Science.gov

Sample records for a-i promoter activity

  1. Effect of TNF{alpha} on activities of different promoters of human apolipoprotein A-I gene

    SciTech Connect

    Orlov, Sergey V.; Mogilenko, Denis A.; Shavva, Vladimir S.; Dizhe, Ella B.; Ignatovich, Irina A.; Perevozchikov, Andrej P.

    2010-07-23

    Research highlights: {yields} TNF{alpha} stimulates the distal alternative promoter of human apoA-I gene. {yields} TNF{alpha} acts by weakening of promoter competition within apoA-I gene (promoter switching). {yields} MEK1/2 and nuclear receptors PPAR{alpha} and LXRs take part in apoA-I promoter switching. -- Abstract: Human apolipoprotein A-I (ApoA-I) is a major structural and functional protein component of high-density lipoproteins. The expression of the apolipoprotein A-I gene (apoA-I) in hepatocytes is repressed by pro-inflammatory cytokines such as IL-1{beta} and TNF{alpha}. Recently, two novel additional (alternative) promoters for human apoA-I gene have been identified. Nothing is known about the role of alternative promoters in TNF{alpha}-mediated downregulation of apoA-I gene. In this article we report for the first time about the different effects of TNF{alpha} on two alternative promoters of human apoA-I gene. Stimulation of HepG2 cells by TNF{alpha} leads to activation of the distal alternative apoA-I promoter and downregulation of the proximal alternative and the canonical apoA-I promoters. This effect is mediated by weakening of the promoter competition within human apoA-I 5'-regulatory region (apoA-I promoter switching) in the cells treated by TNF{alpha}. The MEK1/2-ERK1/2 cascade and nuclear receptors PPAR{alpha} and LXRs are important for TNF{alpha}-mediated apoA-I promoter switching.

  2. Regulation of the promoter of rat apolipoprotein A-I gene in cultured cells

    SciTech Connect

    Chao, Y.; Pan, T.; Wu, T.; Hao, Q.; Yamin, T.; Kroon, P.A.

    1987-05-01

    In order to study the regulation of the promoter of apolipoprotein (apo) A-I gene, they joined the 5' end of rat apo A-I gene (1.9 Kb) to the coding region of bacterial chloramphenicol acetyltransferase (CAT) gene. The chimeric gene produced high levels of CAT activity in both mouse L cells and Hep G2 cells in transient expression assays. Ethanol increased the levels of rat apo A-I promoter activity in both cells. However, dexamethasone increased rat apo A-I promoter activity only in Hep G2 cells. Similar results were obtained in stable expression cell lines. Nucleotide deletion experiments showed DNA sequences between -149 and -469 base pairs upstream from the rat apo A-I transcription site are required for the high level of expression and that the regulatory sequences are located further upstream. These data demonstrated that the 5' end of rat apo A-I gene contains sequences which are responsible for the regulation of apo A-I expression by ethanol and dexamethasone and that the expression and regulation of rat apo A-I promoter are cell specific.

  3. Apolipoprotein A-I Helsinki promotes intracellular acyl-CoA cholesterol acyltransferase (ACAT) protein accumulation.

    PubMed

    Toledo, Juan D; Garda, Horacio A; Cabaleiro, Laura V; Cuellar, Angela; Pellon-Maison, Magali; Gonzalez-Baro, Maria R; Gonzalez, Marina C

    2013-05-01

    Reverse cholesterol transport is a process of high antiatherogenic relevance in which apolipoprotein AI (apoA-I) plays an important role. The interaction of apoA-I with peripheral cells produces through mechanisms that are still poorly understood the mobilization of intracellular cholesterol depots toward plasma membrane. In macrophages, these mechanisms seem to be related to the modulation of the activity of acyl-CoA cholesterol acyltransferase (ACAT), the enzyme responsible for the intracellular cholesterol ester biosynthesis that is stored in lipid droplets. The activation of ACAT and the accumulation of lipid droplets play a key role in the transformation of macrophages into foam cells, leading to the formation of atheroma or atherosclerotic plaque. ApoA-I Helsinki (or ∆K107) is a natural apoA-I variant with a lysine deletion in the central protein region, carriers of which have increased atherosclerosis risk. We herein show that treatment of cultured RAW macrophages or CHOK1 cells with ∆K107, but not with wild-type apoA-I or a variant containing a similar deletion at the C-terminal region (∆K226), lead to a marked increase (more than 10 times) in the intracellular ACAT1 protein level as detected by western blot analysis. However, we could only detect a slight increase in cholesteryl ester produced by ∆K107 mainly when Chol loading was supplied by low-density lipoprotein (LDL). Although a similar choline-phospholipid efflux is evoked by these apoA-I variants, the change in phosphatidylcholine/sphyngomyelin distribution produced by wild-type apoA-I is not observed with either ∆K107 or ∆K226.

  4. Interventions for promoting physical activity

    PubMed Central

    Foster, Charles; Hillsdon, Melvyn; Thorogood, Margaret; Kaur, Asha; Wedatilake, Thamindu

    2014-01-01

    Background Little is known about the effectiveness of strategies to enable people to achieve and maintain recommended levels of physical activity. Objectives To assess the effectiveness of interventions designed to promote physical activity in adults aged 16 years and older, not living in an institution. Search methods We searched The Cochrane Library (issue 1 2005), MEDLINE, EMBASE, CINAHL, PsycLIT, BIDS ISI, SPORTDISCUS, SIGLE, SCISEARCH (from earliest dates available to December 2004). Reference lists of relevant articles were checked. No language restrictions were applied. Selection criteria Randomised controlled trials that compared different interventions to encourage sedentary adults not living in an institution to become physically active. Studies required a minimum of six months follow up from the start of the intervention to the collection of final data and either used an intention-to-treat analysis or, failing that, had no more than 20% loss to follow up. Data collection and analysis At least two reviewers independently assessed each study quality and extracted data. Study authors were contacted for additional information where necessary. Standardised mean differences and 95% confidence intervals were calculated for continuous measures of self-reported physical activity and cardio-respiratory fitness. For studies with dichotomous outcomes, odds ratios and 95% confidence intervals were calculated. Main results The effect of interventions on self-reported physical activity (19 studies; 7598 participants) was positive and moderate (pooled SMD random effects model 0.28 95% CI 0.15 to 0.41) as was the effect of interventions (11 studies; 2195 participants) on cardio-respiratory fitness (pooled SMD random effects model 0.52 95% CI 0.14 to 0.90). There was significant heterogeneity in the reported effects as well as heterogeneity in characteristics of the interventions. The heterogeneity in reported effects was reduced in higher quality studies, when physical

  5. Promoting Business Education through Student Organization Activities.

    ERIC Educational Resources Information Center

    Yelverton, Sandra

    1983-01-01

    Discusses the promotion of business education through the activities of student organizations. Describes specific programs, projects, and leadership development activities and their effectiveness in publicizing business education programs. (JOW)

  6. Activities for Engaging Schools in Health Promotion

    ERIC Educational Resources Information Center

    Bardi, Mohammad; Burbank, Andrea; Choi, Wayne; Chow, Lawrence; Jang, Wesley; Roccamatisi, Dawn; Timberley-Berg, Tonia; Sanghera, Mandeep; Zhang, Margaret; Macnab, Andrew J.

    2014-01-01

    Purpose: The purpose of this paper is to describe activities used to initiate health promotion in the school setting. Design/Methodology/Approach: Description of successful pilot Health Promoting School (HPS) initiatives in Canada and Uganda and the validated measures central to each program. Evaluation methodologies: quantitative data from the…

  7. Promoting Active Involvement in Classrooms

    ERIC Educational Resources Information Center

    Conderman, Greg; Bresnahan, Val; Hedin, Laura

    2012-01-01

    This article presents a rationale for using active involvement techniques, describes large- and small-group methods based on their documented effectiveness and applicability to K-12 classrooms, and illustrates their use. These approaches include ways of engaging students in large groups (e.g., unison responses, response cards, dry-erase boards,…

  8. PARP promoter-mediated activation of a VSG expression site promoter in insect form Trypanosoma brucei.

    PubMed

    Urményi, T P; Van der Ploeg, L H

    1995-03-25

    In trypanosomes the rRNA, PARP and VSG gene promoters mediate alpha-amanitin-resistant transcription of protein coding genes, presumably by RNA polymerase (pol) I. We compared the activity of PARP and VSG promoters integrated at one of the alleles of the largest subunit of pol II genes in insect form trypanosomes. Even though both promoters are roughly equally active in transient transformation assays in insect form trypanosomes, only the PARP promoter functioned effectively when integrated at the pol II largest subunit or other loci. Promoter activity in transient transformation assays is therefore not necessarily predictive of transcriptional activity once integrated into the trypanosome genome. The integrated fully active PARP promoter could upregulate in cis an otherwise poorly active integrated VSG promoter. The PARP promoter nucleotide sequence elements responsible for VSG promoter activation coincided with most of the important PARP promoter elements mapped previously by linker scanning mutagenesis, indicating that it is not a single unique promoter element that was responsible for VSG promoter activation. The data suggest that PARP promoter-mediated activation of the VSG promoter does not result from complementation of the VSG promoter with a single insect form-specific transcription factor whose binding site is missing from the VSG promoter and present in the PARP promoter. We favor a model in which chromatin structure at the locus is altered by the PARP promoter, allowing VSG promoter activation in insect form trypanosomes. We discuss the significance of these observations for the control of VSG promoters in insect form trypanosomes.

  9. Promoting Active Involvement in Today's Classrooms

    ERIC Educational Resources Information Center

    Conderman, Greg; Bresnahan, Val; Hedin, Laura

    2011-01-01

    In today's diverse classrooms and age of accountability, teachers need to use efficient, research-based instructional approaches that engage all students, promote interest and variety in learning and teaching, and provide immediate and continuous informal assessment data. This article presents a rationale for using active involvement techniques,…

  10. Mobile Computer Application for Promoting Physical Activity

    PubMed Central

    McMahon, Siobhan; Vankipuram, Mithra; Fleury, Julie

    2016-01-01

    Despite evidence that physical activity reduces the risk of falls and other causes of disability and death, the majority of older adults do not engage in physical activity on a regular basis. Mobile technology applications have emerged as potential resources for promoting physical activity behavior. This article describes features of a new application, Ready~Steady, highlighting approaches used in its design and development, and implications for clinical practice. Iterative processes enabled the design, development, implementation, and evaluation of the application consistent with the wellness motivation theory, as well as established user-specific strategies and theoretical design principles. Implications in terms of potential benefits and constraints are discussed. Integrating technology that promotes health and wellness in the form of mobile computer applications is a promising adjunct to nursing practice. PMID:23463915

  11. Mobile computer application for promoting physical activity.

    PubMed

    McMahon, Siobhan; Vankipuram, Mithra; Fleury, Julie

    2013-04-01

    Despite evidence that physical activity reduces the risk of falls and other causes of disability and death, the majority of older adults do not engage in physical activity on a regular basis. Mobile technology applications have emerged as potential resources for promoting physical activity behavior. This article describes features of a new application, Ready∼Steady, highlighting approaches used in its design and development, and implications for clinical practice. Iterative processes enabled the design, development, implementation, and evaluation of the application consistent with the wellness motivation theory, as well as established user-specific strategies and theoretical design principles. Implications in terms of potential benefits and constraints are discussed. Integrating technology that promotes health and wellness in the form of mobile computer applications is a promising adjunct to nursing practice.

  12. Transient ECM protease activity promotes synaptic plasticity

    PubMed Central

    Magnowska, Marta; Gorkiewicz, Tomasz; Suska, Anna; Wawrzyniak, Marcin; Rutkowska-Wlodarczyk, Izabela; Kaczmarek, Leszek; Wlodarczyk, Jakub

    2016-01-01

    Activity-dependent proteolysis at a synapse has been recognized as a pivotal factor in controlling dynamic changes in dendritic spine shape and function; however, excessive proteolytic activity is detrimental to the cells. The exact mechanism of control of these seemingly contradictory outcomes of protease activity remains unknown. Here, we reveal that dendritic spine maturation is strictly controlled by the proteolytic activity, and its inhibition by the endogenous inhibitor (Tissue inhibitor of matrix metalloproteinases-1 – TIMP-1). Excessive proteolytic activity impairs long-term potentiation of the synaptic efficacy (LTP), and this impairment could be rescued by inhibition of protease activity. Moreover LTP is altered persistently when the ability of TIMP-1 to inhibit protease activity is abrogated, further demonstrating the role of such inhibition in the promotion of synaptic plasticity under well-defined conditions. We also show that dendritic spine maturation involves an intermediate formation of elongated spines, followed by their conversion into mushroom shape. The formation of mushroom-shaped spines is accompanied by increase in AMPA/NMDA ratio of glutamate receptors. Altogether, our results identify inhibition of protease activity as a critical regulatory mechanism for dendritic spines maturation. PMID:27282248

  13. In trans promoter activation by enhancers in transient transfection.

    PubMed

    Smirnov, N A; Akopov, S B; Didych, D A; Nikolaev, L G

    2017-03-01

    Earlier, it was reported that the strong cytomegalovirus enhancer can activate the cytomegalovirus promoter in trans, i.e. as a separate plasmid co-transfected with a promoter-reporter gene construct. Here we demonstrate that the ability of enhancers to activate promoters in trans in transient transfection experiments is a property of not only viral regulatory elements but also of various genomic enhancers and promoters. Enhancer-promoter activation in trans is promoter- and cell type-specific, and accompanied by physical interaction between promoter and enhancer as revealed by chromosome conformation capture assays. Thus, promoter activation in transient co-transfection of promoters and enhancers shares a number of important traits with long-distance promoter activation by enhancers in living cells and may therefore serve as a model of this fundamental cellular process.

  14. Plant growth-promoting hormones activate mammalian guanylate cyclase activity.

    PubMed

    Vesely, D L; Hudson, J L; Pipkin, J L; Pack, L D; Meiners, S E

    1985-05-01

    In vivo injections of plant growth-promoting hormones increase the growth of animals as well as plants. Plant growth-promoting hormones and positive plant growth regulators are known to increase RNA and protein synthesis. Since cyclic GMP also increases RNA and protein synthesis, the object of the present investigation was to determine whether physiological levels of plant growth-promoting hormones and positive plant growth regulators have part of their mechanism(s) of action through stimulation of the guanylate cyclase (EC 4.6.1.2)-cyclic GMP system. Representatives of the three classes of growth-promoting hormones were investigated. Thus, auxins (indole-3-acetic acid, indole-3-butyric acid, beta-naphthoxyacetic acid, and 2,4,5-trichlorophenoxy acetic acid), gibberellins (gibberellic acid), and cytokinins [N6-benzyl adenine, kinetin (6-furfuryl aminopurine), and beta-(2-furyl) acrylic acid] all increased rat lung, small intestine, liver, and renal cortex guanylate cyclase activity 2- to 4-fold at the 1 microM concentration. Dose response curves revealed that maximal stimulation of guanylate cyclase by these plant growth regulators was at 1 microM; there was no augmented cyclase activity at 1 nM. The guanylate cyclase cationic cofactor manganese was not essential for augmentation of guanylate cyclase by these plant growth-promoting regulators. The antioxidant butylated hydroxytoluene did not block the enhancement of guanylate cyclase by these plant growth-promoting factors. These data suggest that guanylate cyclase may play a role in the mechanism of action of plant growth-promoting hormones and even of positive plant regulators at the cellular level.

