical appraisal of the current literature and existing position statements, engagement of research experts (N = 9 and cross-sectorial individuals/organizations (N = 17, and an extensive stakeholder consultation process (N = 1908. More than 95% of the stakeholders consulted strongly agreed or somewhat agreed with the Position Statement; 14/17 participating individuals/organizations endorsed it; and over 1000 additional individuals and organizations requested their name be listed as a supporter. The final Position Statement on Active Outdoor Play states: “Access to active play in nature and outdoors—with its risks— is essential for healthy child development. We recommend increasing children’s opportunities for self-directed play outdoors in all settings—at home, at school, in child care, the community and nature.” The full Position Statement provides context for the statement, evidence supporting it, and a series of recommendations to increase active outdoor play opportunities to promote healthy child development.

  14. Active Play: Exploring the Influences on Children's School Playground Activities

    Science.gov (United States)

    Hyndman, Brendon; Benson, Amanda; Telford, Amanda

    2016-01-01

    Because children spend so much of their time in schools, their playgrounds offer a good setting for promoting active play in young lives. Teachers, instead of considering active play a taxing demand on their busy day, have begun to develop an informal curriculum for it. The authors review the research on children's active play and explores its…

  15. Activated platelets enhance IL-10 secretion and reduce TNF-α secretion by monocytes

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Hasselbalch, Hans C; Nielsen, Claus H

    2013-01-01

    ), Escherichia coli LPS, or intact Porphyromonas gingivalis. Addition of platelets activated by thrombin-receptor-activating peptide enhanced IL-10 production induced by LPS (p gingivalis (p ....05), and P. gingivalis (p gingivalis-stimulated cultures (p ... of activated platelets. Adherence of platelets increased TG- and TT-induced IL-10 secretion by monocytes (p gingivalis (p

  16. Antifungal activity of epithelial secretions from selected frog species ...

    African Journals Online (AJOL)

    This study aimed to investigate the antifungal activity of skin secretions from selected frogs (Amietia fuscigula, Strongylopus grayi and Xenopus laevis) and one toad (Amietophrynus pantherinus) of the south Western Cape Province of South Africa. Initially, different extraction techniques for the collection of skin secretions ...

  17. Active play opportunities at child care.

    Science.gov (United States)

    Tandon, Pooja S; Saelens, Brian E; Christakis, Dimitri A

    2015-06-01

    Physical activity (PA) is important for children's health and development, yet preschoolers are not meeting PA recommendations. The objective of this study was to examine different PA opportunities at child care and how variation in indoor versus outdoor and free versus teacher-led opportunities relate to children's PA. An observational study of 98 children (mean age 4.5 years, 49% girls) from 10 child care centers. Classrooms were observed for at least 4 full days per center (total 50 days) to categorize time into (1) not an active play opportunity (APO); (2) naptime; (3) APO, outdoor free play; (4) APO, outdoor teacher-led; (5) APO, indoor free play; and (6) APO, indoor teacher-led. Children wore accelerometers during observations. Linear regression models examined the influence of APO categories on moderate-vigorous physical activity (MVPA) and sedentary time. Children's activity was 73% sedentary, 13% light, and 14% MVPA. For 88% of time children did not have APOs, including 26% time as naptime. On average, 48 minutes per day were APOs (41% sedentary, 18% light, and 41% MVPA), 33 minutes per day were outdoors. The most frequent APO was outdoor free play (8% of time); outdoor teacher-led time was Children were more active and less sedentary outdoors versus indoors and during the child-initiated APOs (indoors and outdoors) versus teacher-led APOs. Preschoolers were presented with significantly fewer than recommended opportunities for PA at child care. More APOs are needed for children to meet recommendations, particularly those that encourage more outdoor time, more teacher-led and child-initiated active play, and flexibility in naptime for preschoolers. Copyright © 2015 by the American Academy of Pediatrics.

  18. World History Plays, Puzzles and Activities.

    Science.gov (United States)

    Stevens, Lawrence

    This instructional resource, for grades 7-10, includes a collection of 10 plays with related learning activities. Units of study include: (1) "Alexander the Great and the Greeks"; (2) "The Black Death and the End of the Middle Ages"; (3) "Robert Clive and Imperialism"; (4) "Christopher Columbus and the Age of…

  19. Pathogen-secreted proteases activate a novel plant immune pathway.

    Science.gov (United States)

    Cheng, Zhenyu; Li, Jian-Feng; Niu, Yajie; Zhang, Xue-Cheng; Woody, Owen Z; Xiong, Yan; Djonović, Slavica; Millet, Yves; Bush, Jenifer; McConkey, Brendan J; Sheen, Jen; Ausubel, Frederick M

    2015-05-14

    Mitogen-activated protein kinase (MAPK) cascades play central roles in innate immune signalling networks in plants and animals. In plants, however, the molecular mechanisms of how signal perception is transduced to MAPK activation remain elusive. Here we report that pathogen-secreted proteases activate a previously unknown signalling pathway in Arabidopsis thaliana involving the Gα, Gβ, and Gγ subunits of heterotrimeric G-protein complexes, which function upstream of an MAPK cascade. In this pathway, receptor for activated C kinase 1 (RACK1) functions as a novel scaffold that binds to the Gβ subunit as well as to all three tiers of the MAPK cascade, thereby linking upstream G-protein signalling to downstream activation of an MAPK cascade. The protease-G-protein-RACK1-MAPK cascade modules identified in these studies are distinct from previously described plant immune signalling pathways such as that elicited by bacterial flagellin, in which G proteins function downstream of or in parallel to an MAPK cascade without the involvement of the RACK1 scaffolding protein. The discovery of the new protease-mediated immune signalling pathway described here was facilitated by the use of the broad host range, opportunistic bacterial pathogen Pseudomonas aeruginosa. The ability of P. aeruginosa to infect both plants and animals makes it an excellent model to identify novel immunoregulatory strategies that account for its niche adaptation to diverse host tissues and immune systems.

  20. DREAM plays an important role in platelet activation and thrombogenesis

    Science.gov (United States)

    Kim, Kyungho; Tseng, Alan; Barazia, Andrew; Italiano, Joseph E.

    2017-01-01

    Downstream regulatory element antagonist modulator (DREAM), a transcriptional repressor, is known to modulate pain responses. However, it is unknown whether DREAM is expressed in anucleate platelets and plays a role in thrombogenesis. By using intravital microscopy with DREAM-null mice and their bone marrow chimeras, we demonstrated that both hematopoietic and nonhematopoietic cell DREAMs are required for platelet thrombus formation following laser-induced arteriolar injury. In a FeCl3-induced thrombosis model, we found that compared with wild-type (WT) control and nonhematopoietic DREAM knockout (KO) mice, DREAM KO control and hematopoietic DREAM KO mice showed a significant delay in time to occlusion. Tail bleeding time was prolonged in DREAM KO control mice, but not in WT or DREAM bone marrow chimeric mice. In vivo adoptive transfer experiments further indicated the importance of platelet DREAM in thrombogenesis. We found that DREAM deletion does not alter the ultrastructural features of platelets but significantly impairs platelet aggregation and adenosine triphosphate secretion induced by numerous agonists (collagen-related peptide, adenosine 5′-diphosphate, A23187, thrombin, or U46619). Biochemical studies revealed that platelet DREAM positively regulates phosphoinositide 3-kinase (PI3K) activity during platelet activation. Using DREAM-null platelets and PI3K isoform-specific inhibitors, we observed that platelet DREAM is important for α-granule secretion, Ca2+ mobilization, and aggregation through PI3K class Iβ (PI3K-Iβ). Genetic and pharmacological studies in human megakaryoblastic MEG-01 cells showed that DREAM is important for A23187-induced Ca2+ mobilization and its regulatory function requires Ca2+ binding and PI3K-Iβ activation. These results suggest that platelet DREAM regulates PI3K-Iβ activity and plays an important role during thrombus formation. PMID:27903531

  1. The secrets of highly active older adults.

    Science.gov (United States)

    Franke, Thea; Tong, Catherine; Ashe, Maureen C; McKay, Heather; Sims-Gould, Joanie

    2013-12-01

    Although physical activity is a recognized component in the management of many chronic diseases associated with aging, activity levels tend to progressively decline with increasing age (Manini & Pahor, 2009; Schutzer & Graves, 2004). In this article we examine the key factors that facilitate physical activity in highly active community-dwelling older adults. Using a strengths based approach, we examined the factors that facilitated physical activity in our sample of highly active older adults. Twenty-seven older adults participated in face-to face interviews. We extracted a sub-sample of 10 highly active older adults to be included in the analyses. Based on a framework analysis of our transcripts we identified three factors that facilitate physical activity in our sample, these include: 1) resourcefulness: engagement in self-help strategies such as self-efficacy, self-control and adaptability; 2) social connections: the presence of relationships (friend, neighborhood, institutions) and social activities that support or facilitate high levels of physical activity; and 3) the role of the built and natural environments: features of places and spaces that support and facilitate high levels of physical activity. Findings provide insight into, and factors that facilitate older adults' physical activity. We discuss implications for programs (e.g., accessible community centers, with appropriate programming throughout the lifecourse) and policies geared towards the promotion of physical activity (e.g., the development of spaces that facilitate both physical and social activities). © 2013.

  2. Inhibition of cAMP-Activated Intestinal Chloride Secretion by Diclofenac: Cellular Mechanism and Potential Application in Cholera

    OpenAIRE

    Pongkorpsakol, Pawin; Pathomthongtaweechai, Nutthapoom; Srimanote, Potjanee; Soodvilai, Sunhapas; Chatsudthipong, Varanuj; Muanprasat, Chatchai

    2014-01-01

    Cyclic AMP-activated intestinal Cl- secretion plays an important role in pathogenesis of cholera. This study aimed to investigate the effect of diclofenac on cAMP-activated Cl- secretion, its underlying mechanisms, and possible application in the treatment of cholera. Diclofenac inhibited cAMP-activated Cl- secretion in human intestinal epithelial (T84) cells with IC50 of ∼ 20 µM. The effect required no cytochrome P450 enzyme-mediated metabolic activation. Interestingly, exposures of T84 cell...

  3. Pancreatic β-Cell Electrical Activity and Insulin Secretion: of Mice and Men

    Science.gov (United States)

    Rorsman, Patrik; Ashcroft, Frances M

    2018-01-01

    The pancreatic β-cell plays a key role in glucose homeostasis by secreting insulin, the only hormone capable of lowering the blood glucose concentration. Impaired insulin secretion results in the chronic hyperglycaemia that characterizes type 2 diabetes (T2DM), which currently afflicts >450 million people worldwide. The healthy β-cell acts as a glucose sensor matching its output to the circulating glucose concentration. It does so via metabolically induced changes in electrical activity, which culminate in an increase in the cytoplasmic Ca2+ concentration and initiation of Ca2+-dependent exocytosis of insulin-containing secretory granules. Here, we review recent advances in our understanding of the β-cell transcriptome, electrical activity and insulin exocytosis. We highlight salient differences between mouse and human β-cells, provide models of how the different ion channels contribute to their electrical activity and insulin secretion, and conclude by discussing how these processes become perturbed in T2DM. PMID:29212789

  4. Activity of secreted amylases in Aspergillus

    Energy Technology Data Exchange (ETDEWEB)

    Bocheva, S.S.; Kurnitskaya, L.N.

    1981-01-01

    When A. oryzae was cultivated in a synthetic liquid medium containing maltose as a sole source of C, the activity of extracellular amylase was 8.43-11.92 units/100 mL. Addition of 1.0% and 2.0% NaCl to the medium increased the amylase activity approximately 5- and 10-fold, respectively.

  5. Glutamine-Elicited Secretion of Glucagon-Like Peptide 1 Is Governed by an Activated Glutamate Dehydrogenase.

    Science.gov (United States)

    Andersson, Lotta E; Shcherbina, Liliya; Al-Majdoub, Mahmoud; Vishnu, Neelanjan; Arroyo, Claudia Balderas; Aste Carrara, Jonathan; Wollheim, Claes B; Fex, Malin; Mulder, Hindrik; Wierup, Nils; Spégel, Peter

    2018-03-01

    Glucagon-like peptide 1 (GLP-1), secreted from intestinal L cells, glucose dependently stimulates insulin secretion from β-cells. This glucose dependence prevents hypoglycemia, rendering GLP-1 analogs a useful and safe treatment modality in type 2 diabetes. Although the amino acid glutamine is a potent elicitor of GLP-1 secretion, the responsible mechanism remains unclear. We investigated how GLP-1 secretion is metabolically coupled in L cells (GLUTag) and in vivo in mice using the insulin-secreting cell line INS-1 832/13 as reference. A membrane-permeable glutamate analog (dimethylglutamate [DMG]), acting downstream of electrogenic transporters, elicited similar alterations in metabolism as glutamine in both cell lines. Both DMG and glutamine alone elicited GLP-1 secretion in GLUTag cells and in vivo, whereas activation of glutamate dehydrogenase (GDH) was required to stimulate insulin secretion from INS-1 832/13 cells. Pharmacological inhibition in vivo of GDH blocked secretion of GLP-1 in response to DMG. In conclusion, our results suggest that nonelectrogenic nutrient uptake and metabolism play an important role in L cell stimulus-secretion coupling. Metabolism of glutamine and related analogs by GDH in the L cell may explain why GLP-1 secretion, but not that of insulin, is activated by these secretagogues in vivo. © 2017 by the American Diabetes Association.

  6. Antifungal activity of lectins against yeast of vaginal secretion

    Directory of Open Access Journals (Sweden)

    Bruno Severo Gomes

    2012-06-01

    Full Text Available Lectins are carbohydrate-binding proteins of non-imune origin. This group of proteins is distributed widely in nature and they have been found in viruses, microorganisms, plants and animals. Lectins of plants have been isolated and characterized according to their chemical, physical-chemical, structural and biological properties. Among their biological activities, we can stress its fungicidal action. It has been previously described the effect of the lectins Dviol, DRL, ConBr and LSL obtained from the seeds of leguminous plants on the growth of yeasts isolated from vaginal secretions. In the present work the experiments were carried out in microtiter plates and the results interpreted by both methods: visual observations and a microplate reader at 530nm. The lectin concentrations varied from 0.5 to 256µg/mL, and the inoculum was established between 65-70% of trammitance. All yeast samples isolated from vaginal secretion were evaluated taxonomically, where were observed macroscopic and microscopic characteristics to each species. The LSL lectin did not demonstrate any antifungal activity to any isolate studied. The other lectins DRL, ConBr and DvioL, showed antifungal potential against yeast isolated from vaginal secretion. These findings offering offer a promising field of investigation to develop new therapeutic strategies against vaginal yeast infections, collaborating to improve women's health.

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

    Directory of Open Access Journals (Sweden)

    Rowan Brockman

    2011-06-01

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

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

    Science.gov (United States)

    Brockman, Rowan; Jago, Russell; Fox, Kenneth R

    2011-06-10

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

  9. TEACHING SPEAKING BY ROLE-PLAY ACTIVITY

    Directory of Open Access Journals (Sweden)

    Fadilah Fadilah

    2016-11-01

    Full Text Available The students often find some problems in practising English speaking. The problem frequently found is that their native language causes them difficult to use the foreign language. Other reason is because of motivation lack to practice the second language in daily conversation. They are also too shy and afraid to take part in the conversation. Many factors can cause the problem of the students’ speaking skills namely the students’ interest, the material, and the media among others including the technique in teaching English. There are many ways that can be done by the students to develop their ability in speaking English. The appropriate technique used by the English teacher also supports their interested in practising their speaking. One of the techniques that can be applied is role play.

  10. Expressed prostatic secretion biomarkers improve stratification of NCCN active surveillance candidates: performance of secretion capacity and TMPRSS2:ERG models.

    Science.gov (United States)

    Whelan, Christopher; Kawachi, Mark; Smith, David D; Linehan, Jennifer; Babilonia, Gail; Mejia, Rosa; Wilson, Timothy; Smith, Steven S

    2014-01-01

    Active surveillance is a viable patient option for prostate cancer provided that a clinical determination of low risk and presumably organ confined disease can be made. To standardize risk stratification schemes the NCCN (National Comprehensive Cancer Network®) provides guidelines for the active surveillance option. We determined the effectiveness of expressed prostatic secretion biomarkers for detecting occult risk factors in NCCN active surveillance candidates. Expressed prostatic secretion specimens were obtained before robot-assisted radical prostatectomy. Secretion capacity biomarkers, including total RNA and expressed prostatic secretion specimen volume, were measured by standard techniques. RNA expression biomarkers, including TXNRD1 mRNA, prostate specific antigen mRNA, TMPRSS2:ERG fusion mRNA and PCA3 mRNA, were measured by quantitative reverse-transcription polymerase chain reaction. Of the 528 patients from whom expressed prostatic secretions were collected 216 were eligible for active surveillance under NCCN guidelines. Variable selection on logistic regression identified 2 models, including one featuring types III and VI TMPRSS2:ERG variants, and one featuring 2 secretion capacity biomarkers. Of the 2 high performing models the secretion capacity model was most effective for detecting cases in this group that were up-staged or up-staged plus upgraded. It decreased the risk of up-staging in patients with a negative test almost eightfold and decreased the risk of up-staging plus upgrading about fivefold while doubling the prevalence of up-staging in the positive test group. Noninvasive expressed prostatic secretion testing may improve patient acceptance of active surveillance by dramatically reducing the presence of occult risk factors among those eligible for active surveillance under NCCN guidelines. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  11. Solitary Active Videogame Play Improves Executive Functioning More Than Collaborative Play for Children with Special Needs.

    Science.gov (United States)

    Flynn, Rachel M; Colon, Nirmaliz

    2016-12-01

    This pilot study examined the impact of playing an active videogame on executive functioning (EF) skills for children with special needs, who typically have lower EF skills. Acute EF change was measured in 36 children with a range of special needs, including mental health disorders and developmental disabilities. Participants were assigned to one of two active videogame conditions: playing alone and playing with a peer. Two different EF tasks were conducted pre- and postplay. Children who played alone increased their accuracy performance more than children in the paired-play condition on two measures of EF. The study explored potential covariates of prior videogame experience, age, and enjoyment, but none of these variables related to EF change. This study's findings support active videogame play as an activity that can boost EF skills for children with special needs when they play alone. Future research should continue to examine the relationships between EF and active videogame play with a peer to elucidate the contributions of social interactions.

  12. Is it play? Towards a reconceptualisation of role-play from an activity theory perspective.

    NARCIS (Netherlands)

    van Oers, B.

    2013-01-01

    This article proposes a reconceptualisation of role play on the basis of the Cultural-Historical theory (Vygotskij -Leont'ev - El'konin). The theory conceives of play as a specific mode of activity defined by a format that includes three basic parameters (rules, degrees of freedom and involvement).

  13. Active and separate secretion of fiber and penton base during the early phase of Ad2 or Ad5 infection

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Yuhua; Zhang, Bo; Hou, Weihong; Lin, Hongyu [Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, Beijing (China); Rebetz, Johan [The Rausing Laboratory, Department of Neurosurgery, Lund University, Lund (Sweden); Hong, Saw-See [Viral Infections & Comparative Pathology, UMR-754 UCBL-INRA-EPHE, Université Lyon 1, Lyon Cedex 07 (France); Wang, Youjun; Ran, Liang [Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, Beijing (China); Fan, Xiaolong, E-mail: XFan@bnu.edu.cn [Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, Beijing (China)

    2017-05-15

    Fiber and penton base overproduced in adenovirus (Ad) infected cells can be secreted prior to progeny release and thereby regulate progeny spread. We aimed to investigate the mechanisms of fiber and penton base secretion in Ad2- or Ad5-infected A549 cells. Our flow cytometry analyses detected abundant surface fiber molecules, but little penton base molecules at 12 h post infection. Immunogold staining combined with transmission electron microscopic analyses revealed separate, non-co-localized release of fiber and penton base in the proximity of the plasma membrane. Depolymerization of microtubule and actin cytoskeletons, and inhibition of Rock kinase and myosin II activity together demonstrated cytoskeletal network-dependent fiber secretion. Inhibition of intracellular calcium [Ca{sup 2+}]{sub i} signaling caused diminished fiber secretion, which was associated with diminished progeny production. Thus, fiber and penton base are actively and separately secreted during the early stages of Ad2 or Ad5 infection, their secretion may play important role in Ad life cycle. - Highlights: •Excessive production of structural proteins is common to viral infection, which may regulate the host-virus equilibrium and the spreading of viruses. •The adenovirus (Ad) structural proteins, fiber and penton base, are respectively important for Ad binding to its receptor and subsequent internalization in host cells. In Ad infected cells, these two structural proteins are excessively produced. •The mechanisms underlying the release of fiber and penton base molecules at the early phase of Ad infection is yet poorly understood. •Our studies show that in Ad5 or Ad2 infected A549 cells, fiber and penton base molecules are actively and separately secreted. •Fiber secretion is dependent on cytoskeleton-mediated protein traffic. •Inhibition of myosin II motor and Ca{sup 2+} signaling activity significantly diminishes fiber secretion. •These findings could contribute to our

  14. Active and separate secretion of fiber and penton base during the early phase of Ad2 or Ad5 infection

    International Nuclear Information System (INIS)

    Yan, Yuhua; Zhang, Bo; Hou, Weihong; Lin, Hongyu; Rebetz, Johan; Hong, Saw-See; Wang, Youjun; Ran, Liang; Fan, Xiaolong

    2017-01-01

    Fiber and penton base overproduced in adenovirus (Ad) infected cells can be secreted prior to progeny release and thereby regulate progeny spread. We aimed to investigate the mechanisms of fiber and penton base secretion in Ad2- or Ad5-infected A549 cells. Our flow cytometry analyses detected abundant surface fiber molecules, but little penton base molecules at 12 h post infection. Immunogold staining combined with transmission electron microscopic analyses revealed separate, non-co-localized release of fiber and penton base in the proximity of the plasma membrane. Depolymerization of microtubule and actin cytoskeletons, and inhibition of Rock kinase and myosin II activity together demonstrated cytoskeletal network-dependent fiber secretion. Inhibition of intracellular calcium [Ca 2+ ] i signaling caused diminished fiber secretion, which was associated with diminished progeny production. Thus, fiber and penton base are actively and separately secreted during the early stages of Ad2 or Ad5 infection, their secretion may play important role in Ad life cycle. - Highlights: •Excessive production of structural proteins is common to viral infection, which may regulate the host-virus equilibrium and the spreading of viruses. •The adenovirus (Ad) structural proteins, fiber and penton base, are respectively important for Ad binding to its receptor and subsequent internalization in host cells. In Ad infected cells, these two structural proteins are excessively produced. •The mechanisms underlying the release of fiber and penton base molecules at the early phase of Ad infection is yet poorly understood. •Our studies show that in Ad5 or Ad2 infected A549 cells, fiber and penton base molecules are actively and separately secreted. •Fiber secretion is dependent on cytoskeleton-mediated protein traffic. •Inhibition of myosin II motor and Ca 2+ signaling activity significantly diminishes fiber secretion. •These findings could contribute to our understanding of Ad

  15. Playful Interactions Stimulating Physical Activity in Public Spaces

    DEFF Research Database (Denmark)

    Sturm, Janienke; Bekker, Tilde; Vanden Abeele, Vero

    In this position paper we describe our vision on designing playful interactions to persuade people to be physically active in public spaces. Social embeddedness and playful interaction are the core elements of this vision. We illustrate how our design vision is incorporated into innovative concepts...... to motivate each other to be physically active by creating challenges for each other. Designing playful solutions for public spaces asks for low-threshold solutions that support easy stepping in and stepping out solutions....

  16. High levels of DegU-P activate an Esat-6-like secretion system in Bacillus subtilis.

    Directory of Open Access Journals (Sweden)

    Catarina Baptista

    Full Text Available The recently discovered Type VII/Esat-6 secretion systems seem to be widespread among bacteria of the phyla Actinobacteria and Firmicutes. In some species they play an important role in pathogenic interactions with eukaryotic hosts. Several studies have predicted that the locus yukEDCByueBC of the non-pathogenic, Gram-positive bacterium Bacillus subtilis would encode an Esat-6-like secretion system (Ess. We provide here for the first time evidences for the functioning of this secretion pathway in an undomesticated B. subtilis strain. We show that YukE, a small protein with the typical features of the secretion substrates from the WXG100 superfamily is actively secreted to culture media. YukE secretion depends on intact yukDCByueBC genes, whose products share sequence or structural homology with known components of the S. aureus Ess. Biochemical characterization of YukE indicates that it exists as a dimer both in vitro and in vivo. We also show that the B. subtilis Ess essentially operates in late stationary growth phase in absolute dependence of phosphorylated DegU, the response regulator of the two-component system DegS-DegU. We present possible reasons that eventually have precluded the study of this secretion system in the B. subtilis laboratory strain 168.

  17. N-Glycosylation of Carnosinase Influences Protein Secretion and Enzyme Activity Implications for Hyperglycemia

    NARCIS (Netherlands)

    Riedl, Eva; Koeppel, Hannes; Pfister, Frederick; Peters, Verena; Sauerhoefer, Sibylle; Sternik, Paula; Brinkkoetter, Paul; Zentgraf, Hanswalter; Navis, Gerjan; Henning, Robert H.; Van Den Born, Jacob; Bakker, Stephan J. L.; Janssen, Bart; van der Woude, Fokko J.; Yard, Benito A.

    OBJECTIVE-The (CTG)(n) polymorphism in the serum carnosinase (CN-1) gene affects CN-1 secretion Since CN-1 is heavily glycosylated and glycosylation might influence protein secretion as well, we tested the role of N-glycosylation for CN-1 secretion and enzyme activity. We also tested whether CN-1

  18. 77 FR 34037 - Agency Information Collection Activities; Proposed Collection; Comment Request; Trade Secret...

    Science.gov (United States)

    2012-06-08

    ... Activities; Proposed Collection; Comment Request; Trade Secret Claims for Emergency Planning and Community... Planning and Community Right-to- Know Act (EPCRA). Title: Trade Secret Claims for Emergency Planning and...). Estimated total number of potential respondents: 481. Frequency of response: Trade secret claims are...

  19. Energy expenditure while playing active and inactive video games.

    Science.gov (United States)

    Leatherdale, Scott T; Woodruff, Sarah J; Manske, Stephen R

    2010-01-01

    To examine energy expenditure (EE) when playing active and inactive videogames (VG). Predicted EE was measured among 51 undergraduate students while playing active and inactive VG (Ontario, Canada). Predicted EE was significantly higher playing the active VG compared to the inactive VG according to heart rate monitor (97.4 kcal vs 64.7 kcal) and SenseWear armband (192.4 kcal vs 42.3 kcal) estimates. Active VG may be a viable intervention tool for increasing EE among students who would otherwise be spending time in sedentary screen-based behaviors.

  20. A novel serine protease secreted by medicinal maggots enhances plasminogen activator-induced fibrinolysis

    DEFF Research Database (Denmark)

    van der Plas, Mariena J A; Andersen, Anders S; Nazir, Sheresma

    2014-01-01

    Maggots of the blowfly Lucilia sericata are used for the treatment of chronic wounds. As haemostatic processes play an important role in wound healing, this study focused on the effects of maggot secretions on coagulation and fibrinolysis. The results showed that maggot secretions enhance plasmin...

  1. Inhibition of cAMP-activated intestinal chloride secretion by diclofenac: cellular mechanism and potential application in cholera.

    Science.gov (United States)

    Pongkorpsakol, Pawin; Pathomthongtaweechai, Nutthapoom; Srimanote, Potjanee; Soodvilai, Sunhapas; Chatsudthipong, Varanuj; Muanprasat, Chatchai

    2014-09-01

    Cyclic AMP-activated intestinal Cl- secretion plays an important role in pathogenesis of cholera. This study aimed to investigate the effect of diclofenac on cAMP-activated Cl- secretion, its underlying mechanisms, and possible application in the treatment of cholera. Diclofenac inhibited cAMP-activated Cl- secretion in human intestinal epithelial (T84) cells with IC50 of ∼ 20 µM. The effect required no cytochrome P450 enzyme-mediated metabolic activation. Interestingly, exposures of T84 cell monolayers to diclofenac, either in apical or basolateral solutions, produced similar degree of inhibitions. Analyses of the apical Cl- current showed that diclofenac reversibly inhibited CFTR Cl- channel activity (IC50 ∼ 10 µM) via mechanisms not involving either changes in intracellular cAMP levels or CFTR channel inactivation by AMP-activated protein kinase and protein phosphatase. Of interest, diclofenac had no effect on Na(+)-K(+) ATPases and Na(+)-K(+)-Cl- cotransporters, but inhibited cAMP-activated basolateral K(+) channels with IC50 of ∼ 3 µM. In addition, diclofenac suppressed Ca(2+)-activated Cl- channels, inwardly rectifying Cl- channels, and Ca(2+)-activated basolateral K(+) channels. Furthermore, diclofenac (up to 200 µM; 24 h of treatment) had no effect on cell viability and barrier function in T84 cells. Importantly, cholera toxin (CT)-induced Cl- secretion across T84 cell monolayers was effectively suppressed by diclofenac. Intraperitoneal administration of diclofenac (30 mg/kg) reduced both CT and Vibrio cholerae-induced intestinal fluid secretion by ∼ 70% without affecting intestinal fluid absorption in mice. Collectively, our results indicate that diclofenac inhibits both cAMP-activated and Ca(2+)-activated Cl- secretion by inhibiting both apical Cl- channels and basolateral K+ channels in intestinal epithelial cells. Diclofenac may be useful in the treatment of cholera and other types of secretory diarrheas resulting from intestinal

  2. Inhibition of cAMP-activated intestinal chloride secretion by diclofenac: cellular mechanism and potential application in cholera.

    Directory of Open Access Journals (Sweden)

    Pawin Pongkorpsakol

    2014-09-01

    Full Text Available Cyclic AMP-activated intestinal Cl- secretion plays an important role in pathogenesis of cholera. This study aimed to investigate the effect of diclofenac on cAMP-activated Cl- secretion, its underlying mechanisms, and possible application in the treatment of cholera. Diclofenac inhibited cAMP-activated Cl- secretion in human intestinal epithelial (T84 cells with IC50 of ∼ 20 µM. The effect required no cytochrome P450 enzyme-mediated metabolic activation. Interestingly, exposures of T84 cell monolayers to diclofenac, either in apical or basolateral solutions, produced similar degree of inhibitions. Analyses of the apical Cl- current showed that diclofenac reversibly inhibited CFTR Cl- channel activity (IC50 ∼ 10 µM via mechanisms not involving either changes in intracellular cAMP levels or CFTR channel inactivation by AMP-activated protein kinase and protein phosphatase. Of interest, diclofenac had no effect on Na(+-K(+ ATPases and Na(+-K(+-Cl- cotransporters, but inhibited cAMP-activated basolateral K(+ channels with IC50 of ∼ 3 µM. In addition, diclofenac suppressed Ca(2+-activated Cl- channels, inwardly rectifying Cl- channels, and Ca(2+-activated basolateral K(+ channels. Furthermore, diclofenac (up to 200 µM; 24 h of treatment had no effect on cell viability and barrier function in T84 cells. Importantly, cholera toxin (CT-induced Cl- secretion across T84 cell monolayers was effectively suppressed by diclofenac. Intraperitoneal administration of diclofenac (30 mg/kg reduced both CT and Vibrio cholerae-induced intestinal fluid secretion by ∼ 70% without affecting intestinal fluid absorption in mice. Collectively, our results indicate that diclofenac inhibits both cAMP-activated and Ca(2+-activated Cl- secretion by inhibiting both apical Cl- channels and basolateral K+ channels in intestinal epithelial cells. Diclofenac may be useful in the treatment of cholera and other types of secretory diarrheas resulting from intestinal

  3. Secretion and activation of the Serratia marcescens hemolysin by structurally defined ShlB mutants.

    Science.gov (United States)

    Pramanik, Avijit; Könninger, Ulrich; Selvam, Arun; Braun, Volkmar

    2014-05-01

    The ShlA hemolysin of Serratia marcescens is secreted across the outer membrane by the ShlB protein; ShlB belongs to the two-partner secretion system (type Vb), a subfamily of the Omp85 outer membrane protein assembly and secretion superfamily. During secretion, ShlA is converted from an inactive non-hemolytic form into an active hemolytic form. The structure of ShlB is predicted to consist of the N-terminal α-helix H1, followed by the two polypeptide-transport-associated domains POTRA P1 and P2, and the β-barrel of 16 β-strands. H1 is inserted into the pore of the β-barrel in the outer membrane; P1 and P2 are located in the periplasm. To obtain insights into the secretion and activation of ShlA by ShlB, we isolated ShlB mutants impaired in secretion and/or activation. The triple H1 P1 P2 mutant did not secrete ShlA. The P1 and P2 deletion derivatives secreted reduced amounts of ShlA, of which P1 showed some hemolysis, whereas P2 was inactive. Deletion of loop 6 (L6), which is conserved among exporters of the Omp85 family, compromised activation but retained low secretion. Secretion-negative mutants generated by random mutagenesis were located in loop 6. The inactive secreted ShlA derivatives were complemented in vitro to active ShlA by an N-terminal ShlA fragment (ShlA242) secreted by ShlB. Deletion of H1 did not impair secretion of hemolytic ShlA. The study defines domains of ShlB which are important for ShlA secretion and activation. Copyright © 2013 Elsevier GmbH. All rights reserved.

  4. CHILDREN'S MOVEMENT SKILLS WHEN PLAYING ACTIVE VIDEO GAMES.

    Science.gov (United States)

    Hulteen, Ryan M; Johnson, Tara M; Ridgers, Nicola D; Mellecker, Robin R; Barnett, Lisa M

    2015-12-01

    Active video games (AVGs) may be useful for movement skill practice. This study examined children's skill execution while playing Xbox Kinect™ and during movement skill assessment. Nineteen children (10 boys, 9 girls; M age=7.9 yr., SD=1.4) had their skills assessed before AVG play and then were observed once a week for 6 wk. while playing AVGs for 50 min. While AVG play showed evidence of correct skill performance (at least 30-50% of the time when playing table tennis, tennis, and baseball), nearly all skills were more correctly performed during skill assessment (generally more than 50% of the time). This study may help researchers to better understand the role AVGs could play in enhancing real life movement skills.

  5. Biorhythms in the activity of children during free play.

    Science.gov (United States)

    Wade, M G; Ellis, M J; Bohrer, R E

    1973-07-01

    The interaction between the arousal to action of environmental stimuli and recovery from that activity was presumed to generate biorhythms in the activity level of children. The level of environmental stimuli was manipulated by varying the play-group size and the apparatus, and higher environmental complexity was expected to produce more pronounced rhythms. The heart rates of 16 subjects playing in monad, dyad, and tetrad group sizes, in two playroom configurations, were monitored and spectral analysis used to locate significant biorhythms. There was a tendency toward 40-min (slow frequency) and 15-min (fast frequency) biorhythms. The group size manipulation produced the strongest biorhythmic behavior in the dyadic groups. Apparatus differences were not significant but the configuration containing a minimum quantity of play apparatus produced more variable activity than the configuration containing a large amount of play apparatus.

  6. Biorhythms in the activity of children during free play1

    Science.gov (United States)

    Wade, M. G.; Ellis, M. J.; Bohrer, R. E.

    1973-01-01

    The interaction between the arousal to action of environmental stimuli and recovery from that activity was presumed to generate biorhythms in the activity level of children. The level of environmental stimuli was manipulated by varying the play-group size and the apparatus, and higher environmental complexity was expected to produce more pronounced rhythms. The heart rates of 16 subjects playing in monad, dyad, and tetrad group sizes, in two playroom configurations, were monitored and spectral analysis used to locate significant biorhythms. There was a tendency toward 40-min (slow frequency) and 15-min (fast frequency) biorhythms. The group size manipulation produced the strongest biorhythmic behavior in the dyadic groups. Apparatus differences were not significant but the configuration containing a minimum quantity of play apparatus produced more variable activity than the configuration containing a large amount of play apparatus. PMID:4714575

  7. Playing active video games increases energy expenditure in children.

    Science.gov (United States)

    Graf, Diana L; Pratt, Lauren V; Hester, Casey N; Short, Kevin R

    2009-08-01

    To compare energy expenditure rates in children playing the physically active video games, Dance Dance Revolution (DDR) and Nintendo's Wii Sports in relation to treadmill walking. Energy expenditure, heart rate, step rate, and perceived exertion were measured in 14 boys and 9 girls (ages 10-13 years; BMI at 3-98th percentile for age and gender) while watching television at rest, playing DDR at 2 skill levels, playing Wii bowling and boxing, and walking at 2.6, 4.2, and 5.7 km/h. Arterial elasticity was measured at rest and immediately after gaming. Compared with watching television, energy expenditure while gaming or walking increased 2- to 3-fold. Similarly, high rates of energy expenditure, heart rate, and perceived exertion were elicited from playing Wii boxing, DDR level 2, or walking at 5.7 km/h. This occurred despite variations in step rate among activities, reflecting greater use of upper body during Wii play (lowest step rate) than during walking (highest step rate) or DDR play. Wii bowling and beginner level DDR elicited a 2-fold increase in energy expenditure compared to television watching. Large-artery elasticity declined immediately after both DDR and Wii. The change was inversely related to the increment in energy expenditure above rest achieved during the activity. Energy expenditure during active video game play is comparable to moderate-intensity walking. Thus, for children who spend considerable time playing electronic screen games for entertainment, physically active games seem to be a safe, fun, and valuable means of promoting energy expenditure.

  8. The global regulator Crc plays a multifaceted role in modulation of type III secretion system in Pseudomonas aeruginosa.

    Science.gov (United States)

    Dong, Yi-Hu; Zhang, Xi-Fen; Zhang, Lian-Hui

    2013-02-01

    The opportunistic pathogen Pseudomonas aeruginosa utilizes type III secretion system (T3SS) to translocate effector proteins into eukaryotic host cells that subvert normal host cell functions to the benefit of the pathogen, and results in serious infections. T3SS in P. aeruginosa is controlled by a complex system of regulatory mechanisms and signaling pathways. In this study, we described that Crc, an RNA-binding protein, exerts a positive impact on T3SS in P. aeruginosa, as evidenced by promoter activity assays of several key T3SS genes, transcriptomics, RT-PCR, and immunoblotting in crc mutant. We further demonstrated that the regulatory function of Crc on the T3SS was mediated through the T3SS master regulator ExsA and linked to the Cbr/Crc signaling system. Expression profiling of the crc mutant revealed a downregulation of flagship T3SS genes as well as 16 other genes known to regulate T3SS gene expression in P. aeruginosa. On the basis of these data, we proposed that Crc may exert multifaceted control on the T3SS through various pathways, which may serve to fine-tune this virulence mechanism in response to environmental changes and nutrient sources. © 2012 The Authors. Published by Blackwell Publishing Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

  9. Adrenal androgen secretion and dopaminergic activity in anorexia nervosa.

    Science.gov (United States)

    Devesa, J; Pérez-Fernández, R; Bokser, L; Gaudiero, G J; Lima, L; Casanueva, F F

    1988-01-01

    The aim of the present study was to investigate if the postulated deficient adrenal androgen secretion in Anorexia Nervosa (AN), could be associated with a status of sustained dopaminergic hyperactivity. The adrenal responses to ACTH and PRL response to dopaminergic receptor blockade were studied in seven patients with Anorexia Nervosa and seven regularly menstruating women. AN patients showed lower baseline DHEA-sulphate (DHEA-S), androstenedione (Adione) and prolactin (PRL) levels than controls. The response to ACTH revealed evidences of significantly decreased 17-20 desmolase activity in AN, with apparent predominance of glucocorticoid over androgenic pathways relative to controls. Because dopaminergic receptor blockade with Domperidone (DOM) showed intense dopaminergic hyperactivity in AN, we postulate that the adrenal regression seen in the disease is the consequence of a reduced zona reticularis as a consequence of the lack of trophic support by PRL and/or intermediate lobe proopiomelanocortin (IL-POMC). This is consistent with our previous results in pre-adrenarchal dogs and rabbits.

  10. Antifungal activity of epithelial secretions from selected frog species ...

    African Journals Online (AJOL)

    Ezedom Theresa

    2013-11-06

    Nov 6, 2013 ... Chemical stimulation gave the best yield by mass, and secretions from A. fuscigula showed the best ..... electrical stimulation (Dourado et al., 2007; Kim et al.,. 2007 .... Hematopoietic Stem Cell Transplants: An International.

  11. Where do the children play? The influence of playground equipment on physical activity of children in free play.

    Science.gov (United States)

    Farley, Thomas A; Meriwether, Rebecca A; Baker, Erin T; Rice, Janet C; Webber, Larry S

    2008-03-01

    Promotion of physical activity in children depends on an understanding of how children use play equipment. We conducted observations over 2 years of children in 2nd through 8th grades in a schoolyard with 5 distinct play areas with different amounts of play equipment. Children were more likely to play in areas with more installed play equipment, with densities of children in equipped areas 3.3 to 12.6 times higher than in an open grassy field. There were no significant differences by play area in the percent of children who were physically active at all, but children were more likely to be very active in areas with basketball goals and an installed play structure than in an open field. Playground equipment appeared to have a strong influence on where children played and a moderate influence on levels of activity. To maximize physical activity in children, playgrounds should be designed with ample and diverse play equipment.

  12. Glucose decouples intracellular Ca2+ activity from glucagon secretion in mouse pancreatic islet alpha-cells.

    Directory of Open Access Journals (Sweden)

    Sylvain J Le Marchand

    Full Text Available The mechanisms of glucagon secretion and its suppression by glucose are presently unknown. This study investigates the relationship between intracellular calcium levels ([Ca(2+](i and hormone secretion under low and high glucose conditions. We examined the effects of modulating ion channel activities on [Ca(2+](i and hormone secretion from ex vivo mouse pancreatic islets. Glucagon-secreting α-cells were unambiguously identified by cell specific expression of fluorescent proteins. We found that activation of L-type voltage-gated calcium channels is critical for α-cell calcium oscillations and glucagon secretion at low glucose levels. Calcium channel activation depends on K(ATP channel activity but not on tetrodotoxin-sensitive Na(+ channels. The use of glucagon secretagogues reveals a positive correlation between α-cell [Ca(2+](i and secretion at low glucose levels. Glucose elevation suppresses glucagon secretion even after treatment with secretagogues. Importantly, this inhibition is not mediated by K(ATP channel activity or reduction in α-cell [Ca(2+](i. Our results demonstrate that glucose uncouples the positive relationship between [Ca(2+](i and secretory activity. We conclude that glucose suppression of glucagon secretion is not mediated by inactivation of calcium channels, but instead, it requires a calcium-independent inhibitory pathway.

  13. Pragmatic evaluation of the Go2Play Active Play intervention on physical activity and fundamental movement skills in children.

    Science.gov (United States)

    Johnstone, Avril; Hughes, Adrienne R; Janssen, Xanne; Reilly, John J

    2017-09-01

    Active play is a novel approach to addressing low physical activity levels and fundamental movement skills (FMS) in children. This study aimed to determine if a new school-based, 'Go2Play Active Play' intervention improved school day physical activity and FMS. This was a pragmatic evaluation conducted in Scotland during 2015-16. Participants ( n  = 172; mean age = 7 years) were recruited from seven primary schools taking part in the 5-month intervention, plus 24 participants not receiving the intervention were recruited to act as a comparison group.189 participants had physical activity measured using an Actigraph GT3X accelerometer at baseline and again at follow-up 5 months later. A sub-sample of participants from the intervention ( n  = 102) and comparison ( n  = 21) groups had their FMS assessed using the Test of Gross Motor Development (TGMD-2) at baseline and follow-up. Changes in school day physical activity and FMS variables were examined using repeated measures ANOVA. The main effect was 'group' on 'time' from baseline to follow-up. Results indicated there was a significant interaction for mean counts per minute and percent time in sedentary behavior, light intensity physical activity and moderate to vigorous physical activity (MVPA) (all p  skills score and percentile (both p  = 0.02), but no significant interaction for object control skills score ( p  = 0.1) and percentile ( p  = 0.3). The Go2Play Active Play intervention may be a promising way of improving physical activity and FMS but this needs to be confirmed in an RCT.

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

    Science.gov (United States)

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

    2016-07-01

    Children's physical activity has been correlated with child characteristics and social or physical environment. This study aimed to compare preschoolers' physical activity among various sociodemographic characteristics and to determine barriers, motivators, and environmental factors for active play. A total of 835 preschoolers were included in this analysis. Time spent on active play, quiet play, and screen time was reported by parents. Boys spent significantly more time on active play and screen time than girls. Time spent on quiet play was highest in East Coast Peninsular Malaysia and lowest in Sarawak. Some 40% of children achieved active play recommendation while 27% exceeded daily screen time recommendation. Most parents reported that their child played actively in the house area; and that the main barrier and motivator to active play were safety and child's enjoyment, respectively. These findings demonstrate that sociodemographic characteristics and environment should be considered in designing physical activity intervention programs. © 2016 APJPH.

  15. INTERVALS OF ACTIVE PLAY AND BREAK IN BASKETBALL GAMES

    Directory of Open Access Journals (Sweden)

    Pavle Rubin

    2010-09-01

    Full Text Available The problem of the research comes from the need for decomposition of a basketball game. The aim was to determine the intervals of active game (“live ball” - term defined by rules and break (“dead ball” - term defined by rules, by analyzing basketball games. In order to obtain the relevant information, basketball games from five different competitions (top level of quality were analyzed. The sample consists of seven games played in the 2006/2007 season: NCAA Play - Off Final game, Adriatic League finals, ULEB Cup final game, Euroleague (2 games and the NBA league (2 games. The most important information gained by this research is that the average interval of active play lasts approximately 47 seconds, while the average break interval lasts approximately 57 seconds. This information is significant for coaches and should be used in planning the training process.

  16. Playful persuasion to support older adults’ social and physical activities

    NARCIS (Netherlands)

    Romero Herrera, N.A.; Sturm, Janienke; Bekker, M.M.; Valk, de L.C.T.; Kruitwagen, S.

    2010-01-01

    In this paper we describe a case study in which we examine how to develop playful persuasive solutions to motivate older adults to maintain or increase their social and physical activities. By including various stakeholders (older adults, family, and care givers) and by designing for transitions in

  17. Engagement, enjoyment, and energy expenditure during active video game play.

    Science.gov (United States)

    Lyons, Elizabeth J; Tate, Deborah F; Ward, Dianne S; Ribisl, Kurt M; Bowling, J Michael; Kalyanaraman, Sriram

    2014-02-01

    Playing active video games can produce moderate levels of physical activity, but little is known about how these games motivate players to be active. Several psychological predictors, such as perceptions of competence, control, and engagement, may be associated with enjoyment of a game, which has in turn been hypothesized to predict energy expended during play. However, these relationships have yet to be tested in active video games. Young adults aged 18-35 (N = 97, 50 female) game for 13 minutes while energy expenditure was measured using indirect calorimetry. Self-reported measures of engagement, perceived competence, perceived control, and enjoyment were taken immediately afterward. Mediation was analyzed using path analysis. A path model in which enjoyment mediated the effects of engagement, perceived competence, and perceived control on energy expenditure and BMI directly affected energy expenditure was an adequate fit to the data, χ(2)(1, N = 97) = .199, p = .655; CFI = 1.00; RMSEA video game play. Games that are more enjoyable and engaging may produce greater intensity activity. Developers, practitioners, and researchers should consider characteristics that influence these predictors when creating or recommending active video games. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  18. Dietary protein-induced hepatic IGF-1 secretion mediated by PPARγ activation.

    Science.gov (United States)

    Wan, Xiaojuan; Wang, Songbo; Xu, Jingren; Zhuang, Lu; Xing, Kongping; Zhang, Mengyuan; Zhu, Xiaotong; Wang, Lina; Gao, Ping; Xi, Qianyun; Sun, Jiajie; Zhang, Yongliang; Li, Tiejun; Shu, Gang; Jiang, Qingyan

    2017-01-01

    Dietary protein or amino acid (AA) is a crucial nutritional factor to regulate hepatic insulin-like growth factor-1 (IGF-1) expression and secretion. However, the underlying intracellular mechanism by which dietary protein or AA induces IGF-1 expression remains unknown. We compared the IGF-1 gene expression and plasma IGF-1 level of pigs fed with normal crude protein (CP, 20%) and low-protein levels (LP, 14%). RNA sequencing (RNA-seq) was performed to detect transcript expression in the liver in response to dietary protein. The results showed that serum concentrations and mRNA levels of IGF-1 in the liver were higher in the CP group than in the LP group. RNA-seq analysis identified a total of 1319 differentially expressed transcripts (667 upregulated and 652 downregulated), among which the terms "oxidative phosphorylation", "ribosome", "gap junction", "PPAR signaling pathway", and "focal adhesion" were enriched. In addition, the porcine primary hepatocyte and HepG2 cell models also demonstrated that the mRNA and protein levels of IGF-1 and PPARγ increased with the increasing AA concentration in the culture. The PPARγ activator troglitazone increased IGF-1 gene expression and secretion in a dose dependent manner. Furthermore, inhibition of PPARγ effectively reversed the effects of the high AA concentration on the mRNA expression of IGF-1 and IGFBP-1 in HepG2 cells. Moreover, the protein levels of IGF-1 and PPARγ, as well as the phosphorylation of mTOR, significantly increased in HepG2 cells under high AA concentrations. mTOR phosphorylation can be decreased by the mTOR antagonist, rapamycin. The immunoprecipitation results also showed that high AA concentrations significantly increased the interaction of mTOR and PPARγ. In summary, PPARγ plays an important role in the regulation of IGF-1 secretion and gene expression in response to dietary protein.

  19. Modified Active Videogame Play Results in Moderate-Intensity Exercise.

    Science.gov (United States)

    Monedero, Javier; McDonnell, Adam C; Keoghan, Melissa; O'Gorman, Donal J

    2014-08-01

    Large proportions of the population do not meet current American College of Sports Medicine physical activity recommendations, and innovative approaches are required. Most active videogames do not require a significant amount of energy expenditure. The purpose of this study was to determine if modifying an active videogame increased exercise intensity to meet current physical activity recommendations. After completing a maximal oxygen uptake test, participants did a familiarization session on a separate day. Thirteen healthy participants 24.2±3.4 years of age played (1) a sedentary videogame, (2) an active videogame, and (3) a modified active videogame designed to increase physical activity for 46 minutes in a randomized order on separate days. Oxygen uptake, heart rate, heart rate reserve, percentage of maximal heart rate, metabolic equivalents of task, and energy expenditure were significantly higher during the modified active videogame trial than during the active videogame or sedentary videogame trials and also between the active videogame and sedentary videogame. A simple modification to an existing active videogame was sufficient to reach moderate exercise intensity. Active videogames could provide an important option for increasing daily physical activity and reducing sedentary time.

  20. Do Substance P and Neurokinin A Play Important Roles in the Control of LH Secretion in Ewes?

    Science.gov (United States)

    Fergani, Chrysanthi; Mazzella, Leanne; Coolen, Lique M.; McCosh, Richard B.; Hardy, Steven L.; Newcomb, Nora; Grachev, Pasha; Lehman, Michael N.

    2016-01-01

    There is now general agreement that neurokinin B (NKB) acts via neurokinin-3-receptor (NK3R) to stimulate secretion of GnRH and LH in several species, including rats, mice, sheep, and humans. However, the roles of two other tachykinins, substance P (SP) and neurokinin A, which act primarily via NK1R and NK2R, respectively, are less clear. In rodents, these signaling pathways can stimulate LH release and substitute for NKB signaling; in humans, SP is colocalized with kisspeptin and NKB in the mediobasal hypothalamus. In this study, we examined the possible role of these tachykinins in control of the reproductive axis in sheep. Immunohistochemistry was used to describe the expression of SP and NK1R in the ovine diencephalon and determine whether these proteins are colocalized in kisspeptin or GnRH neurons. SP-containing cell bodies were largely confined to the arcuate nucleus, but NK1R-immunoreactivity was more widespread. However, there was very low coexpression of SP or NK1R in kisspeptin cells and none in GnRH neurons. We next determined the minimal effective dose of these three tachykinins that would stimulate LH secretion when administered into the third ventricle of ovary-intact anestrous sheep. A much lower dose of NKB (0.2 nmol) than of neurokinin A (2 nmol) or SP (10 nmol) consistently stimulated LH secretion. Moreover, the relative potency of these three neuropeptides parallels the relative selectivity of NK3R. Based on these anatomical and pharmacological data, we conclude that NKB-NK3R signaling is the primary pathway for the control of GnRH secretion by tachykinins in ewes. PMID:27704950

  1. Playing educational activities as a condition of cooperation skills

    Directory of Open Access Journals (Sweden)

    Panfilova A. P.

    2016-07-01

    Full Text Available the article made an analysis of the training playing activity from the point of view of its influence on the development of collaboration skills among the participants of game sessions, spelled out the conditions for achieving this goal and the necessary ingredients for the organization of effective interpersonal interaction in the process of learning game, based on the rules and ethical norms that do not allow to manipulate and interact correctly.

  2. Interdisciplinary Design Studio Education: Place through the activity of play

    Directory of Open Access Journals (Sweden)

    Fatos Adiloglu

    2011-09-01

    Full Text Available This paper discusses the activity of play in design education among university students with interdisciplinary background. The study subscribes to social theories of learning and takes into account an international summer school which brought visual communication design and architecture students and instructors together at the intersection of design in Istanbul asking such questions: How can student learning activity in design education are fostered? How can studio experience be formulated to cultivate the understanding of place? In this study the international group acted as a learning community. Istanbul served at her best offering her potential for making connections through exploration and discovery. The paper casts student tasks formulated as playful graphic expression and reflects student statements, unfolding connections made across filters of space, time and movement in the working process of visual design studio. The particular design studio experiences uncover how students reconstructed their own texts. The study as a result releases the fact that one might best come to know a place through the activity of play and this kind of knowing is one that constantly evolving.

  3. Brain activity and desire for Internet video game play.

    Science.gov (United States)

    Han, Doug Hyun; Bolo, Nicolas; Daniels, Melissa A; Arenella, Lynn; Lyoo, In Kyoon; Renshaw, Perry F

    2011-01-01

    Recent studies have suggested that the brain circuitry mediating cue-induced desire for video games is similar to that elicited by cues related to drugs and alcohol. We hypothesized that desire for Internet video games during cue presentation would activate similar brain regions to those that have been linked with craving for drugs or pathologic gambling. This study involved the acquisition of diagnostic magnetic resonance imaging and functional magnetic resonance imaging data from 19 healthy male adults (age, 18-23 years) following training and a standardized 10-day period of game play with a specified novel Internet video game, "War Rock" (K2 Network, Irvine, CA). Using segments of videotape consisting of 5 contiguous 90-second segments of alternating resting, matched control, and video game-related scenes, desire to play the game was assessed using a 7-point visual analogue scale before and after presentation of the videotape. In responding to Internet video game stimuli, compared with neutral control stimuli, significantly greater activity was identified in left inferior frontal gyrus, left parahippocampal gyrus, right and left parietal lobe, right and left thalamus, and right cerebellum (false discovery rate Internet video game showed significantly greater activity in right medial frontal lobe, right and left frontal precentral gyrus, right parietal postcentral gyrus, right parahippocampal gyrus, and left parietal precuneus gyrus. Controlling for total game time, reported desire for the Internet video game in the subjects who played more Internet video game was positively correlated with activation in right medial frontal lobe and right parahippocampal gyrus. The present findings suggest that cue-induced activation to Internet video game stimuli may be similar to that observed during cue presentation in persons with substance dependence or pathologic gambling. In particular, cues appear to commonly elicit activity in the dorsolateral prefrontal, orbitofrontal

  4. Pragmatic evaluation of the Go2Play Active Play intervention on physical activity and fundamental movement skills in children

    Directory of Open Access Journals (Sweden)

    Avril Johnstone

    2017-09-01

    Full Text Available Active play is a novel approach to addressing low physical activity levels and fundamental movement skills (FMS in children. This study aimed to determine if a new school-based, ‘Go2Play Active Play’ intervention improved school day physical activity and FMS. This was a pragmatic evaluation conducted in Scotland during 2015–16. Participants (n = 172; mean age = 7 years were recruited from seven primary schools taking part in the 5-month intervention, plus 24 participants not receiving the intervention were recruited to act as a comparison group.189 participants had physical activity measured using an Actigraph GT3X accelerometer at baseline and again at follow-up 5 months later. A sub-sample of participants from the intervention (n = 102 and comparison (n = 21 groups had their FMS assessed using the Test of Gross Motor Development (TGMD-2 at baseline and follow-up. Changes in school day physical activity and FMS variables were examined using repeated measures ANOVA. The main effect was ‘group’ on ‘time’ from baseline to follow-up. Results indicated there was a significant interaction for mean counts per minute and percent time in sedentary behavior, light intensity physical activity and moderate to vigorous physical activity (MVPA (all p < 0.01 for school day physical activity. There was a significant interaction for gross motor quotient (GMQ score (p = 0.02 and percentile (p = 0.04, locomotor skills score and percentile (both p = 0.02, but no significant interaction for object control skills score (p = 0.1 and percentile (p = 0.3. The Go2Play Active Play intervention may be a promising way of improving physical activity and FMS but this needs to be confirmed in an RCT.

  5. Effect of montelukast on platelet activating factor- and tachykinin induced mucus secretion in the rat

    Directory of Open Access Journals (Sweden)

    Groneberg David A

    2008-02-01

    Full Text Available Abstract Background Platelet activating factor and tachykinins (substance P, neurokinin A, neurokinin B are important mediators contributing to increased airway secretion in the context of different types of respiratory diseases including acute and chronic asthma. Leukotriene receptor antagonists are recommended as add-on therapy for this disease. The cys-leukotriene-1 receptor antagonist montelukast has been used in clinical asthma therapy during the last years. Besides its inhibitory action on bronchoconstriction, only little is known about its effects on airway secretions. Therefore, the aim of this study was to evaluate the effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity. Methods The effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity in the rat were assessed by quantification of secreted 35SO4 labelled mucus macromolecules using the modified Ussing chamber technique. Results Platelet activating factor potently stimulated airway secretion, which was completely inhibited by the platelet activating factor receptor antagonist WEB 2086 and montelukast. In contrast, montelukast had no effect on tachykinin induced tracheal secretory activity. Conclusion Cys-leukotriene-1 receptor antagonism by montelukast reverses the secretagogue properties of platelet activating factor to the same degree as the specific platelet activating factor antagonist WEB 2086 but has no influence on treacheal secretion elicited by tachykinins. These results suggest a role of montelukast in the signal transduction pathway of platelet activating factor induced secretory activity of the airways and may further explain the beneficial properties of cys-leukotriene-1 receptor antagonists.

  6. Cyclosporin A Impairs the Secretion and Activity of ADAMTS13 (A Disintegrin and Metalloprotease with Thrombospondin Type 1 Repeat)*

    Science.gov (United States)

    Hershko, Klilah; Simhadri, Vijaya L.; Blaisdell, Adam; Hunt, Ryan C.; Newell, Jordan; Tseng, Sandra C.; Hershko, Alon Y.; Choi, Jae Won; Sauna, Zuben E.; Wu, Andrew; Bram, Richard J.; Komar, Anton A.; Kimchi-Sarfaty, Chava

    2012-01-01

    The protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat) cleaves multimers of von Willebrand factor, thus regulating platelet aggregation. ADAMTS13 deficiency leads to the fatal disorder thrombotic thrombocytopenic purpura (TTP). It has been observed that cyclosporin A (CsA) treatment, particularly in transplant patients, may sometimes be linked to the development of TTP. Until now, the reason for such a link was unclear. Here we provide evidence demonstrating that cyclophilin B (CypB) activity plays an important role in the secretion of active ADAMTS13. We found that CsA, an inhibitor of CypB, reduces the secretion of ADAMTS13 and leads to conformational changes in the protein resulting in diminished ADAMTS13 proteolytic activity. A direct, functional interaction between CypB (which possesses peptidyl-prolyl cis-trans isomerase (PPIase) and chaperone functions) and ADAMTS13 is demonstrated using immunoprecipitation and siRNA knockdown of CypB. Finally, CypB knock-out mice were found to have reduced ADAMTS13 levels. Taken together, our findings indicate that cyclophilin-mediated activity is an important factor affecting secretion and activity of ADAMTS13. The large number of proline residues in ADAMTS13 is consistent with the important role of cis-trans isomerization in the proper folding of this protein. These results altogether provide a novel mechanistic explanation for CsA-induced TTP in transplant patients. PMID:23144461

  7. Cyclosporin A impairs the secretion and activity of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat).

    Science.gov (United States)

    Hershko, Klilah; Simhadri, Vijaya L; Blaisdell, Adam; Hunt, Ryan C; Newell, Jordan; Tseng, Sandra C; Hershko, Alon Y; Choi, Jae Won; Sauna, Zuben E; Wu, Andrew; Bram, Richard J; Komar, Anton A; Kimchi-Sarfaty, Chava

    2012-12-28

    The protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat) cleaves multimers of von Willebrand factor, thus regulating platelet aggregation. ADAMTS13 deficiency leads to the fatal disorder thrombotic thrombocytopenic purpura (TTP). It has been observed that cyclosporin A (CsA) treatment, particularly in transplant patients, may sometimes be linked to the development of TTP. Until now, the reason for such a link was unclear. Here we provide evidence demonstrating that cyclophilin B (CypB) activity plays an important role in the secretion of active ADAMTS13. We found that CsA, an inhibitor of CypB, reduces the secretion of ADAMTS13 and leads to conformational changes in the protein resulting in diminished ADAMTS13 proteolytic activity. A direct, functional interaction between CypB (which possesses peptidyl-prolyl cis-trans isomerase (PPIase) and chaperone functions) and ADAMTS13 is demonstrated using immunoprecipitation and siRNA knockdown of CypB. Finally, CypB knock-out mice were found to have reduced ADAMTS13 levels. Taken together, our findings indicate that cyclophilin-mediated activity is an important factor affecting secretion and activity of ADAMTS13. The large number of proline residues in ADAMTS13 is consistent with the important role of cis-trans isomerization in the proper folding of this protein. These results altogether provide a novel mechanistic explanation for CsA-induced TTP in transplant patients.

  8. The differences in physical activity levels in preschool children during free play recess and structured play recess

    Directory of Open Access Journals (Sweden)

    Megan L. Frank

    2018-04-01

    Full Text Available Background/Objective: Physical activity (PA is important in reducing childhood obesity, yet a majority of children are not meeting PA guidelines. Schools have been identified as a place to promote childhood PA. The purpose of this study was to determine the best type of physically active recess period to increase preschool-aged children's PA. Methods: PA was measured via accelerometers in preschool-aged children (n = 29 during three, 30-min recess conditions (control; structured play; free play on separate school days. Tertile splits were performed based on PA during the free play condition and children were divided into three groups: highly, moderately and least active. Results: For the aggregated sample, children were more (p ≤ 0.001 active during the free play (1282 ± 662 counts. min−1 and structured play (1416 ± 448 counts. min−1 recess versus the control condition (570 ± 460 counts. min−1 and activity was not different between the free play and structured conditions. However, children who were the most active during free play (1970 ± 647 counts·min−1 decreased (p ≤ 0.05 activity during structured play (1462 ± 535 counts·min−1, whereas children who were moderately active (1031 ± 112 counts·min−1 or the least (530 ± 239 counts·min−1 active during free play increased activity during structured play (1383 ± 345 counts·min−1 moderately active, 1313 ± 413 counts·min−1 least active. Conclusion: Providing a physically-active recess period will contribute to preschool-aged children meeting the recommended PA guidelines; however, different children may respond in a different way based upon the structure of the recess period.

  9. PLAY ACTIVITY WITH MILITARY TOYS AT PRESCHOOL AGE

    Directory of Open Access Journals (Sweden)

    Irina Nikolaevna Aleshina

    2013-12-01

    Full Text Available The article analyzes various attitudes to military toys, both positive and negative, existing in Russia and abroad. Toy weapons are viewed as a separate type of military toy. The study looks at the impact of military toys on children’s emotions and personality. The study looks at how children play games on their own and the way they organize them. We have conducted an experiment where three types of toys were used – military toys, soft toys and objects that act as toy substitutes. The study of games and the roles children took showed their poor playing skills. The research has detected existing connection between imagination and thinking ability and the children’s play activity. None of the children took the role of ‘the defender of the weak’ or ‘Patria’s defender’, which contradicts the results of an opinion survey of children’s parents who think that military toys help to develop ‘patriotism’, ‘courage’, and ‘teach to protect the weak’.Repeated observation of the way the same children play with military toys has shown that they take the role of defenders of the motherland or the weak only after watching TV-programmes or fiction films which show male characters defending their motherland or the weak using weapons, which shows that children’s games have social character.The experiment’s results detected what activity adults, who are concerned with the young generation’s attitude to weapons and violence, should perform. It is vital to strengthen children’s moral, ethical and cognitive spheres first, and only in second place fight against sales of military toys both in Russia and abroad.DOI: http://dx.doi.org/10.12731/2218-7405-2013-8-53

  10. Brain activity and desire for internet video game play

    Science.gov (United States)

    Han, Doug Hyun; Bolo, Nicolas; Daniels, Melissa A.; Arenella, Lynn; Lyoo, In Kyoon; Renshaw, Perry F.

    2010-01-01

    Objective Recent studies have suggested that the brain circuitry mediating cue induced desire for video games is similar to that elicited by cues related to drugs and alcohol. We hypothesized that desire for internet video games during cue presentation would activate similar brain regions to those which have been linked with craving for drugs or pathological gambling. Methods This study involved the acquisition of diagnostic MRI and fMRI data from 19 healthy male adults (ages 18–23 years) following training and a standardized 10-day period of game play with a specified novel internet video game, “War Rock” (K-network®). Using segments of videotape consisting of five contiguous 90-second segments of alternating resting, matched control and video game-related scenes, desire to play the game was assessed using a seven point visual analogue scale before and after presentation of the videotape. Results In responding to internet video game stimuli, compared to neutral control stimuli, significantly greater activity was identified in left inferior frontal gyrus, left parahippocampal gyrus, right and left parietal lobe, right and left thalamus, and right cerebellum (FDR video game (MIGP) cohort showed significantly greater activity in right medial frontal lobe, right and left frontal pre-central gyrus, right parietal post-central gyrus, right parahippocampal gyrus, and left parietal precuneus gyrus. Controlling for total game time, reported desire for the internet video game in the MIGP cohort was positively correlated with activation in right medial frontal lobe and right parahippocampal gyrus. Discussion The present findings suggest that cue-induced activation to internet video game stimuli may be similar to that observed during cue presentation in persons with substance dependence or pathological gambling. In particular, cues appear to commonly elicit activity in the dorsolateral prefrontal, orbitofrontal cortex, parahippocampal gyrus, and thalamus. PMID:21220070

  11. p38 Mitogen-activated protein kinase modulates exocrine secretion in rabbit lacrimal gland.

    Science.gov (United States)

    Carlsson, Stina K; Gierow, J Peter

    2012-03-01

    The lacrimal gland (LG) is an exocrine gland important for secretion of the tear film. The kinase p38 has important signal transduction functions, e.g. in gene transcription, but has previously not been known to modulate exocrine secretion. The aim of the current study was to investigate the role of p38 in carbachol (Cch)-induced LG secretion in LG acinar cells in vitro. Western blotting was used to determine the phosphorylation status of p38 and p42/44 and determine expression of p38 isoforms. To determine the effect of p38 inhibition on LG secretion, PD 169316, a general p38 inhibitor, and SB 239063, an inhibitor of p38α and β, were added to the cells prior to secretion measurements. The results revealed activation of p38 mediated by Cch stimulation and inhibition of Cch-induced secretion as a result of p38 inhibition. The inhibition was observed with PD 169316 isoforms, but not with SB 239063. The p38δ isoform was shown to have robust expression both by Western blotting of acinar cells and immunofluorescence of the whole gland. In conclusion, p38 activation mediates secretion in cholinergic stimulation of rabbit LG cells.

  12. VEGF secretion during hypoxia depends on free radicals-induced Fyn kinase activity in mast cells

    International Nuclear Information System (INIS)

    Garcia-Roman, Jonathan; Ibarra-Sanchez, Alfredo; Lamas, Monica; Gonzalez Espinosa, Claudia

    2010-01-01

    Research highlights: → Bone marrow-derived mast cells (BMMCs) secrete functional VEGF but do not degranulate after Cobalt chloride-induced hypoxia. → CoCl 2 -induced VEGF secretion in mast cells occurs by a Ca 2+ -insensitive but brefeldin A and Tetanus toxin-sensitive mechanism. → Trolox and N-acetylcysteine inhibit hypoxia-induced VEGF secretion but only Trolox inhibits FcεRI-dependent anaphylactic degranulation in mast cells. → Src family kinase Fyn activation after free radical production is necessary for hypoxia-induced VEGF secretion in mast cells. -- Abstract: Mast cells (MC) have an important role in pathologic conditions such as asthma and chronic obstructive pulmonary disease (COPD), where hypoxia conduce to deleterious inflammatory response. MC contribute to hypoxia-induced angiogenesis producing factors such as vascular endothelial growth factor (VEGF), but the mechanisms behind the control of hypoxia-induced VEGF secretion in this cell type is poorly understood. We used the hypoxia-mimicking agent cobalt chloride (CoCl 2 ) to analyze VEGF secretion in murine bone marrow-derived mast cells (BMMCs). We found that CoCl 2 promotes a sustained production of functional VEGF, able to induce proliferation of endothelial cells in vitro. CoCl 2 -induced VEGF secretion was independent of calcium rise but dependent on tetanus toxin-sensitive vesicle-associated membrane proteins (VAMPs). VEGF exocytosis required free radicals formation and the activation of Src family kinases. Interestingly, an important deficiency on CoCl 2 -induced VEGF secretion was observed in Fyn kinase-deficient BMMCs. Moreover, Fyn kinase was activated by CoCl 2 in WT cells and this activation was prevented by treatment with antioxidants such as Trolox and N-acetylcysteine. Our results show that BMMCs are able to release VEGF under hypoxic conditions through a tetanus toxin-sensitive mechanism, promoted by free radicals-dependent Fyn kinase activation.

  13. VEGF secretion during hypoxia depends on free radicals-induced Fyn kinase activity in mast cells

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Roman, Jonathan; Ibarra-Sanchez, Alfredo; Lamas, Monica [Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados del IPN (Cinvestav, IPN) (Mexico); Gonzalez Espinosa, Claudia, E-mail: cgonzal@cinvestav.mx [Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados del IPN (Cinvestav, IPN) (Mexico)

    2010-10-15

    Research highlights: {yields} Bone marrow-derived mast cells (BMMCs) secrete functional VEGF but do not degranulate after Cobalt chloride-induced hypoxia. {yields} CoCl{sub 2}-induced VEGF secretion in mast cells occurs by a Ca{sup 2+}-insensitive but brefeldin A and Tetanus toxin-sensitive mechanism. {yields} Trolox and N-acetylcysteine inhibit hypoxia-induced VEGF secretion but only Trolox inhibits Fc{epsilon}RI-dependent anaphylactic degranulation in mast cells. {yields} Src family kinase Fyn activation after free radical production is necessary for hypoxia-induced VEGF secretion in mast cells. -- Abstract: Mast cells (MC) have an important role in pathologic conditions such as asthma and chronic obstructive pulmonary disease (COPD), where hypoxia conduce to deleterious inflammatory response. MC contribute to hypoxia-induced angiogenesis producing factors such as vascular endothelial growth factor (VEGF), but the mechanisms behind the control of hypoxia-induced VEGF secretion in this cell type is poorly understood. We used the hypoxia-mimicking agent cobalt chloride (CoCl{sub 2}) to analyze VEGF secretion in murine bone marrow-derived mast cells (BMMCs). We found that CoCl{sub 2} promotes a sustained production of functional VEGF, able to induce proliferation of endothelial cells in vitro. CoCl{sub 2}-induced VEGF secretion was independent of calcium rise but dependent on tetanus toxin-sensitive vesicle-associated membrane proteins (VAMPs). VEGF exocytosis required free radicals formation and the activation of Src family kinases. Interestingly, an important deficiency on CoCl{sub 2}-induced VEGF secretion was observed in Fyn kinase-deficient BMMCs. Moreover, Fyn kinase was activated by CoCl{sub 2} in WT cells and this activation was prevented by treatment with antioxidants such as Trolox and N-acetylcysteine. Our results show that BMMCs are able to release VEGF under hypoxic conditions through a tetanus toxin-sensitive mechanism, promoted by free radicals

  14. Proteolytic activity regarding Sarconesiopsis magellanica (Diptera: Calliphoridae) larval excretions and secretions.

    Science.gov (United States)

    Pinilla, Yudi T; Moreno-Pérez, Darwin A; Patarroyo, Manuel A; Bello, Felio J

    2013-12-01

    Sarconesiopsis magellanica (Diptera: Calliphoridae) is a medically important necrophagous fly which is used for establishing the post-mortem interval. Diptera maggots release proteolytic enzymes contained in larval excretion and secretion (ES) products playing a key role in digestion. Special interest in proteolytic enzymes has also been aroused regarding understanding their role in wound healing since they degrade necrotic tissue during larval therapy. This study was thus aimed at identifying and characterising S. magellanica proteolytic enzyme ES products for the first time. These products were obtained from first-, second- and third-instar larvae taken from a previously-established colony. ES proteins were separated by SDS-PAGE and their proteolytic activity was characterised by zymograms and inhibition assays involving BAPNA (Nα-benzoyl-dl-Arg-p-nitroanilide) and SAPNA substrates, using synthetic inhibitors. The protein profile ranged from ∼69kDa to ∼23kDa; several of them coincided with the Lucilia sericata ES protein profile. Serine-protease hydrolysis activity (measured by zymogram) was confirmed when a ∼25kDa band disappeared upon ES incubation with PMSF inhibitor at pH 7.8. Analysis of larval ES proteolytic activity on BAPNA and SAPNA substrates (determined by using TLCK and TPCK specific inhibitors) suggested a greater amount of trypsin-like protease. These results support the need for further experiments aimed at validating S. magellanica use in larval therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Skill-Based and Planned Active Play Versus Free-Play Effects on Fundamental Movement Skills in Preschoolers.