  15. Financial Incentives to Promote Active Travel

    PubMed Central

    Martin, Adam; Suhrcke, Marc; Ogilvie, David

    2012-01-01

    Context Financial incentives, including taxes and subsidies, can be used to encourage behavior change. They are common in transport policy for tackling externalities associated with use of motor vehicles, and in public health for influencing alcohol consumption and smoking behaviors. Financial incentives also offer policymakers a compromise between “nudging,” which may be insufficient for changing habitual behavior, and regulations that restrict individual choice. Evidence acquisition The literature review identified studies published between January 1997 and January 2012 of financial incentives relating to any mode of travel in which the impact on active travel, physical activity, or obesity levels was reported. It encompassed macroenvironmental schemes, such as gasoline taxes, and microenvironmental schemes, such as employer-subsidized bicycles. Five relevant reviews and 20 primary studies (of which nine were not included in the reviews) were identified. Evidence synthesis The results show that more-robust evidence is required if policymakers are to maximize the health impact of fiscal policy relating to transport schemes of this kind. Conclusions Drawing on a literature review and insights from the SLOTH (sleep, leisure, occupation, transportation, and home-based activities) time-budget model, this paper argues that financial incentives may have a larger role in promoting walking and cycling than is acknowledged generally. PMID:23159264

  16. Sequence-specific apolipoprotein A-I effects on lecithin:cholesterol acyltransferase activity.

    PubMed

    Dergunov, Alexander D

    2013-06-01

    Existing kinetic data of cholesteryl ester formation by lecithin:cholesterol acyltransferase in discoidal high-density lipoproteins with 34 mutations of apoA-I that involved all putative helices were grouped by cluster analysis into four noncoincident regions with mutations both without any functional impairment and with profound isolated (V- and K-mutations) or common (VK-mutations) effect on V(max)(app) and K(m)(app). Data were analyzed with a new kinetic model of LCAT activity at interface that exploits the efficiency of LCAT binding to the particle, particle dimensions, and surface concentrations of phosphatidylcholine and cholesterol. V-mutations with major location in the central part and C-domain affected the second-order rate constant of cholesteryl ester formation at the solvolysis of acyl-enzyme intermediate by cholesterol as nucleophile. The central region in apoA-I sequence is suggested to influence the proper positioning of cholesterol molecule toward LCAT active center with major contribution of arginine residue(s). K-mutations with major location in N-domain may affect binding and stability of enzyme-phosphatidylcholine complex. VK-mutations may possess mixed effects; the independent binding measurement may segregate individual steps.

  17. Data describing the effect of DRD4 promoter polymorphisms on promoter activity.

    PubMed

    Tei, Shoin; Mitsuhashi, Hiroaki; Ishiura, Shoichi

    2016-06-01

    This data article tested whether polymorphisms within the dopamine D4 receptor (DRD4) gene promoter can lead to differences in the promoter activity. The variants, a 120-bp variable number tandem repeat (VNTR), -906 T/C, -809 G/A, -616G/C, and -521C/T, were introduced into the DRD4 promoter and the promoter activity was measured in a neural cell line using the luciferase assay. However, no differences were detected among the haplotypes investigated, and the in vitro data obtained from our protocol could not support the involvement of DRD4 promoter polymorphisms in heritable human traits.

  18. Cholesterol Independent Suppression of Lymphocyte Activation, Autoimmunity and Glomerulonephritis by Apolipoprotein A-I in Normocholesterolemic Lupus-Prone Mice

    PubMed Central

    Black, Leland L.; Srivastava, Roshni; Schoeb, Trenton R.; Moore, Ray D.; Barnes, Stephen; Kabarowski, Janusz H.

    2015-01-01

    Apolipoprotein A-I (ApoA-I), the major lipid-binding protein of high-density lipoprotein (HDL), can prevent autoimmunity and suppress inflammation in hypercholesterolemic mice by attenuating lymphocyte cholesterol accumulation and removing tissue oxidized lipids. However, whether ApoA-I mediates immune suppressive or anti-inflammatory effects in normocholesterolemic conditions and the mechanisms involved remain unresolved. We transferred bone marrow from SLE-prone Sle123 mice into normal, ApoA-I knockout (ApoA-I−/−) and ApoA-I transgenic (ApoA-Itg) mice. Increased ApoA-I in ApoA-Itg mice suppressed CD4+ T and B cell activation without changing lymphocyte cholesterol levels or reducing major ApoA-I-binding oxidized fatty acids. Unexpectedly, oxidized fatty acid peroxisome proliferator-activated receptor gamma (PPARγ) ligands 13-hydroxyoctadecadienoic acid (HODE) and 9-HODE were increased in lymphocytes of autoimmune ApoA-Itg mice. ApoA-I reduced Th1 cells independently of changes in CD4+FoxP3+ regulatory T cells or CD11c+ dendritic cell activation and migration. Follicular helper T cells, germinal center B cells and autoantibodies were also lower in ApoA-Itg mice. Transgenic ApoA-I also improved SLE-mediated glomerulonephritis. However, ApoA-I deficiency did not have opposite effects on autoimmunity or glomerulonephritis, possibly due to compensatory increases of ApoE on HDL. We conclude that although compensatory mechanisms prevent pro-inflammatory effects of ApoA-I deficiency in normocholesterolemic mice, increasing ApoA-I can attenuate lymphocyte activation and autoimmunity in SLE independently of cholesterol transport, possibly through oxidized fatty acid PPARγ ligands, and can reduce renal inflammation in glomerulonephritis. PMID:26466956

  19. Characterization of human TCR Vbeta gene promoter. Role of the dodecamer motif in promoter activity.

    PubMed

    Deng, X; Sun, G R; Zheng, Q; Li, Y

    1998-09-11

    During T-lymphocyte development, the T-cell antigen receptor (TCR) gene expression is controlled by its promoter and enhancer elements and regulated in tissue- and development stage-specific manner. To uncover the promoter function and to define positive and negative regulatory elements in TCR gene promoters, the promoter activities from 13 human TCR Vbeta genes were determined by the transient transfection system and luciferase reporter assay. Although most of the TCR Vbeta gene promoters that we tested are inactive by themselves, some promoters were found to be constitutively strong. Among them, Vbeta6.7 is the strongest. 5'-Deletion and fragmentation experiments have narrowed the full promoter activity of Vbeta6.7 to a fragment of 147 base pairs immediately 5' to the transcription initiation site. A decanucleotide motif with the consensus sequence AGTGAYRTCA has been found to be conserved in most TCR Vbeta gene promoters. There are three such decamer motifs in the promoter region of Vbeta6.7, and the contribution of each such motif to the promoter activity has been examined. Further site-directed mutagenesis analyses showed that: 1) when two Ts in the decamer were mutated, the promoter activity was totally abolished; 2) when two additional nucleotides 3' to the end of decamer were mutated, the promoter activity was decreased to two-thirds of the full level; and 3) when the element with the sequence AGTGATGTCACT was inserted into other promoters, the original weak promoters become very strong. Taken together, our data suggest that the positive regulatory element in Vbeta6.7 should be considered a dodecamer rather than a decamer and that it confers strong basal transcriptional activity on TCR Vbeta genes.

  20. Face washing promotion for preventing active trachoma

    PubMed Central

    Ejere, Henry OD; Alhassan, Mahmoud B; Rabiu, Mansur

    2015-01-01

    Background Trachoma remains a major cause of avoidable blindness among underprivileged populations in many developing countries. It is estimated that about 146 million people have active trachoma and nearly six million people are blind due to complications associated with repeat infections. Objectives The objective of this review was to assess the effects of face washing promotion for the prevention of active trachoma in endemic communities. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to January 2015), EMBASE (January 1980 to January 2015), PubMed (January 1948 to January 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to January 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (accessed 10 January 2014), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 26 January 2015. To identify further relevant trials we checked the reference lists of the included trials. Also, we used the Science Citation Index to search for references to publications that cited the trials included in the review. We contacted investigators and experts in the field to identify additional trials. Selection criteria We included randomized controlled trials (RCTs) or quasi-RCTs that compared face washing with no treatment or face washing combined with antibiotics against antibiotics alone. Trial participants were residents of endemic trachoma communities. Data collection and analysis Two review authors independently extracted data and assessed trial quality. We contacted trial

  1. Synthetic muscle promoters: activities exceeding naturally occurring regulatory sequences

    NASA Technical Reports Server (NTRS)

    Li, X.; Eastman, E. M.; Schwartz, R. J.; Draghia-Akli, R.

    1999-01-01

    Relatively low levels of expression from naturally occurring promoters have limited the use of muscle as a gene therapy target. Myogenic restricted gene promoters display complex organization usually involving combinations of several myogenic regulatory elements. By random assembly of E-box, MEF-2, TEF-1, and SRE sites into synthetic promoter recombinant libraries, and screening of hundreds of individual clones for transcriptional activity in vitro and in vivo, several artificial promoters were isolated whose transcriptional potencies greatly exceed those of natural myogenic and viral gene promoters.

  2. Canonical nucleosome organization at promoters forms during genome activation.

    PubMed

    Zhang, Yong; Vastenhouw, Nadine L; Feng, Jianxing; Fu, Kai; Wang, Chenfei; Ge, Ying; Pauli, Andrea; van Hummelen, Paul; Schier, Alexander F; Liu, X Shirley

    2014-02-01

    The organization of nucleosomes influences transcriptional activity by controlling accessibility of DNA binding proteins to the genome. Genome-wide nucleosome binding profiles have identified a canonical nucleosome organization at gene promoters, where arrays of well-positioned nucleosomes emanate from nucleosome-depleted regions. The mechanisms of formation and the function of canonical promoter nucleosome organization remain unclear. Here we analyze the genome-wide location of nucleosomes during zebrafish embryogenesis and show that well-positioned nucleosome arrays appear on thousands of promoters during the activation of the zygotic genome. The formation of canonical promoter nucleosome organization is independent of DNA sequence preference, transcriptional elongation, and robust RNA polymerase II (Pol II) binding. Instead, canonical promoter nucleosome organization correlates with the presence of histone H3 lysine 4 trimethylation (H3K4me3) and affects future transcriptional activation. These findings reveal that genome activation is central to the organization of nucleosome arrays during early embryogenesis.

  3. Promote Physical Activity--It's Proactive Guidance

    ERIC Educational Resources Information Center

    Gartrell, Dan; Sonsteng, Kathleen

    2008-01-01

    Healthy child development relies on physical activity. New curriculum models are effectively integrating physical activity in education programs. The authors describe three such models: S.M.A.R.T. (Stimulating Maturity through Accelerated Readiness Training); Kids in Action, incorporating cardiovascular endurance, muscle strength and endurance,…

  4. Promoting Physical Activity in Afterschool Programs

    ERIC Educational Resources Information Center

    Beighle, Aaron; Beets, Michael W.; Erwin, Heather E.; Huberty, Jennifer; Moore, Justin B.; Stellino, Megan

    2010-01-01

    Children in the United States are not engaging in sufficient amounts of routine physical activity, and this lack is an emerging public health concern (Strong, Malina, Blimkie, Daniels, Dishman, Gutin, et al., 2005). Efforts to increase the physical activity levels of children and adolescents has become a national priority, attracting attention…

  5. Promoting Physical Activity during Early Childhood

    ERIC Educational Resources Information Center

    Vidoni, Carla; Ignico, Arlene

    2011-01-01

    The prevalence of obesity in children and adolescents from low-income families in the USA has become a significant concern over the last 20 years. One of the major contributors to this problem is the lack of physical activity. The purpose of this paper is to describe initiatives designed to: (1) engage young children in physical activity during…

  6. The Relevant Factors in Promoting Reading Activities in Elementary Schools

    ERIC Educational Resources Information Center

    Huang, Han-Chen; Tsai, Yao-Hsu; Huang, Shih-Hsiang

    2015-01-01

    In order to help students absorb knowledge, schools often conduct reading activities. Thorough planning and strategies, however, are needed to insure the effect of reading promotions, and make them a deeply-rooted part of life. This study adopted the analytic hierarchy process (AHP) to discuss the relevant factors in promoting reading activities…

  7. Brazilian physical activity guidelines as a strategy for health promotion

    PubMed Central

    Sebastião, Emerson; Schwingel, Andiara; Chodzko-Zajko, Wojtek

    2014-01-01

    Public health actions endorsed by the federal government, for instance, health promotion initiatives, usually have greater impact at population level compared to other types of initiatives. This commentary aims to instigate debate on the importance and necessity of producing federally endorsed brazilian physical activity guidelines as a strategy for health promotion. PMID:25210830

  8. Physical Activity Promotion in Call Centres: Employers' Perspectives

    ERIC Educational Resources Information Center

    Renton, Sheila J.; Lightfoot, Nancy E.; Maar, Marion A.

    2011-01-01

    This study followed a predominantly qualitative approach to explore the perspectives of employers in Sudbury, Ontario, Canada, call centres (CCs) regarding physical activity (PA) promotion in workplaces, by identifying current practices and employers' motivation to promote PA, as well as perceived facilitators and barriers. In-depth interviews…

  9. Corporate responsibility for childhood physical activity promotion in the UK.

    PubMed

    Leone, Liliana; Ling, Tom; Baldassarre, Laura; Barnett, Lisa M; Capranica, Laura; Pesce, Caterina

    2016-12-01

    The alarming epidemic of obesity and physical inactivity at paediatric age urges societies to rise to the challenge of ensuring an active lifestyle. As one response to this, business enterprises are increasingly engaged in promoting sport and physical activity (PA) initiatives within the frame of corporate social responsibility (CSR). However, comparative analyses among industry sectors of CSR strategies for PA promotion with a particular focus on children are still lacking. This study aimed to explore (i) what are the CSR strategies for PA promotion adopted in different industry sectors and (ii) whether corporate engagement in promoting PA for children is supportive of children's rights to play and be physically active. Corporate pledges pertaining to CSR initiatives to promote PA were analysed. The hypothesis was that companies from different sectors employ different CSR strategies and that companies with a higher profile as regard to public health concerns for children tend to legitimate their action by adopting a compensatory strategy. Results show that the issue of PA promotion is largely represented within CSR commitments. CSR strategies for PA promotion vary across industry sectors and the adoption of a compensatory strategy for rising childhood obesity allows only a limited exploitation of the potential of CSR commitments for the provision of children's rights to play and be physically active. Actors within the fields of public health ethics, human rights and CSR should be considered complementary to develop mainstreaming strategies and improve monitoring systems of PA promotion in children.

  10. Brazilian physical activity guidelines as a strategy for health promotion.

    PubMed

    Sebastião, Emerson; Schwingel, Andiara; Chodzko-Zajko, Wojtek

    2014-08-01

    Public health actions endorsed by the federal government, for instance, health promotion initiatives, usually have greater impact at population level compared to other types of initiatives. This commentary aims to instigate debate on the importance and necessity of producing federally endorsed brazilian physical activity guidelines as a strategy for health promotion.

  11. RNA Dimerization Promotes PKR Dimerization and Activation

    PubMed Central

    Heinicke, Laurie A.; Wong, C. Jason; Lary, Jeffrey; Nallagatla, Subba Rao; Diegelman-Parente, Amy; Zheng, Xiaofeng; Cole, James L.; Bevilacqua, Philip C.

    2009-01-01

    The double-stranded RNA (dsRNA)-activated protein kinase (PKR) plays a major role in the innate immune response in humans. PKR binds dsRNA non-sequence specifically and requires a minimum of 15 bp dsRNA for one protein to bind and 30 bp dsRNA to induce protein dimerization and activation by autophosphorylation. PKR phosphorylates eIF2α, a translation initiation factor, resulting in the inhibition of protein synthesis. We investigated the mechanism of PKR activation by an RNA hairpin with a number of base pairs intermediate between these 15 to 30 bp limits: HIV-I TAR RNA, a 23 bp hairpin with three bulges that is known to dimerize. To test whether RNA dimerization affects PKR dimerization and activation, TAR monomers and dimers were isolated from native gels and assayed for RNA and protein dimerization. To modulate the extent of dimerization, we included TAR mutants with different secondary features. Native gel mixing experiments and analytical ultracentrifugation indicate that TAR monomers bind one PKR monomer and that TAR dimers bind two or three PKRs, demonstrating that RNA dimerization drives the binding of multiple PKR molecules. Consistent with functional dimerization of PKR, TAR dimers activated PKR while TAR monomers did not, and RNA dimers with fewer asymmetrical secondary structure defects, as determined by enzymatic structure mapping, were more potent activators. Thus, the secondary structure defects in the TAR RNA stem function as antideterminants to PKR binding and activation. Our studies support that dimerization of a 15–30 bp hairpin RNA, which effectively doubles its length, is a key step in driving activation of PKR and provide a model for how RNA folding can be related to human disease. PMID:19445956

  12. A Review of Smartphone Applications for Promoting Physical Activity

    PubMed Central

    Coughlin, Steven S.; Whitehead, Mary; Sheats, Joyce Q.; Mastromonico, Jeff; Smith, Selina

    2016-01-01

    Introduction Rapid developments in technology have encouraged the use of smartphones in health promotion research and practice. Although many applications (apps) relating to physical activity are available from major smartphone platforms, relatively few have been tested in research studies to determine their effectiveness in promoting health. Methods In this article, we summarize data on use of smartphone apps for promoting physical activity based upon bibliographic searches with relevant search terms in PubMed and CINAHL. Results After screening the abstracts or full texts of articles, 15 eligible studies of the acceptability or efficacy of smartphone apps for increasing physical activity were identified. Of the 15 included studies, 6 were qualitative research studies, 8 were randomized control trials, and one was a nonrandomized study with a pre-post design. The results indicate that smartphone apps can be efficacious in promoting physical activity although the magnitude of the intervention effect is modest. Participants of various ages and genders respond favorably to apps that automatically track physical activity (e.g., steps taken), track progress toward physical activity goals, and are user-friendly and flexible enough for use with several types of physical activity. Discussion Future studies should utilize randomized controlled trial research designs, larger sample sizes, and longer study periods to establish the physical activity measurement and intervention capabilities of smartphones. There is a need for culturally appropriate, tailored health messages to increase knowledge and awareness of health behaviors such as physical activity. PMID:27034992

  13. The Role of Physical Activity Assessments for School-Based Physical Activity Promotion

    ERIC Educational Resources Information Center

    Welk, Gregory J.

    2008-01-01

    The emphasis in public health on lifestyle physical activity in recent years has focused attention on the promotion of lifetime physical activity as the primary objective of physical education. If used properly, physical activity and physical fitness assessments can enhance individual promotion of physical activity and also provide valuable…

  14. [Regulation of myostatin promoter activity by myocyte enhancer factor 2].

    PubMed

    Li, Jia; Deng, Jie; Zhang, Junlin; Cheng, De; Wang, Huayan

    2012-08-01

    Myostatin (Mstn) is a member of the transforming growth factor-beta superfamily that functions as a negative regulator of skeletal muscle growth and differentiation in mammals. The transcriptional regulation of Mstn is controlled by multiple genes including MEF2, which raise the importance of identifying the binding sites of MEF2 on myostatin promoter region and mechanisms underlying. In this study, we investigated the transcriptional regulation of MEF2 on porcine Mstn promoter activity in C2C12 cells. Sequence analysis of the 1 969 bp porcine Mstn promoter region revealed that it contained three potential MEF2 motifs. Using a serial deletion strategy, we tested the activity of several promoter fragments by luciferase assay. Overexpression of MEF2C, but not MEF2A increased Mstn promoter activity in all the promoter fragments with MEF2 motifs by two to six folds, in both C2C12 myoblasts and myotubes. When we transfected exogenous MEF2C, Mstn mRNA level was also upregulated in C2C12 cells, but the protein level was only significantly increased in myotubes. Thus, we propose that MEF2C could modulate and restrain myogenesis by Mstn activation and Mstn-dependent gene processing in porcine. Our research also provided potential targets and an effective molecule to regulate Mstn expression and gave a new way to explore the functional performance of Mstn.

  15. Health promotion in active-duty military women with children.

    PubMed

    Agazio, Janice G; Ephraim, Paula M; Flaherty, Norma B; Gurney, Cynthia A

    2002-01-01

    The purpose of this study was to determine the extent to which selected demographic characteristics, definition of health, perceived health status, perceived self-efficacy, and resources are related to the health promoting behaviors of active-duty women with children and to describe qualitatively the experience of being an active-duty mother. Grounded in Pender's (1996) Health Promotion Model, this study used methodological triangulation to test a hypothesized model. A sample of 141 active-duty women with children using military health services participated. Resource availability and commitment were key components of being successful at balancing home and work demands.

  16. trans-Activation of a globin promoter in nonerythroid cells.

    PubMed Central

    Evans, T; Felsenfeld, G

    1991-01-01

    We show that expression in fibroblasts of a single cDNA, encoding the erythroid DNA-binding protein Eryf1 (GF-1, NF-E1), very efficiently activates transcription of a chicken alpha-globin promoter, trans-Activation in these cells occurred when Eryf1 bound to a single site within a minimal globin promoter. In contrast, efficient activation in erythroid cells required multiple Eryf1 binding sites. Our results indicate that mechanisms exist that are capable of modulating the trans-acting capabilities of Eryf1 in a cell-specific manner, without affecting DNA binding. The response of the minimal globin promoter to Eryf1 in fibroblasts was at least as great as for optimal constructions in erythroid cells. Therefore, the assay provides a very simple and sensitive system with which to study gene activation by a tissue-specific factor. Images PMID:1990287

  17. Recreation and Health Agencies: Working Together to Promote Physical Activity.

    ERIC Educational Resources Information Center

    Phillipp, JoAnn; Dusenbury, Linda J.

    1994-01-01

    The Colorado Department of Health formed the Cardiovascular Disease (CVD) Prevention Coalition to address Colorado's problem with CVD. The article describes the work of the Coalition's Physical Activity Subcommittee, the Subcommittee's Exer-Deck tool to promote increased physical activity, and the training of professionals to work collaboratively…

  18. Promoting active living in healthy cities of Europe.

    PubMed

    Faskunger, Johan

    2013-10-01

    Local governments in Europe have a vital role in promoting physical activity in the daily life of citizens. However, explicit investment in active living has been limited. One of the four core themes for Phase IV (2003-2008) of the World Health Organization (WHO) European Healthy Cities Network (WHO-EHCN) was to encourage local governments and their partners to implement programs in favor of active living. This study analyzes the performance of network cities during this period. Responses to a general evaluation questionnaire are analyzed by content according to a checklist, and categorized into themes and dimensions. Most cities viewed "active living" as an important issue for urban planning; to improve visual appeal, enhance social cohesion, create a more sustainable transport system to promote walkability and cyclability and to reduce inequalities in public health. Almost all member cities reported on existing policies that support the promotion of active living. However, only eight (of the 59) responding cities mentioned an integrated framework specific for active living. Many efforts to promote active living are nested in programs to prevent obesity among adults or children. Future challenges include establishing integrated policies specifically for active living, introducing a larger range of actions, as well as increasing funding and capacity to make a difference at the population level.

  19. Comprehensive School-Based Physical Activity Promotion: A Review

    ERIC Educational Resources Information Center

    Erwin, Heather; Beighle, Aaron; Carson, Russell L.; Castelli, Darla M.

    2013-01-01

    Physical activity (PA) participation levels among youth remain well below national recommendations. Thus, a variety of strategies to promote youth PA have been advocated, including multifaceted, school-based approaches. One identified as having great potential is a comprehensive school physical activity program (CSPAP). The goal of a CSPAP is to…

  20. Worksite Health Promotion Activities. 1992 National Survey. Summary Report.

    ERIC Educational Resources Information Center

    Public Health Service (DHHS), Rockville, MD. Office of Disease Prevention and Health Promotion.

    The survey reported in this document examined worksite health promotion and disease prevention activities in 1,507 private worksites in the United States. Specificlly, the survey assessed policies, practices, services, facilities, information, and activities sponsored by employers to improve the health of their employees, and assessed health…

  1. Hair Growth Promotion Activity and Its Mechanism of Polygonum multiflorum

    PubMed Central

    Li, Yunfei; Han, Mingnuan; Lin, Pei; He, Yanran; Yu, Jie; Zhao, Ronghua

    2015-01-01

    Polygonum multiflorum Radix (PMR) has long history in hair growth promotion and hair coloring in clinical applications. However, several crucial problems in its clinic usage and mechanisms are still unsolved or lack scientific evidences. In this research, C57BL/6J mice were used to investigate hair growth promotion activity and possible mechanism of PMR and Polygonum multiflorum Radix Preparata (PMRP). Hair growth promotion activities were investigated by hair length, hair covered skin ratio, the number of follicles, and hair color. Regulation effects of several cytokines involved in the hair growth procedure were tested, such as fibroblast growth factor (FGF-7), Sonic Hedgehog (SHH), β-catenin, insulin-like growth factor-1 (IGF-1), and hepatocyte growth factor (HGF). Oral PMR groups had higher hair covered skin ratio (100 ± 0.00%) than oral PMRP groups (48%~88%). However, topical usage of PMRP had about 90% hair covered skin ratio. Both oral administration of PMR and topically given PMRP showed hair growth promotion activities. PMR was considered to be more suitable for oral administration, while PMRP showed greater effects in external use. The hair growth promotion effect of oral PMR was most probably mediated by the expression of FGF-7, while topical PMRP promoted hair growth by the stimulation of SHH expression. PMID:26294926

  2. Commercial activities and the promotion of health in schools.

    PubMed

    Raine, Gary

    2013-11-01

    Many companies nowadays consider schools to be an important setting for marketing to children. However, important concerns can be raised from a health promotion perspective about the potential negative impact of commercial activities on the health and well-being of pupils. As this discussion paper will demonstrate, some commercial activities raise concerns in relation to physical health and obesity, not only by potentially undermining formal curriculum messages, but also through the active promotion of specific products, particularly those high in fat, sugar or salt. Nonetheless, the issues raised by commercial activities are not solely limited to effects on physical health. By allowing commercial activities, schools risk instilling in pupils consumer-orientated values. This is significant as such values have been linked to the development of poor health and well-being. Furthermore, the presence in schools of commercial activities will also militate against informed decision-making and be disempowering. There is also evidence that business-sponsored teaching materials can contain biased and misleading information. The potential negative impacts of commercial activities are inconsistent with goals in relation to the promotion of health and the principles of health-promoting schools.

  3. [Health promotion through physical activity: territorial models and experiences].

    PubMed

    Romano-Spica, V; Parlato, A; Palumbo, D; Lorenzo, E; Frangella, C; Montuori, E; Anastasi, D; Visciano, A; Liguori, G

    2008-01-01

    Scientific evidences support the preventive role of physical activity in relation to different multifactorial pathologies. Health's promotion through the spreading of lifestyles that encourage movement, does not represent just an action in contrast with "sedentary life" risk-factor, but also a priority for "quality" of life, with relevant economical and social benefits. WHO indicates physical activity as one of the priorities for an effective prevention. Besides, the EU supports the realization and the diffusion of some prevention-programs. Main pilot experiences developed in Italy and other countries are summarized. Attention is focused on the role of the competences and structures involved in an integrated approach based on availability of medical support, social services and local structures, considering recent developments in health prevention and promotion. In Italy and Europe, new opportunities to implement health promotion through physical activity are offered by the development of higher education in movement and sport sciences.

  4. Promoters active in interphase are bookmarked during mitosis by ubiquitination.

    PubMed

    Arora, Mansi; Zhang, Jie; Heine, George F; Ozer, Gulcin; Liu, Hui-wen; Huang, Kun; Parvin, Jeffrey D

    2012-11-01

    We analyzed modification of chromatin by ubiquitination in human cells and whether this mark changes through the cell cycle. HeLa cells were synchronized at different stages and regions of the genome with ubiquitinated chromatin were identified by affinity purification coupled with next-generation sequencing. During interphase, ubiquitin marked the chromatin on the transcribed regions of ∼70% of highly active genes and deposition of this mark was sensitive to transcriptional inhibition. Promoters of nearly half of the active genes were highly ubiquitinated specifically during mitosis. The ubiquitination at the coding regions in interphase but not at promoters during mitosis was enriched for ubH2B and dependent on the presence of RNF20. Ubiquitin labeling of both promoters during mitosis and transcribed regions during interphase, correlated with active histone marks H3K4me3 and H3K36me3 but not a repressive histone modification, H3K27me3. The high level of ubiquitination at the promoter chromatin during mitosis was transient and was removed within 2 h after the cells exited mitosis and entered the next cell cycle. These results reveal that the ubiquitination of promoter chromatin during mitosis is a bookmark identifying active genes during chromosomal condensation in mitosis, and we suggest that this process facilitates transcriptional reactivation post-mitosis.

  5. Using Virtual Pets to Promote Physical Activity in Children: An Application of the Youth Physical Activity Promotion Model.

    PubMed

    Ahn, Sun Joo Grace; Johnsen, Kyle; Robertson, Tom; Moore, James; Brown, Scott; Marable, Amanda; Basu, Aryabrata

    2015-01-01

    A virtual pet was developed based on the framework of the youth physical activity promotion model and tested as a vehicle for promoting physical activity in children. Children in the treatment group interacted with the virtual pet for three days, setting physical activity goals and teaching tricks to the virtual pet when their goals were met. The virtual pet became more fit and learned more sophisticated tricks as the children achieved activity goals. Children in the control group interacted with a computer system presenting equivalent features but without the virtual pet. Physical activity and goal attainment were evaluated using activity monitors. Results indicated that children in the treatment group engaged in 1.09 more hours of daily physical activity (156% more) than did those in the control group. Physical activity self-efficacy and beliefs served as mediators driving this increase in activity. Children that interacted with the virtual pet also expressed higher intentions than children in the control group to continue physical activity in the future. Theoretical and practical potentials of using a virtual pet to systematically promote physical activity in children are discussed.

  6. Healthy and wellbeing activities' promotion using a Big Data approach.

    PubMed

    Gachet Páez, Diego; de Buenaga Rodríguez, Manuel; Puertas Sánz, Enrique; Villalba, María Teresa; Muñoz Gil, Rafael

    2016-08-04

    The aging population and economic crisis specially in developed countries have as a consequence the reduction in funds dedicated to health care; it is then desirable to optimize the costs of public and private healthcare systems, reducing the affluence of chronic and dependent people to care centers; promoting healthy lifestyle and activities can allow people to avoid chronic diseases as for example hypertension. In this article, we describe a system for promoting an active and healthy lifestyle for people and to recommend with guidelines and valuable information about their habits. The proposed system is being developed around the Big Data paradigm using bio-signal sensors and machine-learning algorithms for recommendations.