    Science.gov (United States)

    Roach, Lindsay; Keats, Melanie

    2018-01-01

    Fundamental movement skill interventions are important for promoting physical activity, but the optimal intervention model for preschool children remains unclear. We compared two 8-week interventions, a structured skill-station and a planned active play approach, to a free-play control condition on pre- and postintervention fundamental movement skills. We also collected data regarding program attendance and perceived enjoyment. We found a significant interaction effect between intervention type and time. A Tukey honest significant difference analysis supported a positive intervention effect showing a significant difference between both interventions and the free-play control condition. There was a significant between-group difference in group attendance such that mean attendance was higher for both the free-play and planned active play groups relative to the structured skill-based approach. There were no differences in attendance between free-play and planned active play groups, and there were no differences in enjoyment ratings between the two intervention groups. In sum, while both interventions led to improved fundamental movement skills, the active play approach offered several logistical advantages. Although these findings should be replicated, they can guide feasible and sustainable fundamental movement skill programs within day care settings.

  16. On detecting the playing/non-playing activity of musicians in symphonic music videos

    NARCIS (Netherlands)

    Bazzica, A.; Liem, C.C.S.; Hanjalic, A.

    2016-01-01

    Information on whether a musician in a large symphonic orchestra plays her instrument at a given time stamp or not is valuable for a wide variety of applications aiming at mimicking and enriching the classical music concert experience on modern multimedia platforms. In this work, we propose a novel

  17. Active and non-active video gaming among Dutch adolescents: who plays and how much?

    Science.gov (United States)

    Simons, Monique; de Vet, Emely; Brug, Johannes; Seidell, Jaap; Chinapaw, Mai J M

    2014-11-01

    The aim of study was to determine prevalence and identify demographic correlates of active and non-active gaming among adolescents. Cross-sectional. A survey, assessing game behavior and correlates, was conducted among adolescents (12-16 years, n = 373), recruited via schools. Multivariable logistic regression analyses were conducted to examine demographic correlates of active gaming (≥ 1 h per week) and non-active gaming (>7h per week). Of all participants (n=373), 3% reported to play exclusively active games, 40% active games and non-active games, 40% exclusively non-active games, and 17% not playing video games at all. Active gaming adolescents played active games on average on 1.5 (sd = 1.2) days per school week for 36 (sd = 32.9)min and 1 (sd = 0.54) day per weekend for 42 (sd = 36.5)min. Non-active gaming adolescents played on average on 3.3 (sd = 1.6) days per school week for 65 (sd = 46.0)min and 1.4 (sd = 0.65) days per weekend for 80 (sd = 50.8)min. Adolescents attending lower levels of education were more likely to play active games ≥ 1 h per week than adolescents attending higher educational levels. Boys and older adolescents were more likely to play non-active games >7h per week, than girls or younger adolescents. Many adolescents play active games, especially those following a lower educational level, but time spent in this activity is relatively low compared to non-active gaming. To be feasible as a public health strategy, active gaming interventions should achieve more time is spent on active gaming at the expense of non-active gaming. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  18. Maternal attitude and child interest in various play activities before and after mother-child play sessions

    Directory of Open Access Journals (Sweden)

    Soedjatmiko Soedjatmiko

    2018-01-01

    Full Text Available Background Play stimulates children’s growth and development. When mothers and their children play, a positive attitude from the mother and adequate interest from the child is required. Little is known about the play activities that effectively stimulate such positive maternal attitude and child interest. Objective To assess for associations between various play activities with maternal attitude and child interest before and after mother-child play sessions. Methods Pre-post intervention questionnaires were distributed to mothers before and after playing with their children. Children were aged 1-5 years, from two play sites (in Surabaya and Makassar, and included using purposive sampling. Eight types of toys/play activities were provided. The allocated time for answering the 17-question survey was 15 minutes. Average scores before and after the mother-child play sessions were analyzed using paired T-test. Results We collected 264 valid questionnaires, 235 in Surabaya and 29 in Makassar. Improvement of maternal attitude after the mother-child play session was found in 132 mothers [mean diff. 0.07 (SD 0.42; 95%CI -0.117 to -0.015; P=0.011]. Play activities with significant improvements in maternal attitude were jigsaw puzzle [mean diff. 0.09 (SD 0.66; 95% CI 0.007 to 0.167;P= 0.033, Lego blocks (mean diff.-0.10 (SD 0.69; 95%CI -0.186 to -0.018; P=0.017, mini-gardening (mean diff. -0.15 (SD 0.75; 95%CI -0.238 to -0.057; P=0.002, sandbox [mean diff.-0.24 (SD 0.83; 95%CI -0.339 to – 0.138; P < 0.001], fishing [mean diff. -0.17 (SD 0.68; 95%CI -0.253 to -0.088; P < 0.001], and animal figurines [mean diff. -0.21 (SD 0.75; 95%CI -0.3 to -0.117;P <0.001]. Improvement of child interest was found in 161 children [mean diff. 0.20 (SD 0.52; 95%CI -0.264 to -0.116; P<0.001]. Play activities with significant improvements in child interest were jigsaw puzzle, Lego blocks, origami, mini-gardening, fishing, and animal figurines. Conclusion Some mother

  19. M19 modulates skeletal muscle differentiation and insulin secretion in pancreatic β-cells through modulation of respiratory chain activity.

    Directory of Open Access Journals (Sweden)

    Linda Cambier

    Full Text Available Mitochondrial dysfunction due to nuclear or mitochondrial DNA alterations contributes to multiple diseases such as metabolic myopathies, neurodegenerative disorders, diabetes and cancer. Nevertheless, to date, only half of the estimated 1,500 mitochondrial proteins has been identified, and the function of most of these proteins remains to be determined. Here, we characterize the function of M19, a novel mitochondrial nucleoid protein, in muscle and pancreatic β-cells. We have identified a 13-long amino acid sequence located at the N-terminus of M19 that targets the protein to mitochondria. Furthermore, using RNA interference and over-expression strategies, we demonstrate that M19 modulates mitochondrial oxygen consumption and ATP production, and could therefore regulate the respiratory chain activity. In an effort to determine whether M19 could play a role in the regulation of various cell activities, we show that this nucleoid protein, probably through its modulation of mitochondrial ATP production, acts on late muscle differentiation in myogenic C2C12 cells, and plays a permissive role on insulin secretion under basal glucose conditions in INS-1 pancreatic β-cells. Our results are therefore establishing a functional link between a mitochondrial nucleoid protein and the modulation of respiratory chain activities leading to the regulation of major cellular processes such as myogenesis and insulin secretion.

  20. Antibacterial activity of the parotid glands secretions of sudanese indigenous african toad (Bufo spp.)

    International Nuclear Information System (INIS)

    Abugabr, H. E.; Elhussein, S. A.; Mahmoud, Z. N.

    2009-01-01

    The study revealed a well-built first line innate immunity system in Bufo Spp., the skin extracts illustrated a very active antibiotic attitude which inhibited the growth of human pathogenic bacteria species, Escherichia coli (ATCC 19615), staphylococcus aureus(ATCC29213) and streptococcus pyogenes (ATCC25922). Heat treatment of secretion supported the fact that the antibacterial components possess an enzymatic attitude. Gel filtration chromatography accompanied with sensitivity tests against S.aureus showed the existence of four groups responsible for antibacterial activity in the parotoid glands secretions.(Author)

  1. The motivation of children to play an active video game.

    Science.gov (United States)

    Chin A Paw, Marijke J M; Jacobs, Wietske M; Vaessen, Ellen P G; Titze, Sylvia; van Mechelen, Willem

    2008-04-01

    The purpose of this pilot study was to evaluate the effect of a weekly multiplayer class on the motivation of children aged 9-12 years to play an interactive dance simulation video game (IDSVG) at home over a period of 12 weeks. A sample of 27 children was randomly assigned to (1) a home group instructed to play the IDSVG at home; (2) a multiplayer group instructed to play the IDSVG at home and to participate in a weekly IDSVG multiplayer class. Participants were asked to play the IDSVG as often as they liked and report the playing time daily on a calendar for a 12-week period. Motivation to play was assessed by the playing duration of IDSVG in minutes and the dropout during the study. Mean age of the 16 children who completed the study was 10.6+/-0.8 years. During the 12-week intervention period, the multiplayer group played approximately twice as many minutes (901min) as the home group (376min, p=0.13). Dropout was significantly (p=0.02) lower in the multiplayer group (15%) than in the home group (64%). Our findings suggest that multiplayer classes may increase children's motivation to play interactive dance simulation video games.

  2. Fuel-Stimulated Insulin Secretion Depends upon Mitochondria Activation and the Integration of Mitochondrial and Cytosolic Substrate Cycles

    Directory of Open Access Journals (Sweden)

    Gary W. Cline

    2011-10-01

    Full Text Available The pancreatic islet β-cell is uniquely specialized to couple its metabolism and rates of insulin secretion with the levels of circulating nutrient fuels, with the mitochondrial playing a central regulatory role in this process. In the β-cell, mitochondrial activation generates an integrated signal reflecting rates of oxidativephosphorylation, Kreb's cycle flux, and anaplerosis that ultimately determines the rate of insulin exocytosis. Mitochondrial activation can be regulated by proton leak and mediated by UCP2, and by alkalinization to utilize the pH gradient to drive substrate and ion transport. Converging lines of evidence support the hypothesis that substrate cycles driven by rates of Kreb's cycle flux and by anaplerosis play an integral role in coupling responsive changes in mitochondrial metabolism with insulin secretion. The components and mechanisms that account for the integrated signal of ATP production, substrate cycling, the regulation of cellular redox state, and the production of other secondary signaling intermediates are operative in both rodent and human islet β-cells.

  3. Antibacterial, modulatory activity of antibiotics and toxicity from Rhinella jimi (Stevaux, 2002) (Anura: Bufonidae) glandular secretions.

    Science.gov (United States)

    Sales, Débora Lima; Morais-Braga, Maria Flaviana Bezerra; Santos, Antonia Thassya Lucas Dos; Machado, Antonio Judson Targino; Araujo Filho, João Antonio de; Dias, Diógenes de Queiroz; Cunha, Francisco Assis Bezerra da; Saraiva, Rogério de Aquino; Menezes, Irwin Rose Alencar de; Coutinho, Henrique Douglas Melo; Costa, José Galberto Martins; Ferreira, Felipe Silva; Alves, Rômulo Romeu da Nóbrega; Almeida, Waltécio de Oliveira

    2017-08-01

    The increase in microorganisms with resistance to medications has caused a strong preoccupation within the medical and scientific community. Animal toxins studies, such as parotoid glandular secretions from amphibians, possesses a great potential in the development of drugs, such as antimicrobials, as these possess bioactive compounds. It was evaluated Rhinella jimi (Stevaux, 2002) glandular secretions against standard and multi-resistant bacterial strains; the effect of secretions combined with drugs; and determined the toxicity using two biologic in vivo models, and a in vitro model with mice livers. Standard strains were used for the determination of the Minimum Inhibitory Concentration (MIC), while for the modulatory activity of antibiotics, the clinical isolates Escherichia coli 06, Pseudomonas aeruginosa 03 and Staphylococcus aureus 10 were used. Modulatory activity was evaluated by the broth microdilution method with aminoglycosides and β-lactams as target antibiotics. The secretions in association with the antibiotics have a significant reduction in MIC, both the aminoglycosides and β-lactams. The toxicity and cytotoxicity results were lower than the values used in the modulation. R. jimi glandular secretions demonstrated clinically relevant results regarding the modulation of the tested antimicrobials. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Activity and energy expenditure in older people playing active video games.

    Science.gov (United States)

    Taylor, Lynne M; Maddison, Ralph; Pfaeffli, Leila A; Rawstorn, Jonathan C; Gant, Nicholas; Kerse, Ngaire M

    2012-12-01

    Tayl To quantify energy expenditure in older adults playing interactive video games while standing and seated, and secondarily to determine whether participants' balance status influenced the energy cost associated with active video game play. Cross-sectional study. University research center. Community-dwelling adults (N=19) aged 70.7±6.4 years. Participants played 9 active video games, each for 5 minutes, in random order. Two games (boxing and bowling) were played in both seated and standing positions. Energy expenditure was assessed using indirect calorimetry while at rest and during game play. Energy expenditure was expressed in kilojoules per minute and metabolic equivalents (METs). Balance was assessed using the mini-BESTest, the Activities-specific Balance Confidence Scale, and the Timed Up and Go (TUG). Mean ± SD energy expenditure was significantly greater for all game conditions compared with rest (all P≤.01) and ranged from 1.46±.41 METs to 2.97±1.16 METs. There was no significant difference in energy expenditure, activity counts, or perceived exertion between equivalent games played while standing and seated. No significant correlations were observed between energy expenditure or activity counts and balance status. Active video games provide light-intensity exercise in community-dwelling older people, whether played while seated or standing. People who are unable to stand may derive equivalent benefits from active video games played while seated. Further research is required to determine whether sustained use of active video games alters physical activity levels in community settings for this population. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  5. Parents' Perceptions of Preschool Activities: Exploring Outdoor Play

    Science.gov (United States)

    Jayasuriya, Avanthi; Williams, Marcia; Edwards, Todd; Tandon, Pooja

    2016-01-01

    Research Findings: Outdoor play is important for children's health and development, yet many preschool-age children in child care settings do not receive the recommended 60 min/day of outdoor play. Child care providers have previously described parent-related barriers to increasing outdoor playtime, including parents not providing appropriate…

  6. Setting them up for lifetime activity: Play competence perceptions and physical activity in young children.

    Science.gov (United States)

    Barnett, Lisa M; Ridgers, Nicola D; Hesketh, Kylie; Salmon, Jo

    2017-09-01

    Possessing positive physical perceived competence is important for physical activity in older children. Young children are primarily physically active through play-based behaviour rather than through organised sports and activities, so understanding how play perceptions might influence physical activity behaviour is important. The study purpose was to assess if perceived active play competence is associated with young children's physical activity. Cross sectional study. This paper uses two different samples drawn from the same Australian city, both collected in 2013. The first sample included 152 children (49% boys) aged 4-5 years (M=4.7, SD=0.47), the second sample included 78 children (55% boys) aged 5-8 years (M=6.6, SD=0.93). The Pictorial Scale of Perceived Movement Skill Competence was used to assess children's perceived competence in six skill-related play activities. Moderate- to vigorous-intensity physical activity (MVPA) was assessed for 8 consecutive days via accelerometers. A general linear model with the mean minutes in MVPA per day as the outcome, perceived play competence as the independent variable and adjusting for relevant confounders was performed in each sample. Perceived active play competence was not related to MVPA min/day (B=0.44, p=0.323) in the younger sample, but was in the older sample (B=1.53, p=0.026), explaining 24% of adjusted variance. Positive findings in the older sample show school-aged children need exposure to play based activities in order to develop the positive self-perception needed to engage in MVPA every day. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  7. Platelet-activating factor increases platelet-dependent glycoconjugate secretion from tracheal submucosal gland

    International Nuclear Information System (INIS)

    Sasaki, T.; Shimura, S.; Ikeda, K.; Sasaki, H.; Takishima, T.

    1989-01-01

    Using isolated glands from feline trachea, we examined the effect of platelet-activating factor (PAF) on radiolabeled glycoconjugate release and glandular contraction by measuring induced tension in the absence or presence of platelets. PAF alone did not produce any significant glandular contraction nor any significant change in glycoconjugate release from isolated glands. In the presence of purified platelets containing no plasma, PAF (10(-8) to 10(-5) M) produced significant glycoconjugate secretion in a dose-dependent fashion, but it produced no significant glandular contraction. PAF-evoked glycoconjugate secretion was time dependent, reaching a peak response of 277% of control 15-30 min after the exposure of isolated glands to 10(-5) M PAF in the presence of platelets and returning to 135% of controls at 2 h. Platelets alone did not produce any significant stimulation in glycoconjugate release. CV-3988, a known PAF antagonist, inhibited the secretory response to PAF. Methysergide, a known antagonist to receptors for 5-hydroxytryptamine, did not alter PAF-evoked glycoconjugate secretion. Both indomethacin and SQ 29,548, a thromboxane receptor antagonist, abolished the PAF-evoked glycoconjugate secretion from isolated submucosal glands. Epithiomethanothromboxane A2, a stable thromboxane A2 analogue, produced a significant increase in glycoconjugate secretion in a dose-dependent fashion. These findings indicate that PAF increases glycoconjugate release in the presence of platelets and that the increase is dependent on some aspect of platelet function, namely thromboxane generation

  8. Viability, Apoptosis, Proliferation, Activation, and Cytokine Secretion of Human Keratoconus Keratocytes after Cross-Linking

    Directory of Open Access Journals (Sweden)

    Xuefei Song

    2015-01-01

    Full Text Available Purpose. The purpose of this study was to determine the impact of cross-linking (CXL on viability, apoptosis, proliferation, activation, and cytokine secretion of human keratoconus (KC keratocytes, in vitro. Methods. Primary KC keratocytes were cultured in DMEM/Ham’s F12 medium supplemented with 10% FCS and underwent UVA illumination (370 nm, 2 J/cm2 during exposure to 0.1% riboflavin and 20% Dextran in PBS. Twenty-four hours after CXL, viability was assessed using Alamar blue assay; apoptosis using APO-DIRECT Kit; proliferation using ELISA-BrdU kit; and CD34 and alpha-smooth muscle actin (α-SMA expression using flow cytometry. Five and 24 hours after CXL, FGFb, HGF, TGFβ1, VEGF, KGF, IL-1β, IL-6, and IL-8 secretion was measured using enzyme-linked-immunoabsorbent assay (ELISA. Results. Following CXL, cell viability and proliferation decreased (P0.06. Five hours after CXL, FGFb secretion increased significantly (P=0.037; however no other cytokine secretion differed significantly from controls after 5 or 24 hours (P>0.12. Conclusions. Cross-linking decreases viability, triggers apoptosis, and inhibits proliferation, without an impact on multipotent hematopoietic stem cell transformation and myofibroblastic transformation of KC keratocytes. CXL triggers FGFb secretion of KC keratocytes transiently (5 hours, normalizing after 24 hours.

  9. Tumor-secreted LOXL2 activates fibroblasts through FAK signaling

    DEFF Research Database (Denmark)

    Barker, Holly E; Bird, Demelza; Lang, Georgina

    2013-01-01

    models. Here, we discovered that tumor-derived LOXL2 directly activated stromal fibroblasts in the tumor microenvironment. Genetic manipulation or antibody inhibition of LOXL2 in orthotopically grown mammary tumors reduced the expression of α-smooth muscle actin (α-SMA). Using a marker for reticular....... Importantly, in vitro assays revealed that tumor-derived LOXL2 and a recombinant LOXL2 protein induced fibroblast branching on collagen matrices, as well as increased fibroblast-mediated collagen contraction and invasion of fibroblasts through extracellular matrix. Moreover, LOXL2 induced the expression of α...

  10. Mining anaerobic digester consortia metagenomes for secreted carbohydrate active enzymes

    DEFF Research Database (Denmark)

    Wilkens, Casper; Busk, Peter Kamp; Pilgaard, Bo

    thermophilic and mesophilic ADs a wide variety of carbohydrate active enzyme functions were discovered in the metagenomic sequencing of the microbial consortia. The most dominating type of glycoside hydrolases were β-glucosidases (up to 27%), α-amylases (up to 10%), α-glucosidases (up to 8%), α......, and food wastes (Alvarado et al., 2014). The processes and the roles of the microorganisms that are involved in biomass conversion and methane production in ADs are still not fully understood. We are investigating thermophilic and mesophilic ADs that use wastewater surplus sludge for methane production...... was done with the Peptide Pattern Recognition (PPR) program (Busk and Lange, 2013), which is a novel non-alignment based approach that can predict function of e.g. CAZymes. PPR identifies a set of short conserved sequences, which can be used as a finger print when mining genomes for novel enzymes. In both...

  11. Computer Programming: An Activity as Compelling as Game Play

    Directory of Open Access Journals (Sweden)

    Tom Goulding

    2010-04-01

    Full Text Available Game motif programming exercises (GM-Games were developed to help novices develop complex client server game systems within their freshman year. GM-Games foster a strong work ethic in as much as they reproduce the challenges and excitement associated with game play; yet their purpose is the development of advanced programming skills. We have found that young people are just as interested in mastering programming skills as they are in mastering the shooting, racing or strategy skills required in many entertainment games. We describe in this paper how GM-Games imitate many of the aspects of game play.

  12. Loss of a neural AMP-activated kinase mimics the effects of elevated serotonin on fat, movement, and hormonal secretions.

    Directory of Open Access Journals (Sweden)

    Katherine A Cunningham

    2014-06-01

    Full Text Available AMP-activated protein kinase (AMPK is an evolutionarily conserved master regulator of metabolism and a therapeutic target in type 2 diabetes. As an energy sensor, AMPK activity is responsive to both metabolic inputs, for instance the ratio of AMP to ATP, and numerous hormonal cues. As in mammals, each of two genes, aak-1 and aak-2, encode for the catalytic subunit of AMPK in C. elegans. Here we show that in C. elegans loss of aak-2 mimics the effects of elevated serotonin signaling on fat reduction, slowed movement, and promoting exit from dauer arrest. Reconstitution of aak-2 in only the nervous system restored wild type fat levels and movement rate to aak-2 mutants and reconstitution in only the ASI neurons was sufficient to significantly restore dauer maintenance to the mutant animals. As in elevated serotonin signaling, inactivation of AAK-2 in the ASI neurons caused enhanced secretion of dense core vesicles from these neurons. The ASI neurons are the site of production of the DAF-7 TGF-β ligand and the DAF-28 insulin, both of which are secreted by dense core vesicles and play critical roles in whether animals stay in dauer or undergo reproductive development. These findings show that elevated levels of serotonin promote enhanced secretions of systemic regulators of pro-growth and differentiation pathways through inactivation of AAK-2. As such, AMPK is not only a recipient of hormonal signals but can also be an upstream regulator. Our data suggest that some of the physiological phenotypes previously attributed to peripheral AAK-2 activity on metabolic targets may instead be due to the role of this kinase in neural serotonin signaling.

  13. FTO Inhibits Insulin Secretion and Promotes NF-κB Activation through Positively Regulating ROS Production in Pancreatic β cells.

    Directory of Open Access Journals (Sweden)

    Hong-Qi Fan

    Full Text Available FTO (Fat mass and obesity-associated is associated with increased risk of obesity and type 2 diabetes incurrence. Pancreas islet β cells dysfunction and insulin resistance are major causes of type 2 diabetes. However, whether FTO plays an important functional role in pancreatic β cells as well as the related molecular mechanism is still unclear. In the present study, the tissue expression profile of FTO was firstly determined using quantitative PCR and western blot. FTO is widely expressed in various tissues and presented with relative high expression in pancreas tissue, especially in endocrine pancreas. FTO overexpression in MIN6 cells achieved by lentivirus delivery significantly inhibits insulin secretion in the presence of glucose stimulus as well as KCl. FTO silence has no effect on insulin secretion of MIN6 cells. However, FTO overexpression doesn't affect the transcription of insulin gene. Furthermore, reactive oxygen species (ROS production and NF-κB activation are significantly promoted by FTO overexpression. Inhibition of intracellular ROS production by N-acetyl-L-cysteine (NAC can alleviate NF-κB activation and restore the insulin secretion mediated by FTO overexpression. A whole transcript-microarray is employed to analyze the differential gene expression mediated by FTO overexpression. The genes which are modulated by FTO are involved in many important biological pathways such as G-protein coupled receptor signaling and NF-κB signaling. Therefore, our study indicates that FTO may contribute to pancreas islet β cells dysfunction and the inhibition of FTO activity is a potential target for the treatment of diabetes.

  14. Antimicrobial activity of the pygidial gland secretion of three ground beetle species (Insecta: Coleoptera: Carabidae)

    Science.gov (United States)

    Nenadić, Marija; Soković, Marina; Glamočlija, Jasmina; Ćirić, Ana; Perić-Mataruga, Vesna; Ilijin, Larisa; Tešević, Vele; Vujisić, Ljubodrag; Todosijević, Marina; Vesović, Nikola; Ćurčić, Srećko

    2016-04-01

    The antimicrobial properties of the pygidial gland secretions released by the adults of the three ground beetle species, Carabus ullrichii, C. coriaceus, and Abax parallelepipedus, have been tested. Microdilution method was applied for detection of minimal inhibitory concentrations (MICs), minimal bactericidal concentrations (MBCs), and minimal fungicidal concentrations (MFCs). Additionally, morpho-histology of the pygidial glands is investigated. We have tested 16 laboratory and clinical strains of human pathogens—eight bacterial both gram-positive and gram-negative species and eight fungal species. The pygidial secretion samples of C. ullrichii have showed the strongest antimicrobial effect against all strains of treated bacteria and fungi. Staphylococcus aureus, Lysteria monocytogenes, and Salmonella typhimurium proved to be the most sensitive bacterial strains. Penicillium funiculosum proved to be the most sensitive micromycete, while P. ochrochloron and P. verrucosum var . cyclopium the most resistant micromycetes. The pygidial secretion of C. coriaceus has showed antibacterial potential solely against Pseudomonas aeruginosa and antifungal activity against Aspergillus fumigatus, A. versicolor, A. ochraceus, and P. ochrochloron. Antibacterial properties of pygidial gland secretion of A. parallelepipedus were achieved against P. aeruginosa, while antifungal activity was detected against five of the eight tested micromycetes (A. fumigatus, A. versicolor, A. ochraceus, Trichoderma viride, and P. verrucosum var . cyclopium). Commercial antibiotics Streptomycin and Ampicillin and mycotics Ketoconazole and Bifonazole, applied as the positive controls, showed higher antibacterial/antifungal properties for all bacterial and fungal strains. The results of this observation might have a significant impact on the environmental aspects and possible medical purpose in the future.

  15. The motivation of children to play an active video game

    NARCIS (Netherlands)

    Chin A Paw, M.J.M.; Jacobs, W.M.; Vaessen, E.P.G.; Titze, S.; van Mechelen, W.

    2008-01-01

    The purpose of this pilot study was to evaluate the effect of a weekly multiplayer class on the motivation of children aged 9-12 years to play an interactive dance simulation video game (IDSVG) at home over a period of 12 weeks. A sample of 27 children was randomly assigned to (1) a home group

  16. Day care quality and children's free play activities.

    Science.gov (United States)

    Vandell, D L; Powers, C P

    1983-07-01

    Social and nonsocial behavior of white, middle-class preschoolers in high, moderate, and low quality day care centers were contrasted. Children in high quality centers were more likely to interact positively with adults, while children in lower quality programs were more likely to engage in solitary play and aimless wandering.

  17. Metabolic changes associated with playing active video game ...

    African Journals Online (AJOL)

    Twenty adults (10 males and 10 females) between 19 and 25 years of age played Nintendo Wii Boxing™ for 15 minutes. ... the VO2max assessment. ... opponent when compared to when at rest (1.1 ± 0.1 kcal•min-1), while no significant differences were found between the two video game opponents or males and females.

  18. JNK mitogen-activated protein kinase limits calcium-dependent chloride secretion across colonic epithelial cells.

    LENUS (Irish Health Repository)

    Donnellan, Fergal

    2010-01-01

    Neuroimmune agonists induce epithelial Cl(-) secretion through elevations in intracellular Ca2+ or cAMP. Previously, we demonstrated that epidermal growth factor receptor (EGFR) transactivation and subsequent ERK MAPK activation limits secretory responses to Ca2+-dependent, but not cAMP-dependent, agonists. Although JNK MAPKs are also expressed in epithelial cells, their role in regulating transport function is unknown. Here, we investigated the potential role for JNK in regulating Cl(-) secretion in T(84) colonic epithelial cells. Western blot analysis revealed that a prototypical Ca2+-dependent secretagogue, carbachol (CCh; 100 microM), induced phosphorylation of both the 46-kDa and 54-kDa isoforms of JNK. This effect was mimicked by thapsigargin (TG), which specifically elevates intracellular Ca2+, but not by forskolin (FSK; 10 microM), which elevates cAMP. CCh-induced JNK phosphorylation was attenuated by the EGFR inhibitor, tyrphostin-AG1478 (1 microM). Pretreatment of voltage-clamped T(84) cells with SP600125 (2 microM), a specific JNK inhibitor, potentiated secretory responses to both CCh and TG but not to FSK. The effects of SP600125 on CCh-induced secretion were not additive with those of the ERK inhibitor, PD98059. Finally, in apically permeabilized T(84) cell monolayers, SP600125 potentiated CCh-induced K+ conductances but not Na+\\/K+ATPase activity. These data demonstrate a novel role for JNK MAPK in regulating Ca2+ but not cAMP-dependent epithelial Cl(-) secretion. JNK activation is mediated by EGFR transactivation and exerts its antisecretory effects through inhibition of basolateral K+ channels. These data further our understanding of mechanisms regulating epithelial secretion and underscore the potential for exploitation of MAPK-dependent signaling in treatment of intestinal transport disorders.

  19. An Intracellular Peptidyl-Prolyl cis/trans Isomerase Is Required for Folding and Activity of the Staphylococcus aureus Secreted Virulence Factor Nuclease.

    Science.gov (United States)

    Wiemels, Richard E; Cech, Stephanie M; Meyer, Nikki M; Burke, Caleb A; Weiss, Andy; Parks, Anastacia R; Shaw, Lindsey N; Carroll, Ronan K

    2017-01-01

    Staphylococcus aureus is an important human pathogen that relies on a large repertoire of secreted and cell wall-associated proteins for pathogenesis. Consequently, the ability of the organism to cause disease is absolutely dependent on its ability to synthesize and successfully secrete these proteins. In this study, we investigate the role of peptidyl-prolyl cis/trans isomerases (PPIases) on the activity of the S. aureus secreted virulence factor nuclease (Nuc). We identify a staphylococcal cyclophilin-type PPIase (PpiB) that is required for optimal activity of Nuc. Disruption of ppiB results in decreased nuclease activity in culture supernatants; however, the levels of Nuc protein are not altered, suggesting that the decrease in activity results from misfolding of Nuc in the absence of PpiB. We go on to demonstrate that PpiB exhibits PPIase activity in vitro, is localized to the bacterial cytosol, and directly interacts with Nuc in vitro to accelerate the rate of Nuc refolding. Finally, we demonstrate an additional role for PpiB in S. aureus hemolysis and demonstrate that the S. aureus parvulin-type PPIase PrsA also plays a role in the activity of secreted virulence factors. The deletion of prsA leads to a decrease in secreted protease and phospholipase activity, similar to that observed in other Gram-positive pathogens. Together, these results demonstrate, for the first time to our knowledge, that PPIases play an important role in the secretion of virulence factors in S. aureus IMPORTANCE: Staphylococcus aureus is a highly dangerous bacterial pathogen capable of causing a variety of infections throughout the human body. The ability of S. aureus to cause disease is largely due to an extensive repertoire of secreted and cell wall-associated proteins, including adhesins, toxins, exoenzymes, and superantigens. These virulence factors, once produced, are typically transported across the cell membrane by the secretory (Sec) system in a denatured state. Consequently

  20. Play Equipment, Physical Activity Opportunities, and Children's Activity Levels at Childcare

    Directory of Open Access Journals (Sweden)

    Jessica S. Gubbels

    2012-01-01

    Full Text Available This study investigated the association between physical activity facilities at childcare (e.g., play equipment and physical activity of 2- and 3-year olds. Observations of physical activity intensity were performed among 175 children at 9 childcare centers in The Netherlands, using the OSRAC-P. The physical activity facilities were assessed for indoors and outdoors separately, using the EPAO instrument. Regular (single-level multivariate and multilevel linear regression analyses examined the association of the facilities and child characteristics (age and sex with children's activity levels. Various physical activity facilities were available in all childcare centers (e.g., balls. Riding toys and a small playing area were associated with lower indoor physical activity levels. Outdoor physical activity levels were positively associated with the availability of portable jumping equipment and the presence of a structured track on the playground. Portable slides, fixed swinging equipment, and sandboxes were negatively associated with outdoor activity levels. In addition, the 3-year old children were more active outdoors than the 2-year olds. In conclusion, not all physical activity facilities at childcare were indeed positively associated with children's activity levels. The current findings provide concrete leads for childcare providers regarding which factors they can improve in the physical environment to facilitate children's physical activity.

  1. Activation of PPARd and RXRa stimulates fatty acid oxidatin and insulin secretion inpancreatic beta-cells

    DEFF Research Database (Denmark)

    Børgesen, Michael; Ravnskjær, Kim; Frigerio, Francesca

    as a central effector of unsaturated fatty acids in pancreatic ß-cells. Interestingly, activation of PPARd increases basal as well as glucose-stimulated insulin secretion of INS-1E cells. This increase is further potentiated by RXR agonists. This observation suggests that PPARd may mediate some of the positive......ACTIVATION OF PPARd AND RXRa STIMULATES FATTY ACID OXIDATION AND INSULIN SECRETION IN PANCREATIC b-CELLS Michael Boergesen1, Kim Ravnskjaer2, Francesca Frigerio3, Allan E. Karlsen4, Pierre Maechler3 and Susanne Mandrup1 1 Department of Biochemistry and Molecular Biology, University of Southern...... of genes as PPARd specific agonists and stimulates ß-oxidation. Importantly, oleate-induction of gene expression and ß-oxidation in INS-1E cells is abolished by knock-down of PPARd using adenoviral transfer of shRNA. Thus, PPARd appears to be a central regulator of fatty acid metabolism as well...

  2. Protein secretion in human mammary epithelial cells following HER1 receptor activation: influence of HER2 and HER3 expression

    International Nuclear Information System (INIS)

    Zhang, Yi; Gonzalez, Rachel M; Zangar, Richard C

    2011-01-01

    Protein secretion by mammary cells results in autocrine and paracrine signaling that defines cell growth, migration and the extracellular environment. Even so, we have a limited understanding of the cellular processes that regulate protein secretion. In this study, we utilize human epithelial mammary cell (HMEC) lines that were engineered to express different levels of HER1, HER2 and HER3. Using an ELISA microarray platform, we evaluate the effects of epidermal growth factor family receptor (HER) expression on protein secretion in the HMEC lines upon initiation of HER1 receptor activation. The secreted proteins include three HER1 ligands, interleukins 1α and 18, RANTES, vascular-endothelial and platelet-derived growth factors, matrix metalloproteases 1, 2 and 9, and the extracellular portion of the HER1 and HER2 proteins. In addition, we investigate whether MAPK/Erk and PI3K/Akt signaling regulate protein secretion in these cell lines and if so, whether the involvement of HER2 or HER3 receptor alters their response to MAPK/Erk and PI3K/Akt signal pathway inhibition in terms of protein secretion. Differential expression of HER2 and HER3 receptors alters the secretion of a variety of growth factors, cytokines, and proteases. Some alterations in protein secretion are still observed when MAPK/Erk or PI3K/Akt signaling is inhibited. This study suggests that HER overexpression orchestrates broad changes in the tumor microenvironment by altering the secretion of a diverse variety of biologically active proteins

  3. What is the meaning and nature of active play for today's children in the UK?

    Science.gov (United States)

    Brockman, Rowan; Fox, Kenneth R; Jago, Russell

    2011-03-07

    Preventing the decline in physical activity which occurs around 10-11 years of age is a public health priority. Physically active play can make unique contributions to children's development which cannot be obtained from more structured forms of physical activity. Encouraging active play in children's leisure time has potential to increase physical activity levels while promoting optimal child development. Aspired wisdom states that contemporary British children no longer play outdoors, but systematic evidence for this is lacking. We need to build a more informed picture of contemporary children's play before we consider interventions to increase it. Eleven focus groups were conducted with 77, 10-11 year old children from four primary schools in Bristol, UK. Focus groups examined: 1) children's perceptions of 'play'; 2) how much of their play is active play; and 3) contexts of children's active play. All focus groups were audio-taped and transcribed verbatim. Data were analysed using a thematic approach. Children's perceptions of play were broad and included both physically active and sedentary behaviours. Children reported that they frequently engaged in active play and valued both the physical and social benefits it provided. Whereas boys frequently reported having a 'kick about' or riding bikes as their preferred forms of active play, girls were less likely to report a specific activity. Additionally, boys reported greater independent mobility in their active play compared to girls. Finally, boys were more likely to report playing with neighbourhood friends but girls more frequently reported playing with family members. Promoting active play in children's leisure time may increase the physical activity of children, but interventions may need to be tailored according to gender.

  4. What is the meaning and nature of active play for today's children in the UK?

    Directory of Open Access Journals (Sweden)

    Jago Russell

    2011-03-01

    Full Text Available Abstract Background Preventing the decline in physical activity which occurs around 10-11 years of age is a public health priority. Physically active play can make unique contributions to children's development which cannot be obtained from more structured forms of physical activity. Encouraging active play in children's leisure time has potential to increase physical activity levels while promoting optimal child development. Aspired wisdom states that contemporary British children no longer play outdoors, but systematic evidence for this is lacking. We need to build a more informed picture of contemporary children's play before we consider interventions to increase it. Methods Eleven focus groups were conducted with 77, 10-11 year old children from four primary schools in Bristol, UK. Focus groups examined: 1 children's perceptions of 'play'; 2 how much of their play is active play; and 3 contexts of children's active play. All focus groups were audio-taped and transcribed verbatim. Data were analysed using a thematic approach. Results Children's perceptions of play were broad and included both physically active and sedentary behaviours. Children reported that they frequently engaged in active play and valued both the physical and social benefits it provided. Whereas boys frequently reported having a 'kick about' or riding bikes as their preferred forms of active play, girls were less likely to report a specific activity. Additionally, boys reported greater independent mobility in their active play compared to girls. Finally, boys were more likely to report playing with neighbourhood friends but girls more frequently reported playing with family members. Conclusions Promoting active play in children's leisure time may increase the physical activity of children, but interventions may need to be tailored according to gender.

  5. Online-offline activities and game-playing behaviors of avatars in a massive multiplayer online role-playing game

    Science.gov (United States)

    Jiang, Zhi-Qiang; Zhou, Wei-Xing; Tan, Qun-Zhao

    2009-11-01

    Massive multiplayer online role-playing games (MMORPGs) are very popular in China, which provides a potential platform for scientific research. We study the online-offline activities of avatars in an MMORPG to understand their game-playing behavior. The statistical analysis unveils that the active avatars can be classified into three types. The avatars of the first type are owned by game cheaters who go online and offline in preset time intervals with the online duration distributions dominated by pulses. The second type of avatars is characterized by a Weibull distribution in the online durations, which is confirmed by statistical tests. The distributions of online durations of the remaining individual avatars differ from the above two types and cannot be described by a simple form. These findings have potential applications in the game industry.

  6. Footballs versus Barbies: Childhood Play Activities as Predictors of Sport Participation by Women.

    Science.gov (United States)

    Guiliano, Traci A.; Popp, Kathryn E.; Knight, Jennifer L.

    2000-01-01

    Examined the extent to which women's childhood play activities predicted future sport participation. College athletes and nonathletes completed a survey on childhood play and adult sports experiences. Playing with masculine toys and games, playing in predominantly male or mixed groups, and being a tomboy characterized women who later became…

  7. Platelet activating factor receptor binding plays a critical role in jet fuel-induced immune suppression

    International Nuclear Information System (INIS)

    Ramos, Gerardo; Kazimi, Nasser; Nghiem, Dat X.; Walterscheid, Jeffrey P.; Ullrich, Stephen E.

    2004-01-01

    Applying military jet fuel (JP-8) or commercial jet fuel (Jet-A) to the skin of mice suppresses the immune response in a dose-dependant manner. The release of biological response modifiers, particularly prostaglandin E 2 (PGE 2 ), is a critical step in activating immune suppression. Previous studies have shown that injecting selective cyclooxygenase-2 inhibitors into jet fuel-treated mice blocks immune suppression. Because the inflammatory phospholipid mediator, platelet-activating factor (PAF), up-regulates cyclooxygenase-2 production and PGE 2 synthesis by keratinocytes, we tested the hypothesis that PAF-receptor binding plays a role in jet fuel-induced immune suppression. Treating keratinocyte cultures with PAF and/or jet fuel (JP-8 and Jet-A) stimulates PGE 2 secretion. Jet fuel-induced PGE 2 production was suppressed by treating the keratinocytes with specific PAF-receptor antagonists. Injecting mice with PAF, or treating the skin of the mice with JP-8, or Jet-A, induced immune suppression. Jet fuel-induced immune suppression was blocked when the jet fuel-treated mice were injected with PAF-receptor antagonists before treatment. Jet fuel treatment has been reported to activate oxidative stress and treating the mice with anti-oxidants (Vitamins C, or E or beta-hydroxy toluene), before jet fuel application, interfered with immune suppression. These findings confirm previous studies showing that PAF-receptor binding can modulate immune function. Furthermore, they suggest that PAF-receptor binding may be an early event in the induction of immune suppression by immunotoxic environmental agents that target the skin

  8. Spondylolysis in Active Adolescents: Expediting Return to Play.

    Science.gov (United States)

    Moeller, James L.; Rifat, Sami F.

    2001-01-01

    Spondylolysis is a common cause of back pain in active adolescents. For prolonged pain, an aggressive workup and specific diagnosis are needed. History and physical exam findings are not diagnostic. Tests beyond radiographs (computed tomography, bone scans, and magnetic resonance imaging) are necessary to determine metabolic activity and full…

  9. Playing Goffman's Information Game: A Classroom Activity Involving Student Interactions

    Science.gov (United States)

    McCoy, Charles Allan

    2017-01-01

    Goffman's dramaturgical approach is frequently used to introduce undergraduate students to the sociological understanding of human interaction. While a number of scholars have designed engaging student activities that highlight Goffman's approach, most of these activities tend to involve atypical embarrassing interactions or norm-breaking…

  10. Sweet Taste Receptor Activation in the Gut Is of Limited Importance for Glucose-Stimulated GLP-1 and GIP Secretion

    DEFF Research Database (Denmark)

    Saltiel, Monika Yosifova; Kuhre, Rune Ehrenreich; Christiansen, Charlotte Bayer

    2017-01-01

    Glucose stimulates the secretion of the incretin hormones: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). It is debated whether the sweet taste receptor (STR) triggers this secretion. We investigated the role of STR activation for glucose-stimulated incretin...

  11. Physical activity and play in kindergarten age children

    DEFF Research Database (Denmark)

    Caroli, Margherita; Malecka-Tendera, Ewa; Epifani, Susi

    2011-01-01

    PERISCOPE project assesses factors promoting or preventing obesity development in early age. A specifi c aim is to assess preschool children ’ s physical activity habits in three different European countries. PERISCOPE has been implemented in 1094 children attending kindergartens in Denmark, Italy...... and Poland. The parents ’ and children ’ s physical activity habits and attitudes assessed by a questionnaire fi lled by the parents. Overweight and obesity assessed by Cole ’ s BMI cut-off points. Statistical analysis performed by χ^2 test and the test of proportion. Denmark shows the lowest rate (14...... hour (p active, the Polish are in the middle and the Italians are the least active. The difference in infrastructures (safety of walking streets, access...

  12. Effects of Behavioral Contingencies on Adolescent Active Videogame Play and Overall Activity: A Randomized Trial.

    Science.gov (United States)

    Norman, Gregory J; Adams, Marc A; Ramirez, Ernesto R; Carlson, Jordan A; Kerr, Jacqueline; Godbole, Suneeta; Dillon, Lindsay; Marshall, Simon J

    2013-06-01

    This study evaluated the effect of four active videogames (AVGs) varying in behavioral contingencies (behavior-consequence relations) on adolescent AVG play and overall activity levels over 4 weeks. Each AVG, manufactured by SSD/Xavix(®) (Shiseido Co. of Japan, Tokyo, Japan), was coded and scored for the number of positive and aversive behavioral contingencies within the games. "Bowling" and "Tennis" were classified as having "higher contingency scores," and "Boxing" and aerobic fitness training were classified as having "lower contingency scores." Adolescents (n=63; 11-15 years old; 62% male; 38% Hispanic; 44% overweight or obese) were randomized to play one of the four AVGs at home and recorded game play sessions in a paper log. Baseline and week 4 assessments were completed at home; week 1, 2, and 3 assessments were completed by telephone. Accelerometers were worn during baseline and weeks 1 and 4. Accelerometer-measured sedentary and light activity hours/day were stable over time, whereas moderate-vigorous physical activity minutes/day increased in the higher contingency group and decreased in the lower contingency group (interaction effect, 6.43, P=0.024). Reported game play minutes decreased in both groups from week 1 to week 4 (-29.42 minutes, P=0.001). There was some support for the hypothesis that AVGs with more behavioral contingencies, compared with AVGs with fewer behavioral contingencies, result in more physical activity. However, overall AVG play decreased substantially after the first week. Further study is needed to better understand how behavioral contingencies can be used in AVGs to enhance their potential to provide health benefits to game players.

  13. Activation of the sigma-1 receptor by haloperidol metabolites facilitates brain-derived neurotrophic factor secretion from human astroglia.

    Science.gov (United States)

    Dalwadi, Dhwanil A; Kim, Seongcheol; Schetz, John A

    2017-05-01

    Glial cells play a critical role in neuronal support which includes the production and release of the neurotrophin brain-derived neurotrophic factor (BDNF). Activation of the sigma-1 receptor (S1R) has been shown to attenuate inflammatory stress-mediated brain injuries, and there is emerging evidence that this may involve a BDNF-dependent mechanism. In this report we studied S1R-mediated BDNF release from human astrocytic glial cells. Astrocytes express the S1R, which mediates BDNF release when stimulated with the prototypical S1R agonists 4-PPBP and (+)-SKF10047. This effect could be antagonized by a selective concentration of the S1R antagonist BD1063. Haloperidol is known to have high affinity interactions with the S1R, yet it was unable to facilitate BDNF release. Remarkably, however, two metabolites of haloperidol, haloperidol I and haloperidol II (reduced haloperidol), were discovered to facilitate BDNF secretion and this effect was antagonized by BD1063. Neither 4-PPBP, nor either of the haloperidol metabolites affected the level of BDNF mRNA as assessed by qPCR. These results demonstrate for the first time that haloperidol metabolites I and II facilitate the secretion of BDNF from astrocytes by acting as functionally selective S1R agonists. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Relations between Playing Activities and Fine Motor Development

    Science.gov (United States)

    Suggate, Sebastian; Stoeger, Heidrun; Pufke, Eva

    2017-01-01

    Children's fine motor skills (FMS) are being increasingly recognized as an important aspect of preschool development; yet, we know very little about the experiences that foster their development. We utilized a parent-administered children's fine and gross motor activities questionnaire (MAQ) to investigate links with FMS. We recruited a sample of…

  15. Physical Activity Plays an Important Role in Body Weight Regulation

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Chaput

    2011-01-01

    Full Text Available Emerging literature highlights the need to incorporate physical activity into every strategy intended to prevent weight gain as well as to maintain weight loss over time. Furthermore, physical activity should be part of any plan to lose weight. The stimulus of exercise provides valuable metabolic adaptations that improve energy and macronutrient balance regulation. A tight coupling between energy intake and energy expenditure has been documented at high levels of physical exercise, suggesting that exercise may improve appetite control. The regular practice of physical activity has also been reported to reduce the risk of stress-induced weight gain. A more personalized approach is recommended when planning exercise programs in a clinical weight loss setting in order to limit the compensatory changes associated to exercise-induced weight loss. With modern environment promoting overeating and sedentary behavior, there is an urgent need for a concerted action including legislative measures to promote healthy active living in order to curb the current epidemic of chronic diseases.

  16. Children and adolescent physical activity participation and enjoyment during active play.

    Science.gov (United States)

    Moghaddaszadeh, Asal; Ahmadi, Yasamin; Belcastro, Angelo N

    2017-10-01

    Girls' (9-19 years) participation in physical activity (PA) is known to decrease at a faster rate than boys. A reduction in PA attractiveness (enjoyment) and lower psychosocial profile of girls approaching biological maturity may underlie the decreasing rate of PA participation. Since engaging children in active play programs improves health related quality of life indictors and enjoyment levels; the purposes of this study were to: 1) assess psychosocial status and PA attractiveness/enjoyment of boys and girls to an eight-week active play program; and 2) investigate the relationships among PA participation, psychosocial status and PA attractiveness with both age and maturity status for boys and girls following an active play PA program. Thirty-three children (age 9.8±1.3 years; weight 43.1±13.4 kg; BMI 20.8±3.2 kg/m2) were recruited to participate in an active play program for 8 weeks (4x/week; 1hr/d). M-S estimates ranged from -6.7 to -2.5 years away from biological maturity Daily program PA was assessed and compared to pre-post measures of psychosocial functioning and PA attractiveness. Statistical procedures were performed using ANOVA and/or Pearson's correlation r (SPSS v. 22.0) with P=0.05. PA participation in the active play program showed a group average of 39±11% time spent in moderate-vigorous PA (%MVPA) with boys averaging 45% MVPA and girls averaging 30% MVPA (Pattractiveness scores for boys did not change following the program; whereas girls improved from 67±13% to 76±9% (Pattractiveness to %MVPA, 80% of girls reporting positive changes or no change; in contrast 56% of boys responded with negative/less PA attractiveness. PA attractiveness for all children was negatively associated with age (r=-0.19) and/or M-S (r=-0.29). The relationships, however, were gender specific with boys exhibiting a coefficient of -0.28 (age) and -0.61 (M-S) (Pattractiveness promoted less decline in %MVPA for M-S (r=0.18) compared to age (r=-0.17). For girls, approaching

  17. Conazole fungicides inhibit Leydig cell testosterone secretion and androgen receptor activation in vitro

    Directory of Open Access Journals (Sweden)

    Maarke J.E. Roelofs

    2014-01-01

    Full Text Available Conazole fungicides are widely used in agriculture despite their suspected endocrine disrupting properties. In this study, the potential (anti-androgenic effects of ten conazoles were assessed and mutually compared with existing data. Effects of cyproconazole (CYPRO, fluconazole (FLUC, flusilazole (FLUS, hexaconazole (HEXA, myconazole (MYC, penconazole (PEN, prochloraz (PRO, tebuconazole (TEBU, triadimefon (TRIA, and triticonazole (TRIT were examined using murine Leydig (MA-10 cells and human T47D-ARE cells stably transfected with an androgen responsive element and a firefly luciferase reporter gene. Six conazoles caused a decrease in basal testosterone (T secretion by MA-10 cells varying from 61% up to 12% compared to vehicle-treated control. T secretion was concentration-dependently inhibited after exposure of MA-10 cells to several concentrations of FLUS (IC50 = 12.4 μM or TEBU (IC50 = 2.4 μM in combination with LH. The expression of steroidogenic and cholesterol biosynthesis genes was not changed by conazole exposure. Also, there were no changes in reactive oxygen species (ROS formation that could explain the altered T secretion after exposure to conazoles. Nine conazoles decreased T-induced AR activation (IC50s ranging from 10.7 to 71.5 μM and effect potencies (REPs were calculated relative to the known AR antagonist flutamide (FLUT. FLUC had no effect on AR activation by T. FLUS was the most potent (REP = 3.61 and MYC the least potent (REP = 0.03 AR antagonist. All other conazoles had a comparable REP from 0.12 to 0.38. Our results show distinct in vitro anti-androgenic effects of several conazole fungicides arising from two mechanisms: inhibition of T secretion and AR antagonism, suggesting potential testicular toxic effects. These effects warrant further mechanistic investigation and clearly show the need for accurate exposure data in order to perform proper (human risk assessment of this class of compounds.

  18. Post-secretional activation of Protease IV by quorum sensing in Pseudomonas aeruginosa

    OpenAIRE

    Oh, Jungmin; Li, Xi-Hui; Kim, Soo-Kyong; Lee, Joon-Hee

    2017-01-01

    Protease IV (PIV), a key virulence factor of Pseudomonas aeruginosa is a secreted lysyl-endopeptidase whose expression is induced by quorum sensing (QS). We found that PIV expressed in QS mutant has severe reduction of activity in culture supernatant (CS), even though it is overexpressed to high level. PIV purified from the QS mutant (M-PIV) had much lower activity than the PIV purified from wild type (P-PIV). We found that the propeptide cleaved from prepro-PIV was co-purified with M-PIV, bu...

  19. Activation of AMPK inhibits cholera toxin stimulated chloride secretion in human and murine intestine.

    Directory of Open Access Journals (Sweden)

    Ailín C Rogers

    Full Text Available Increased intestinal chloride secretion through chloride channels, such as the cystic fibrosis transmembrane conductance regulator (CFTR, is one of the major molecular mechanisms underlying enterotoxigenic diarrhea. It has been demonstrated in the past that the intracellular energy sensing kinase, the AMP-activated protein kinase (AMPK, can inhibit CFTR opening. We hypothesized that pharmacological activation of AMPK can abrogate the increased chloride flux through CFTR occurring during cholera toxin (CTX mediated diarrhea. Chloride efflux was measured in isolated rat colonic crypts using real-time fluorescence imaging. AICAR and metformin were used to activate AMPK in the presence of the secretagogues CTX or forskolin (FSK. In order to substantiate our findings on the whole tissue level, short-circuit current (SCC was monitored in human and murine colonic mucosa using Ussing chambers. Furthermore, fluid accumulation was measured in excised intestinal loops. CTX and forskolin (FSK significantly increased chloride efflux in isolated colonic crypts. The increase in chloride efflux could be offset by using the AMPK activators AICAR and metformin. In human and mouse mucosal sheets, CTX and FSK increased SCC. AICAR and metformin inhibited the secretagogue induced rise in SCC, thereby confirming the findings made in isolated crypts. Moreover, AICAR decreased CTX stimulated fluid accumulation in excised intestinal segments. The present study suggests that pharmacological activation of AMPK effectively reduces CTX mediated increases in intestinal chloride secretion, which is a key factor for intestinal water accumulation. AMPK activators may therefore represent a supplemental treatment strategy for acute diarrheal illness.

  20. Post-secretional activation of Protease IV by quorum sensing in Pseudomonas aeruginosa.

    Science.gov (United States)

    Oh, Jungmin; Li, Xi-Hui; Kim, Soo-Kyong; Lee, Joon-Hee

    2017-06-30

    Protease IV (PIV), a key virulence factor of Pseudomonas aeruginosa is a secreted lysyl-endopeptidase whose expression is induced by quorum sensing (QS). We found that PIV expressed in QS mutant has severe reduction of activity in culture supernatant (CS), even though it is overexpressed to high level. PIV purified from the QS mutant (M-PIV) had much lower activity than the PIV purified from wild type (P-PIV). We found that the propeptide cleaved from prepro-PIV was co-purified with M-PIV, but never with P-PIV. Since the activity of M-PIV was restored by adding the CS of QS-positive and PIV-deficient strain, we hypothesized that the propeptide binds to and inhibits PIV, and is degraded to activate PIV by a QS-dependent factor. In fact, the CS of the QS-positive and PIV-deficient strain was able to degrade the propeptide. Since the responsible factor should be a QS-dependently expressed extracellular protease, we tested QS-dependent proteases of P. aeruginosa and found that LasB (elastase) can degrade the propeptide and activate M-PIV. We purified the propeptide of PIV and confirmed that the propeptide can bind to and inhibit PIV. We suggest that PIV is post-secretionally activated through the extracellular degradation of the propeptide by LasB, a QS-dependent protease.

  1. Matrix Metalloproteinase-3 (MMP-3) Is an Endogenous Activator of the MMP-9 Secreted by Placental Leukocytes: Implication in Human Labor.

    Science.gov (United States)

    Flores-Pliego, Arturo; Espejel-Nuñez, Aurora; Castillo-Castrejon, Marisol; Meraz-Cruz, Noemi; Beltran-Montoya, Jorge; Zaga-Clavellina, Veronica; Nava-Salazar, Sonia; Sanchez-Martinez, Maribel; Vadillo-Ortega, Felipe; Estrada-Gutierrez, Guadalupe

    2015-01-01

    The activity of matrix degrading enzymes plays a leading role in the rupture of the fetal membranes under normal and pathological human labor, and matrix metalloproteinase-9 (MMP-9) it is considered a biomarker of this event. To gain further insight into local MMP-9 origin and activation, in this study we analyzed the contribution of human placental leukocytes to MMP-9 secretion and explored the local mechanisms of the pro-enzyme activation. Placental blood leukocytes were obtained from women at term gestation without labor and maintained in culture up to 72 h. MMP-9 activity in the culture supernatants was determined by zymography and using a specific substrate. The presence of a potential pro-MMP-9 activator in the culture supernatants was monitored using a recombinant biotin-labeled human pro-MMP-9. To characterize the endogenous pro-MMP-9 activator, MMP-1, -3, -7 and -9 were measured by multiplex assay in the supernatants, and an inhibition assay of MMP-9 activation was performed using an anti-human MMP-3 and a specific MMP-3 inhibitor. Finally, production of MMP-9 and MMP-3 in placental leukocytes obtained from term pregnancies with and without labor was assessed by immunofluorescence. Placental leukocytes spontaneously secreted pro-MMP-9 after 24 h of culture, increasing significantly at 48 h (P≤0.05), when the active form of MMP-9 was detected. Culture supernatants activated the recombinant pro-MMP-9 showing that placental leukocytes secrete the activator. A significant increase in MMP-3 secretion by placental leukocytes was observed since 48 h in culture (P≤0.05) and up to 72 h (P≤0.001), when concentration reached its maximum value. Specific activity of MMP-9 decreased significantly (P≤0.005) when an anti-MMP-3 antibody or a specific MMP-3 inhibitor were added to the culture media. Placental leukocytes from term labor produced more MMP-9 and MMP-3 compared to term non-labor cells. In this work we confirm that placental leukocytes from human term

  2. Parent participation plays an important part in promoting physical activity

    Directory of Open Access Journals (Sweden)

    Anna-Karin Lindqvist

    2015-08-01

    Full Text Available Although physical activity (PA is an important and modifiable determinant of health, in Sweden only 15% of boys and 10% of girls aged 15 years old achieve the recommended levels of PA 7 days per week. Adolescents’ PA levels are associated with social influence exerted by parents, friends, and teachers. The purpose of this study was to describe parents’ experiences of being a part of their adolescents’ empowerment-inspired PA intervention. A qualitative interview study was performed at a school in the northern part of Sweden. A total of 10 parents were interviewed, and the collected data were analyzed with qualitative content analysis. Three subthemes were combined into one main theme, demonstrating that parents are one important part of a successful PA intervention. The life of an adolescent has many options and demands that make it difficult to prioritize PA. Although parents felt that they were important in supporting their adolescent, a successful PA intervention must have multiple components. Moreover, the parents noted that the intervention had a positive effect upon not only their adolescents’, but also their own PA. Interventions aimed at promoting PA among adolescents should include measures to stimulate parent participation, have an empowerment approach, and preferably be school-based.

  3. The effects of gender, motor skills and play area on the free play activities of 8-11 year old school children.

    Science.gov (United States)

    Harten, Nathan; Olds, Tim; Dollman, Jim

    2008-09-01

    Two studies were conducted to examine the interactions between gender, play area, motor skills and free play activity in 8-11 year old school children. In both studies, boys were more active than girls. In boys, but not in girls, energy expenditure was greater for high-skill than for low-skill children (p = 0.0002), and increased as play area increased (p = 0.01). These results suggest that motor skills and play space are important variables in determining the free play activity of boys, but not of girls. This may be related to widely different play styles among boys and girls.

  4. The Effect of Bad Human Activities on Marine Life as Portrayed in Sammy's Adventure: the Secret Passage

    OpenAIRE

    LATHIFAH, ISNA NUR

    2015-01-01

    Keywords: ecocriticism, bad humans activities, marine life, Sammy's Adventure: the Secret Passage movie. The balance of marine life is often damaged by irresponsible humans who do not care about their environment. This problem has inspired some works to criticize humans' reckless behavior toward environment, especially ocean. Sammy's Adventure: the Secret Passage is one of the examples that have been created to criticize the bad human activities in the ocean. This research applies ecocritici...

  5. [ERK activation effects on GABA secretion inhibition induced by SDF-1 in hippocampal neurons of rats].

    Science.gov (United States)

    Zhang, Zi-juan; Guo, Mei-xia; Xing, Ying

    2015-09-01

    To investigate the effect of extracellular regulating kinase (ERK) signaling pathway on the secretion of gamma-aminobutyric acid (GABA) in cultured rat hippocampal neurons induced by stromal cell derived factor-1 (SDF-1). The hippocampal neurons of newborn SD rats were cultured and identified in vitro; the phosphorylation level of ERK1/2 was examined by Western blot; ELISA was used to detect the effect of PD98059, a ERK1/2 specific blocker on GABA secretion of cultured hippocampal neurons and Western blot were adopted to measure the protein expression levels of glutamate decarboxylase (GAD65/67) and gamma aminobutyric acid transporter (GAT); after blocking ERK1/2 signaling pathway with PD98059; RT-PCR was used to detect the mRNA expression levels of GAT-1 and GAD65 after treated with PD98059. The levels of ERKl/2 phosphorylation were increased significantly by SDF1 acting on hippocampal neurons, and CX-CR4 receptor blocker AMD3100, could inhibit SDF-1 induced ERK1/2 activation; SDF-1 could inhibit the secretion of GABA in cultured hippocampal neurons, and ERK1/2 specific inhibitor PD98059, could partly reverse the inhibition of GABA secretion by SDF-1. The effects of SDF-1 on cultured hippocampal neurons was to decrease the mRNA genesis of glutamic acid decarboxylase GAD65 and GABA transporter GAT-1, besides, ERK inhibitor PD98059 could effectively flip the effect of SDF-1. The results of Western blot showed that SDF-1 could inhibit the protein expression of GAT-1 and GAD65/67 in hippocampal neurons and the inhibition of GAT-1 and GAD65/67 protein expression could be partially restored by ERK1/2 blocker. SDF-1 acts on the CXCR4 of hippocampal neurons in vitro, and inhibits the expression of GAD by activating the ERK1/2 signaling pathway, and this may represent one possible pathway of GABA secretion inhibition.

  6. An understanding of Japanese children's perceptions of fun, barriers, and facilitators of active free play.

    Science.gov (United States)

    Lee, YingHua; Takenaka, Koji; Kanosue, Kazuyuki

    2015-09-01

    Physical activity contributes to children's physical and mental well-being. Research suggests that active free play helps to maintain and increase physical activity in children and also contributes to social and emotional well-being. To date, these studies have focused on Western countries. Thus, this study was conducted to gain insights into the factors of perceptions of fun, barriers, and facilitators affecting active free play from the perspective of Japanese children using focus group interviews. In Japan, 12 focus groups were conducted with 60 children aged 9-11 years. Children's perceptions of fun in active free play were categorized into socializing, achievement, emotions, and freedom. Additionally, active boys' groups were interested in free play and adventure play; girls' groups were interested in free play with less physical movement and challenges; inactive boys' groups were interested in relaxing and competitive play with bodily contact. However, children mentioned that busy schedules, weather, and health-related factors acted as main barriers. Lastly, children noted facilitators include setting schedules, having access to equipment and playgrounds, and holding special events. The findings provide insights into active free play-related factors for active and inactive Japanese children and also clarify the differences between Japanese and Western children. Such findings will contribute to designing interventions to increase active free play. © The Author(s) 2013.

  7. Plant flavones enhance antimicrobial activity of respiratory epithelial cell secretions against Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Benjamin M Hariri

    Full Text Available Flavones are a class of natural plant secondary metabolites that have anti-inflammatory and anti-bacterial effects. Some flavones also activate the T2R14 bitter taste receptor, which is expressed in motile cilia of the sinonasal epithelium and activates innate immune nitric oxide (NO production. Flavones may thus be potential therapeutics for respiratory infections. Our objective was to examine the anti-microbial effects of flavones on the common sinonasal pathogens Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa, evaluating both planktonic and biofilm growth. Flavones had only very low-level antibacterial activity alone. They did not reduce biofilm formation, but did reduce production of the important P. aeruginosa inflammatory mediator and ciliotoxin pyocyanin. However, flavones exhibited synergy against P. aeruginosa in the presence of antibiotics or recombinant human lysozyme. They also enhanced the efficacy of antimicrobials secreted by cultured and primary human airway cells grown at air-liquid interface. This suggests that flavones may have anti-gram-negative potential as topical therapeutics when combined with antibiotics or in the context of innate antimicrobials secreted by the respiratory or other epithelia. This may have an additive effect when combined with T2R14-activated NO production. Additional studies are necessary to understand which flavone compounds or mixtures are the most efficacious.

  8. Secreted Immunomodulatory Proteins of Staphylococcus aureus Activate Platelets and Induce Platelet Aggregation.

    Science.gov (United States)

    Binsker, Ulrike; Palankar, Raghavendra; Wesche, Jan; Kohler, Thomas P; Prucha, Josephine; Burchhardt, Gerhard; Rohde, Manfred; Schmidt, Frank; Bröker, Barbara M; Mamat, Uwe; Pané-Farré, Jan; Graf, Anica; Ebner, Patrick; Greinacher, Andreas; Hammerschmidt, Sven

    2018-04-01

    Staphylococcus aureus can cause bloodstream infections associated with infective endocarditis (IE) and disseminated intravascular coagulopathy (DIC). Both complications involve platelets. In view of an increasing number of antibiotic-resistant strains, new approaches to control systemic S. aureus infection are gaining importance. Using a repertoire of 52 recombinant S. aureus proteins in flow cytometry-based platelet activation and aggregation assays, we identified, in addition to the extracellular adherence protein Eap, three secreted staphylococcal proteins as novel platelet activating proteins. Eap and the chemotaxis inhibitory protein of S. aureus (CHIPS), the formyl peptide receptor-like 1 inhibitory protein (FLIPr) and the major autolysin Atl induced P-selectin expression in washed platelets and platelet-rich plasma. Similarly, AtlA, CHIPS and Eap induced platelet aggregation in whole blood. Fluorescence microscopy illustrated that P-selectin expression is associated with calcium mobilization and re-organization of the platelet actin cytoskeleton. Characterization of the functionally active domains of the major autolysin AtlA and Eap indicates that the amidase domain of Atl and the tandem repeats 3 and 4 of Eap are crucial for platelet activation. These results provide new insights in S. aureus protein interactions with platelets and identify secreted proteins as potential treatment targets in case of antibiotic-resistant S. aureus infection. Schattauer GmbH Stuttgart.

  9. Flotillin scaffold activity contributes to type VII secretion system assembly in Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Benjamin Mielich-Süss

    2017-11-01

    Full Text Available Scaffold proteins are ubiquitous chaperones that promote efficient interactions between partners of multi-enzymatic protein complexes; although they are well studied in eukaryotes, their role in prokaryotic systems is poorly understood. Bacterial membranes have functional membrane microdomains (FMM, a structure homologous to eukaryotic lipid rafts. Similar to their eukaryotic counterparts, bacterial FMM harbor a scaffold protein termed flotillin that is thought to promote interactions between proteins spatially confined to the FMM. Here we used biochemical approaches to define the scaffold activity of the flotillin homolog FloA of the human pathogen Staphylococcus aureus, using assembly of interacting protein partners of the type VII secretion system (T7SS as a case study. Staphylococcus aureus cells that lacked FloA showed reduced T7SS function, and thus reduced secretion of T7SS-related effectors, probably due to the supporting scaffold activity of flotillin. We found that the presence of flotillin mediates intermolecular interactions of T7SS proteins. We tested several small molecules that interfere with flotillin scaffold activity, which perturbed T7SS activity in vitro and in vivo. Our results suggest that flotillin assists in the assembly of S. aureus membrane components that participate in infection and influences the infective potential of this pathogen.

  10. Differently Designed Playgrounds and Preschooler's Physical Activity Play

    Science.gov (United States)

    Luchs, Antje; Fikus, Monika

    2018-01-01

    New playground concepts--favouring natural play characteristics--emerge. The aim of our free play study is to explore the relation between newly established natural playgrounds and the widely spread contemporary ones in terms of physical activity levels. The playground features differ in vegetation, topography, size and play equipment. The…

  11. Influences of Technology-Related Playful Activity and Thought on Moral Development

    Science.gov (United States)

    Bergen, Doris; Davis, Darrel

    2011-01-01

    Many early developmental theorists such as Freud, Erikson, Piaget, and Vygotsky suggested that play--which the authors of this article define as both playful activity and playful thought--had the power to influence the moral emotions, behaviors, and reasoning of children. More recent researchers have also found evidence of moral development in…

  12. Autophagy Inhibition Contributes to ROS-Producing NLRP3-Dependent Inflammasome Activation and Cytokine Secretion in High Glucose-Induced Macrophages.

    Science.gov (United States)

    Dai, Jiezhi; Zhang, Xiaotian; Li, Li; Chen, Hua; Chai, Yimin

    2017-01-01

    Type 2 diabetes is a persistent inflammatory response that impairs the healing process. We hypothesized that stimulation with high glucose following a pro-inflammatory signal would lead to autophagy inhibition, reactive oxygen species (ROS) production and eventually to the activation of the Nod-like receptor protein (NLRP) -3. Macrophages were isolated from human diabetic wound. We measured the expression of NLRP3, caspase1 and interleukin-1 beta (IL-1β) by western blot and real-time PCR, and the surface markers on cells by flow cytometry. THP-1-derived macrophages exposed to high glucose were applied to study the link between autophagy, ROS and NLRP3 activation. LC3-II, P62, NLRP3 inflammation and IL-1β expression were measured by western blot and real-time PCR. ROS production was measured with a Cellular Reactive Oxygen Species Detection Assay Kit. Macrophages isolated from diabetic wounds exhibited a pro-inflammatory phenotype, including sustained NLRP3 inflammasome activity associated with IL-1β secretion. Our data showed that high glucose inhibited autophagy, induced ROS production, and activated NLRP3 inflammasome and cytokine secretion in THP-1-derived macrophages. To study high glucose-induced NLRP3 inflammasome signalling, we performed studies using an autophagy inducer, a ROS inhibitor and a NLRP3 inhibitor and found that all reduced the NLRP3 inflammasome activation and cytokine secretion. Sustained NLRP3 inflammasome activity in wound-derived macrophages contributes to the hyper-inflammation in human diabetic wounds. Autophagy inhibition and ROS generation play an essential role in high glucose-induced NLRP3 inflammasome activation and cytokine secretion in macrophages. © 2017 The Author(s). Published by S. Karger AG, Basel.

  13. Activated human T cells secrete exosomes that participate in IL-2 mediated immune response signaling.

    Directory of Open Access Journals (Sweden)

    Jessica Wahlgren

    Full Text Available It has previously been shown that nano-meter sized vesicles (30-100 nm, exosomes, secreted by antigen presenting cells can induce T cell responses thus showing the potential of exosomes to be used as immunological tools. Additionally, activated CD3⁺ T cells can secrete exosomes that have the ability to modulate different immunological responses. Here, we investigated what effects exosomes originating from activated CD3⁺ T cells have on resting CD3⁺ T cells by studying T cell proliferation, cytokine production and by performing T cell and exosome phenotype characterization. Human exosomes were generated in vitro following CD3⁺ T cell stimulation with anti-CD28, anti-CD3 and IL-2. Our results show that exosomes purified from stimulated CD3⁺ T cells together with IL-2 were able to generate proliferation in autologous resting CD3⁺ T cells. The CD3⁺ T cells stimulated with exosomes together with IL-2 had a higher proportion of CD8⁺ T cells and had a different cytokine profile compared to controls. These results indicate that activated CD3⁺ T cells communicate with resting autologous T cells via exosomes.

  14. Distinct activities of Bartonella henselae type IV secretion effector proteins modulate capillary-like sprout formation.

    Science.gov (United States)

    Scheidegger, F; Ellner, Y; Guye, P; Rhomberg, T A; Weber, H; Augustin, H G; Dehio, C

    2009-07-01

    The zoonotic pathogen Bartonella henselae (Bh) can lead to vasoproliferative tumour lesions in the skin and inner organs known as bacillary angiomatosis and bacillary peliosis. The knowledge on the molecular and cellular mechanisms involved in this pathogen-triggered angiogenic process is confined by the lack of a suitable animal model and a physiologically relevant cell culture model of angiogenesis. Here we employed a three-dimensional in vitro angiogenesis assay of collagen gel-embedded endothelial cell (EC) spheroids to study the angiogenic properties of Bh. Spheroids generated from Bh-infected ECs displayed a high capacity to form sprouts, which represent capillary-like projections into the collagen gel. The VirB/VirD4 type IV secretion system and a subset of its translocated Bartonella effector proteins (Beps) were found to profoundly modulate this Bh-induced sprouting activity. BepA, known to protect ECs from apoptosis, strongly promoted sprout formation. In contrast, BepG, triggering cytoskeletal rearrangements, potently inhibited sprouting. Hence, the here established in vitro model of Bartonella- induced angiogenesis revealed distinct and opposing activities of type IV secretion system effector proteins, which together with a VirB/VirD4-independent effect may control the angiogenic activity of Bh during chronic infection of the vasculature.

  15. Vibrio parahaemolyticus type VI secretion system 1 is activated in marine conditions to target bacteria, and is differentially regulated from system 2.

    Directory of Open Access Journals (Sweden)

    Dor Salomon

    Full Text Available Vibrio parahaemolyticus is a marine bacterium that thrives in warm climates. It is a leading cause of gastroenteritis resulting from consumption of contaminated uncooked shellfish. This bacterium harbors two putative type VI secretion systems (T6SS. T6SSs are widespread protein secretion systems found in many Gram-negative bacteria, and are often tightly regulated. For many T6SSs studied to date, the conditions and cues, as well as the regulatory mechanisms that control T6SS activity are unknown. In this study, we characterized the environmental conditions and cues that activate both V. parahaemolyticus T6SSs, and identified regulatory mechanisms that control T6SS gene expression and activity. We monitored the expression and secretion of the signature T6SS secreted proteins Hcp1 and Hcp2, and found that both T6SSs are differentially regulated by quorum sensing and surface sensing. We also showed that T6SS1 and T6SS2 require different temperature and salinity conditions to be active. Interestingly, T6SS1, which is found predominantly in clinical isolates, was most active under warm marine-like conditions. Moreover, we found that T6SS1 has anti-bacterial activity under these conditions. In addition, we identified two transcription regulators in the T6SS1 gene cluster that regulate Hcp1 expression, but are not required for immunity against self-intoxication. Further examination of environmental isolates revealed a correlation between the presence of T6SS1 and virulence of V. parahaemolyticus against other bacteria, and we also showed that different V. parahaemolyticus isolates can outcompete each other. We propose that T6SS1 and T6SS2 play different roles in the V. parahaemolyticus lifestyles, and suggest a role for T6SS1 in enhancing environmental fitness of V. parahaemolyticus in marine environments when competing for a niche in the presence of other bacterial populations.

  16. Comparing Role-Playing Activities in Second Life and Face-to-Face Environments

    Science.gov (United States)

    Gao, Fei; Noh, Jeongmin J.; Koehler, Matthew J.

    2009-01-01

    This study compared student performances in role-playing activities in both a face-to-face (FTF) environment and a virtual 3D environment, Second Life (SL). We found that students produced a similar amount of communication in the two environments, but the communication styles were different. In SL role-playing activities, students took more…

  17. Peroxisome proliferator-activated receptor δ modulates MMP-2 secretion and elastin expression in human dermal fibroblasts exposed to ultraviolet B radiation.

    Science.gov (United States)

    Ham, Sun Ah; Yoo, Taesik; Hwang, Jung Seok; Kang, Eun Sil; Paek, Kyung Shin; Park, Chankyu; Kim, Jin-Hoi; Do, Jeong Tae; Seo, Han Geuk

    2014-10-01

    Changes in skin connective tissues mediated by ultraviolet (UV) radiation have been suggested to cause the skin wrinkling normally associated with premature aging of the skin. Recent investigations have shown that peroxisome proliferator-activated receptor (PPAR) δ plays multiple biological roles in skin homeostasis. We attempted to investigate whether PPARδ modulates elastin protein levels and secretion of matrix metalloproteinase (MMP)-2 in UVB-irradiated human dermal fibroblasts (HDFs) and mouse skin. These studies were undertaken in primary HDFs or HR-1 hairless mice using Western blot analyses, small interfering (si)RNA-mediated gene silencing, and Fluorescence microscopy. In HDFs, UVB irradiation induced increased secretion of MMP-2 and reduced levels of elastin. Activation of PPARδ by GW501516, a ligand specific for PPARδ, markedly attenuated UVB-induced MMP-2 secretion with a concomitant increase in the level of elastin. These effects were reduced by the presence of siRNAs against PPARδ or treatment with GSK0660, a specific inhibitor of PPARδ. Furthermore, GW501516 elicited a dose- and time-dependent increase in the expression of elastin. Modulation of MMP-2 secretion and elastin levels by GW501516 was associated with a reduction in reactive oxygen species (ROS) production in HDFs exposed to UVB. Finally, in HR-1 hairless mice, administration of GW501516 significantly reduced UVB-induced MMP-2 expression with a concomitant increase in elastin levels, and these effects were significantly reduced by the presence of GSK0660. Our results suggest that PPARδ-mediated modulation of MMP-2 secretion and elastin expression may contribute to the maintenance of skin integrity by inhibiting ROS generation. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  18. Activity of Genital Tract Secretions and Synthetic Antimicrobial Peptides against Group B Streptococcus.

    Science.gov (United States)

    Agarwal, Nidhi; Buckley, Niall; Nakra, Natasha; Gialanella, Philip; Yuan, Weirong; Ghartey, Jeny P

    2015-12-01

    Genital tract secretions inhibit Escherichia coli (E. coli) through antimicrobial peptides (AMP) secreted by the host and vaginal microbiota. However, there are limited data against group B Streptococcus (GBS). Group B Streptococcus were incubated with cervico-vaginal lavage (CVL) samples from healthy non-pregnant women (n = 12) or synthetic AMP and monitored for bacterial growth using a turbidimetric approach. E. coli inhibitory activity was determined by a colony-forming unit assay. None of the CVL samples inhibited GBS. The human neutrophil peptide-1 and human defensin 5 inhibited GBS growth by ≥80% at concentrations ≥20 μg/mL and ≥50 μg/mL, respectively, while human beta-defensin 2 and LL-37 did not inhibit at highest concentration tested (100 μg/mL). In contrast, all AMP inhibited E. coli. Antimicrobial peptides may protect against E. coli colonization but have more limited activity against GBS. Future studies will focus on augmenting host defense with specific AMP to prevent genitourinary infection with these pathogenic organisms. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Distinct licensing of IL-18 and IL-1β secretion in response to NLRP3 inflammasome activation.

    Directory of Open Access Journals (Sweden)

    Rebecca L Schmidt

    Full Text Available Inflammasome activation permits processing of interleukins (IL-1β and 18 and elicits cell death (pyroptosis. Whether these responses are independently licensed or are "hard-wired" consequences of caspase-1 (casp1 activity has not been clear. Here, we show that that each of these responses is independently regulated following activation of NLRP3 inflammasomes by a "non-canonical" stimulus, the secreted Listeria monocytogenes (Lm p60 protein. Primed murine dendritic cells (DCs responded to p60 stimulation with reactive oxygen species (ROS production and secretion of IL-1β and IL-18 but not pyroptosis. Inhibitors of ROS production inhibited secretion of IL-1β, but did not impair IL-18 secretion. Furthermore, DCs from caspase-11 (casp11-deficient 129S6 mice failed to secrete IL-1β in response to p60 but were fully responsive for IL-18 secretion. These findings reveal that there are distinct licensing requirements for processing of IL-18 versus IL-1β by NLRP3 inflammasomes.

  20. Physical Activity Play and Preschool Children's Peer Acceptance: Distinctions between Rough-and-Tumble and Exercise Play

    Science.gov (United States)

    Lindsey, Eric W.

    2014-01-01

    Research Findings: Two forms of exercise play (toy mediated and non-mediated) and 2 forms of rough-and-tumble (R&T) play (chase and fighting) were examined in relation to preschoolers' peer competence. A total of 148 preschoolers (78 boys, 89 Euro-Americans) were observed during free play at their university-sponsored child care center. The…

  1. Activation of transmembrane bile acid receptor TGR5 stimulates insulin secretion in pancreatic β cells

    International Nuclear Information System (INIS)

    Kumar, Divya P.; Rajagopal, Senthilkumar; Mahavadi, Sunila; Mirshahi, Faridoddin; Grider, John R.; Murthy, Karnam S.; Sanyal, Arun J.

    2012-01-01

    Highlights: ► G protein coupled receptor TGR5 is expressed in mouse and human islets. ► TGR5 is coupled to activation of Gs and Ca 2+ release via cAMP/Epac/PLC-ε pathway. ► Activation of TGR5 by bile salts and selective ligands causes insulin secretion. ► TGR5 could be a potential therapeutic target to treat diabetes. -- Abstract: Bile acids act as signaling molecules and stimulate the G protein coupled receptor, TGR5, in addition to nuclear farnesoid X receptor to regulate lipid, glucose and energy metabolism. Bile acid induced activation of TGR5 in the enteroendocrine cells promotes glucagon like peptide-1 (GLP-1) release, which has insulinotropic effect in the pancreatic β cells. In the present study, we have identified the expression of TGR5 in pancreatic β cell line MIN6 and also in mouse and human pancreatic islets. TGR5 selective ligands, oleanolic acid (OA) and INT-777 selectively activated Gα s and caused an increase in intracellular cAMP and Ca 2+ . OA and INT-777 also increased phosphoinositide (PI) hydrolysis and the increase was blocked by NF449 (a selective Gα s inhibitor) or (U73122) (PI hydrolysis inhibitor). OA, INT-777 and lithocholic acid increased insulin release in MIN6 and human islets and the increase was inhibited by treatment with NF449, (U73122) or BAPTA-AM (chelator of calcium), but not with myristoylated PKI (PKA inhibitor), suggesting that the release is dependent on G s /cAMP/Ca 2+ pathway. 8-pCPT-2′-O-Me-cAMP, a cAMP analog, which activates Epac, but not PKA also stimulated PI hydrolysis. In conclusion, our study demonstrates that the TGR5 expressed in the pancreatic β cells regulates insulin secretion and highlights the importance of ongoing therapeutic strategies targeting TGR5 in the control of glucose homeostasis.

  2. Plasma membrane factor XIIIA transglutaminase activity regulates osteoblast matrix secretion and deposition by affecting microtubule dynamics.

    Directory of Open Access Journals (Sweden)

    Hadil F Al-Jallad

    2011-01-01

    Full Text Available Transglutaminase activity, arising potentially from transglutaminase 2 (TG2 and Factor XIIIA (FXIIIA, has been linked to osteoblast differentiation where it is required for type I collagen and fibronectin matrix deposition. In this study we have used an irreversible TG-inhibitor to 'block -and-track' enzyme(s targeted during osteoblast differentiation. We show that the irreversible TG-inhibitor is highly potent in inhibiting osteoblast differentiation and mineralization and reduces secretion of both fibronectin and type I collagen and their release from the cell surface. Tracking of the dansyl probe by Western blotting and immunofluorescence microscopy demonstrated that the inhibitor targets plasma membrane-associated FXIIIA. TG2 appears not to contribute to crosslinking activity on the osteoblast surface. Inhibition of FXIIIA with NC9 resulted in defective secretory vesicle delivery to the plasma membrane which was attributable to a disorganized microtubule network and decreased microtubule association with the plasma membrane. NC9 inhibition of FXIIIA resulted in destabilization of microtubules as assessed by cellular Glu-tubulin levels. Furthermore, NC9 blocked modification of Glu-tubulin into 150 kDa high-molecular weight Glu-tubulin form which was specifically localized to the plasma membrane. FXIIIA enzyme and its crosslinking activity were colocalized with plasma membrane-associated tubulin, and thus, it appears that FXIIIA crosslinking activity is directed towards stabilizing the interaction of microtubules with the plasma membrane. Our work provides the first mechanistic cues as to how transglutaminase activity could affect protein secretion and matrix deposition in osteoblasts and suggests a novel function for plasma membrane FXIIIA in microtubule dynamics.

  3. Vascular, but not luminal, activation of FFAR1 (GPR40) stimulates GLP-1 secretion from isolated perfused rat small intestine

    DEFF Research Database (Denmark)

    Christensen, Louise Wulff; Kuhre, Rune Ehrenreich; Janus, Charlotte

    2015-01-01

    -protein-cou- pled receptor, FFAR1 (previously GPR40), expressed on L cells and activated by long-chain fatty acids (LCFAs) is a potential target. A link between FFAR1 activation and GLP-1 secretion has been demonstrated in cellular models and small-molecule FFAR1 agonists have been developed. In this study, we exam......- ined the effect of FFAR1 activation on GLP-1 secretion using isolated, per- fused small intestines from rats, a physiologically relevant model allowing distinction between direct and indirect effects of FFAR1 activation. The endogenous FFAR1 ligand, linoleic acid (LA), and four synthetic FFAR1 ago...

  4. Lactobacillus proteins are associated with the bactericidal activity against E. coli of female genital tract secretions.

    Directory of Open Access Journals (Sweden)

    Sabah Kalyoussef

    Full Text Available Female genital tract secretions are bactericidal for Escherichia (E. coli ex vivo. However, the intersubject variability and molecules that contribute to this activity have not been defined.The bactericidal activity and concentration of immune mediators in cervicovaginal lavage (CVL collected from 99 healthy women were determined.CVL reduced the number of E. coli colonies by 68% [-26, 100] (median [range]. CVL were active against laboratory and clinical isolates of E. coli, but were inactive against Lactobacillus species. Bactericidal activity correlated with the concentration of protein recovered (p90% inhibitory activity (active and two with<30% activity were subjected to MS/MS proteomic analysis. 215 proteins were identified and six were found exclusively in active samples. Four of these corresponded to Lactobacillus crispatus or jensenii proteins. Moreover, culture supernatants from Lactobacillus jensenii were bactericidal for E. coli.Both host and commensal microbiota proteins contribute to mucosal defense. Identification of these proteins will facilitate the development of strategies to maintain a healthy vaginal microbiome and prevent colonization with pathogenic bacteria such as E. coli that increase the risk for urinary tract infections, preterm labor and perinatal infection.

  5. The impact of pregnancy on anti-HIV activity of cervicovaginal secretions.

    Science.gov (United States)

    Hughes, Brenna L; Dutt, Riana; Raker, Christina; Barthelemy, Melody; Rossoll, Richard M; Ramratnam, Bharat; Wira, Charles R; Cu-Uvin, Susan

    2016-12-01

    Mucosal immunity of the female genital tract plays a critical role in defense against sexually transmitted infections like HIV. Pregnancy is associated with both structural and immunologic alterations in the genital mucosa, but the impact of these changes on its ability to suppress HIV infection is unknown. Current epidemiologic data are conflicting as to whether pregnancy increases the risk of HIV acquisition. The purpose of this study was to define the association between antimicrobial peptides and chemokines in cervicovaginal secretions and in vitro HIV infectivity among pregnant and nonpregnant women. Forty pregnant and 37 nonpregnant women were enrolled in a prospective longitudinal cohort study at a single tertiary care women's hospital in Providence, RI. Cervicovaginal lavage was performed at each study visit. For pregnant women, study visits occurred once per trimester, and there was an optional postpartum visit. For nonpregnant women, study visits occurred across a single cycle that was timed to occur in the proliferative, ovulatory, and secretory phases based on the presumption of a regular menstrual cycle. The impact of cervicovaginal lavage on HIV infectivity was evaluated using a TZM-bl assay and compared between pregnant and nonpregnant women for each visit. The previously validated TZM-bl assay, which uses a luciferase reporting gene to indicate HIV infection of TZM-bl cells, was measured with a luminometer with higher relative light units that indicate greater levels of in vitro HIV infection. Immune mediators were measured with a multiplex bead assay. HIV infectivity and median concentration of each mediator were compared between pregnant and nonpregnant groups with the Wilcoxon rank sum test. Cervicovaginal fluid from pregnant and nonpregnant women significantly decreased HIV infectivity in both groups compared with positive control (virus only; PHIV infectivity in both groups across all visits, except at the postpartum visit in the pregnant

  6. Bacillus subtilis PrsA is required in vivo as an extracytoplasmic chaperone for secretion of active enzymes synthesized either with or without pro-sequences

    DEFF Research Database (Denmark)

    Jabobs, Myra F; Andersen, Jens Bo; Kontinen, Vesa P.

    1993-01-01

    In prsA (protein secretion) mutants of Bacillus subtilis, decreased levels of exoproteins, including alpha-amylase and subtilisins, are found extracellularly. The effect of prsA on subtilisin secretion is elaborated here. Extracytoplasmic folding and secretion of active subtilisin is assisted...

  7. Vanadate-induced inhibition of renin secretion is unrelated to inhibition Na,K-ATPase activity

    Energy Technology Data Exchange (ETDEWEB)

    Churchill, P.C.; Rossi, N.F.; Churchill, M.C.; Ellis, V.R. (Wayne State Univ. School of Medicine, Detroit, MI (USA))

    1990-01-01

    There is evidence that three inhibitors of Na,K-ATPase activity-ouabain, K-free extracellular fluid, and vanadate--inhibit renin secretion by increasing Ca{sup 2+} concentration in juxtaglomerular cells, but in the case of vanadate, it is uncertain whether the increase in Ca{sup 2+} is due to a decrease in Ca{sup 2+} efflux or to an increase in Ca{sup 2+} influx through potential operated Ca channels. In the present experiments, the rat renal cortical slice preparation was used to compare and contrast the effects of ouabain, of K-free fluid, and of vanadate on renin secretion, in the absence and presence of methoxyverapamil, A Ca channel blocker. Basal renin secretory rate averaged 7.7 {plus minus} 0.3 GU/g/60 min, and secretory rate was reduced to nearly zero by 1 mM ouabain, by K-free fluid, by 0.5 mM vanadate, and by K-depolarization. Although 0.5 {mu}M methoxyverapamil completely blocked the inhibitory effect of K-depolarization, it failed to antagonize the inhibitory effects of ouabain, of K-free fluid, and of vanadate.

  8. Early to Late Endosome Trafficking Controls Secretion and Zymogen Activation in Rodent and Human Pancreatic Acinar Cells.

    Science.gov (United States)

    Messenger, Scott W; Thomas, Diana Dh; Cooley, Michelle M; Jones, Elaina K; Falkowski, Michelle A; August, Benjamin K; Fernandez, Luis A; Gorelick, Fred S; Groblewski, Guy E

    2015-11-01

    Pancreatic acinar cells have an expanded apical endosomal system, the physiological and pathophysiological significance of which is still emerging. Phosphatidylinositol-3,5-bisphosphate (PI(3,5)P 2 ) is an essential phospholipid generated by PIKfyve, which phosphorylates phosphatidylinositol-3-phosphate (PI(3)P). PI(3,5)P 2 is necessary for maturation of early endosomes (EE) to late endosomes (LE). Inhibition of EE to LE trafficking enhances anterograde endosomal trafficking and secretion at the plasma membrane by default through a recycling endosome (RE) intermediate. We assessed the effects of modulating PIKfyve activity on apical trafficking and pancreatitis responses in pancreatic acinar cells. Inhibition of EE to LE trafficking was achieved using pharmacological inhibitors of PIKfyve, expression of dominant negative PIKfyve K1877E, or constitutively active Rab5-GTP Q79L. Anterograde endosomal trafficking was manipulated by expression of constitutively active and dominant negative Rab11a mutants. The effects of these agents on secretion, endolysosomal exocytosis of lysosome associated membrane protein (LAMP1), and trypsinogen activation in response to high-dose CCK-8, bile acids and cigarette toxin was determined. PIKfyve inhibition increased basal and stimulated secretion. Adenoviral overexpression of PIKfyve decreased secretion leading to cellular death. Expression of Rab5-GTP Q79L or Rab11a-GTP Q70L enhanced secretion. Conversely, dominant-negative Rab11a-GDP S25N reduced secretion. High-dose CCK inhibited endolysosomal exocytosis that was reversed by PIKfyve inhibition. PIKfyve inhibition blocked intracellular trypsin accumulation and cellular damage responses to high CCK-8, tobacco toxin, and bile salts in both rodent and human acini. These data demonstrate that EE-LE trafficking acutely controls acinar secretion and the intracellular activation of zymogens leading to the pathogenicity of acute pancreatitis.

  9. Mammalian protein secretion without signal peptide removal. Biosynthesis of plasminogen activator inhibitor-2 in U-937 cells

    International Nuclear Information System (INIS)

    Ye, R.D.; Wun, T.C.; Sadler, J.E.

    1988-01-01

    Plasminogen activator inhibitor-2 (PAI-2) is a serine protease inhibitor that regulates plasmin generation by inhibiting urokinase and tissue plasminogen activator. The primary structure of PAI-2 suggests that it may be secreted without cleavage of a single peptide. To confirm this hypothesis we have studied the glycosylation and secretion of PAI-2 in human monocytic U-937 cells by metabolic labeling, immunoprecipitation, glycosidase digestion, and protein sequencing. PAI-2 is variably glycosylated on asparagine residues to yield intracellular intermediates with zero, one, two, or three high mannose-type oligosaccharide units. Secretion of the N-glycosylated species began by 1 h of chase and the secreted molecules contained both complex-type N-linked and O-linked oligosaccharides. Enzymatically deglycosylated PAI-2 had an electrophoretic mobility identical to that of the nonglycosylated precursor and also to that of PAI-2 synthesized in vitro in a rabbit reticulocyte lysate from synthetic mRNA derived from full length PAI-2 cDNA. The amino-terminal protein sequence of secreted PAI-2 began with the initiator methionine residue. These results indicate that PAI-2 is glycosylated and secreted efficiently without the cleavage of a signal peptide. PAI-2 shares this property with its nearest homologue in the serine protease inhibitor family, chicken ovalbumin, and appears to be the first well characterized example of this phenomenon among natural mammalian proteins

  10. Innate immunity in the vagina (Part II): Anti-HIV activity and antiviral content of human vaginal secretions.

    Science.gov (United States)

    Patel, Mickey V; Ghosh, Mimi; Fahey, John V; Ochsenbauer, Christina; Rossoll, Richard M; Wira, Charles R

    2014-07-01

    Whether the concentrations of antiviral proteins, and anti-HIV activity, within human vaginal secretions change across the menstrual cycle is unknown. Using a menstrual cup, vaginal secretions from pre-menopausal women were recovered at the proliferative (d6-8), mid-cycle (d13-15), and secretory (d21-23) stages of the menstrual cycle. Antiviral protein concentration was determined by ELISA, and anti-HIV activity assessed using the TZM-bl reporter cell line. CCL20, RANTES, elafin, HBD2, SDF-1α, and IL-8 levels were detectable in the secretions. Vaginal secretions had anti-HIV activity against specific clade B strains of HIV, with significant inhibition of IIIB and increased infectivity of transmitted/founder CH077.t. No significant differences in either antiviral protein concentration or anti-HIV activity with respect to menstrual cycle stage were measured, but marked differences were observed in both parameters over the course of the cycle between different women and in consecutive cycles from the same woman. The vagina contains a complement of antiviral proteins. The variation in anti-HIV activity demonstrates that immune protection in the vagina is not constant. Intra- and interindividual variations suggest that factors in addition to sex hormones influence antiviral protection. Lastly, the menstrual cup is a new model for recovering undiluted vaginal secretions from women throughout their reproductive life. © 2014 John Wiley & Sons Ltd.

  11. Immunity in the Vagina (Part II): Anti-HIV Activity and Antiviral Content of Human Vaginal Secretions

    Science.gov (United States)

    Patel, Mickey V.; Ghosh, Mimi; Fahey, John V.; Ochsenbauer, Christina; Rossoll, Richard M.; Wira, Charles R.

    2015-01-01

    Problem Whether the concentrations of antiviral proteins, and anti-HIV activity, within human vaginal secretions changes across the menstrual cycle is unknown. Method of Study Using a menstrual cup, vaginal secretions from premenopausal women were recovered at the proliferative (d6–8), mid-cycle (d13–15) and secretory (d21–23) stages of the menstrual cycle. Antiviral protein concentration was determined by ELISA, and anti-HIV activity assessed using the TZM-bl reporter cell line. Results CCL20, RANTES, elafin, HBD2, SDF-1α and IL-8 levels were detectable in the secretions. Vaginal secretions had anti-HIV activity against specific clade B strains of HIV, with significant inhibition of IIIB and increased infectivity of transmitted/founder CH077.t. No significant differences in either antiviral protein concentration or anti-HIV activity with respect to menstrual cycle stage were measured, but marked differences were observed in both parameters over the course of the cycle between different women, and in consecutive cycles from the same woman. Conclusion The vagina contains a complement of antiviral proteins. The variation in anti-HIV activity demonstrates that immune protection in the vagina is not constant. Intra- and inter-individual variations suggest that factors in addition to sex hormones influence antiviral protection. Lastly, the menstrual cup is a new model for recovering undiluted vaginal secretions from women throughout their reproductive life. PMID:24806967

  12. A Comparison of Solo and Multiplayer Active Videogame Play in Children with Unilateral Cerebral Palsy.

    Science.gov (United States)

    Howcroft, Jennifer; Fehlings, Darcy; Wright, Virginia; Zabjek, Karl; Andrysek, Jan; Biddiss, Elaine

    2012-08-01

    Active videogames (AVGs) have potential in terms of physical activity and therapy for children with cerebral palsy. However, the effect of social interaction on AVG play has not yet been assessed. The objective of this study is to determine if multiplayer AVG versus solo affects levels of energy expenditure and movement patterns. Fifteen children (9.77 [standard deviation (SD) 1.78] years old) with hemiplegic cerebral palsy (Gross Motor Function Classification System Level I) participated in solo and multiplayer Nintendo(®) "Wii™ Boxing" (Nintendo, Inc., Redmond, WA) AVG play while energy expenditure and punching frequency were monitored. Moderate levels of physical activity were achieved with no significant differences in energy measures during multiplayer and solo play. Dominant arm punching frequency increased during the multiplayer session from 95.75 (SD 37.93) punches/minute to 107.77 (SD 36.99) punches/minute. Conversely, hemiplegic arm punching frequency decreased from 39.05 (SD 29.57) punches/minutes to 30.73 (SD 24.74) punches/minutes during multiplayer game play. Children enjoyed multiplayer more than solo play. Opportunities to play AVGs with friends and family may translate to more frequent participation in this moderate physical activity. Conversely, increased hemiplegic limb use during solo play may have therapeutic advantages. As such, new strategies are recommended to promote use of the hemiplegic hand during multiplayer AVG play and to optimize commercial AVG systems for applications in virtual reality therapy.

  13. Motivation within Role-Playing as a Means to Intensify College Students' Educational Activity

    Science.gov (United States)

    Burenkova, Olga Mikhailovna; Arkhipova, Irina Vladimirovna; Semenov, Sergei Aleksandrovich; Samarenkina, Saniya Zakirzyanovna

    2015-01-01

    This article covers college students' educational activity issues while studying a foreign language; analyzes special aspects of motivation introduction, their specific features. It also defines role and structure of role-playing. The authors come to the conclusion that introduction of role-playing in an educational process will bring it closer to…

  14. Glomerular parietal epithelial cell activation induces collagen secretion and thickening of Bowman's capsule in diabetes.

    Science.gov (United States)

    Holderied, Alexander; Romoli, Simone; Eberhard, Jonathan; Konrad, Lukas A; Devarapu, Satish K; Marschner, Julian A; Müller, Susanna; Anders, Hans-Joachim

    2015-03-01

    The metabolic and hemodynamic alterations in diabetes activate podocytes to increase extracellular matrix (ECM) production, leading to thickening of the glomerular basement membrane (GBM). We hypothesized that diabetes would activate parietal epithelial cells (PECs) in a similar manner and cause thickening of Bowman's capsules. Periodic acid Schiff staining of human kidney biopsies of 30 patients with diabetic nephropathy (DN) revealed a significantly thicker Bowman's capsule as compared with 20 non-diabetic controls. The average thickness was 4.55±0.21 μm in the group of patients with DN compared with 2.92±0.21 μm in the group of non-diabetic controls (PBowman's capsule showed strong association with CD44-positive PECs. In summary, metabolic alterations in diabetes activate PECs to increase the expression and secretion of Bowman's capsule proteins. This process may contribute to the thickening of the Bowman's capsule, similar to the thickening of the GBM that is driven by activated podocytes. These data may also imply that activated PECs contribute to ECM production once they migrate to the glomerular tuft, a process resulting in glomerular scaring, for example, in diabetic glomerulosclerosis.

  15. The Central Metabolism Regulator EIIAGlc Switches Salmonella from Growth Arrest to Acute Virulence through Activation of Virulence Factor Secretion

    Directory of Open Access Journals (Sweden)

    Alain Mazé

    2014-06-01

    Full Text Available The ability of Salmonella to cause disease depends on metabolic activities and virulence factors. Here, we show that a key metabolic protein, EIIAGlc, is absolutely essential for acute infection, but not for Salmonella survival, in a mouse typhoid fever model. Surprisingly, phosphorylation-dependent EIIAGlc functions, including carbohydrate transport and activation of adenylate cyclase for global regulation, do not explain this virulence phenotype. Instead, biochemical studies, in vitro secretion and translocation assays, and in vivo genetic epistasis experiments suggest that EIIAGlc binds to the type three secretion system 2 (TTSS-2 involved in systemic virulence, stabilizes its cytoplasmic part including the crucial TTSS-2 ATPase, and activates virulence factor secretion. This unexpected role of EIIAGlc reveals a striking direct link between central Salmonella metabolism and a crucial virulence mechanism.

  16. Subcellular localization, mobility, and kinetic activity of glucokinase in glucose-responsive insulin-secreting cells.

    Science.gov (United States)

    Stubbs, M; Aiston, S; Agius, L

    2000-12-01

    We investigated the subcellular localization, mobility, and activity of glucokinase in MIN6 cells, a glucose-responsive insulin-secreting beta-cell line. Glucokinase is present in the cytoplasm and a vesicular/granule compartment that is partially colocalized with insulin granules. The granular staining of glucokinase is preserved after permeabilization of the cells with digitonin. There was no evidence for changes in distribution of glucokinase between the cytoplasm and the granule compartment during incubation of the cells with glucose. The rate of release of glucokinase and of phosphoglucoisomerase from digitonin-permeabilized cells was slower when cells were incubated at an elevated glucose concentration (S0.5 approximately 15 mmol/l). This effect of glucose was counteracted by competitive inhibitors of glucokinase (5-thioglucose and mannoheptulose) but was unaffected by fructose analogs and may be due to changes in cell shape or conformation of the cytoskeleton that are secondary to glucose metabolism. Based on the similar release of glucokinase and phosphoglucoisomerase, we found no evidence for specific binding of cytoplasmic digitonin-extractable glucokinase. The affinity of beta-cells for glucose is slightly lower than that in cell extracts and, unlike that in hepatocytes, is unaffected by fructose, tagatose, or a high-K+ medium, which is consistent with the lack of change in glucokinase distribution or release. We conclude that glucokinase is present in two locations, cytoplasm and the granular compartment, and that it does not translocate between them. This conclusion is consistent with the lack of adaptive changes in the glucose phosphorylation affinity. The glucokinase activity associated with the insulin granules may have a role in either direct or indirect coupling between glucose phosphorylation and insulin secretion.

  17. Detergent Isolation Stabilizes and Activates the Shigella Type III Secretion System Translocator Protein IpaC.

    Science.gov (United States)

    Bernard, Abram R; Duarte, Shari M; Kumar, Prashant; Dickenson, Nicholas E

    2016-07-01

    Shigella rely on a type III secretion system as the primary virulence factor for invasion and colonization of human hosts. Although there are an estimated 90 million Shigella infections, annually responsible for more than 100,000 deaths worldwide, challenges isolating and stabilizing many type III secretion system proteins have prevented a full understanding of the Shigella invasion mechanism and additionally slowed progress toward a much needed Shigella vaccine. Here, we show that the non-denaturing zwitterionic detergent N, N-dimethyldodecylamine N-oxide (LDAO) and non-ionic detergent n-octyl-oligo-oxyethylene efficiently isolated the hydrophobic Shigella translocator protein IpaC from the co-purified IpaC/IpgC chaperone-bound complex. Both detergents resulted in monomeric IpaC that exhibits strong membrane binding and lysis characteristics while the chaperone-bound complex does not, suggesting that the stabilizing detergents provide a means of following IpaC "activation" in vitro. Additionally, biophysical characterization found that LDAO provides significant thermal and temporal stability to IpaC, protecting it for several days at room temperature and brief exposure to temperatures reaching 90°C. In summary, this work identified and characterized conditions that provide stable, membrane active IpaC, providing insight into key interactions with membranes and laying a strong foundation for future vaccine formulation studies taking advantage of the native immunogenicity of IpaC and the stability provided by LDAO. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  18. Investigation of habitual pitch during free play activities for preschool-aged children.

    Science.gov (United States)

    Chen, Yang; Kimelman, Mikael D Z; Micco, Katie

    2009-01-01

    This study is designed to compare the habitual pitch measured in two different speech activities (free play activity and traditionally used structured speech activity) for normally developing preschool-aged children to explore to what extent preschoolers vary their vocal pitch among different speech environments. Habitual pitch measurements were conducted for 10 normally developing children (2 boys, 8 girls) between the ages of 31 months and 71 months during two different activities: (1) free play; and (2) structured speech. Speech samples were recorded using a throat microphone connected with a wireless transmitter in both activities. The habitual pitch (in Hz) was measured for all collected speech samples by using voice analysis software (Real-Time Pitch). Significantly higher habitual pitch is found during free play in contrast to structured speech activities. In addition, there is no showing of significant difference of habitual pitch elicited across a variety of structured speech activities. Findings suggest that the vocal usage of preschoolers appears to be more effortful during free play than during structured activities. It is recommended that a comprehensive evaluation for young children's voice needs to be based on the speech/voice samples collected from both free play and structured activities.

  19. Playing Active Video Games may not develop movement skills: An intervention trial

    OpenAIRE

    Barnett, Lisa M.; Ridgers, Nicola D.; Reynolds, John; Hanna, Lisa; Salmon, Jo

    2015-01-01

    Background: To investigate the impact of playing sports Active Video Games on children's actual and perceived object control skills. Methods: Intervention children played Active Video Games for 6 weeks (1 h/week) in 2012. The Test of Gross Motor Development-2 assessed object control skill. The Pictorial Scale of Perceived Movement Skill Competence assessed perceived object control skill. Repeated measurements of object control and perceived object control were analysed for the whole sample, u...

  20. Secretion management in the mechanically ventilated patient.

    Science.gov (United States)

    Branson, Richard D

    2007-10-01

    Secretion management in the mechanically ventilated patient includes routine methods for maintaining mucociliary function, as well as techniques for secretion removal. Humidification, mobilization of the patient, and airway suctioning are all routine procedures for managing secretions in the ventilated patient. Early ambulation of the post-surgical patient and routine turning of the ventilated patient are common secretion-management techniques that have little supporting evidence of efficacy. Humidification is a standard of care and a requisite for secretion management. Both active and passive humidification can be used. The humidifier selected and the level of humidification required depend on the patient's condition and the expected duration of intubation. In patients with thick, copious secretions, heated humidification is superior to a heat and moisture exchanger. Airway suctioning is the most important secretion removal technique. Open-circuit and closed-circuit suctioning have similar efficacy. Instilling saline prior to suctioning, to thin the secretions or stimulate a cough, is not supported by the literature. Adequate humidification and as-needed suctioning are the foundation of secretion management in the mechanically ventilated patient. Intermittent therapy for secretion removal includes techniques either to simulate a cough, to mechanically loosen secretions, or both. Patient positioning for secretion drainage is also widely used. Percussion and postural drainage have been widely employed for mechanically ventilated patients but have not been shown to reduce ventilator-associated pneumonia or atelectasis. Manual hyperinflation and insufflation-exsufflation, which attempt to improve secretion removal by simulating a cough, have been described in mechanically ventilated patients, but neither has been studied sufficiently to support routine use. Continuous lateral rotation with a specialized bed reduces atelectasis in some patients, but has not been shown

  1. Bile salt receptor complex activates a pathogenic type III secretion system

    Science.gov (United States)

    Li, Peng; Rivera-Cancel, Giomar; Kinch, Lisa N; Salomon, Dor; Tomchick, Diana R; Grishin, Nick V; Orth, Kim

    2016-01-01

    Bile is an important component of the human gastrointestinal tract with an essential role in food absorption and antimicrobial activities. Enteric bacterial pathogens have developed strategies to sense bile as an environmental cue to regulate virulence genes during infection. We discovered that Vibrio parahaemolyticus VtrC, along with VtrA and VtrB, are required for activating the virulence type III secretion system 2 in response to bile salts. The VtrA/VtrC complex activates VtrB in the presence of bile salts. The crystal structure of the periplasmic domains of the VtrA/VtrC heterodimer reveals a β-barrel with a hydrophobic inner chamber. A co-crystal structure of VtrA/VtrC with bile salt, along with biophysical and mutational analysis, demonstrates that the hydrophobic chamber binds bile salts and activates the virulence network. As part of a family of conserved signaling receptors, VtrA/VtrC provides structural and functional insights into the evolutionarily conserved mechanism used by bacteria to sense their environment. DOI: http://dx.doi.org/10.7554/eLife.15718.001 PMID:27377244

  2. Bile salt receptor complex activates a pathogenic type III secretion system

    Energy Technology Data Exchange (ETDEWEB)

    Li, Peng; Rivera-Cancel, Giomar; Kinch, Lisa N.; Salomon, Dor; Tomchick, Diana R.; Grishin, Nick V.; Orth, Kim

    2016-07-05

    Bile is an important component of the human gastrointestinal tract with an essential role in food absorption and antimicrobial activities. Enteric bacterial pathogens have developed strategies to sense bile as an environmental cue to regulate virulence genes during infection. We discovered thatVibrio parahaemolyticusVtrC, along with VtrA and VtrB, are required for activating the virulence type III secretion system 2 in response to bile salts. The VtrA/VtrC complex activates VtrB in the presence of bile salts. The crystal structure of the periplasmic domains of the VtrA/VtrC heterodimer reveals a β-barrel with a hydrophobic inner chamber. A co-crystal structure of VtrA/VtrC with bile salt, along with biophysical and mutational analysis, demonstrates that the hydrophobic chamber binds bile salts and activates the virulence network. As part of a family of conserved signaling receptors, VtrA/VtrC provides structural and functional insights into the evolutionarily conserved mechanism used by bacteria to sense their environment.

  3. Pretreatment with quercetin prevents changes in lymphocytes E-NTPDase/E-ADA activities and cytokines secretion in hyperlipidemic rats.

    Science.gov (United States)

    Braun, Josiane B S; Ruchel, Jader B; Manzoni, Alessandra G; Abdalla, Fátima H; Casalli, Emerson A; Castilhos, Lívia G; Passos, Daniela F; Leal, Daniela B R

    2017-11-29

    Hyperlipidemia (HL) is a condition associated with endothelial dysfunction and inflammatory disorders. Purinergic system ectoenzymes play an important role in modulating the inflammatory and immune response. This study investigated whether the preventive treatment with quercetin is able to prevent changes caused by hyperlipidemia in the purinergic system, through the activities of E-NTPDase and E-ADA in lymphocytes, and quantify the nucleotides and nucleoside, and the secretion of anti- and proinflammatory cytokines. Animals were divided into saline/control, saline/quercetin 5 mg/kg, saline/quercetin 25 mg/kg, saline/quercetin 50 mg/kg, saline/simvastatin (0.04 mg/kg), hyperlipidemia, hyperlipidemia/quercetin 5 mg/kg, hyperlipidemia/quercetin 25 mg/kg, hyperlipidemia/quercetin 50 mg/kg, and hyperlipidemia/simvastatin. Animals were pretreated with quercetin for 30 days and hyperlipidemia was subsequently induced by intraperitoneal administration of 500 mg/kg of poloxamer-407. Simvastatin was administered after the induction of hyperlipidemia. Lymphocytes were isolated and E-NTPDase and E-ADA activities were determined. Serum was separated for the cytokines and nucleotide/nucleoside quantification. E-NTPDase and E-ADA activities were increased in lymphocytes from hyperlipidemic rats and pretreatment with quercetin was able to prevent the increase in the activities of these enzymes caused by hyperlipidemia. Hyperlipidemic rats when receiving pretreatment with quercetin and treatment with simvastatin showed decreased levels of ATP and ADP when compared to the untreated hyperlipidemic group. The IFN-γ and IL-4 cytokines were increased in the hyperlipidemic group when compared with control group, and decreased when hyperlipidemic rats received the pretreatment with quercetin. However, pretreatment with quercetin was able to prevent the alterations caused by hyperlipidemia probably by regulating the inflammatory process. We can suggest that the quercetin is a

  4. Development of various reaction abilities and their relationships with favorite play activities in preschool children.

    Science.gov (United States)

    Miyaguchi, Kazuyoshi; Demura, Shinich; Sugiura, Hiroki; Uchiyama, Masanobu; Noda, Masahiro

    2013-10-01

    This study examines the development of various reaction movements in preschool children and the relationship between reaction times and favorite play activities. The subjects were 167 healthy preschool children aged 4-6 (96 boys and 71 girls). This study focused on the reaction times of the upper limbs (reaction 1: release; reaction 2: press) and the whole body (reaction 3: forward jump). The activities frequently played in preschools are largely divided into dynamic play activities (tag, soccer, gymnastics set, dodge ball, and jump rope) and static play activities (drawing, playing house, reading, playing with sand, and building blocks). The subjects chose 3 of 10 cards picturing their favorite play activities, depicting 10 different activities. All intraclass correlation coefficients of measured reaction times were high (0.73-0.79). In addition, each reaction time shortened with age. Reaction 1 showed a significant and low correlation with reaction 3 (r = 0.37). The effect size of the whole body reaction time was the largest. Whole body reaction movement, which is largely affected by the exercise output function, develops remarkably in childhood. Children who liked "tag" were faster in all reaction times. The children who chose "soccer" were faster in reactions 2 and 3. In contrast, children who liked "playing house" tended to have slower reaction times. Dynamic activities, such as tag and soccer, promote development of reaction speed and agility in movements involving the whole body. Preschool teachers and physical educators should re-examine the effect of tag and use it periodically as one of the exercise programs to avoid unexpected falls and injuries in everyday life.

  5. Activation of transmembrane bile acid receptor TGR5 stimulates insulin secretion in pancreatic {beta} cells

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Divya P.; Rajagopal, Senthilkumar; Mahavadi, Sunila [Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Mirshahi, Faridoddin [Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Grider, John R. [Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Murthy, Karnam S., E-mail: skarnam@vcu.edu [Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Sanyal, Arun J., E-mail: asanyal@mcvh-vcu.edu [Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA (United States)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer G protein coupled receptor TGR5 is expressed in mouse and human islets. Black-Right-Pointing-Pointer TGR5 is coupled to activation of Gs and Ca{sup 2+} release via cAMP/Epac/PLC-{epsilon} pathway. Black-Right-Pointing-Pointer Activation of TGR5 by bile salts and selective ligands causes insulin secretion. Black-Right-Pointing-Pointer TGR5 could be a potential therapeutic target to treat diabetes. -- Abstract: Bile acids act as signaling molecules and stimulate the G protein coupled receptor, TGR5, in addition to nuclear farnesoid X receptor to regulate lipid, glucose and energy metabolism. Bile acid induced activation of TGR5 in the enteroendocrine cells promotes glucagon like peptide-1 (GLP-1) release, which has insulinotropic effect in the pancreatic {beta} cells. In the present study, we have identified the expression of TGR5 in pancreatic {beta} cell line MIN6 and also in mouse and human pancreatic islets. TGR5 selective ligands, oleanolic acid (OA) and INT-777 selectively activated G{alpha}{sub s} and caused an increase in intracellular cAMP and Ca{sup 2+}. OA and INT-777 also increased phosphoinositide (PI) hydrolysis and the increase was blocked by NF449 (a selective G{alpha}{sub s} inhibitor) or (U73122) (PI hydrolysis inhibitor). OA, INT-777 and lithocholic acid increased insulin release in MIN6 and human islets and the increase was inhibited by treatment with NF449, (U73122) or BAPTA-AM (chelator of calcium), but not with myristoylated PKI (PKA inhibitor), suggesting that the release is dependent on G{sub s}/cAMP/Ca{sup 2+} pathway. 8-pCPT-2 Prime -O-Me-cAMP, a cAMP analog, which activates Epac, but not PKA also stimulated PI hydrolysis. In conclusion, our study demonstrates that the TGR5 expressed in the pancreatic {beta} cells regulates insulin secretion and highlights the importance of ongoing therapeutic strategies targeting TGR5 in the control of glucose homeostasis.

  6. Epithelial Cell–Derived Secreted and Transmembrane 1a Signals to Activated Neutrophils during Pneumococcal Pneumonia

    Science.gov (United States)

    Kamata, Hirofumi; Yamamoto, Kazuko; Wasserman, Gregory A.; Zabinski, Mary C.; Yuen, Constance K.; Lung, Wing Yi; Gower, Adam C.; Belkina, Anna C.; Ramirez, Maria I.; Deng, Jane C.; Quinton, Lee J.; Jones, Matthew R.

    2016-01-01

    Airway epithelial cell responses are critical to the outcome of lung infection. In this study, we aimed to identify unique contributions of epithelial cells during lung infection. To differentiate genes induced selectively in epithelial cells during pneumonia, we compared genome-wide expression profiles from three sorted cell populations: epithelial cells from uninfected mouse lungs, epithelial cells from mouse lungs with pneumococcal pneumonia, and nonepithelial cells from those same infected lungs. Of 1,166 transcripts that were more abundant in epithelial cells from infected lungs compared with nonepithelial cells from the same lungs or from epithelial cells of uninfected lungs, 32 genes were identified as highly expressed secreted products. Especially strong signals included two related secreted and transmembrane (Sectm) 1 genes, Sectm1a and Sectm1b. Refinement of sorting strategies suggested that both Sectm1 products were induced predominantly in conducting airway epithelial cells. Sectm1 was induced during the early stages of pneumococcal pneumonia, and mutation of NF-κB RelA in epithelial cells did not diminish its expression. Instead, type I IFN signaling was necessary and sufficient for Sectm1 induction in lung epithelial cells, mediated by signal transducer and activator of transcription 1. For target cells, Sectm1a bound to myeloid cells preferentially, in particular Ly6GbrightCD11bbright neutrophils in the infected lung. In contrast, Sectm1a did not bind to neutrophils from uninfected lungs. Sectm1a increased expression of the neutrophil-attracting chemokine CXCL2 by neutrophils from the infected lung. We propose that Sectm1a is an epithelial product that sustains a positive feedback loop amplifying neutrophilic inflammation during pneumococcal pneumonia. PMID:27064756

  7. Epithelial Cell-Derived Secreted and Transmembrane 1a Signals to Activated Neutrophils during Pneumococcal Pneumonia.

    Science.gov (United States)

    Kamata, Hirofumi; Yamamoto, Kazuko; Wasserman, Gregory A; Zabinski, Mary C; Yuen, Constance K; Lung, Wing Yi; Gower, Adam C; Belkina, Anna C; Ramirez, Maria I; Deng, Jane C; Quinton, Lee J; Jones, Matthew R; Mizgerd, Joseph P

    2016-09-01

    Airway epithelial cell responses are critical to the outcome of lung infection. In this study, we aimed to identify unique contributions of epithelial cells during lung infection. To differentiate genes induced selectively in epithelial cells during pneumonia, we compared genome-wide expression profiles from three sorted cell populations: epithelial cells from uninfected mouse lungs, epithelial cells from mouse lungs with pneumococcal pneumonia, and nonepithelial cells from those same infected lungs. Of 1,166 transcripts that were more abundant in epithelial cells from infected lungs compared with nonepithelial cells from the same lungs or from epithelial cells of uninfected lungs, 32 genes were identified as highly expressed secreted products. Especially strong signals included two related secreted and transmembrane (Sectm) 1 genes, Sectm1a and Sectm1b. Refinement of sorting strategies suggested that both Sectm1 products were induced predominantly in conducting airway epithelial cells. Sectm1 was induced during the early stages of pneumococcal pneumonia, and mutation of NF-κB RelA in epithelial cells did not diminish its expression. Instead, type I IFN signaling was necessary and sufficient for Sectm1 induction in lung epithelial cells, mediated by signal transducer and activator of transcription 1. For target cells, Sectm1a bound to myeloid cells preferentially, in particular Ly6G(bright)CD11b(bright) neutrophils in the infected lung. In contrast, Sectm1a did not bind to neutrophils from uninfected lungs. Sectm1a increased expression of the neutrophil-attracting chemokine CXCL2 by neutrophils from the infected lung. We propose that Sectm1a is an epithelial product that sustains a positive feedback loop amplifying neutrophilic inflammation during pneumococcal pneumonia.

  8. Changes in brain activity in response to problem solving during the abstinence from online game play.

    Science.gov (United States)

    Kim, Sun Mi; Han, Doug Hyun; Lee, Young Sik; Kim, Jieun E; Renshaw, Perry F

    2012-06-01

    Several studies have suggested that addictive disorders including substance abuse and pathologic gambling might be associated with dysfunction on working memory and prefrontal activity. We hypothesized that excessive online game playing is associated with deficits in prefrontal cortex function and that recovery from excessive online game playing might improve prefrontal cortical activation in response to working memory stimulation. Thirteen adolescents with excessive online game playing (AEOP) and ten healthy adolescents (HC) agreed to participate in this study. The severity of online game play and playing time were evaluated for a baseline measurement and again following four weeks of treatment. Brain activation in response to working memory tasks (simple and complex calculations) at baseline and subsequent measurements was assessed using BOLD functional magnetic resonance imaging (fMRI). Compared to the HC subjects, the AEOP participants exhibited significantly greater activity in the right middle occipital gyrus, left cerebellum posterior lobe, left premotor cortex and left middle temporal gyrus in response to working memory tasks during baseline measurements. After four weeks of treatment, the AEOP subjects showed increased activity within the right dorsolateral prefrontal cortex and left occipital fusiform gyrus. After four weeks of treatment, changes in the severity of online game playing were negatively correlated with changes in the mean β value of the right dorsolateral prefrontal cortex in response to complex stimulation. We suggest that the effects of online game addiction on working memory may be similar to those observed in patients with substance dependence.

  9. Type VI secretion system MIX-effectors carry both antibacterial and anti-eukaryotic activities.

    Science.gov (United States)

    Ray, Ann; Schwartz, Nika; de Souza Santos, Marcela; Zhang, Junmei; Orth, Kim; Salomon, Dor

    2017-11-01

    Most type VI secretion systems (T6SSs) described to date are protein delivery apparatuses that mediate bactericidal activities. Several T6SSs were also reported to mediate virulence activities, although only few anti-eukaryotic effectors have been described. Here, we identify three T6SSs in the marine bacterium Vibrio proteolyticus and show that T6SS1 mediates bactericidal activities under warm marine-like conditions. Using comparative proteomics, we find nine potential T6SS1 effectors, five of which belong to the polymorphic MIX-effector class. Remarkably, in addition to six predicted bactericidal effectors, the T6SS1 secretome includes three putative anti-eukaryotic effectors. One of these is a MIX-effector containing a cytotoxic necrotizing factor 1 domain. We demonstrate that T6SS1 can use this MIX-effector to target phagocytic cells, resulting in morphological changes and actin cytoskeleton rearrangements. In conclusion, the V. proteolyticus T6SS1, a system homologous to one found in pathogenic vibrios, uses a suite of polymorphic effectors that target both bacteria and eukaryotic neighbors. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  10. Deletion of creB in Aspergillus oryzae increases secreted hydrolytic enzyme activity.

    Science.gov (United States)

    Hunter, A J; Morris, T A; Jin, B; Saint, C P; Kelly, J M

    2013-09-01

    Aspergillus oryzae has been used in the food and beverage industry for centuries, and industrial strains have been produced by multiple rounds of selection. Targeted gene deletion technology is particularly useful for strain improvement in such strains, particularly when they do not have a well-characterized meiotic cycle. Phenotypes of an Aspergillus nidulans strain null for the CreB deubiquitinating enzyme include effects on growth and repression, including increased activity levels of various enzymes. We show that Aspergillus oryzae contains a functional homologue of the CreB deubiquitinating enzyme and that a null strain shows increased activity levels of industrially important secreted enzymes, including cellulases, xylanases, amylases, and proteases, as well as alleviated inhibition of spore germination on glucose medium. Reverse transcription-quantitative PCR (RT-qPCR) analysis showed that the increased levels of enzyme activity in both Aspergillus nidulans and Aspergillus oryzae are mirrored at the transcript level, indicating transcriptional regulation. We report that Aspergillus oryzae DAR3699, originally isolated from soy fermentation, has a similar phenotype to that of a creB deletion mutant of the RIB40 strain, and it contains a mutation in the creB gene. Collectively, the results for Aspergillus oryzae, Aspergillus nidulans, Trichoderma reesei, and Penicillium decumbens show that deletion of creB may be broadly useful in diverse fungi for increasing production of a variety of enzymes.

  11. Temperature oscillations drive cycles in the activity of MMP-2,9 secreted by a human trabecular meshwork cell line.

    Science.gov (United States)

    Li, Stanley Ka-Lok; Banerjee, Juni; Jang, Christopher; Sehgal, Amita; Stone, Richard A; Civan, Mortimer M

    2015-02-05

    Aqueous humor inflow falls 50% during sleeping hours without proportional fall in IOP, partly reflecting reduced outflow facility. The mechanisms underlying outflow facility cycling are unknown. One outflow facility regulator is matrix metalloproteinase (MMP) release from trabecular meshwork (TM) cells. Because anterior segment temperature must oscillate due to core temperature cycling and eyelid closure during sleep, we tested whether physiologically relevant temperature oscillations drive cycles in the activity of secreted MMP. Temperature of transformed normal human TM cells (hTM5 line) was fixed or alternated 12 hours/12 hours between 33°C and 37°C. Activity of secreted MMP-2 and MMP-9 was measured by zymography, and gene expression by RT-PCR and quantitative PCR. Raising temperature to 37°C increased, and lowering to 33°C reduced, activity of secreted MMP. Switching between 37°C and 33°C altered MMP-9 by 40% ± 3% and MMP-2 by 22% ± 2%. Peripheral circadian clocks did not mediate temperature-driven cycling of MMP secretion because MMP-release oscillations did not persist at constant temperature after 3 to 6 days of alternating temperatures, and temperature cycles did not entrain clock-gene expression in these cells. Furthermore, inhibiting heat shock transcription factor 1, which links temperature and peripheral clock-gene oscillations, inhibited MMP-9 but not MMP-2 temperature-driven MMP cycling. Inhibition of heat-sensitive TRPV1 channels altered total MMP secretion but not temperature-induced modulations. Inhibiting cold-sensitive TRPM-8 channels had no effect. Physiologically relevant temperature oscillations drive fluctuations of secreted MMP-2 and MMP-9 activity in hTM5 cells independent of peripheral clock genes and temperature-sensitive TRP channels. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  12. Changes in cue-induced, prefrontal cortex activity with video-game play.

    Science.gov (United States)

    Han, Doug Hyun; Kim, Yang Soo; Lee, Yong Sik; Min, Kyung Joon; Renshaw, Perry F

    2010-12-01

    Brain responses, particularly within the orbitofrontal and cingulate cortices, to Internet video-game cues in college students are similar to those observed in patients with substance dependence in response to the substance-related cues. In this study, we report changes in brain activity between baseline and following 6 weeks of Internet video-game play. We hypothesized that subjects with high levels of self-reported craving for Internet video-game play would be associated with increased activity in the prefrontal cortex, particularly the orbitofrontal and anterior cingulate cortex. Twenty-one healthy university students were recruited. At baseline and after a 6-week period of Internet video-game play, brain activity during presentation of video-game cues was assessed using 3T blood oxygen level dependent functional magnetic resonance imaging. Craving for Internet video-game play was assessed by self-report on a 7-point visual analogue scale following cue presentation. During a standardized 6-week video-game play period, brain activity in the anterior cingulate and orbitofrontal cortex of the excessive Internet game-playing group (EIGP) increased in response to Internet video-game cues. In contrast, activity observed in the general player group (GP) was not changed or decreased. In addition, the change of craving for Internet video games was positively correlated with the change in activity of the anterior cingulate in all subjects. These changes in frontal-lobe activity with extended video-game play may be similar to those observed during the early stages of addiction.

  13. Insulin secretion enhancing activity of roselle calyx extract in normal and streptozotocin-induced diabetic rats

    Science.gov (United States)

    Wisetmuen, Eamruthai; Pannangpetch, Patchareewan; Kongyingyoes, Bunkerd; Kukongviriyapan, Upa; Yutanawiboonchai, Wiboonchai; Itharat, Arunporn

    2013-01-01

    Background and Objective: Our recent study revealed the antihyperglycemic activity of an ethanolic extract of roselle calyxes (Hibiscus sabdariffa) in diabetic rats. The present study had, therefore, an objective to investigate the mechanism underlying this activity. Materials and Methods: Male Sprague Dawley rats were induced to be diabetes by intraperitoneal injection of 45 mg/kg streptozotocin (STZ). Normal rats as well as diabetic rats were administered with the ethanolic extract of H. sabdariffa calyxes (HS-EE) at 0.1 and 1.0 g/kg/day, respectively, for 6 weeks. Then, blood glucose and insulin levels, at basal and glucose-stimulated secretions, were measured. The pancreas was dissected to examine histologically. Results: HS-EE 1.0 g/kg/day significantly decreased the blood glucose level by 38 ± 12% in diabetic rats but not in normal rats. In normal rats, treatment with 1.0 g/kg HS-EE increased the basal insulin level significantly as compared with control normal rats (1.28 ± 0.25 and 0.55 ± 0.05 ng/ml, respectively). Interestingly, diabetic rats treated with 1.0 g/kg HS-EE also showed a significant increase in basal insulin level as compared with the control diabetic rats (0.30 ± 0.05 and 0.15 ± 0.01 ng/ml, respectively). Concerning microscopic histological examination, HS-EE 1.0 g/kg significantly increased the number of islets of Langerhans in both normal rats (1.2 ± 0.1 and 2.0 ± 0.1 islet number/10 low-power fields (LPF) for control and HS-EE treated group, respectively) and diabetic rats (1.0 ± 0.3 and 3.9 ± 0.6 islet number/10 LPF for control and HS-EE treated group, respectively). Conclusion: The antidiabetic activity of HS-EE may be partially mediated via the stimulating effect on insulin secretion. PMID:23798879

  14. Irradiation Effect on Secreting Function, Amylase Activity and Nucleic Acid Contents of Rat Parotid Gland

    International Nuclear Information System (INIS)

    Cho, Young Jin; Park, Tae Won

    1990-01-01

    This experiment was performed to clarify the effects of 60 Co gamma irradiation on secretory function, amylase activity and contents of nucleic acids of parotid gland in rat. Experimental animals were divided into 6th hours, 3rd, 7th, 14th and 28th days after irradiation and control. The experimental animals are singly irradiated with 20 Gy (2,000 rad) through protective lead block. Secretory function of parotid gland was evaluated by uptake and clearance of 99m TcO 4 . 99m TcO 4 , 0.2μ ci/gm, was injected into peritonium in uptake groups. Rats were sacrificed with cervical dislocation after 30 minutes and gland was excised. In the clearance group, pilocarpine nitrate (8 mg/kg) was intraperitoneally injected at 30 minutes after 99m TcO 4 injection and rats were sacrificed 30 minutes after pilocarpine infection. Radioactivity of excised parotid gland was measured by using of gamma counter and stimulation-secretion coefficient, uptake radioactivity divided by clearance radioactivity, was calculated. Amylase activity and contents of DNA and RNA were determined by spectrophotometry. The results obtained were as follows: 1. In the uptake test, the radioactivity of 99m TcO 4 per unit weight increase in experimental group except 6th hours group, compared with control groups and showed a peak at 3rd days after irradiation. 2. In the clearance test, the radioactivity of 99m TcO 4 per unit weight rose to a peak at 3rd days after irradiation and gradually recovered thereafter. 3. Stimulation-secretion coefficient of parotid gland decreased at 6th hours, 3rd and 7th days after irradiation, and gradually increased. 4. Amylase activity of parotid gland decreased in 3rd and 7th days group, and especially lowest in 3rd days after irradiation. 5. The contents of DNA showed no definite difference in all the experimental groups, but RNA was seemed to decrease with time after irradiation.

  15. Technical activity profile and influence of body anthropometry on playing performance in female elite team handball

    DEFF Research Database (Denmark)

    Michalsik, Lars B; Aagaard, Per; Madsen, Klavs

    2015-01-01

    regular tournament match seasons. Technical match activities were distributed in 6 major types of playing actions (shots, breakthroughs, fast breaks, technical errors, defensive errors, and tackles) and further divided into various subcategories (e.g., type of shot, hard or light tackles, claspings......, screenings, and blockings). Furthermore, anthropometric measurements were performed. Each player had 28.3 ± 11.0 (group means ± SD) high-intense playing actions per match with a total effective playing time of 50.70 ± 5.83 minutes. On average, each player made 2.8 ± 2.6 fast breaks, gave 7.9 ± 14...... that female elite TH players during competitive games intermittently perform a high number of short-term, high-intense technical playing actions making modern female elite TH a physically demanding team sport. No sign of technical fatigue were observed, since the amount of intense technical playing actions...

  16. Children with Autism Spectrum Disorder and Patterns of Participation in Daily Physical and Play Activities

    Directory of Open Access Journals (Sweden)

    Amir Hossein Memari

    2015-01-01

    Full Text Available Autism spectrum disorder (ASD indicates several neurodevelopmental impairments which may end in impairments in motor or physical activities. Daily physical activity involvement was investigated in a total of 83 children (52 boys and 31 girls with ASD aged 6–15 years. Results indicated that only 10 (12% of children with ASD were physically active. Children were predominantly engaged in solitary play rather than social play activities. Gender, family income, and household structure were found to be associated with activity scores. Financial burden and lack of opportunities were noted as the leading barriers to physical activities. In conclusion, findings indicated a low rate of physical activity participation in children with ASD that is closely associated with sociodemographic variables.

  17. Narrative increases step counts during active video game play among children

    Science.gov (United States)

    Active video games (AVGs) capable of inducing physical activity (PA) level offer a novel alternative to child obesity. Unfortunately, children's motivation to play AVG decreases quickly, underscoring the need to find new methods to maintain their engagement. According to narrative transportation th...

  18. Plan before You Play: An Activity for Teaching the Managerial Process

    Science.gov (United States)

    Althouse, Norm R.; Hedges, Peggy L.

    2015-01-01

    This article describes a 60-minute classroom activity using LEGO® bricks that demonstrates and reinforces the importance of the managerial process. The activity, Plan Before You Play (PBP), is targeted to introductory business classes, and differs from others in that it requires little investment or up-front planning, is easily scalable, and, with…

  19. Quantitative Secretome Analysis of Activated Jurkat Cells Using Click Chemistry-Based Enrichment of Secreted Glycoproteins.

    Science.gov (United States)

    Witzke, Kathrin E; Rosowski, Kristin; Müller, Christian; Ahrens, Maike; Eisenacher, Martin; Megger, Dominik A; Knobloch, Jürgen; Koch, Andrea; Bracht, Thilo; Sitek, Barbara

    2017-01-06

    Quantitative secretome analyses are a high-performance tool for the discovery of physiological and pathophysiological changes in cellular processes. However, serum supplements in cell culture media limit secretome analyses, but serum depletion often leads to cell starvation and consequently biased results. To overcome these limiting factors, we investigated a model of T cell activation (Jurkat cells) and performed an approach for the selective enrichment of secreted proteins from conditioned medium utilizing metabolic marking of newly synthesized glycoproteins. Marked glycoproteins were labeled via bioorthogonal click chemistry and isolated by affinity purification. We assessed two labeling compounds conjugated with either biotin or desthiobiotin and the respective secretome fractions. 356 proteins were quantified using the biotin probe and 463 using desthiobiotin. 59 proteins were found differentially abundant (adjusted p-value ≤0.05, absolute fold change ≥1.5) between inactive and activated T cells using the biotin method and 86 using the desthiobiotin approach, with 31 mutual proteins cross-verified by independent experiments. Moreover, we analyzed the cellular proteome of the same model to demonstrate the benefit of secretome analyses and provide comprehensive data sets of both. 336 proteins (61.3%) were quantified exclusively in the secretome. Data are available via ProteomeXchange with identifier PXD004280.

  20. Effect of certain active components from traditional Chinese medicinal herbs on Aβ secretion rate with L-[35S]-Methionine

    International Nuclear Information System (INIS)

    Hu Yaer; Zhang Naizheng; Li Aimin; Xia Zongqin

    2006-01-01

    To observe the effect of certain active components from traditional Chinese medicinal herbs on Aβ secretion rates with L-[ 35 S]-Methionine, β-amyloid peptide (Aβ) in SK-N-SH cell lines stably transfected with APP695 was metabolically labeled with L-[ 35 S]-Methionine. the supernatant from culture medium was immunoprecipitated with monoclonal antibody against Aβ 22-35 , Western blot was carried out, and the gray density of Aβ band in the autoradiograph was measured by an image analysis system. The active components from certain traditional Chinese medicinal herbs (ZMS from Zhimu and AST and HT from Huangqi) were added to the culture medium at a final concentration of 10 -5 mol/L. An Aβ band in the autoradiograph was clearly viewed in the culture medium after 24 h incorporation of [ -35 S]-Methionine which represent the secretion rate of Aβ by the cells. One of the 3 tested components (AST) could significantly reduce the Aβ secretion rate while the other two showed no effect. The preliminary result showed that certain active component from traditional Chinese medicines could decrease the Aβ secretion rate but other active components could not. Combined use of the AST and ZMS was more effective than single AST. (authors)

  1. Propionic acid secreted from propionibacteria induces NKG2D ligand expression on human-activated T lymphocytes and cancer cells

    DEFF Research Database (Denmark)

    Andresen, Lars; Hansen, Karen Aagaard; Jensen, Helle

    2009-01-01

    We found that propionic acid secreted from propionibacteria induces expression of the NKG2D ligands MICA/B on activated T lymphocytes and different cancer cells, without affecting MICA/B expression on resting peripheral blood cells. Growth supernatant from propionibacteria or propionate alone cou...

  2. Daily portraits of five and six-year old boys: the play activity

    Directory of Open Access Journals (Sweden)

    Flavia Bignardi da Silva Nunes

    2013-08-01

    Full Text Available Introduction: Daily life experiences provide maturity along human development, and the environments in which they occur are essential for this process. These experiences help to build children’s personalities and the way they deal with the world around them. Objectives: In this study, we aimed to understand the occupational behavior of four children aged five to six years old through their mothers’ reports. Methodology: The average time spent with daily activities is described, and playing was a central theme of analysis. We analyzed the preferences, companies and emotional characteristics of the play activity. We used an Activity Clock and semi-structured interviews with the children’s mothers as data collection instruments. Results: The main results show that most of their daily life time is spent with sleep, school and play activities. They indicate that children prefer games that challenge acquisitions that are under construction. Regarding company, these children still have their mothers as a reference to the play activity, but also peers their age or a little older. Conclusion: Play has an important representation in the daily occupational lives of these children and it stands as a key life experience to acquire skills and face challenges.

  3. Adherence to active play and electronic media guidelines in preschool children: gender and parental education considerations.

    Science.gov (United States)

    Loprinzi, Paul D; Schary, David P; Cardinal, Bradley J

    2013-01-01

    The primary purpose of the present study was to examine adherence to current active play and electronic media use guidelines in a sample of US preschool-aged children and to examine whether differences occurred across gender and parental education. 164 parents completed an on-line survey to estimate preschool children's active play and sedentary behaviors. For weekdays, 50% of the sample met the active play guideline with this increasing to 65% during the weekend. With respect to electronic media use, 90% of the sample met guidelines during the week, with the percentage meeting guidelines dropping to 78% during the weekend. A greater percentage of preschool children from high parental education families (83.4 ± 3.3) met electronic media use guidelines on the weekends, compared to preschool children from low parental education families (59.4 ± 8.1) (p = 0.002). Our findings indicate that a substantial portion of preschool children are not meeting active play guidelines and that adherence to active play and electronic media use guidelines may be influenced by parental education.

  4. HybridPLAY: A New Technology to Foster Outdoors Physical Activity, Verbal Communication and Teamwork.

    Science.gov (United States)

    Díaz, Diego José; Boj, Clara; Portalés, Cristina

    2016-04-23

    This paper presents HybridPLAY, a novel technology composed of a sensor and mobile-based video games that transforms urban playgrounds into game scenarios. With this technology we aim to stimulate physical activity and playful learning by creating an entertaining environment in which users can actively participate and collaborate. HybridPLAY is different from other existing technologies that enhance playgrounds, as it is not integrated in them but can be attached to the different elements of the playgrounds, making its use more ubiquitous (i.e., not restricted to the playgrounds). HybridPLAY was born in 2007 as an artistic concept, and evolved after different phases of research and testing by almost 2000 users around the world (in workshops, artistic events, conferences, etc.). Here, we present the temporal evolution of HybridPLAY with the different versions of the sensors and the video games, and a detailed technical description of the sensors and the way interactions are produced. We also present the outcomes after the evaluation by users at different events and workshops. We believe that HybridPLAY has great potential to contribute to increased physical activity in kids, and also to improve the learning process and monitoring at school centres by letting users create the content of the apps, leading to new narratives and fostering creativity.

  5. HybridPLAY: A New Technology to Foster Outdoors Physical Activity, Verbal Communication and Teamwork

    Directory of Open Access Journals (Sweden)

    Diego José Díaz

    2016-04-01

    Full Text Available This paper presents HybridPLAY, a novel technology composed of a sensor and mobile-based video games that transforms urban playgrounds into game scenarios. With this technology we aim to stimulate physical activity and playful learning by creating an entertaining environment in which users can actively participate and collaborate. HybridPLAY is different from other existing technologies that enhance playgrounds, as it is not integrated in them but can be attached to the different elements of the playgrounds, making its use more ubiquitous (i.e., not restricted to the playgrounds. HybridPLAY was born in 2007 as an artistic concept, and evolved after different phases of research and testing by almost 2000 users around the world (in workshops, artistic events, conferences, etc.. Here, we present the temporal evolution of HybridPLAY with the different versions of the sensors and the video games, and a detailed technical description of the sensors and the way interactions are produced. We also present the outcomes after the evaluation by users at different events and workshops. We believe that HybridPLAY has great potential to contribute to increased physical activity in kids, and also to improve the learning process and monitoring at school centres by letting users create the content of the apps, leading to new narratives and fostering creativity.