  7. Characterization of a highly active promoter, PBbgpd, in Beauveria bassiana.

    PubMed

    Liao, Xing-gang; Fang, Wei-guo; Zhang, Yong-jun; Fan, Yan-hua; Wu, Xing-wei; Zhou, Qun; Pei, Yan

    2008-08-01

    The promoter of glyceraldehyde-3-phosphate dehydrogenase (gpd) gene from Aspergillus nidulans (PgpdA) is widely used to direct expression of target genes constitutively in fungi. However, in some species, a heterogeneous promoter is found to be of low efficiency. To obtain a high-efficiency promoter for transformation of Beauveria bassiana, an entomopathogenic fungus widely used as an mycoinsecticide, a glyceraldehyde-3-phosphate dehydrogenase gene (Bbgpd) promoter, was cloned and characterized. Four deletion constructs (-2118, -1153, -726, and -354) of the 5'-upstream sequence of Bbgpd linked to a bar::gus fusion gene (phosphinothricin-resistance::beta-glucuronidase fused gene), which were used as selected marker gene and report gene, respectively, were generated. GUS activities of transgenic strains harboring -726, -1153, and -2118 deletion constructs were much stronger than that of the promoter of Aspergillus nidulans gpdA (PgpdA), with a twofold to threefold increase over that in the PgpdA construct. The -726 fragment was necessary to direct GUS expression in B. bassiana. No -354 transgenic progenies were obtained, possibly because it failed to initiate the transcription of bar::gus fusion gene. A remarkable increase of GUS activity was found between the -1153 and -726 constructs, indicating that some active transcriptional elements were located in this region. With a high expression level and relatively short sequence, PBbgpd can be used to drive target genes in B. bassiana transgenic research.

  8. Construction and Evaluation of a Maize Chimeric Promoter with Activity in Kernel Endosperm and Embryo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chimeric promoters contain DNA sequences from different promoters. Chimeric promoters are developed to increase the level of recombinant protein expression, precisely control transgene activity, or to escape homology-based gene silencing. Sets of chimeric promoters, each containing different lengt...

  9. RSPOs facilitated HSC activation and promoted hepatic fibrogenesis

    PubMed Central

    Yin, Xinguang; Yi, Huixing; Wang, Linlin; Wu, Wanxin; Wu, Xiaojun; Yu, Linghua

    2016-01-01

    Roof plate-specific spondin (RSPO) proteins are potent Wnt pathway agonists and involve in a broad range of developmental and physiological processes. This study investigated the activities and mechanisms of RSPOs in liver fibrogenesis, especially in hepatic stellate cell (HSC) activation. HSC activation was assessed by fibrosis biomarker (α-smooth muscle actin and Collagen-I), phenotypic change (accumulation of lipid droplets), and increased proliferation. Similarly, Wnt pathway activity was evaluated by the expression of nuclear β-catenin and T cell-specific transcription factors (TCF) activity. We found RSPOs were overexpressed in human fibrotic liver tissue and the expressions were correlated with liver fibrosis stages. In vitro studies showed RSPOs level increased during HSC activation, and stimuli with RSPOs enhanced Wnt pathway activity and promoted HSC activation subsequently. Furthermore, in vivo experiments demonstrated that the knockdown of RSPOs suppressed both Wnt pathway activity and HSC activation. Interestingly, the inhibitor of the Wnt signaling pathway Dickkopf1 impairs RSPOs effects on HSCs. Taken together, our results revealed that RSPOs facilitated HSC activation and promote liver fibrogenesis by enhancing the Wnt pathway. PMID:27572318

  10. Regularities in the E. coli promoters composition in connection with the DNA strands interaction and promoter activity

    PubMed Central

    Berezhnoy, Andrey Yu; Shckorbatov, Yuriy G.; Hisanori, Kiryu

    2006-01-01

    The energy of interaction between DNA strands in promoters is of great functional importance. Visualization of the energy of DNA strands distribution in promoter sequences was achieved. The separation of promoters in groups by their energetic properties enables evaluation of the dependence of promoter strength on the energetic properties. The analysis of groups (clusters) of promoters distributed by the energy of DNA strands interaction in −55, −35, −10 and +6 sequences indicates their connection with the transcriptional activity. PMID:17111465

  11. A systematic review of physical activity promotion strategies.

    PubMed Central

    Hillsdon, M; Thorogood, M

    1996-01-01

    We have reviewed randomised controlled trials of physical activity promotion to provide recent and reliable information on the effectiveness of physical activity promotion. Computerised databases and references of references were searched. Experts were contacted and asked for information about existing work. Studies assessed were randomised controlled trials of healthy, free living, adult subjects, where exercise behaviour was the dependent variable. Eleven trials were identified. No United Kingdom based studies were found. Interventions that encourage walking and do not require attendance at a facility are most likely to lead to sustainable increases in overall physical activity. Brisk walking has the greatest potential for increasing overall activity levels of a sedentary population and meeting current public health recommendations. The small number of trials limits the strength of any conclusions and highlights the need for more research. PMID:8799589

  12. Health Promotion Guidance Activity of Youth Sports Clubs

    ERIC Educational Resources Information Center

    Kokko, Sami; Kannas, Lasse; Villberg, Jari; Ormshaw, Michael

    2011-01-01

    Purpose: This paper aims to clarify the extent to which youth sports clubs guide their coaches to recognise health promotion as a part of the coaching practice. The guidance activity of clubs is seen parallel to internal organisational communication. Design/methodology/approach: A survey of 93 (from 120, 78 per cent) youth sports clubs in Finland…

  13. Help Yourself! Activities To Promote Safety and Self-Esteem.

    ERIC Educational Resources Information Center

    Ross, Kate

    First in a series of books designed to accompany the compact disk "Help Yourself," this book provides suggestions for classroom activities using the CD songs as a springboard into a curriculum for promoting self-esteem and safety skills among preschool children. Each section begins with sheet music and complete lyrics for each of the 12 songs,…

  14. Promoter-specific co-activation by Drosophila Mastermind

    PubMed Central

    Caudy, Michael A.

    2008-01-01

    Mastermind (Mam) is a co-activator protein of binary complexes consisting of Suppressor of Hairless (Su(H)) and Notch Intracellular Domain (NICD) proteins assembled on cis-regulatory regions of target genes activated by Notch signaling. Current evidence indicates that Mastermind is necessary and sufficient for the formation of a functional Su(H)/NICD/Mam ternary complex on at least one specific architecture of Su(H) binding sites, called the SPS element (Su(H) Paired Sites). However, using transcription assays with a combination of native and synthetic Notch target gene promoters in Drosophila cultured cells, we show here that co-activation of Su(H)/NICD complexes on SPS elements by Mam is promoter-specific. Our novel results suggest this promoter specificity is mediated by additional unknown cis-regulatory elements present in the native promoters that are required for the recruitment of Mam and formation of functional Su(H)/NICD/Mam complexes on SPS elements. Together, the findings in this study suggest Mam is not always necessary and sufficient for co-activation of binary Su(H)/NICD complexes on SPS elements. PMID:18930034

  15. The Protest as a Teaching Technique for Promoting Feminist Activism.

    ERIC Educational Resources Information Center

    Rose, Suzanna

    An assignment about protesting was given to students in an upper-level undergraduate women's studies course to provide them with experience and skills in political protesting and to promote feminist activism. The students selected for their assignments: (1) a letter writing campaign against Robert Bork's Supreme Court nomination; (2) a picket…

  16. The Role of Values in Promoting Physical Activity

    ERIC Educational Resources Information Center

    Kosma, Maria; Buchanan, David R.; Hondzinski, Jan

    2015-01-01

    Despite the proliferation of theory-based behavior-change programs to promote physical activity, obesity and diabetes rates continue to rise. Given the notable ineffective interventions, it is important to examine why these efforts have been largely unsuccessful and to consider potential alternatives. The purpose of this article is to consider the…

  17. Images and Influences in the Promotion of Physical Activity

    ERIC Educational Resources Information Center

    Overdorf, Virginia

    2005-01-01

    This article presents the author's presentation on the 13th Delphine Hanna Commemorative Lecture in 2004. The presentation examines some of the problems and issues that must be addressed in order to promote physical activity in the academy and beyond. While there is no all embracing prescription, the author hopes to offer some suggestions that…

  18. Healthy and Active Ageing: Social Capital in Health Promotion

    ERIC Educational Resources Information Center

    Koutsogeorgou, Eleni; Davies, John Kenneth; Aranda, Kay; Zissi, Anastasia; Chatzikou, Maria; Cerniauskaite, Milda; Quintas, Rui; Raggi, Alberto; Leonardi, Matilde

    2014-01-01

    Objectives: This paper examines the context of health promotion actions that are focused on/contributing to strengthening social capital by increasing community participation, reciprocal trust and support as the means to achieve better health and more active ageing. Method: The methodology employed was a literature review/research synthesis, and a…

  19. Predicting Physical Activity Promotion in Health Care Settings.

    ERIC Educational Resources Information Center

    Faulkner, Guy; Biddle, Stuart

    2001-01-01

    Tested the theory of planned behavior's (TPB) ability to predict stage of change for physical activity promotion among health professionals. Researchers measured attitudes, subjective norms, intentions, perceived behavioral control, and stage of change, then later reassessed stage of change. TPB variables of attitude, subjective norms, perceived…

  20. SPECIAL MOTIVATIONAL ACTIVITIES FOR PROMOTING CERTAIN PROBLEM AREAS IN READING.

    ERIC Educational Resources Information Center

    DAWSON, MARVIN; SPENCER, GARY D.

    A CURRICULUM GUIDE PRODUCED AT AN INSERVICE TRAINING COURSE ON "PROBLEMS IN TEACHING READING" BY TEACHERS FROM CARROLL COUNTY SCHOOLS, GEORGIA, IN THE SPRING OF 1966 IS PRESENTED. IT OFFERS GENERAL MOTIVATIONAL READING ACTIVITIES WHICH PROMOTE GROWTH IN CERTAIN PROBLEM AREAS IN READING. RECOGNIZING THAT THERE CAN BE NO EFFECTIVE LEARNING…

  1. Active Chemical Thermodynamics promoted by activity of cortical actin

    NASA Astrophysics Data System (ADS)

    Bhattacharya, Bhaswati; Chaudhuri, Abhishek; Gowrishankar, Kripa; Rao, Madan

    2011-03-01

    The spatial distribution and dynamics of formation and breakup of the nanoclusters of cell surface proteins is controlled by the active remodeling dynamics of the underlying cortical actin. To explain these observations, we have proposed a novel mechanism of nanoclustering, involving the transient binding to and advection along constitutively occuring ``asters'' of cortical actin. We study the consequences of such active actin-based clustering, in the context of chemical reactions involving conformational changes of cell surface proteins. We find that the active remodeling of cortical actin, can give rise to a dramatic increase in efficiency and extent of conformational spread, even at low levels of expression at the cell surface. We define a activity temperature (τa) arising due to actin activities which can be used to describe chemical thermodynamics of the system. We plot TTT (time-temparature-transformation) curves and compute the Arrhenius factors which depend on τa . With this, the active asters can be treated as enzymes whose enzymatic reaction rate can be related to the activity.

  2. Technology to promote and increase physical activity in heart failure.

    PubMed

    Franklin, Nina C

    2015-01-01

    Regular physical activity is firmly recommended as part of a multifaceted approach to heart failure (HF) self-management. Unfortunately, research indicates that most patients are less likely to engage in and adhere to such activities. The widespread use of information and communication technology tools and resources offers an innovative and potentially beneficial avenue for increasing physical activity levels in HF patients. This article presents specific ways in which advances in information and communication technologies, including Internet- and mobile-based communications, social media platforms, and self-monitoring health devices, can serve as a means to broadly promote increasing levels of physical activity to improve health outcomes in the HF population.

  3. Health-promoting physical activity of adults with mental retardation.

    PubMed

    Stanish, Heidi I; Temple, Viviene A; Frey, Georgia C

    2006-01-01

    This literature review describes the physical activity behavior of adults with mental retardation consistent with the U.S. Surgeon General's recommendation of 30 minutes of moderate intensity physical activity on 5 or more days per week. The proportion of participants achieving this criterion ranges from 17.5 to 33%. These data are likely to be generous estimates of activity as individuals included in physical activity studies to date have been relatively young and healthy volunteers with mild to moderate limitations. Major sources of physical activity were walking and cycling for transport, chores and work, dancing, and Special Olympics. There is a pressing need to conduct studies using appropriately powered representative samples and to validate measures that assess physical activity less directly; including methodologies in which proxy respondents are used. Accurate information about existing patterns of behavior will enhance the development of effective strategies to promote physical activity among persons with mental retardation.

  4. Phenylethylchromones with In Vitro Antitumor Promoting Activity from Aquilaria filaria.

    PubMed

    Suzuki, Airi; Miyake, Katsunori; Saito, Yohei; Rasyid, Faradiba Abdul; Tokuda, Harukuni; Takeuchi, Misa; Suzuki, Nobutaka; Ichiishi, Eiichiro; Fujie, Tetsuo; Goto, Masuo; Sasaki, Yohei; Nakagawa-Goto, Kyoko

    2017-02-01

    A new chromone, 2-(2-hydroxy-2-phenylethyl)chromone (1), was isolated together with ten known phenylethyl chromones from MeOH extracts of agarwood (Aquilaria filaria). The selected compounds were evaluated in an antiproliferative assay against five human tumor cell lines, including a multidrug-resistant cell line. They were also tested for antitumor promoting activity, as mediated by 12-O-tetradecanoylphorbol-13-acetate-induced activation of the Epstein-Barr virus early antigen in Raji cells. Among all compounds, 4',7-dimethyoxy-6-hydroxychromone (2) displayed broad spectrum antiproliferative activity against all tumor cell lines tested with IC50 values of 25-38 µM, while 8 was selectively inhibitory against multidrug-resistant cells. All tested compounds suppressed tumor promotion at noncytotoxic concentrations. 4',6-Dihydroxyphenylethylchromone (7) exhibited the most potent effect with an IC50 value of 319 mol ratio relative to 12-O-tetradecanoylphorbol-13-acetate. This study is the first to report the antitumor promoting activity of 2-(2-phenylethyl)chromone derivatives, as well as the selective antiproliferative activity of 8 against a multidrug-resistant tumor cell line.

  5. Applying Transtheoretical Model to Promote Physical Activities Among Women

    PubMed Central

    Pirzadeh, Asiyeh; Mostafavi, Firoozeh; Ghofranipour, Fazllolah; Feizi, Awat

    2015-01-01

    Background: Physical activity is one of the most important indicators of health in communities but different studies conducted in the provinces of Iran showed that inactivity is prevalent, especially among women. Objectives: Inadequate regular physical activities among women, the importance of education in promoting the physical activities, and lack of studies on the women using transtheoretical model, persuaded us to conduct this study with the aim of determining the application of transtheoretical model in promoting the physical activities among women of Isfahan. Materials and Methods: This research was a quasi-experimental study which was conducted on 141 women residing in Isfahan, Iran. They were randomly divided into case and control groups. In addition to the demographic information, their physical activities and the constructs of the transtheoretical model (stages of change, processes of change, decisional balance, and self-efficacy) were measured at 3 time points; preintervention, 3 months, and 6 months after intervention. Finally, the obtained data were analyzed through t test and repeated measures ANOVA test using SPSS version 16. Results: The results showed that education based on the transtheoretical model significantly increased physical activities in 2 aspects of intensive physical activities and walking, in the case group over the time. Also, a high percentage of people have shown progress during the stages of change, the mean of the constructs of processes of change, as well as pros and cons. On the whole, a significant difference was observed over the time in the case group (P < 0.01). Conclusions: This study showed that interventions based on the transtheoretical model can promote the physical activity behavior among women. PMID:26834796

  6. School health guidelines to promote healthy eating and physical activity.

    PubMed

    2011-09-16

    During the last 3 decades, the prevalence of obesity has tripled among persons aged 6--19 years. Multiple chronic disease risk factors, such as high blood pressure, high cholesterol levels, and high blood glucose levels are related to obesity. Schools have a responsibility to help prevent obesity and promote physical activity and healthy eating through policies, practices, and supportive environments. This report describes school health guidelines for promoting healthy eating and physical activity, including coordination of school policies and practices; supportive environments; school nutrition services; physical education and physical activity programs; health education; health, mental health, and social services; family and community involvement; school employee wellness; and professional development for school staff members. These guidelines, developed in collaboration with specialists from universities and from national, federal, state, local, and voluntary agencies and organizations, are based on an in-depth review of research, theory, and best practices in healthy eating and physical activity promotion in school health, public health, and education. Because every guideline might not be appropriate or feasible for every school to implement, individual schools should determine which guidelines have the highest priority based on the needs of the school and available resources.