  6. HybridPLAY: A New Technology to Foster Outdoors Physical Activity, Verbal Communication and Teamwork

    Science.gov (United States)

    Díaz, Diego José; Boj, Clara; Portalés, Cristina

    2016-01-01

    This paper presents HybridPLAY, a novel technology composed of a sensor and mobile-based video games that transforms urban playgrounds into game scenarios. With this technology we aim to stimulate physical activity and playful learning by creating an entertaining environment in which users can actively participate and collaborate. HybridPLAY is different from other existing technologies that enhance playgrounds, as it is not integrated in them but can be attached to the different elements of the playgrounds, making its use more ubiquitous (i.e., not restricted to the playgrounds). HybridPLAY was born in 2007 as an artistic concept, and evolved after different phases of research and testing by almost 2000 users around the world (in workshops, artistic events, conferences, etc.). Here, we present the temporal evolution of HybridPLAY with the different versions of the sensors and the video games, and a detailed technical description of the sensors and the way interactions are produced. We also present the outcomes after the evaluation by users at different events and workshops. We believe that HybridPLAY has great potential to contribute to increased physical activity in kids, and also to improve the learning process and monitoring at school centres by letting users create the content of the apps, leading to new narratives and fostering creativity. PMID:27120601

  7. Meaning and purposes of the play activity for childhood education’ teachers

    Directory of Open Access Journals (Sweden)

    Dijnane Fernanda Vedovatto Iza

    2015-11-01

    Full Text Available In this paper we discusses the importance of the childish education teachers clearly know about the meaning and the sense of the play activities with children 0 a 6 years old. This is part of doctor thesis from among of goals, one of them was to unveil the meaning and sense of the play activities attributed by childish education teachers. Part of the methodology used in the research involved interview with five childish education teachers who participated of a course about o theme and, so, video-records about yours routines and activities with the children. The results denote that the meaning and sense attributed by these teachers at to propose play activities for the children are connected to understanding of this activity as generating of the learns for this ages and, therefore, it needs to be developed with pleasure. The changes in the practices with the children are attribute to the courses which the teachers change experiences, discusses problems, suggest solutions and enlarge the possibilities about yours practices with children, which can to mean the improvement of the childish education quality. From There the importance of the public politics invest in the actions to the continuing childish teacher education by partnership with the university, so that the teachers can enlarge yours conceptions about the play activities and feel safety about to propose and to encourage these activities between children.

  8. The type VI secretion system encoded in SPI-6 plays a role in gastrointestinal colonization and systemic spread of Salmonella enterica serovar Typhimurium in the chicken.

    Directory of Open Access Journals (Sweden)

    David Pezoa

    Full Text Available The role of the Salmonella Pathogenicity Islands (SPIs in pathogenesis of Salmonella enterica Typhimurium infection in the chicken is poorly studied, while many studies have been completed in murine models. The Type VI Secretion System (T6SS is a recently described protein secretion system in Gram-negative bacteria. The genus Salmonella contains five phylogenetically distinct T6SS encoded in differentially distributed genomic islands. S. Typhimurium harbors a T6SS encoded in SPI-6 (T6SSSPI-6, which contributes to the ability of Salmonella to colonize mice. On the other hand, serotype Gallinarum harbors a T6SS encoded in SPI-19 (T6SSSPI-19 that is required for colonization of chicks. In this work, we investigated the role of T6SSSPI-6 in infection of chicks by S. Typhimurium. Oral infection of White Leghorn chicks showed that a ΔT6SSSPI-6 mutant had reduced colonization of the gut and internal organs, compared with the wild-type strain. Transfer of the intact T6SSSPI-6 gene cluster into the T6SS mutant restored bacterial colonization. In addition, our results showed that transfer of T6SSSPI-19 from S. Gallinarum to the ΔT6SSSPI-6 mutant of S. Typhimurium not only complemented the colonization defect but also resulted in a transient increase in the colonization of the cecum and ileum of chicks at days 1 and 3 post-infection. Our data indicates that T6SSSPI-6 contributes to chicken colonization and suggests that both T6SSSPI-6 and T6SSSPI-19 perform similar functions in vivo despite belonging to different phylogenetic families.

  9. Is playing exergames really exercising? A meta-analysis of energy expenditure in active video games.

    Science.gov (United States)

    Peng, Wei; Lin, Jih-Hsuan; Crouse, Julia

    2011-11-01

    This article reports a meta-analysis of energy expenditure (EE) of playing active video games (AVGs). In particular, heart rate (HR), oxygen consumption (VO2), and EE were assessed and three moderators for the effects of AVGs--types of AVG, player age, and player weight status--were analyzed. The results show that playing AVGs significantly increased HR, VO2, and EE from resting. The effect sizes of playing AVGs on HR, VO2, and EE were similar to traditional physical activities. AVG type and player age were significant moderators for the effects of AVGs. The finding suggests that AVGs are effective technologies that may facilitate light- to moderate-intensity physical activity promotion.

  10. Ecological literacy and concepts formation in childhood education through playful activities

    Directory of Open Access Journals (Sweden)

    Ana Célia de Brito Miranda

    2010-07-01

    Full Text Available This study aimed to investigate the concept formation involved in the study of food chain by utilizing the vygotskian referential and playful activities. The teacher-researcher planned the activities that were experienced by a group of children in an elementary school aged 4 to 5. The topic chosen intended to support ecological literacy and the construction of scientific concepts in children. For the data collect, the study employed diverse instruments of a playful nature, such as theatre, games, drawings, and video-recorded interviews. The study showed a generally positive influence of playful activities to develop a perception of belonging to the food chain and becoming aware of the importance of caring for animals in order to preserve life, as well as an evolution inside the phases proposed by Vygotsky.

  11. In-vitro secretion of inhibin-like activity by Sertoli cells from normal and prenatally irradiated immature rats

    International Nuclear Information System (INIS)

    Ultee-van Gessel, A.M.; Leemborg, F.G.; Jong, F.H. de; Molen, H.J. van der

    1986-01-01

    The influence of in-vitro conditions on the production of inhibin by Sertoli cells from 21-day-old normal and prenatally irradiated rat testes was studied by measuring inhibin activity in culture media, using the suppression of the release of FSH from cultured rat pituitary cells. Sertoli cells secreted inhibin-like activity during at least 21 days of culture, and cells cultured at 37 0 C produced significantly more inhibin than those cultured at 32 0 C. The presence of fetal calf serum had no significant effect on inhibin production at 32 0 C, while at 37 0 C the production was decreased. The presence of ovine FSH stimulated inhibin secretion, while inhibin concentrations in Sertoli cell culture media were decreased after the addition of testosterone. Testosterone, added together with ovine FSH, suppressed inhibin secretion when compared with the levels found in the presence of FSH alone. The presence of spermatogenic cells decreased the release of inhibin. From these results it was concluded that both Sertoli cells isolated from normal immature rat testes and those from testes without spermatogenic cells can secrete inhibin-like activity in culture. A number of discrepancies with in-vivo observations was observed. (author)

  12. Effect of Sex and Body Mass Index on Children's Physical Activity Intensity during Free Play at an Indoor Soft Play Center: An Exploratory Study.

    Science.gov (United States)

    Jones, Michelle A

    2017-09-12

    Background : Indoor soft play can provide a safe but exciting physical activity opportunity regardless of environmental conditions. Relatively little is known about the quality or quantity of physical activity engaged in by children during indoor free soft play. The aim of this study was to evaluate the contribution indoor free soft play can make in enabling children to meet physical activity guidelines and to evaluate the effects of sex and body mass index category. Methods : Seventy-two boys and girls aged five to 10 years engaged in un-controlled indoor free soft play with a mean duration of 120.7 (27.1) min, during which physical activity was monitored using Actigraph accelerometers. Results : Children spent an average of 61.7 (24.2) min engaging in moderate to vigorous physical activity (MVPA) and 51.4% ( n = 37) achieved the recommended 60 min of MVPA through the single visit to the indoor soft play center. Boys (68.3 (25.7) min) engaged in significantly ( p < 0.05) more MVPA than girls (55.8 (21.4) min). Normal weight (65.7 (23.3) min) children engaged in significantly more MVPA than overweight children (48.0 (18.9) min). Conclusions : Attendance at a soft play indoor center has the potential to support children to engage in sufficient MVPA and overcome environmental factors that can restrict physical activity opportunities.

  13. Effect of Sex and Body Mass Index on Children’s Physical Activity Intensity during Free Play at an Indoor Soft Play Center: An Exploratory Study

    Science.gov (United States)

    2017-01-01

    Background: Indoor soft play can provide a safe but exciting physical activity opportunity regardless of environmental conditions. Relatively little is known about the quality or quantity of physical activity engaged in by children during indoor free soft play. The aim of this study was to evaluate the contribution indoor free soft play can make in enabling children to meet physical activity guidelines and to evaluate the effects of sex and body mass index category. Methods: Seventy-two boys and girls aged five to 10 years engaged in un-controlled indoor free soft play with a mean duration of 120.7 (27.1) min, during which physical activity was monitored using Actigraph accelerometers. Results: Children spent an average of 61.7 (24.2) min engaging in moderate to vigorous physical activity (MVPA) and 51.4% (n = 37) achieved the recommended 60 min of MVPA through the single visit to the indoor soft play center. Boys (68.3 (25.7) min) engaged in significantly (p < 0.05) more MVPA than girls (55.8 (21.4) min). Normal weight (65.7 (23.3) min) children engaged in significantly more MVPA than overweight children (48.0 (18.9) min). Conclusions: Attendance at a soft play indoor center has the potential to support children to engage in sufficient MVPA and overcome environmental factors that can restrict physical activity opportunities. PMID:28895904

  14. Exploring children's seasonal play to promote active lifestyles in Auckland, New Zealand.

    Science.gov (United States)

    Ergler, Christina R; Kearns, Robin; Witten, Karen

    2016-09-01

    Studies of seasonal barriers for outdoor activities seldom view families' play practices as grounded in the everyday experience of the natural elements. This paper brings 20 families' mundane outdoor play experiences in Auckland's temperate climate to the fore. Through drawings and interviews, families residing in both suburban detached houses and central city apartments revealed locally constituted beliefs about appropriate play spaces (e.g. garden, park). While the majority of participants retreated to indoor activities during winter, some children and their parents viewed the outdoors as the only opportunity for 'real fun'. We advocate the importance of a better understanding of children's seasonal outdoor play. In particular, we argue that in order to promote year-round healthy levels of outdoor activities it is necessary to understand variations in societal, neighbourhood and family values attributed to outdoor activities. Further, to develop a more nuanced understanding of the locational complexities of outdoor play it is important to understand the meanings of, and practices associated with, seasonal and weather conditions in different international locations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. A meta-study of qualitative research examining determinants of children's independent active free play.

    Science.gov (United States)

    Lee, Homan; Tamminen, Katherine A; Clark, Alexander M; Slater, Linda; Spence, John C; Holt, Nicholas L

    2015-01-24

    To produce a meta-study by completing a systematic review of qualitative research examining determinants of independent active free play in children. Following systematic electronic and manual searches and application of inclusion/exclusion criteria, 46 studies were retained and subjected to meta-method, meta-theory, and meta-data analyses, followed by a final meta-synthesis. Identified determinants of independent active free play were child characteristics (age, competence, and gender), parental restrictions (safety concerns and surveillance), neighborhood and physical environment (fewer children to play with, differences in preferences for play spaces between parents and children, accessibility and proximity, and maintenance), societal changes (reduced sense of community, good parenting ideal, changing roles of parents, privatization of playtime and play spaces), and policy issues (need to give children voice). An ecological model depicting these factors, and the relationships therein, was created. This comprehensive meta-study helps establish a knowledge base for children's independent active free play research by synthesizing a previously fragmented set of studies. Parents' perceived safety concerns are the primary barrier to children's active free play. These safety concerns are moderated by child-level factors (age, competence, gender) and broader social issues. Interventions should focus on community-level solutions that include children's perspectives. From a methods perspective, the reviewed studies used a range of data collection techniques, but methodological details were often inadequately reported. The theoretical sophistication of research in this area could be improved. To this end, the synthesis reported in this study provides a framework for guiding future research.

  16. Pituitary adenylate cyclase-activating polypeptide stimulates renin secretion via activation of PAC1 receptors

    DEFF Research Database (Denmark)

    Hautmann, Matthias; Friis, Ulla G; Desch, Michael

    2007-01-01

    Besides of its functional role in the nervous system, the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in the regulation of cardiovascular function. Therefore, PACAP is a potent vasodilator in several vascular beds, including the renal vasculature. Because...

  17. Enhancing the effect of secreted cyclophilin B on immunosuppressive activity of cyclosporine.

    Science.gov (United States)

    Denys, A; Allain, F; Masy, E; Dessaint, J P; Spik, G

    1998-04-27

    Cyclophilin B (CyPB) is a cyclosporine (CsA)-binding protein, located within intracellular vesicles and secreted in biological fluids. In previous works, we reported that CyPB specifically interacts with the T-cell membrane and potentiates the ability of CsA to inhibit CD3-induced proliferation of T lymphocytes. CyPB levels were measured in plasma from healthy donors and transplant patients. The role of extracellular CyPB on the distribution and activity of CsA was investigated first by studies on the uptake of free and CyPB-complexed drug by blood cells, and second by studies on the inhibitory effects of these two compounds on the CD3-induced proliferation of peripheral blood mononuclear cells. A significant increase in plasma CyPB level was observed for CsA-treated patients (13+/-6.4 nM, n=42) in comparison with untreated donors (4.3+/-2.1 nM, n=34). In vitro, extracellular CyPB dose dependently modified CsA distribution between plasma, erythrocyte, and lymphocyte contents, by both retaining the complexed drug extracellularly and promoting its specific accumulation within peripheral blood mononuclear cells. Moreover, the enhanced ability of CyPB-complexed CsA to suppress CD3-induced T-cell proliferation was preserved in the presence of other blood cells, implying specific targeting of the drug to sensitive cells. Furthermore, although a large interindividual variability of sensitivity to the drug was confirmed for 18 individuals, we found that CyPB potentiated the activity of CsA in restoring a high sensitivity to the immunosuppressant. These results suggest that plasma CyPB may contribute to the acceptance and the good maintenance of organ transplantation by enhancing the immunosuppressive activity of CsA through a receptor-mediated incorporation of CyPB-complexed CsA within peripheral blood lymphocytes.

  18. Meaning and purposes of the play activity for childhood education’ teachers

    OpenAIRE

    Dijnane Fernanda Vedovatto Iza; Maria Aparecida Mello

    2015-01-01

    In this paper we discusses the importance of the childish education teachers clearly know about the meaning and the sense of the play activities with children 0 a 6 years old. This is part of doctor thesis from among of goals, one of them was to unveil the meaning and sense of the play activities attributed by childish education teachers. Part of the methodology used in the research involved interview with five childish education teachers who participated of a course about o theme and, so, vi...

  19. Open Secrets

    OpenAIRE

    Madison, Michael

    2017-01-01

    The law of trade secrets is often conceptualized in bilateral terms, as creating and enforcing rights between trade secret owners, on the one hand, and misappropriators on the other hand. This paper, a chapter in a forthcoming collection on the law of trade secrets, argues that trade secrets and the law that guards them can serve structural and insitutional roles as well. Somewhat surprisingly, given the law’s focus on secrecy, among the institutional products of trade secrets law are commons...

  20. AhR-dependent secretion of PDGF-BB by human classically activated macrophages exposed to DEP extracts stimulates lung fibroblast proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Jaguin, Marie [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France); Fardel, Olivier [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France); Pôle Biologie, Centre Hospitalier Universitaire (CHU) Rennes, 2 rue Henri Le Guilloux, 35033 Rennes Cedex (France); Lecureur, Valérie, E-mail: valerie.lecureur@univ-rennes1.fr [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 Avenue du Pr Léon Bernard, 35043 Rennes Cedex (France)

    2015-06-15

    Lung diseases are aggravated by exposure to diesel exhaust particles (DEPs) found in air pollution. Macrophages are thought to play a crucial role in lung immune response to these pollutants, even if the mechanisms involved remain incompletely characterized. In the present study, we demonstrated that classically and alternative human macrophages (MΦ) exhibited increased secretion of PDGF-B in response to DEP extract (DEPe). This occurred via aryl hydrocarbon receptor (AhR)-activation because DEPe-induced PDGF-B overexpression was abrogated after AhR expression knock-down by RNA interference, in both M1 and M2 polarizing MΦ. In addition, TCDD and benzo(a)pyrene, two potent AhR ligands, also significantly increased mRNA expression of PDGF-B in M1 MΦ, whereas some weak ligands of AhR did not. We next evaluated the impact of conditioned media (CM) from MΦ culture exposed to DEPe or of recombinant PDGF-B onto lung fibroblast proliferation. The tyrosine kinase inhibitor, AG-1295, prevents phosphorylations of PDGF-Rβ, AKT and ERK1/2 and the proliferation of MRC-5 fibroblasts induced by recombinant PDGF-B and by CM from M1 polarizing MΦ, strongly suggesting that the PDGF-BB secreted by DEPe-exposed MΦ is sufficient to activate the PDGF-Rβ pathway of human lung fibroblasts. In conclusion, we demonstrated that human MΦ, whatever their polarization status, secrete PDGF-B in response to DEPe and that PDGF-B is a target gene of AhR. Therefore, induction of PDGF-B by DEP may participate in the deleterious effects towards human health triggered by such environmental urban contaminants. - Highlights: • PDGF-B expression and secretion are increased by DEPe exposure in human M1 and M2 MΦ. • DEPe-induced PDGF-B expression is aryl-hydrocarbon-dependent. • DEPe-exposed M1 MΦ secrete sufficient PDGF-B to increase lung fibroblast proliferation.

  1. Video game play, child diet, and physical activity behavior change: A randomized clinical trial

    Science.gov (United States)

    Video games designed to promote behavior change are a promising venue to enable children to learn healthier behaviors. The purpose is to evaluate the outcome from playing "Escape from Diab" (Diab) and "Nanoswarm: Invasion from Inner Space" (Nano) video games on children's diet, physical activity, an...

  2. The Play Curricular Activity Reflection Discussion Model for Game-Based Learning

    Science.gov (United States)

    Foster, Aroutis; Shah, Mamta

    2015-01-01

    This article elucidates the process of game-based learning in classrooms through the use of the Play Curricular activity Reflection Discussion (PCaRD) model. A mixed-methods study was conducted at a high school to implement three games with the PCaRD model in a year-long elective course. Data sources included interviews and observations for…

  3. Video game play, child diet, and physical activity behavior change a randomized clinical trial.

    Science.gov (United States)

    Baranowski, Tom; Baranowski, Janice; Thompson, Debbe; Buday, Richard; Jago, Russ; Griffith, Melissa Juliano; Islam, Noemi; Nguyen, Nga; Watson, Kathleen B

    2011-01-01

    Video games designed to promote behavior change are a promising venue to enable children to learn healthier behaviors. Evaluate outcome from playing "Escape from Diab" (Diab) and "Nanoswarm: Invasion from Inner Space" (Nano) video games on children's diet, physical activity, and adiposity. Two-group RCT; assessments occurred at baseline, immediately after Diab, immediately after Nano, and 2 months later. Data were collected in 2008-2009, and analyses were conducted in 2009-2010. 133 children aged 10-12 years, initially between 50th percentile and 95th percentile BMI. Treatment group played Diab and Nano in sequence. Control Group played diet and physical activity knowledge-based games on popular websites. Servings of fruit, vegetable, and water; minutes of moderate to vigorous physical activity. At each point of assessment: 3 nonconsecutive days of 24-hour dietary recalls; 5 consecutive days of physical activity using accelerometers; and assessment of height, weight, waist circumference, and triceps skinfold. A repeated measures ANCOVA was conducted (analyzed in 2009-2010). Children playing these video games increased fruit and vegetable consumption by about 0.67 servings per day (pchange. Copyright © 2011 American Journal of Preventive Medicine. All rights reserved.

  4. Sustainability and Science Learning: Perceptions from 8th Grade Students Involved with a Role Playing Activity

    Science.gov (United States)

    Freire, Sofia; Baptista, Mónica; Freire, Ana

    2016-01-01

    Raising awareness about sustainability is an urgent need and as such education for sustainability has gained relevancy for the last decades. It is acknowledged that science education can work as an important context for educating for sustainability. The goal of the present paper is to describe a role-playing activity about the construction of a…

  5. Developing Adolescents' Resistance to Sexual Coercion through Role-Playing Activities in a Virtual World

    Science.gov (United States)

    McGinn, Marion; Arnedillo-Sánchez, Inmaculada

    2015-01-01

    This paper explores the use of a three dimensional virtual world (3-DVW) to delivery assertiveness training to young adolescents. The case study aims to understand how a sense of presence in VWs facilitates and affect the performance of students role-playing activities to enhance their ability to resist sexual coercion. The results indicate that a…

  6. Association of Active Play-Related Parenting Behaviors, Orientations, and Practices with Preschool Sedentary Behavior

    Science.gov (United States)

    Loprinzi, Paul D.; Cardinal, Bradley J.; Kane, Christy; Lee, Hyo; Beets, Michael W.

    2014-01-01

    Background: Parents' behaviors, practices, beliefs, and attitudes greatly influence children's active play behavior; however, little research has examined these parental influences on preschool children's sedentary behavior (SB). Purpose: The purpose of this study was to examine the association between parental influences on preschool SB. Methods:…

  7. Thermodynamic secrets of multidrug resistance: A new take on transport mechanisms of secondary active antiporters.

    Science.gov (United States)

    Zhang, Xuejun C; Liu, Min; Lu, Guangyuan; Heng, Jie

    2018-03-01

    Multidrug resistance (MDR) presents a growing challenge to global public health. Drug extrusion transporters play a critical part in MDR; thus, their mechanisms of substrate recognition are being studied in great detail. In this work, we review common structural features of key transporters involved in MDR. Based on our membrane potential-driving hypothesis, we propose a general energy-coupling mechanism for secondary-active antiporters. This putative mechanism provides a common framework for understanding poly-specificity of most-if not all-MDR transporters. © 2017 The Protein Society.

  8. An intergenerational study of perceptions of changes in active free play among families from rural areas of Western Canada.

    Science.gov (United States)

    Holt, Nicholas L; Neely, Kacey C; Spence, John C; Carson, Valerie; Pynn, Shannon R; Boyd, Kassi A; Ingstrup, Meghan; Robinson, Zac

    2016-08-19

    Children's engagement in active free play has declined across recent generations. Therefore, the purpose of this study was to examine perceptions of intergenerational changes in active free play among families from rural areas. We addressed two research questions: (1) How has active free play changed across three generations? (2) What suggestions do participants have for reviving active free play? Data were collected via 49 individual interviews with members of 16 families (15 grandparents, 16 parents, and 18 children) residing in rural areas/small towns in the Province of Alberta (Canada). Interview recordings were transcribed verbatim and subjected to thematic analysis guided by an ecological framework of active free play. Factors that depicted the changing nature of active free play were coded in the themes of less imagination/more technology, safety concerns, surveillance, other children to play with, purposeful physical activity, play spaces/organized activities, and the good parenting ideal. Suggestions for reviving active free play were coded in the themes of enhance facilities to keep kids entertained, provide more opportunities for supervised play, create more community events, and decrease use of technology. These results reinforce the need to consider multiple levels of social ecology in the study of active free play, and highlight the importance of community-based initiatives to revive active free play in ways that are consistent with contemporary notions of good parenting.

  9. An intergenerational study of perceptions of changes in active free play among families from rural areas of Western Canada

    Directory of Open Access Journals (Sweden)

    Nicholas L. Holt

    2016-08-01

    Full Text Available Abstract Background Children’s engagement in active free play has declined across recent generations. Therefore, the purpose of this study was to examine perceptions of intergenerational changes in active free play among families from rural areas. We addressed two research questions: (1 How has active free play changed across three generations? (2 What suggestions do participants have for reviving active free play? Methods Data were collected via 49 individual interviews with members of 16 families (15 grandparents, 16 parents, and 18 children residing in rural areas/small towns in the Province of Alberta (Canada. Interview recordings were transcribed verbatim and subjected to thematic analysis guided by an ecological framework of active free play. Results Factors that depicted the changing nature of active free play were coded in the themes of less imagination/more technology, safety concerns, surveillance, other children to play with, purposeful physical activity, play spaces/organized activities, and the good parenting ideal. Suggestions for reviving active free play were coded in the themes of enhance facilities to keep kids entertained, provide more opportunities for supervised play, create more community events, and decrease use of technology. Conclusions These results reinforce the need to consider multiple levels of social ecology in the study of active free play, and highlight the importance of community-based initiatives to revive active free play in ways that are consistent with contemporary notions of good parenting.

  10. Secreted glycoprotein BmApoD1 plays a critical role in anti-oxidation and anti-apoptosis in Bombyx mori.

    Science.gov (United States)

    Zhou, Yanyan; Wang, Li; Li, Rongqiao; Liu, Minmin; Li, Xiaotong; Su, Hang; Xu, Yusong; Wang, Huabing

    2018-01-01

    Recent studies highlighted that apolipoprotein D (ApoD) and its homologs exert neuroprotective and antioxidant functions in mammals and Drosophila. Unlike mammals and Drosophila, lepidopteran insects possess three distinct ApoD homologs. However, few information on their functions in lepidopteran insects are available. In this study, we investigated the protective potential of a novel ApoD homolog, BmApoD1, in Bombyx mori. Quantitative PCR analyses demonstrated that BmApoD1 is extensively expressed at low levels during the larval stage but abundantly expressed in the testis during the pupal and adult stages. Tryptophan fluorescence titration demonstrated that recombinant BmApoD1 protein can bind retinoic acid and ergosterol. In addition, we provided evidence that N-linked glycans of BmApoD1 are essential to BmApoD1 secretion, and three residues, namely, Asp69, Asp104, and Asp196, are the glycosylation sites of BmApoD1. Furthermore, we showed that BmApoD1 is significantly up-regulated in the larvae after oxidant or starvation treatment. The recombinant BmApoD1 protein can protect cells from oxidative stress induced by H 2 O 2 and reduce actinomycin D-induced cell apoptosis. These observations, together with the transcriptional up-regulation of BmApoD1 in several tissues upon oxidative insult, identify BmApoD1 as a potent antioxidant. Our results demonstrate that BmApoD1 is critical for metabolic adaptation of B. mori to environmental challenges. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Placental lactogen secretion during prolonged-pregnancy in the rat: the ovary plays a pivotal role in the control of placental function.

    Science.gov (United States)

    Shiota, K; Furuyama, N; Takahashi, M

    1991-10-01

    The serum of rats at mid-pregnancy contains at least 2 distinct placental lactogen (PL)-like substances tentatively termed placental lactogen-alpha (PL-alpha) and placental lactogen-beta (PL-beta) (Endocrinol Japon 38: 533-540, 1991). We have investigated the secretory patterns of three placental lactogens (PL-alpha, PL-beta and placental lactogen-II) during normal pregnancy and in two prolonged-pregnancy models. Pregnancy was prolonged by the introduction of new corpora lutea by inducing ovulation on day 15 of pregnancy by successive treatments with PMSG (30 IU/rat, sc on day 12) and hCG (10 IU/rat, iv on day 14), and in the second model by progesterone implants on day 15 of pregnancy. During normal pregnancy, each of the 3 PLs exhibited only one secretory peak in the serum; PL-alpha and PL-beta on day 12 and placental lactogen II (PL-II) on day 20. Interestingly, in the rats with new sets of corpora lutea, serum PL-alpha and PL-beta levels began to increase again on day 18 and showed peaks on day 20 for PL-alpha and on day 22 for PL-beta. In this model, the initiation of PL-II secretion was not affected, but high levels were maintained until day 26, when parturition occurred. In rats receiving either PMSG or hCG, the secretory patterns of the PLs were similar to as those during normal pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Acidity enhances the effectiveness of active chemical defensive secretions of sea hares, Aplysia californica, against spiny lobsters, Panulirus interruptus.

    Science.gov (United States)

    Shabani, Shkelzen; Yaldiz, Seymanur; Vu, Luan; Derby, Charles D

    2007-12-01

    Sea hares such as Aplysia californica, gastropod molluscs lacking a protective shell, can release a purple cloud of chemicals when vigorously attacked by predators. This active chemical defense is composed of two glandular secretions, ink and opaline, both of which contain an array of compounds. This secretion defends sea hares against predators such as California spiny lobsters Panulirus interruptus via multiple mechanisms, one of which is phagomimicry, in which secretions containing feeding chemicals attract and distract predators toward the secretion and away from the sea hare. We show here that ink and opaline are highly acidic, both having a pH of approximately 5. We examined if the acidity of ink and opaline affects their phagomimetic properties. We tested behavioral and electrophysiological responses of chemoreceptor neurons in the olfactory and gustatory organs of P. interruptus, to ink and opaline of A. californica within their natural range of pH values, from approximately 5 to 8. Both behavioral and electrophysiological responses to ink and opaline were enhanced at low pH, and low pH alone accounted for most of this effect. Our data suggest that acidity enhances the phagomimetic chemical defense of sea hares.

  13. Interleukin-33-Activated Islet-Resident Innate Lymphoid Cells Promote Insulin Secretion through Myeloid Cell Retinoic Acid Production.

    Science.gov (United States)

    Dalmas, Elise; Lehmann, Frank M; Dror, Erez; Wueest, Stephan; Thienel, Constanze; Borsigova, Marcela; Stawiski, Marc; Traunecker, Emmanuel; Lucchini, Fabrizio C; Dapito, Dianne H; Kallert, Sandra M; Guigas, Bruno; Pattou, Francois; Kerr-Conte, Julie; Maechler, Pierre; Girard, Jean-Philippe; Konrad, Daniel; Wolfrum, Christian; Böni-Schnetzler, Marianne; Finke, Daniela; Donath, Marc Y

    2017-11-21

    Pancreatic-islet inflammation contributes to the failure of β cell insulin secretion during obesity and type 2 diabetes. However, little is known about the nature and function of resident immune cells in this context or in homeostasis. Here we show that interleukin (IL)-33 was produced by islet mesenchymal cells and enhanced by a diabetes milieu (glucose, IL-1β, and palmitate). IL-33 promoted β cell function through islet-resident group 2 innate lymphoid cells (ILC2s) that elicited retinoic acid (RA)-producing capacities in macrophages and dendritic cells via the secretion of IL-13 and colony-stimulating factor 2. In turn, local RA signaled to the β cells to increase insulin secretion. This IL-33-ILC2 axis was activated after acute β cell stress but was defective during chronic obesity. Accordingly, IL-33 injections rescued islet function in obese mice. Our findings provide evidence that an immunometabolic crosstalk between islet-derived IL-33, ILC2s, and myeloid cells fosters insulin secretion. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Reducing the activity and secretion of microbial antioxidants enhances the immunogenicity of BCG.

    Directory of Open Access Journals (Sweden)

    Shanmugalakshmi Sadagopal

    Full Text Available In early clinical studies, the live tuberculosis vaccine Mycobacterium bovis BCG exhibited 80% protective efficacy against pulmonary tuberculosis (TB. Although BCG still exhibits reliable protection against TB meningitis and miliary TB in early childhood it has become less reliable in protecting against pulmonary TB. During decades of in vitro cultivation BCG not only lost some genes due to deletions of regions of the chromosome but also underwent gene duplication and other mutations resulting in increased antioxidant production.To determine whether microbial antioxidants influence vaccine immunogenicity, we eliminated duplicated alleles encoding the oxidative stress sigma factor SigH in BCG Tice and reduced the activity and secretion of iron co-factored superoxide dismutase. We then used assays of gene expression and flow cytometry with intracellular cytokine staining to compare BCG-specific immune responses in mice after vaccination with BCG Tice or the modified BCG vaccine. Compared to BCG, the modified vaccine induced greater IL-12p40, RANTES, and IL-21 mRNA in the spleens of mice at three days post-immunization, more cytokine-producing CD8+ lymphocytes at the peak of the primary immune response, and more IL-2-producing CD4+ lymphocytes during the memory phase. The modified vaccine also induced stronger secondary CD4+ lymphocyte responses and greater clearance of challenge bacilli.We conclude that antioxidants produced by BCG suppress host immune responses. These findings challenge the hypothesis that the failure of extensively cultivated BCG vaccines to prevent pulmonary tuberculosis is due to over-attenuation and suggest instead a new model in which BCG evolved to produce more immunity-suppressing antioxidants. By targeting these antioxidants it may be possible to restore BCG's ability to protect against pulmonary TB.

  15. Requirement for noncognate interaction with T cells for the activation of B cell immunoglobulin secretion by IL-2

    DEFF Research Database (Denmark)

    Owens, T

    1991-01-01

    23.1+ TH1 clone E9.D4 in F23.1 (anti-T cell receptor V-beta 8)-coated microwells. This induced polyclonal B cell activation to enter cell cycle (thymidine incorporation) at 2 days and to secrete immunoglobulin at 5 days. An anti-IL-2 mAb (S4B6) inhibited antibody production completely. Anti-IL-2 did......The mechanism whereby noncognate contact with activated IL-2-producing Type 1 helper T cells (TH1) induces B cell activation was examined. Small resting B cells from C57B1/6 mice were cultured, in the absence of any ligand for surface Ig, with irradiated cells of the hapten-specific, CBA-derived, F...... not inhibit either LPS-induced B cell responses, or T cell activation (measured as IL-3 secretion). Anti-IL-2 receptor (anti-Tac) mAbs also inhibited T-dependent B cell responses, without affecting LPS responses. An anti-IFN-gamma mAb partially inhibited Ig secretion, without affecting entry into cycle. LPS...

  16. Spa47 is an oligomerization-activated type three secretion system (T3SS) ATPase from Shigella flexneri.

    Science.gov (United States)

    Burgess, Jamie L; Jones, Heather B; Kumar, Prashant; Toth, Ronald T; Middaugh, C Russell; Antony, Edwin; Dickenson, Nicholas E

    2016-05-01

    Gram-negative pathogens often use conserved type three secretion systems (T3SS) for virulence. The Shigella type three secretion apparatus (T3SA) penetrates the host cell membrane and provides a unidirectional conduit for injection of effectors into host cells. The protein Spa47 localizes to the base of the apparatus and is speculated to be an ATPase that provides the energy for T3SA formation and secretion. Here, we developed an expression and purification protocol, producing active Spa47 and providing the first direct evidence that Spa47 is a bona fide ATPase. Additionally, size exclusion chromatography and analytical ultracentrifugation identified multiple oligomeric species of Spa47 with the largest greater than 8 fold more active for ATP hydrolysis than the monomer. An ATPase inactive Spa47 point mutant was then engineered by targeting a conserved Lysine within the predicted Walker A motif of Spa47. Interestingly, the mutant maintained a similar oligomerization pattern as active Spa47, but was unable to restore invasion phenotype when used to complement a spa47 null S. flexneri strain. Together, these results identify Spa47 as a Shigella T3SS ATPase and suggest that its activity is linked to oligomerization, perhaps as a regulatory mechanism as seen in some related pathogens. Additionally, Spa47 catalyzed ATP hydrolysis appears to be essential for host cell invasion, providing a strong platform for additional studies dissecting its role in virulence and providing an attractive target for anti-infective agents. © 2016 The Protein Society.

  17. Gender-specific activity demands experienced during semiprofessional basketball game play.

    Science.gov (United States)

    Scanlan, Aaron T; Dascombe, Ben J; Kidcaff, Andrew P; Peucker, Jessica L; Dalbo, Vincent J

    2015-07-01

    To compare game activity demands between female and male semiprofessional basketball players. Female (n=12) and male (n=12) semiprofessional basketball players were monitored across 3 competitive games. Time-motion-analysis procedures quantified player activity into predefined movement categories across backcourt (BC) and frontcourt (FC) positions. Activity frequencies, durations, and distances were calculated relative to live playing time (min). Work:rest ratios were also calculated using the video data. Game activity was compared between genders for each playing position and all players. Female players performed at greater running work-rates than male players (45.7±1.4 vs. 42.1±1.7 m/min, P=.05), while male players performed more dribbling than female players (2.5±0.3 vs. 3.0±0.2 s/min; 8.4±0.3 vs. 9.7±0.7 m/min, P=.05). Positional analyses revealed that female BC players performed more low-intensity shuffling (P=.04) and jumping (P=.05), as well as longer (P=.04) jogging durations, than male BC players. Female FC players executed more upper-body activity (P=.03) and larger work:rest ratios (Pbasketball. Furthermore, position-specific variations between female and male basketball players should be considered. These data may prove useful in the development of gender-specific conditioning plans relative to playing position in basketball.

  18. Play, Playfulness, Creativity and Innovation

    Directory of Open Access Journals (Sweden)

    Patrick Bateson

    2014-05-01

    Full Text Available Play, as defined by biologists and psychologists, is probably heterogeneous. On the other hand, playfulness may be a unitary motivational state. Playful play as opposed to activities that merge into aggression is characterized by positive mood, intrinsic motivation, occurring in a protected context and easily disrupted by stress. Playful play is a good measure of positive welfare. It can occupy a substantial part of the waking-life of a young mammal or bird. Numerous functions for play have been proposed and they are by no means mutually exclusive, but some evidence indicates that those individual animals that play most are most likely to survive and reproduce. The link of playful play to creativity and hence to innovation in humans is strong. Considerable evidence suggests that coming up with new ideas requires a different mindset from usefully implementing a new idea.

  19. Developing pharmacy student communication skills through role-playing and active learning.

    Science.gov (United States)

    Luiz Adrian, Julie Ann; Zeszotarski, Paula; Ma, Carolyn

    2015-04-25

    To evaluate the impact on pharmacy students of a communication course, which used role-playing to develop active-learning skills. Students role-playing pharmacists in patient care scenarios were critiqued by students and pharmacist faculty members. Grading was performed using the rubric inspired by Bruce Berger's Communication Skills for Pharmacists. Written skills were evaluated using student written critique questionnaires. Students completed precourse and postcourse self-assessment surveys. Preceptor evaluations were analyzed for course impact. Students demonstrated improvement in oral skills based on role-play scores (45.87/50) after practice sessions. The average score based on the student questionnaire was 9.31/10. Gain was demonstrated in all defined course objectives. Impact on introductory pharmacy practice experience (IPPE) communication objectives was insignificant. Student evaluations for course and teaching strategy reflected a high average. Study results demonstrated improvement in oral and written communication skills that may help improve interprofessional teamwork between pharmacists and other health care providers.

  20. Evidence for the presence of proteolytically active secreted aspartic proteinase 1 of Candida parapsilosis in the cell wall

    Czech Academy of Sciences Publication Activity Database

    Vinterová, Zuzana; Šanda, Miloslav; Dostál, Jiří; Hrušková-Heidingsfeldová, Olga; Pichová, Iva

    2011-01-01

    Roč. 20, č. 12 (2011), s. 2004-2012 ISSN 0961-8368 R&D Projects: GA MŠk(CZ) LC531; GA ČR GA310/09/1945 Institutional research plan: CEZ:AV0Z40550506 Keywords : Candida parapsilosis * secreted aspartic proteinases * Sapp1p * cell wall * biotin * proteolytic activity Subject RIV: CE - Biochemistry Impact factor: 2.798, year: 2011

  1. Sport activities differentiating match-play improvement in elite youth footballers - a 2-year longitudinal study.

    Science.gov (United States)

    Güllich, Arne; Kovar, Peter; Zart, Sebastian; Reimann, Ansgar

    2017-02-01

    This study examined contributions of different types of sport activities to the development of elite youth soccer performance. Match-play performance of 44 German male players was assessed by expert coaches twice, 24 months apart (age 11.1-13.1 years), based on videotaped 5v5 matches. Player pairs were matched by identical age and initial performance at t 1 . Each player was assigned to a group of either "Strong" or "Weak Responders" based on a higher or lower subsequent performance improvement at t 2 within each pair (mean Δperformance 29% vs. 7%). A questionnaire recorded current and earlier amounts of organised practice/training and non-organised sporting play, in soccer and other sports, respectively. Group comparison revealed that "Strong Responders" accumulated more non-organised soccer play and organised practice/training in other sports, but not more organised soccer practice/training. Subsequent multivariate analyses (multiple linear regression analyses (MLR)) highlighted that higher resultant match-play performance at t 2 was accounted for R 2 adj  = 0.65 by performance at t 1 , together with more non-organised soccer play and organised engagement in other sports, respectively, and greater current, but less earlier volume of organised soccer. The findings suggest that variable early sporting experience facilitates subsequent soccer performance development in German elite youth footballers.

  2. Exercise intensity levels in children with cerebral palsy while playing with an active video game console.

    Science.gov (United States)

    Robert, Maxime; Ballaz, Laurent; Hart, Raphael; Lemay, Martin

    2013-08-01

    Children with cerebral palsy (CP) are prone to secondary complications related to physical inactivity and poor cardiorespiratory capacity. This problem could be greatly attenuated through the use of video games that incorporate physical activity for 2 reasons: Video games already represent an important component of leisure time in younger people, and such games can lead to a high level of exercise intensity in people who are healthy. The study objective was to evaluate exercise intensity in children with spastic diplegic CP and children who were typically developing while playing with an active video game console. This was a cross-sectional study. Ten children (7-12 years old) with spastic diplegic CP (Gross Motor Function Classification System level I or II) and 10 children who were age matched and typically developing were evaluated in a movement analysis laboratory. Four games were played with the active video game console (jogging, bicycling, snowboarding, and skiing) for 40 minutes. Heart rate was recorded during the entire playing period with a heart rate belt monitor. Exercise intensity was defined as the percentage of heart rate reserve (HRR). In addition, lower extremity motion analysis was carried out during the final minute of the playing period for the jogging and bicycling games. No difference between groups was observed for any variables. A main effect of games was observed for the amount of time spent at an intensity greater than 40% of HRR. Specifically, more than 50% of the playing time for the jogging game and more than 30% of the playing time for the bicycling game were spent at an intensity greater than 40% of HRR. In addition, the jogging game produced a larger range of motion than the bicycling game. A limitation of this study was the relatively small and heterogeneous sample. For all 4 games, similar exercise intensity levels were observed for children who were typically developing and children with CP, suggesting that children with CP could

  3. Playing Active Video Games may not develop movement skills: An intervention trial

    Science.gov (United States)

    Barnett, Lisa M.; Ridgers, Nicola D.; Reynolds, John; Hanna, Lisa; Salmon, Jo

    2015-01-01

    Background: To investigate the impact of playing sports Active Video Games on children's actual and perceived object control skills. Methods: Intervention children played Active Video Games for 6 weeks (1 h/week) in 2012. The Test of Gross Motor Development-2 assessed object control skill. The Pictorial Scale of Perceived Movement Skill Competence assessed perceived object control skill. Repeated measurements of object control and perceived object control were analysed for the whole sample, using linear mixed models, which included fixed effects for group (intervention or control) and time (pre and post) and their interaction. The first model adjusted for sex only and the second model also adjusted for age, and prior ball sports experience (yes/no). Seven mixed-gender focus discussions were conducted with intervention children after programme completion. Results: Ninety-five Australian children (55% girls; 43% intervention group) aged 4 to 8 years (M 6.2, SD 0.95) participated. Object control skill improved over time (p = 0.006) but there was no significant difference (p = 0.913) between groups in improvement (predicted means: control 31.80 to 33.53, SED = 0.748; intervention 30.33 to 31.83, SED = 0.835). A similar result held for the second model. Similarly the intervention did not change perceived object control in Model 1 (predicted means: control: 19.08 to 18.68, SED = 0.362; intervention 18.67 to 18.88, SED = 0.406) or Model 2. Children found the intervention enjoyable, but most did not perceive direct equivalence between Active Video Games and ‘real life’ activities. Conclusions: Whilst Active Video Game play may help introduce children to sport, this amount of time playing is unlikely to build skill. PMID:26844136

  4. Playing Active Video Games may not develop movement skills: An intervention trial

    Directory of Open Access Journals (Sweden)

    Lisa M. Barnett

    2015-01-01

    Full Text Available Background: To investigate the impact of playing sports Active Video Games on children's actual and perceived object control skills. Methods: Intervention children played Active Video Games for 6 weeks (1 h/week in 2012. The Test of Gross Motor Development-2 assessed object control skill. The Pictorial Scale of Perceived Movement Skill Competence assessed perceived object control skill. Repeated measurements of object control and perceived object control were analysed for the whole sample, using linear mixed models, which included fixed effects for group (intervention or control and time (pre and post and their interaction. The first model adjusted for sex only and the second model also adjusted for age, and prior ball sports experience (yes/no. Seven mixed-gender focus discussions were conducted with intervention children after programme completion. Results: Ninety-five Australian children (55% girls; 43% intervention group aged 4 to 8 years (M 6.2, SD 0.95 participated. Object control skill improved over time (p = 0.006 but there was no significant difference (p = 0.913 between groups in improvement (predicted means: control 31.80 to 33.53, SED = 0.748; intervention 30.33 to 31.83, SED = 0.835. A similar result held for the second model. Similarly the intervention did not change perceived object control in Model 1 (predicted means: control: 19.08 to 18.68, SED = 0.362; intervention 18.67 to 18.88, SED = 0.406 or Model 2. Children found the intervention enjoyable, but most did not perceive direct equivalence between Active Video Games and ‘real life’ activities. Conclusions: Whilst Active Video Game play may help introduce children to sport, this amount of time playing is unlikely to build skill.

  5. Playing Active Video Games may not develop movement skills: An intervention trial.

    Science.gov (United States)

    Barnett, Lisa M; Ridgers, Nicola D; Reynolds, John; Hanna, Lisa; Salmon, Jo

    2015-01-01

    To investigate the impact of playing sports Active Video Games on children's actual and perceived object control skills. Intervention children played Active Video Games for 6 weeks (1 h/week) in 2012. The Test of Gross Motor Development-2 assessed object control skill. The Pictorial Scale of Perceived Movement Skill Competence assessed perceived object control skill. Repeated measurements of object control and perceived object control were analysed for the whole sample, using linear mixed models, which included fixed effects for group (intervention or control) and time (pre and post) and their interaction. The first model adjusted for sex only and the second model also adjusted for age, and prior ball sports experience (yes/no). Seven mixed-gender focus discussions were conducted with intervention children after programme completion. Ninety-five Australian children (55% girls; 43% intervention group) aged 4 to 8 years (M 6.2, SD 0.95) participated. Object control skill improved over time (p = 0.006) but there was no significant difference (p = 0.913) between groups in improvement (predicted means: control 31.80 to 33.53, SED = 0.748; intervention 30.33 to 31.83, SED = 0.835). A similar result held for the second model. Similarly the intervention did not change perceived object control in Model 1 (predicted means: control: 19.08 to 18.68, SED = 0.362; intervention 18.67 to 18.88, SED = 0.406) or Model 2. Children found the intervention enjoyable, but most did not perceive direct equivalence between Active Video Games and 'real life' activities. Whilst Active Video Game play may help introduce children to sport, this amount of time playing is unlikely to build skill.

  6. Dental Calculus Stimulates Interleukin-1β Secretion by Activating NLRP3 Inflammasome in Human and Mouse Phagocytes.

    Directory of Open Access Journals (Sweden)

    Jorge Luis Montenegro Raudales

    Full Text Available Dental calculus is a mineralized deposit associated with periodontitis. The bacterial components contained in dental calculus can be recognized by host immune sensors, such as Toll-like receptors (TLRs, and induce transcription of proinflammatory cytokines, such as IL-1β. Studies have shown that cellular uptake of crystalline particles may trigger NLRP3 inflammasome activation, leading to the cleavage of the IL-1β precursor to its mature form. Phagocytosis of dental calculus in the periodontal pocket may therefore lead to the secretion of IL-1β, promoting inflammatory responses in periodontal tissues. However, the capacity of dental calculus to induce IL-1β secretion in human phagocytes has not been explored. To study this, we stimulated human polymorphonuclear leukocytes (PMNs and peripheral blood mononuclear cells (PBMCs with dental calculus collected from periodontitis patients, and measured IL-1β secretion by ELISA. We found that calculus induced IL-1β secretion in both human PMNs and PBMCs. Calculus also induced IL-1β in macrophages from wild-type mice, but not in macrophages from NLRP3- and ASC-deficient mice, indicating the involvement of NLRP3 and ASC. IL-1β induction was inhibited by polymyxin B, suggesting that LPS is one of the components of calculus that induces pro-IL-1β transcription. To analyze the effect of the inorganic structure, we baked calculus at 250°C for 1 h. This baked calculus failed to induce pro-IL-1β transcription. However, it did induce IL-1β secretion in lipid A-primed cells, indicating that the crystalline structure of calculus induces inflammasome activation. Furthermore, hydroxyapatite crystals, a component of dental calculus, induced IL-1β in mouse macrophages, and baked calculus induced IL-1β in lipid A-primed human PMNs and PBMCs. These results indicate that dental calculus stimulates IL-1β secretion via NLRP3 inflammasome in human and mouse phagocytes, and that the crystalline structure has a

  7. Dental Calculus Stimulates Interleukin-1β Secretion by Activating NLRP3 Inflammasome in Human and Mouse Phagocytes.

    Science.gov (United States)

    Montenegro Raudales, Jorge Luis; Yoshimura, Atsutoshi; Sm, Ziauddin; Kaneko, Takashi; Ozaki, Yukio; Ukai, Takashi; Miyazaki, Toshihiro; Latz, Eicke; Hara, Yoshitaka

    2016-01-01

    Dental calculus is a mineralized deposit associated with periodontitis. The bacterial components contained in dental calculus can be recognized by host immune sensors, such as Toll-like receptors (TLRs), and induce transcription of proinflammatory cytokines, such as IL-1β. Studies have shown that cellular uptake of crystalline particles may trigger NLRP3 inflammasome activation, leading to the cleavage of the IL-1β precursor to its mature form. Phagocytosis of dental calculus in the periodontal pocket may therefore lead to the secretion of IL-1β, promoting inflammatory responses in periodontal tissues. However, the capacity of dental calculus to induce IL-1β secretion in human phagocytes has not been explored. To study this, we stimulated human polymorphonuclear leukocytes (PMNs) and peripheral blood mononuclear cells (PBMCs) with dental calculus collected from periodontitis patients, and measured IL-1β secretion by ELISA. We found that calculus induced IL-1β secretion in both human PMNs and PBMCs. Calculus also induced IL-1β in macrophages from wild-type mice, but not in macrophages from NLRP3- and ASC-deficient mice, indicating the involvement of NLRP3 and ASC. IL-1β induction was inhibited by polymyxin B, suggesting that LPS is one of the components of calculus that induces pro-IL-1β transcription. To analyze the effect of the inorganic structure, we baked calculus at 250°C for 1 h. This baked calculus failed to induce pro-IL-1β transcription. However, it did induce IL-1β secretion in lipid A-primed cells, indicating that the crystalline structure of calculus induces inflammasome activation. Furthermore, hydroxyapatite crystals, a component of dental calculus, induced IL-1β in mouse macrophages, and baked calculus induced IL-1β in lipid A-primed human PMNs and PBMCs. These results indicate that dental calculus stimulates IL-1β secretion via NLRP3 inflammasome in human and mouse phagocytes, and that the crystalline structure has a partial role in

  8. Dental Calculus Stimulates Interleukin-1β Secretion by Activating NLRP3 Inflammasome in Human and Mouse Phagocytes

    Science.gov (United States)

    Montenegro Raudales, Jorge Luis; Yoshimura, Atsutoshi; SM, Ziauddin; Kaneko, Takashi; Ozaki, Yukio; Ukai, Takashi; Miyazaki, Toshihiro; Latz, Eicke; Hara, Yoshitaka

    2016-01-01

    Dental calculus is a mineralized deposit associated with periodontitis. The bacterial components contained in dental calculus can be recognized by host immune sensors, such as Toll-like receptors (TLRs), and induce transcription of proinflammatory cytokines, such as IL-1β. Studies have shown that cellular uptake of crystalline particles may trigger NLRP3 inflammasome activation, leading to the cleavage of the IL-1β precursor to its mature form. Phagocytosis of dental calculus in the periodontal pocket may therefore lead to the secretion of IL-1β, promoting inflammatory responses in periodontal tissues. However, the capacity of dental calculus to induce IL-1β secretion in human phagocytes has not been explored. To study this, we stimulated human polymorphonuclear leukocytes (PMNs) and peripheral blood mononuclear cells (PBMCs) with dental calculus collected from periodontitis patients, and measured IL-1β secretion by ELISA. We found that calculus induced IL-1β secretion in both human PMNs and PBMCs. Calculus also induced IL-1β in macrophages from wild-type mice, but not in macrophages from NLRP3- and ASC-deficient mice, indicating the involvement of NLRP3 and ASC. IL-1β induction was inhibited by polymyxin B, suggesting that LPS is one of the components of calculus that induces pro-IL-1β transcription. To analyze the effect of the inorganic structure, we baked calculus at 250°C for 1 h. This baked calculus failed to induce pro-IL-1β transcription. However, it did induce IL-1β secretion in lipid A-primed cells, indicating that the crystalline structure of calculus induces inflammasome activation. Furthermore, hydroxyapatite crystals, a component of dental calculus, induced IL-1β in mouse macrophages, and baked calculus induced IL-1β in lipid A-primed human PMNs and PBMCs. These results indicate that dental calculus stimulates IL-1β secretion via NLRP3 inflammasome in human and mouse phagocytes, and that the crystalline structure has a partial role in

  9. "Fair Play": A Videogame Designed to Address Implicit Race Bias Through Active Perspective Taking.

    Science.gov (United States)

    Gutierrez, Belinda; Kaatz, Anna; Chu, Sarah; Ramirez, Dennis; Samson-Samuel, Clem; Carnes, Molly

    2014-12-01

    Having diverse faculty in academic health centers will help diversify the healthcare workforce and reduce health disparities. Implicit race bias is one factor that contributes to the underrepresentation of Black faculty. We designed the videogame "Fair Play" in which players assume the role of a Black graduate student named Jamal Davis. As Jamal, players experience subtle race bias while completing "quests" to obtain a science degree. We hypothesized that participants randomly assigned to play the game would have greater empathy for Jamal and lower implicit race bias than participants randomized to read narrative text describing Jamal's experience. University of Wisconsin-Madison graduate students were recruited via e-mail and randomly assigned to play "Fair Play" or read narrative text through an online link. Upon completion, participants took an Implicit Association Test to measure implicit bias and answered survey questions assessing empathy toward Jamal and awareness of bias. As hypothesized, gameplayers showed the least implicit bias but only when they also showed high empathy for Jamal (P=0.013). Gameplayers did not show greater empathy than text readers, and women in the text condition reported the greatest empathy for Jamal (P=0.008). However, high empathy only predicted lower levels of implicit bias among those who actively took Jamal's perspective through gameplay (P=0.014). A videogame in which players experience subtle race bias as a Black graduate student has the potential to reduce implicit bias, possibly because of a game's ability to foster empathy through active perspective taking.

  10. Pituitary adenylate cyclase-activating polypeptide promotes eccrine gland sweat secretion

    DEFF Research Database (Denmark)

    Sasaki, S; Watanabe, J; Ohtaki, H

    2017-01-01

    BACKGROUND: Sweat secretion is the major function of eccrine sweat glands; when this process is disturbed (paridrosis), serious skin problems can arise. To elucidate the causes of paridrosis, an improved understanding of the regulation, mechanisms and factors underlying sweat production is requir...

  11. METs in adults while playing active video games: a metabolic chamber study.

    Science.gov (United States)

    Miyachi, Motohiko; Yamamoto, Kenta; Ohkawara, Kazunori; Tanaka, Shigeho

    2010-06-01

    Active video game systems controlled through arm gestures and motions (Nintendo Wii Sports) and video games controlled through force plate (Wii Fit Plus) are becoming increasingly popular. This study was performed to determine the energy expenditure (EE) during Wii Fit Plus and Wii Sports game activities. Twelve adult men and women performed all the activities of Wii Sports (five activities: golf, bowling, tennis, baseball, and boxing) and Wii Fit Plus (63 activities classified as yoga, resistance, balance, and aerobic exercises). Each activity was continued for at least 8 min to obtain a steady-state EE. Because EE was assessed in an open-circuit indirect metabolic chamber consisting of an airtight room (20,000 or 15,000 L), subjects were freed of apparatus to collect expired gas while playing the games. MET value was calculated from resting EE and steady-state EE during activity. The mean MET values of all 68 activities were distributed over a wide range from 1.3 METs (Lotus Focus) to 5.6 METs (single-arm stand). The mean MET values in yoga, balance, resistance, and aerobic exercise of Wii Fit Plus and Wii Sports were 2.1, 2.0, 3.2, 3.4, and 3.0 METs, respectively. Forty-six activities (67%) were classified as light intensity (6.0 METs). Time spent playing one-third of the activities supplied by motion- and gesture-controlled video games can count toward the daily amount of exercise required according to the guidelines provided by the American College of Sports Medicine and the American Heart Association, which focus on 30 min of moderate-intensity daily physical activity 5 d x wk(-1).

  12. Active and non-active video gaming among Dutch adolescents: Who plays and how much?

    NARCIS (Netherlands)

    Simons, M.; Vet, E. de; Brug, J.; Seidell, J.; Chinapaw, M.J.M.

    2014-01-01

    Objectives: The aim of study was to determine prevalence and identify demographic correlates of active and non-active gaming among adolescents. Design: Cross-sectional. Methods: A survey, assessing game behavior and correlates, was conducted among adolescents (12-16 years, n= 373), recruited via

  13. Active and non-active video gaming among Dutch adolescents: Who plays and how much?

    NARCIS (Netherlands)

    simons, M.; de Vet, E.W.M.L.; Brug, J.; Seidell, J.C.; Chin A Paw, M.J.M.

    2014-01-01

    OBJECTIVES: The aim of study was to determine prevalence and identify demographic correlates of active and non-active gaming among adolescents. DESIGN: Cross-sectional. METHODS: A survey, assessing game behavior and correlates, was conducted among adolescents (12-16 years, n = 373), recruited via

  14. Active and non-active video gaming among Dutch adolescents : who plays and how much?

    NARCIS (Netherlands)

    Simons, Monique|info:eu-repo/dai/nl/323255639; de Vet, Emely; Brug, Johannes; Seidell, Jaap; Chinapaw, Mai J M

    2014-01-01

    OBJECTIVES: The aim of study was to determine prevalence and identify demographic correlates of active and non-active gaming among adolescents. DESIGN: Cross-sectional. METHODS: A survey, assessing game behavior and correlates, was conducted among adolescents (12-16 years, n = 373), recruited via

  15. Mathematical Modeling of Interacting Glucose-Sensing Mechanisms and Electrical Activity Underlying Glucagon-Like Peptide 1 Secretion.

    Directory of Open Access Journals (Sweden)

    Michela Riz

    2015-12-01

    Full Text Available Intestinal L-cells sense glucose and other nutrients, and in response release glucagon-like peptide 1 (GLP-1, peptide YY and other hormones with anti-diabetic and weight-reducing effects. The stimulus-secretion pathway in L-cells is still poorly understood, although it is known that GLP-1 secreting cells use sodium-glucose co-transporters (SGLT and ATP-sensitive K+-channels (K(ATP-channels to sense intestinal glucose levels. Electrical activity then transduces glucose sensing to Ca2+-stimulated exocytosis. This particular glucose-sensing arrangement with glucose triggering both a depolarizing SGLT current as well as leading to closure of the hyperpolarizing K(ATP current is of more general interest for our understanding of glucose-sensing cells. To dissect the interactions of these two glucose-sensing mechanisms, we build a mathematical model of electrical activity underlying GLP-1 secretion. Two sets of model parameters are presented: one set represents primary mouse colonic L-cells; the other set is based on data from the GLP-1 secreting GLUTag cell line. The model is then used to obtain insight into the differences in glucose-sensing between primary L-cells and GLUTag cells. Our results illuminate how the two glucose-sensing mechanisms interact, and suggest that the depolarizing effect of SGLT currents is modulated by K(ATP-channel activity. Based on our simulations, we propose that primary L-cells encode the glucose signal as changes in action potential amplitude, whereas GLUTag cells rely mainly on frequency modulation. The model should be useful for further basic, pharmacological and theoretical investigations of the cellular signals underlying endogenous GLP-1 and peptide YY release.

  16. Effect of a family focused active play intervention on sedentary time and physical activity in preschool children.

    Science.gov (United States)

    O'Dwyer, Mareesa V; Fairclough, Stuart J; Knowles, Zoe; Stratton, Gareth

    2012-10-01

    Early childhood provides a window of opportunity for the promotion of physical activity. Given the limited effectiveness of interventions to date, new approaches are needed. Socio-ecological models suggest that involving parents as intervention targets may be effective in fostering healthier lifestyles in children. This study describes the effectiveness of a family-focused 'Active Play' intervention in decreasing sedentary time and increasing total physical activity in preschool children. Seventy-seven families were recruited from 8 randomly selected SureStart children's centres in the North West of England. Centres were randomly assigned to either an intervention (n = 4) or a comparison group (n = 4). Parents and children in the intervention group received a 10-week active play programme delivered by trained active play professionals; this included an activity and educational component. Families in the comparison group were asked to maintain their usual routine. Each participating parent and child wore a uni-axial accelerometer for 7 days at baseline and post-test. Week and weekend day sedentary time and total physical activity adjusted for child- and home- level covariates were analysed using multilevel analyses. Significant intervention effects were observed for sedentary time and physical activity for both week and weekend days. Children in the intervention group engaged in 1.5% and 4.3% less sedentary time during week and weekend days, respectively and 4.5% and 13.1% more physical activity during week and weekend days, respectively than children in the comparison group. Parent's participation in sport and their physical activity levels, child's sex, availability of media in the home and attendance at organised activities were significant predictors of sedentary time and physical activity in this age group. A 10-week family focused active play intervention produced positive changes in sedentary time and total physical activity levels in preschool children

  17. Impaired endogenous nighttime melatonin secretion relates to intrarenal renin-angiotensin system activation and renal damage in patients with chronic kidney disease.

    Science.gov (United States)

    Ishigaki, Sayaka; Ohashi, Naro; Isobe, Shinsuke; Tsuji, Naoko; Iwakura, Takamasa; Ono, Masafumi; Sakao, Yukitoshi; Tsuji, Takayuki; Kato, Akihiko; Miyajima, Hiroaki; Yasuda, Hideo

    2016-12-01

    Activation of the intrarenal renin-angiotensin system (RAS) plays a critical role in the pathophysiology of chronic kidney disease (CKD) and hypertension. The circadian rhythm of intrarenal RAS activation leads to renal damage and hypertension, which are associated with diurnal blood pressure (BP) variation. The activation of intrarenal RAS following reactive oxygen species (ROS) activation, sympathetic hyperactivity and nitric oxide (NO) inhibition leads to the development of renal damage. Melatonin is a hormone regulating the circadian rhythm, and has multiple functions such as anti-oxidant and anti-adrenergic effects and enhancement of NO bioavailability. Nocturnal melatonin concentrations are lower in CKD patients. However, it is not known if impaired endogenous melatonin secretion is related to BP, intrarenal RAS, or renal damage in CKD patients. We recruited 53 CKD patients and conducted 24-h ambulatory BP monitoring. urine was collected during the daytime and nighttime. We investigated the relationship among the melatonin metabolite urinary 6-sulphatoxymelatonin (U-aMT6s), BP, renal function, urinary angiotensinogen (U-AGT), and urinary albumin (U-Alb). Patients' U-aMT6s levels were significantly and negatively correlated with clinical parameters such as renal function, systolic BP, U-AGT, and U-Alb, during both day and night. Multiple regression analyses for U-aMT6s levels were performed using age, gender, renal function, and each parameter (BPs, U-AGT or U-Alb), at daytime and nighttime. U-aMT6s levels were significantly associated with U-AGT (β = -0.31, p = 0.044) and U-Alb (β = -0.25, p = 0.025) only at night. Impaired nighttime melatonin secretion may be associated with nighttime intrarenal RAS activation and renal damage in CKD patients.

  18. Monocytes/macrophages support mammary tumor invasivity by co-secreting lineage-specific EGFR ligands and a STAT3 activator

    International Nuclear Information System (INIS)

    Vlaicu, Philip; Mertins, Philipp; Mayr, Thomas; Widschwendter, Peter; Ataseven, Beyhan; Högel, Bernhard; Eiermann, Wolfgang; Knyazev, Pjotr; Ullrich, Axel

    2013-01-01

    Tumor-associated macrophages (TAM) promote malignant progression, yet the repertoire of oncogenic factors secreted by TAM has not been clearly defined. We sought to analyze which EGFR- and STAT3-activating factors are secreted by monocytes/macrophages exposed to tumor cell-secreted factors. Following exposure of primary human monocytes and macrophages to supernatants of a variety of tumor cell lines, we have analyzed transcript and secreted protein levels of EGFR family ligands and of STAT3 activators. To validate our findings, we have analyzed TAM infiltration levels, systemic and local protein levels as well as clinical data of primary breast cancer patients. Primary human monocytes and macrophages respond to tumor cell-derived factors by secreting EGFR- and STAT3-activating ligands, thus inducing two important oncogenic pathways in carcinoma cells. Tumor cell-secreted factors trigger two stereotype secretory profiles in peripheral blood monocytes and differentiated macrophages: monocytes secrete epiregulin (EREG) and oncostatin-M (OSM), while macrophages secrete heparin-binding EGF-like growth factor (HB-EGF) and OSM. HB-EGF and OSM cooperatively induce tumor cell chemotaxis. HB-EGF and OSM are co-expressed by TAM in breast carcinoma patients, and plasma levels of both ligands correlate strongly. Elevated HB-EGF levels accompany TAM infiltration, tumor growth and dissemination in patients with invasive disease. Our work identifies systemic markers for TAM involvement in cancer progression, with the potential to be developed into molecular targets in cancer therapy

  19. Active release technique in hamstrings strain: Rehabilitation and return to play – a case study

    Directory of Open Access Journals (Sweden)

    Hariharasudhan Ravichandran

    2017-01-01

    Full Text Available Hamstring injuries and its rehabilitation in competitive events such as football targets safe and early return to play. This is because hamstring injuries are more related to prolonged recovery time and high rate of re-injury. In this case study, Zakeer Mundampara, 26-year-old footballer of Chennaiyin FC team (Indian super league tournament, who was rehabilitated for Grade 2 hamstring strain was briefed. To describe the importance of conservative rehabilitation in hamstring injuries and report on player's rehabilitation program and clinical outcome. Zakeer Mundampara was conservatively treated with active release technique for 2 weeks duration. Data collected includes passive knee extension test range of motion and verbal rating score. After 2 weeks of rehabilitation, Zakeer Mundampara had nearly full range of pain-free movement, normal gait and trained to run safely. By the 3rd week, he started to perform all sports specific drills. He was rehabilitated and set fit to play after 4 weeks from the date of injury. Active release technique is effective in hamstring injuries. In this case study, rehabilitation program with an emphasis on active release technique is found to be effective in returning the footballer back to play.

  20. Children's active free play in local neighborhoods: a behavioral mapping study.

    Science.gov (United States)

    Veitch, J; Salmon, J; Ball, K

    2008-10-01

    Many Australian children are more sedentary than they should be, and almost one in five are currently overweight or obese. Some children may face difficulties finding opportunities to be active, having poor access to safe public open spaces or having low independent mobility limiting their access to places to play. This study aimed to examine children's access to places in their neighborhood for active free play and how these vary by age, sex and socioeconomic status (SES). Behavioral maps of the local neighborhood were completed by children (8-12 years) from five primary schools across different areas of Melbourne. Children living in low SES outer-urban neighborhoods had to travel greater distances to access local parks compared with those in inner-urban mid and high SES areas. One-third (32%) of children reported an independent mobility range of <100 m from home. In conclusion, for some children opportunities to engage in active free play in the local neighborhood may be limited due to lack of parks in close proximity to home and restricted independent mobility. It is important to collaborate with local governments, urban planners and community groups to improve access to neighborhood parks and to promote a sense of neighborhood safety.

  1. Incretin secretion: direct mechanisms

    DEFF Research Database (Denmark)

    Balk-Møller, Emilie; Holst, Jens Juul; Kuhre, Rune Ehrenreich

    2014-01-01

    The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are secreted from gastro-intestinal K- and L-cells, respectively, and play an important role in post-prandial blood glucose regulation. They do this by direct stimulation of the pancreatic β...... enzyme responsible for incretin degradation (dipeptidyl peptidase-4) is inhibited (drugs are already on the market) while the secretion of endogenous GLP-1 secretion is stimulated at the same time may prove particularly rewarding. In this section we review current knowledge on the mechanisms for direct...

  2. Dangerous Activities within an Invisible Playground: A Study of Emergent Male Football Play and Teachers' Perspectives of Outdoor Free Play in the Early Years of Primary School

    Science.gov (United States)

    Jarvis, Pam

    2007-01-01

    This research was carried out during a study which focused upon the rough and tumble play of children in the early years department of a suburban primary school in northern England. The child sample's playtime activities were ethnographically observed over a period of 18 calendar months, during which time interviews were also carried out with the…

  3. Bufadienolides from parotoid gland secretions of Cuban toad Peltophryne fustiger (Bufonidae): Inhibition of human kidney Na(+)/K(+)-ATPase activity.

    Science.gov (United States)

    Perera Córdova, Wilmer H; Leitão, Suzana Guimarães; Cunha-Filho, Geraldino; Bosch, Roberto Alonso; Alonso, Isel Pascual; Pereda-Miranda, Rogelio; Gervou, Rodrigo; Touza, Natália Araújo; Quintas, Luis Eduardo M; Noël, François

    2016-02-01

    Parotoid gland secretions of toad species are a vast reservoir of bioactive molecules with a wide range of biological properties. Herein, for the first time, it is described the isolation by preparative reversed-phase HPLC and the structure elucidation by NMR spectroscopy and/or mass spectrometry of nine major bufadienolides from parotoid gland secretions of the Cuban endemic toad Peltophryne fustiger: ψ-bufarenogin, gamabufotalin, bufarenogin, arenobufagin, 3-(N-suberoylargininyl) marinobufagin, bufotalinin, telocinobufagin, marinobufagin and bufalin. In addition, the secretion was analyzed by UPLC-MS/MS which also allowed the identification of azelayl arginine. The effect of arenobufagin, bufalin and ψ-bufarenogin on Na(+)/K(+)-ATPase activity in a human kidney preparation was evaluated. These bufadienolides fully inhibited the Na(+)/K(+)-ATPase in a concentration-dependent manner, although arenobufagin (IC50 = 28.3 nM) and bufalin (IC50 = 28.7 nM) were 100 times more potent than ψ-bufarenogin (IC50 = 3020 nM). These results provided evidence about the importance of the hydroxylation at position C-14 in the bufadienolide skeleton for the inhibitory activity on the Na(+)/K(+)-ATPase. Published by Elsevier Ltd.

  4. Does playing a sports active video game improve young children's ball skill competence?

    Science.gov (United States)

    Johnson, Tara M; Ridgers, Nicola D; Hulteen, Ryan M; Mellecker, Robin R; Barnett, Lisa M

    2016-05-01

    Actual and perceived object control (commonly ball) skill proficiency is associated with higher physical activity in children and adolescents. Active video games (AVGs) encourage whole body movement to control/play the electronic gaming system and therefore provide an opportunity for screen time to become more active. The purpose of this study was to determine whether playing sports AVGs has a positive influence on young children's actual and perceived object control skills. Two group pre/post experimental design study. Thirty-six children aged 6-10 years old from one school were randomly allocated to a control or intervention condition. The Test of Gross Motor Development-3 assessed object control skill. The Pictorial Scale of Perceived Competence for Young Children assessed perceived object control skill. The intervention consisted of 6×50min lunchtime AVG sessions on the Xbox Kinect. Two to three sport games were chosen for participants to play each session. General linear models with either perceived object control or actual object control skill as the outcome variables were conducted. Each base model adjusted for intervention status and pre-score of the respective outcome variable. Additional models adjusted for potential confounding variables (sex of child and game at home). No significant differences between the control and intervention groups were observed for both outcomes. This study found that playing the Xbox Kinect does not significantly influence children's perceived or actual object control skills, suggesting that the utility of the Xbox Kinect for developing perceived and actual object control skill competence is questionable. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  5. Active and non-active video gaming among Dutch adolescents: Who plays and how much?

    NARCIS (Netherlands)

    Simons, M.; Vet, de E.W.M.L.; Brug, J.; Seidell, J.C.; Chinapaw, M.

    2014-01-01

    Objective: The aim of study was to determine prevalence and identify demographic correlates of activeand non-active gaming among adolescents.Design: Cross-sectional.Methods: A survey, assessing game behavior and correlates, was conducted among adolescents (12–16years, n = 373), recruited via

  6. BIOLOGICAL ACTIVITY OF SKIN SECRETIONS IN THE PERCIDAE FAMILY OF FISH WITH REGARD TO ERYSIPELOTHRIX RHUSIOPATHIAE BACTERIA

    Directory of Open Access Journals (Sweden)

    А. Нulaі

    2015-09-01

    Full Text Available Purpose. To determine the effect of skin secretions in Percidae family of fish (Sander lucioperca, Perca fluviatilis on the cultures of pathogenic E. rhusiopathiae bacteria. Methodology. Filter paper was placed on the skin of live fish; after 1 minute it was removed, and the extraction of water-soluble components in the rate of 0.1 cm3 of water per 1 cm2 area of the paper was carried out. The resulting solutions of the secretions of fish skin glands were sterilized by vacuum filtration through the filters with a pore diameter The test samples contained E. rhusiopathiae cultures and fish skin secretions in 1:10, 1:100, 1:1000 and 1:10000 dilutions. The control samples contained a similar ratio of sterile water and cultures of the experimental bacteria type. The content of E. rhusiopathiae cells in the experimental and control samples was determined after 48 hours, the samples were stored at a temperature of +18... +20 °C. Findings. The presence of water-soluble extracts of skin secretions obtained from Percidae family of freshwater fish in the environment causes an increase in the density of E. rhusiopathiae bacteria cultures. The degree of the detected stimulating effect of E. rhusiopathiae directly depend on the concentration of the secretions of fish skin glands in the experimental samples. Under the conditions of freshwater ecosystems, such fish as S. lucioperca and P. fluviatilis and E. rhusiopathiae bacteria may form biocenotical relations of the trophic, topical and phoric types. Originality. The quantitative data proving the biological activity of skin secretions in Percidae family of fish with regard to E. rhusiopathiae pathogenic bacteria have been obtained for the first time. Practical Value. One of the factors contributing to E. rhusiopathiae bacteria staying in freshwater conditions for a long time can be their biocenotical relations with the components of freshwater biocenoses, including such fish as S. lucioperca and P

  7. On play and playing.

    Science.gov (United States)

    Rudan, Dusko

    2013-12-01

    The paper offers a review of the development of the concept of play and playing. The true beginnings of the development of the theories of play are set as late as in the 19th century. It is difficult to define play as such; it may much more easily be defined through its antipode--work. In the beginning, play used to be connected with education; it was not before Freud's theory of psychoanalysis and Piaget's developmental psychology that the importance of play in a child's development began to be explained in more detail. The paper further tackles the role of play in the adult age. Detailed attention is paid to psychodynamic and psychoanalytic authors, in particular D. W. Winnicott and his understanding of playing in the intermediary (transitional) empirical or experiential space. In other words, playing occupies a space and time of its own. The neuroscientific concept of playing is also tackled, in the connection with development as well.

  8. AMP-activated protein kinase and adenosine are both metabolic modulators that regulate chloride secretion in the shark rectal gland ( Squalus acanthias).

    Science.gov (United States)

    Neuman, Rugina I; van Kalmthout, Juliette A M; Pfau, Daniel J; Menendez, Dhariyat M; Young, Lawrence H; Forrest, John N

    2018-04-01

    The production of endogenous adenosine during secretagogue stimulation of CFTR leads to feedback inhibition limiting further chloride secretion in the rectal gland of the dogfish shark (Squalus acanthias). In the present study, we examined the role of AMP-kinase (AMPK) as an energy sensor also modulating chloride secretion through CFTR. We found that glands perfused with forskolin and isobutylmethylxanthine (F + I), potent stimulators of chloride secretion in this ancient model, caused significant phosphorylation of the catalytic subunit Thr 172 of AMPK. These findings indicate that AMPK is activated during energy-requiring stimulated chloride secretion. In molecular studies, we confirmed that the activating Thr 172 site is indeed present in the α-catalytic subunit of AMPK in this ancient gland, which reveals striking homology to AMPKα subunits sequenced in other vertebrates. When perfused rectal glands stimulated with F + I were subjected to severe hypoxic stress or perfused with pharmacologic inhibitors of metabolism (FCCP or oligomycin), phosphorylation of AMPK Thr 172 was further increased and chloride secretion was dramatically diminished. The pharmacologic activation of AMPK with AICAR-inhibited chloride secretion, as measured by short-circuit current, when applied to the apical side of shark rectal gland monolayers in primary culture. These results indicate that that activated AMPK, similar to adenosine, transmits an inhibitory signal from metabolism, that limits chloride secretion in the shark rectal gland.

  9. Development of the Assistance to Participate Scale (APS) for children's play and leisure activities.

    Science.gov (United States)

    Bourke-Taylor, H; Law, M; Howie, L; Pallant, J F

    2009-09-01

    This paper describes the development and psychometric evaluation of the Assistance to Participate Scale (APS). The APS measures the assistance that a school-aged child with a disability requires to participate in play and leisure activities from the primary carer's perspective. Mixed methodology using an instrument design model was used to complete two studies. First, a qualitative research design was used to generate items and scoring criteria for the APS. Second, a quantitative study evaluated the instrument using data collected from 152 mothers with children aged 5-18 years. Statistical analysis assessed the underlying structure, internal consistency and construct validity of the APS. Exploratory factor analysis revealed two correlated components, reflecting home-based and community-based play activities. Both subscales and the total APS scale showed good internal consistency. The APS correlated as predicted with individual domains and overall scores for other validated measures (Pediatric Evaluation of Disability Inventory caregiver scales and Pediatric Quality of Life Inventory) with correlations ranging from rho = 0.42 to rho = 0.77. The APS was able to discriminate between groups of children based on type of schooling (regular or segregated), need for equipment/assistive devices, frequency of lifting and disability. The APS provides professionals with a brief psychometrically sound tool that measures the amount of caregiver assistance provided to a child with a disability to participate in play and recreation. The APS may be used as an outcome measure and to evaluate and predict the amount and type of additional assistance families need to facilitate their child's participation in an important aspect of the child's daily life and development: play and recreation.

  10. Antifungal activity of the pygidial gland secretion of Laemostenus punctatus (Coleoptera: Carabidae) against cave-dwelling micromycetes

    Science.gov (United States)

    Nenadić, Marija; Ljaljević-Grbić, Milica; Stupar, Miloš; Vukojević, Jelena; Ćirić, Ana; Tešević, Vele; Vujisić, Ljubodrag; Todosijević, Marina; Vesović, Nikola; Živković, Nemanja; Ćurčić, Srećko

    2017-06-01

    The antifungal potential of the pygidial gland secretion of the troglophilic ground beetle Laemostenus punctatus from a cave in Southeastern Serbia against cave-dwelling micromycetes, isolated from the same habitat, has been investigated. Eleven collected samples were analyzed and 32 isolates of cave-dwelling fungi were documented. A total of 14 fungal species were identified as members of the genera Aspergillus, Penicillium, Alternaria, Cladosporium, Rhizopus, Trichoderma, Arthrinium, Aureobasidium, Epicoccum, Talaromyces, and Fusarium. Five isolates were selected for testing the antifungal activity of the pygidial gland secretion: Talaromyces duclauxi, Aspergillus brunneouniseriatus, Penicillium sp., Rhizopus stolonifer, and Trichoderma viride. The microdilution method has been applied to detect minimal inhibitory concentrations (MICs) and minimal fungicidal concentrations (MFCs). The most sensitive isolate was Penicillium sp., while the other isolates demonstrated a high level of resistance to the tested agent. L. punctatus has developed a special mechanism of producing specific compounds that act synergistically within the secretion mixture, which are responsible for the antifungal action against pathogens from the cave. The results open opportunities for further research in the field of ground beetle defense against pathogens, which could have an important application in human medicine, in addition to the environmental impact, primarily.

  11. Panax ginseng total protein promotes proliferation and secretion of collagen in NIH/3T3 cells by activating extracellular signal-related kinase pathway

    Directory of Open Access Journals (Sweden)

    Xuenan Chen

    2017-07-01

    Conclusion: Our studies suggest that GTP promoted proliferation and secretion of collagen in NIH/3T3 cells by activating the ERK signal pathway, which shed light on a potential function of GTP in promoting wound healing.

  12. Lactobacillus crispatus dominant vaginal microbiome is associated with inhibitory activity of female genital tract secretions against Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Jeny P Ghartey

    Full Text Available Female genital tract secretions inhibit E. coli ex vivo and the activity may prevent colonization and provide a biomarker of a healthy microbiome. We hypothesized that high E. coli inhibitory activity would be associated with a Lactobacillus crispatus and/or jensenii dominant microbiome and differ from that of women with low inhibitory activity.Vaginal swab cell pellets from 20 samples previously obtained in a cross-sectional study of near-term pregnant and non-pregnant healthy women were selected based on having high (>90% inhibition or low (<20% inhibition anti-E. coli activity. The V6 region of the 16S ribosomal RNA gene was amplified and sequenced using the Illumina HiSeq 2000 platform. Filtered culture supernatants from Lactobacillus crispatus, Lactobacillus iners, and Gardnerella vaginalis were also assayed for E. coli inhibitory activity.Sixteen samples (10 with high and 6 with low activity yielded evaluable microbiome data. There was no difference in the predominant microbiome species in pregnant compared to non-pregnant women (n = 8 each. However, there were significant differences between women with high compared to low E. coli inhibitory activity. High activity was associated with a predominance of L. crispatus (p<0.007 and culture supernatants from L. crispatus exhibited greater E. coli inhibitory activity compared to supernatants obtained from L. iners or G. vaginalis. Notably, the E. coli inhibitory activity varied among different strains of L. crispatus.Microbiome communities with abundant L. crispatus likely contribute to the E. coli inhibitory activity of vaginal secretions and efforts to promote this environment may prevent E. coli colonization and related sequelae including preterm birth.

  13. Exploring the Impact of Role-Playing on Peer Feedback in an Online Case-Based Learning Activity

    Science.gov (United States)

    Ching, Yu-Hui

    2014-01-01

    This study explored the impact of role-playing on the quality of peer feedback and learners' perception of this strategy in a case-based learning activity with VoiceThread in an online course. The findings revealed potential positive impact of role-playing on learners' generation of constructive feedback as role-playing was associated with higher…

  14. Adrenergic receptors and gastric secretion in dogs. Is a "tonic balance" relationship between vagal and beta 2-adrenergic activity a possibility?

    DEFF Research Database (Denmark)

    Gottrup, F; Hovendal, C; Bech, K

    1984-01-01

    The relative influence of adrenergic receptors on gastric acid secretion in the dog stomach with different vagal activity or "tone" is almost unknown. beta-adrenoceptors seem to be most important for the direct effect of adrenergic stimulation on acid secretion. In this study the effects...... acid secretion was not influenced significantly by beta-blockade. Similar dose-response curves were found for non-vagotomized dogs with high beta 2-adrenergic tone and dogs with low vagal tone (vagotomy) after pentagastrin and histamine stimulated acid secretion. This study indicates...... that a counterbalance between beta 2-adrenergic and cholinergic vagal tone exists. A "tonic balance theory" is suggested and is probably involved in the resulting acid secretion after vagotomy....

  15. The locomotor activity of soccer players based on playing positions during the 2010 World Cup.

    Science.gov (United States)

    Soroka, Andrzej

    2018-06-01

    The aim of this study was to define the locomotor activity of footballer players during the 2010 World Cup and to assess what differences existed among different playing positions. Research was conducted using research material collected from the Castrol Performance Index, a kinematic game analysis system that records player movements during a game by use of semi-automatic cameras. A total of 599 players who participated in the championships were analyzed. The results were evaluated using one-way analysis of variance (ANOVA) and a post-hoc test that calculated the Honestly Significant Difference (HSD) in order to determine which mean values significantly differed among the player positions. It was found that midfielders covered on average the largest distance during a match (10,777.6 m, Plocomotor activity at high and sprint intensities (2936.8 m and 108.4 m, respectively). Additionally, midfielders also spent the largest amount of time at performing at a high intensity (10.6%). Strikers also featured high levels of the above parameters; the total length of distance covered with high intensities was found to be on average 2586.7 m, the distance covered at sprint intensity was 105 m. The footballers, playing at the championship level feature excellent locomotor preparation. This fact is undoubtedly supported by the aerobic training of high intensity. Such training allows footballers to extend the distance they cover during the match, increase the intensity of locomotor activities and sprint speed distance.

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

    Science.gov (United States)

    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 being active. Three hundred 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 hours watching television, playing video games, or spending time on the computer. While over half of respondents reported that their children get more than 2 hours of physical activity on school days, 14% of children were reported to be physically active less than 1 hour 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

  17. Developing Pharmacy Student Communication Skills through Role-Playing and Active Learning

    Science.gov (United States)

    Zeszotarski, Paula; Ma, Carolyn

    2015-01-01

    Objective. To evaluate the impact on pharmacy students of a communication course, which used role-playing to develop active-learning skills. Design. Students role-playing pharmacists in patient care scenarios were critiqued by students and pharmacist faculty members. Grading was performed using the rubric inspired by Bruce Berger’s Communication Skills for Pharmacists. Written skills were evaluated using student written critique questionnaires. Students completed precourse and postcourse self-assessment surveys. Preceptor evaluations were analyzed for course impact. Assessment. Students demonstrated improvement in oral skills based on role-play scores (45.87/50) after practice sessions. The average score based on the student questionnaire was 9.31/10. Gain was demonstrated in all defined course objectives. Impact on introductory pharmacy practice experience (IPPE) communication objectives was insignificant. Student evaluations for course and teaching strategy reflected a high average. Conclusion. Study results demonstrated improvement in oral and written communication skills that may help improve interprofessional teamwork between pharmacists and other health care providers. PMID:25995519

  18. Differential Role of Cathepsins S and B In Hepatic APC-Mediated NKT Cell Activation and Cytokine Secretion.

    Science.gov (United States)

    de Mingo Pulido, Álvaro; de Gregorio, Estefanía; Chandra, Shilpi; Colell, Anna; Morales, Albert; Kronenberg, Mitchell; Marí, Montserrat

    2018-01-01

    Natural killer T (NKT) cells exhibit a specific tissue distribution, displaying the liver the highest NKT/conventional T cell ratio. Upon antigen stimulation, NKT cells secrete Th1 cytokines, including interferon γ (IFNγ), and Th2 cytokines, including IL-4 that recruit and activate other innate immune cells to exacerbate inflammatory responses in the liver. Cysteine cathepsins control hepatic inflammation by regulating κB-dependent gene expression. However, the contribution of cysteine cathepsins other than Cathepsin S to NKT cell activation has remained largely unexplored. Here we report that cysteine cathepsins, cathepsin B (CTSB) and cathepsin S (CTSS), regulate different aspects of NKT cell activation. Inhibition of CTSB or CTSS reduced hepatic NKT cell expansion in a mouse model after LPS challenge. By contrast, only CTSS inhibition reduced IFNγ and IL-4 secretion after in vivo α-GalCer administration. Accordingly, in vitro studies reveal that only CTSS was able to control α-GalCer-dependent loading in antigen-presenting cells (APCs), probably due to altered endolysosomal protein degradation. In summary, our study discloses the participation of cysteine cathepsins, CTSB and CTSS, in the activation of NKT cells in vivo and in vitro .

  19. Differential Role of Cathepsins S and B In Hepatic APC-Mediated NKT Cell Activation and Cytokine Secretion

    Directory of Open Access Journals (Sweden)

    Álvaro de Mingo Pulido

    2018-02-01

    Full Text Available Natural killer T (NKT cells exhibit a specific tissue distribution, displaying the liver the highest NKT/conventional T cell ratio. Upon antigen stimulation, NKT cells secrete Th1 cytokines, including interferon γ (IFNγ, and Th2 cytokines, including IL-4 that recruit and activate other innate immune cells to exacerbate inflammatory responses in the liver. Cysteine cathepsins control hepatic inflammation by regulating κB-dependent gene expression. However, the contribution of cysteine cathepsins other than Cathepsin S to NKT cell activation has remained largely unexplored. Here we report that cysteine cathepsins, cathepsin B (CTSB and cathepsin S (CTSS, regulate different aspects of NKT cell activation. Inhibition of CTSB or CTSS reduced hepatic NKT cell expansion in a mouse model after LPS challenge. By contrast, only CTSS inhibition reduced IFNγ and IL-4 secretion after in vivo α-GalCer administration. Accordingly, in vitro studies reveal that only CTSS was able to control α-GalCer-dependent loading in antigen-presenting cells (APCs, probably due to altered endolysosomal protein degradation. In summary, our study discloses the participation of cysteine cathepsins, CTSB and CTSS, in the activation of NKT cells in vivo and in vitro.

  20. Alkali pH directly activates ATP-sensitive K+ channels and inhibits insulin secretion in beta-cells.

    Science.gov (United States)

    Manning Fox, Jocelyn E; Karaman, Gunce; Wheeler, Michael B

    2006-11-17

    Glucose stimulation of pancreatic beta-cells is reported to lead to sustained alkalization, while extracellular application of weak bases is reported to inhibit electrical activity and decrease insulin secretion. We hypothesize that beta-cell K(ATP) channel activity is modulated by alkaline pH. Using the excised patch-clamp technique, we demonstrate a direct stimulatory action of alkali pH on recombinant SUR1/Kir6.2 channels due to increased open probability. Bath application of alkali pH similarly activates native islet beta-cell K(ATP) channels, leading to an inhibition of action potentials, and hyperpolarization of membrane potential. In situ pancreatic perfusion confirms that these cellular effects of alkali pH are observable at a functional level, resulting in decreases in both phase 1 and phase 2 glucose-stimulated insulin secretion. Our data are the first to report a stimulatory effect of a range of alkali pH on K(ATP) channel activity and link this to downstream effects on islet beta-cell function.

  1. ENERGY EXPENDITURE AND INTENSITY OF PHYSICAL ACTIVITY IN SOCCER REFEREES DURING MATCH-PLAY

    Directory of Open Access Journals (Sweden)

    Alberto Inácio da Silva

    2008-09-01

    Full Text Available The aim of this study was to determine the caloric expenditure and the intensity of physical activities performed by official soccer referees during a match expressed in Metabolic Equivalent (METs. The physical activity of referees accredited by CBF (Brazilian Confederation of Soccer was video-recorded during twenty-nine official games of Paraná Championship (Brasil, Series A and B of the 2005/2006. Computerized video analysis was used to determine the time spent in 6 locomotor activities (standing still, walking, jogging, backwards running, running and sprint. The frequency and duration of each activity were recorded and these data were utilized to calculate the distance covered by the referee. Energy expenditure values were estimated, utilizing specific equations, from the time players spent in each motor activity. The referees observed in this study had a mean age of 38.9 ± 3.8 years, body mass of 86.1 ± 7.1 kg, stature of 1.80 ± 0.07 m and a body mass index of 26.5 ± 0.6 kg·m-2. During match-play, referees covered an average distance of 9155.4 ± 70.3 meters (8411 - 9765, with a mean energy expenditure of 734.7 ± 65 kcal. This energy expenditure was significantly reduced in the second half: 359.9 ± 6.3 vs 374.7 ± 6.6 kcal (p = 0.006, and averaged to be moderate energy intensity (5 METs with predominant utilization of the aerobic energy system. In total, during 67% of match-play the intensity was equal or lower than 3.8 METs and in 33% it was higher than 9.8 METs. The pattern of movement observed in the present study confirms that soccer refereeing may be considered as a highly intermittent exercise mode. The high to low-intensity activity ratio may be defined as 1:7.1. In conclusion, referees officiating in professional soccer matches in Brazil should perform a physical conditioning regime that provides the stamina required at this level and consume appropriate and adequate nutrition to meet the energetic demands for match-play

  2. The Influence of Physical Qualities on Activity Profiles of Female Australian Football Match-Play.

    Science.gov (United States)

    Black, Georgia M; Gabbett, Tim J; Johnston, Rich D; Cole, Michael H; Naughton, Geraldine; Dawson, Brian

    2017-10-16

    The rapid transition of female Australian football players from amateur to semi-elite competitions has the potential for athletes to be underprepared for match-play. To gain an understanding the match demands of female football, the aims of this study were three-fold: (1) to highlight the physical qualities that discriminate selected and non-selected female Australian Football players, (2) to investigate activity profiles of female Australian Football players, and (3) to gain an understanding of the influence of physical qualities on running performance in female Australian Football match-play. Twenty-two female Australian football (AF) state academy players (mean ± SD age, 23.2 ± 4.5 years) and 27 non-selected players (mean ± SD age, 23.4 ± 4.9 years) participated in this study. The Yo-Yo Intermittent Recovery Test (Level 1), countermovement jump and 30m sprint tests were completed prior to the competitive season. During 14 matches, players wore global positioning system (GPS) units to describe the running demands of female AF match-play. Selected players were faster over 30 metres (ES=0.57; p=0.04) and covered greater distances on the Yo-Yo IR1 test (ES=1.09; pfemale AF players were faster and had greater intermittent running ability than players not selected to a State academy program. An emphasis should be placed on the development of physical fitness in this playing group to ensure optimal preparation for the national competition.

  3. Epstein Barr virus Latent Membrane Protein-1 enhances dendritic cell therapy lymph node migration, activation, and IL-12 secretion.

    Directory of Open Access Journals (Sweden)

    James M Termini

    Full Text Available Dendritic cells (DC are a promising cell type for cancer vaccines due to their high immunostimulatory capacity. However, improper maturation of DC prior to treatment may account for the limited efficacy of DC vaccine clinical trials. Latent Membrane Protein-1 (LMP1 of Epstein-Barr virus was examined for its ability to mature and activate DC as a gene-based molecular adjuvant for DC vaccines. DC were transduced with an adenovirus 5 vector (Ad5 expressing LMP1 under the control of a Tet-inducible promoter. Ad5-LMP1 was found to mature and activate both human and mouse DC. LMP1 enhanced in vitro migration of DC toward CCL19, as well as in vivo migration of DC to the inguinal lymph nodes of mice following intradermal injection. LMP1-transduced DC increased T cell proliferation in a Pmel-1 adoptive transfer model and enhanced survival in B16-F10 melanoma models. LMP1-DC also enhanced protection in a vaccinia-Gag viral challenge assay. LMP1 induced high levels of IL-12p70 secretion in mouse DC when compared to standard maturation protocols. Importantly, LMP1-transduced human DC retained the capacity to secrete IL-12p70 and TNF in response to DC restimulation. In contrast, DC matured with Monocyte Conditioned Media-Mimic cocktail (Mimic were impaired in IL-12p70 secretion following restimulation. Overall, LMP1 matured and activated DC, induced migration to the lymph node, and generated high levels of IL-12p70 in a murine model. We propose LMP1 as a promising molecular adjuvant for DC vaccines.

  4. Effect of dietary roughage level on chewing activity, ruminal pH, and saliva secretion in lactating Holstein cows.

    Science.gov (United States)

    Jiang, F G; Lin, X Y; Yan, Z G; Hu, Z Y; Liu, G M; Sun, Y D; Liu, X W; Wang, Z H

    2017-04-01

    Increasing dietary roughage level is a commonly used strategy to prevent subacute ruminal acidosis. We hypothesized that high-roughage diets could promote chewing activity, saliva secretion, and hence more alkaline to buffer rumen pH. To verify the hypothesis, 12 multiparous Holstein cows in mid lactation were randomly allocated to 4 treatments in a triplicated 4 × 4 Latin square experiment with one cow in each treatment surgically fitted with a ruminal cannula. Treatments were diets containing 40, 50, 60, or 70% of roughage on a DM basis. Increasing dietary roughage level decreased DM, CP, OM, starch, and NE L intake, increased ADF intake, and decreased milk yield linearly. Intake of NDF was quite stable across treatments and ranged from 7.8 to 8.1 kg/d per cow. Daily eating time increased linearly with increased roughage level. The increase in eating time was due to increased eating time per meal but not number of meals per day, which was stable and ranged from 8.3 to 8.5 meals per day across treatments. Increasing dietary roughage level had no effect on ruminating time (min/d), the number of ruminating periods (rumination periods per d), and chewing time per ruminating period (min/ruminating period). Ruminating time per kilogram of NDF intake and total chewing time per kilogram of ADF intake were similar across treatments (57.4 and 183.8 min/kg, respectively). Increasing dietary roughage level linearly increased daily total chewing time; linearly elevated the mean, maximum, and minimum ruminal pH; and linearly decreased total VFA concentration and molar proportion of propionate in ruminal fluid. Saliva secretion during eating was increased, the secretion during rumination was unaffected, but the secretion during resting tended to decrease with increased dietary roughage level. As a result, total saliva secretion was not affected by treatments. In conclusion, the results of the present study did not support the concept that high-roughage diets elevated ruminal p

  5. Effect of a 6-Week Active Play Intervention on Fundamental Movement Skill Competence of Preschool Children.

    Science.gov (United States)

    Foulkes, J D; Knowles, Z; Fairclough, S J; Stratton, G; O'Dwyer, M; Ridgers, N D; Foweather, L

    2017-04-01

    This study examined the effectiveness of an active play intervention on fundamental movement skills of 3- to 5-year-old children from deprived communities. In a cluster randomized controlled trial design, six preschools received a resource pack and a 6-week local authority program involving staff training with help implementing 60-minute weekly sessions and postprogram support. Six comparison preschools received a resource pack only. Twelve skills were assessed at baseline, postintervention, and at a 6-month follow-up using the Children's Activity and Movement in Preschool Study Motor Skills Protocol. One hundred and sixty-two children (Mean age = 4.64 ± 0.58 years; 53.1% boys) were included in the final analyses. There were no significant differences between groups for total fundamental movement skill, object-control skill or locomotor skill scores, indicating a need for program modification to facilitate greater skill improvements.

  6. Peroxisome proliferator-activated receptor α agonists modulate Th1 and Th2 chemokine secretion in normal thyrocytes and Graves' disease

    International Nuclear Information System (INIS)

    Antonelli, Alessandro; Ferrari, Silvia Martina; Frascerra, Silvia; Corrado, Alda; Pupilli, Cinzia; Bernini, Giampaolo; Benvenga, Salvatore; Ferrannini, Ele; Fallahi, Poupak

    2011-01-01

    Until now, no data are present about the effect of peroxisome proliferator-activated receptor (PPAR)α activation on the prototype Th1 [chemokine (C-X-C motif) ligand (CXCL)10] (CXCL10) and Th2 [chemokine (C-C motif) ligand 2] (CCL2) chemokines secretion in thyroid cells. The role of PPARα and PPARγ activation on CXCL10 and CCL2 secretion was tested in Graves' disease (GD) and control primary thyrocytes stimulated with interferon (IFN)γ and tumor necrosis factor (TNF)α. IFNγ stimulated both CXCL10 and CCL2 secretion in primary GD and control thyrocytes. TNFα alone stimulated CCL2 secretion, while had no effect on CXCL10. The combination of IFNγ and TNFα had a synergistic effect both on CXCL10 and CCL2 chemokines in GD thyrocytes at levels comparable to those of controls. PPARα activators inhibited the secretion of both chemokines (stimulated with IFNγ and TNFα) at a level higher (for CXCL10, about 60-72%) than PPARγ agonists (about 25-35%), which were confirmed to inhibit CXCL10, but not CCL2. Our data show that CCL2 is modulated by IFNγ and TNFα in GD and normal thyrocytes. Furthermore we first show that PPARα activators inhibit the secretion of CXCL10 and CCL2 in thyrocytes, suggesting that PPARα may be involved in the modulation of the immune response in the thyroid.

  7. Secreted phospholipase A2 of Clonorchis sinensis activates hepatic stellate cells through a pathway involving JNK signalling.

    Science.gov (United States)

    Wu, Yinjuan; Li, Ye; Shang, Mei; Jian, Yu; Wang, Caiqin; Bardeesi, Adham Sameer A; Li, Zhaolei; Chen, Tingjin; Zhao, Lu; Zhou, Lina; He, Ai; Huang, Yan; Lv, Zhiyue; Yu, Xinbing; Li, Xuerong

    2017-03-16

    Secreted phospholipase A2 (sPLA2) is a protein secreted by Clonorchis sinensis and is a component of excretory and secretory products (CsESPs). Phospholipase A2 is well known for its role in liver fibrosis and inhibition of tumour cells. The JNK signalling pathway is involved in hepatic stellate cells (HSCs) activation. Blocking JNK activity with SP600125 inhibits HSCs activation. In a previous study, the protein CssPLA2 was expressed in insoluble inclusion bodies. Therefore, it's necessary to express CssPLA2 in water-soluble form and determine whether the enzymatic activity of CssPLA2 or cell signalling pathways is involved in liver fibrosis caused by clonorchiasis. Balb/C mice were given an abdominal injection of MBP-CssPLA2. Liver sections with HE and Masson staining were observed to detect accumulation of collagen. Western blot of mouse liver was done to detect the activation of JNK signalling pathway. In vitro, HSCs were incubated with MBP-CssPLA2 to detect the activation of HSCs as well as the activation of JNK signalling pathway. The mutant of MBP-CssPLA2 without enzymatic activity was constructed and was also incubated with HSCs to check whether activation of the HSCs was related to the enzymatic activity of MBP-CssPLA2. The recombinant protein MBP-CssPLA2 was expressed soluble and of good enzymatic activity. A mutant of CssPLA2, without enzymatic activity, was also constructed. In vivo liver sections of Balb/C mice that were given an abdominal injection of 50 μg/ml MBP-CssPLA2 showed an obvious accumulation of collagen and a clear band of P-JNK1 could be seen by western blot of the liver tissue. In vitro, MBP-CssPLA2, as well as the mutant, was incubated with HSCs and it was proved that activation of HSCs was related to activation of the JNK signalling pathway instead of the enzymatic activity of MBP-CssPLA2. Activation of HSCs by CssPLA2 is related to the activation of the JNK signalling pathway instead of the enzymatic activity of CssPLA2. This finding

  8. Adolescent exergame play for weight loss and psychosocial improvement: a controlled physical activity intervention.

    Science.gov (United States)

    Staiano, Amanda E; Abraham, Anisha A; Calvert, Sandra L

    2013-03-01

    Overweight and obese youth, who face increased risk of medical complications including heart disease and type II diabetes, can benefit from sustainable physical activity interventions that result in weight loss. This study examined whether a 20-week exergame (i.e., videogame that requires gross motor activity) intervention can produce weight loss and improve psychosocial outcomes for 54 overweight and obese African-American adolescents. Participants were recruited from a public high school and randomly assigned to competitive exergame, cooperative exergame, or control conditions. All exergame participants were encouraged to play the Nintendo Wii Active game for 30-60 min per school day in a lunch-time or after-school program. Cooperative exergame participants worked with a peer to expend calories and earn points together, whereas competitive exergame participants competed against a peer. Control participants continued regular daily activities. Outcome measures included changes in weight, peer support, self-efficacy, and self-esteem, measured at baseline, and at ∼10 and 20 weeks. Growth curve analysis revealed that cooperative exergame players lost significantly more weight (mean = 1.65 kg; s.d. = 4.52) than the control group, which did not lose weight. The competitive exergame players did not differ significantly from the other conditions. Cooperative exergame players also significantly increased in self-efficacy compared to the control group, and both exergame conditions significantly increased in peer support more than the control group. Exergames, especially played cooperatively, can be an effective technological tool for weight loss among youth. Copyright © 2012 The Obesity Society.

  9. Methylglyoxal and carboxyethyllysine reduce glutamate uptake and S100B secretion in the hippocampus independently of RAGE activation.

    Science.gov (United States)

    Hansen, Fernanda; Battú, Cíntia Eickhoff; Dutra, Márcio Ferreira; Galland, Fabiana; Lirio, Franciane; Broetto, Núbia; Nardin, Patrícia; Gonçalves, Carlos-Alberto

    2016-02-01

    Diabetes is a metabolic disease characterized by high fasting-glucose levels. Diabetic complications have been associated with hyperglycemia and high levels of reactive compounds, such as methylglyoxal (MG) and advanced glycation endproducts (AGEs) formation derived from glucose. Diabetic patients have a higher risk of developing neurodegenerative diseases, such as Alzheimer's disease or Parkinson's disease. Herein, we examined the effect of high glucose, MG and carboxyethyllysine (CEL), a MG-derived AGE of lysine, on oxidative, metabolic and astrocyte-specific parameters in acute hippocampal slices, and investigated some of the mechanisms that could mediate these effects. Glucose, MG and CEL did not alter reactive oxygen species (ROS) formation, glucose uptake or glutamine synthetase activity. However, glutamate uptake and S100B secretion were decreased after MG and CEL exposure. RAGE activation and glycation reactions, examined by aminoguanidine and L-lysine co-incubation, did not mediate these changes. Acute MG and CEL exposure, but not glucose, were able to induce similar effects on hippocampal slices, suggesting that conditions of high glucose concentrations are primarily toxic by elevating the rates of these glycation compounds, such as MG, and by generation of protein cross-links. Alterations in the secretion of S100B and the glutamatergic activity mediated by MG and AGEs can contribute to the brain dysfunction observed in diabetic patients.

  10. Not Just "A Walking the Dog": Dog Walking and Pet Play and Their Association With Recommended Physical Activity Among Adolescents.

    Science.gov (United States)

    Martin, Karen E; Wood, Lisa; Christian, Hayley; Trapp, Georgina S A

    2015-01-01

    To examine the role of pet play and dog walking in children's and adolescents' leisure time, and the relationship between these activities and physical activity. The study design was observational. The study setting was metropolitan Perth and nonmetropolitan regions in Western Australia. The study included 1097 primary school (mean age, 10.1 years; SD, 1.6 years) and 657 secondary school (mean age, 14.0 years; SD, 1.3 years) students. Validated measures of total physical activity, dog walking, and pet play activity (prevalence and time) were calculated. Generalized linear models tested for differences between proportions, while adjusting for socioeconomic status, age, and school-level clustering. Approximately one third of primary school and one quarter of secondary school students reported that they walked the dog at least once in the last week. Pet play was the most common play activity for primary and secondary school girls, and the second and third most popular play activity for secondary and primary school boys, respectively. Secondary school students who walked the dog or played with pets spent an average of 1 hour per week on each activity, and they were significantly more likely (p physical activity recommendations than secondary school students not reporting these activities. Given the significant proportion of young people who frequently engage in dog walking and pet play, and the high level of pet ownership in many Western countries, promotion of these activities to support young people's health is warranted.

  11. Corticosteroid-Induced MKP-1 Represses Pro-Inflammatory Cytokine Secretion by Enhancing Activity of Tristetraprolin (TTP) in ASM Cells.

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    Prabhala, Pavan; Bunge, Kristin; Ge, Qi; Ammit, Alaina J

    2016-10-01

    Exaggerated cytokine secretion drives pathogenesis of a number of chronic inflammatory diseases, including asthma. Anti-inflammatory pharmacotherapies, including corticosteroids, are front-line therapies and although they have proven clinical utility, the molecular mechanisms responsible for their actions are not fully understood. The corticosteroid-inducible gene, mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1, DUSP1) has emerged as a key molecule responsible for the repressive effects of steroids. MKP-1 is known to deactivate p38 MAPK phosphorylation and can control the expression and activity of the mRNA destabilizing protein-tristetraprolin (TTP). But whether corticosteroid-induced MKP-1 acts via p38 MAPK-mediated modulation of TTP function in a pivotal airway cell type, airway smooth muscle (ASM), was unknown. While pretreatment of ASM cells with the corticosteroid dexamethasone (preventative protocol) is known to reduce ASM synthetic function in vitro, the impact of adding dexamethasone after stimulation (therapeutic protocol) had not been explored. Whether dexamethasone modulates TTP in a p38 MAPK-dependent manner in this cell type was also unknown. We address this herein and utilize an in vitro model of asthmatic inflammation where ASM cells were stimulated with the pro-asthmatic cytokine tumor necrosis factor (TNF) and the impact of adding dexamethasone 1 h after stimulation assessed. IL-6 mRNA expression and protein secretion was significantly repressed by dexamethasone acting in a temporally distinct manner to increase MKP-1, deactivate p38 MAPK, and modulate TTP phosphorylation status. In this way, dexamethasone-induced MKP-1 acts via p38 MAPK to switch on the mRNA destabilizing function of TTP to repress pro-inflammatory cytokine secretion from ASM cells. J. Cell. Physiol. 231: 2153-2158, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Collagenolytic activities of the major secreted cathepsin L peptidases involved in the virulence of the helminth pathogen, Fasciola hepatica.

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    Mark W Robinson

    Full Text Available BACKGROUND: The temporal expression and secretion of distinct members of a family of virulence-associated cathepsin L cysteine peptidases (FhCL correlates with the entry and migration of the helminth pathogen Fasciola hepatica in the host. Thus, infective larvae traversing the gut wall secrete cathepsin L3 (FhCL3, liver migrating juvenile parasites secrete both FhCL1 and FhCL2 while the mature bile duct parasites, which are obligate blood feeders, secrete predominantly FhCL1 but also FhCL2. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that FhCL1, FhCL2 and FhCL3 exhibit differences in their kinetic parameters towards a range of peptide substrates. Uniquely, FhCL2 and FhCL3 readily cleave substrates with Pro in the P2 position and peptide substrates mimicking the repeating Gly-Pro-Xaa motifs that occur within the primary sequence of collagen. FhCL1, FhCL2 and FhCL3 hydrolysed native type I and II collagen at neutral pH but while FhCL1 cleaved only non-collagenous (NC, non-Gly-X-Y domains FhCL2 and FhCL3 exhibited collagenase activity by cleaving at multiple sites within the α1 and α2 triple helix regions (Col domains. Molecular simulations created for FhCL1, FhCL2 and FhCL3 complexed to various seven-residue peptides supports the idea that Trp67 and Tyr67 in the S2 subsite of the active sites of FhCL3 and FhCL2, respectively, are critical to conferring the unique collagenase-like activity to these enzymes by accommodating either Gly or Pro residues at P2 in the substrate. The data also suggests that FhCL3 accommodates hydroxyproline (Hyp-Gly at P3-P2 better than FhCL2 explaining the observed greater ability of FhCL3 to digest type I and II collagens compared to FhCL2 and why these enzymes cleave at different positions within the Col domains. CONCLUSIONS/SIGNIFICANCE: These studies further our understanding of how this helminth parasite regulates peptidase expression to ensure infection, migration and establishment in host tissues.

  13. Non-Cationic Proteins Are Associated with HIV Neutralizing Activity in Genital Secretions of Female Sex Workers.

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    Birse, Kenzie D M; Cole, Amy L; Hirbod, Taha; McKinnon, Lyle; Ball, Terry B; Westmacott, Garrett R; Kimani, Joshua; Plummer, Frank; Cole, Alexander M; Burgener, Adam; Broliden, Kristina

    2015-01-01

    Cationic proteins found in cervicovaginal secretions (CVS) are known to contribute to the early antiviral immune response against HIV-infection in vitro. We here aimed to define additional antiviral factors that are over-expressed in CVS from female sex workers at high risk of infection. CVS were collected from Kenyan HIV-seronegative (n = 34) and HIV-seropositive (n = 12) female sex workers, and were compared with those from HIV-seronegative low-risk women (n = 12). The highly exposed seronegative (HESN) sex workers were further divided into those with less (n = 22) or more (n = 12) than three years of documented sex work. Cationic protein-depleted CVS were assessed for HIV-neutralizing activity by a PBMC-based HIV-neutralizing assay, and then characterized by proteomics. HIV neutralizing activity was detected in all unprocessed CVS, however only CVS from the female sex worker groups maintained its HIV neutralizing activity after cationic protein-depletion. Differentially abundant proteins were identified in the cationic protein-depleted secretions including 26, 42, and 11 in the HESN>3 yr, HESNHIV-positive groups, respectively. Gene ontology placed these proteins into functional categories including proteolysis, oxidation-reduction, and epidermal development. The proteins identified in this study include proteins previously associated with the HESN phenotype in other cohorts as well as novel proteins not yet associated with anti-HIV activities. While cationic proteins appear to contribute to the majority of the intrinsic HIV neutralizing activity in the CVS of low-risk women, a broader range of non-cationic proteins were associated with HIV neutralizing activity in HESN and HIV-positive female sex workers. These results indicate that novel protein factors found in CVS of women with high-risk sexual practices may have inherent antiviral activity, or are involved in other aspects of anti-HIV host defense, and warrant further exploration into their mode of action.

  14. Ganoderma lucidum stimulates NK cell cytotoxicity by inducing NKG2D/NCR activation and secretion of perforin and granulysin.

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    Chang, Chih-Jung; Chen, Yi-Yuan M; Lu, Chia-Chen; Lin, Chuan-Sheng; Martel, Jan; Tsai, Sheng-Hui; Ko, Yun-Fei; Huang, Tsung-Teng; Ojcius, David M; Young, John D; Lai, Hsin-Chih

    2014-04-01

    Ganoderma lucidum (G. lucidum) is a medicinal mushroom long used in Asia as a folk remedy to promote health and longevity. Recent studies indicate that G. lucidum activates NK cells, but the molecular mechanism underlying this effect has not been studied so far. To address this question, we prepared a water extract of G. lucidum and examined its effect on NK cells. We observed that G. lucidum treatment increases NK cell cytotoxicity by stimulating secretion of perforin and granulysin. The mechanism of activation involves an increased expression of NKG2D and natural cytotoxicity receptors (NCRs), as well as increased phosphorylation of intracellular MAPKs. Our results indicate that G. lucidum induces NK cell cytotoxicity against various cancer cell lines by activating NKG2D/NCR receptors and MAPK signaling pathways, which together culminate in exocytosis of perforin and granulysin. These observations provide a cellular and molecular mechanism to account for the reported anticancer effects of G. lucidum extracts in humans.

  15. Light-regulated phosphorylation of maize phosphoenolpyruvate carboxykinase plays a vital role in its activity.

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    Chao, Qing; Liu, Xiao-Yu; Mei, Ying-Chang; Gao, Zhi-Fang; Chen, Yi-Bo; Qian, Chun-Rong; Hao, Yu-Bo; Wang, Bai-Chen

    2014-05-01

    Phosphoenolpyruvate carboxykinase (PEPCK)-the major decarboxylase in PEPCK-type C4 plants-is also present in appreciable amounts in the bundle sheath cells of NADP-malic enzyme-type C4 plants, such as maize (Zea mays), where it plays an apparent crucial role during photosynthesis (Wingler et al., in Plant Physiol 120(2):539-546, 1999; Furumoto et al., in Plant Mol Biol 41(3):301-311, 1999). Herein, we describe the use of mass spectrometry to demonstrate phosphorylation of maize PEPCK residues Ser55, Thr58, Thr59, and Thr120. Western blotting indicated that the extent of Ser55 phosphorylation dramatically increases in the leaves of maize seedlings when the seedlings are transferred from darkness to light, and decreases in the leaves of seedlings transferred from light to darkness. The effect of light on phosphorylation of this residue is opposite that of the effect of light on PEPCK activity, with the decarboxylase activity of PEPCK being less in illuminated leaves than in leaves left in the dark. This inverse relationship between PEPCK activity and the extent of phosphorylation suggests that the suppressive effect of light on PEPCK decarboxylation activity might be mediated by reversible phosphorylation of Ser55.

  16. Highly active promoters and native secretion signals for protein production during extremely low growth rates in Aspergillus niger.

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    Wanka, Franziska; Arentshorst, Mark; Cairns, Timothy C; Jørgensen, Thomas; Ram, Arthur F J; Meyer, Vera

    2016-08-20

    The filamentous ascomycete Aspergillus niger is used in many industrial processes for the production of enzymes and organic acids by batch and fed-batch cultivation. An alternative technique is continuous cultivation, which promises improved yield and optimized pipeline efficiency. In this work, we have used perfusion (retentostat) cultivation to validate two promoters that are suitable for A. niger continuous cultivation of industrially relevant products. Firstly, promoters of genes encoding either an antifungal protein (Panafp) or putative hydrophobin (PhfbD) were confirmed as active throughout retentostat culture by assessing mRNA and protein levels using a luciferase (mluc) reporter system. This demonstrated the anafp promoter mediates a high but temporally variable expression profile, whereas the hfbD promoter mediates a semi-constant, moderate-to-high protein expression during retentostat culture. In order to assess whether these promoters were suitable to produce heterologous proteins during retentostat cultivation, the secreted antifungal protein (AFP) from Aspergillus giganteus, which has many potential biotechnological applications, was expressed in A. niger during retentostat cultivation. Additionally, this assay was used to concomitantly validate that native secretion signals encoded in anafp and hfbD genes can be harnessed for secretion of heterologous proteins. Afp mRNA and protein abundance were comparable to luciferase measurements throughout retentostat cultivation, validating the use of Panafp and PhfbD for perfusion cultivation. Finally, a gene encoding the highly commercially relevant thermal hysteresis protein (THP) was expressed in this system, which did not yield detectable protein. Both hfbD and anafp promoters are suitable for production of useful products in A. niger during perfusion cultivation. These findings provide a platform for further optimisations for high production of heterologous proteins with industrial relevance.

  17. Social Behaviors and Active Videogame Play in Children with Autism Spectrum Disorder.

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    Chung, Peter J; Vanderbilt, Douglas L; Soares, Neelkamal S

    2015-06-01

    Children with autism spectrum disorder (ASD) often display problematic and excessive videogame play. Using active videogames (AVGs) may have physical benefits, but its effects on socialization are unknown. We conducted an A-B-A' experiment comparing sedentary videogames and AVGs for three dyads of a child with ASD and his sibling. An augmented reality (AR) game was used to introduce AVGs. Sessions were coded for communication, positive affect, and aggression. One dyad had increases in positive affect with AVGs. Otherwise, social behaviors were unchanged or worse. The AR game demonstrated consistent elevations in social behaviors. Use of AVGs has inconsistent effects on social behavior for children with ASD. Further research is needed to understand mediators of response to AVGs. AR games should be evaluated for potential benefits on socialization and positive affect.

  18. Individual, social and physical environmental correlates of children's active free-play: a cross-sectional study

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    Ball Kylie

    2010-02-01

    Full Text Available Abstract Background Children's unstructured outdoor free-play (or active free-play has the potential to make an important contribution to children's overall physical activity levels. Limited research has, however, examined physical activity in this domain. This study examined associations between individual, social and physical environmental factors and the frequency with which children play in particular outdoor locations outside school hours. This study also investigated whether the frequency of playing in outdoor locations was associated with children's overall physical activity levels. Methods Participants including 8-9 year old children and their parents (n = 187 were recruited from a selection of primary schools of varying socioeconomic status across metropolitan Melbourne, Australia. Parents completed a survey and children's overall physical activity levels were measured by accelerometry. Regression models examined the odds of children playing in various outdoor settings according to particular correlates. Results Inverse associations were found between preference for activities not involving physical activity, and the likelihood of children playing in the yard at home on the weekend (OR = 0.65; CI = 0.45,0.95. Positive correlates of children playing in their own street included: parental perceptions that it was safe for their child to play in their street (weekdays [OR = 6.46; CI = 2.84,14.71], weekend days [OR = 6.01; CI = 2.68,13.47]; children having many friends in their neighbourhood (OR = 2.63; CI = 1.21,5.76; and living in a cul-de-sac (weekdays [OR = 3.99; CI = 1.65,9.66], weekend days [OR = 3.49; CI = 1.49,8.16]. Positive correlates of more frequent play in the park/playground on weekdays included family going to the park together on a weekly basis on weekdays (OR = 6.8; CI = 3.4,13.6; and on weekend days (OR = 7.36; CI = 3.6,15.0. No differences in mean mins/day of moderate-vigorous physical activity were found between children

  19. Pancreatic bicarbonate secretion involves two proton pumps.

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    Novak, Ivana; Wang, Jing; Henriksen, Katrine L; Haanes, Kristian A; Krabbe, Simon; Nitschke, Roland; Hede, Susanne E

    2011-01-07

    Pancreas secretes fluid rich in digestive enzymes and bicarbonate. The alkaline secretion is important in buffering of acid chyme entering duodenum and for activation of enzymes. This secretion is formed in pancreatic ducts, and studies to date show that plasma membranes of duct epithelium express H(+)/HCO(3)(-) transporters, which depend on gradients created by the Na(+)/K(+)-ATPase. However, the model cannot fully account for high-bicarbonate concentrations, and other active transporters, i.e. pumps, have not been explored. Here we show that pancreatic ducts express functional gastric and non-gastric H(+)-K(+)-ATPases. We measured intracellular pH and secretion in small ducts isolated from rat pancreas and showed their sensitivity to H(+)-K(+) pump inhibitors and ion substitutions. Gastric and non-gastric H(+)-K(+) pumps were demonstrated on RNA and protein levels, and pumps were localized to the plasma membranes of pancreatic ducts. Quantitative analysis of H(+)/HCO(3)(-) and fluid transport shows that the H(+)-K(+) pumps can contribute to pancreatic secretion in several species. Our results call for revision of the bicarbonate transport physiology in pancreas, and most likely other epithelia. Furthermore, because pancreatic ducts play a central role in several pancreatic diseases, it is of high relevance to understand the role of H(+)-K(+) pumps in pathophysiology.

  20. MAML1 enhances the transcriptional activity of Runx2 and plays a role in bone development.

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    Takashi Watanabe

    Full Text Available Mastermind-like 1 (MAML1 is a transcriptional co-activator in the Notch signaling pathway. Recently, however, several reports revealed novel and unique roles for MAML1 that are independent of the Notch signaling pathway. We found that MAML1 enhances the transcriptional activity of runt-related transcription factor 2 (Runx2, a transcription factor essential for osteoblastic differentiation and chondrocyte proliferation and maturation. MAML1 significantly enhanced the Runx2-mediated transcription of the p6OSE2-Luc reporter, in which luciferase expression was controlled by six copies of the osteoblast specific element 2 (OSE2 from the Runx2-regulated osteocalcin gene promoter. Interestingly, a deletion mutant of MAML1 lacking the N-terminal Notch-binding domain also enhanced Runx2-mediated transcription. Moreover, inhibition of Notch signaling did not affect the action of MAML1 on Runx2, suggesting that the activation of Runx2 by MAML1 may be caused in a Notch-independent manner. Overexpression of MAML1 transiently enhanced the Runx2-mediated expression of alkaline phosphatase, an early marker of osteoblast differentiation, in the murine pluripotent mesenchymal cell line C3H10T1/2. MAML1(-/- embryos at embryonic day 16.5 (E16.5 had shorter bone lengths than wild-type embryos. The area of primary spongiosa of the femoral diaphysis was narrowed. At E14.5, extended zone of collagen type II alpha 1 (Col2a1 and Sox9 expression, markers of chondrocyte differentiation, and decreased zone of collagen type X alpha 1 (Col10a1 expression, a marker of hypertrophic chondrocyte, were observed. These observations suggest that chondrocyte maturation was impaired in MAML1(-/- mice. MAML1 enhances the transcriptional activity of Runx2 and plays a role in bone development.

  1. Early to Late Endosome Trafficking Controls Secretion and Zymogen Activation in Rodent and Human Pancreatic Acinar CellsSummary

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    Scott W. Messenger

    2015-11-01

    Full Text Available Background & Aims: Pancreatic acinar cells have an expanded apical endosomal system, the physiologic and pathophysiologic significance of which is still emerging. Phosphatidylinositol-3,5-bisphosphate [PI(3,5P2] is an essential phospholipid generated by phosphatidylinositol 3-phosphate 5-kinase (PIKfyve, which phosphorylates phosphatidylinositol-3-phosphate (PI3P. PI(3,5P2 is necessary for maturation of early endosomes (EE to late endosomes (LE. Inhibition of EE to LE trafficking enhances anterograde endosomal trafficking and secretion at the plasma membrane by default through a recycling endosome (RE intermediate. We assessed the effects of modulating PIKfyve activity on apical trafficking and pancreatitis responses in pancreatic acinar cells. Methods: Inhibition of EE to LE trafficking was achieved using pharmacologic inhibitors of PIKfyve, expression of dominant negative PIKfyve K1877E, or constitutively active Rab5-GTP Q79L. Anterograde endosomal trafficking was manipulated by expression of constitutively active and dominant negative Rab11a mutants. The effects of these agents on secretion, endolysosomal exocytosis of lysosome associated membrane protein (LAMP1, and trypsinogen activation in response to supramaximal cholecystokinin (CCK-8, bile acids, and cigarette toxin was determined. Results: PIKfyve inhibition increased basal and stimulated secretion. Adenoviral overexpression of PIKfyve decreased secretion leading to cellular death. Expression of Rab5-GTP Q79L or Rab11a-GTP Q70L enhanced secretion. Conversely, dominant-negative Rab11a-GDP S25N reduced secretion. High-dose CCK inhibited endolysosomal exocytosis that was reversed by PIKfyve inhibition. PIKfyve inhibition blocked intracellular trypsin accumulation and cellular damage responses to supramaximal CCK-8, tobacco toxin, and bile salts in both rodent and human acini. Conclusions: These data demonstrate that EE-LE trafficking acutely controls acinar secretion and the intracellular

  2. Acute but not chronic activation of brain glucagon-like peptide-1 receptors enhances glucose-stimulated insulin secretion in mice.

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    Tudurí, E; Beiroa, D; Porteiro, B; López, M; Diéguez, C; Nogueiras, R

    2015-08-01

    To investigate the role of brain glucagon-like peptide-1 (GLP-1) in pancreatic β-cell function. To determine the role of brain GLP-1 receptor (GLP-1R) on β-cell function, we administered intracerebroventricular (i.c.v.) infusions of GLP-1 or the specific GLP-1 antagonist exendin-9 (Ex-9), in both an acute and a chronic setting. We observed that acute i.c.v. GLP-1 infusion potentiates glucose-stimulated insulin secretion (GSIS) and improves glucose tolerance, whereas central GLP-1R blockade with Ex-9 impaired glucose excursion after a glucose load. Sustained activation of central nervous system GLP-1R, however, did not produce any effect on either GSIS or glucose tolerance. Similarly, ex vivo GSIS performed in islets from mice chronically infused with i.c.v. GLP-1 resulted in no differences compared with controls. In addition, in mice fed a high-fat diet we observed that acute i.c.v. GLP-1 infusion improved glucose tolerance without changes in GSIS, while chronic GLP-1R activation had no effect on glucose homeostasis. Our results indicate that, under non-clamped conditions, brain GLP-1 plays a functional neuroendocrine role in the acute regulation of glucose homeostasis in both lean and obese rodents. © 2015 John Wiley & Sons Ltd.

  3. The energy cost of playing active video games in children with obesity and children of a healthy weight.

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    O'Donovan, C; Roche, E F; Hussey, J

    2014-08-01

    Increasing physical activity and reducing sedentary behaviour form a large part of the treatment of paediatric obesity. However, many children today spend prolonged periods of time playing sedentary video games. Active video games (AVGs) represent a novel and child friendly form of physical activity. To measure the energy cost of playing two AVGs in children with obesity and healthy age- and gender-matched children. The energy cost of gaming and heart rates achieved during gaming conditions were compared between groups. AVG play can result in light-to-moderate intensity physical activity (2.7-5.4 metabolic equivalents). When corrected for fat-free mass those with obesity expended significantly less energy than healthy weight peers playing Nintendo Wii Fit Free Jogging (P = 0.017). No significant difference was seen between groups in the energy cost of playing Boxing. Certain AVGs, particularly those that require lower limb movement, could be used to increase total energy expenditure, replace more sedentary activities, or achieve moderate intensity physical activity among children with obesity. There seems to be some differences in how children with obesity and children of a healthy weight play AVGs. This could result in those with obesity expending less energy than their lean peers during AVG play. © 2013 The Authors. Pediatric Obesity © 2013 International Association for the Study of Obesity.

  4. Do family environment factors play a role in adolescents' involvement in organized activities?

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    Badura, Petr; Madarasova Geckova, Andrea; Sigmundova, Dagmar; Sigmund, Erik; van Dijk, Jitse P; Reijneveld, Sijmen A

    2017-08-01

    The study assessed the association of family environment factors with adolescents' participation in organized leisure-time activities (OLTA). We used data on 10,472 Czech adolescents aged 11-15 years (49.2% boys) from the 2013/2014 Health Behaviour in School-aged Children study. The associations of family support, the presence of parental screen-time rules and joint family activities with participation in at least one OLTA were assessed using logistic regression. High family support and the presence of parental screen-time rules were associated with higher odds of OLTA participation. Moreover, adolescents playing sports, indoor games and going for walks with their families at least weekly were more likely to participate in OLTA. Conversely, those spending time in joint family TV/video watching on most days were less likely to do so. A supportive family environment and direct parental involvement in their adolescent children's leisure are associated with OLTA participation in early to middle adolescence. Copyright © 2017 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  5. A robust active control system for shimmy damping in the presence of free play and uncertainties

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    Orlando, Calogero; Alaimo, Andrea

    2017-02-01

    Shimmy vibration is the oscillatory motion of the fork-wheel assembly about the steering axis. It represents one of the major problem of aircraft landing gear because it can lead to excessive wear, discomfort as well as safety concerns. Based on the nonlinear model of the mechanics of a single wheel nose landing gear (NLG), electromechanical actuator and tire elasticity, a robust active controller capable of damping shimmy vibration is designed and investigated in this study. A novel Decline Population Swarm Optimization (PDSO) procedure is introduced and used to select the optimal parameters for the controller. The PDSO procedure is based on a decline demographic model and shows high global search capability with reduced computational costs. The open and closed loop system behavior is analyzed under different case studies of aeronautical interest and the effects of torsional free play on the nose landing gear response are also studied. Plant parameters probabilistic uncertainties are then taken into account to assess the active controller robustness using a stochastic approach.

  6. Attitudes of Students Studying in Coaching And Sport Management Department Towards Playing Games Involving Physical Activity

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    Hüseyin ÖZTÜRK

    2016-12-01

    Full Text Available This study has been prepared to determine attitudes of students studying in Coaching and Sport Management departments towards playing game including physcical activity. The sample of study consists of 388 students having sudied in Gaziantep University Coaching and Sport Management Department in 2014-2015 academic year.So as to determine the attitudes of students, the’’Playfulnessscale" was used. Statistical analysis of the data obtained in this study was made by using the SPSS 22.0 software packages. While evaluating the data for statistical analyzes, for frequency, percentage, mean, standard deviation, and comparison of two independent groups the t-test was used and for comparison of more than two independent groups ANOVA and LSD multiple comparison tests were used. According to results of study, It seems that statistically there is no significant difference between student’s genders,ages and their attitudes towards palying game including physical activity and according to their departments there is no significant difference among their attitudes but there is a significant difference between the fundimension and social cohesion dimension.

  7. Does playing a sports active video game improve object control skills of children with autism spectrum disorder?

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    Jacqueline Edwards

    2017-03-01

    Conclusion: The use of AVGs as a play-based intervention may not provide enough opportunity for children to perform the correct movement patterns to influence skill. However, play of such games may influence perceptions of skill ability in children with ASD, which could improve motivation to participate in physical activities.

  8. Drawing as Social Play: Shared Meaning-Making in Young Children's Collective Drawing Activities

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    Kukkonen, Tiina; Chang-Kredl, Sandra

    2018-01-01

    The ability to construct shared meaning with peers is important for young children's social and linguistic development. Previous studies have mainly focused on shared meaning-making within cooperative pretend play with little mention of other childhood activities that might promote intersubjectivity. This study investigated the group play that…

  9. Efflux pumps of Mycobacterium tuberculosis play a significant role in antituberculosis activity of potential drug candidates.

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    Balganesh, Meenakshi; Dinesh, Neela; Sharma, Sreevalli; Kuruppath, Sanjana; Nair, Anju V; Sharma, Umender

    2012-05-01

    Active efflux of drugs mediated by efflux pumps that confer drug resistance is one of the mechanisms developed by bacteria to counter the adverse effects of antibiotics and chemicals. To understand these efflux mechanisms in Mycobacterium tuberculosis, we generated knockout (KO) mutants of four efflux pumps of the pathogen belonging to different classes. We measured the MICs and kill values of two different compound classes on the wild type (WT) and the efflux pump (EP) KO mutants in the presence and absence of the efflux inhibitors verapamil and l-phenylalanyl-l-arginyl-β-naphthylamide (PAβN). Among the pumps studied, the efflux pumps belonging to the ABC (ATP-binding cassette) class, encoded by Rv1218c, and the SMR (small multidrug resistance) class, encoded by Rv3065, appear to play important roles in mediating the efflux of different chemical classes and antibiotics. Efflux pumps encoded by Rv0849 and Rv1258c also mediate the efflux of these compounds, but to a lesser extent. Increased killing is observed in WT M. tuberculosis cells by these compounds in the presence of either verapamil or PAβN. The efflux pump KO mutants were more susceptible to these compounds in the presence of efflux inhibitors. We have shown that these four efflux pumps of M. tuberculosis play a vital role in mediating efflux of different chemical scaffolds. Inhibitors of one or several of these efflux pumps could have a significant impact in the treatment of tuberculosis. The identification and characterization of Rv0849, a new efflux pump belonging to the MFS (major facilitator superfamily) class, are reported.

  10. Children with developmental coordination disorder play active virtual reality games differently than children with typical development.

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    Gonsalves, Leandra; Campbell, Amity; Jensen, Lynn; Straker, Leon

    2015-03-01

    Active virtual reality gaming (AVG) may be useful for children with developmental coordination disorder (DCD) to practice motor skills if their movement patterns are of good quality while engaged in AVG. This study aimed to examine: (1) the quality of motor patterns of children with DCD participating in AVG by comparing them with children with typical development (TD) and (2) whether differences existed in the motor patterns utilized with 2 AVG types: Sony PlayStation 3 Move and Microsoft Xbox 360 Kinect. This was a quasi-experimental, biomechanical laboratory-based study. Twenty-one children with DCD, aged 10 to 12 years, and 19 age- and sex-matched children with TD played a match of table tennis on each AVG type. Hand path, wrist angle, and elbow angle were recorded using a motion analysis system. Linear mixed-model analyses were used to determine differences between DCD and TD groups and Move and Kinect AVG type for forehands and backhands. Children with DCD utilized a slower hand path speed (backhand mean difference [MD]=1.20 m/s; 95% confidence interval [95% CI]=0.41, 1.98); greater wrist extension (forehand MD=34.3°; 95% CI=22.6, 47.0); and greater elbow flexion (forehand MD=22.3°; 95% CI=7.4, 37.1) compared with children with TD when engaged in AVG. There also were differences in movement patterns utilized between AVG types. Only simple kinematic measures were compared, and no data regarding movement outcome were assessed. If a therapeutic treatment goal is to promote movement quality in children with DCD, clinical judgment is required to select the most appropriate AVG type and determine whether movement quality is adequate for unsupervised practice. © 2015 American Physical Therapy Association.

  11. MCL Plays an Anti-Inflammatory Role in Mycobacterium tuberculosis-Induced Immune Response by Inhibiting NF-κB and NLRP3 Inflammasome Activation

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    Qingwen Zhang

    2017-01-01

    Full Text Available Mycobacterium tuberculosis (Mtb remains a significant menace to global health as it induces granulomatous lung lesions and systemic inflammatory responses during active tuberculosis (TB. Micheliolide (MCL, a sesquiterpene lactone, was recently reported to have a function of relieving LPS-induced inflammatory response, but the regulative role of MCL on the immunopathology of TB still remains unknown. In this experiment, we examined the inhibitory effect of MCL on Mtb-induced inflammatory response in mouse macrophage-like cell line Raw264.7 by downregulating the activation of nuclear factor kappa B (NF-κB and NLRP3 inflammasome. Evidences showed that MCL decreased the secretion of Mtb-induced inflammatory cytokines (IL-1β and TNF-α in a dose-dependent manner. Meanwhile, MCL dramatically suppressed Mtb-induced activation of iNOS and COX2 as well as subsequent production of NO. Furthermore, MCL inhibited Mtb-induced phosphorylation of Akt (Ser 473 in Raw264.7. According to our results, MCL plays an important role in modulating Mtb-induced inflammatory response through PI3K/Akt/NF-κB pathway and subsequently downregulating the activation of NLRP3 inflammasome. Therefore, MCL may represent as a potential drug candidate in the adjuvant treatment of TB by regulating host immune response.

  12. Anti-HIV activity in cervical-vaginal secretions from HIV-positive and -negative women correlate with innate antimicrobial levels and IgG antibodies.

    Directory of Open Access Journals (Sweden)

    Mimi Ghosh

    2010-06-01

    Full Text Available We investigated the impact of antimicrobials in cervicovaginal lavage (CVL from HIV(+ and HIV(- women on target cell infection with HIV. Since female reproductive tract (FRT secretions contain a spectrum of antimicrobials, we hypothesized that CVL from healthy HIV(+ and (- women inhibit HIV infection.CVL from 32 HIV(+ healthy women with high CD4 counts and 15 healthy HIV(- women were collected by gently washing the cervicovaginal area with 10 ml of sterile normal saline. Following centrifugation, anti-HIV activity in CVL was determined by incubating CVL with HIV prior to addition to TZM-bl cells. Antimicrobials and anti-gp160 HIV IgG antibodies were measured by ELISA. When CXCR4 and CCR5 tropic HIV-1 were incubated with CVL from HIV(+ women prior to addition to TZM-bl cells, anti-HIV activity in CVL ranged from none to 100% inhibition depending on the viral strains used. CVL from HIV(- controls showed comparable anti-HIV activity. Analysis of CH077.c (clone of an R5-tropic, mucosally-transmitted founder virus viral inhibition by CVL was comparable to laboratory strains. Measurement of CVL for antimicrobials HBD2, trappin-2/elafin, SLPI and MIP3alpha indicated that each was present in CVL from HIV(+ and HIV(- women. HBD2 and MIP3alpha correlated with anti-HIV activity as did anti-gp160 HIV IgG antibodies in CVL from HIV(+ women.These findings indicate that CVL from healthy HIV(+ and HIV(- women contain innate and adaptive defense mechanisms that inhibit HIV infection. Our data suggest that innate endogenous antimicrobials and HIV-specific IgG in the FRT can act in concert to contribute toward the anti-HIV activity of the CVL and may play a role in inhibition of HIV transmission to women.

  13. Measuring phospholipase D activity in insulin-secreting pancreatic beta-cells and insulin-responsive muscle cells and adipocytes.

    Science.gov (United States)

    Cazzolli, Rosanna; Huang, Ping; Teng, Shuzhi; Hughes, William E

    2009-01-01

    Phospholipase D (PLD) is an enzyme producing phosphatidic acid and choline through hydrolysis of phosphatidylcholine. The enzyme has been identified as a member of a variety of signal transduction cascades and as a key regulator of numerous intracellular vesicle trafficking processes. A role for PLD in regulating glucose homeostasis is emerging as the enzyme has recently been identified in events regulating exocytosis of insulin from pancreatic beta-cells and also in insulin-stimulated glucose uptake through controlling GLUT4 vesicle exocytosis in muscle and adipose tissue. We present methodologies for assessing cellular PLD activity in secretagogue-stimulated insulin-secreting pancreatic beta-cells and also insulin-stimulated adipocyte and muscle cells, two of the principal insulin-responsive cell types controlling blood glucose levels.

  14. Antimicrobial activity and high thermostability of a novel BLIS secreted by Enterococcus Mundtii isolated from Lebanese cow’s milk

    Directory of Open Access Journals (Sweden)

    Imad AL Kassaa

    2016-12-01

    Full Text Available AL Kassaa, I., Safourim, N., Mostafa, N. and Hamze, M. Antimicrobial activity and high thermostability of a novel BLIS secreted by Enterococcus Mundtii isolated from lebanese cow’s milk. 2016. Lebanese Science Journal, 17(2: 166-176. Lactic acid bacteria (LAB are used in many fields such as fermentation agents, increasing nutritional value and improving organoleptic quality of food. Also they are used as probiotics and preservatives against pathogens and spoilage microbes by producing antimicrobial substances such as bacteriocins. Fifty cow’s milk samples were collected and 175 LAB isolates were isolated and identified by using biochemical method. Fifteen isolates showed an antimicrobial activity against Listeria monocytogenes ATCC® 19115™. One strain, BL4 which showed the strongest activity, was chosen to extract and characterize its antimicrobial substance in order to evaluate its potential use as a new food protective agent. This strain was identified as Enterococcus mundtii by pyrosequencing method. The active substance was extracted using solvent method. This Bacteriocin like Inhibitory Substances “BLIS” can support a high temperature (121 ˚C for a long time and resist pH variation. The BLIS BL4 can be considered as a peptide active against many food pathogen and food-spoilage microbes, such as Listeria monocytogenes and Penicillium spp. BLIS BL4 can be used in food application as bio-preservative to reduce food-spoilage and food-borne diseases in food products.

  15. Exploring the Impact of Role-Playing on Peer Feedback in an Online Case-Based Learning Activity

    Directory of Open Access Journals (Sweden)

    Yu-Hui Ching

    2014-07-01

    Full Text Available This study explored the impact of role-playing on the quality of peer feedback and learners’ perception of this strategy in a case-based learning activity with VoiceThread in an online course. The findings revealed potential positive impact of role-playing on learners’ generation of constructive feedback as role-playing was associated with higher frequency of problem identification in the peer comments. Sixty percent of learners perceived the role-play strategy useful in assisting them to compose and provide meaningful feedback. Multiple motivations drove learners in making decisions on role choice when responding to their peers, mostly for peer benefits. Finally, 90% of learners reported the peer feedback useful or somewhat useful. Based on the findings of this study, we discussed educational and instructional design implications and future directions to further the line of research using role-play strategy to enhance peer feedback activity.

  16. Physical Activity Levels in Children With and Without Autism Spectrum Disorder When Playing Active and Sedentary Xbox Kinect Videogames.

    Science.gov (United States)

    Golden, Daphne; Getchell, Nancy

    2017-04-01

    We compare physical activity during bouts of sedentary videogaming (SVG), active videogaming (AVG), and paced walking in children with and without autism spectrum disorder (ASD) to determine the effectiveness of AVG in providing moderate-to-vigorous physical activity. Participants included nine males (8-11 years old) with ASD and eight age-matched males who were typically developing. Both groups had anthropometric and motor proficiency (Movement Assessment Battery for Children II) measures taken before testing. Participants attended three randomly assigned acquisition sessions: 20 minutes of paced walking at 4.5 metabolic equivalents, AVG, and SVG. Videogaming occurred on an Xbox ® Kinect. An Actical accelerometer provided activity counts (AC) and percentage of time in moderate-to-vigorous physical activity (%MVPA). These were compared using 3 × 2 repeated measures analysis of variance for each measure. Main effects for conditions existed for %MVPA (P < 0.0001) and AC (P < 0.0001). Post hoc Bonferroni comparisons indicated that AVG had significantly higher AC (P < 0.001) and % MVPA (P < 0.001) than SVG, but was significantly lower than paced walking (AC P < 0.001; %MVPA P < 0.01). Overall, participants spent 76.25% of their time in MVPA during AVG compared to 99.4% during paced walking and 2.31% in SVG. No main effects for groups or group by condition interaction effects were found for either measure. AVG may provide an appealing means by which all individuals can increase their overall physical activity levels, although AVG should not be seen as a replacement for walking or other forms of PA. Although further research is necessary, the finding that both groups performed similarly in AVG suggests that games can potentially be played without modifications or adaptations to gaming units, which may provide several advantages in terms of social/cost/ease of accessing unit.