  7. Neuronal activity promotes myelination via a cAMP pathway.

    PubMed

    Malone, Misti; Gary, Devin; Yang, In Hong; Miglioretti, Anna; Houdayer, Thierry; Thakor, Nitish; McDonald, John

    2013-06-01

    Neuronal activity promotes myelination in vivo and in vitro. However, the molecular events that mediate activity-dependent myelination are not completely understood. Seven, daily 1 h sessions of patterned electrical stimulation (ESTIM) promoted myelin segment formation in mixed cultures of dorsal root ganglion (DRG) neurons and oligodendrocytes (OLs); the increase in myelination was frequency-dependent. Myelin segment formation was also enhanced following exposure of DRGs to ESTIM prior to OL addition, suggesting that ESTIM promotes myelination in a manner involving neuron-specific signaling. Cyclic adenosine monophosphate (cAMP) levels in DRGs were increased three-fold following ESTIM, and artificially increasing cAMP mimicked the ability of ESTIM to promote myelination. Alternatively, inhibiting the cAMP pathway suppressed ESTIM-induced myelination. We used compartmentalized, microfluidic platforms to isolate DRG soma from OLs and assessed cell-type specific effects of ESTIM on myelination. A selective increase or decrease in DRG cAMP levels resulted in enhanced or suppressed myelination, respectively. This work describes a novel role for the cAMP pathway in neurons that results in enhanced myelination.

  8. TERT promoter mutations and monoallelic activation of TERT in cancer

    PubMed Central

    Huang, F W; Bielski, C M; Rinne, M L; Hahn, W C; Sellers, W R; Stegmeier, F; Garraway, L A; Kryukov, G V

    2015-01-01

    Here we report that promoter mutations in telomerase (TERT), the most common noncoding mutations in cancer, give rise to monoallelic expression of TERT. Through deep RNA sequencing, we find that TERT activation in human cancer cell lines can occur in either mono- or biallelic manner. Without exception, hotspot TERT promoter mutations lead to the re-expression of only one allele, accounting for approximately half of the observed cases of monoallelic TERT expression. Furthermore, we show that monoallelic TERT expression is highly prevalent in certain tumor types and widespread across a broad spectrum of cancers. Taken together, these observations provide insights into the mechanisms of TERT activation and the ramifications of noncoding mutations in cancer. PMID:26657580

  9. Libraries of Synthetic TALE-Activated Promoters: Methods and Applications.

    PubMed

    Schreiber, T; Tissier, A

    2016-01-01

    The discovery of proteins with programmable DNA-binding specificities triggered a whole array of applications in synthetic biology, including genome editing, regulation of transcription, and epigenetic modifications. Among those, transcription activator-like effectors (TALEs) due to their natural function as transcription regulators, are especially well-suited for the development of orthogonal systems for the control of gene expression. We describe here the construction and testing of libraries of synthetic TALE-activated promoters which are under the control of a single TALE with a given DNA-binding specificity. These libraries consist of a fixed DNA-binding element for the TALE, a TATA box, and variable sequences of 19 bases upstream and 43 bases downstream of the DNA-binding element. These libraries were cloned using a Golden Gate cloning strategy making them usable as standard parts in a modular cloning system. The broad range of promoter activities detected and the versatility of these promoter libraries make them valuable tools for applications in the fine-tuning of expression in metabolic engineering projects or in the design and implementation of regulatory circuits.

  10. Mannoproteins from Cryptococcus neoformans promote dendritic cell maturation and activation.

    PubMed

    Pietrella, Donatella; Corbucci, Cristina; Perito, Stefano; Bistoni, Giovanni; Vecchiarelli, Anna

    2005-02-01

    Our previous data show that mannoproteins (MPs) from Cryptococcus neoformans are able to induce protective responses against both C. neoformans and Candida albicans. Here we provide evidence that MPs foster maturation and activation of human dendritic cells (DCs). Maturation was evaluated by the ability of MPs to facilitate expression of costimulatory molecules such as CD40, CD86, CD83, and major histocompatibility complex classes I and II and to inhibit receptors such as CD14, CD16, and CD32. Activation of DCs was measured by the capacity of MPs to promote interleukin-12 and tumor necrosis factor alpha secretion. DC-induced maturation and interleukin-12 induction are largely mediated by engagement of mannose receptors and presume MP internalization and degradation. DC activation leads to IkappaBalpha phosphorylation, which is necessary for nuclear factor kappaB transmigration into the nucleus. MP-loaded DCs are efficient stimulators of T cells and show a remarkable capacity to promote CD4 and CD8 proliferation. In conclusion, we have evidenced a novel regulatory role of MPs that promotes their candidacy as a vaccine against fungi.

  11. Mannoproteins from Cryptococcus neoformans Promote Dendritic Cell Maturation and Activation

    PubMed Central

    Pietrella, Donatella; Corbucci, Cristina; Perito, Stefano; Bistoni, Giovanni; Vecchiarelli, Anna

    2005-01-01

    Our previous data show that mannoproteins (MPs) from Cryptococcus neoformans are able to induce protective responses against both C. neoformans and Candida albicans. Here we provide evidence that MPs foster maturation and activation of human dendritic cells (DCs). Maturation was evaluated by the ability of MPs to facilitate expression of costimulatory molecules such as CD40, CD86, CD83, and major histocompatibility complex classes I and II and to inhibit receptors such as CD14, CD16, and CD32. Activation of DCs was measured by the capacity of MPs to promote interleukin-12 and tumor necrosis factor alpha secretion. DC-induced maturation and interleukin-12 induction are largely mediated by engagement of mannose receptors and presume MP internalization and degradation. DC activation leads to IκBα phosphorylation, which is necessary for nuclear factor κB transmigration into the nucleus. MP-loaded DCs are efficient stimulators of T cells and show a remarkable capacity to promote CD4 and CD8 proliferation. In conclusion, we have evidenced a novel regulatory role of MPs that promotes their candidacy as a vaccine against fungi. PMID:15664921

  12. 7 CFR 981.441 - Credit for market promotion activities, including paid advertising.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Credit for market promotion activities, including paid... promotion activities, including paid advertising. (a) In order for a handler to receive credit for his/her...) Other market promotion activities. Credit-Back shall be granted for market promotion other than...

  13. Promoter-proximal polyadenylation sites reduce transcription activity

    PubMed Central

    Andersen, Pia K.; Lykke-Andersen, Søren; Jensen, Torben Heick

    2012-01-01

    Gene expression relies on the functional communication between mRNA processing and transcription. We previously described the negative impact of a point-mutated splice donor (SD) site on transcription. Here we demonstrate that this mutation activates an upstream cryptic polyadenylation (CpA) site, which in turn causes reduced transcription. Functional depletion of U1 snRNP in the context of the wild-type SD triggers the same CpA event accompanied by decreased RNA levels. Thus, in accordance with recent findings, U1 snRNP can shield premature pA sites. The negative impact of unshielded pA sites on transcription requires promoter proximity, as demonstrated using artificial constructs and supported by a genome-wide data set. Importantly, transcription down-regulation can be recapitulated in a gene context devoid of splice sites by placing a functional bona fide pA site/transcription terminator within ∼500 base pairs of the promoter. In contrast, promoter-proximal positioning of a pA site-independent histone gene terminator supports high transcription levels. We propose that optimal communication between a pA site-dependent gene terminator and its promoter critically depends on gene length and that short RNA polymerase II-transcribed genes use specialized termination mechanisms to maintain high transcription levels. PMID:23028143

  14. Quantifying promoter activity during the developmental cycle of Chlamydia trachomatis

    PubMed Central

    Cong, Yanguang; Gao, Leiqiong; Zhang, Yan; Xian, Yuqi; Hua, Ziyu; Elaasar, Hiba; Shen, Li

    2016-01-01

    Chlamydia trachomatis is an important human pathogen that undergoes a characteristic development cycle correlating with stage-specific gene expression profiles. Taking advantage of recent developments in the genetic transformation in C. trachomatis, we constructed a versatile green fluorescent protein (GFP) reporter system to study the development-dependent function of C. trachomatis promoters in an attempt to elucidate the mechanism that controls C. trachomatis adaptability. We validated the use of the GFP reporter system by visualizing the activity of an early euo gene promoter. Additionally, we uncovered a new ompA promoter, which we named P3, utilizing the GFP reporter system combined with 5′ rapid amplification of cDNA ends (RACE), in vitro transcription assays, real-time quantitative RT-PCR (RT-qPCR), and flow cytometry. Mutagenesis of the P3 region verifies that P3 is a new class of C. trachomatis σ66-dependent promoter, which requires an extended −10 TGn motif for transcription. These results corroborate complex developmentally controlled ompA expression in C. trachomatis. The exploitation of genetically labeled C. trachomatis organisms with P3-driven GFP allows for the observation of changes in ompA expression in response to developmental signals. The results of this study could be used to complement previous findings and to advance understanding of C. trachomatis genetic expression. PMID:27263495

  15. Physiologically activated mammary fibroblasts promote postpartum mammary cancer

    PubMed Central

    Guo, Qiuchen; Burchard, Julja; Spellman, Paul

    2017-01-01

    Women diagnosed with breast cancer within 5 years of childbirth have poorer prognosis than nulliparous or pregnant women. Weaning-induced breast involution is implicated, as the collagen-rich, immunosuppressive microenvironment of the involuting mammary gland is tumor promotional in mice. To investigate the role of mammary fibroblasts, isolated mammary PDGFRα+ cells from nulliparous and postweaning mice were assessed for activation phenotype and protumorigenic function. Fibroblast activation during involution was evident by increased expression of fibrillar collagens, lysyl oxidase, Tgfb1, and Cxcl12 genes. The ability of mammary tumors to grow in an isogenic, orthotopic transplant model was increased when tumor cells were coinjected with involution-derived compared with nulliparous-derived mammary fibroblasts. Mammary tumors in the involution-fibroblast group had increased Ly6C+ monocytes at the tumor border, and decreased CD8+ T cell infiltration and tumor cell death. Ibuprofen treatment suppressed involution-fibroblast activation and tumor promotional capacity, concurrent with decreases in tumor Ly6C+ monocytes, and increases in intratumoral CD8+ T cell infiltration, granzyme levels, and tumor cell death. In total, our data identify a COX/prostaglandin E2 (PGE2)–dependent activated mammary fibroblast within the involuting mammary gland that displays protumorigenic, immunosuppressive activity, identifying fibroblasts as potential targets for the prevention and treatment of postpartum breast cancer. PMID:28352652

  16. DUX4 promotes transcription of FRG2 by directly activating its promoter in facioscapulohumeral muscular dystrophy

    PubMed Central

    2014-01-01

    Background The most common form of facioscapulohumeral muscular dystrophy (FSHD) is caused by a genetic contraction of the polymorphic D4Z4 macrosatellite repeat array in the subtelomeric region of chromosome 4q. In some studies, genes centromeric to the D4Z4 repeat array have been reported to be over-expressed in FSHD, including FRG1 and FRG2, presumably due to decreased long-distance repression by the shorter array through a mechanism similar to position-effect variegation. Differential regulation of FRG1 in FSHD has never been unequivocally proven, however, FRG2 has been reproducibly shown to be induced in primary FSHD-derived muscle cells when differentiated in vitro. The molecular function of FRG2 and a possible contribution to FSHD pathology remain unclear. Recent evidence has identified the mis-expression of DUX4, located within the D4Z4 repeat unit, in skeletal muscle as the cause of FSHD. DUX4 is a double homeobox transcription factor that has been shown to be toxic when expressed in muscle cells. Methods We used a combination of expression analysis by qRT/PCR and RNA sequencing to determine the transcriptional activation of FRG2 and DUX4. We examined this in both differentiating control and FSHD derived muscle cell cultures or DUX4 transduced control cell lines. Next, we used ChIP-seq analysis and luciferase reporter assays to determine the potential DUX4 transactivation effect on the FRG2 promoter. Results We show that DUX4 directly activates the expression of FRG2. Increased expression of FRG2 was observed following expression of DUX4 in myoblasts and fibroblasts derived from control individuals. Moreover, we identified DUX4 binding sites at the FRG2 promoter by chromatin immunoprecipitation followed by deep sequencing and confirmed the direct regulation of DUX4 on the FRG2 promoter by luciferase reporter assays. Activation of luciferase was dependent on both DUX4 expression and the presence of the DUX4 DNA binding motifs in the FRG2 promoter

  17. Promoting physical activity among Taiwanese and American adolescents.

    PubMed

    Wu, Tsu-Yin; Pender, Nola; Yang, Ke-Ping

    2002-03-01

    The purpose of this paper is to present a comparative analysis of the determinants of physical activity among adolescents in Taiwan and in the United States. Pender's Health Promotion Model (HPM) served as the theoretical framework for both studies (Pender, 1996). The major determinants of health behavior in the HPM are perceived benefits, perceived barriers, self-efficacy, activity-related affect, interpersonal influences, situational influences, commitment to a plan of action, and immediate competing demands. In Taiwan, 969 middle school students (55% males; 45% females) from Taipei provided data for the study. In the United States, the sample was collected from 286 late elementary and middle school students (48% males; 52% females). Results showed the gender differences in activity levels were apparent in the youths from both countries. In both Taiwanese and American youths, boys were more active than girls. Cross-cultural differences in the importance of barriers to physical activity emerged. Among Taiwanese adolescents, barriers did not emerge as a significant direct predictor of physical activity as they did among US adolescents. Perceived efficacy directly predicted physical activity among Taiwanese youths while it indirectly predicted physical activity and appeared to be mediated by beliefs regarding exercise benefits and barriers among American youths. In addition, the paths of effect for interpersonal influences were different when Taiwanese and US youths were compared. The findings from this paper have important and culturally-relevant information that can inform future physical activity intervention studies with diverse adolescents.

  18. Evaluation of hair growth promoting activity of Phyllanthus niruri

    PubMed Central

    Patel, Satish; Sharma, Vikas; S. Chauhan, Nagendra; Thakur, Mayank; Dixit, Vinod Kumar

    2015-01-01

    Objective: This study was designed to investigate the potential Phyllanthus niruri (P. niruri ) extracts in promotion of hair growth. Materials and Methods: Here, we studied the hair growth promoting activity of petroleum ether extract of P. niruri following its topical administration. Alopecia was induced in albino rats by subcutaneous administration of testosterone for 21 days. Evaluation of hair loss inhibition was done by concurrent administration of extract and monitoring parameters like follicular density, anagen/telogen (A/T) ratio and histological observation of animal skin sections. Finasteride solution was applied topically as standard. In vitro experiments were also performed to study the effect of extract on the activity of 5α-reductase enzyme Results: Groups treated with petroleum ether extract of plant showed hair re-growth as reflected by follicular density, A/T ratio and skin sections. Histopathology and morphologic observations of hair re-growth at shaved sites showed active follicular proliferation. In vitro experiments results showed inhibitory activity of petroleum ether extract on type-2 5α-reductase enzyme and an increase in the amount of testosterone with increasing concentrations. Conclusion: It could be concluded that petroleum ether extracts of P. niruri might be useful in the treatment of testosterone-induced alopecia in the experimental animal by inhibiting 5α-reductase enzyme. PMID:26693408

  19. Nuclear factor Y regulates ancient budgerigar hepadnavirus core promoter activity.

    PubMed

    Shen, Zhongliang; Liu, Yanfeng; Luo, Mengjun; Wang, Wei; Liu, Jing; Liu, Wei; Pan, Shaokun; Xie, Youhua

    2016-09-16

    Endogenous viral elements (EVE) in animal genomes are the fossil records of ancient viruses and provide invaluable information on the origin and evolution of extant viruses. Extant hepadnaviruses include avihepadnaviruses of birds and orthohepadnaviruses of mammals. The core promoter (Cp) of hepadnaviruses is vital for viral gene expression and replication. We previously identified in the budgerigar genome two EVEs that contain the full-length genome of an ancient budgerigar hepadnavirus (eBHBV1 and eBHBV2). Here, we found eBHBV1 Cp and eBHBV2 Cp were active in several human and chicken cell lines. A region from nt -85 to -11 in eBHBV1 Cp was critical for the promoter activity. Bioinformatic analysis revealed a putative binding site of nuclear factor Y (NF-Y), a ubiquitous transcription factor, at nt -64 to -50 in eBHBV1 Cp. The NF-Y core binding site (ATTGG, nt -58 to -54) was essential for eBHBV1 Cp activity. The same results were obtained with eBHBV2 Cp and duck hepatitis B virus Cp. The subunit A of NF-Y (NF-YA) was recruited via the NF-Y core binding site to eBHBV1 Cp and upregulated the promoter activity. Finally, the NF-Y core binding site is conserved in the Cps of all the extant avihepadnaviruses but not of orthohepadnaviruses. Interestingly, a putative and functionally important NF-Y core binding site is located at nt -21 to -17 in the Cp of human hepatitis B virus. In conclusion, our findings have pinpointed an evolutionary conserved and functionally critical NF-Y binding element in the Cps of avihepadnaviruses.

  20. Electrical Stimulation Promotes Wound Healing by Enhancing Dermal Fibroblast Activity and Promoting Myofibroblast Transdifferentiation

    PubMed Central

    Rouabhia, Mahmoud; Park, Hyunjin; Meng, Shiyun; Derbali, Habib; Zhang, Ze

    2013-01-01

    Electrical stimulation (ES) has long been used as an alternative clinical treatment and an effective approach to modulate cellular behaviours. In this work we investigated the effects of ES on human skin fibroblast activity, myofibroblast transdifferentiation and the consequence on wound healing. Normal human fibroblasts were seeded on heparin-bioactivated PPy/PLLA conductive membranes, cultured for 24 h, and then exposed to ES of 50 or 200 mV/mm for 2, 4, or 6 h. Following ES, the cells were either subjected to various analyses or re-seeded to investigate their healing capacity. Our findings show that ES had no cytotoxic effect on the fibroblasts, as demonstrated by the similar LDH activity levels in the ES-exposed and non-exposed cultures, and by the comparable cell viability under both conditions. Furthermore, the number of viable fibroblasts was higher following exposure to 6 h of ES than in the non-exposed culture. This enhanced cell growth was likely due to the ES up-regulated secretion of FGF-1 and FGF-2. In an in vitro scratch-wound assay where cell monolayer was used as a healing model, the electrically stimulated dermal fibroblasts migrated faster following exposure to ES and recorded a high contractile behaviour toward the collagen gel matrix. This enhanced contraction was supported by the high level of α-smooth muscle actin expressed by the fibroblasts following exposure to ES, indicating the characteristics of myofibroblasts. Remarkably, the modulation of fibroblast growth continued long after ES. In conclusion, this work demonstrates for the first time that exposure to ES promoted skin fibroblast growth and migration, increased growth factor secretion, and promoted fibroblast to myofibroblast transdifferentiation, thus promoting wound healing. PMID:23990967

  1. Promotion

    PubMed Central

    Alam, Hasan B.

    2013-01-01

    This article gives an overview of the promotion process in an academic medical center. A description of different promotional tracks, tenure and endowed chairs, and the process of submitting an application is provided. Finally, some practical advice about developing skills and attributes that can help with academic growth and promotion is dispensed. PMID:24436683

  2. Cytotoxicity and structure activity relationship studies of maplexins A-I, gallotannins from red maple (Acer rubrum).

    PubMed

    González-Sarrías, Antonio; Yuan, Tao; Seeram, Navindra P

    2012-05-01

    Maplexins A-I are a series of structurally related gallotannins recently isolated from the red maple (Acer rubrum) species. They differ in number and location of galloyl derivatives attached to 1,5-anhydro-glucitol. Here, maplexins A-I were evaluated for anticancer effects against human tumorigenic (colon, HCT-116; breast, MCF-7) and non-tumorigenic (colon, CCD-18Co) cell lines. The maplexins which contained two (maplexins C-D) or three (maplexins E-I) galloyl derivatives each, inhibited cancer cell growth while those with only one galloyl group (maplexins A-B) did not. Moreover, maplexins C-D showed greater antiproliferative effects than maplexins E-I (IC(50)=59.8-67.9 and 95.5-108.5 μM vs. 73.7-165.2 and 115.5-182.5 μM against HCT-116 and MCF-7 cells, respectively). Notably, the cancer cells were up to 2.5-fold more sensitive to the maplexins than the normal cells. In further mechanistic studies, maplexins C-D (at 75 μM concentrations) induced apoptosis and arrested cell cycle (in the S-phase) of the cancer cells. These results suggest that the number of galloyl groups attached to the 1,5-anhydro-glucitol moiety in these gallotannins are important for antiproliferative activity. Also, this is the first in vitro anticancer study of maplexins.

  3. Mycobacterium tuberculosis 19-kDa lipoprotein promotes neutrophil activation.

    PubMed

    Neufert, C; Pai, R K; Noss, E H; Berger, M; Boom, W H; Harding, C V

    2001-08-01

    Certain microbial substances, e.g., LPS, can activate neutrophils or prime them to enhance their response to other activating agents, e.g., fMLP. We investigated the role of the Mycobacterium tuberculosis (MTB) 19-kDa lipoprotein in activation of human neutrophils. MTB 19-kDa lipoprotein initiated phenotypic changes characteristic of neutrophil activation, including down-regulation of CD62 ligand (L-selectin) and up-regulation of CD35 (CR1) and CD11b/CD18 (CR3, Mac-1). In addition, exposure of neutrophils to MTB 19-kDa lipoprotein enhanced the subsequent oxidative burst in response to fMLP as assessed by oxidation of dihydrorhodamine 123 (determined by flow cytometry). LPS also produced these effects with similar kinetics, but an oligodeoxynucleotide containing a CpG motif failed to induce any priming or activation response. Although the effects of LPS required the presence of serum, neutrophil activation by MTB 19-kDa lipoprotein occurred independently of serum factors, suggesting the involvement of different receptors and signaling mechanisms for LPS and MTB 19-kDa lipoprotein. Thus, MTB 19-kDa lipoprotein serves as a pathogen-associated molecular pattern that promotes neutrophil priming and activation.

  4. Strategies for promoting physical activity in clinical practice.

    PubMed

    Sallis, Robert; Franklin, Barry; Joy, Liz; Ross, Robert; Sabgir, David; Stone, James

    2015-01-01

    The time has come for healthcare systems to take an active role in the promotion of physical activity (PA). The connection between PA and health has been clearly established and exercise should be viewed as a cost effective medication that is universally prescribed as a first line treatment for virtually every chronic disease. While there are potential risks associated with exercise, these can be minimized with a proper approach and are far outweighed by the benefits. Key to promoting PA in the clinical setting is the use of a PA Vital Sign in which every patient's exercise habits are assessed and recorded in their medical record. Those not meeting the recommended 150min per week of moderate intensity PA should be encouraged to increase their PA levels with a proper exercise prescription. We can improve compliance by assessing our patient's barriers to being more active and employing new and evolving technology like accelerometers and smart phones applications, along with various websites and programs that have proven efficacy.

  5. Exploring Park Director Roles in Promoting Community Physical Activity

    PubMed Central

    Marsh, Terence; Derose, Kathryn Pitkin; Cohen, Deborah A.

    2013-01-01

    Background Parks provide numerous opportunities for physical activity (PA). Previous studies have evaluated parks’ physical features, but few have assessed how park staff influence PA. Methods We conducted semi -structured interviews with 49 park directors, focusing on perceptions of their role, park programs, marketing and outreach, external collaborations, and PA promotion. Directors also completed a questionnaire providing demographics, education and training, and other personal characteristics. Results Park directors’ descriptions of their roles varied widely, from primarily administrative to emphasizing community interaction, though most (70–80%) reported offering programs and community interaction as primary. Including PA in current programs and adding PA-specific programs were the most commonly reported ways of increasing PA. Also noted were facility and staffing improvements, and conducting citywide marketing. Many directors felt inadequately trained in marketing. Most parks reported community collaborations, but they appeared fairly superficial. An increasing administrative burden and bureaucracy were recurring themes throughout the interviews. Conclusions Staff training in marketing and operation of PA programs is needed. Partnerships with health departments and organizations can help facilitate the PA promotion potential of parks. As there are competing views of how parks should be managed, standardized benchmarks to evaluate efficiency may help to optimize usage and PA promotion. PMID:22733875

  6. [Comparison of the relative luciferase activity in secondary CEF by different heterogenous strong promoters, MDV gB promoter and the composed promoters].

    PubMed

    Qiu, Ya-Feng; Ge, Fei-Fei; Xu, Xue-Qing; Chen, Pu-Yan

    2006-04-01

    To improve the protection efficiency of the recombinant Marek' s disease viruses (MDV) in chickens with or without maternal antibodies,the work of selecting the optimal promoters for the construction of recombinant MDV was carried out. Combined with the efficient genetic manipulation, the composed promoters was constructed by use of the MDV gB core promoter with the regulatory elements from the early immediately promoter and enhancer of hCMV, the promoter and enhancer of SV40 or the partial enhancer of hCMV. And these composed promoters were ligased to the luciferase to construct the eukaryotic expressing vectors and named PhCMV-gB, Psv-gB and Pen-gB, respectively. In vitro, these vectors and internal standard plasmid (pSV-beta-LacZ) were transiently co-transfected into secondary CEF by FuGene 6 Transfection Reagent. Furthermore, cells were harvested 48 hours after transfection. Then the luciferase activity was detected by a luciferase assay kit, at the same time, the beta-galactosidase enzyme activity was detected by a beta-galactosidase enzyme assay kit, and the luciferase activity was corrected by the beta-galactosidase enzyme activity to get the relative luciferase activity. The relative luciferase activity was used as the transcriptional activity. By comparison of the relative luciferase activity of every promoter, it was found that these composed promoters could more effectively drive the reporter gene expression than the full legth of gB promoter did. Among them, PhCMV-gB robustly drove the reporter gene expression. On the other hand, PSV-gB and Pen-gB appeared to have the same strength; But compared with the commercial strong promoters, the transcriptional activity of the composed promoter were less than as or the same as that of the strong promoters. Therefore, at a sense, it can be proposed that these composed promoters have not only the characteristic of MDV gB promoter, but also that of the commercial strong promoters. These provide the choices for

  7. Anti-CD20 single chain variable antibody fragment-apolipoprotein A-I chimera containing nanodisks promote targeted bioactive agent delivery to CD20-positive lymphomas.

    PubMed

    Crosby, Natasha M; Ghosh, Mistuni; Su, Betty; Beckstead, Jennifer A; Kamei, Ayako; Simonsen, Jens B; Luo, Bing; Gordon, Leo I; Forte, Trudy M; Ryan, Robert O

    2015-08-01

    A fusion protein comprising an α-CD20 single chain variable fragment (scFv) antibody, a spacer peptide, and human apolipoprotein (apo) A-I was constructed and expressed in Escherichia coli. The lipid interaction properties intrinsic to apoA-I as well as the antigen recognition properties of the scFv were retained by the chimera. scFv•apoA-I was formulated into nanoscale reconstituted high-density lipoprotein particles (termed nanodisks; ND) and incubated with cultured cells. α-CD20 scFv•apoA-I ND bound to CD20-positive non-Hodgkins lymphoma (NHL) cells (Ramos and Granta) but not to CD20-negative T lymphocytes (i.e., Jurkat). Binding to NHL cells was partially inhibited by pre-incubation with rituximab, a monoclonal antibody directed against CD20. Confocal fluorescence microscopy analysis of Granta cells following incubation with α-CD20 scFv•apoA-I ND formulated with the intrinsically fluorescent hydrophobic polyphenol, curcumin, revealed α-CD20 scFv•apoA-I localizes to the cell surface, while curcumin off-loads and gains entry to the cell. Compared to control incubations, viability of cultured NHL cells was decreased upon incubation with α-CD20 scFv•apoA-I ND harboring curcumin. Thus, formulation of curcumin ND with α-CD20 scFv•apoA-I as the scaffold component confers cell targeting and enhanced bioactive agent delivery, providing a strategy to minimize toxicity associated with chemotherapeutic agents.

  8. IL-33 activates tumor stroma to promote intestinal polyposis

    PubMed Central

    Maywald, Rebecca L.; Doerner, Stephanie K.; Pastorelli, Luca; De Salvo, Carlo; Benton, Susan M.; Dawson, Emily P.; Lanza, Denise G.; Berger, Nathan A.; Markowitz, Sanford D.; Lenz, Heinz-Josef; Nadeau, Joseph H.; Pizarro, Theresa T.; Heaney, Jason D.