  17. Brain Activity in Fairness Consideration during Asset Distribution: Does the Initial Ownership Play a Role?

    Science.gov (United States)

    Wu, Yin; Hu, Jie; van Dijk, Eric; Leliveld, Marijke C.; Zhou, Xiaolin

    2012-01-01

    Previous behavioral studies have shown that initial ownership influences individuals’ fairness consideration and other-regarding behavior. However, it is not entirely clear whether initial ownership influences the brain activity when a recipient evaluates the fairness of asset distribution. In this study, we randomly assigned the bargaining property (monetary reward) to either the allocator or the recipient in the ultimatum game and let participants of the study, acting as recipients, receive either disadvantageous unequal, equal, or advantageous unequal offers from allocators while the event-related potentials (ERPs) were recorded. Behavioral results showed that participants were more likely to reject disadvantageous unequal and equal offers when they initially owned the property as compared to when they did not. The two types of unequal offers evoked more negative going ERPs (the MFN) than the equal offers in an early time window and the differences were not modulated by the initial ownership. In a late time window, however, the P300 responses to division schemes were affected not only by the type of unequal offers but also by whom the property was initially assigned to. These findings suggest that while the MFN may function as a general mechanism that evaluates whether the offer is consistent or inconsistent with the equity rule, the P300 is sensitive to top-down controlled processes, into which factors related to the allocation of attentional resources, including initial ownership and personal interests, come to play. PMID:22761850

  18. Learning through role-playing games: an approach for active learning and teaching

    Directory of Open Access Journals (Sweden)

    Marco Antonio Ferreira Randi

    Full Text Available This study evaluates the use of role-playing games (RPGs as a methodological approach for teaching cellular biology, assessing student satisfaction, learning outcomes, and retention of acquired knowledge. First-year undergraduate medical students at two Brazilian public universities attended either an RPG-based class (RPG group or a lecture (lecture-based group on topics related to cellular biology. Pre- and post-RPG-based class questionnaires were compared to scores in regular exams and in an unannounced test one year later to assess students' attitudes and learning. From the 230 students that attended the RPG classes, 78.4% responded that the RPG-based classes were an effective tool for learning; 55.4% thought that such classes were better than lectures but did not replace them; and 81% responded that they would use this method. The lecture-based group achieved a higher grade in 1 of 14 regular exam questions. In the medium-term evaluation (one year later, the RPG group scored higher in 2 of 12 questions. RPG classes are thus quantitatively as effective as formal lectures, are well accepted by students, and may serve as educational tools, giving students the chance to learn actively and potentially retain the acquired knowledge more efficiently.

  19. PRIDE FOR PLAY: PERSONAL RESPONSIBILITY IN DAILY EFFORT FOR PARTICIPATION IN LIFELONG ACTIVITY FOR YOUTHS. A SINGAPOREAN CONTEXT

    Directory of Open Access Journals (Sweden)

    Michael Chia

    2007-09-01

    Full Text Available Singapore, a developed city state of four million people is experiencing the pitfalls that come with rapid modernisation and economic progress- elevated disease risk factors among adults and young people. Weekly compulsory physical education classes of 70 minutes in schools and the associated sports activities after classes are inadequate to meet emergent physical activity guidelines of a daily accumulation of at least 90 minutes of physical activity of at least moderate intensity. Daily play sessions that are exclusive of an active daily recess, physical education classes taught by trained specialists and after-school sport sessions, can provide many developmental and holistic health benefits that may carry over into adulthood. A school environment that is play-encouraging, play-enabling and play-inviting can be a useful, innovative and natural way of inculcating a love for movement and help redress a serious trend of physical activity insufficiency while youngsters engage electronic gaming activities. Pilot initiatives for the PRIDE (personal responsibility in daily effort for PLAY (participation in lifelong activity for youths programme is a radicalised approach in a number of primary schools in Singapore to infuse daily physical play of between 20 to 45 minutes during curriculum hours. The hope is that PRIDE for PLAY will reap benefits of improved holistic health of youngsters- better physical, social, emotional and mental attributes. While PRIDE for PLAY is no panacea to all of the ills of modernisation, it will go some way in helping the students of tomorrow to be physically healthy, socially more engaged and tolerant of others, mentally more apt to problem-solve and emotionally more proficient to embrace working life in adulthood

  20. Contributing Factors on Malaysia Preschool Teachers' Belief, Attitude and Competence in Using Play Activities

    Science.gov (United States)

    Jantan, Hafsah Binti; Bin Hamdan, Abdul Rahim; Yahya, Fauziah Hj; Saleh, Halimatussadiah Binti; Ong, Mohd Hanafi Bin Azman

    2015-01-01

    This study focused on preschool teachers' belief, attitude, knowledge and competence in using play in Malaysia. Its purpose is to find out indicators significantly contribute to belief, attitude, knowledge and competence in play of preschool teachers in Malaysia. The method used was factor analysis in order to confirm indicators in each variable…

  1. Enhancing Role-Play Activities with Pocket Camcorder Technology: Strategies for Counselor-Educators

    Science.gov (United States)

    Walter, Sara Meghan; Thanasiu, Page L.

    2011-01-01

    Counselor-educators can benefit from specific guidelines and creative suggestions when implementing role-play and technology-related teaching strategies in counseling training programs. Therefore, the purpose of this article is to: (a) discuss the use of role-play and video recording in counselor education; (b) introduce counselor-educators to…

  2. Glioma-secreted soluble factors stimulate microglial activation: The role of interleukin-1β and tumor necrosis factor-α.

    Science.gov (United States)

    Hwang, Ji-Sun; Jung, Eun-Hye; Kwon, Mi-Youn; Han, Inn-Oc

    2016-09-15

    We aimed to elucidate the effect of soluble factors secreted by glioma on microglial activation. Conditioned medium (CM) from glioma cells, CRT-MG and C6, significantly induced nitric oxide (NO) production and stimulated the mRNA expression of inducible NO synthase (iNOS), interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-α) and cyclooxygenase 2 (COX-2) in BV2 cells. Glioma CM stimulated p38 mitogen-activated protein kinase (MAPK) phosphorylation, and a p38 MAPK inhibitor, SB203580, suppressed CM-induced NO production in BV2 cells. In addition, CM stimulated nuclear factor-kappaB (NF-κB) DNA binding and transcriptional activity, which was repressed by SB203580. Gliomas displayed higher mRNA expression and release of TNF-α and IL-1β than primary astrocyte cells. Neutralization of TNF-α and IL-1β in C6-CM using a neutralizing antibody inhibited NO/iNOS expression in BV-2 cells. These results indicate potential contribution of diffusible tumor-derived factors to regulate microglial activation and subsequent tumor microenvironment. Copyright © 2016. Published by Elsevier B.V.

  3. Estimating Whether Replacing Time in Active Outdoor Play and Sedentary Video Games With Active Video Games Influences Youth's Mental Health.

    Science.gov (United States)

    Janssen, Ian

    2016-11-01

    The primary objective was to use isotemporal substitution models to estimate whether replacing time spent in sedentary video games (SVGs) and active outdoor play (AOP) with active video games (AVGs) would be associated with changes in youth's mental health. A representative sample of 20,122 Canadian youth in Grades 6-10 was studied. The exposure variables were average hours/day spent playing AVGs, SVGs, and AOP. The outcomes consisted of a negative and internalizing mental health indicator (emotional problems), a positive and internalizing mental health indicator (life satisfaction), and a positive and externalizing mental health indicator (prosocial behavior). Isotemporal substitution models estimated the extent to which replacing time spent in SVGs and AOP with an equivalent amount of time in AVGs had on the mental health indicators. Replacing 1 hour/day of SVGs with 1 hour/day of AVGs was associated with a 6% (95% confidence interval: 3%-9%) reduced probability of high emotional problems, a 4% (2%-7%) increased probability of high life satisfaction, and a 13% (9%-16%) increased probability of high prosocial behavior. Replacing 1 hour/day of AOP with 1 hour/day of AVGs was associated with a 7% (3%-11%) increased probability of high emotional problems, a 3% (1%-5%) reduced probability of high life satisfaction, and a 6% (2%-9%) reduced probability of high prosocial behavior. Replacing SVGs with AVGs was associated with more preferable mental health indicators. Conversely, replacing AOP with AVGs was associated with more deleterious mental health indicators. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  4. EspC, an Autotransporter Protein Secreted by Enteropathogenic Escherichia coli, Causes Apoptosis and Necrosis through Caspase and Calpain Activation, Including Direct Procaspase-3 Cleavage

    Directory of Open Access Journals (Sweden)

    Antonio Serapio-Palacios

    2016-06-01

    Full Text Available Enteropathogenic Escherichia coli (EPEC has the ability to antagonize host apoptosis during infection through promotion and inhibition of effectors injected by the type III secretion system (T3SS, but the total number of these effectors and the overall functional relationships between these effectors during infection are poorly understood. EspC produced by EPEC cleaves fodrin, paxillin, and focal adhesion kinase (FAK, which are also cleaved by caspases and calpains during apoptosis. Here we show the role of EspC in cell death induced by EPEC. EspC is involved in EPEC-mediated cell death and induces both apoptosis and necrosis in epithelial cells. EspC induces apoptosis through the mitochondrial apoptotic pathway by provoking (i a decrease in the expression levels of antiapoptotic protein Bcl-2, (ii translocation of the proapoptotic protein Bax from cytosol to mitochondria, (iii cytochrome c release from mitochondria to the cytoplasm, (iv loss of mitochondrial membrane potential, (v caspase-9 activation, (vi cleavage of procaspase-3 and (vii an increase in caspase-3 activity, (viii PARP proteolysis, and (ix nuclear fragmentation and an increase in the sub-G1 population. Interestingly, EspC-induced apoptosis was triggered through a dual mechanism involving both independent and dependent functions of its EspC serine protease motif, the direct cleavage of procaspase-3 being dependent on this motif. This is the first report showing a shortcut for induction of apoptosis by the catalytic activity of an EPEC protein. Furthermore, this atypical intrinsic apoptosis appeared to induce necrosis through the activation of calpain and through the increase of intracellular calcium induced by EspC. Our data indicate that EspC plays a relevant role in cell death induced by EPEC.

  5. Peroxisome proliferator-activated receptor {alpha} agonists modulate Th1 and Th2 chemokine secretion in normal thyrocytes and Graves' disease

    Energy Technology Data Exchange (ETDEWEB)

    Antonelli, Alessandro, E-mail: a.antonelli@med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Ferrari, Silvia Martina, E-mail: sm.ferrari@int.med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Frascerra, Silvia, E-mail: lafrasce@gmail.com [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Corrado, Alda, E-mail: dala_res@hotmail.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Pupilli, Cinzia, E-mail: c.pupilli@dfc.unifi.it [Endocrinology Unit, Azienda Ospedaliera Careggi and University of Florence, Viale Morgagni 85, I-50134, Florence (Italy); Bernini, Giampaolo, E-mail: g.bernini@int.med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Benvenga, Salvatore, E-mail: s.benvenga@me.nettuno.it [Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Messina, Piazza Pugliatti 1, I-98122, Messina (Italy); Ferrannini, Ele, E-mail: eferrannini@med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Fallahi, Poupak, E-mail: poupak@int.med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy)

    2011-07-01

    Until now, no data are present about the effect of peroxisome proliferator-activated receptor (PPAR){alpha} activation on the prototype Th1 [chemokine (C-X-C motif) ligand (CXCL)10] (CXCL10) and Th2 [chemokine (C-C motif) ligand 2] (CCL2) chemokines secretion in thyroid cells. The role of PPAR{alpha} and PPAR{gamma} activation on CXCL10 and CCL2 secretion was tested in Graves' disease (GD) and control primary thyrocytes stimulated with interferon (IFN){gamma} and tumor necrosis factor (TNF){alpha}. IFN{gamma} stimulated both CXCL10 and CCL2 secretion in primary GD and control thyrocytes. TNF{alpha} alone stimulated CCL2 secretion, while had no effect on CXCL10. The combination of IFN{gamma} and TNF{alpha} had a synergistic effect both on CXCL10 and CCL2 chemokines in GD thyrocytes at levels comparable to those of controls. PPAR{alpha} activators inhibited the secretion of both chemokines (stimulated with IFN{gamma} and TNF{alpha}) at a level higher (for CXCL10, about 60-72%) than PPAR{gamma} agonists (about 25-35%), which were confirmed to inhibit CXCL10, but not CCL2. Our data show that CCL2 is modulated by IFN{gamma} and TNF{alpha} in GD and normal thyrocytes. Furthermore we first show that PPAR{alpha} activators inhibit the secretion of CXCL10 and CCL2 in thyrocytes, suggesting that PPAR{alpha} may be involved in the modulation of the immune response in the thyroid.

  6. Pathophysiologic Changes in Extracellular pH Modulate Parathyroid Calcium-Sensing Receptor Activity and Secretion via a Histidine-Independent Mechanism.

    Science.gov (United States)

    Campion, Katherine L; McCormick, Wanda D; Warwicker, Jim; Khayat, Mohd Ezuan Bin; Atkinson-Dell, Rebecca; Steward, Martin C; Delbridge, Leigh W; Mun, Hee-Chang; Conigrave, Arthur D; Ward, Donald T

    2015-09-01

    The calcium-sensing receptor (CaR) modulates renal calcium reabsorption and parathyroid hormone (PTH) secretion and is involved in the etiology of secondary hyperparathyroidism in CKD. Supraphysiologic changes in extracellular pH (pHo) modulate CaR responsiveness in HEK-293 (CaR-HEK) cells. Therefore, because acidosis and alkalosis are associated with altered PTH secretion in vivo, we examined whether pathophysiologic changes in pHo can significantly alter CaR responsiveness in both heterologous and endogenous expression systems and whether this affects PTH secretion. In both CaR-HEK and isolated bovine parathyroid cells, decreasing pHo from 7.4 to 7.2 rapidly inhibited CaR-induced intracellular calcium (Ca(2+)i) mobilization, whereas raising pHo to 7.6 potentiated responsiveness to extracellular calcium (Ca(2+)o). Similar pHo effects were observed for Ca(2+)o-induced extracellular signal-regulated kinase phosphorylation and actin polymerization and for L-Phe-induced Ca(2+)i mobilization. Intracellular pH was unaffected by acute 0.4-unit pHo changes, and the presence of physiologic albumin concentrations failed to attenuate the pHo-mediated effects. None of the individual point mutations created at histidine or cysteine residues in the extracellular domain of CaR attenuated pHo sensitivity. Finally, pathophysiologic pHo elevation reversibly suppressed PTH secretion from perifused human parathyroid cells, and acidosis transiently increased PTH secretion. Therefore, pathophysiologic pHo changes can modulate CaR responsiveness in HEK-293 and parathyroid cells independently of extracellular histidine residues. Specifically, pathophysiologic acidification inhibits CaR activity, thus permitting PTH secretion, whereas alkalinization potentiates CaR activity to suppress PTH secretion. These findings suggest that acid-base disturbances may affect the CaR-mediated control of parathyroid function and calcium metabolism in vivo. Copyright © 2015 by the American Society of

  7. Sweet Play

    Science.gov (United States)

    Leung, Shuk-kwan S.; Lo, Jane-Jane

    2010-01-01

    This article features Sweet play math, a "math by the month" activity that involves decorating and making sugar cubes. Teachers may want to substitute straws, paper squares, alphabet blocks, or such commercially made manipulatives as Unifix[R] cubes for the real sweets. Given no allergy concerns, teachers and students alike would enjoy some sweet…

  8. Aesthetic Play

    DEFF Research Database (Denmark)

    Bang, Jytte Susanne

    2012-01-01

    The present article explores the role of music-related artefacts and technologies in children’s lives. More specifically, it analyzes how four 10- to 11-year old girls use CDs and DVD games in their music-play activities and which developmental themes and potentials may accrue from such activitie...

  9. Water Play

    Science.gov (United States)

    Cline, Jane E.; Smith, Brandy A.

    2016-01-01

    The inclusion of activities to develop sensory awareness, spatial thinking, and physical dexterity, operationalized through hands-on science lessons such as water play, have long been part of early childhood education. This practical article addresses Next Generation Science Standards K-2 ETS1-3 and K-2 ETS1-2 by having four-year-old…

  10. The power of play: Innovations in Getting Active Summit 2011: a science panel proceedings report from the American Heart Association.

    Science.gov (United States)

    Lieberman, Debra A; Chamberlin, Barbara; Medina, Ernie; Franklin, Barry A; Sanner, Brigid McHugh; Vafiadis, Dorothea K

    2011-05-31

    To examine the influence active-play video gaming (also referred to as exergaming, exertainment, and active gaming) might have on improving health-related skills, enhancing self-esteem and self-efficacy, promoting social support, and ultimately motivating positive changes in health behaviors, the American Heart Association convened The Power of Play: Innovations in Getting Active Summit. The summit, as well as a follow-up science panel, was hosted by the American Heart Association and Nintendo of America. The science panel discussed the current state of research on active-play video gaming and its potential to serve as a gateway experience that might motivate players to increase the amount and intensity of physical activity in their daily lives. The panel identified the need for continued research on the gateway concept and on other behavioral health outcomes that could result from active-play video games and considered how these games could potentially affect disparate populations. The summit represented an exciting first step in convening healthcare providers, behavioral researchers, and professionals from the active-play video game industry to discuss the potential health benefits of active-play video games. Research is needed to improve understanding of processes of behavior change with active games. Future games and technologies may be designed with the goal to optimize physical activity participation, increase energy expenditure, and effectively address the abilities and interests of diverse and targeted populations. The summit helped the participants gain an understanding of what is known, identified gaps in current research, and supported a dialogue for continued collaboration.

  11. Stimulation of toll-like receptor 2 with bleomycin results in cellular activation and secretion of pro-inflammatory cytokines and chemokines

    International Nuclear Information System (INIS)

    Razonable, Raymund R.; Henault, Martin; Paya, Carlos V.

    2006-01-01

    The clinical use of bleomycin results in systemic and pulmonary inflammatory syndromes that are mediated by the production of cytokines and chemokines. In this study, we demonstrate that cell activation is initiated upon the recognition of bleomycin as a pathogen-associated molecular pattern by toll-like receptor (TLR) 2. The THP1 human monocytic cell line, which constitutively expresses high levels of TLR2, secretes interleukin (IL)-1β, IL-8, and tumor necrosis factor (TNF)-α during bleomycin exposure. The TLR2-dependent nature of cell activation and cytokine secretion is supported by (1) the inability of TLR2-deficient human embryonic kidney (HEK) 293 cells to exhibit nuclear factor-kappa B (NF-κB) activation and secrete IL-8 in response to bleomycin; (2) the acquired ability of HEK293 to exhibit NF-κB activation and secrete IL-8 upon experimental expression of TLR2; and (3) the inhibition of cell activation in TLR2-expressing HEK293 and THP1 by anti-TLR2 monoclonal antibody. Collectively, these observations identify TLR2 activation as a critical event that triggers NF-κB activation and secretion of cytokines and chemokines during bleomycin exposure. Our in vitro findings could serve as a molecular mechanism underlying the pro-inflammatory toxicity associated with bleomycin. Whether bleomycin engages with other cellular receptors that results in activation of alternate signaling pathways and whether the TLR2-agonist activity of bleomycin contribute to its anti-neoplastic property deserve further study

  12. High Fat Diet Attenuates the Anticontractile Activity of Aortic PVAT via a Mechanism Involving AMPK and Reduced Adiponectin Secretion

    Directory of Open Access Journals (Sweden)

    Tarek A. M. Almabrouk

    2018-02-01

    Full Text Available Background and aim: Perivascular adipose tissue (PVAT positively regulates vascular function through production of factors such as adiponectin but this effect is attenuated in obesity. The enzyme AMP-activated protein kinase (AMPK is present in PVAT and is implicated in mediating the vascular effects of adiponectin. In this study, we investigated the effect of an obesogenic high fat diet (HFD on aortic PVAT and whether any changes involved AMPK.Methods: Wild type Sv129 (WT and AMPKα1 knockout (KO mice aged 8 weeks were fed normal diet (ND or HFD (42% kcal fat for 12 weeks. Adiponectin production by PVAT was assessed by ELISA and AMPK expression studied using immunoblotting. Macrophages in PVAT were identified using immunohistochemistry and markers of M1 and M2 macrophage subtypes evaluated using real time-qPCR. Vascular responses were measured in endothelium-denuded aortic rings with or without attached PVAT. Carotid wire injury was performed and PVAT inflammation studied 7 days later.Key results: Aortic PVAT from KO and WT mice was morphologically indistinct but KO PVAT had more infiltrating macrophages. HFD caused an increased infiltration of macrophages in WT mice with increased expression of the M1 macrophage markers Nos2 and Il1b and the M2 marker Chil3. In WT mice, HFD reduced the anticontractile effect of PVAT as well as reducing adiponectin secretion and AMPK phosphorylation. PVAT from KO mice on ND had significantly reduced adiponectin secretion and no anticontractile effect and feeding HFD did not alter this. Wire injury induced macrophage infiltration of PVAT but did not cause further infiltration in KO mice.Conclusions: High-fat diet causes an inflammatory infiltrate, reduced AMPK phosphorylation and attenuates the anticontractile effect of murine aortic PVAT. Mice lacking AMPKα1 phenocopy many of the changes in wild-type aortic PVAT after HFD, suggesting that AMPK may protect the vessel against deleterious changes in response to

  13. Associations of object control motor skill proficiency, game play competence, physical activity and cardiorespiratory fitness among primary school children.

    Science.gov (United States)

    Miller, Andrew; Eather, Narelle; Duncan, Mitch; Lubans, David Revalds

    2018-06-18

    This study investigated if object control relates to children's game play competence, and examined these competencies as correlates of physical activity and cardiorespiratory fitness. Game play (Game Performance Assessment Instrument), object control (The Test Gross Motor Development-3), moderate-to-vigorous physical activity (Accelerometry), and cardiorespiratory fitness (20-metre shuttle) assessments were completed for 107 children (57% Female, 43% Male) aged 9-12 years (M 10.53, SD 0.65). Two-level regression of object control on game play competence, and object control and game play competence on physical activity and cardiorespiratory fitness assessed associations. Object control competence was positively associated with game play competence (Std. B = 0.25, t (104.77) = 2.38, p = 0.001). Game play competence (Std. B = 0.33, t (99.81) = 5.21, p competence (Std. B = 0.20, t (106.93) = 2.96, p = 0.003). Likewise, game competence (Std. B = 0.39, t (104.41) = 4.36, p fitness than object control competence (Std. B = 0.22, t (106.69) = 2.63, p = 0.002). Object control and game competence are both important as correlates of physical activity and cardiorespiratory fitness in children.

  14. Genetic and biochemical characterization of the cell wall hydrolase activity of the major secreted protein of Lactobacillus rhamnosus GG.

    Directory of Open Access Journals (Sweden)

    Ingmar J J Claes

    Full Text Available Lactobacillus rhamnosus GG (LGG produces two major secreted proteins, designated here Msp1 (LGG_00324 or p75 and Msp2 (LGG_00031 or p40, which have been reported to promote the survival and growth of intestinal epithelial cells. Intriguingly, although each of these proteins shares homology with cell wall hydrolases, a physiological function that correlates with such an enzymatic activity remained to be substantiated in LGG. To investigate the bacterial function, we constructed knock-out mutants in the corresponding genes aiming to establish a genotype to phenotype relation. Microscopic examination of the msp1 mutant showed the presence of rather long and overly extended cell chains, which suggests that normal daughter cell separation is hampered. Subsequent observation of the LGG wild-type cells by immunofluorescence microscopy revealed that the Msp1 protein accumulates at the septum of exponential-phase cells. The cell wall hydrolyzing activity of the Msp1 protein was confirmed by zymogram analysis. Subsequent analysis by RP-HPLC and mass spectrometry of the digestion products of LGG peptidoglycan (PG by Msp1 indicated that the Msp1 protein has D-glutamyl-L-lysyl endopeptidase activity. Immunofluorescence microscopy and the failure to construct a knock-out mutant suggest an indispensable role for Msp2 in priming septum formation in LGG.

  15. Using Analogy Role-Play Activity in an Undergraduate Biology Classroom to Show Central Dogma Revision

    Science.gov (United States)

    Takemura, Masaharu; Kurabayashi, Mario

    2014-01-01

    For the study of biology in an undergraduate classroom, a classroom exercise was developed: an analogy role-play to learn mechanisms of gene transcription and protein translation (central dogma). To develop the central dogma role-play exercise, we made DNA and mRNA using paper sheets, tRNA using a wire dress hanger, and amino acids using Lego®…

  16. Secret Places.

    Science.gov (United States)

    Ridolfi, Kerry

    1997-01-01

    Argues that children are as deep as the ocean, with secret places inside of them waiting to be opened. Notes that it is powerful for students to learn they can make sense of the world through words, and describes inviting them into poetry as they read poetry, create poetry packets, and write and revise poems. (SR)

  17. Use of Active-Play Video Games to Enhance Aerobic Fitness in Schizophrenia: Feasibility, Safety, and Adherence.

    Science.gov (United States)

    Kimhy, David; Khan, Samira; Ayanrouh, Lindsey; Chang, Rachel W; Hansen, Marie C; Lister, Amanda; Ballon, Jacob S; Vakhrusheva, Julia; Armstrong, Hilary F; Bartels, Matthew N; Sloan, Richard P

    2016-02-01

    Active-play video games have been used to enhance aerobic fitness in various clinical populations, but their use among individuals with schizophrenia has been limited. Feasibility, acceptability, safety, and adherence data were obtained for use of aerobic exercise (AE) equipment by 16 individuals with schizophrenia during a 12-week AE program consisting of three one-hour exercise sessions per week. Equipment included exercise video games for Xbox 360 with Kinect motion sensing devices and traditional exercise equipment. Most participants (81%) completed the training, attending an average of 79% of sessions. The proportion of time spent playing Xbox (39%) exceeded time spent on any other type of equipment. When using Xbox, participants played 2.24±1.59 games per session and reported high acceptability and enjoyment ratings, with no adverse events. Measures of feasibility, acceptability, adherence, and safety support the integration of active-play video games into AE training for people with schizophrenia.

  18. Real-time monitoring prefrontal activities during online video game playing by functional near-infrared spectroscopy.

    Science.gov (United States)

    Li, Yue; Zhang, Lei; Long, Kehong; Gong, Hui; Lei, Hao

    2018-02-16

    A growing body of literature has suggested that video game playing can induce functional and structural plasticity of the brain. The underlying mechanisms, however, remain poorly understood. In this study, functional near-infrared spectroscopy (fNIRS) was used to record prefrontal activities in 24 experienced game players when they played a massively multiplayer online battle arena video game, League of Legends (LOL), under naturalistic conditions. It was observed that game onset was associated with significant activations in the ventrolateral prefrontal cortex (VLPFC) and concomitant deactivations in the dorsolateral prefrontal cortex (DLPFC) and frontal pole area (FPA). Game events, such as slaying an enemy and being slain by an enemy evoked region-specific time-locked hemodynamic/oxygenation responses in the prefrontal cortex (PFC). It was proposed that the VLPFC activities during LOL playing are likely responses to visuo-motor task load of the game, while the DLPFC/FPA activities may be involved in the constant shifts of attentional states and allocation of cognitive resources required by game playing. The present study demonstrated that it is feasible to use fNIRS to monitor real-time prefrontal activity during online video game playing. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Play Matters

    DEFF Research Database (Denmark)

    Sicart (Vila), Miguel Angel

    ? In Play Matters, Miguel Sicart argues that to play is to be in the world; playing is a form of understanding what surrounds us and a way of engaging with others. Play goes beyond games; it is a mode of being human. We play games, but we also play with toys, on playgrounds, with technologies and design......, but not necessarily fun. Play can be dangerous, addictive, and destructive. Along the way, Sicart considers playfulness, the capacity to use play outside the context of play; toys, the materialization of play--instruments but also play pals; playgrounds, play spaces that enable all kinds of play; beauty...

  20. Examining Motivations to Play Pokémon GO and Their Influence on Perceived Outcomes and Physical Activity.

    Science.gov (United States)

    Marquet, Oriol; Alberico, Claudia; Adlakha, Deepti; Hipp, J Aaron

    2017-10-24

    Pokémon GO is the most played augmented reality game in history. With more than 44 million players at the peak of its popularity, the game has sparked interest on its effects on the young population's health. This pilot study examined motivations to start playing Pokémon GO among a sample of US college students, and how motivations were associated with perceived outcomes of the playing experience and physical activity derived while playing. In November 2016, we asked a sample of 47 US college students (all Pokémon GO players) to complete online surveys and install an ecological momentary assessment (EMA) tool and step counter on their smartphones. The EMA tool prompted a set of questions on playing behavior and physical activity, 3 times per day (12:00 PM, 7:00 PM, and 10:00 PM), for 7 days. We used a factorial analysis to identify 3 distinctive groups of players based on their motivations to start playing Pokémon GO. We tested differences across motivation groups related to 5 unique outcomes using 1-way analysis of variance. We extracted 3 interpretable factors from the clustering of motivations to start playing Pokémon GO: Pokémon and video game fans (n=26, 55% of the sample), physical activity seekers (n=8, 17%), and curious & social (n=13, 28%). The clusters differed significantly on the enjoyment of different aspects of the game, particularly battling, discovering new places, and meeting new people, as well as differences in agreement that playing improved mood and made them more social. Days when playing Pokémon GO were associated with higher number of steps reported at the end of the day, especially among physical activity seekers, but also for Pokémon and video game fans. All groups perceived traffic as a major threat to playing. Days during which Pokémon GO was played were positively associated with a set of beneficial health behaviors, including higher physical activity levels, more socialization, and better mood. Results, however, depended on

  1. Comparison of electromyographic activity and range of neck motion in violin students with and without neck pain during playing.

    Science.gov (United States)

    Park, Kyue-nam; Kwon, Oh-yun; Ha, Sung-min; Kim, Su-jung; Choi, Hyun-jung; Weon, Jong-hyuck

    2012-12-01

    Neck pain is common in violin students during a musical performance. The purpose of this study was to compare electromyographic (EMG) activity in superficial neck muscles with neck motion when playing the violin as well as neck range of motion (ROM) at rest, between violin students with and without neck pain. Nine violin students with neck pain and nine age- and gender-matched subjects without neck pain were recruited. Muscle activity of the bilateral upper trapezius, sternocleidomastoid, and superficial cervical extensor muscles was measured using surface EMG. Kinematic data on neck motion while playing and active neck ROM were also measured using a three-dimensional motion analysis system. Independent t-tests were used to compare EMG activity with kinematic data between groups. These analyses revealed that while playing, both the angle of left lateral bending and leftward rotation of the cervical spine were significantly greater in the neck pain group than among those without neck pain. Similarly, EMG activity of the left upper trapezius, both cervical extensors, and both sternocleidomastoid muscles were significantly greater in the neck pain group. The active ROM of left axial rotation was significantly lower in the neck pain group. These results suggest that an asymmetric playing posture and the associated increased muscle activity as well as decreased neck axial rotation may contribute to neck pain in violin students.

  2. SECRETLY ECCENTRIC: THE GIANT PLANET AND ACTIVITY CYCLE OF GJ 328

    International Nuclear Information System (INIS)

    Robertson, Paul; Endl, Michael; Cochran, William D.; MacQueen, Phillip J.; Boss, Alan P.

    2013-01-01

    We announce the discovery of a ∼2 Jupiter-mass planet in an eccentric 11 yr orbit around the K7/M0 dwarf GJ 328. Our result is based on 10 years of radial velocity (RV) data from the Hobby-Eberly and Harlan J. Smith telescopes at McDonald Observatory, and from the Keck Telescope at Mauna Kea. Our analysis of GJ 328's magnetic activity via the Na I D features reveals a long-period stellar activity cycle, which creates an additional signal in the star's RV curve with amplitude 6-10 m s –1 . After correcting for this stellar RV contribution, we see that the orbit of the planet is more eccentric than suggested by the raw RV data. GJ 328b is currently the most massive, longest-period planet discovered around a low-mass dwarf

  3. Shared Genetic Control of Brain Activity During Sleep and Insulin Secretion: A Laboratory-Based Family Study.

    Science.gov (United States)

    Morselli, Lisa L; Gamazon, Eric R; Tasali, Esra; Cox, Nancy J; Van Cauter, Eve; Davis, Lea K

    2018-01-01

    Over the past 20 years, a large body of experimental and epidemiologic evidence has linked sleep duration and quality to glucose homeostasis, although the mechanistic pathways remain unclear. The aim of the current study was to determine whether genetic variation influencing both sleep and glucose regulation could underlie their functional relationship. We hypothesized that the genetic regulation of electroencephalographic (EEG) activity during non-rapid eye movement sleep, a highly heritable trait with fingerprint reproducibility, is correlated with the genetic control of metabolic traits including insulin sensitivity and β-cell function. We tested our hypotheses through univariate and bivariate heritability analyses in a three-generation pedigree with in-depth phenotyping of both sleep EEG and metabolic traits in 48 family members. Our analyses accounted for age, sex, adiposity, and the use of psychoactive medications. In univariate analyses, we found significant heritability for measures of fasting insulin sensitivity and β-cell function, for time spent in slow-wave sleep, and for EEG spectral power in the delta, theta, and sigma ranges. Bivariate heritability analyses provided the first evidence for a shared genetic control of brain activity during deep sleep and fasting insulin secretion rate. © 2017 by the American Diabetes Association.

  4. Calcium has a permissive role in interleukin-1beta-induced c-jun N-terminal kinase activation in insulin-secreting cells

    DEFF Research Database (Denmark)

    Størling, Joachim; Zaitsev, Sergei V; Kapelioukh, Iouri L

    2005-01-01

    The c-jun N-terminal kinase (JNK) signaling pathway mediates IL-1beta-induced apoptosis in insulin-secreting cells, a mechanism relevant to the destruction of pancreatic beta-cells in type 1 and 2 diabetes. However, the mechanisms that contribute to IL-1beta activation of JNK in beta-cells are la...

  5. RSA-Based Secret Handshakes

    OpenAIRE

    Vergnaud , Damien

    2006-01-01

    A secret handshake mechanism allows two entities, members of a same group, to authenticate each other secretly. This primitive was introduced recently by Balfanz, Durfee, Shankar, Smetters, Staddon and Wong and, so far, all the schemes proposed are based on discrete log systems. This paper proposes three new secret handshake protocols secure against active impersonator and detector adversaries. Inspired by two RSA-based key agreement protocols introduced by Okamoto and Tanaka in 1989 and Gira...

  6. Studies quantifying modulatory effects of inhaled NO2 and SO2 on tracheal mucus secretion, proliferative activity of airway epithelium and architecture of lung parenchyma

    International Nuclear Information System (INIS)

    Wagner, U.; Barth, P.J.; Bredenbroeker, D.; Haase, H.; Locher, A.; Janssen, P.; Yu, F.; Wichert, P. von

    1995-10-01

    The following studies were designed to quantify changes in tracheal mucus secretion and epithelial proliferation of peripheral airways induced by inhaled NO 2 and SO 2 . Groups of male Sprague-Dawley rats were exposed alternatively to 1, 5, 10 and 20 ppm NO 2 and SO 2 the exposure-time being 3 or 25 days (d) respectively. Studies of tracheal mucus secretion radiolabelling mucins with 35 S clearly demonstrated a concentration dependant modulation of mucus secretion. We were able to demonstrate for the first time a significant increase of mucus secretion due to submucosal application of the peptide hormone GLP-1(7-36)amide. We were able to demonstrate amylin to be a potent secretagogue, dose-dependently stimulating mucus secretion. Our morphologic data reveal the effects caused by concentrations between 4-5 ppm NO 2 to be so small, that they are hardly detectable at light microscopic level. The assessment of proliferative activity, however, clearly demonstrates an increased proliferation due to even lower concentrations indicating, that even 1 ppm is able to cause epithelial impairment with consecutive regeneration. Double-labelling techniques of proliferation markers and the 10 kD Clara cell specific antigen reveal the Clara cell to be the only source for epithelial regeneration in peripheral airways under the reported experimental conditions of this study. (orig.) [de

  7. Synapses of Amphids Defective (SAD-A) Kinase Promotes Glucose-stimulated Insulin Secretion through Activation of p21-activated Kinase (PAK1) in Pancreatic β-Cells*

    Science.gov (United States)

    Nie, Jia; Sun, Chao; Faruque, Omar; Ye, Guangming; Li, Jia; Liang, Qiangrong; Chang, Zhijie; Yang, Wannian; Han, Xiao; Shi, Yuguang

    2012-01-01

    The p21-activated kinase-1 (PAK1) is implicated in regulation of insulin exocytosis as an effector of Rho GTPases. PAK1 is activated by the onset of glucose-stimulated insulin secretion (GSIS) through phosphorylation of Thr-423, a major activation site by Cdc42 and Rac1. However, the kinase(s) that phosphorylates PAK1 at Thr-423 in islet β-cells remains elusive. The present studies identified SAD-A (synapses of amphids defective), a member of AMP-activated protein kinase-related kinases exclusively expressed in brain and pancreas, as a key regulator of GSIS through activation of PAK1. We show that SAD-A directly binds to PAK1 through its kinase domain. The interaction is mediated by the p21-binding domain (PBD) of PAK1 and requires both kinases in an active conformation. The binding leads to direct phosphorylation of PAK1 at Thr-423 by SAD-A, triggering the onset of GSIS from islet β-cells. Consequently, ablation of PAK1 kinase activity or depletion of PAK1 expression completely abolishes the potentiating effect of SAD-A on GSIS. Consistent with its role in regulating GSIS, overexpression of SAD-A in MIN6 islet β-cells significantly stimulated cytoskeletal remodeling, which is required for insulin exocytosis. Together, the present studies identified a critical role of SAD-A in the activation of PAK1 during the onset of insulin exocytosis. PMID:22669945

  8. Synapses of amphids defective (SAD-A) kinase promotes glucose-stimulated insulin secretion through activation of p21-activated kinase (PAK1) in pancreatic β-Cells.

    Science.gov (United States)

    Nie, Jia; Sun, Chao; Faruque, Omar; Ye, Guangming; Li, Jia; Liang, Qiangrong; Chang, Zhijie; Yang, Wannian; Han, Xiao; Shi, Yuguang

    2012-07-27

    The p21-activated kinase-1 (PAK1) is implicated in regulation of insulin exocytosis as an effector of Rho GTPases. PAK1 is activated by the onset of glucose-stimulated insulin secretion (GSIS) through phosphorylation of Thr-423, a major activation site by Cdc42 and Rac1. However, the kinase(s) that phosphorylates PAK1 at Thr-423 in islet β-cells remains elusive. The present studies identified SAD-A (synapses of amphids defective), a member of AMP-activated protein kinase-related kinases exclusively expressed in brain and pancreas, as a key regulator of GSIS through activation of PAK1. We show that SAD-A directly binds to PAK1 through its kinase domain. The interaction is mediated by the p21-binding domain (PBD) of PAK1 and requires both kinases in an active conformation. The binding leads to direct phosphorylation of PAK1 at Thr-423 by SAD-A, triggering the onset of GSIS from islet β-cells. Consequently, ablation of PAK1 kinase activity or depletion of PAK1 expression completely abolishes the potentiating effect of SAD-A on GSIS. Consistent with its role in regulating GSIS, overexpression of SAD-A in MIN6 islet β-cells significantly stimulated cytoskeletal remodeling, which is required for insulin exocytosis. Together, the present studies identified a critical role of SAD-A in the activation of PAK1 during the onset of insulin exocytosis.

  9. An ABC-transporter and an outer membrane lipoprotein participate in posttranslational activation of type VI secretion in Pseudomonas aeruginosa

    Science.gov (United States)

    Casabona, Maria G.; Silverman, Julie M.; Sall, Khady M.; Boyer, Frédéric; Couté, Yohann; Poirel, Jessica; Grunwald, Didier; Mougous, Joseph D.; Elsen, Sylvie; Attree, Ina

    2012-01-01

    Pseudomonas aeruginosa is capable of injecting protein toxins into other bacterial cells through one of its three type VI secretion systems (T6SS). The activity of this T6SS is tightly regulated on the posttranslational level by phosphorylation-dependent and -independent pathways. The phosphorylation-dependent pathway consists of a Thr kinase/phosphatase pair (PpkA/PppA) that acts on a forkhead domain-containing protein Fha1, and a periplasmic protein, TagR, that positively regulates PpkA. In the present work, we biochemically and functionally characterize three additional proteins of the phosphorylation-dependent regulatory cascade that controls T6S activation: TagT, TagS and TagQ. We show that similar to TagR, these proteins act upstream of the PpkA/PppA checkpoint and influence phosphorylation of Fha1 and export of Hcp1 and Tse1. Localization studies demonstrate that TagQ is an outer membrane lipoprotein and TagR is associated with the outer membrane. Consistent with their homology to lipoprotein outer membrane localization (Lol) components, TagT and TagS form a stable inner membrane complex with ATPase activity. However, we find that outer membrane association of T6SS lipoproteins TagQ and TssJ1, and TagR, is unaltered in a ΔtagTS background. Notably, we found that TagQ is indispensible for anchoring of TagR to the outer membrane fraction. As T6S-dependent fitness of P. aeruginosa requires TagT, S, R and Q, we conclude that these proteins likely participate in a trans-membrane signaling pathway that promotes H1-T6SS activity under optimal environmental conditions. PMID:22765374

  10. An ABC transporter and an outer membrane lipoprotein participate in posttranslational activation of type VI secretion in Pseudomonas aeruginosa.

    Science.gov (United States)

    Casabona, Maria G; Silverman, Julie M; Sall, Khady M; Boyer, Frédéric; Couté, Yohann; Poirel, Jessica; Grunwald, Didier; Mougous, Joseph D; Elsen, Sylvie; Attree, Ina

    2013-02-01

    Pseudomonas aeruginosa is capable of injecting protein toxins into other bacterial cells through one of its three type VI secretion systems (T6SSs). The activity of this T6SS is tightly regulated on the posttranslational level by phosphorylation-dependent and -independent pathways. The phosphorylation-dependent pathway consists of a Threonine kinase/phosphatase pair (PpkA/PppA) that acts on a forkhead domain-containing protein, Fha1, and a periplasmic protein, TagR, that positively regulates PpkA. In the present work, we biochemically and functionally characterize three additional proteins of the phosphorylation-dependent regulatory cascade that controls T6S activation: TagT, TagS and TagQ. We show that similar to TagR, these proteins act upstream of the PpkA/PppA checkpoint and influence phosphorylation of Fha1 and, apparatus assembly and effector export. Localization studies demonstrate that TagQ is an outer membrane lipoprotein and TagR is associated with the outer membrane. Consistent with their homology to lipoprotein outer membrane localization (Lol) components, TagT and TagS form a stable inner membrane complex with ATPase activity. However, we find that outer membrane association of T6SS lipoproteins TagQ and TssJ1, and TagR, is unaltered in a ΔtagTS background. Notably, we found that TagQ is indispensible for anchoring of TagR to the outer membrane fraction. As T6S-dependent fitness of P. aeruginosa requires TagT, S, R and Q, we conclude that these proteins likely participate in a trans-membrane signalling pathway that promotes H1-T6SS activity under optimal environmental conditions. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

  11. Exogenous Thyropin from p41 Invariant Chain Diminishes Cysteine Protease Activity and Affects IL-12 Secretion during Maturation of Human Dendritic Cells.

    Directory of Open Access Journals (Sweden)

    Tina Zavašnik-Bergant

    Full Text Available Dendritic cells (DC play a pivotal role as antigen presenting cells (APC and their maturation is crucial for effectively eliciting an antigen-specific immune response. The p41 splice variant of MHC class II-associated chaperone, called invariant chain p41 Ii, contains an amino acid sequence, the p41 fragment, which is a thyropin-type inhibitor of proteolytic enzymes. The effects of exogenous p41 fragment and related thyropin inhibitors acting on human immune cells have not been reported yet. In this study we demonstrate that exogenous p41 fragment can enter the endocytic pathway of targeted human immature DC. Internalized p41 fragment has contributed to the total amount of the immunogold labelled p41 Ii-specific epitope, as quantified by transmission electron microscopy, in particular in late endocytic compartments with multivesicular morphology where antigen processing and binding to MHC II take place. In cell lysates of treated immature DC, diminished enzymatic activity of cysteine proteases has been confirmed. Internalized exogenous p41 fragment did not affect the perinuclear clustering of acidic cathepsin S-positive vesicles typical of mature DC. p41 fragment is shown to interfere with the nuclear translocation of NF-κB p65 subunit in LPS-stimulated DC. p41 fragment is also shown to reduce the secretion of interleukin-12 (IL-12/p70 during the subsequent maturation of treated DC. The inhibition of proteolytic activity of lysosomal cysteine proteases in immature DC and the diminished capability of DC to produce IL-12 upon their subsequent maturation support the immunomodulatory potential of the examined thyropin from p41 Ii.

  12. Egg cell-secreted EC1 triggers sperm cell activation during double fertilization.

    Science.gov (United States)

    Sprunck, Stefanie; Rademacher, Svenja; Vogler, Frank; Gheyselinck, Jacqueline; Grossniklaus, Ueli; Dresselhaus, Thomas

    2012-11-23

    Double fertilization is the defining characteristic of flowering plants. However, the molecular mechanisms regulating the fusion of one sperm with the egg and the second sperm with the central cell are largely unknown. We show that gamete interactions in Arabidopsis depend on small cysteine-rich EC1 (EGG CELL 1) proteins accumulating in storage vesicles of the egg cell. Upon sperm arrival, EC1-containing vesicles are exocytosed. The sperm endomembrane system responds to exogenously applied EC1 peptides by redistributing the potential gamete fusogen HAP2/GCS1 (HAPLESS 2/GENERATIVE CELL SPECIFIC 1) to the cell surface. Furthermore, fertilization studies with ec1 quintuple mutants show that successful male-female gamete interactions are necessary to prevent multiple-sperm cell delivery. Our findings provide evidence that mutual gamete activation, regulated exocytosis, and sperm plasma membrane modifications govern flowering plant gamete interactions.

  13. Lessons from "A Really Useful Engine"[TM]: Using Thomas the Tank Engine[TM] to Examine the Relationship between Play as a Leading Activity, Imagination and Reality in Children's Contemporary Play Worlds

    Science.gov (United States)

    Edwards, Susan

    2011-01-01

    This paper examines Vygotsky's conception of play as a leading activity in the contexts of children's contemporary play worlds. Commencing with an examination of the relationship between leading activities and the development of psychological functions, the paper moves into a consideration of the relationship between imagination and reality as a…

  14. What's Eating into School Recess? Implications of Extended Eating for Free Play and Physical Activity

    Science.gov (United States)

    Wyver, Shirley; Engelen, Lina; Bundy, Anita; Naughton, Geraldine

    2012-01-01

    An assumption made when designing recess interventions in schools is that there is a clear demarcation between eating time and play time. We used observational data conducted as part of the Sydney Playground Project to test if this assumption was correct. The Sydney Playground Project is a cluster randomised controlled trial of a recess…

  15. Dangerous Forms – Playing by the Visual Rules. Ecological Approach to Videogames as Activity

    DEFF Research Database (Denmark)

    Meldgaard, Betty Li Malvang

    2011-01-01

    The purpose of the dissertation is to investigate the role of perception while palying videogames. The main thesis is that theories of perception have been largely overlooked within the videogame research field. The basic assumption is that to address the perceptual implications of game play...

  16. Effects of "Fair Play Game" Strategy on Moderate to Vigorous Physical Activity in Physical Education

    Science.gov (United States)

    Azevedo, Liane B.; Vidoni, Carla; Dinsdale, Sarah

    2016-01-01

    Less than 50% of a PE lesson is usually spent in MVPA. A dependent-group contingency strategy, "Fair Play Game," has shown effectiveness in increasing MVPA during PE lessons among students from affluent schools. The purpose of this study was to determine the effectiveness of this strategy on MVPA among students from an undeserved…

  17. Cdk5 inhibitory peptide (CIP inhibits Cdk5/p25 activity induced by high glucose in pancreatic beta cells and recovers insulin secretion from p25 damage.

    Directory of Open Access Journals (Sweden)

    Ya-Li Zheng

    Full Text Available Cdk5/p25 hyperactivity has been demonstrated to lead to neuron apoptosis and degenerations. Chronic exposure to high glucose (HG results in hyperactivity of Cdk5 and reduced insulin secretion. Here, we set out to determine whether abnormal upregulation of Cdk5/p25 activity may be induced in a pancreatic beta cell line, Min6 cells. We first confirmed that p25 were induced in overexpressed p35 cells treated with HG and increased time course dependence. Next, we showed that no p25 was detected under short time HG stimulation (4-12 hrs, however was detectable in the long exposure in HG cells (24 hrs and 48 hrs. Cdk5 activity in the above cells was much higher than low glucose treated cells and resulted in more than 50% inhibition of insulin secretion. We confirmed these results by overexpression of p25 in Min6 cells. As in cortical neurons, CIP, a small peptide, inhibited Cdk5/p25 activity and restored insulin secretion. The same results were detected in co-infection of dominant negative Cdk5 (DNCdk5 with p25. CIP also reduced beta cells apoptosis induced by Cdk5/p25. These studies indicate that Cdk5/p25 hyperactivation deregulates insulin secretion and induces cell death in pancreatic beta cells and suggests that CIP may serve as a therapeutic agent for type 2 diabetes.

  18. ACHIEVEMENT GOALS AND INTENSIVITY OF PHYSICAL ACTIVITY DURING FREE PLAY IN CHILDREN: THE MODERATING ROLE OF PERCEIVED SPORT CONFIDENCE

    Directory of Open Access Journals (Sweden)

    R. Lochbaum Marc

    2015-11-01

    Full Text Available Purpose: to examine the moderating role of sport confidence and resultant the achievement goal profile with physical activity intensity during free play. Material: participants were 28 children participating in an after-school program. The 28 children completed measures of task and ego goal orientations and sport confidence two weeks prior to having their heart rate monitored during a free play session. Results: indicated that children with high sport confidence were characterized ( p 1.10 by higher task and ego orientations and average heart rate over the course of the free play session when compared to the low sport confidence children. The moderate sport confidence children were not significantly different than the other groups expect for ego orientation though effect sizes indicated this group tended towards being more similar to the high sport confidence group. The results were confounded as all children in the low sport confidence condition were girls. Conclusions: Sport confidence moderates physical activity intensity during free play in children and is characterized by a higher ego orientation and generally higher task orientation. But given all of the low confident children were females, intervention work is needed at early ages with girls to build sport confidence and motivations for both goal orientations to hopefully increase physical activity intensity during free play.

  19. The Physiologic and Behavioral Implications of Playing Active and Sedentary Video Games in a Seated and Standing Position.

    Science.gov (United States)

    Sanders, Gabriel J; Rebold, Michael; Peacock, Corey A; Williamson, Meagan L; Santo, Antonio S; Barkley, Jacob E

    Previous studies have assessed physiologic response while playing video games per manufacturer instructions with participants standing during active video game play and seated during sedentary game play. It is not known whether an assigned seated or standing position affects positional preference and oxygen consumption (VO2) while gaming. The purpose of the study was to assess VO2 and preference of playing active and sedentary video games in a seated and standing position. VO2 was assessed in 25 participants during four, 20-minute conditions; resting, PlayStation 2 Madden NFL Football 2011, Nintendo Wii-Sports Boxing and Nintendo Wii Madden NFL Football 2011. Each condition was divided into two positional conditions (10 minutes seated, 10 minutes standing) and each participant indicated their positional preference after each 20-minute condition. Standing VO2 (4.4 ± 0.2 ml • kg-1 • min-1 PS2, 4.6 ± 0.1 ml • kg-1 • min-1 Wii Madden, 6.8 ± 0.3 ml • kg-1 • min-1Wii Boxing) was significantly (p ≤ 0.001) greater than seated VO2 (4.0 ± 0.1 ml • kg-1 • min-1 PS2, 4.2 ± 0.1 ml • kg-1 • min-1 Wii Madden, 6.1 ± 0.3 ml • kg-1 • min-1Wii Boxing) for each gaming condition. Participants preferred (p ≤ 0.001) to sit for all gaming conditions except Wii Boxing. Playing video games while standing increases VO2 to a greater extent than playing the same games in a seated position. Standing was only preferred for the most physiologically challenging game, Wii Boxing. Gaming position should be considered when assessing the physiologic and behavioral outcomes of playing video games.

  20. Proteomic Analysis Shows Constitutive Secretion of MIF and p53-associated Activity of COX-2−/− Lung Fibroblasts

    Directory of Open Access Journals (Sweden)

    Mandar Dave

    2017-12-01

    Full Text Available The differential expression of two closelyassociated cyclooxygenase isozymes, COX-1 and COX-2, exhibited functions beyond eicosanoid metabolism. We hypothesized that COX-1 or COX-2 knockout lung fibroblasts may display altered protein profiles which may allow us to further differentiate the functional roles of these isozymes at the molecular level. Proteomic analysis shows constitutive production of macrophage migration inhibitory factor (MIF in lung fibroblasts derived from COX-2−/− but not wild-type (WT or COX-1−/− mice. MIF was spontaneously released in high levels into the extracellular milieu of COX2−/− fibroblasts seemingly from the preformed intracellular stores, with no change in the basal gene expression of MIF. The secretion and regulation of MIF in COX-2−/− was “prostaglandin-independent.” GO analysis showed that concurrent with upregulation of MIF, there is a significant surge in expression of genes related to fibroblast growth, FK506 binding proteins, and isomerase activity in COX-2−/− cells. Furthermore, COX-2−/− fibroblasts also exhibit a significant increase in transcriptional activity of various regulators, antagonists, and co-modulators of p53, as well as in the expression of oncogenes and related transcripts. Integrative Oncogenomics Cancer Browser (IntroGen analysis shows downregulation of COX-2 and amplification of MIF and/or p53 activity during development of glioblastomas, ependymoma, and colon adenomas. These data indicate the functional role of the MIF-COX-p53 axis in inflammation and cancer at the genomic and proteomic levels in COX-2-ablated cells. This systematic analysis not only shows the proinflammatory state but also unveils a molecular signature of a pro-oncogenic state of COX-1 in COX-2 ablated cells.

  1. The influence of differential processing of procathepsin H on its aminopeptidase activity, secretion and subcellular localization in human cell lines.

    Science.gov (United States)

    Rojnik, Matija; Jevnikar, Zala R; Doljak, Bojan; Turk, Samo; Zidar, Nace; Kos, Janko

    2012-10-01

    Cathepsin H is a unique member of the cysteine cathepsins that acts primarily as an aminopeptidase. Like other cysteine cathepsins, it is synthesized as an inactive precursor and activated by proteolytic removal of its propeptide. Here we demonstrate that, in human cells, the processing of the propeptide is an autocatalytic, multistep process proceeding from an inactive 41kDa pro-form, through a 30kDa intermediate form, to the 28kDa mature form. Tyr87P and Gly90P were identified as the two major endopeptidase cleavage sites, converting the 30kDa form into the mature 28kDa form. The level of processing differs significantly in different human cell lines. In monocyte-derived macrophages U937 and prostate cancer cells PC-3, the 28kDa form is predominant, whereas in osteoblasts HOS the processing from the 30kDa form to the 28kDa form is significantly lower. The aminopeptidase activity of the enzyme and its subcellular localization are independent of the product, however the 30kDa form was not secreted in HOS cells. The activity of the resulting cathepsin H in U937 cells was significantly lower than that in HOS cells, presumably due to the high levels of endogenous cysteine protease inhibitor cystatin F present specifically in this cell line. These results provide an insight into the dependence of human cathepsin H processing and regulation on cell type. Copyright © 2012 Elsevier GmbH. All rights reserved.

  2. Corydalis edulis Maxim. Promotes Insulin Secretion via the Activation of Protein Kinase Cs (PKCs) in Mice and Pancreatic β Cells.

    Science.gov (United States)

    Zheng, Jiao; Zhao, Yunfang; Lun, Qixing; Song, Yuelin; Shi, Shepo; Gu, Xiaopan; Pan, Bo; Qu, Changhai; Li, Jun; Tu, Pengfei

    2017-01-16

    Corydalis edulis Maxim., a widely grown plant in China, had been proposed for the treatment for type 2 diabetes mellitus. In this study, we found that C. edulis extract (CE) is protective against diabetes in mice. The treatment of hyperglycemic and hyperlipidemic apolipoprotein E (ApoE)-/- mice with a high dose of CE reduced serum glucose by 28.84% and serum total cholesterol by 17.34% and increased insulin release. We also found that CE significantly enhanced insulin secretion in a glucose-independent manner in hamster pancreatic β cell (HIT-T15). Further investigation revealed that CE stimulated insulin exocytosis by a protein kinase C (PKC)-dependent signaling pathway and that CE selectively activated novel protein kinase Cs (nPKCs) and atypical PKCs (aPKCs) but not conventional PKCs (cPKCs) in HIT-T15 cells. To the best of our knowledge, our study is the first to identify the PKC pathway as a direct target and one of the major mechanisms underlying the antidiabetic effect of CE. Given the good insulinotropic effect of this herbal medicine, CE is a promising agent for the development of new drugs for treating diabetes.

  3. Stretch induced endothelin-1 secretion by adult rat astrocytes involves calcium influx via stretch-activated ion channels (SACs)

    International Nuclear Information System (INIS)

    Ostrow, Lyle W.; Suchyna, Thomas M.; Sachs, Frederick

    2011-01-01

    Highlights: → Endothelin-1 expression by adult rat astrocytes correlates with cell proliferation. → Stretch-induced ET-1 is inhibited by GsMtx-4, a specific inhibitor of Ca 2+ permeant SACs. → The less specific SAC inhibitor streptomycin also inhibits ET-1 secretion. → Stretch-induced ET-1 production depends on a calcium influx. → SAC pharmacology may provide a new class of therapeutic agents for CNS pathology. -- Abstract: The expression of endothelins (ETs) and ET-receptors is often upregulated in brain pathology. ET-1, a potent vasoconstrictor, also inhibits the expression of astrocyte glutamate transporters and is mitogenic for astrocytes, glioma cells, neurons, and brain capillary endothelia. We have previously shown that mechanical stress stimulates ET-1 production by adult rat astrocytes. We now show in adult astrocytes that ET-1 production is driven by calcium influx through stretch-activated ion channels (SACs) and the ET-1 production correlates with cell proliferation. Mechanical stimulation using biaxial stretch ( 2+ threshold. This coupling of mechanical stress to the astrocyte endothelin system through SACs has treatment implications, since all pathology deforms the surrounding parenchyma.

  4. Corticosteroid-Induced MKP-1 Represses Pro-Inflammatory Cytokine Secretion by Enhancing Activity of Tristetraprolin (TTP) in ASM Cells

    NARCIS (Netherlands)

    Prabhala, Pavan; Ammit, Alaina; Bunge, Kristin; Ge, Qi

    2016-01-01

    Exaggerated cytokine secretion drives pathogenesis of a number of chronic inflammatory diseases, including asthma. Anti-inflammatory pharmacotherapies, including corticosteroids, are front-line therapies and although they have proven clinical utility, the molecular mechanisms responsible for their

  5. Effects of oral stimulation with capsaicin on salivary secretion and neural activities in the autonomic system and the brain

    Directory of Open Access Journals (Sweden)

    Yoko Kono

    2018-06-01

    Conclusion: These results suggest that oral stimulation with capsaicin may be effective in improving oral conditions by increasing salivary flow and SIgA secretion, and in enhancing physical and mental conditions as indicated by sympathetic nerve and EEG changes.

  6. Astrocytes play a key role in activation of microglia by persistent Borna disease virus infection

    Directory of Open Access Journals (Sweden)

    Sauder Christian

    2008-11-01

    Full Text Available Abstract Neonatal Borna disease virus (BDV infection of the rat brain is associated with microglial activation and damage to certain neuronal populations. Since persistent BDV infection of neurons is nonlytic in vitro, activated microglia have been suggested to be responsible for neuronal cell death in vivo. However, the mechanisms of activation of microglia in neonatally BDV-infected rat brains remain unclear. Our previous studies have shown that activation of microglia by BDV in culture requires the presence of astrocytes as neither the virus nor BDV-infected neurons alone activate microglia. Here, we evaluated the mechanisms whereby astrocytes can contribute to activation of microglia in neuron-glia-microglia mixed cultures. We found that persistent infection of neuronal cells leads to activation of uninfected astrocytes as measured by elevated expression of RANTES. Activation of astrocytes then produces activation of microglia as evidenced by increased formation of round-shaped, MHCI-, MHCII- and IL-6-positive microglia cells. Our analysis of possible molecular mechanisms of activation of astrocytes and/or microglia in culture indicates that the mediators of activation may be soluble heat-resistant, low molecular weight factors. The findings indicate that astrocytes may mediate activation of microglia by BDV-infected neurons. The data are consistent with the hypothesis that microglia activation in the absence of neuronal damage may represent initial steps in the gradual neurodegeneration observed in brains of neonatally BDV-infected rats.

  7. Salivary Gland Secretion.

    Science.gov (United States)

    Dorman, H. L.; And Others

    1981-01-01

    Describes materials and procedures for an experiment utilizing a live dog to demonstrate: (1) physiology of the salivary gland; (2) parasympathetic control of the salivary gland; (3) influence of varying salivary flow rates on sodium and potassium ions, osmolarity and pH; and (4) salivary secretion as an active process. (DS)

  8. "No Time to Play": Perceptions toward Physical Activity in Youth with Cystic Fibrosis

    Science.gov (United States)

    Moola, Fiona; Faulkner, Guy E. J.; Schneiderman, Jane E.

    2012-01-01

    Although physical activity may reduce lung function decline in youth with cystic fibrosis (CF), most patients are inactive. Little is known about why youth with CF are inactive or how to facilitate physical activity. This study explored perceptions toward physical activity in 14 youth with CF at a Canadian Hospital. Qualitative interviews were…

  9. Effectiveness of Group Activity Play Therapy on Internalizing and Externalizing Behavior Problems of Preadolescent Orphans in Uganda

    Science.gov (United States)

    Ojiambo, Deborah

    2011-01-01

    This pilot study investigated the impact of group activity play therapy (GAPT) on displaced orphans aged 10 to 12 years living in a large children's village in Uganda. Teachers and housemothers identified 60 preadolescents exhibiting clinical levels of internalizing and externalizing behavior problems. The participants' ethnicity was African and…

  10. Learners' Interpersonal Beliefs and Generated Feedback in an Online Role-Playing Peer-Feedback Activity: An Exploratory Study

    Science.gov (United States)

    Ching, Yu-Hui; Hsu, Yu-Chang

    2016-01-01

    Peer feedback affords interaction and critical thinking opportunities for learners in online courses. However, various factors prevent learners from taking advantage of these promising benefits. This study explored learners' perceptions of the interpersonal factors in a role-playing peer-feedback activity, and examined the types of peer feedback…

  11. Teaching Children with Autism to Play a Video Game Using Activity Schedules and Game-Embedded Simultaneous Video Modeling

    Science.gov (United States)

    Blum-Dimaya, Alyssa; Reeve, Sharon A.; Reeve, Kenneth F.; Hoch, Hannah

    2010-01-01

    Children with autism have severe and pervasive impairments in social interactions and communication that impact most areas of daily living and often limit independent engagement in leisure activities. We taught four children with autism to engage in an age-appropriate leisure skill, playing the video game Guitar Hero II[TM], through the use of (a)…

  12. Feasibility of Conducting a Randomized Trial to Promote Healthy Eating, Active Play and Sustainability Awareness in Early Childhood Curricula

    Science.gov (United States)

    Morris, Heather; Skouteris, Helen; Edwards, Susan; Rutherford, Leonie Margaret; Cutter-Mackenzie, Amy; O'Connor, Amanda; Mantilla, Ana; Huang, Terry TK; Lording, Kate Marion; Williams-Smith, Janet

    2016-01-01

    We sought to evaluate the feasibility of conducting a randomized trial to evaluate the efficacy of a preschool/kindergarten curriculum intervention designed to increase 4-year-old children's knowledge of healthy eating, active play and the sustainability consequences of their food and toy choices. Ninety intervention and 65 control parent/child…

  13. Literacy-Related Play Activities and Preschool Staffs' Strategies to Support Children's Concept Development

    Science.gov (United States)

    Norling, Martina; Lillvist, Anne

    2016-01-01

    This study investigates language-promoting strategies and support of concept development displayed by preschool staffs' when interacting with preschool children in literacy-related play activities. The data analysed consisted of 39 minutes of video, selected systematically from a total of 11 hours of video material from six Swedish preschool…

  14. Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and Contributes to Microglial Activation

    Directory of Open Access Journals (Sweden)

    Miguel Angel Burguillos

    2015-03-01

    Full Text Available Inflammatory response induced by microglia plays a critical role in the demise of neuronal populations in neuroinflammatory diseases. Although the role of toll-like receptor 4 (TLR4 in microglia’s inflammatory response is fully acknowledged, little is known about endogenous ligands that trigger TLR4 activation. Here, we report that galectin-3 (Gal3 released by microglia acts as an endogenous paracrine TLR4 ligand. Gal3-TLR4 interaction was further confirmed in a murine neuroinflammatory model (intranigral lipopolysaccharide [LPS] injection and in human stroke subjects. Depletion of Gal3 exerted neuroprotective and anti-inflammatory effects following global brain ischemia and in the neuroinflammatory LPS model. These results suggest that Gal3-dependent-TLR4 activation could contribute to sustained microglia activation, prolonging the inflammatory response in the brain.

  15. Development of a measurement approach to assess time children participate in organized sport, active travel, outdoor active play, and curriculum-based physical activity.

    Science.gov (United States)

    Borghese, Michael M; Janssen, Ian

    2018-03-22

    Children participate in four main types of physical activity: organized sport, active travel, outdoor active play, and curriculum-based physical activity. The objective of this study was to develop a valid approach that can be used to concurrently measure time spent in each of these types of physical activity. Two samples (sample 1: n = 50; sample 2: n = 83) of children aged 10-13 wore an accelerometer and a GPS watch continuously over 7 days. They also completed a log where they recorded the start and end times of organized sport sessions. Sample 1 also completed an outdoor time log where they recorded the times they went outdoors and a description of the outdoor activity. Sample 2 also completed a curriculum log where they recorded times they participated in physical activity (e.g., physical education) during class time. We describe the development of a measurement approach that can be used to concurrently assess the time children spend participating in specific types of physical activity. The approach uses a combination of data from accelerometers, GPS, and activity logs and relies on merging and then processing these data using several manual (e.g., data checks and cleaning) and automated (e.g., algorithms) procedures. In the new measurement approach time spent in organized sport is estimated using the activity log. Time spent in active travel is estimated using an existing algorithm that uses GPS data. Time spent in outdoor active play is estimated using an algorithm (with a sensitivity and specificity of 85%) that was developed using data collected in sample 1 and which uses all of the data sources. Time spent in curriculum-based physical activity is estimated using an algorithm (with a sensitivity of 78% and specificity of 92%) that was developed using data collected in sample 2 and which uses accelerometer data collected during class time. There was evidence of excellent intra- and inter-rater reliability of the estimates for all of these types of

  16. Systematic high-yield production of human secreted proteins in Escherichia coli

    International Nuclear Information System (INIS)

    Dai Xueyu; Chen Qiang; Lian Min; Zhou Yanfeng; Zhou Mo; Lu Shanyun; Chen Yunjia; Luo Jingchu; Gu Xiaocheng; Jiang Ying; Luo Ming; Zheng Xiaofeng

    2005-01-01

    Human secreted proteins play a very important role in signal transduction. In order to study all potential secreted proteins identified from the human genome sequence, systematic production of large amounts of biologically active secreted proteins is a prerequisite. We selected 25 novel genes as a trial case for establishing a reliable expression system to produce active human secreted proteins in Escherichia coli. Expression of proteins with or without signal peptides was examined and compared in E. coli strains. The results indicated that deletion of signal peptides, to a certain extent, can improve the expression of these proteins and their solubilities. More importantly, under expression conditions such as induction temperature, N-terminus fusion peptides need to be optimized in order to express adequate amounts of soluble proteins. These recombinant proteins were characterized as well-folded proteins. This system enables us to rapidly obtain soluble and highly purified human secreted proteins for further functional studies

  17. When children play, they feel better : organized activity participation and health in adolescents

    NARCIS (Netherlands)

    Badura, Petr; Geckova, Andrea Madarasova; Sigmundova, Dagmar; van Dijk, Jitse P.; Reijneveld, Sijmen A.

    2015-01-01

    Background: Participation in organized leisure-time activities (OLTA) has been linked to healthy youth development. This study aimed to assess whether participation in OLTA is associated with both physical and mental health in adolescents, and whether this association differs by pattern of activity

  18. Prevalence and Stability of Active Play, Restricted Movement and Television Viewing in Infants

    Science.gov (United States)

    Hesketh, Kylie D.; Crawford, David A.; Abbott, Gavin; Campbell, Karen J.; Salmon, Jo

    2015-01-01

    This study describes engagement in and stability of physical activity and sedentary behaviours in early life, and assesses associations with sex, maternal education and developmental stage. Maternal-report data at child age 4, 9 and 20 months were collected from 542 families in the Melbourne Infant Feeding Activity and Nutrition Trial Program.…

  19. Active Teaching of Diffusion through History of Science, Computer Animation and Role Playing

    Science.gov (United States)

    Krajsek, Simona Strgulc; Vilhar, Barbara

    2010-01-01

    We developed and tested a lesson plan for active teaching of diffusion in secondary schools (grades 10-13), which stimulates understanding of the thermal (Brownian) motion of particles as the principle underlying diffusion. During the lesson, students actively explore the Brownian motion through microscope observations of irregularly moving small…

  20. Associations between Parental and Friend Social Support and Children's Physical Activity and Time Spent outside Playing.

    Science.gov (United States)

    Loucaides, Constantinos A; Tsangaridou, Niki

    2017-01-01

    The purpose of this study was to examine the structural validity of a parent and a child questionnaire that assessed parental and friends' influences on children's physical activity and investigate the associations between the derived factors, physical activity, and time spent outside. Children ( N = 154, mean age = 11.7) and 144 of their parents completed questionnaires assessing parental and friends' influences on children's physical activity. Children wore a pedometer for six days. Exploratory factor analyses revealed four factors for the parental and five for the child's questionnaire that explained 66.71% and 63.85% of the variance, respectively. Five factors were significantly associated with physical activity and five significantly associated with time spent outside. Higher correlations were revealed between "general friend support," "friends' activity norms," and physical activity ( r = 0.343 and 0.333 resp., p friend support" and time spent outside ( r = 0.460, p parental and friends' influences on physical activity from both parents and children may provide a more complete picture of influences. Parents and friends seem to influence children's physical activity behavior and time spent outside, but friends' influences may have a stronger impact on children's behaviors.

  1. Constitutively Active MAVS Inhibits HIV-1 Replication via Type I Interferon Secretion and Induction of HIV-1 Restriction Factors.

    Directory of Open Access Journals (Sweden)

    Sachin Gupta

    Full Text Available Type I interferon is known to inhibit HIV-1 replication through the induction of interferon stimulated genes (ISG, including a number of HIV-1 restriction factors. To better understand interferon-mediated HIV-1 restriction, we constructed a constitutively active form of the RIG-I adapter protein MAVS. Constitutive MAVS was generated by fusion of full length MAVS to a truncated form of the Epstein Barr virus protein LMP1 (ΔLMP1. Supernatant from ΔLMP1-MAVS-transfected 293T cells contained high levels of type I interferons and inhibited HIV replication in both TZM-bl and primary human CD4+ T cells. Supernatant from ΔLMP1-MAVS-transfected 293T cells also inhibited replication of VSV-G pseudotyped single cycle SIV in TZM-bl cells, suggesting restriction was post-entry and common to both HIV and SIV. Gene array analysis of ΔLMP1-MAVS-transfected 293T cells and trans-activated CD4+ T cells showed significant upregulation of ISG, including previously characterized HIV restriction factors Viperin, Tetherin, MxB, and ISG56. Interferon blockade studies implicated interferon-beta in this response. In addition to direct viral inhibition, ΔLMP1-MAVS markedly enhanced secretion of IFN-β and IL-12p70 by dendritic cells and the activation and maturation of dendritic cells. Based on this immunostimulatory activity, an adenoviral vector (Ad5 expressing ΔLMP1-MAVS was tested as a molecular adjuvant in an HIV vaccine mouse model. Ad5-Gag antigen combined with Ad5-ΔLMP1-MAVS enhanced control of vaccinia-gag replication in a mouse challenge model, with 4/5 animals showing undetectable virus following challenge. Overall, ΔLMP1-MAVS is a promising reagent to inhibit HIV-1 replication in infected tissues and enhance vaccine-mediated immune responses, while avoiding toxicity associated with systemic type I interferon administration.