    2015-01-01

    Tumor epithelial cells develop within a microenvironment consisting of extracellular matrix, growth factors, and cytokines produced by nonepithelial stromal cells. In response to paracrine signals from tumor epithelia, stromal cells modify the microenvironment to promote tumor growth and metastasis. Here, we identify interleukin 33 (IL-33) as a regulator of tumor stromal cell activation and mediator of intestinal polyposis. In human colorectal cancer, IL-33 expression was induced in the tumor epithelium of adenomas and carcinomas, and expression of the IL-33 receptor, IL1RL1 (also referred to as IL1-R4 or ST2), localized predominantly to the stroma of adenoma and both the stroma and epithelium of carcinoma. Genetic and antibody abrogation of responsiveness to IL-33 in the ApcMin/+ mouse model of intestinal tumorigenesis inhibited proliferation, induced apoptosis, and suppressed angiogenesis in adenomatous polyps, which reduced both tumor number and size. Similar to human adenomas, IL-33 expression localized to tumor epithelial cells and expression of IL1RL1 associated with two stromal cell types, subepithelial myofibroblasts and mast cells, in ApcMin/+ polyps. In vitro, IL-33 stimulation of human subepithelial myofibroblasts induced the expression of extracellular matrix components and growth factors associated with intestinal tumor progression. IL-33 deficiency reduced mast cell accumulation in ApcMin/+ polyps and suppressed the expression of mast cell-derived proteases and cytokines known to promote polyposis. Based on these findings, we propose that IL-33 derived from the tumor epithelium promotes polyposis through the coordinated activation of stromal cells and the formation of a protumorigenic microenvironment. PMID:25918379

  9. Active Fantasy Sports: Rationale and Feasibility of Leveraging Online Fantasy Sports to Promote Physical Activity

    PubMed Central

    Majewski, Sara; Standish, Melanie; Agarwal, Pooja; Podowski, Aleksandra; Carson, Rebecca; Eyesus, Biruk; Shah, Aakash; Schneider, Kristin L

    2014-01-01

    Background The popularity of active video games (AVGs) has skyrocketed over the last decade. However, research suggests that the most popular AVGs, which rely on synchronous integration between players’ activity and game features, fail to promote physical activity outside of the game or for extended periods of engagement. This limitation has led researchers to consider AVGs that involve asynchronous integration of players’ ongoing physical activity with game features. Rather than build an AVG de novo, we selected an established sedentary video game uniquely well suited for the incorporation of asynchronous activity: online fantasy sports. Objective The primary aim of this study was to explore the feasibility of a new asynchronous AVG—active fantasy sports—designed to promote physical activity. Methods We conducted two pilot studies of an active fantasy sports game designed to promote physical activity. Participants wore a low cost triaxial accelerometer and participated in an online fantasy baseball (Study 1, n=9, 13-weeks) or fantasy basketball (Study 2, n=10, 17-weeks) league. Privileges within the game were made contingent on meeting weekly physical activity goals (eg, averaging 10,000 steps/day). Results Across the two studies, the feasibility of integrating physical activity contingent features and privileges into online fantasy sports games was supported. Participants found the active fantasy sports game enjoyable, as or more enjoyable than traditional (sedentary) online fantasy sports (Study 1: t 8=4.43, P<.01; Study 2: t 9=2.09, P=.07). Participants in Study 1 increased their average steps/day, t 8=2.63, P<.05, while participants in Study 2 maintained (ie, did not change) their activity, t 9=1.57, P=.15). In postassessment interviews, social support within the game was cited as a key motivating factor for increasing physical activity. Conclusions Preliminary evidence supports potential for the active fantasy sports system as a sustainable and

  10. Shp2 SUMOylation promotes ERK activation and hepatocellular carcinoma development

    PubMed Central

    Deng, Rong; Zhao, Xian; Qu, YingYing; Chen, Cheng; Zhu, Changhong; Zhang, Hailong; Yuan, Haihua; Jin, Hui; Liu, Xin; Wang, Yanli; Chen, Qin; Huang, Jian; Yu, Jianxiu

    2015-01-01

    Shp2, an ubiquitously expressed protein tyrosine phosphatase, is essential for regulation of Ras/ERK signaling pathway and tumorigenesis. Here we report that Shp2 is modified by SUMO1 at lysine residue 590 (K590) in its C-terminus, which is reduced by SUMO1-specific protease SENP1. Analysis of wild-type Shp2 and SUMOylation-defective Shp2K590R mutant reveals that SUMOylation of Shp2 promotes EGF-stimulated ERK signaling pathway and increases anchorage-independent cell growth and xenografted tumor growth of hepatocellular carcinoma (HCC) cell lines. Furthermore, we find that mutant Shp2K590R reduces its binding with the scaffolding protein Gab1, and consistent with this, knockdown of SENP1 increased the interaction between Shp2 and Gab1. More surprisingly, we show that human Shp2 (hShp2) and mouse Shp2 (mShp2) have differential effects on ERK activation as a result of different SUMOylation level, which is due to the event of K590 at hShp2 substituted by R594 at mShp2. In summary, our data demonstrate that SUMOylation of Shp2 promotes ERK activation via facilitating the formation of Shp2-Gab1 complex and thereby accelerates HCC cell and tumor growth, which presents a novel regulatory mechanism underlying Shp2 in regulation of HCC development. PMID:25823821

  11. Activation of the Renin-Angiotensin System Promotes Colitis Development

    PubMed Central

    Shi, Yongyan; Liu, Tianjing; He, Lei; Dougherty, Urszula; Chen, Li; Adhikari, Sarbani; Alpert, Lindsay; Zhou, Guolin; Liu, Weicheng; Wang, Jiaolong; Deb, Dilip K.; Hart, John; Liu, Shu Q.; Kwon, John; Pekow, Joel; Rubin, David T.; Zhao, Qun; Bissonnette, Marc; Li, Yan Chun

    2016-01-01

    The renin-angiotensin system (RAS) plays pathogenic roles in renal and cardiovascular disorders, but whether it is involved in colitis is unclear. Here we show that RenTgMK mice that overexpress active renin from the liver developed more severe colitis than wild-type controls. More than 50% RenTgMK mice died whereas all wild-type mice recovered. RenTgMK mice exhibited more robust mucosal TH17 and TH1/TH17 responses and more profound colonic epithelial cell apoptosis compared to wild-type controls. Treatment with aliskiren (a renin inhibitor), but not hydralazine (a smooth muscle relaxant), ameliorated colitis in RenTgMK mice, although both drugs normalized blood pressure. Chronic infusion of angiotensin II into wild-type mice mimicked the severe colitic phenotype of RenTgMK mice, and treatment with losartan [an angiotensin type 1 receptor blocker (ARB)] ameliorated colitis in wild-type mice, confirming a colitogenic role for the endogenous RAS. In human biopsies, pro-inflammatory cytokines were suppressed in patients with inflammatory bowel disease who were on ARB therapy compared to patients not receiving ARB therapy. These observations demonstrate that activation of the RAS promotes colitis in a blood pressure independent manner. Angiotensin II appears to drive colonic mucosal inflammation by promoting intestinal epithelial cell apoptosis and mucosal TH17 responses in colitis development. PMID:27271344

  12. Vanadium promotes hydroxyl radical formation by activated human neutrophils.

    PubMed

    Fickl, Heidi; Theron, Annette J; Grimmer, Heidi; Oommen, Joyce; Ramafi, Grace J; Steel, Helen C; Visser, Susanna S; Anderson, Ronald

    2006-01-01

    This study was undertaken to investigate the effects of vanadium in the +2, +3, +4, and +5 valence states on superoxide generation, myeloperoxidase (MPO) activity, and hydroxyl radical formation by activated human neutrophils in vitro, using lucigenin-enhanced chemiluminescence (LECL), autoiodination, and electron spin resonance with 5,5-dimethyl-l-pyrroline N-oxide as the spin trap, respectively. At concentrations of up to 25 microM, vanadium, in the four different valence states used, did not affect the LECL responses of neutrophils activated with either the chemoattractant, N-formyl-l-methionyl-l-leucyl-l-phenylalanine (1 microM), or the phorbol ester, phorbol 12-myristate 12-acetate (25 ng/ml). However, exposure to vanadium in the +2, +3, and +4, but not the +5, valence states was accompanied by significant augmentation of hydroxyl radical formation by activated neutrophils and attenuation of MPO-mediated iodination. With respect to hydroxyl radical formation, similar effects were observed using cell-free systems containing either hydrogen peroxide (100 microM) or xanthine/xanthine oxidase together with vanadium (+2, +3, +4), while the activity of purified MPO was inhibited by the metal in these valence states. These results demonstrate that vanadium in the +2, +3, and +4 valence states interacts prooxidatively with human neutrophils, competing effectively with MPO for hydrogen peroxide to promote formation of the highly toxic hydroxyl radical.

  13. A Social Identity Approach to Understanding and Promoting Physical Activity.

    PubMed

    Stevens, Mark; Rees, Tim; Coffee, Pete; Steffens, Niklas K; Haslam, S Alexander; Polman, Remco

    2017-03-27

    Against the backdrop of a global physical inactivity crisis, attempts to both understand and positively influence physical activity behaviours are characterized by a focus on individual-level factors (e.g. cognitions, attitudes, motivation). We outline a new perspective, drawn from an emerging body of work exploring the applicability of social identity and self-categorization theories to domains of sport and health, from which to understand and address this pervasive problem. This social identity approach suggests that the groups to which people belong can be, and often are, incorporated into their sense of self and, through this, are powerful determinants of physical activity-related behaviour. We start by reviewing the current state of physical activity research and highlighting the potential for the social identity approach to help understand how social factors influence these behaviours. Next, we outline the theoretical underpinnings of the social identity approach and provide three key examples that speak to the analytical and practical value of the social identity approach in physical activity settings. Specifically, we argue that social identity (1) can be harnessed to promote engagement in physical activity, (2) underpins exercise group behaviour, and (3) underpins effective leadership in exercise settings. We conclude by identifying prospects for a range of theory-informed research developments.

  14. Active Aging Promotion: Results from the Vital Aging Program

    PubMed Central

    Caprara, Mariagiovanna; Molina, María Ángeles; Schettini, Rocío; Santacreu, Marta; Orosa, Teresa; Mendoza-Núñez, Víctor Manuel; Rojas, Macarena; Fernández-Ballesteros, Rocío

    2013-01-01

    Active aging is one of the terms in the semantic network of aging well, together with others such as successful, productive, competent aging. All allude to the new paradigm in gerontology, whereby aging is considered from a positive perspective. Most authors in the field agree active aging is a multidimensional concept, embracing health, physical and cognitive fitness, positive affect and control, social relationships and engagement. This paper describes Vital Aging, an individual active aging promotion program implemented through three modalities: Life, Multimedia, and e-Learning. The program was developed on the basis of extensive evidence about individual determinants of active aging. The different versions of Vital Aging are described, and four evaluation studies (both formative and summative) are reported. Formative evaluation reflected participants' satisfaction and expected changes; summative evaluations yielded some quite encouraging results using quasi-experimental designs: those who took part in the programs increased their physical exercise, significantly improved their diet, reported better memory, had better emotional balance, and enjoyed more cultural, intellectual, affective, and social activities than they did before the course, thus increasing their social relationships. These results are discussed in the context of the common literature within the field and, also, taking into account the limitations of the evaluations accomplished. PMID:23476644

  15. Evaluation of the health promotion activities of paediatric nurses: is the Ottawa Charter for Health Promotion a useful framework?

    PubMed

    Roden, Janet; Jarvis, Lynda

    2012-06-01

    Researchers were involved in an evaluative approach to examine the health promotion activities of paediatric nurses from a paediatric tertiary hospital centre (N = 83) and five paediatric non-tertiary hospital centres (N = 48) from Sydney, Australia. The aims of this study were to understand the nature of heath promotion in paediatric nursing practice by examining nurses' attitudes, investigating paediatric nurses' involvement in the five action area of the Ottawa Charter, and identifying barriers to the implementation of health promotion in practice. The researchers developed a health promotion survey based around the Ottawa Charter for Health Promotion (World Health Organisation, 1986a), and a literature review of nurses' involvement in health promotion. Results showed that tertiary paediatric nurses undertook more varied health promotion activities such as creating supportive environments (CSE), reorienting health services (RHS) and building healthy public policy (BHPP) than did non-tertiary paediatric nurses who were involved in only one action area of the Charter, that of developing personal skills (DPS). This research revealed that within paediatric nursing practice the action areas of the Ottawa Charter of BHPP and CSE were important; and that there is support for the advocacy role of paediatric nurses. There is also evidence that paediatric nurses may have health promotion knowledge deficits associated with the Ottawa Charter, and that the environment of multidisciplinary allied health professionals in a tertiary paediatric centre may positively influence senior paediatric nurses and their capacity to be involved in varied health promotion activities associated with the Ottawa Charter.

  16. Promoting Active Learning: The Use of Computational Software Programs

    NASA Astrophysics Data System (ADS)

    Dickinson, Tom

    The increased emphasis on active learning in essentially all disciplines is proving beneficial in terms of a student's depth of learning, retention, and completion of challenging courses. Formats labeled flipped, hybrid and blended facilitate face-to-face active learning. To be effective, students need to absorb a significant fraction of the course material prior to class, e.g., using online lectures and reading assignments. Getting students to assimilate and at least partially understand this material prior to class can be extremely difficult. As an aid to achieving this preparation as well as enhancing depth of understanding, we find the use of software programs such as Mathematica®or MatLab®, very helpful. We have written several Mathematica®applications and student exercises for use in a blended format two semester E&M course. Formats include tutorials, simulations, graded and non-graded quizzes, walk-through problems, exploration and interpretation exercises, and numerical solutions of complex problems. A good portion of this activity involves student-written code. We will discuss the efficacy of these applications, their role in promoting active learning, and the range of possible uses of this basic scheme in other classes.

  17. Sleep after spatial learning promotes covert reorganization of brain activity.

    PubMed

    Orban, Pierre; Rauchs, Géraldine; Balteau, Evelyne; Degueldre, Christian; Luxen, André; Maquet, Pierre; Peigneux, Philippe

    2006-05-02

    Sleep promotes the integration of recently acquired spatial memories into cerebral networks for the long term. In this study, we examined how sleep deprivation hinders this consolidation process. Using functional MRI, we mapped regional cerebral activity during place-finding navigation in a virtual town, immediately after learning and 3 days later, in subjects either allowed regular sleep (RS) or totally sleep-deprived (TSD) on the first posttraining night. At immediate and delayed retrieval, place-finding navigation elicited increased brain activity in an extended hippocampo-neocortical network in both RS and TSD subjects. Behavioral performance was equivalent between groups. However, striatal navigation-related activity increased more at delayed retrieval in RS than in TSD subjects. Furthermore, correlations between striatal response and behavioral performance, as well as functional connectivity between the striatum and the hippocampus, were modulated by posttraining sleep. These data suggest that brain activity is restructured during sleep in such a way that navigation in the virtual environment, initially related to a hippocampus-dependent spatial strategy, becomes progressively contingent in part on a response-based strategy mediated by the striatum. Both neural strategies eventually relate to equivalent performance levels, indicating that covert reorganization of brain patterns underlying navigation after sleep is not necessarily accompanied by overt changes in behavior.

  18. Heparin and Methionine Oxidation Promote the Formation of Apolipoprotein A-I Amyloid Comprising α-Helical and β-Sheet Structures.

    PubMed

    Townsend, David; Hughes, Eleri; Hussain, Rohanah; Siligardi, Giuliano; Baldock, Sarah; Madine, Jillian; Middleton, David A

    2017-03-13

    Peptides derived from apolipoprotein A-I (apoA-I), the main component of high-density lipoprotein (HDL), constitute the main component of amyloid deposits that colocalize with atherosclerotic plaques. Here we investigate the molecular details of full-length, lipid-deprived apoA-I after assembly into insoluble aggregates under physiologically relevant conditions known to induce aggregation in vitro. Unmodified apoA-I is shown to remain soluble at pH 7 for at least 3 days, retaining its native α-helical-rich structure. Upon acidification to pH 4, apoA-I rapidly assembles into insoluble nonfibrillar aggregates lacking the characteristic cross-β features of amyloid. In the presence of heparin, the rate and thioflavin T responsiveness of the aggregates formed at pH 4 increase and short amyloid-like fibrils are observed, which give rise to amyloid-characteristic X-ray reflections at 4.7 and 10 Å. Solid-state nuclear magnetic resonance (SSNMR) and synchrotron radiation circular dichroism spectroscopy of fibrils formed in the presence of heparin show they retain some α-helical characteristics together with new β-sheet structures. Interestingly, SSNMR indicates a similar molecular structure of aggregates formed in the absence of heparin at pH 6 after oxidation of the three methionine residues, although their morphology is rather different from that of the heparin-derived fibrils. We propose a model for apoA-I aggregation in which perturbations of a four-helix bundle-like structure, induced by interactions of heparin or methionine oxidation, cause the partially helical N-terminal residues to disengage from the remaining, intact helices, thereby allowing self-assembly via β-strand associations.

  19. [Actively promote the development of neuro-ophthalmology in China].

    PubMed

    Wei, Shi-hui; Zhao, Jia-liang

    2010-12-01

    Neuro-ophthalmology is a medical subspecialty concerned on the nervous system diseases with ocular manifestations, this could be both sensory and motor, including ocular movements, papillary responses, and the structure changes of the brain and nervous system with ocular manifestations. Although neuro-ophthalmology in China has achieved some progress, certain problems still exist, such as the professional neuro-ophthalmology team and related academic organization are still absent in China; neuro-ophthalmology knowledge has not been popularized; the new technologies for diagnosis and treatment in neuro-ophthalmology have not been absorbed and applied; the coordination and cooperation with other related disciplines are not enough. We should actively promote the development of neuro-ophthalmology in China, including organization of a professional team of neuro-ophthalmology, popularization of neuro-ophthalmology knowledge to the ophthalmologists, development of research work in neuro-ophthalmology and the collaboration with international neuro-ophthalmologists.