  2. Salmonella-secreted Virulence Factors

    Energy Technology Data Exchange (ETDEWEB)

    Heffron, Fred; Niemann, George; Yoon, Hyunjin; Kidwai, Afshan S.; Brown, Roslyn N.; McDermott, Jason E.; Smith, Richard D.; Adkins, Joshua N.

    2011-05-01

    In this short review we discuss secreted virulence factors of Salmonella, which directly affect Salmonella interaction with its host. Salmonella secretes protein to subvert host defenses but also, as discussed, to reduce virulence thereby permitting the bacteria to persist longer and more successfully disperse. The type III secretion system (TTSS) is the best known and well studied of the mechanisms that enable secretion from the bacterial cytoplasm to the host cell cytoplasm. Other secretion systems include outer membrane vesicles, which are present in all Gram-negative bacteria examined to date, two-partner secretion, and type VI secretion will also be addressed. Excellent reviews of Salmonella secreted effectors have focused on themes such as actin rearrangements, vesicular trafficking, ubiquitination, and the activities of the virulence factors themselves. This short review is based on S. Typhimurium infection of mice because it is a model of typhoid like disease in humans. We have organized effectors in terms of events that happen during the infection cycle and how secreted effectors may be involved.

  3. Preschoolers´ Physical Activity and Time on Task During a Mastery Motivational Climate and Free Play

    Directory of Open Access Journals (Sweden)

    Danielle D Wadsworth

    2014-08-01

    Full Text Available The purpose of the present study was to determine the effect of a structured, mastery motivation physical education climate and an unstructured physical activity climate on time spent on task in a small sample of preschool children. Children enrolled in a public, federal-subsidized childcare center (N= 12 participated in two 45 minute physical activity programs within the school day. The structured climate consisted of a biweekly program of motor skill instruction that was based upon the key principles of a mastery motivational climate. The unstructured program was a daily 45 minute free play environment. Actigraph accelerometers monitored children’s participation in physical activity and time-on task was observed by a momentary time sampling technique. Results showed that time on-task significantly improved following a mastery motivational climate, and children spent 36% of their time in moderate-to-vigorous activity in this climate.  In contrast, time on-task did not significantly improve following participation in a free play environment and participants spent a majority of their time in sedentary behavior and accumulated no vigorous physical activity. Our results indicate that participation in physical activity impacts a preschooler’s ability to stay on task and the amount of physical activity accumulated during physical activity programming is dependent upon the climate delivered.

  4. Pituitary adenylate cyclase activating polypeptide plays a role in olfactory memory formation in chicken.

    Science.gov (United States)

    Józsa, Rita; Hollósy, Tibor; Tamás, Andrea; Tóth, Gábor; Lengvári, István; Reglodi, Dóra

    2005-11-01

    PACAP plays an important role during development of the nervous system and is also involved in memory processing. The aim of the present study was to investigate the function of PACAP in chicken embryonic olfactory memory formation by blocking PACAP at a sensitive period in ovo. Chicken were exposed daily to strawberry scent in ovo from embryonic day 15. Control eggs were treated only with saline, while other eggs received a single injection of the PACAP antagonist PACAP6-38 at day 15. The consumption of scented and unscented water was measured daily after hatching. Animals exposed to strawberry scent in ovo showed no preference. However, chickens exposed to PACAP6-38, showed a clear preference for plain water, similarly to unexposed chicken. Our present study points to PACAP's possible importance in embryonic olfactory memory formation.

  5. Increasing Physical Activity among Adults with Disabilities: Doctors Can Play a Key Role

    Centers for Disease Control (CDC) Podcasts

    In this podcast, Dr. Dianna Carroll, a senior health scientist with CDC’s Division of Human Development and Disability, talks about the role of doctors and other health professionals in increasing physical activity among adults with disabilities.

  6. The activity of 11β-hydroxysteroid dehydrogenase type 2 enzyme and cortisol secretion in patients with adrenal incidentalomas.

    Science.gov (United States)

    Morelli, Valentina; Polledri, Elisa; Mercadante, Rosa; Zhukouskaya, Volha; Palmieri, Serena; Beck-Peccoz, Paolo; Spada, Anna; Fustinoni, Silvia; Chiodini, Iacopo

    2016-09-01

    In adrenal incidentaloma (AI) patients, beside the cortisol secretion, a different 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) activity, measurable by 24-h urinary cortisol/cortisone ratio (R-UFF/UFE) (the higher R-UFF/UFE the lower HSD11B2 activity), could influence the occurrence of the subclinical hypercortisolism (SH)-related complications (hypertension, type 2 diabetes, obesity). We evaluated whether in AI patients, UFF levels are associated to UFE levels, and the HSD11B2 activity to the complications presence. In 156 AI patients (93F, age 65.2 ± 9.5 years), the following were measured: serum cortisol after 1 mg-dexamethasone test (1 mg-DST), ACTH, UFF, UFE levels, and R-UFF/UFE (by liquid chromatography-tandem mass spectrometry), the latter was also evaluated in 63 matched-controls. We diagnosed SH (n = 22) in the presence of ≥2 among ACTH levels, and 1 mg-DST >83 nmol/L. Patients showed higher UFF levels and R-UFF/UFE than controls (75.9 ± 43.1 vs 54.4 ± 22.9 nmol/24 h and 0.26 ± 0.12 vs 0.20 ± 0.07, p levels (291 ± 91.1 vs 268 ± 61.5, p = 0.069). The R-UFF/UFE was higher in patients with high (h-UFF, n = 28, 0.41 ± 0.20) than in those with normal (n-UFF, 0.22 ± 0.10, p levels and in patients with SH than in those without SH (0.30 ± 0.12 vs 0.25 ± 0.12, p = 0.04). UFF levels were associated with R-UFF/UFE (r = 0.849, p levels in n-UFF patients but not in h-UFF patients, and it is not associated with the SH complications.

  7. Evaluation of Children Playing a New-Generation Motion-Sensitive Active Videogame by Accelerometry and Indirect Calorimetry.

    Science.gov (United States)

    Reading, Stacey A; Prickett, Karel

    2013-06-01

    New-generation active videogames (AVGs) use motion-capture video cameras to connect a player's arm, leg, and body movements through three-dimensional space to on-screen activity. We sought to determine if the whole-body movements required to play the AVG elicited moderate-intensity physical activity (PA) in children. A secondary aim was to examine the utility of using accelerometry to measure the activity intensity of AVG play in this age group. The PA levels of boys (n=26) and girls (n=15) 5-12 years of age were measured by triaxial accelerometry (n=25) or accelerometry and indirect calorimetry (IC) (n=16) while playing the "Kinect Adventures!" videogame for the Xbox Kinect (Microsoft(®), Redmond, WA) gaming system. The experiment simulated a typical 20-minute in-home free-play gaming session. Using 10-second recording epochs, the average (mean±standard deviation) PA intensity over 20 minutes was 4.4±0.9, 3.2±0.7, and 3.3±0.6 metabolic equivalents (METs) when estimated by IC or vertical axis (Crouter et al. intermittent lifestyle equation for vertical axis counts/10 seconds [Cva2RM]) and vector magnitude (Crouter et al. intermittent lifestyle equation for vector magnitude counts/10 seconds [Cvm2RM]) accelerometry. In total, 16.9±3.2 (IC), 10.6±4.5 (Cva2RM), and 11.1±3.9 (Cvm2RM) minutes of game playing time were at a 3 MET intensity or higher. In this study, children played the Xbox Kinect AVG at moderate-intensity PA levels. The study also showed that current accelerometry-based methods underestimated the PA of AVG play compared with IC. With proper guidance and recommendations for use, video motion-capture AVG systems could reduce sedentary screen time and increase total daily moderate PA levels for children. Further study of these AVG systems is warranted.

  8. Role-Playing Mitosis.

    Science.gov (United States)

    Wyn, Mark A.; Stegink, Steven J.

    2000-01-01

    Introduces a role playing activity that actively engages students in the learning process of mitosis. Students play either chromosomes carrying information, or cells in the cell membrane. (Contains 11 references.) (Author/YDS)

  9. Oxidative stress plays a role in high glucose-induced activation of pancreatic stellate cells

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Gyeong Ryul; Lee, Esder; Chun, Hyun-Ji; Yoon, Kun-Ho; Ko, Seung-Hyun; Ahn, Yu-Bae; Song, Ki-Ho, E-mail: kihos@catholic.ac.kr

    2013-09-20

    Highlights: •High glucose increased production of reactive oxygen species in cultured pancreatic stellate cells. •High glucose facilitated the activation of these cells. •Antioxidant treatment attenuated high glucose-induced activation of these cells. -- Abstract: The activation of pancreatic stellate cells (PSCs) is thought to be a potential mechanism underlying islet fibrosis, which may contribute to progressive β-cell failure in type 2 diabetes. Recently, we demonstrated that antioxidants reduced islet fibrosis in an animal model of type 2 diabetes. However, there is no in vitro study demonstrating that high glucose itself can induce oxidative stress in PSCs. Thus, PSCs were isolated and cultured from Sprague Dawley rats, and treated with high glucose for 72 h. High glucose increased the production of reactive oxygen species. When treated with high glucose, freshly isolated PSCs exhibited myofibroblastic transformation. During early culture (passage 1), PSCs treated with high glucose contained an increased number of α-smooth muscle actin-positive cells. During late culture (passages 2–5), PSCs treated with high glucose exhibited increases in cell proliferation, the expression of fibronectin and connective tissue growth factor, release of interleukin-6, transforming growth factor-β and collagen, and cell migration. Finally, the treatment of PSCs with high glucose and antioxidants attenuated these changes. In conclusion, we demonstrated that high glucose increased oxidative stress in primary rat PSCs, thereby facilitating the activation of these cells, while antioxidant treatment attenuated high glucose-induced PSC activation.

  10. Oxidative stress plays a role in high glucose-induced activation of pancreatic stellate cells

    International Nuclear Information System (INIS)

    Ryu, Gyeong Ryul; Lee, Esder; Chun, Hyun-Ji; Yoon, Kun-Ho; Ko, Seung-Hyun; Ahn, Yu-Bae; Song, Ki-Ho

    2013-01-01

    Highlights: •High glucose increased production of reactive oxygen species in cultured pancreatic stellate cells. •High glucose facilitated the activation of these cells. •Antioxidant treatment attenuated high glucose-induced activation of these cells. -- Abstract: The activation of pancreatic stellate cells (PSCs) is thought to be a potential mechanism underlying islet fibrosis, which may contribute to progressive β-cell failure in type 2 diabetes. Recently, we demonstrated that antioxidants reduced islet fibrosis in an animal model of type 2 diabetes. However, there is no in vitro study demonstrating that high glucose itself can induce oxidative stress in PSCs. Thus, PSCs were isolated and cultured from Sprague Dawley rats, and treated with high glucose for 72 h. High glucose increased the production of reactive oxygen species. When treated with high glucose, freshly isolated PSCs exhibited myofibroblastic transformation. During early culture (passage 1), PSCs treated with high glucose contained an increased number of α-smooth muscle actin-positive cells. During late culture (passages 2–5), PSCs treated with high glucose exhibited increases in cell proliferation, the expression of fibronectin and connective tissue growth factor, release of interleukin-6, transforming growth factor-β and collagen, and cell migration. Finally, the treatment of PSCs with high glucose and antioxidants attenuated these changes. In conclusion, we demonstrated that high glucose increased oxidative stress in primary rat PSCs, thereby facilitating the activation of these cells, while antioxidant treatment attenuated high glucose-induced PSC activation

  11. Visfatin Is Actively Secreted In Vitro From U-937 Macrophages, but Only Passively Released From 3T3-L1 Adipocytes and HepG2 Hepatocytes

    Czech Academy of Sciences Publication Activity Database

    Svoboda, Petr; Křížová, E.; Čeňková, K.; Vápenková, K.; Zídková, J.; Zídek, Václav; Škop, V.

    2017-01-01

    Roč. 66, č. 4 (2017), s. 709-714 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA16-04859S; GA ČR(CZ) GA13-04580S Institutional support: RVO:67985823 Keywords : Nampt * Visfatin * active secretion * adipocytes * hepatocytes * macrophages Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Endocrinology and metabolism (including diabetes, hormones) Impact factor: 1.461, year: 2016

  12. Alternatively Activated Macrophages Play an Important Role in Vascular Remodeling and Hemorrhaging in Patients with Brain Arteriovenous Malformation.

    Science.gov (United States)

    Nakamura, Yukihiko; Sugita, Yasuo; Nakashima, Shinji; Okada, Yousuke; Yoshitomi, Munetake; Kimura, Yoshizou; Miyoshi, Hiroaki; Morioka, Motohiro; Ohshima, Koichi

    2016-03-01

    Angiogenic and immunoactive lesions in brain arteriovenous malformation (BAVM) contribute to hemorrhagic events and the growth of BAVMs. However, the detailed mechanism is unclear. Our objective is to clarify the relationship between hemorrhagic events of BAVM and alternatively activated macrophages in the perinidal dilated capillary network (PDCN). We examined microsurgical specimens of BVMs (n = 29) and focused on the PDCN area. Ten autopsied brains without intracranial disease were the controls. We performed immunostaining of the inflammatory and endothelial cell markers, macrophage markers (CD163 and CD68), and vascular endothelial growth factor A (VEGF-A). We evaluated each cell's density and the vessel density in the PDCN and analyzed the relationship to hemorrhagic events of BAVM. The PDCN was involved in all the resected arteriovenous malformations, and these vessels showed a high rate of CD105 expression (72.0 ± 10.64%), indicating newly proliferating vessels. Alternatively activated macrophages were found, with a high rate (85.6%) for all macrophages (controls, 56.6%). In the hemorrhagic cases, the cell density was significantly higher than that in the nonhemorrhagic cases and controls (hemorrhagic group, 290 ± 44 cells/mm(2); nonhemorrhagic group, 180 ± 59 cells/mm(2); and control, 19 ± 8 cells/mm(2)). The cell density of alternatively activated macrophages showed a positive correlation with the vessel density of the PDCN. Double immunostaining showed that VEGF-A was secreted by alternatively activated macrophages. Our data suggest that alternatively activated macrophages may have some relationships with angiogenesis of PDCN and hemorrhagic event of BAVM. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  13. Home environment as a predictor of child's language: A mediating role of family literacy activities and symbolic play

    Directory of Open Access Journals (Sweden)

    Urška Fekonja-Peklaj

    2015-06-01

    Full Text Available In our study, we explored the ways in which SES-related factors of family environment affect child's language across toddlerhood and early childhood. We proposed a mediational path model in which we presumed that family literacy activities and parental encouragement of symbolic play acted as mediating variables, mediating the effect of parental education, family possessions and parent-to-child speech on child's language. The sample included 99 families with children, aged from 1 to 6 years. The data were collected in the family home, mostly via direct observation and by using a semi-structured interview with parents. The findings suggest that high-SES parents and parents who used a more complex and supportive speech, more frequently involved their children in different literacy activities. The effect of the parent-to-child speech on child's language proved to be mediated by parental use of mental transformations during symbolic play with a child.

  14. An analysis of playing activity of 19-21-years-old footballers in the leading teams of Europe

    Directory of Open Access Journals (Sweden)

    Nikolaenko V.V.

    2012-11-01

    Full Text Available Competition activity of footballers of 19-21-years-old age in the professional commands of Europe on football is considered. Data for research serves the normatively-legal documents of football Federations of leading European championships (request folias and protocols of matches. It was attached the construction of the statistical grouping that in dynamic allow to analyze playing activity of footballers of 19-21-years-old age at the stage of preparation to the higher achievements. It is appraised the influence of the competition loading on the organism of sportsmen of this age. It is defined that participating of 19-21-years athletes in team of professional commands-leaders of UEFA rating. The necessity of research of psychophysiological and morphological characteristics of sportsmen of different playing lines in football, their usage in control and selection in professional teams were defined.

  15. Physical Activity and Energy Expenditure during an After-School Running Club: Laps versus Game Play

    Science.gov (United States)

    Kahan, David; McKenzie, Thomas L.

    2018-01-01

    Background: After-school programs (ASPs) have the potential to contribute to student physical activity (PA), but there is limited empirical evidence to guide program development and implementation. Methods: We used pedometry to assess the overall effectiveness of an elementary school ASP running program relative to national and state PA…

  16. Parental Support Exceeds Parenting Style for Promoting Active Play in Preschool Children

    Science.gov (United States)

    Schary, David P.; Cardinal, Bradley J.; Loprinzi, Paul D.

    2012-01-01

    Emerging evidence suggests that parenting style may directly or indirectly influence school-aged children's activity behaviour. Given that relatively fewer studies have been conducted among preschool-aged children, this study's primary purpose was to examine the direct relationships between parental support and parenting style on preschool…

  17. Other-Repetition as a Resource for Participation in the Activity of Playing a Video Game

    Science.gov (United States)

    Piirainen-Marsh, Arja; Tainio, Liisa

    2009-01-01

    This article offers an empirically based contribution to the growing body of studies using Conversation Analysis (CA) as a tool for analyzing second/foreign language learning in and through interaction. Building on a sociointeractional view of learning as grounded in the structures of participation in social activities, we apply CA methods to…

  18. Do family environment factors play a role in adolescents' involvement in organized activities?

    NARCIS (Netherlands)

    Badura, Petr; Madarasova Geckova, Andrea; Sigmundova, Dagmar; Sigmund, Erik; van Dijk, Jitse P; Reijneveld, Sijmen A

    The study assessed the association of family environment factors with adolescents' participation in organized leisure-time activities (OLTA). We used data on 10,472 Czech adolescents aged 11-15 years (49.2% boys) from the 2013/2014 Health Behaviour in School-aged Children study. The associations of

  19. Active Learning through Role Playing: Virtual Babies in a Child Development Course

    Science.gov (United States)

    Poling, Devereaux A.; Hupp, Julie M.

    2009-01-01

    The authors designed an active learning project for a child development course in which students apply core concepts to a hypothetical baby they "raise" during the term. Students applied developmental topics to their unique, developing child. The project fostered student learning and enthusiasm for the material. The project's versatility makes it…

  20. Analyzing the Learning Process of an Online Role-Playing Discussion Activity

    Science.gov (United States)

    Hou, Huei-Tse

    2012-01-01

    Instructional activities based on online discussion strategies have gained prevalence in recent years. Within this context, a crucial research topic is to design innovative and appropriate online discussion strategies that assist learners in attaining a deeper level of interaction and higher cognitive skills. By analyzing the process of online…

  1. EphB2 activity plays a pivotal role in pediatric medulloblastoma cell adhesion and invasion

    NARCIS (Netherlands)

    Sikkema, Arend H.; den Dunnen, Wilfred F. A.; Hulleman, Esther; van Vuurden, Dannis G.; Garcia-Manero, Guillermo; Yang, Hui; Scherpen, Frank J. G.; Kampen, Kim R.; Hoving, Eelco W.; Kamps, Willem A.; Diks, Sander H.; Peppelenbosch, Maikel P.; de Bont, Eve Line S. J. M.

    Eph/ephrin signaling has bcen implicated in various types of key cancer-enhancing processes, like migration, proliferation, and angiogenesis. In medulloblastoma, invading tumor cells characteristically lead to early recurrence and a decreased prognosis. Based on kinase-activity profiling data

  2. The immunomodulatory effect of Zingiber cassumunar ethanolic extract on phagocytic activity, nitrit oxide and reaxtive oxygen intermediate secretions of macrophage in mice

    Science.gov (United States)

    Nurkhasanah; Santoso, R. D.; Fauziah, R.

    2017-11-01

    Immunomodulators could protect the body from a variety of infectious agents and boost immunity. Zingiber cassumunar rhizome or bangle potentially showed as an immunomodulator through increasing of macrophage activity in vitro. The objective of the study was to determine the effect of Z. cassumunar rhizome ethanolic extract on phagocytic activity, nitrite oxide (NO) and reactive oxygen intermediate (ROI) secretions in macrophages in vivo. A total of 200 g of Z. cassumunar rhizome was powdered, macerated in 96% ethanol and evaporated to get concentrated extract. Mice were divided into 5 groups as follow: the normal group was given by water only, the negative control group was given by a 0.94% CMC-Na suspension, the treatment groups were given by 250, 500 and 1000 mg/kgBW, respectively, of Z. cassumunar ethanolic extract. The extract was administered orally for 7 days. On the 8th day the mice were injected intraperitoneally 0.7 mg/kg BW of lipopolysaccharide. Four hours later macrophage was isolated. Furthermore, the determination of the phagocytic activity, NO and ROI secretions levels of macrophage were performed. The treatments of 250, 500 and 1000 mg/kg BW of Z. cassumunar ethanolic extract significantly increase the ROI and NO secretions levels (p0.05) of macrophage. Z. cassumunar ethanolic extract have immunomodulatory effect in vivo.

  3. What is the role played by physical activity and exercise in the frailty syndrome? Perspectives for future research.

    Science.gov (United States)

    de Souto Barreto, Philipe

    2010-01-01

    Exercise and physical activity play an important role in physical frailty, but we do not know if they are markers, components and/or correlates of this syndrome. The purpose of this paper is briefly to discuss the potential roles played by physical activity and exercise on the development and progression of frailty, and to propose directions for future research in this field. Exercise practice lowers the levels of some frailty markers, such as tumor necrosis factor-alpha, interleukin-6, C-reactive protein, and uric acid, and also resistance to insulin. The influence of exercise on the main frailty domains is also well established in the literature. Exercise improves muscle strength, gait speed, cognition (particularly executive control related-tasks), weight maintenance, mood and, to a lesser extent, feelings of energy. Although exercise and physical activity positively influence the main frailty markers and domains, most findings were obtained for other elderly populations (e.g., healthy elderly, clinical populations). For future research, efforts must be made to define some key concepts (exercise or physical activity) in selecting study samples and in establishing intervention length. Attention must also be paid to identifying the most efficacious exercise interventions regarding type, frequency, intensity and session duration, and approaching a dose-response relationship between a physically active life-style and frailty. Thus, further research, especially longitudinal randomized controlled trials, is needed to understand the role of physical activity and exercise in the frailty syndrome.

  4. Does playing a sports active video game improve object control skills of children with autism spectrum disorder?

    OpenAIRE

    Edwards, Jacqueline; Jeffrey, Sarah; May, Tamara; Rinehart, Nicole J.; Barnett, Lisa M.

    2017-01-01

    Background: Active video games (AVGs) encourage whole body movements to interact or control the gaming system, allowing the opportunity for skill development. Children with autism spectrum disorder (ASD) show decreased fundamental movement skills in comparison with their typically developing (TD) peers and might benefit from this approach. This pilot study investigates whether playing sports AVGs can increase the actual and perceived object control (OC) skills of 11 children with ASD aged 6–1...

  5. Genetic and biochemical characterization of the cell wall hydrolase activity of the major secreted protein of Lactobacillus rhamnosus GG

    NARCIS (Netherlands)

    Claes, I.J.; Schoofs, G.; Regulski, K.; Vos, de W.M.

    2012-01-01

    Lactobacillus rhamnosus GG (LGG) produces two major secreted proteins, designated here Msp1 (LGG_00324 or p75) and Msp2 (LGG_00031 or p40), which have been reported to promote the survival and growth of intestinal epithelial cells. Intriguingly, although each of these proteins shares homology with

  6. Venom allergen-like proteins in secretions of plant-parasitic nematodes activate and suppress extracellular plant immune receptors

    NARCIS (Netherlands)

    Lozano Torres, J.L.

    2014-01-01

    Parasitic worms threaten human, animal and plant health by infecting people, livestock and crops worldwide. Animals and plants share an anciently evolved innate immune system. Parasites modulate this immune system by secreting proteins to maintain their parasitic lifestyle. This thesis

  7. Suppression or activation of immune responses by predicted secreted proteins of the soybean rust pathogen Phakopsora pachyrhizi

    Science.gov (United States)

    Rust fungi, such as Phakopsora pachyrhizi, are major threats to crop production. They form specialized haustoria that are intimately associated with plant cells. These haustoria have roles in acquiring nutrients and secreting effector proteins that manipulate host immune systems. Functional characte...

  8. Pancreatic bicarbonate secretion involves two proton pumps

    DEFF Research Database (Denmark)

    Novak, Ivana; Wang, Jing; Henriksen, Katrine L.

    2011-01-01

    Pancreas secretes fluid rich in digestive enzymes and bicarbonate. The alkaline secretion is important in buffering of acid chyme entering duodenum and for activation of enzymes. This secretion is formed in pancreatic ducts, and studies to date show that plasma membranes of duct epithelium expres...

  9. Increasing Physical Activity among Adults with Disabilities: Doctors Can Play a Key Role

    Centers for Disease Control (CDC) Podcasts

    2014-04-22

    In this podcast, Dr. Dianna Carroll, a senior health scientist with CDC’s Division of Human Development and Disability, talks about the role of doctors and other health professionals in increasing physical activity among adults with disabilities.  Created: 4/22/2014 by National Center on Birth Defects and Developmental Disabilities (NCBDDD).   Date Released: 5/7/2014.

  10. Cell fusion in osteoclasts plays a critical role in controlling bone mass and osteoblastic activity

    International Nuclear Information System (INIS)

    Iwasaki, Ryotaro; Ninomiya, Ken; Miyamoto, Kana; Suzuki, Toru; Sato, Yuiko

    2008-01-01

    The balance between osteoclast and osteoblast activity is central for maintaining the integrity of bone homeostasis. Here we show that mice lacking dendritic cell specific transmembrane protein (DC-STAMP), an essential molecule for osteoclast cell-cell fusion, exhibited impaired bone resorption and upregulation of bone formation by osteoblasts, which do not express DC-STAMP, which led to increased bone mass. On the contrary, DC-STAMP over-expressing transgenic (DC-STAMP-Tg) mice under the control of an actin promoter showed significantly accelerated cell-cell fusion of osteoclasts and bone resorption, with decreased osteoblastic activity and bone mass. Bone resorption and formation are known to be regulated in a coupled manner, whereas DC-STAMP regulates bone homeostasis in an un-coupled manner. Thus our results indicate that inhibition of a single molecule provides both decreased osteoclast activity and increased bone formation by osteoblasts, thereby increasing bone mass in an un-coupled and a tissue specific manner.

  11. Windows 8 secrets

    CERN Document Server

    Thurrott, Paul

    2012-01-01

    Tips, tricks, treats, and secrets revealed on Windows 8 Microsoft is introducing a major new release of its Windows operating system, Windows 8, and what better way to learn all its ins and outs than from two internationally recognized Windows experts and Microsoft insiders, authors Paul Thurrott and Rafael Rivera? They cut through the hype to get at useful information you'll not find anywhere else, including what role this new OS plays in a mobile and tablet world. Regardless of your level of knowledge, you'll discover little-known facts about how things work, what's new and different, and h

  12. Inhibition of neurotensin-stimulated mast cell secretion and carboxypeptidase A activity by the peptide inhibitor of carboxypeptidase A and neurotensin-receptor antagonist SR 48692.

    Science.gov (United States)

    Miller, L A; Cochrane, D E; Feldberg, R S; Carraway, R E

    1998-06-01

    Neurotensin (NT), a peptide found in brain and several peripheral tissues, is a potent stimulus for mast cell secretion and its actions are blocked by the specific NT receptor antagonist, SR 48692. Subsequent to stimulation, NT is rapidly degraded by mast cell carboxypeptidase A (CPA). In the experiments described here, we tested for the involvement of CPA activity in the activation of mast cell secretion by the peptide, NT. Mast cells were isolated from the peritoneal and pleural cavities of rats, purified over metrizamide gradients and incubated at 37 degrees C in Locke solution or Locke containing the appropriate inhibitors. For some experiments, media derived from mast cells stimulated by compound 48/80 were used as a source of mast cell CPA activity. Treatment of mast cells with the highly specific peptide inhibitor of CPA derived from potato (PCI) inhibited histamine release in response to NT and NT8-13 (the biologically active region of NT). This inhibition required some 20 min to develop and was only partially reversed by a 20-min wash period. PCI (10 microM) did not inhibit histamine release in response to NT1-12, bradykinin, compound 48/80, the calcium ionophore, A23187, or anti-IgE serum. PCI also inhibited mast cell CPA activity. SR 48692, a highly selective antagonist of the brain NT receptor and of NT-stimulated mast cell secretion, also inhibited mast cell CPA activity as well as bovine pancreatic CPA activity in a concentration-dependent manner. It is suggested that the mast cell binding site for NT and the active site for CPA may share similar characteristics. The results are discussed in terms of NT mechanism of action on the mast cell.

  13. Active Play in After-school Programmes: development of an intervention and description of a matched-pair cluster-randomised trial assessing physical activity play in after-school programmes.

    Science.gov (United States)

    Riiser, Kirsti; Helseth, Sølvi; Ellingsen, Hanna; Fallang, Bjørg; Løndal, Knut

    2017-08-04

    Interventions delivered in after-school programmes (ASPs) have the potential to become a means of ensuring adequate physical activity among schoolchildren. This requires a motivational climate, allowing for self-determined play. If trained, ASP staff may represent a valuable resource for supporting such play. Increasing knowledge and supportive skills among ASP staff may also potentially increase their motivation for work. The purpose of this article is to describe the development of the 'Active Play in ASP' intervention, which aims to promote physical activity among first graders attending ASP, and to present a protocol for a matched-pair cluster-randomised trial to evaluate the intervention. Informed by experiences from practice, evidence-based knowledge and theory, the intervention was developed in a stepwise process including focus group meetings and a small-scale pilot test. The intervention contains a course programme for ASP staff to increase their skills in how to support physical activity through play. In a cluster randomised controlled trial, the ASPs will be matched and randomly allocated to receive the 7-month intervention or to a control group. Outcomes will be assessed at baseline, after 7 and 19 months. First graders attending the ASPs included are eligible. The primary outcome will be accelerometer-determined minutes in moderate to vigorous physical activity in the ASP. The study uses a mixed methods approach including observations and interviews to provide rich descriptions of the concept of children's physical activity in ASP. Moreover, the trial will assess whether the ASP staff benefits from participation in the intervention in terms of increased work motivation. Lastly, process evaluations of programme fidelity, satisfaction and suggestions on improvement will be performed. The study is approved by the Data Protection Official for Research (reference no 46008). Results will be presented in conferences and peer-reviewed journals. Clinical Trials

  14. LcrG secretion is not required for blocking of Yops secretion in Yersinia pestis

    Directory of Open Access Journals (Sweden)

    Matson Jyl S

    2008-02-01

    Full Text Available Abstract Background LcrG, a negative regulator of the Yersinia type III secretion apparatus has been shown to be primarily a cytoplasmic protein, but is secreted at least in Y. pestis. LcrG secretion has not been functionally analyzed and the relevance of LcrG secretion on LcrG function is unknown. Results An LcrG-GAL4AD chimera, originally constructed for two-hybrid analyses to analyze LcrG protein interactions, appeared to be not secreted but the LcrG-GAL4AD chimera retained the ability to regulate Yops secretion. This result led to further investigation to determine the significance of LcrG secretion on LcrG function. Additional analyses including deletion and substitution mutations of amino acids 2–6 in the N-terminus of LcrG were constructed to analyze LcrG secretion and LcrG's ability to control secretion. Some changes to the N-terminus of LcrG were found to not affect LcrG's secretion or LcrG's secretion-controlling activity. However, substitution of poly-isoleucine in the N-terminus of LcrG did eliminate LcrG secretion but did not affect LcrG's secretion controlling activity. Conclusion These results indicate that secretion of LcrG, while observable and T3SS mediated, is not relevant for LcrG's ability to control secretion.

  15. GTPase activity plays a key role in the pathobiology of LRRK2.

    Directory of Open Access Journals (Sweden)

    Yulan Xiong

    2010-04-01

    Full Text Available Mutations in the leucine-rich repeat kinase 2 (LRRK2 gene are associated with late-onset, autosomal-dominant, familial Parkinson's disease (PD and also contribute to sporadic disease. The LRRK2 gene encodes a large protein with multiple domains, including functional Roc GTPase and protein kinase domains. Mutations in LRRK2 most likely cause disease through a toxic gain-of-function mechanism. The expression of human LRRK2 variants in cultured primary neurons induces toxicity that is dependent on intact GTP binding or kinase activities. However, the mechanism(s underlying LRRK2-induced neuronal toxicity is poorly understood, and the contribution of GTPase and/or kinase activity to LRRK2 pathobiology is not well defined. To explore the pathobiology of LRRK2, we have developed a model of LRRK2 cytotoxicity in the baker's yeast Saccharomyces cerevisiae. Protein domain analysis in this model reveals that expression of GTPase domain-containing fragments of human LRRK2 are toxic. LRRK2 toxicity in yeast can be modulated by altering GTPase activity and is closely associated with defects in endocytic vesicular trafficking and autophagy. These truncated LRRK2 variants induce similar toxicity in both yeast and primary neuronal models and cause similar vesicular defects in yeast as full-length LRRK2 causes in primary neurons. The toxicity induced by truncated LRRK2 variants in yeast acts through a mechanism distinct from toxicity induced by human alpha-synuclein. A genome-wide genetic screen identified modifiers of LRRK2-induced toxicity in yeast including components of vesicular trafficking pathways, which can also modulate the trafficking defects caused by expression of truncated LRRK2 variants. Our results provide insight into the basic pathobiology of LRRK2 and suggest that the GTPase domain may contribute to the toxicity of LRRK2. These findings may guide future therapeutic strategies aimed at attenuating LRRK2-mediated neurodegeneration.

  16. p38 mitogen-activated protein kinase plays a key role in regulating MAPKAPK2 expression

    International Nuclear Information System (INIS)

    Sudo, Tatsuhiko; Kawai, Kayoko; Matsuzaki, Hiroshi; Osada, Hiroyuki

    2005-01-01

    One of three major families of the mitogen-activated kinases (MAPK), p38 as well as JNK, has been shown to transduce extracellular stress stimuli into cellular responses by phospho-relay cascades. Among p38 families, p38α is a widely characterized isoform and the biological phenomena are explained by its kinase activity regulating functions of its downstream substrates. However, its specific contributions to each phenomenon are yet not fully elucidated. For better understanding of the role of MAPKs, especially p38α, we utilized newly established mouse fibroblast cell lines originated from a p38α null mouse, namely, a parental cell line without p38α gene locus, knockout of p38α (KOP), Zeosin-resistant (ZKOP), revertant of p38α (RKOP), and Exip revertant (EKOP). EKOP is smaller in size but grows faster than the others. Although comparable amounts of ERK and JNK are expressed in each cell line, ERK is highly phosphorylated in EKOP even in normal culture conditions. Serum stimulation after serum starvation led to ERK phosphorylation in RKOP and ZKOP, but not in EKOP as much. On the contrary, relative phosphorylation level of JNK to total JNK in response to UV was low in RKOP. And its phosphorylation as well as total JNK is slightly lower in EKOP. RKOP is less sensitive to UV irradiation as judged by the survival rate. Stress response upon UV or sorbitol stimuli, leading to mitogen activate protein kinase activated kinase 2 (MAPKAPK2) phosphorylation, was only observed in RKOP. Further experiments reveal that MAPKAPK2 expression is largely suppressed in ZKOP and EKOP. Its expression was recovered by re-introduction of p38α. The loss of MAPKAPK2 expression accompanied by the defect of p38α is confirmed in an embryonic extract prepared from p38α null mice. These data demonstrate that p38 signal pathway is regulated not only by phosphorylation but also by modulation of the expression of its component. Together, we have established cell lines that can be used in

  17. Plasmodium falciparum Adhesins Play an Essential Role in Signalling and Activation of Invasion into Human Erythrocytes.

    Directory of Open Access Journals (Sweden)

    Wai-Hong Tham

    2015-12-01

    Full Text Available The most severe form of malaria in humans is caused by the protozoan parasite Plasmodium falciparum. The invasive form of malaria parasites is termed a merozoite and it employs an array of parasite proteins that bind to the host cell to mediate invasion. In Plasmodium falciparum, the erythrocyte binding-like (EBL and reticulocyte binding-like (Rh protein families are responsible for binding to specific erythrocyte receptors for invasion and mediating signalling events that initiate active entry of the malaria parasite. Here we have addressed the role of the cytoplasmic tails of these proteins in activating merozoite invasion after receptor engagement. We show that the cytoplasmic domains of these type 1 membrane proteins are phosphorylated in vitro. Depletion of PfCK2, a kinase implicated to phosphorylate these cytoplasmic tails, blocks P. falciparum invasion of red blood cells. We identify the crucial residues within the PfRh4 cytoplasmic domain that are required for successful parasite invasion. Live cell imaging of merozoites from these transgenic mutants show they attach but do not penetrate erythrocytes implying the PfRh4 cytoplasmic tail conveys signals important for the successful completion of the invasion process.

  18. High-level secretion of tissue factor-rich extracellular vesicles from ovarian cancer cells mediated by filamin-A and protease-activated receptors.

    Science.gov (United States)

    Koizume, Shiro; Ito, Shin; Yoshioka, Yusuke; Kanayama, Tomohiko; Nakamura, Yoshiyasu; Yoshihara, Mitsuyo; Yamada, Roppei; Ochiya, Takahiro; Ruf, Wolfram; Miyagi, Etsuko; Hirahara, Fumiki; Miyagi, Yohei

    2016-01-01

    Thromboembolic events occur frequently in ovarian cancer patients. Tissue factor (TF) is often overexpressed in tumours, including ovarian clear-cell carcinoma (CCC), a subtype with a generally poor prognosis. TF-coagulation factor VII (fVII) complexes on the cell surface activate downstream coagulation mechanisms. Moreover, cancer cells secrete extracellular vesicles (EVs), which act as vehicles for TF. We therefore examined the characteristics of EVs produced by ovarian cancer cells of various histological subtypes. CCC cells secreted high levels of TF within EVs, while the high-TF expressing breast cancer cell line MDA-MB-231 shed fewer TF-positive EVs. We also found that CCC tumours with hypoxic tissue areas synthesised TF and fVII in vivo, rendering the blood of xenograft mice bearing these tumours hypercoagulable compared with mice bearing MDA-MB-231 tumours. Incorporation of TF into EVs and secretion of EVs from CCC cells exposed to hypoxia were both dependent on the actin-binding protein, filamin-A (filA). Furthermore, production of these EVs was dependent on different protease-activated receptors (PARs) on the cell surface. These results show that CCC cells could produce large numbers of TF-positive EVs dependent upon filA and PARs. This phenomenon may be the mechanism underlying the increased incidence of venous thromboembolism in ovarian cancer patients.

  19. Histoplasma capsulatum-Induced Cytokine Secretion in Lung Epithelial Cells Is Dependent on Host Integrins, Src-Family Kinase Activation, and Membrane Raft Recruitment.

    Science.gov (United States)

    Maza, Paloma K; Suzuki, Erika

    2016-01-01

    Histoplasma capsulatum var. capsulatum is a dimorphic fungus that causes histoplasmosis, a human systemic mycosis with worldwide distribution. In the present work, we demonstrate that H. capsulatum yeasts are able to induce cytokine secretion by the human lung epithelial cell line A549 in integrin- and Src-family kinase (SFK)-dependent manners. This conclusion is supported by small interfering RNA (siRNA) directed to α3 and α5 integrins, and PP2, an inhibitor of SFK activation. siRNA and PP2 reduced IL-6 and IL-8 secretion in H. capsulatum-infected A549 cell cultures. In addition, α3 and α5 integrins from A549 cells were capable of associating with H. capsulatum yeasts, and this fungus promotes recruitment of these integrins and SFKs to A549 cell membrane rafts. Corroborating this finding, membrane raft disruption with the cholesterol-chelator methyl-β-cyclodextrin reduced the levels of integrins and SFKs in these cell membrane domains. Finally, pretreatment of A549 cells with the cholesterol-binding compound, and also a membrane raft disruptor, filipin, significantly reduced IL-6 and IL-8 levels in A549-H.capsulatum cultures. Taken together, these results indicate that H. capsulatum yeasts induce secretion of IL-6 and IL-8 in human lung epithelial cells by interacting with α3 and α5 integrins, recruiting these integrins to membrane rafts, and promoting SFK activation.

  20. Biphasic electrical targeting plays a significant role in schwann cell activation.

    Science.gov (United States)

    Kim, In Sook; Song, Yun Mi; Cho, Tae Hyung; Pan, Hui; Lee, Tae Hyung; Kim, Sung June; Hwang, Soon Jung

    2011-05-01

    Electrical stimulation (ES) is a promising technique for axonal regeneration of peripheral nerve injuries. However, long-term, continuous ES in the form of biphasic electric current (BEC) to stimulate axonal regeneration has rarely been attempted and the effects of BEC on Schwann cells are unknown. We hypothesized that long-term, continuous ES would trigger the activation of Schwann cells, and we therefore investigated the effect of BEC on the functional differentiation of primary human mesenchymal stromal cells (hMSCs) into Schwann cells, as well as the activity of primary Schwann cells. Differentiation of hMSCs into Schwann cells was determined by coculture with rat pheochromocytoma cells (PC12 cell line). We also investigated the in vivo effects of long-term ES (4 weeks) on axonal outgrowth of a severed sciatic nerve with a 7-mm gap after retraction of the nerve ends in rats by implanting an electronic device to serve as a neural conduit. PC12 cells cocultured with hMSCs electrically stimulated during culture in Schwann cell differentiation medium (Group I) had longer neurites and a greater percentage of PC12 cells were neurite-sprouting than when cocultured with hMSCs cultured in growth medium (control group) or unstimulated hMSCs in the same culture conditions as used for Group I (Group II). Group I cells showed significant upregulation of Schwann cell-related neurotrophic factors such as nerve growth factor and glial-derived neurotrophic factor compared to Group II cells at both the mRNA and protein levels. Primary Schwann cells responded to continuous BEC with increased proliferation and the induction of nerve growth factor and glial-derived neurotrophic factor, similar to Group I cells, and in addition, induction of brain-derived neurotrophic factor was observed. Immunohistochemical investigation of sciatic nerve regenerates revealed that BEC increased axonal outgrowth significantly. These results demonstrate that BEC enhanced the functional activity of

  1. A noncognate interaction with anti-receptor antibody-activated helper T cells induces small resting murine B cells to proliferate and to secrete antibody

    DEFF Research Database (Denmark)

    Owens, T

    1988-01-01

    on resting B cells (even in the presence of intact F23.1 antibody), but could induce antibody secretion by anti-Ig-preactivated B cells. Both F23.1+ clones (E9.D4 and 4.35F2) and one F23.1- clone (D2.2) could synergize with supernatants from activated E9.D4 T cells to induce B cell activation. F(ab')2......Culture of small resting allogeneic B cells (of an irrelevant haplotype) with two clones of T helper (Th) cells that were activated by the F23.1 anti-T cell receptor antibody led to the activation of B cells to proliferate and to secrete antibody. Th cell supernatants by themselves had no effect...... fragments of F23.1 induced E9.D4 to activate B cells as efficiently as intact F23.1 and B cell populations that had been incubated with F23.1 were not activated when cultured with E9.D4, although T cells recognized cell-presented F23.1 and were weakly activated. Reduction of the density of F23.1 adsorbed...

  2. Playing on the edge

    DEFF Research Database (Denmark)

    Cermak-Sassenrath, Daniel

    2018-01-01

    and specific ways. For instance, gambling for money, party and drinking games, professional play and show sports, art installations, violent and military propaganda computer games, pervasive/mobile gaming, live-action role playing, festivals, performances, and games such as Ghosting and Planking. It is argued......Everything gets more interesting, challenging, or intense the closer it gets to the edge, and so does play. How edgy can play become and still be play? Based on Huizinga’s notion of play, this chapter discusses how a wide range of playful activities pushes the boundaries of play in different...... that in concert with a number of characteristics that mark an activity as play, play is essentially a subjective perspective and individual decision of the player. Huizinga calls this attitude the play spirit, which informs a player’s actions and is in turn sustained by them. Edgy digital or mobile games do...

  3. Sweet taste receptor expressed in pancreatic beta-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion.

    Directory of Open Access Journals (Sweden)

    Yuko Nakagawa

    Full Text Available BACKGROUND: Sweet taste receptor is expressed in the taste buds and enteroendocrine cells acting as a sugar sensor. We investigated the expression and function of the sweet taste receptor in MIN6 cells and mouse islets. METHODOLOGY/PRINCIPAL FINDINGS: The expression of the sweet taste receptor was determined by RT-PCR and immunohistochemistry. Changes in cytoplasmic Ca(2+ ([Ca(2+](c and cAMP ([cAMP](c were monitored in MIN6 cells using fura-2 and Epac1-camps. Activation of protein kinase C was monitored by measuring translocation of MARCKS-GFP. Insulin was measured by radioimmunoassay. mRNA for T1R2, T1R3, and gustducin was expressed in MIN6 cells. In these cells, artificial sweeteners such as sucralose, succharin, and acesulfame-K increased insulin secretion and augmented secretion induced by glucose. Sucralose increased biphasic increase in [Ca(2+](c. The second sustained phase was blocked by removal of extracellular calcium and addition of nifedipine. An inhibitor of inositol(1, 4, 5-trisphophate receptor, 2-aminoethoxydiphenyl borate, blocked both phases of [Ca(2+](c response. The effect of sucralose on [Ca(2+](c was inhibited by gurmarin, an inhibitor of the sweet taste receptor, but not affected by a G(q inhibitor. Sucralose also induced sustained elevation of [cAMP](c, which was only partially inhibited by removal of extracellular calcium and nifedipine. Finally, mouse islets expressed T1R2 and T1R3, and artificial sweeteners stimulated insulin secretion. CONCLUSIONS: Sweet taste receptor is expressed in beta-cells, and activation of this receptor induces insulin secretion by Ca(2+ and cAMP-dependent mechanisms.

  4. The role of play

    NARCIS (Netherlands)

    Schouten, B.A.M.

    2011-01-01

    Play is seen as an activity that is fun, voluntary, offers escape, and is fundamentally exciting. Play is however, more than that; it is a working model of flexibility! There is a vital link between play, psychological development and learning. Moreover, the importance of play has gained importance

  5. PPAR-γ activation increases insulin secretion through the up-regulation of the free fatty acid receptor GPR40 in pancreatic β-cells.

    Directory of Open Access Journals (Sweden)

    Hyo-Sup Kim

    Full Text Available BACKGROUND: It has been reported that peroxisome proliferator-activated receptor (PPAR-γ and their synthetic ligands have direct effects on pancreatic β-cells. We investigated whether PPAR-γ activation stimulates insulin secretion through the up-regulation of GPR40 in pancreatic β-cells. METHODS: Rat insulinoma INS-1 cells and primary rat islets were treated with rosiglitazone (RGZ and/or adenoviral PPAR-γ overexpression. OLETF rats were treated with RGZ. RESULTS: PPAR-γ activation with RGZ and/or adenoviral PPAR-γ overexpression increased free fatty acid (FFA receptor GPR40 expression, and increased insulin secretion and intracellular calcium mobilization, and was blocked by the PLC inhibitors, GPR40 RNA interference, and GLUT2 RNA interference. As a downstream signaling pathway of intracellular calcium mobilization, the phosphorylated levels of CaMKII and CREB, and the downstream IRS-2 and phospho-Akt were significantly increased. Despite of insulin receptor RNA interference, the levels of IRS-2 and phospho-Akt was still maintained with PPAR-γ activation. In addition, the β-cell specific gene expression, including Pdx-1 and FoxA2, increased in a GPR40- and GLUT2-dependent manner. The levels of GPR40, phosphorylated CaMKII and CREB, and β-cell specific genes induced by RGZ were blocked by GW9662, a PPAR-γ antagonist. Finally, PPAR-γ activation up-regulated β-cell gene expressions through FoxO1 nuclear exclusion, independent of the insulin signaling pathway. Based on immunohistochemical staining, the GLUT2, IRS-2, Pdx-1, and GPR40 were more strongly expressed in islets from RGZ-treated OLETF rats compared to control islets. CONCLUSION: These observations suggest that PPAR-γ activation with RGZ and/or adenoviral overexpression increased intracellular calcium mobilization, insulin secretion, and β-cell gene expression through GPR40 and GLUT2 gene up-regulation.

  6. Effecf of pH and some cations on activity of acid phosphatase secreted from Ustilago sp. isolated from acid sulphate soil

    Directory of Open Access Journals (Sweden)

    Chairatana Nilnond

    2007-03-01

    Full Text Available Acid phosphatase secreted from Ustilago sp. is able to hydrolyze organic phosphorus. These soil yeast microorganisms were isolated from rice roots grown in acid sulphate soil that generally contains highamount of aluminum (Al, iron (Fe and manganese (Mn ions. Therefore, the objectives of this study were to examine the effect of pH and some cations on acid phosphatase activity. Two isolates of Ustilago sp., AR101and AR102, were cultured in 100 mL of modified Pikovskaya's broth containing Na-phytate, pH 4, and acid phosphatase activity was determined at pH 2.0-7.0. Effect of Al, Fe, and Mn, including calcium (Ca ions,on growth of AR101 and AR102, secreted acid phosphatase activity, and the ability of acid phosphatase on the phosphorus release from Na-phytate by Ustilago sp. were investigated. It was found that the optimum pH for acid phosphatase activity was 3.5-4.5. The activity of acid phosphatase secreted from AR101 (3,690nmol min-1 mL-1 was remarkably higher than that from AR102 (956 nmol min-1 mL-1. Aluminum, iron, manganese and calcium ions in the medium did not affect the growth of either isolate. The activity of secretedacid phosphatase of AR101 was inhibited by Al and Ca ion, and synthesis of acid phosphatase of Ustilago sp. AR102 was possibly stimulated by Fe ion. Both AR101 and AR102 solubilized Na-phytate, resulting in therelease of P. However, some amount of released P was then precipitated with Al and Fe ions as the highly insoluble Fe- or Al- phosphate.

  7. Hands-On Surgical Training Workshop: an Active Role-Playing Patient Education for Adolescents.

    Science.gov (United States)

    Wongkietkachorn, Apinut; Boonyawong, Pangpoom; Rhunsiri, Peera; Tantiphlachiva, Kasaya

    2017-09-01

    Most patient education involves passive learning. To improve patient education regarding surgery, an active learning workshop-based teaching method is proposed. The objective of this study was to assess level of patient surgical knowledge, achievement of workshop learning objectives, patient apprehension about future surgery, and participant workshop satisfaction after completing a surgical training workshop. A four-station workshop (surgical scrub, surgical suture, laparoscopic surgery, and robotic surgery) was developed to teach four important components of the surgical process. Healthy, surgery-naive adolescents were enrolled to attend this 1-h workshop-based training program. Training received by participants was technically and procedurally identical to training received by actual surgeons. Pre- and post-workshop questionnaires were used to assess learning outcomes. There were 1312 participants, with a mean age 15.9 ± 1.1 years and a gender breakdown of 303 males and 1009 females. For surgical knowledge, mean pre-workshop and post-workshop scores were 6.1 ± 1.5 and 7.5 ± 1.5 (out of 10 points), respectively (p education is an effective way to improve understanding of surgery-related processes. This teaching method may also decrease apprehension that patients or potential patients harbor regarding a future surgical procedure.

  8. Chlamydia abortus Pmp18.1 Induces IL-1β Secretion by TLR4 Activation through the MyD88, NF-κB, and Caspase-1 Signaling Pathways.

    Science.gov (United States)

    Pan, Qing; Zhang, Qiang; Chu, Jun; Pais, Roshan; Liu, Shanshan; He, Cheng; Eko, Francis O

    2017-01-01

    The polymorphic membrane protein D (Pmp18D) is a 160-kDa outer membrane protein that is conserved and plays an important role in Chlamydia abortus pathogenesis. We have identified an N-terminal fragment of Pmp18D (designated Pmp18.1) as a possible subunit vaccine antigen. In this study, we evaluated the vaccine potential of Pmp18.1 by investigating its ability to induce innate immune responses in dendritic cells and the signaling pathway(s) involved in rPmp18.1-induced IL-1β secretion. We next investigated the immunomodulatory impact of VCG, in comparison with the more established Th1-promoting adjuvants, CpG and FL, on rPmp18.1-mediated innate immune activation. Finally, the effect of siRNA targeting TLR4, MyD88, NF-κB p50, and Caspase-1 mRNA in DCs on IL-1β cytokine secretion was also investigated. Bone marrow-derived dendritic cells (BMDCs) were stimulated with rPmp18.1 in the presence or absence of VCG or CpG or FL and the magnitude of cytokines produced was assessed using a multiplex cytokine ELISA assay. Expression of costimulatory molecules and Toll-like receptors (TLRs) was analyzed by flow cytometry. Quantitation of intracellular levels of myeloid differentiation factor 88 (MyD88), nuclear factor kappa beta (NF-κB p50/p65), and Caspase-1 was evaluated by Western immunoblotting analysis while NF-κB p65 nuclear translocation was assessed by confocal microscopy. The results showed DC stimulation with rPmp18.1 provoked the secretion of proinflammatory cytokines and upregulated expression of TLRs and co-stimulatory molecules associated with DC maturation. These responses were significantly ( p ≤ 0.001) enhanced by VCG but not CpG or FL. In addition, rPmp18.1 activated the expression of MyD88, NF-κB p50, and Caspase-1 as well as the nuclear expression of NF-κB p65 in treated DCs. Furthermore, targeting TLR4, MyD88, NF-κB p50, and Caspase-1 mRNA in BMDCs with siRNA significantly reduced their expression levels, resulting in decreased IL-1β cytokine

  9. Chlamydia abortus Pmp18.1 Induces IL-1β Secretion by TLR4 Activation through the MyD88, NF-κB, and Caspase-1 Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Qing Pan

    2017-12-01

    Full Text Available The polymorphic membrane protein D (Pmp18D is a 160-kDa outer membrane protein that is conserved and plays an important role in Chlamydia abortus pathogenesis. We have identified an N-terminal fragment of Pmp18D (designated Pmp18.1 as a possible subunit vaccine antigen. In this study, we evaluated the vaccine potential of Pmp18.1 by investigating its ability to induce innate immune responses in dendritic cells and the signaling pathway(s involved in rPmp18.1-induced IL-1β secretion. We next investigated the immunomodulatory impact of VCG, in comparison with the more established Th1-promoting adjuvants, CpG and FL, on rPmp18.1-mediated innate immune activation. Finally, the effect of siRNA targeting TLR4, MyD88, NF-κB p50, and Caspase-1 mRNA in DCs on IL-1β cytokine secretion was also investigated. Bone marrow-derived dendritic cells (BMDCs were stimulated with rPmp18.1 in the presence or absence of VCG or CpG or FL and the magnitude of cytokines produced was assessed using a multiplex cytokine ELISA assay. Expression of costimulatory molecules and Toll-like receptors (TLRs was analyzed by flow cytometry. Quantitation of intracellular levels of myeloid differentiation factor 88 (MyD88, nuclear factor kappa beta (NF-κB p50/p65, and Caspase-1 was evaluated by Western immunoblotting analysis while NF-κB p65 nuclear translocation was assessed by confocal microscopy. The results showed DC stimulation with rPmp18.1 provoked the secretion of proinflammatory cytokines and upregulated expression of TLRs and co-stimulatory molecules associated with DC maturation. These responses were significantly (p ≤ 0.001 enhanced by VCG but not CpG or FL. In addition, rPmp18.1 activated the expression of MyD88, NF-κB p50, and Caspase-1 as well as the nuclear expression of NF-κB p65 in treated DCs. Furthermore, targeting TLR4, MyD88, NF-κB p50, and Caspase-1 mRNA in BMDCs with siRNA significantly reduced their expression levels, resulting in decreased IL-1

  10. Playful Membership

    DEFF Research Database (Denmark)

    Åkerstrøm Andersen, Niels; Pors, Justine Grønbæk

    2014-01-01

    This article studies the implications of current attempts by organizations to adapt to a world of constant change by introducing the notion of playful organizational membership. To this end we conduct a brief semantic history of organizational play and argue that when organizations play, employees...... are expected to engage in playful exploration of alternative selves. Drawing on Niklas Luhmann's theory of time and decision-making and Gregory Bateson's theory of play, the article analyses three empirical examples of how games play with conceptions of time. We explore how games represent an organizational...

  11. Development and use of an observation tool for active gaming and movement (OTAGM) to measure children's movement skill components during active video game play.

    Science.gov (United States)

    Rosa, Rita L; Ridgers, Nicola D; Barnett, Lisa M

    2013-12-01

    This article presents a direct observational tool for assessing children's body movements and movement skills during active video games. The Observation Tool of Active Gaming and Movement (OTGAM) was informed by the Test of Gross Motor Development-2. 18 elementary school children (12 boys, 6 girls; M age = 6.1 yr., SD = 0.9) were observed during Nintendo Wii game play. Using the OTAGM, researchers were able to capture and quantify the children's body movements and movement skills during active play of video games. Furthermore, the OTAGM captured specific components of object control skills: strike, throw, and roll. Game designers, health promotion practitioners, and researchers could use this information to enhance children's physical activity and movement skills.

  12. Relative Expression Levels Rather Than Specific Activity Plays the Major Role in Determining In Vivo AKT Isoform Substrate Specificity

    Directory of Open Access Journals (Sweden)

    Rachel S. Lee

    2011-01-01

    Full Text Available The AKT protooncogene mediates many cellular processes involved in normal development and disease states such as cancer. The three structurally similar isoforms: AKT1, AKT2, and AKT3 exhibit both functional redundancy and isoform-specific functions; however the basis for their differential signalling remains unclear. Here we show that in vitro, purified AKT3 is ∼47-fold more active than AKT1 at phosphorylating peptide and protein substrates. Despite these marked variations in specific activity between the individual isoforms, a comprehensive analysis of phosphorylation of validated AKT substrates indicated only subtle differences in signalling via individual isoforms in vivo. Therefore, we hypothesise, at least in this model system, that relative tissue/cellular abundance, rather than specific activity, plays the dominant role in determining AKT substrate specificity in situ.

  13. Activity Profiles and Physiological Responses of Representative Tag Football Players in Relation to Playing Position and Physical Fitness

    Science.gov (United States)

    2015-01-01

    This study determined the physical fitness, match-activity profiles and physiological responses of representative tag football players and examined the relationship between physical fitness and the match-activity profile. Microtechnology devices and heart rate (HR) chest straps were used to determine the match-activity profiles of sixteen tag football players for five matches during the 2014 Australian National Championships. The relationships between lower body muscular power, straight line running speed and Yo-Yo intermittent recovery test level 2 (Yo-Yo IR2) and the match-activity profile were examined using Pearson’s correlation coefficients. Outside players had greater lower body muscular power (ES = 0.98) and straight line running speed (ES = 1.03–1.18) than inside players, and also covered greater very high-speed running (VHSR) distance/min (ES = 0.67) and reached higher peak running speeds (ES = 0.95) during matches. Inside and outside players performed a similar number of repeated high-intensity effort (RHIE) bouts and reported similar mean and maximum efforts per RHIE bout. However, there were differences between playing positions for mean and maximal RHIE effort durations (ES = 0.69–1.15) and mean RHIE bout recovery (ES = 0.56). Inside and outside players also reported small to moderate differences (ES = 0.43–0.80) for times spent in each HR zone. There were a number of moderate to very large correlations between physical fitness measures and match-activity profile variables. This study found lower body muscular power, straight line running speed and Yo-Yo IR2 to be related to the match-activities of representative tag football players, although differences between inside and outside players suggest that athlete testing and training practices should be modified for different playing positions. PMID:26642320

  14. Will Nintendo "Wii Fit" Get You Fit? An Evaluation of the Energy Expenditure from Active-Play Videogames.

    Science.gov (United States)

    Xian, Ying; Kakinami, Lisa; Peterson, Eric D; Mustian, Karen M; Fernandez, I Diana

    2014-04-01

    This study aimed to determine whether Nintendo(®) (Redmond, WA) "Wii Fit™" games can help individuals meet physical activity recommendations. Thirty young healthy volunteers were recruited for this randomized crossover study to evaluate the energy expenditure associated with (1) a 30-minute "Wii Fit Free Run," (2) three 10-minute bouts of "Wii Fit" aerobic games ("Rhythm Boxing," "Super Hula Hoop," and "Advanced Steps"), and (3) 30-minute treadmill running/walking. Energy expenditure was measured by indirect calorimetry using breath-by-breath analyses of O2 consumption and CO2 production. The "Wii Fit" conditions produced a moderate exercise intensity (5.0, 4.1, 3.9, and 3.8 metabolic equivalents [METs] in "Free Run," "Rhythm Boxing," "Super Hula Hoop," and "Advanced Steps"), whereas the treadmill running/walking produced a vigorous exercise intensity (METs=8.0). Based on federal guidelines, an individual could achieve the minimum weekly goal of 500 MET-minutes by playing selected "Wii Fit" aerobics games for 20-26 minutes a day, 5 days a week. Although not as vigorous as the treadmill, active-play videogames such as "Wii Fit" may provide an alternative way to encourage exercise and increase adoption and adherence to the physical activity guidelines.

  15. Improving the Physical Activity and Outdoor Play Environment of Family Child Care Homes in Nebraska Through Go Nutrition and Physical Activity Self-Assessment for Child Care.

    Science.gov (United States)

    Dinkel, Danae; Dev, Dipti; Guo, Yage; Hulse, Emily; Rida, Zainab; Sedani, Ami; Coyle, Brian

    2018-05-09

    The purpose of this study was to determine if the Go Nutrition and Physical Activity Self-Assessment in Child Care (Go NAP SACC) intervention was effective in improving best practices in the areas of infant and child physical activity and outdoor play and learning in family child care homes (FCCHs) in Nebraska. FCCHs (n = 201) participated in a pre-post evaluation using the Infant and Child Physical Activity and Outdoor Play and Learning assessments from the Go NAP SACC validated measure to assess compliance with best practices. At post, FCCHs demonstrated significant differences in 85% of the Infant and Child Physical Activity items (17 of 20) and 80% of the Outdoor Play and Learning items (12 of 15). Significant differences in best practices between urban and rural FCCH providers were also found. Go NAP SACC appears to be an effective intervention in Nebraska as, after participation in the initiative, providers were improving child care physical activity best practices. Additional research is needed to objectively determine if these changes resulted in objective improvements in children's physical activity levels. Further, efforts are needed to develop and/or identify geographic-specific resources for continued improvement.

  16. Interleukin 2 secretion by lectin-activated human blood lymphocytes is markedly augmented by vascular endothelial cells

    International Nuclear Information System (INIS)

    Guinan, E.C.; Pober, J.S.

    1986-01-01

    Since the initial interaction (and possible activation) of a blood borne T lymphocyte involves contact with the endothelial lining of the vasculature at the site of an immune response, the authors have examined the effect of cultured human endothelial cells (HEC) upon polyclonal T cell activation. Addition of 10 4 HEC to 10 4 -10 5 peripheral blood lymphocytes (PBL) stimulated with phytohemagglutinin (PHA, 0.3-10 μg/ml) leads to marked augmentation of interleukin 2 (IL-2) production. The relative increase in IL-2 (mean of 3 expts. +/- SEM) is present at 24 h (5.8 fold +/- 1.5) and become more marked at 48 h (12.6 fold +/- 3.5) and 72 h (18.5 fold +/- 3.7). This relative enhancement is greater for HEC added to 10 4 than 10 5 PBL and is also greater when 10 4 rather than 2 x 10 3 HEC are added to a given number of PBL. This increased IL-2 concentration has two biological consequences. First, at suboptimal PHA doses or at low PBL number, PBL proliferation as measured by 3 H-thymidine incorporation is increased up to two fold. Second, the phenotype of the proliferating cells appears altered, including a decrease in mean density of IL-2 receptor. The authors hypothesize that such modulation of the concentration of locally produced IL-2 may play a key role in the nature of an immune response, influencing both its magnitude and the functional profile of the activated and amplified effector cells

  17. Antiplatelet Activity of Morus alba Leaves Extract, Mediated via Inhibiting Granule Secretion and Blocking the Phosphorylation of Extracellular-Signal-Regulated Kinase and Akt

    Science.gov (United States)

    Rhee, Man Hee; Sung, Yoon-Young; Yang, Won-Kyung; Kim, Seung Hyung; Kim, Ho-Kyoung

    2014-01-01

    Ethnopharmacological Relevance. Morus alba L. leaves (MAE) have been used in fork medicine for the treatment of beriberi, edema, diabetes, hypertension, and atherosclerosis. However, underlying mechanism of MAE on cardiovascular protection remains to be elucidated. Therefore, we investigated whether MAE affect platelet aggregation and thrombosis. Materials and Methods. The anti-platelet activity of MAE was studied using rat platelets. The extent of anti-platelet activity of MAE was assayed in collagen-induced platelet aggregation. ATP and serotonin release was carried out. The activation of integrin α IIb β 3 and phosphorylation of signaling molecules, including MAPK and Akt, were investigated with cytofluorometer and immunoblotting, respectively. The thrombus formation in vivo was also evaluated in arteriovenous shunt model of rats. Results. HPLC chromatographic analysis revealed that MAE contained rutin and isoquercetin. MAE dose-dependently inhibited collagen-induced platelet aggregation. MAE also attenuated serotonin secretion and thromboxane A2 formation. In addition, the extract in vivo activity showed that MAE at 100, 200, and 400 mg/kg significantly and dose-dependently attenuated thrombus formation in rat arterio-venous shunt model by 52.3% (P < 0.001), 28.3% (P < 0.01), and 19.1% (P < 0.05), respectively. Conclusions. MAE inhibit platelet activation, TXB2 formation, serotonin secretion, aggregation, and thrombus formation. The plant extract could be considered as a candidate to anti-platelet and antithrombotic agent. PMID:24701244

  18. Assessing play-based activities, child talk, and single session outcome in family therapy with young children.

    Science.gov (United States)

    Willis, Amber B; Walters, Lynda H; Crane, D Russell

    2014-07-01

    This exploratory, observational study was designed to reveal descriptive information regarding therapists' actual practices with preschool- and school-aged children in a single session of family therapy and to investigate change mechanisms in family play therapy that have been proposed to make this approach effective. A purposive sample of 30 families receiving family therapy was recruited and video-taped during a family session where at least one child between the ages of 4 and 12 was present. Following the session, the therapist and parent(s) completed questionnaires while one of the children (aged 4-12) was interviewed. Session recordings were coded, minute-by-minute, for participant talk time, visual aids or props used, and therapy technique type (e.g., play-based/activity vs. talk-only techniques). Hierarchical regression and canonical correlational analyses revealed evidence supporting the theory that play-based techniques promote young children's participation, enhance the quality of the child-therapist relationship, and build positive emotional experiences in family therapy. © 2013 American Association for Marriage and Family Therapy.

  19. AtlA functions as a peptidoglycan lytic transglycosylase in the Neisseria gonorrhoeae type IV secretion system.

    Science.gov (United States)

    Kohler, Petra L; Hamilton, Holly L; Cloud-Hansen, Karen; Dillard, Joseph P

    2007-08-01

    Type IV secretion systems require peptidoglycan lytic transglycosylases for efficient secretion, but the function of these enzymes is not clear. The type IV secretion system gene cluster of Neisseria gonorrhoeae encodes two peptidoglycan transglycosylase homologues. One, LtgX, is similar to peptidoglycan transglycosylases from other type IV secretion systems. The other, AtlA, is similar to endolysins from bacteriophages and is not similar to any described type IV secretion component. We characterized the enzymatic function of AtlA in order to examine its role in the type IV secretion system. Purified AtlA was found to degrade macromolecular peptidoglycan and to produce 1,6-anhydro peptidoglycan monomers, characteristic of lytic transglycosylase activity. We found that AtlA can functionally replace the lambda endolysin to lyse Escherichia coli. In contrast, a sensitive measure of lysis demonstrated that AtlA does not lyse gonococci expressing it or gonococci cocultured with an AtlA-expressing strain. The gonococcal type IV secretion system secretes DNA during growth. A deletion of ltgX or a substitution in the putative active site of AtlA severely decreased DNA secretion. These results indicate that AtlA and LtgX are actively involved in type IV secretion and that AtlA is not involved in lysis of gonococci to release DNA. This is the first demonstration that a type IV secretion peptidoglycanase has lytic transglycosylase activity. These data show that AtlA plays a role in type IV secretion of DNA that requires peptidoglycan breakdown without cell lysis.

  20. Play Therapy

    Science.gov (United States)

    Lawver, Timothy; Blankenship, Kelly

    2008-01-01

    Play therapy is a treatment modality in which the therapist engages in play with the child. Its use has been documented in a variety of settings and with a variety of diagnoses. Treating within the context of play brings the therapist and the therapy to the level of the child. By way of an introduction to this approach, a case is presented of a six-year-old boy with oppositional defiant disorder. The presentation focuses on the events and interactions of a typical session with an established patient. The primary issues of the session are aggression, self worth, and self efficacy. These themes manifest themselves through the content of the child’s play and narration of his actions. The therapist then reflects these back to the child while gently encouraging the child toward more positive play. Though the example is one of nondirective play therapy, a wide range of variation exists under the heading of play therapy. PMID:19724720

  1. Activity-based protein profiling of secreted cellulolytic enzyme activity dynamics in Trichoderma reesei QM6a, NG14, and RUT-C30

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Lindsey N.; Culley, David E.; Hofstad, Beth A.; Chauvigne-Hines, Lacie M.; Zink, Erika M.; Purvine, Samuel O.; Smith, Richard D.; Callister, Stephen J.; Magnuson, Jon M.; Wright, Aaron T.

    2013-12-01

    Development of alternative, non-petroleum based sources of bioenergy that can be applied in the short-term find great promise in the use of highly abundant and renewable lignocellulosic plant biomass.1 This material obtained from different feedstocks, such as forest litter or agricultural residues, can yield liquid fuels and other chemical products through biorefinery processes.2 Biofuels are obtained from lignocellulosic materials by chemical pretreatment of the biomass, followed by enzymatic decomposition of cellulosic and hemicellulosic compounds into soluble sugars that are converted to desired chemical products via microbial metabolism and fermentation.3, 4 To release soluble sugars from polymeric cellulose multiple enzymes are required, including endoglucanase, exoglucanase, and β-glucosidase.5, 6 However, the enzymatic hydrolysis of cellulose into soluble sugars remains a significant limiting factor to the efficient and economically viable utilization of lignocellulosic biomass for transport fuels.7, 8 The primary industrial source of cellulose and hemicellulases is the mesophilic soft-rot fungus Trichoderma reesei,9 having widespread applications in food, feed, textile, pulp, and paper industries.10 The genome encodes 200 glycoside hydrolases, including 10 cellulolytic and 16 hemicellulolytic enzymes.11 The hypercellulolytic catabolite derepressed strain RUT-C30 was obtained through a three-step UV and chemical mutagenesis of the original T. reesei strain QM6a,12, 13 in which strains M7 and NG14 were intermediate, having higher cellulolytic activity than the parent strain but less activity and higher catabolite repression than RUT-C30.14 Numerous methods have been employed to optimize the secreted enzyme cocktail of T. reesei including cultivation conditions, operational parameters, and mutagenesis.3 However, creating an optimal and economical enzyme mixture for production-scale biofuels synthesis may take thousands of experiments to identify.

  2. Developmental coordination disorder, generalized self-efficacy toward physical activity, and participation in organized and free play activities.

    Science.gov (United States)

    Cairney, John; Hay, John A; Faught, Brent E; Wade, Terrance J; Corna, Laurie; Flouris, Andreas

    2005-10-01

    To test a theoretical model linking developmental coordination disorder (DCD) to reduced physical activity (PA) through the mediating influence of generalized self-efficacy regarding PA. This was a cross-sectional investigation of students in grades 4 through 8 from 5 elementary schools in the Niagara region of Ontario, Canada (n=590). Motor proficiency was evaluated using the short-form Bruininks-Oseretsky Test of Motor Proficiency. Generalized self-efficacy was assessed using the Children's Self-Perceptions of Adequacy in and Predilection for Physical Activity scale, and PA levels were evaluated using a 61-item Participation Questionnaire. Structural equation modeling was used to test the influence of generalized self-efficacy on the relationship between DCD and PA. In this sample, 7.5% (n=44) of the children met the requirements for probable DCD. The effect of DCD on PA was mediated by generalized self-efficacy. In this model, 28% of the variance in children's PA was predicted by generalized self-efficacy and DCD. Our results suggest that children with DCD are less likely to be physically active and that generalized self-efficacy can account for a considerable proportion of this relationship. The implications for appropriate interventions to increase PA among children with DCD are discussed.

  3. An ancestral role for the mitochondrial pyruvate carrier in glucose-stimulated insulin secretion

    Directory of Open Access Journals (Sweden)

    Kyle S. McCommis

    2016-08-01

    Full Text Available Objective: Transport of pyruvate into the mitochondrial matrix by the Mitochondrial Pyruvate Carrier (MPC is an important and rate-limiting step in its metabolism. In pancreatic β-cells, mitochondrial pyruvate metabolism is thought to be important for glucose sensing and glucose-stimulated insulin secretion. Methods: To evaluate the role that the MPC plays in maintaining systemic glucose homeostasis, we used genetically-engineered Drosophila and mice with loss of MPC activity in insulin-producing cells. Results: In both species, MPC deficiency results in elevated blood sugar concentrations and glucose intolerance accompanied by impaired glucose-stimulated insulin secretion. In mouse islets, β-cell MPC-deficiency resulted in decreased respiration with glucose, ATP-sensitive potassium (KATP channel hyperactivity, and impaired insulin release. Moreover, treatment of pancreas-specific MPC knockout mice with glibenclamide, a sulfonylurea KATP channel inhibitor, improved defects in islet insulin secretion and abnormalities in glucose homeostasis in vivo. Finally, using a recently-developed biosensor for MPC activity, we show that the MPC is rapidly stimulated by glucose treatment in INS-1 insulinoma cells suggesting that glucose sensing is coupled to mitochondrial pyruvate carrier activity. Conclusions: Altogether, these studies suggest that the MPC plays an important and ancestral role in insulin-secreting cells in mediating glucose sensing, regulating insulin secretion, and controlling systemic glycemia. Keywords: Stimulus-coupled secretion, Insulin, β-Cell, Diabetes, Pyruvate, Mitochondria, Drosophila

  4. Normal and abnormal secretion by haemopoietic cells

    Science.gov (United States)

    STINCHCOMBE, JANE C; GRIFFITHS, GILLIAN M

    2001-01-01

    The secretory lysosomes found in haemopoietic cells provide a very efficient mechanism for delivering the effector proteins of many immune cells in response to antigen recognition. Although secretion shows some similarities to the secretion of specialized granules in other secretory cell types, some aspects of secretory lysosome release appear to be unique to melanocytes and cells of the haemopoietic lineage. Mast cells and platelets have provided excellent models for studying secretion, but recent advances in characterizing the immunological synapse allow a very fine dissection of the secretory process in T lymphocytes. These studies show that secretory lysosomes are secreted from the centre of the talin ring at the synapse. Proper secretion requires a series of Rab and cytoskeletal elements which play critical roles in the specialized secretion of lysosomes in haemopoietic cells. PMID:11380687

  5. Playful Literacy

    DEFF Research Database (Denmark)

    Froes, Isabel

    these practices, which compose the taxonomy of tablet play. My contribution lies in identifying and proposing a series of theoretical concepts that complement recent theories related to play and digital literacy studies. The data collected through observations informed some noteworthy aspects, including how...... with tablets’ physical and digital affordances shape children’s digital play. This thesis presents how young children’s current practices when playing with tablets inform digital experiences in Denmark and Japan. Through an interdisciplinary lens and a grounded theory approach, I have identified and mapped...... vocabulary in children’s digital play experiences. These early digital experiences set the rules for the playgrounds and assert digital tablets as twenty-first-century toys, shaping young children’s playful literacy....

  6. Glucose, other secretagogues, and nerve growth factor stimulate mitogen-activated protein kinase in the insulin-secreting beta-cell line, INS-1

    DEFF Research Database (Denmark)

    Frödin, M; Sekine, N; Roche, E

    1995-01-01

    The signaling pathways whereby glucose and hormonal secretagogues regulate insulin-secretory function, gene transcription, and proliferation of pancreatic beta-cells are not well defined. We show that in the glucose-responsive beta-cell line INS-1, major secretagogue-stimulated signaling pathways...... converge to activate 44-kDa mitogen-activated protein (MAP) kinase. Thus, glucose-induced insulin secretion was found to be associated with a small stimulatory effect on 44-kDa MAP kinase, which was synergistically enhanced by increased levels of intracellular cAMP and by the hormonal secretagogues......-1. Phorbol ester, an activator of protein kinase C, stimulated 44-kDa MAP kinase by both Ca(2+)-dependent and -independent pathways. Nerve growth factor, independently of changes in cytosolic Ca2+, efficiently stimulated 44-kDa MAP kinase without causing insulin release, indicating that activation...

  7. TLR7/TLR8 Activation Restores Defective Cytokine Secretion by Myeloid Dendritic Cells but Not by Plasmacytoid Dendritic Cells in HIV-Infected Pregnant Women and Newborns.

    Directory of Open Access Journals (Sweden)

    Elaine Cristina Cardoso

    Full Text Available Mother-to-child transmission (MTCT of HIV-1 has been significantly reduced with the use of antiretroviral therapies, resulting in an increased number of HIV-exposed uninfected infants. The consequences of HIV infection on the innate immune system of both mother-newborn are not well understood. In this study, we analyzed peripheral blood and umbilical cord blood (CB collected from HIV-1-infected and uninfected pregnant women. We measured TNF-α, IL-10 and IFN-α secretion after the stimulation of the cells with agonists of both extracellular Toll-like receptors (TLRs (TLR2, TLR4 and TLR5 and intracellular TLRs (TLR7, TLR7/8 and TLR9. Moreover, as an indicator of the innate immune response, we evaluated the responsiveness of myeloid dendritic cells (mDCs and plasmacytoid DCs (pDCs to TLRs that are associated with the antiviral response. Our results showed that peripheral blood mononuclear cells (PBMCs from HIV-1-infected mothers and CB were defective in TNF-α production after activation by TLR2, TLR5, TLR3 and TLR7. However, the TNF-α response was preserved after TLR7/8 (CL097 stimulation, mainly in the neonatal cells. Furthermore, only CL097 activation was able to induce IL-10 and IFN-α secretion in both maternal and CB cells in the infected group. An increase in IFN-α secretion was observed in CL097-treated CB from HIV-infected mothers compared with control mothers. The effectiveness of CL097 stimulation was confirmed by observation of similar mRNA levels of interferon regulatory factor-7 (IRF-7, IFN-α and TNF-α in PBMCs of both groups. The function of both mDCs and pDCs was markedly compromised in the HIV-infected group, and although TLR7/TLR8 activation overcame the impairment in TNF-α secretion by mDCs, such stimulation was unable to reverse the dysfunctional type I IFN response by pDCs in the HIV-infected samples. Our findings highlight the dysfunction of innate immunity in HIV-infected mother-newborn pairs. The activation of the TLR7

  8. TLR7/TLR8 Activation Restores Defective Cytokine Secretion by Myeloid Dendritic Cells but Not by Plasmacytoid Dendritic Cells in HIV-Infected Pregnant Women and Newborns.

    Science.gov (United States)

    Cardoso, Elaine Cristina; Pereira, Nátalli Zanete; Mitsunari, Gabrielle Eimi; Oliveira, Luanda Mara da Silva; Ruocco, Rosa Maria S A; Francisco, Rossana Pulcineli Vieira; Zugaib, Marcelo; da Silva Duarte, Alberto José; Sato, Maria Notomi

    2013-01-01

    Mother-to-child transmission (MTCT) of HIV-1 has been significantly reduced with the use of antiretroviral therapies, resulting in an increased number of HIV-exposed uninfected infants. The consequences of HIV infection on the innate immune system of both mother-newborn are not well understood. In this study, we analyzed peripheral blood and umbilical cord blood (CB) collected from HIV-1-infected and uninfected pregnant women. We measured TNF-α, IL-10 and IFN-α secretion after the stimulation of the cells with agonists of both extracellular Toll-like receptors (TLRs) (TLR2, TLR4 and TLR5) and intracellular TLRs (TLR7, TLR7/8 and TLR9). Moreover, as an indicator of the innate immune response, we evaluated the responsiveness of myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) to TLRs that are associated with the antiviral response. Our results showed that peripheral blood mononuclear cells (PBMCs) from HIV-1-infected mothers and CB were defective in TNF-α production after activation by TLR2, TLR5, TLR3 and TLR7. However, the TNF-α response was preserved after TLR7/8 (CL097) stimulation, mainly in the neonatal cells. Furthermore, only CL097 activation was able to induce IL-10 and IFN-α secretion in both maternal and CB cells in the infected group. An increase in IFN-α secretion was observed in CL097-treated CB from HIV-infected mothers compared with control mothers. The effectiveness of CL097 stimulation was confirmed by observation of similar mRNA levels of interferon regulatory factor-7 (IRF-7), IFN-α and TNF-α in PBMCs of both groups. The function of both mDCs and pDCs was markedly compromised in the HIV-infected group, and although TLR7/TLR8 activation overcame the impairment in TNF-α secretion by mDCs, such stimulation was unable to reverse the dysfunctional type I IFN response by pDCs in the HIV-infected samples. Our findings highlight the dysfunction of innate immunity in HIV-infected mother-newborn pairs. The activation of the TLR7/8 pathway

  9. Playful Interaction

    DEFF Research Database (Denmark)

    2003-01-01

    The video Playful Interaction describes a future architectural office, and envisions ideas and concepts for playful interactions between people, materials and appliances in a pervasive and augmented working environment. The video both describes existing developments, technologies and designs...... as well as ideas not yet implemented such as playful modes of interaction with an augmented ball. Playful Interaction has been used as a hybrid of a vision video and a video prototype (1). Externally the video has been used to visualising our new ideas, and internally the video has also worked to inspire...

  10. Mediatized play

    DEFF Research Database (Denmark)

    Johansen, Stine Liv

    Children’s play must nowadays be understood as a mediatized field in society and culture. Media – understood in a very broad sense - holds severe explanatory power in describing and understanding the practice of play, since play happens both with, through and inspired by media of different sorts........ In this presentation the case of ‘playing soccer’ will be outlined through its different mediated manifestations, including soccer games and programs on TV, computer games, magazines, books, YouTube videos and soccer trading cards....

  11. Play Practices and Play Moods

    DEFF Research Database (Denmark)

    Karoff, Helle Skovbjerg

    2013-01-01

    The aim of this article is to develop a view of play as a relation between play practices and play moods based on an empirical study of children's everyday life and by using Bateson's term of ‘framing’ [(1955/2001). In Steps to an ecology of mind (pp. 75–80). Chicago: University of Chicago Press......], Schmidt's notion of ‘commonness’ [(2005). Om respekten. København: Danmarks Pædagogiske Universitets Forlag; (2011). On respect. Copenhagen: Danish School of Education University Press] and Heidegger's term ‘mood’ [(1938/1996). Time and being. Cornwall: Wiley-Blackwell.]. Play mood is a state of being...... in which we are open and ready, both to others and their production of meaning and to new opportunities for producing meaning. This play mood is created when we engage with the world during play practices. The article points out four types of play moods – devotion, intensity, tension and euphorica – which...

  12. Ixeris dentata extract regulates salivary secretion through the activation of aquaporin-5 and prevents diabetes-induced xerostomia.

    Science.gov (United States)

    Bhattarai, Kashi Raj; Lee, Sang-Won; Kim, Seung Hyun; Kim, Hyung-Ryong; Chae, Han-Jung

    2017-01-01

    The aim of this study was to investigate the effects of Ixeris dentata (IXD) extract to improve the salivation rate in dry mouth induced by diabetes. Both control and diabetic rats were treated with a sublingual spray of either water or IXD extract to determine the effects of IXD on salivation. During the study, we observed that IXD extract treatment increased the salivary flow rate in diabetic rats. The expression of α-amylase was increased significantly in both saliva and glandular tissue lysates of IXD-treated diabetic rats. Aquaporin-5 protein expression was abnormally low in the salivary glands of diabetic rats, which increased hyposalivation and led to salivary dysfunction. However, a single oral spray of IXD extract drastically increased the expression of aquaporin-5 in salivary gland acinar and ductal cells in diabetic rats. Moreover, IXD extract induced expression of Na + /H + exchangers in the salivary gland, which suggests that Na + /H + exchangers modulate salivary secretions and aid in the fluid-secretion mechanism. Furthermore, transient treatment with IXD extract increased the intracellular calcium in human salivary gland cells. Taken together, these results suggest the potential value of an IXD extract for the treatment of diabetes-induced hyposalivation and xerostomia.

  13. Catechin secretion and phytotoxicity

    Science.gov (United States)

    Kaushik, Shail

    2010-01-01

    Research indicates that the invasiveness of Centaurea stoebe is attributed to the stronger allelopathic effects on the native North American species than on the related European species, which is one of the unquestionable aspects of the “novel weapons hypothesis (NWH).” Studies originating from controlled to field conditions have shown that C. stoebe utilizes its biochemical potential to exert its invasiveness. The roots of C. stoebe secrete a potent phytotoxin, catechin, which has a detrimental effect on the surrounding plant species. Although, studies on catechin secretion and phytotoxicity represent one of the most well studied systems describing negative plant-plant interactions, it has also sparked controversies lately due to its phytotoxicity dosages and secretion effluxes. Previous reports negate the phytotoxic and pro-oxidant nature of catechin.1–3 In our recent study we have shown that catechin is highly phytotoxic against Arabidopsis thaliana and Festuca idahoensis. We also show that (±) catechin applied to roots of A. thaliana induces reactive oxygen species (ROS) confirming the pro-oxidant nature of catechin. In addition, activation of signature cell death genes such as acd2 and cad1 post catechin treatment in A. thaliana ascertains the phytotoxic nature of catechin. PMID:21057643

  14. Brucella Rough Mutant Induce Macrophage Death via Activating IRE1α Pathway of Endoplasmic Reticulum Stress by Enhanced T4SS Secretion.

    Science.gov (United States)

    Li, Peng; Tian, Mingxing; Bao, Yanqing; Hu, Hai; Liu, Jiameng; Yin, Yi; Ding, Chan; Wang, Shaohui; Yu, Shengqing

    2017-01-01

    Brucella is a Gram-negative facultative intracellular pathogen that causes the worldwide zoonosis, known as brucellosis. Brucella virulence relies mostly on its ability to invade and replicate within phagocytic cells. The type IV secretion system (T4SS) and lipopolysaccharide are two major Brucella virulence factors. Brucella rough mutants reportedly induce the death of infected macrophages, which is T4SS dependent. However, the underlying molecular mechanism remains unclear. In this study, the T4SS secretion capacities of Brucella rough mutant and its smooth wild-type strain were comparatively investigated, by constructing the firefly luciferase fused T4SS effector, BPE123 and VceC. In addition, quantitative real-time PCR and western blotting were used to analyze the T4SS expression. The results showed that T4SS expression and secretion were enhanced significantly in the Brucella rough mutant. We also found that the activity of the T4SS virB operon promoter was notably increased in the Brucella rough mutant, which depends on quorum sensing-related regulators of VjbR upregulation. Cell infection and cell death assays revealed that deletion of vjbR in the Brucella rough mutant absolutely abolished cytotoxicity within macrophages by downregulating T4SS expression. This suggests that up-regulation of T4SS promoted by VjbR in rough mutant Δ rfbE contribute to macrophage death. In addition, we found that the Brucella rough mutant induce macrophage death via activating IRE1α pathway of endoplasmic reticulum stress. Taken together, our study provide evidence that in comparison to the Brucella smooth wild-type strain, VjbR upregulation in the Brucella rough mutant increases transcription of the virB operon, resulting in overexpression of the T4SS gene, accompanied by the over-secretion of effecter proteins, thereby causing the death of infected macrophages via activating IRE1α pathway of endoplasmic reticulum stress, suggesting novel insights into the molecular

  15. Brucella Rough Mutant Induce Macrophage Death via Activating IRE1α Pathway of Endoplasmic Reticulum Stress by Enhanced T4SS Secretion

    Directory of Open Access Journals (Sweden)

    Peng Li

    2017-09-01

    Full Text Available Brucella is a Gram-negative facultative intracellular pathogen that causes the worldwide zoonosis, known as brucellosis. Brucella virulence relies mostly on its ability to invade and replicate within phagocytic cells. The type IV secretion system (T4SS and lipopolysaccharide are two major Brucella virulence factors. Brucella rough mutants reportedly induce the death of infected macrophages, which is T4SS dependent. However, the underlying molecular mechanism remains unclear. In this study, the T4SS secretion capacities of Brucella rough mutant and its smooth wild-type strain were comparatively investigated, by constructing the firefly luciferase fused T4SS effector, BPE123 and VceC. In addition, quantitative real-time PCR and western blotting were used to analyze the T4SS expression. The results showed that T4SS expression and secretion were enhanced significantly in the Brucella rough mutant. We also found that the activity of the T4SS virB operon promoter was notably increased in the Brucella rough mutant, which depends on quorum sensing-related regulators of VjbR upregulation. Cell infection and cell death assays revealed that deletion of vjbR in the Brucella rough mutant absolutely abolished cytotoxicity within macrophages by downregulating T4SS expression. This suggests that up-regulation of T4SS promoted by VjbR in rough mutant ΔrfbE contribute to macrophage death. In addition, we found that the Brucella rough mutant induce macrophage death via activating IRE1α pathway of endoplasmic reticulum stress. Taken together, our study provide evidence that in comparison to the Brucella smooth wild-type strain, VjbR upregulation in the Brucella rough mutant increases transcription of the virB operon, resulting in overexpression of the T4SS gene, accompanied by the over-secretion of effecter proteins, thereby causing the death of infected macrophages via activating IRE1α pathway of endoplasmic reticulum stress, suggesting novel insights into the

  16. Playing Shakespeare.

    Science.gov (United States)

    Bashian, Kathleen Ryniker

    1993-01-01

    Describes a yearlong project at 12 Catholic middle schools in the Diocese of Arlington, Virginia, to incorporate the plays of William Shakespeare into the curriculum. Teachers attended university lectures and directed students in performances of the plays. Concludes that Shakespeare can be understood and enjoyed by middle school students. (BCY)

  17. Just watching the game ain't enough: striatal fMRI reward responses to successes and failures in a video game during active and vicarious playing.

    Science.gov (United States)

    Kätsyri, Jari; Hari, Riitta; Ravaja, Niklas; Nummenmaa, Lauri

    2013-01-01

    Although the multimodal stimulation provided by modern audiovisual video games is pleasing by itself, the rewarding nature of video game playing depends critically also on the players' active engagement in the gameplay. The extent to which active engagement influences dopaminergic brain reward circuit responses remains unsettled. Here we show that striatal reward circuit responses elicited by successes (wins) and failures (losses) in a video game are stronger during active than vicarious gameplay. Eleven healthy males both played a competitive first-person tank shooter game (active playing) and watched a pre-recorded gameplay video (vicarious playing) while their hemodynamic brain activation was measured with 3-tesla functional magnetic resonance imaging (fMRI). Wins and losses were paired with symmetrical monetary rewards and punishments during active and vicarious playing so that the external reward context remained identical during both conditions. Brain activation was stronger in the orbitomedial prefrontal cortex (omPFC) during winning than losing, both during active and vicarious playing. In contrast, both wins and losses suppressed activations in the midbrain and striatum during active playing; however, the striatal suppression, particularly in the anterior putamen, was more pronounced during loss than win events. Sensorimotor confounds related to joystick movements did not account for the results. Self-ratings indicated losing to be more unpleasant during active than vicarious playing. Our findings demonstrate striatum to be selectively sensitive to self-acquired rewards, in contrast to frontal components of the reward circuit that process both self-acquired and passively received rewards. We propose that the striatal responses to repeated acquisition of rewards that are contingent on game related successes contribute to the motivational pull of video-game playing.

  18. Just watching the game ain’t enough: Striatal fMRI reward responses to successes and failures in a video game during active and vicarious playing

    Directory of Open Access Journals (Sweden)

    Jari eKätsyri

    2013-06-01

    Full Text Available Although the multimodal stimulation provided by modern audiovisual video games is pleasing by itself, the rewarding nature of video game playing depends critically also on the players’ active engagement in the gameplay. The extent to which active engagement influences dopaminergic brain reward circuit responses remains unsettled. Here we show that striatal reward circuit responses elicited by successes (wins and failures (losses in a video game are stronger during active than vicarious gameplay. Eleven healthy males both played a competitive first-person tank shooter game (active playing and watched a pre-recorded gameplay video (vicarious playing while their hemodynamic brain activation was measured with 3-tesla functional magnetic resonance imaging (fMRI. Wins and losses were paired with symmetrical monetary rewards and punishments during active and vicarious playing so that the external reward context remained identical during both conditions. Brain activation was stronger in the orbitomedial prefrontal cortex (omPFC during winning than losing, both during active and vicarious playing conditions. In contrast, both wins and losses suppressed activations in the midbrain and striatum during active playing; however, the striatal suppression, particularly in the anterior putamen, was more pronounced during loss than win events. Sensorimotor confounds related to joystick movements did not account for the results. Self-ratings indicated losing to be more unpleasant during active than vicarious playing. Our findings demonstrate striatum to be selectively sensitive to self-acquired rewards, in contrast to frontal components of the reward circuit that process both self-acquired and passively received rewards. We propose that the striatal responses to repeated acquisition of rewards that are contingent on game related successes contribute to the motivational pull of video-game playing.

  19. Role of Nitric Oxide in the Regulation of Renin and Vasopressin Secretion

    Science.gov (United States)

    Reid, Ian A.

    1994-01-01

    Research during recent years has established nitric oxide as a unique signaling molecule that plays important roles in the regulation of the cardiovascular, nervous, immune, and other systems. Nitric oxide has also been implicated in the control of the secretion of hormones by the pancreas, hypothalamus, and anterior pituitary gland, and evidence is accumulating that it contributes to the regulation of the secretion of renin and vasopressin, hormones that play key roles in the control of sodium and water balance. Several lines of evidence have implicated nitric oxide in the control of renin secretion. The enzyme nitric oxide synthase is present in vascular and tubular elements of the kidney, particularly in cells of the macula densa, a structure that plays an important role in the control of renin secretion. Guanylyl cyclase, a major target for nitric oxide, is also present in the kidney. Drugs that inhibit nitric oxide synthesis generally suppress renin release in vivo and in vitro, suggesting a stimulatory role for the L-arginine/nitric oxide pathway in the control of renin secretion. Under some conditions, however, blockade of nitric oxide synthesis increases renin secretion. Recent studies indicate that nitric oxide not only contributes to the regulation of basal renin secretion, but also participates in the renin secretory responses to activation of the renal baroreceptor, macula densa, and beta adrenoceptor mechanisms that regulate renin secretion. Histochemical and immunocytochemical studies have revealed the presence of nitric oxide synthase in the supraoptic and paraventricular nuclei of the hypothalamus and in the posterior pituitary gland. Colocalization of nitric oxide synthase and vasopressin has been demonstrated in some hypothalamic neurons. Nitric oxide synthase activity in the hypothalamus and pituitary is increased by maneuvers known to stimulate vasopressin secretion, including salt loading and dehydration, Administration of L-arginine and nitric

  20. Promises and Challenges in Continuous Tracking Utilizing Amino Acids in Skin Secretions for Active Multi-Factor Biometric Authentication for Cybersecurity.

    Science.gov (United States)

    Agudelo, Juliana; Privman, Vladimir; Halámek, Jan

    2017-07-05

    We consider a new concept of biometric-based cybersecurity systems for active authentication by continuous tracking, which utilizes biochemical processing of metabolites present in skin secretions. Skin secretions contain a large number of metabolites and small molecules that can be targeted for analysis. Here we argue that amino acids found in sweat can be exploited for the establishment of an amino acid profile capable of identifying an individual user of a mobile or wearable device. Individual and combinations of amino acids processed by biocatalytic cascades yield physical (optical or electronic) signals, providing a time-series of several outputs that, in their entirety, should suffice to authenticate a specific user based on standard statistical criteria. Initial results, motivated by biometrics, indicate that single amino acid levels can provide analog signals that vary according to the individual donor, albeit with limited resolution versus noise. However, some such assays offer digital separation (into well-defined ranges of values) according to groups such as age, biological sex, race, and physiological state of the individual. Multi-input biocatalytic cascades that handle several amino acid signals to yield a single digital-type output, as well as continuous-tracking time-series data rather than a single-instance sample, should enable active authentication at the level of an individual. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Contribution of the organic anion transporter OAT2 to the renal active tubular secretion of creatinine and mechanism for serum creatinine elevations caused by cobicistat.

    Science.gov (United States)

    Lepist, Eve-Irene; Zhang, Xuexiang; Hao, Jia; Huang, Jane; Kosaka, Alan; Birkus, Gabriel; Murray, Bernard P; Bannister, Roy; Cihlar, Tomas; Huang, Yong; Ray, Adrian S

    2014-08-01

    Many xenobiotics including the pharmacoenhancer cobicistat increase serum creatinine by inhibiting its renal active tubular secretion without affecting the glomerular filtration rate. This study aimed to define the transporters involved in creatinine secretion, applying that knowledge to establish the mechanism for xenobiotic-induced effects. The basolateral uptake transporters organic anion transporter OAT2 and organic cation transporters OCT2 and OCT3 were found to transport creatinine. At physiologic creatinine concentrations, the specific activity of OAT2 transport was over twofold higher than OCT2 or OCT3, establishing OAT2 as a likely relevant creatinine transporter and further challenging the traditional view that creatinine is solely transported by a cationic pathway. The apical multidrug and toxin extrusion transporters MATE1 and MATE2-K demonstrated low-affinity and high-capacity transport. All drugs known to affect creatinine inhibited OCT2 and MATE1. Similar to cimetidine and ritonavir, cobicistat had the greatest effect on MATE1 with a 50% inhibition constant of 0.99 μM for creatinine transport. Trimethoprim potently inhibited MATE2-K, whereas dolutegravir preferentially inhibited OCT2. Cimetidine was unique, inhibiting all transporters that interact with creatinine. Thus, the clinical observation of elevated serum creatinine in patients taking cobicistat is likely a result of OCT2 transport, facilitating intracellular accumulation, and MATE1 inhibition.

  2. Contribution of the organic anion transporter OAT2 to the renal active tubular secretion of creatinine and mechanism for serum creatinine elevations caused by cobicistat

    Science.gov (United States)

    Lepist, Eve-Irene; Zhang, Xuexiang; Hao, Jia; Huang, Jane; Kosaka, Alan; Birkus, Gabriel; Murray, Bernard P; Bannister, Roy; Cihlar, Tomas; Huang, Yong; Ray, Adrian S

    2014-01-01

    Many xenobiotics including the pharmacoenhancer cobicistat increase serum creatinine by inhibiting its renal active tubular secretion without affecting the glomerular filtration rate. This study aimed to define the transporters involved in creatinine secretion, applying that knowledge to establish the mechanism for xenobiotic-induced effects. The basolateral uptake transporters organic anion transporter OAT2 and organic cation transporters OCT2 and OCT3 were found to transport creatinine. At physiologic creatinine concentrations, the specific activity of OAT2 transport was over twofold higher than OCT2 or OCT3, establishing OAT2 as a likely relevant creatinine transporter and further challenging the traditional view that creatinine is solely transported by a cationic pathway. The apical multidrug and toxin extrusion transporters MATE1 and MATE2-K demonstrated low-affinity and high-capacity transport. All drugs known to affect creatinine inhibited OCT2 and MATE1. Similar to cimetidine and ritonavir, cobicistat had the greatest effect on MATE1 with a 50% inhibition constant of 0.99 μM for creatinine transport. Trimethoprim potently inhibited MATE2-K, whereas dolutegravir preferentially inhibited OCT2. Cimetidine was unique, inhibiting all transporters that interact with creatinine. Thus, the clinical observation of elevated serum creatinine in patients taking cobicistat is likely a result of OCT2 transport, facilitating intracellular accumulation, and MATE1 inhibition. PMID:24646860

  3. Processing of thyrotropin-releasing hormone prohormone (pro-TRH) generates a biologically active peptide, prepro-TRH-(160-169), which regulates TRH-induced thyrotropin secretion

    International Nuclear Information System (INIS)

    Bulant, M.; Vaudry, H.; Roussel, J.P.; Astier, H.; Nicolas, P.

    1990-01-01

    Rat thyrotropin-releasing hormone (TRH) prohormone contains five copies of the TRH progenitor sequence Gln-His-Pro-Gly linked together by connecting sequences whose biological activity is unknown. Both the predicted connecting peptide prepro-TRH-(160-169) (Ps4) and TRH are predominant storage forms of TRH precursor-related peptides in the hypothalamus. To determine whether Ps4 is co-released with TRH, rat median eminence slices were perfused in vitro. Infusion of depolarizing concentrations of KCl induced stimulation of release of Ps4- and TRH-like immunoreactivity. The possible effect of Ps4 on thyrotropin release was investigated in vitro using quartered anterior pituitaries. Infusion of Ps4 alone had no effect on thyrotropin secretion but potentiated TRH-induced thyrotropin release in a dose-dependent manner. In addition, the occurrence of specific binding sites for 125 I-labeled Tyr-Ps4 in the distal lobe of the pituitary was demonstrated by binding analysis and autoradiographic localization. These findings indicate that these two peptides that arise from a single multifunctional precursor, the TRH prohormone, act in a coordinate manner on the same target cells to promote hormonal secretion. These data suggest that differential processing of the TRH prohormone may have the potential to modulate the biological activity of TRH

  4. Extracellular vesicles secreted from cancer cell lines stimulate secretion of MMP-9, IL-6, TGF-β1 and EMMPRIN.

    Directory of Open Access Journals (Sweden)

    Jasmina S Redzic

    Full Text Available Extracellular vesicles (EVs are key contributors to cancer where they play an integral role in cell-cell communication and transfer pro-oncogenic molecules to recipient cells thereby conferring a cancerous phenotype. Here, we purified EVs using straightforward biochemical approaches from multiple cancer cell lines and subsequently characterized these EVs via multiple biochemical and biophysical methods. In addition, we used fluorescence microscopy to directly show internalization of EVs into the recipient cells within a few minutes upon addition of EVs to recipient cells. We confirmed that the transmembrane protein EMMPRIN, postulated to be a marker of EVs, was indeed secreted from all cell lines studied here. We evaluated the response to EV stimulation in several different types of recipient cells lines and measured the ability of these purified EVs to induce secretion of several factors highly upregulated in human cancers. Our data indicate that purified EVs preferentially stimulate secretion of several proteins implicated in driving cancer in monocytic cells but only harbor limited activity in epithelial cells. Specifically, we show that EVs are potent stimulators of MMP-9, IL-6, TGF-β1 and induce the secretion of extracellular EMMPRIN, which all play a role in driving immune evasion, invasion and inflammation in the tumor microenvironment. Thus, by using a comprehensive approach that includes biochemical, biological, and spectroscopic methods, we have begun to elucidate the stimulatory roles.

  5. Secretion Trap Tagging of Secreted and Membrane-Spanning Proteins Using Arabidopsis Gene Traps

    Science.gov (United States)

    Andrew T. Groover; Joseph R. Fontana; Juana M. Arroyo; Cristina Yordan; W. Richard McCombie; Robert A. Martienssen

    2003-01-01

    Secreted and membrane-spanning proteins play fundamental roles in plant development but pose challenges for genetic identification and characterization. We describe a "secretion trap" screen for gene trap insertions in genes encoding proteins routed through the secretory pathway. The gene trap transposon encodes a ß-glucuronidase reporter enzyme...

  6. Identification of lipid fraction constituents from grasshopper (Chorthippus spp.) abdominal secretion with potential activity in wound healing with the use of GC-MS/MS technique.

    Science.gov (United States)

    Buszewska-Forajta, Magdalena; Siluk, Danuta; Struck-Lewicka, Wiktoria; Raczak-Gutknecht, Joanna; Markuszewski, Michał J; Kaliszan, Roman

    2014-02-01

    In recent years biologically active compounds isolated from insects call special interest of drug researchers. According to some Polish etnopharmacological observations, secretion from the grasshopper's abdomen (Orthoptera family) is believed to speed up the process of wound healing. In the present work we focused on determination of main components of the lipid fraction of material from grasshopper abdomen using GC-MS/MS. Samples were qualitatively analyzed using gas chromatography coupled with mass spectrometry. Both liquid-liquid extraction and solid-phase extraction pretreatment methods were used to concentrate and fractionate the compounds from the insect. In the derivatized fractions ca. 350 compounds were identified, including substances of known biological activity. The potential agents affecting wound healing have been indicated. A set of compounds characteristic for all the studied Chorthippus spp., have been identified. Data analysis revealed different lipidomic profiles of grasshoppers depending on the insects origin and collection area. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Analysis of playing activity of footballers 19-21-years-old age in the leading commands of Europe.

    Directory of Open Access Journals (Sweden)

    Nikolaenko V.V.

    2012-10-01

    Full Text Available Competition activity of footballers is considered 19-21-years-old age in the professional commands of Europe. For research it was served as information normatively-legal documents of Federations of football of leading European championships (request letters and protocols of matches. In research it was necessary to be attached to the construction of the statistical groupings, that allowed to analyse in a dynamics playing activity of footballers on the stage of training to higher achievements. Influence of the competition loadings is appraised on the organism of sportsmen. Participating of sportsmen of this age is set in compositions of professional commands - leaders of rating of UEFA. It is set that the basic failing in preparation of the Ukrainian young footballers is surplus pursuit after a result and accent on physical preparation. It gives advantage above other commands which work above the technique of game (Holland, Germany, Spain in youth football. However, when players from youth football pass to the grown man, results sharply fall and felt substantial blanks in individual technical preparedness.

  8. Urokinase-type plasminogen activator receptor plays a role in neutrophil migration during lipopolysaccharide-induced peritoneal inflammation but not during Escherichia coli-induced peritonitis

    NARCIS (Netherlands)

    Renckens, Rosemarijn; Roelofs, Joris J. T. H.; Florquin, Sandrine; van der Poll, Tom

    2006-01-01

    BACKGROUND: Urokinase-type plasminogen activator receptor (uPAR) is expressed on many different cells, including leukocytes. uPAR has been implicated to play a role in neutrophil migration to sites of inflammation. METHODS: To determine the role that uPAR plays in neutrophil recruitment in response

  9. Ectosomes: a new mechanism for non-exosomal secretion of tau protein.

    Directory of Open Access Journals (Sweden)

    Simon Dujardin

    Full Text Available Tau is a microtubule-associated protein that aggregates in neurodegenerative disorders known as tauopathies. Recently, studies have suggested that Tau may be secreted and play a role in neural network signalling. However, once deregulated, secreted Tau may also participate in the spreading of Tau pathology in hierarchical pathways of neurodegeneration. The mechanisms underlying neuron-to-neuron Tau transfer are still unknown; given the known role of extra-cellular vesicles in cell-to-cell communication, we wondered whether these vesicles could carry secreted Tau. We found, among vesicles, that Tau is predominately secreted in ectosomes, which are plasma membrane-originating vesicles, and when it accumulates, the exosomal pathway is activated.

  10. Structural and Biochemical Characterization of Spa47 Provides Mechanistic Insight into Type III Secretion System ATPase Activation and Shigella Virulence Regulation.

    Science.gov (United States)

    Burgess, Jamie L; Burgess, R Alan; Morales, Yalemi; Bouvang, Jenna M; Johnson, Sean J; Dickenson, Nicholas E

    2016-12-09

    Like many Gram-negative pathogens, Shigella rely on a complex type III secretion system (T3SS) to inject effector proteins into host cells, take over host functions, and ultimately establish infection. Despite these critical roles, the energetics and regulatory mechanisms controlling the T3SS and pathogen virulence remain largely unclear. In this study, we present a series of high resolution crystal structures of Spa47 and use the structures to model an activated Spa47 oligomer, finding that ATP hydrolysis may be supported by specific side chain contributions from adjacent protomers within the complex. Follow-up mutagenesis experiments targeting the predicted active site residues validate the oligomeric model and determined that each of the tested residues are essential for Spa47 ATPase activity, although they are not directly responsible for stable oligomer formation. Although N-terminal domain truncation was necessary for crystal formation, it resulted in strictly monomeric Spa47 that is unable to hydrolyze ATP, despite maintaining the canonical ATPase core structure and active site residues. Coupled with studies of ATPase inactive full-length Spa47 point mutants, we find that Spa47 oligomerization and ATP hydrolysis are needed for complete T3SS apparatus formation, a proper translocator secretion profile, and Shigella virulence. This work represents the first structure-function characterization of Spa47, uniquely complementing the multitude of included Shigella T3SS phenotype assays and providing a more complete understanding of T3SS ATPase-mediated pathogen virulence. Additionally, these findings provide a strong platform for follow-up studies evaluating regulation of Spa47 oligomerization in vivo as a much needed means of treating and perhaps preventing shigellosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Structural and Biochemical Characterization of Spa47 Provides Mechanistic Insight into Type III Secretion System ATPase Activation and Shigella Virulence Regulation*

    Science.gov (United States)

    Burgess, Jamie L.; Burgess, R. Alan; Morales, Yalemi; Bouvang, Jenna M.; Johnson, Sean J.; Dickenson, Nicholas E.

    2016-01-01

    Like many Gram-negative pathogens, Shigella rely on a complex type III secretion system (T3SS) to inject effector proteins into host cells, take over host functions, and ultimately establish infection. Despite these critical roles, the energetics and regulatory mechanisms controlling the T3SS and pathogen virulence remain largely unclear. In this study, we present a series of high resolution crystal structures of Spa47 and use the structures to model an activated Spa47 oligomer, finding that ATP hydrolysis may be supported by specific side chain contributions from adjacent protomers within the complex. Follow-up mutagenesis experiments targeting the predicted active site residues validate the oligomeric model and determined that each of the tested residues are essential for Spa47 ATPase activity, although they are not directly responsible for stable oligomer formation. Although N-terminal domain truncation was necessary for crystal formation, it resulted in strictly monomeric Spa47 that is unable to hydrolyze ATP, despite maintaining the canonical ATPase core structure and active site residues. Coupled with studies of ATPase inactive full-length Spa47 point mutants, we find that Spa47 oligomerization and ATP hydrolysis are needed for complete T3SS apparatus formation, a proper translocator secretion profile, and Shigella virulence. This work represents the first structure-function characterization of Spa47, uniquely complementing the multitude of included Shigella T3SS phenotype assays and providing a more complete understanding of T3SS ATPase-mediated pathogen virulence. Additionally, these findings provide a strong platform for follow-up studies evaluating regulation of Spa47 oligomerization in vivo as a much needed means of treating and perhaps preventing shigellosis. PMID:27770024

  12. Arabidopsis ABI5 plays a role in regulating ROS homeostasis by activating CATALASE 1 transcription in seed germination.

    Science.gov (United States)

    Bi, Chao; Ma, Yu; Wu, Zhen; Yu, Yong-Tao; Liang, Shan; Lu, Kai; Wang, Xiao-Fang

    2017-05-01

    It has been known that ABA INSENSITIVE 5 (ABI5) plays a vital role in regulating seed germination. In the present study, we showed that inhibition of the catalase activity with 3-amino-1,2,4-triazole (3-AT) inhibits seed germination of Col-0, abi5 mutants and ABI5-overexpression transgenic lines. Compared with Col-0, the seeds of abi5 mutants showed more sensitive to 3-AT during seed germination, while the seeds of ABI5-overexpression transgenic lines showed more insensitive. H 2 O 2 showed the same effect on seed germination of Col-0, abi5 mutants and ABI5-overexpression transgenic lines as 3-AT. These results suggest that ROS is involved in the seed germination mediated by ABI5. Further, we observed that T-DNA insertion mutants of the three catalase members in Arabidopsis displayed 3-AT-insensitive or -hypersensitive phenotypes during seed germination, suggesting that these catalase members regulate ROS homeostasis in a highly complex way. ABI5 affects reactive oxygen species (ROS) homeostasis by affecting CATALASE expression and catalase activity. Furthermore, we showed that ABI5 directly binds to the CAT1 promoter and activates CAT1 expression. Genetic evidence supports the idea that CAT1 functions downstream of ABI5 in ROS signaling during seed germination. RNA-sequencing analysis indicates that the transcription of the genes involved in ROS metabolic process or genes responsive to ROS stress is impaired in abi5-1 seeds. Additionally, expression changes in some genes correlative to seed germination were showed due to the change in ABI5 expression under 3-AT treatment. Together, all the findings suggest that ABI5 regulates seed germination at least partly by affecting ROS homeostasis.

  13. Postphenomenological Play

    DEFF Research Database (Denmark)

    Hammar, Emil

    This paper aims to identify an understanding of digital games in virtual environments by using Don Ihde’s (1990) postphenomenological approach to how technology mediates the world to human beings in conjunction with Hans-Georg Gadamer’s (1993) notion of play . Through this tentatively proposed am...... amalgamation of theories I point towards an alternative understanding of the relationship between play and game as not only dialectic, but also as socially and ethically relevant qua the design and implementation of the game as technology....

  14. A Case Study: Analyzing City Vitality with Four Pillars of Activity-Live, Work, Shop, and Play.

    Science.gov (United States)

    Griffin, Matt; Nordstrom, Blake W; Scholes, Jon; Joncas, Kate; Gordon, Patrick; Krivenko, Elliott; Haynes, Winston; Higdon, Roger; Stewart, Elizabeth; Kolker, Natali; Montague, Elizabeth; Kolker, Eugene

    2016-03-01

    This case study evaluates and tracks vitality of a city (Seattle), based on a data-driven approach, using strategic, robust, and sustainable metrics. This case study was collaboratively conducted by the Downtown Seattle Association (DSA) and CDO Analytics teams. The DSA is a nonprofit organization focused on making the city of Seattle and its Downtown a healthy and vibrant place to Live, Work, Shop, and Play. DSA primarily operates through public policy advocacy, community and business development, and marketing. In 2010, the organization turned to CDO Analytics ( cdoanalytics.org ) to develop a process that can guide and strategically focus DSA efforts and resources for maximal benefit to the city of Seattle and its Downtown. CDO Analytics was asked to develop clear, easily understood, and robust metrics for a baseline evaluation of the health of the city, as well as for ongoing monitoring and comparisons of the vitality, sustainability, and growth. The DSA and CDO Analytics teams strategized on how to effectively assess and track the vitality of Seattle and its Downtown. The two teams filtered a variety of data sources, and evaluated the veracity of multiple diverse metrics. This iterative process resulted in the development of a small number of strategic, simple, reliable, and sustainable metrics across four pillars of activity: Live, Work, Shop, and Play. Data during the 5 years before 2010 were used for the development of the metrics and model and its training, and data during the 5 years from 2010 and on were used for testing and validation. This work enabled DSA to routinely track these strategic metrics, use them to monitor the vitality of Downtown Seattle, prioritize improvements, and identify new value-added programs. As a result, the four-pillar approach became an integral part of the data-driven decision-making and execution of the Seattle community's improvement activities. The approach described in this case study is actionable, robust, inexpensive

  15. Activation patterns of vasopressinergic and oxytocinergic brain regions following social play exposure in juvenile male and female rats.

    Science.gov (United States)

    Reppucci, C J; Gergely, C K; Veenema, A H

    2018-02-09

    Social play is a highly rewarding and motivated behavior predominately displayed by juveniles and expressed by nearly all mammalian species. Prior work suggested that the vasopressin (AVP) and oxytocin (OT) systems can regulate the expression of social play in sex-specific ways. Here we investigated whether there are sex differences in the recruitment of vasopressinergic and oxytocinergic brain regions following social play exposure in juvenile rats. Single-housed rats were allowed to play, in their home cage, with an age- and sex-matched unfamiliar conspecific for 10 min, or received similar handling but no partner. Double-labeled fluorescent immunohistochemistry for Fos and either AVP or OT was completed in adjacent series of tissue to determine recruitment of AVP- and OT-immunoreactive neurons in response to social play. Exposure to social play did not increase recruitment of AVP or OT neurons in the supraoptic (SO) or paraventricular (PVH) hypothalamic nuclei of either sex compared to the no-play control condition. Interestingly, there was a robust sex difference in SO recruitment, irrespective of social play condition, with males exhibiting twice the recruitment of SO-AVP and SO-OT neurons compared to females. Lastly, exposure to social play increased recruitment of the posterior bed nuclei of the stria terminalis (pBST) and the posterodorsal medial amygdalar nucleus (MEApd) compared to the no-play control condition, and this effect was most pronounced in females. Our findings revealed sex differences in the recruitment of brain regions (i) independent of play condition (i.e., SO) possibly representing a sex difference in the baseline levels of AVP and OT signaling required for typical functioning and (ii) specific to play condition (i.e., pBST, MEApd). In sum, this study provides further evidence that the neural substrates underlying social play behavior are sex-specific. This article is protected by copyright. All rights reserved. This article is protected

  16. Metabolic Thresholds and Validated Accelerometer Cutoff Points for the Actigraph GT1M in Young Children Based on Measurements of Locomotion and Play Activities

    Science.gov (United States)

    Jimmy, Gerda; Dossegger, Alain; Seiler, Roland; Mader, Urs

    2012-01-01

    The purpose of the current study was to determine metabolic thresholds and subsequent activity intensity cutoff points for the ActiGraph GT1M with various epochs spanning from 5 to 60 sec in young children. Twenty-two children, aged 4 to 9 years, performed 10 different activities including locomotion and play activities. Energy expenditure was…

  17. Current Therapies That Modify Glucagon Secretion

    DEFF Research Database (Denmark)

    Grøndahl, Magnus F.; Keating, Damien J.; Vilsbøll, Tina

    2017-01-01

    and provide insights into how antidiabetic drugs influence glucagon secretion as well as a perspective on the future of glucagon-targeting drugs. Recent Findings: Several older as well as recent investigations have evaluated the effect of antidiabetic agents on glucagon secretion to understand how glucagon...... may be involved in the drugs’ efficacy and safety profiles. Based on these findings, modulation of glucagon secretion seems to play a hitherto underestimated role in the efficacy and safety of several glucose-lowering drugs. Summary: Numerous drugs currently available to diabetologists are capable...... of altering glucagon secretion: metformin, sulfonylurea compounds, insulin, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter 2 inhibitors and amylin mimetics. Their diverse effects on glucagon secretion are of importance for their individual efficacy...

  18. Loose excitation-secretion coupling in astrocytes.

    Science.gov (United States)

    Vardjan, Nina; Parpura, Vladimir; Zorec, Robert

    2016-05-01

    Astrocytes play an important housekeeping role in the central nervous system. Additionally, as secretory cells, they actively participate in cell-to-cell communication, which can be mediated by membrane-bound vesicles. The gliosignaling molecules stored in these vesicles are discharged into the extracellular space after the vesicle membrane fuses with the plasma membrane. This process is termed exocytosis, regulated by SNARE proteins, and triggered by elevations in cytosolic calcium levels, which are necessary and sufficient for exocytosis in astrocytes. For astrocytic exocytosis, calcium is sourced from the intracellular endoplasmic reticulum store, although its entry from the extracellular space contributes to cytosolic calcium dynamics in astrocytes. Here, we discuss calcium management in astrocytic exocytosis and the properties of the membrane-bound vesicles that store gliosignaling molecules, including the vesicle fusion machinery and kinetics of vesicle content discharge. In astrocytes, the delay between the increase in cytosolic calcium activity and the discharge of secretions from the vesicular lumen is orders of magnitude longer than that in neurons. This relatively loose excitation-secretion coupling is likely tailored to the participation of astrocytes in modulating neural network processing. © 2015 Wiley Periodicals, Inc.

  19. Playful Organizations

    DEFF Research Database (Denmark)

    Pors, Justine Grønbæk; Åkerstrøm Andersen, Niels

    2015-01-01

    intact. In its final sections, the article discusses what happens to conditions of decision-making when organisations do not just see undecidability as a given condition, but as a limited resource indispensable for change and renewal. The article advances discussions of organisational play by exploring...

  20. Clay Play

    Science.gov (United States)

    Rogers, Liz; Steffan, Dana

    2009-01-01

    This article describes how to use clay as a potential material for young children to explore. As teachers, the authors find that their dialogue about the potential of clay as a learning medium raises many questions: (1) What makes clay so enticing? (2) Why are teachers noticing different play and conversation around the clay table as compared to…

  1. Group play

    DEFF Research Database (Denmark)

    Tychsen, Anders; Hitchens, Michael; Brolund, Thea

    2008-01-01

    Role-playing games (RPGs) are a well-known game form, existing in a number of formats, including tabletop, live action, and various digital forms. Despite their popularity, empirical studies of these games are relatively rare. In particular there have been few examinations of the effects of the v......Role-playing games (RPGs) are a well-known game form, existing in a number of formats, including tabletop, live action, and various digital forms. Despite their popularity, empirical studies of these games are relatively rare. In particular there have been few examinations of the effects...... of the various formats used by RPGs on the gaming experience. This article presents the results of an empirical study, examining how multi-player tabletop RPGs are affected as they are ported to the digital medium. Issues examined include the use of disposition assessments to predict play experience, the effect...... of group dynamics, the influence of the fictional game characters and the comparative play experience between the two formats. The results indicate that group dynamics and the relationship between the players and their digital characters, are integral to the quality of the gaming experience in multiplayer...

  2. Playing Teacher.

    Science.gov (United States)

    Gilbert, Juan E.

    The acceptance of animation technologies is increasing. Video games, such as Sony PlayStation (SONY, 2002), have become part of the culture for young people from kindergarten through undergraduate school. Animation technologies have been implemented into educational systems in the form of animated pedagogical agents (Johnson, 2000). The research…

  3. A randomized trial to assess anti-HIV activity in female genital tract secretions and soluble mucosal immunity following application of 1% tenofovir gel.

    Directory of Open Access Journals (Sweden)

    Marla J Keller

    2011-01-01

    Full Text Available Preclinical and early phase clinical microbicide studies have not consistently predicted the outcome of efficacy trials. To address this gap, candidate biomarkers of microbicide pharmacodynamics and safety were evaluated in a double-blind, placebo-controlled trial of tenofovir gel, the first microbicide to demonstrate significant protection against HIV acquisition.30 women were randomized to apply a single daily dose of tenofovir or placebo gel for 14 consecutive days. Anti-HIV activity was measured in cervicovaginal lavage (CVL on Days 0, 3, 7, 14 and 21 by luciferase assay as a surrogate marker of pharmacodynamics. Endogenous activity against E. coli and HSV-2 and concentrations of immune mediators were quantified in CVL as candidate biomarkers of safety. Tenofovir levels were measured in CVL and blood.A significant increase in anti-HIV activity was detected in CVL from women who applied tenofovir gel compared to their endogenous anti-HIV activity in genital tract secretions on Day 0 and compared to activity in CVL from women in the placebo group. The activity correlated significantly with CVL concentration of tenofovir (r = 0.6, p<0.001 and fit a sigmoid E(max pharmacodynamic model. Anti-HIV activity in CVL from women who applied tenofovir persisted when virus was introduced in semen, whereas endogenous anti-HIV activity decreased. Tenofovir did not trigger an inflammatory response or induce sustained loss in endogenous antimicrobial activity or immune mediators.Tenofovir gel had no deleterious impact on soluble mucosal immunity. The increased anti-HIV activity in CVL, which persisted in the presence of semen and correlated with tenofovir concentration, is consistent with the efficacy observed in a recent clinical trial. These results promote quantified CVL anti-HIV activity as a surrogate of tissue pharmacodynamics and as a potential biomarker of adherence to product. This simple, feasible and inexpensive bioassay may promote the development

  4. Immunoglobins in mammary secretions

    DEFF Research Database (Denmark)

    Hurley, W L; Theil, Peter Kappel

    2013-01-01

    Immunoglobulins secreted in colostrum and milk by the lactating mammal are major factors providing immune protection to the newborn. Immunoglobulins in mammary secretions represent the cumulative immune response of the lactating animal to exposure to antigenic stimulation that occurs through...... the immunoglobulins found in mammary secretions in the context of their diversity of structure, origin, mechanisms of transfer, and function....

  5. The child play behavior and activity questionnaire: a parent-report measure of childhood gender-related behavior in China.

    Science.gov (United States)

    Yu, Lu; Winter, Sam; Xie, Dong

    2010-06-01

    Boys and girls establish relatively stable gender stereotyped behavior patterns by middle childhood. Parent-report questionnaires measuring children's gender-related behavior enable researchers to conduct large-scale screenings of community samples of children. For school-aged children, two parent-report instruments, the Child Game Participation Questionnaire (CGPQ) and the Child Behavior and Attitude Questionnaire (CBAQ), have long been used for measuring children's sex-dimorphic behaviors in Western societies, but few studies have been conducted using these measures for Chinese populations. The current study aimed to empirically examine and modify the two instruments for their applications to Chinese society. Parents of 486 Chinese boys and 417 Chinese girls (6-12 years old) completed a questionnaire comprising items from the CGPQ and CBAQ, and an additional 14 items specifically related to Chinese gender-specific games. Items revealing gender differences in a Chinese sample were identified and used to construct a Child Play Behavior and Activity Questionnaire (CPBAQ). Four new scales were generated through factor analysis: a Gender Scale, a Girl Typicality Scale, a Boy Typicality Scale, and a Cross-Gender Scale (CGS). These scales had satisfactory internal reliabilities and large effect sizes for gender. The CPBAQ is believed to be a promising instrument for measuring children's gender-related behavior in China.

  6. Profiling of Cytokines Secreted by Conventional Aqueous Outflow Pathway Endothelial Cells Activated In Vitro and Ex Vivo With Laser Irradiation.

    Science.gov (United States)

    Alvarado, Jorge A; Chau, Phuonglan; Wu, Jianfeng; Juster, Richard; Shifera, Amde Selassie; Geske, Michael

    2015-11-01

    To profile which cytokine genes are differentially expressed (DE) as up- or downregulated by cultured human trabecular meshwork (TMEs) and Schlemm's canal endothelial cells (SCEs) after three experimental treatments consisting of selective laser trabeculoplasty (SLT) irradiation, exposure to media conditioned either by SLT-irradiated TMEs (TME-cm) or by SCEs (SCE-cm). Also, to profile which cytokines are upregulated ex vivo in SLT-irradiated human conventional aqueous outflow pathway (CAOP) tissues. After each treatment, Affymetrix microarray assays were used to detect upregulated and downregulated genes for cytokines and their receptors in TMEs and SCEs. ELISA and protein antibody arrays were used to detect upregulated cytokines secreted in SLT-irradiated CAOP tissues ex vivo. The SLT irradiation upregulated numerous cytokine genes in TMEs, but only a few in SCEs. Exposure to TME- and SCE-cm induced SCEs to upregulate many more cytokine genes than TMEs. Selective laser trabeculoplasty irradiation and exposure to TME-cm downregulated several cytokine genes in TMEs but none in SCEs. Selective laser trabeculoplasty irradiation induced one upregulated and three downregulated cytokine-receptor genes in TMEs but none in SCEs. Exposure to TME-cm induced upregulation of one and downregulation of another receptor gene in TMEs, whereas two unique cytokine-receptor genes were upregulated in SCEs. Cytokine protein expression analysis showed that at least eight cytokines were upregulated in SLT-irradiated human CAOP tissues in situ/ex vivo. This study has helped us identify a cytokine signaling pathway and to consider newly identified mechanisms regulating aqueous outflow that may lay the foundation for the future development of cytokine-based glaucoma therapies.

  7. Gastroprotective activity of ferruginol in mice and rats: effects on gastric secretion, endogenous prostaglandins and non-protein sulfhydryls.

    Science.gov (United States)

    Areche, Carlos; Theoduloz, Cristina; Yáñez, Tania; Souza-Brito, Alba R M; Barbastefano, Víctor; de Paula, Débora; Ferreira, Anderson L; Schmeda-Hirschmann, Guillermo; Rodríguez, Jaime A

    2008-02-01

    The gastroprotective mechanism of the natural diterpene ferruginol was assessed in mice and rats. The involvement of gastric prostaglandins (PGE(2)), reduced glutathione, nitric oxide or capsaicin receptors was evaluated in mice either treated or untreated with indometacin, N-ethylmaleimide (NEM), N-nitro-L-arginine methyl ester (L-NAME) or ruthenium red, respectively, and then orally treated with ferruginol or vehicle. Gastric lesions were induced by oral administration of ethanol. The effects of ferruginol on the parameters of gastric secretion were assessed in pylorus-ligated rats. Gastric PGE(2) content was determined in rats treated with ferruginol and/or indometacin. The reduction of gastric glutathione (GSH) content was determined in rats treated with ethanol after oral administration of ferruginol, lansoprazole or vehicle. Finally, the acute oral toxicity was assessed in mice. Indometacin reversed the gastroprotective effect of ferruginol (25 mg kg(-1)) but not NEM, ruthenium red or L-NAME. The diterpene (25 mg kg(-1)) increased the gastric juice volume and its pH value, and reduced the titrable acidity but was devoid of effect on the gastric mucus content. Ferruginol (25, 50 mg kg(-1)) increased gastric PGE(2) content in a dose-dependent manner and prevented the reduction in GSH observed due to ethanol-induced gastric lesions in rats. Single oral doses up to 3 g kg(-1) ferruginol did not elicit mortality or acute toxic effects in mice. Our results showed that ferruginol acted as a gastroprotective agent stimulating the gastric PGE(2) synthesis, reducing the gastric acid output and improving the antioxidant capacity of the gastric mucosa by maintaining the GSH levels.

  8. A proteome study of secreted prostatic factors affecting osteoblastic activity: galectin-1 is involved in differentiation of human bone marrow stromal cells

    DEFF Research Database (Denmark)

    Andersen, H; Jensen, Ole N; Moiseeva, Elena P

    2003-01-01

    Prostate cancer cells metastasize to bone causing a predominantly osteosclerotic response. It has been shown that cells from the human prostate cancer cell line PC3 secrete factors that influence the behavior of osteoblast-like cells. Some of these factors with mitogenic activity have been found...... to be proteins with molecular weights between 20 and 30 kDa, but the identity of the osteoblastic mitogenic factor or factors produced by prostate cancer cells is still unknown. Therefore, the aim of this study was to characterize the protein profile of conditioned medium (CM) from PC3 cells in the molecular......BMS) cells. Furthermore, we tested whether adhesion of PC3 cells to plastic, laminin, fibronectin, and collagen type I was influenced by lactose, which inhibits galectin-1. Galectin-1 (1000 ng/ml) inhibited the proliferation of hBMS cells up to 70 +/- 12% (treated/control) of control in contrast to PC3 CM...

  9. The ethyl acetate fraction of corn silk exhibits dual antioxidant and anti-glycation activities and protects insulin-secreting cells from glucotoxicity.

    Science.gov (United States)

    Chang, Chia-Chuan; Yuan, Wei; Roan, Hsiao-Yuh; Chang, Jia-Ling; Huang, Hsiu-Chen; Lee, Yu-Ching; Tsay, Huey Jen; Liu, Hui-Kang

    2016-11-03

    In this study, we aimed to develop a Stigmata Maydis (corn silk) fraction with dual bio-activities against oxidative stress and protein glycation to protect β-cells from diabetes-induced failure. Corn silk fractions were prepared by partition and chemically characterised by thin-layer chromatography. Free radical scavenging assay, glycation assay, and cell-based viability test (neutral red) were employed to decide the best fraction. Cell death analysis was executed by annexin V/ Propidium iodide staining. Cell proliferation was measured by WST-1. Finally, β-cell function was evaluated by β-cell marker gene expression (RT-PCR) and acute insulin secretion test. Four corn silk fractions were prepared from an ethanolic crude extract of corn silk. In vitro assays indicate ethyl acetate fraction (YMS-EA) was the most potent fraction. YMS-EA also attenuated the hydrogen peroxide- or methylglyoxal-induced induction of reactive oxygen species, reduction of cell viability, and inhibition of cell proliferation. However, YMS-EA was unable to prevent hydrogen peroxide-induced apoptosis or advanced glycation end-products-induced toxicity. Under hyperglycemic conditions, YMS-EA effectively reduced ROS levels, improved mRNA expression of insulin, glucokinase, and PDX-1, and enhanced glucose-stimulated insulin secretion. The similarity of bioactivities among apigenin, luteolin, and YMS-EA indicated that dual activities of YMS-EA might be derived from those compounds. We concluded that YMS-EA fraction could be developed as a preventive food agent against the glucotoxicity to β-cells in Type 2 diabetes.

  10. Playing facilitator

    DEFF Research Database (Denmark)

    Houmøller, Ellen; Marchetti, Emanuela

    2015-01-01

    event called InnoEvent, addressed to students in the fields of multimedia and healthcare. Being interested in studying games and role-play as tools to support independent learning in the field of design thinking and team-building, following Dewey’s (1938) theory of learning experience, we ran two...... workshops based on two classic role-play games: The Silent Game (Brandt, 2006) and The Six Thinking Hats (de Bono, 1985). These games were created to support students in learning design thinking in groups and are assigned positive values in literature, hence we expected a smooth process. However, our...... experience was rather characterized by conflictual negotiations with the students. Data from our observations and from interviews with group representatives show that the students took a discontinuous learning path, characterised by a false start, failure, and a thorough reconsideration of their work...

  11. Active play and screen time in US children aged 4 to 11 years in relation to sociodemographic and weight status characteristics: a nationally representative cross-sectional analysis

    Directory of Open Access Journals (Sweden)

    Must Aviva

    2008-10-01

    Full Text Available Abstract Background The high prevalence of childhood obesity underscores the importance of monitoring population trends in children's activity and screen time, and describing associations with child age, gender, race/ethnicity, and weight status. Our objective was to estimate the proportion of young children in the US who have low levels of active play or high levels of screen time, or who have both these behaviors, and to describe associations with age, gender, race/ethnicity, and weight status. Methods We analyzed data collected during the National Health and Nutrition Examination Surveys 2001–2004, a US nationally representative cross-sectional study. We studied 2964 children aged 4.00 to 11.99 years. Our main outcomes were reported weekly times that the child played or exercised hard enough to sweat or breathe hard (active play, daily hours the child watched television/videos, used computers, or played computer games (screen time, and the combination of low active play and high screen time. Low active play was defined as active play 6 times or less per week. High screen time was defined as more than 2 hours per day. We accounted for the complex survey design in analyses and report proportions and 95% confidence intervals. We used Wald Chi-square to test for differences between proportions. To identify factors associated with low active play and high screen time, we used multivariate logistic regression. Results Of US children aged 4 to 11 years, 37.3% (95% confidence interval, 34.1% to 40.4% had low levels of active play, 65.0% (95% CI, 61.4% to 68.5% had high screen time, and 26.3% (95% CI, 23.8% to 28.9% had both these behaviors. Characteristics associated with a higher probability of simultaneously having low active play and high screen time were older age, female gender, non-Hispanic black race/ethnicity, and having a BMI-for-age ≥95th percentile of the CDC growth reference. Conclusion Many young children in the US are reported to

  12. Recently activated naive CD4 T cells can help resting B cells, and can produce sufficient autocrine IL-4 to drive differentiation to secretion of T helper 2-type cytokines.

    Science.gov (United States)

    Croft, M; Swain, S L

    1995-05-01

    Development of T cells during primary responses was investigated using pigeon cytochrome C-specific naive Th from TCR transgenic mice. Naive CD4 cells did not activate and help resting B cells. This failure was found to be primarily because the resting B cells were incapable of stimulating the naive Th. Provision of a costimulatory signal such as anti-CD28, or addition of APCs that express costimulatory molecules, such as dendritic cells, activated B cells, and B7+ and B7+ICAM(+)-expressing fibroblasts, induced naive Th activation and promoted T cell-dependent help for IgM secretion. T cell activation for as little as 24 h promoted helper activity, and Ig secretion required production of small amounts of IL-4 by the activated naive Th. On initial stimulation, naive Th secrete only IL-2. By mRNA analysis, activated naive Th were also shown to produce IL-4, however induction of IL-4 message only occurred 24 h after initial activation and required additional stimulation with Ag. A single exposure of naive CD4 to Ag/APC followed by 4 to 12 days in culture led to generation of effector Th which secreted IL-2 and some IFN-gamma, and no detectable IL-4 or IL-5, and which could only help B cells to IgM secretion. In contrast, similar cultures that received Ag/APC one or more times during this period generated effector cells capable of secreting easily detectable titers of IL-4 and IL-5, as well as IL-2 and IFN-gamma, and able to now promote IgG1 and IgE responses. Generation of these Th0-like effectors was accompanied by increasing amounts of IL-4 secreted during the culture period after each restimulation, and addition of anti-IL-4 in culture inhibited development of the capacity to produce Th2 cytokines. These studies reinforce the notion that naive CD4 must interact with a costimulatory professional APC, rather than a resting B cell, for initiation of the primary response, but show that such an interaction can result in rapid development of the ability to interact with

  13. Hypoxia-inducible Lipid Droplet-associated (HILPDA) Is a Novel Peroxisome Proliferator-activated Receptor (PPAR) Target Involved in Hepatic Triglyceride Secretion

    NARCIS (Netherlands)

    Mattijsen, F.; Georgiadi, A.; Andasarie, T.; Szalowska, E.; Zota, A.; Krones-Herzig, A.; Kersten, A.H.

    2014-01-01

    Peroxisome proliferator-activated receptors (PPARs) play major roles in the regulation of hepatic lipid metabolism through the control of numerous genes involved in processes such as lipid uptake and fatty acid oxidation. Here we identify hypoxia-inducible lipid droplet-associated (Hilpda/Hig2) as a

  14. Gastric secretion elicited by conditioning in rats.

    Science.gov (United States)

    Caboclo, José Liberato Ferreira; Cury, Francico de Assis; Borin, Aldenis Albanese; Caboclo, Luís Otávio Sales Ferreira; Ribeiro, Maria Fernanda Sales Caboclo; de Freitas, Pedro José; Andersson, Sven

    2009-01-01

    To investigate whether interdigestive gastric acid secretion can be controlled by a possible memory-related cortical mechanism. To evaluate gastric secretion in rats, we used a methodology that allows gastric juice collection in rats in their habitual conditions (without any restraining) by pairing sound as the conditioning stimulus (CS) and food as the unconditioning stimulus (US). The levels of gastric acid secretion under basal conditions and under sound stimulation were recorded and the circulating gastrin levels determined. When the gastric juice was collected in the course of the conditioning procedure, the results showed that under noise stimulation a significant increase in gastric acid secretion occurred after 10 days of conditioning (p<0.01). The significance was definitively demonstrated after 13 days of conditioning (p<0.001). Basal secretions of the conditioned rats reached a significant level after 16 days of conditioning. The levels of noise-stimulated gastric acid secretion were the highest so far described in physiological experiments carried out in rats and there were no significant increases in the circulating gastrin levels. The results point to the important role played by cortical structures in the control of interdigestive gastric acid secretion in rats. If this mechanism is also present in humans, it may be involved in diseases caused by inappropriate gastric acid secretion during the interprandial periods.

  15. Playing with social identities

    DEFF Research Database (Denmark)

    Winther-Lindqvist, Ditte Alexandra

    2013-01-01

    as pretence, children’s play is understood as an activity involving rules of the social order (roles and positions) as well as identification processes (imagined situations). The theoretical argumentation builds on empirical examples obtained in two different Danish day-care centres. The chapter is informed...... by ethnographic observations and draws on illustrative examples with symbolic group play as well as game-play with rules (soccer) among 5 year old boys. Findings suggest that day-care children’s play, involves negotiation of roles, positioning and identification, and rules – and that these negotiations......This chapter offers support for Vygotsky’s claim that all play involves both an imagined situation as well as rules. Synthesising Schousboe’s comprehensive model of spheres of realities in playing (see Chapter 1, this volume) with Lev Vygotskys insight that all playing involve rules as well...

  16. Soreness during non-music activities is associated with playing-related musculoskeletal problems: an observational study of 731 child and adolescent instrumentalists

    Directory of Open Access Journals (Sweden)

    Sonia Ranelli

    2014-06-01

    Full Text Available Question: Is exposure to non-music-related activities associated with playing-related musculoskeletal problems in young instrumentalists? Is non-music-activity-related soreness associated with playing-related musculoskeletal problems in this group of instrumentalists? Design: Observational study using a questionnaire and physical measures. Participants: 859 instrumentalists aged 7 to 17 years from the School of Instrumental Music program. Results: Of the 731 respondents who completed the questionnaire adequately, 412 (56% experienced instrument-playing problems; 219 (30% had symptoms severe enough to interfere with normal playing. Children commonly reported moderate exposure to non-music-related activities, such as watching television (61%, vigorous physical activity (57%, writing (51% and computer use (45%. Greater exposure to any non-music activity was not associated with playing problems, with odds ratios ranging from 1.01 (95% CI 0.7 to 1.5 for watching television to 2.08 (95% CI 0.5 to 3.3 for intensive hand activities. Four hundred and seventy eight (65% children reported soreness related to non-music activities, such as vigorous physical activity (52%, writing (40%, computer use (28%, intensive hand activities (22%, electronic game use (17% and watching television (15%. Non-music-activity-related soreness was significantly associated with instrument playing problems, adjusting for gender and age, with odds ratios ranging from 2.6 (95% CI 1.7 to 3.9 for soreness whilst watching television, to 4.3 (95% CI 2.6 to 7.1 for soreness during intensive hand activities. Conclusion: Non-music-activity-related soreness co-occurs significantly with playing problems in young instrumentalists. The finding of significant co-occurrence of music and non-music-related soreness in respondents in this study suggests that intervention targets for young instrumentalists could include risk factors previously identified in the general child and adolescent

  17. Infection of human monocyte-derived dendritic cells by ANDES Hantavirus enhances pro-inflammatory state, the secretion of active MMP-9 and indirectly enhances endothelial permeability

    Directory of Open Access Journals (Sweden)

    Lopez-Lastra Marcelo

    2011-05-01

    Full Text Available Abstract Background Andes virus (ANDV, a rodent-borne Hantavirus, is the major etiological agent of Hantavirus cardiopulmonary syndrome (HCPS in South America, which is mainly characterized by a vascular leakage with high rate of fatal outcomes for infected patients. Currently, neither specific therapy nor vaccines are available against this pathogen. ANDV infects both dendritic and epithelial cells, but in despite that the severity of the disease directly correlates with the viral RNA load, considerable evidence suggests that immune mechanisms rather than direct viral cytopathology are responsible for plasma leakage in HCPS. Here, we assessed the possible effect of soluble factors, induced in viral-activated DCs, on endothelial permeability. Activated immune cells, including DC, secrete gelatinolytic matrix metalloproteases (gMMP-2 and -9 that modulate the vascular permeability for their trafficking. Methods A clinical ANDES isolate was used to infect DC derived from primary PBMC. Maturation and pro-inflammatory phenotypes of ANDES-infected DC were assessed by studying the expression of receptors, cytokines and active gMMP-9, as well as some of their functional status. The ANDES-infected DC supernatants were assessed for their capacity to enhance a monolayer endothelial permeability using primary human vascular endothelial cells (HUVEC. Results Here, we show that in vitro primary DCs infected by a clinical isolate of ANDV shed virus RNA and proteins, suggesting a competent viral replication in these cells. Moreover, this infection induces an enhanced expression of soluble pro-inflammatory factors, including TNF-α and the active gMMP-9, as well as a decreased expression of anti-inflammatory cytokines, such as IL-10 and TGF-β. These viral activated cells are less sensitive to apoptosis. Moreover, supernatants from ANDV-infected DCs were able to indirectly enhance the permeability of a monolayer of primary HUVEC. Conclusions Primary human DCs

  18. Playing Possum

    Directory of Open Access Journals (Sweden)

    Enrico Euli

    2016-07-01

    Full Text Available Our society is drenched in the catastrophe; where the growth of financial crisis, environmental cataclysm and militarization represents its gaudiest and mortifying phenomena. Humans struggle with depression, sense of impotence, anguish towards a future considered a threat.  A possibility to keep us alive can be represented by the enhancement of our ability in ‘playing Possum’, an exercise of desisting and renitence: to firmly say ‘no’. To say no to a world that proposes just one way of being and living free, that imposes as the only unavoidable possible destiny.

  19. Playful Technology

    DEFF Research Database (Denmark)

    Johansen, Stine Liv; Eriksson, Eva

    2013-01-01

    In this paper, the design of future services for children in Danish public libraries is discussed, in the light of new challenges and opportunities in relation to new media and technologies. The Danish government has over the last few years initiated and described a range of initiatives regarding...... in the library,