  20. Activating STAT3 Alpha for Promoting Healing of Neurons

    NASA Technical Reports Server (NTRS)

    Conway, Greg

    2008-01-01

    A method of promoting healing of injured or diseased neurons involves pharmacological activation of the STAT3 alpha protein. Usually, injured or diseased neurons heal incompletely or not at all for two reasons: (1) they are susceptible to apoptosis (cell death); and (2) they fail to engage in axogenesis that is, they fail to re-extend their axons to their original targets (e.g., muscles or other neurons) because of insufficiency of compounds, denoted neurotrophic factors, needed to stimulate such extension. The present method (see figure) of treatment takes advantage of prior research findings to the effect that the STAT3 alpha protein has anti-apoptotic and pro-axogenic properties.

  1. Ratite oils promote keratinocyte cell growth and inhibit leukocyte activation.

    PubMed

    Bennett, Darin C; Leung, Gigi; Wang, Eddy; Ma, Sam; Lo, Blanche K K; McElwee, Kevin J; Cheng, Kimberly M

    2015-09-01

    Traditionally, native Australian aborigines have used emu oil for the treatment of inflammation and to accelerate wound healing. Studies on mice suggest that topically applied emu oil may have anti-inflammatory properties and may promote wound healing. We investigated the effects of ratite oils (6 emu, 3 ostrich, 1 rhea) on immortalized human keratinocytes (HaCaT cells) in vitro by culturing the cells in media with oil concentrations of 0%, 0.5%, and 1.0%. Peking duck, tea tree, and olive oils were used as comparative controls. The same oils at 0.5% concentration were evaluated for their influence on peripheral blood mononuclear cell (PBMC) survival over 48 hr and their ability to inhibit IFNγ production in PBMCs activated by phytohemagglutinin (PHA) in ELISpot assays. Compared to no oil control, significantly shorter population doubling time durations were observed for HaCaT cells cultured in emu oil (1.51×faster), ostrich oil (1.46×faster), and rhea oil (1.64×faster). Tea tree oil demonstrated significant antiproliferative activity and olive oil significantly prolonged (1.35×slower) cell population doubling time. In contrast, almost all oils, particularly tea tree oil, significantly reduced PBMC viability. Different oils had different levels of inhibitory effect on IFNγ production with individual emu, ostrich, rhea, and duck oil samples conferring full inhibition. This preliminary investigation suggests that emu oil might promote wound healing by accelerating the growth rate of keratinocytes. Combined with anti-inflammatory properties, ratite oil may serve as a useful component in bandages and ointments for the treatment of wounds and inflammatory skin conditions.

  2. Ratite oils promote keratinocyte cell growth and inhibit leukocyte activation

    PubMed Central

    Bennett, Darin C.; Leung, Gigi; Wang, Eddy; Ma, Sam; Lo, Blanche K. K.; McElwee, Kevin J.; Cheng, Kimberly M.

    2015-01-01

    Traditionally, native Australian aborigines have used emu oil for the treatment of inflammation and to accelerate wound healing. Studies on mice suggest that topically applied emu oil may have anti-inflammatory properties and may promote wound healing. We investigated the effects of ratite oils (6 emu, 3 ostrich, 1 rhea) on immortalized human keratinocytes (HaCaT cells) in vitro by culturing the cells in media with oil concentrations of 0%, 0.5%, and 1.0%. Peking duck, tea tree, and olive oils were used as comparative controls. The same oils at 0.5% concentration were evaluated for their influence on peripheral blood mononuclear cell (PBMC) survival over 48 hr and their ability to inhibit IFNγ production in PBMCs activated by phytohemagglutinin (PHA) in ELISpot assays. Compared to no oil control, significantly shorter population doubling time durations were observed for HaCaT cells cultured in emu oil (1.51 × faster), ostrich oil (1.46 × faster), and rhea oil (1.64 × faster). Tea tree oil demonstrated significant antiproliferative activity and olive oil significantly prolonged (1.35 × slower) cell population doubling time. In contrast, almost all oils, particularly tea tree oil, significantly reduced PBMC viability. Different oils had different levels of inhibitory effect on IFNγ production with individual emu, ostrich, rhea, and duck oil samples conferring full inhibition. This preliminary investigation suggests that emu oil might promote wound healing by accelerating the growth rate of keratinocytes. Combined with anti-inflammatory properties, ratite oil may serve as a useful component in bandages and ointments for the treatment of wounds and inflammatory skin conditions. PMID:26217022

  3. Promoting Uranium Immobilization by the Activities of Microbial Phosphatases

    SciTech Connect

    Robert J. Martinez; Melanie J. Beazley; Samuel M. Webb; Martial Taillefert; and Patricia A. Sobecky

    2007-04-19

    The overall objective of this project is to examine the activity of nonspecific phosphohydrolases present in naturally occurring subsurface microorganisms for the purpose of promoting the immobilization of radionuclides through the production of uranium [U(VI)] phosphate precipitates. Specifically, we hypothesize that the precipitation of U(VI) phosphate minerals may be promoted through the microbial release and/or accumulation of PO4 3- as a means to detoxify radionuclides and heavy metals. An experimental approach was designed to determine the extent of phosphatase activity in bacteria previously isolated from contaminated subsurface soils collected at the ERSP Field Research Center (FRC) in Oak Ridge, TN. Screening of 135 metal resistant isolates for phosphatase activity indicated the majority (75 of 135) exhibited a phosphatase-positive phenotype. During this phase of the project, a PCR based approach has also been designed to assay FRC isolates for the presence of one or more classes of the characterized non-specific acid phophastase (NSAP) genes likely to be involved in promoting U(VI) precipitation. Testing of a subset of Pb resistant (Pbr) Arthrobacter, Bacillus and Rahnella strains indicated 4 of the 9 Pbr isolates exhibited phosphatase phenotypes suggestive of the ability to bioprecipitate U(VI). Two FRC strains, a Rahnella sp. strain Y9602 and a Bacillus sp. strain Y9-2, were further characterized. The Rahnella sp. exhibited enhanced phosphatase activity relative to the Bacillus sp. Whole-cell enzyme assays identified a pH optimum of 5.5, and inorganic phosphate accumulated in pH 5.5 synthetic groundwater (designed to mimic FRC conditions) incubations of both strains in the presence of a model organophosphorus substrate provided as the sole C and P source. Kinetic experiments showed that these two organisms can grow in the presence of 200 μM dissolved uranium and that Rahnella is much more efficient in precipitating U(VI) than Bacillus sp. The

  4. Core promoter analysis of porcine Six1 gene and its regulation of the promoter activity by CpG methylation.

    PubMed

    Wu, Wangjun; Ren, Zhuqing; Liu, Honglin; Wang, Linjie; Huang, Ruihua; Chen, Jie; Zhang, Lin; Li, Pinghua; Xiong, Yuanzhu

    2013-10-25

    Six1, an evolutionary conserved transcription factor, has been shown to play an important role in organogenesis and diseases. However, no reports were shown to investigate its transcriptional regulatory mechanisms. In the present study, we first identified porcine Six1 gene core promoter region (+170/-360) using luciferase reporter assay system and found that promoter activities were significantly higher in the mouse myoblast C2C12 cells than that in the mouse fibroblast C3H10T1/2 cells, implying that Six1 promoter could possess muscle-specific characteristics. Moreover, our results showed that promoter activities of Six1 were decreased as induction of differentiation of C2C12 cells, which was accompanied by the down-regulation of mRNA expression of Six1 gene. In addition, we found that the DNA methylation of Six1 promoters in vitro obviously influences the promoter activities and the DNA methylation level of Six1 promoter core region was negatively correlated to Six1 gene expression in vivo. Taken together, we preliminarily clarified transcriptional regulatory mechanisms of Six1 gene, which should be useful for investigating its subtle transcriptional regulatory mechanisms in the future. On the other hand, based on Six1 involved in tumorigenesis, our data also provide a genetic foundation to control the generation of diseases via pursuing Six1 as therapeutic target gene.

  5. International Association for Promoting Geoethics (IAPG): an update on activities

    NASA Astrophysics Data System (ADS)

    Di Capua, Giuseppe; Bobrowsky, Peter; Kieffer, Susan; Peppoloni, Silvia; Tinti, Stefano

    2016-04-01

    The International Association for Promoting Geoethics (IAPG: http://www.geoethics.org) was founded on August 2012 to unite global geoscientists to raise the awareness of the scientific community regarding the importance of the ethical, social and cultural implications of geoscience research, education, and practice. IAPG is an international, multidisciplinary and scientific platform for discussion on ethical problems and dilemmas in Earth Sciences, promoting geoethical themes through scientific publications and conferences, strengthening the research base on geoethics, and focusing on case-studies as models for the development of effective and operative strategies. IAPG is legally recognized as a not-for-profit organization. It is a non-governmental, non-political, non-party institution, at all times free from racial, gender, religious or national prejudices. Its network continues to grow with more than 900 members in 103 countries, including 20 national sections. IAPG operates exclusively through donations and personal funds of its members. The results achieved since inception have been recognized by numerous international organizations. In particular, IAPG has obtained the status of affiliated organization by the International Union of Geological Sciences (IUGS), American Geosciences Institute (AGI), Geological Society of America (GSA), and the Geological Society of London (GSL). IAPG has enlarged its official relationships also through agreements on collaboration with other organizations, such as the American Geophysical Union (AGU), EuroGeoSurveys (EGS), European Federation of Geologists (EFG), Association of Environmental & Engineering Geologists (AEG), International Geoscience Education Organisation (IGEO), African Association of Women in Geosciences (AAWG), and others. IAPG considers publications as an indispensable activity to strengthen geoethics from a scientific point of view, so members are active in the publication of articles and editing of books on

  6. Promoting uranium immobilization by the activities of microbial phophatases

    SciTech Connect

    Sobecky, Patricia A.; Martial Taillefert

    2006-06-01

    The following is a summary of progress in our project ''Promoting uranium immobilization by the activities of microbial phosphatases'' during the second year of the project. (1). Assignment of microbial phosphatases to molecular classes. One objective of this project is to determine the relationship of phosphatase activity to metal resistance in subsurface strains and possible contributions of horizontal gene transfer (HGT) to the dissemination of nonspecific acid phosphatase genes. Non-specific acid phosphohydrolases are a broad group of secreted microbial phosphatases that function in acidic-to-neutral pH ranges and utilize a wide range of organophosphate substrates. To address this objective we have designed a collection of PCR primer sets based on known microbial acid phosphatase sequences. Genomic DNA is extracted from subsurface FRC isolates and amplicons of the expected sizes are sequenced and searched for conserved signature motifs. During this reporting period we have successfully designed and tested a suite of PCR primers for gram-positive and gram-negative groups of the following phosphatase classes: (1) Class A; (2) Class B; and (3) Class C (gram negative). We have obtained specific PCR products for each of the classes using the primers we have designed using control strains as well as with subsurface isolates.

  7. How to Identify Success Among Networks That Promote Active Living

    PubMed Central

    Litt, Jill; Varda, Danielle; Reed, Hannah; Retrum, Jessica; Tabak, Rachel; Gustat, Jeanette; Tompkins, Nancy O’Hara

    2017-01-01

    Objectives We evaluated organization- and network-level factors that influence organizations’ perceived success. This is important for managing interorganizational networks, which can mobilize communities to address complex health issues such as physical activity, and for achieving change. Methods In 2011, we used structured interview and network survey data from 22 states in the United States to estimate multilevel random-intercept models to understand organization- and network-level factors that explain perceived network success. Results A total of 53 of 59 “whole networks” met the criteria for inclusion in the analysis (89.8%). Coordinators identified 559 organizations, with 3 to 12 organizations from each network taking the online survey (response rate: 69.7%; range: 33%–100%). Occupying a leadership position (P < .01), the amount of time with the network (P < .05), and support from community leaders (P < .05) emerged as correlates of perceived success. Conclusions Organizations’ perceptions of success can influence decisions about continuing involvement and investment in networks designed to promote environment and policy change for active living. Understanding these factors can help leaders manage complex networks that involve diverse memberships, varied interests, and competing community-level priorities. PMID:26378863

  8. Sonic Hedgehog Promotes Cementoblastic Differentiation via Activating the BMP Pathways.

    PubMed

    Bae, Won-Jung; Auh, Q-Schick; Lim, Hyun-Chang; Kim, Gyu-Tae; Kim, Hyun-Soo; Kim, Eun-Cheol

    2016-10-01

    Although sonic hedgehog (SHH), an essential molecule in embryogenesis and organogenesis, stimulates proliferation of human periodontal ligament (PDL) stem cells, the effects of recombinant human SHH (rh-SHH) on osteoblastic differentiation are unclear. To reveal the role of SHH in periodontal regeneration, expression of SHH in mouse periodontal tissues and its effects on the osteoblastic/cementoblastic differentiation in human cementoblasts were investigated. SHH is immunolocalized to differentiating cementoblasts, PDL cells, and osteoblasts of the developing mouse periodontium. Addition of rh-SHH increased cell growth, ALP activity, and mineralization nodule formation, and upregulated mRNA expression of osteoblastic and cementoblastic markers. The osteoblastic/cementoblastic differentiation of rh-SHH was abolished by the SHH inhibitor cyclopamine (Cy) and the BMP antagonist noggin. rh-SHH increased the expression of BMP-2 and -4 mRNA, as well as levels of phosphorylated Akt, ERK, p38, and JNK, and of MAPK and NF-κB activation, which were reversed by noggin, Cy, and BMP-2 siRNA. Collectively, this study is the first to demonstrate that SHH can promote cell growth and cell osteoblastic/cementoblastic differentiation via BMP pathway. Thus, SHH plays important roles in the development of periodontal tissue, and might represent a new therapeutic target for periodontitis and periodontal regeneration.

  9. Promotion of adiponectin multimerization by emodin: a novel AMPK activator with PPARγ-agonist activity.

    PubMed

    Chen, Zhifen; Zhang, Lu; Yi, Junyang; Yang, Zhuanbo; Zhang, Zhijie; Li, Zhen

    2012-11-01

    Adiponectin is an important insulin-sensitizing adipokine with multiple beneficial effects on obesity-associated medical complications. It is secreted from adipocytes into circulation as high, medium, and low molecular weight forms (HMW, MMW, and LMW). Each oligomeric form of adiponectin exerts non-overlapping biological functions, with the HMW oligomer possessing the most potent insulin-sensitizing activity. In this study, we reported that emodin, a natural product and active ingredient of various Chinese herbs, activates AMPK in both 3T3-L1 adipocytes and 293T cells. Activation of AMPK by emodin promotes the assembly of HMW adiponectin and increases the ratio of HMW adiponectin to total adiponectin in 3T1-L1 adipocytes. Emodin might activate AMPK by an indirect mechanism similar to berberine. We also found that emodin activates PPARγ and promotes differentiation and adiponectin expression during differentiation of 3T3-L1 preadipocytes. Therefore, emodin is a novel AMPK activator with PPARγ-agonist activity. Our results demonstrate that the effects of emodin on adiponectin expression and multimerization are the ultimate effects resulting from both AMPK activation and PPARγ activation. The dual-activity makes emodin or the derivatives potential drug candidates for the treatment of type 2 diabetes and other obesity-related metabolic diseases.

  10. Emotions promote social interaction by synchronizing brain activity across individuals

    PubMed Central

    Nummenmaa, Lauri; Glerean, Enrico; Viinikainen, Mikko; Jääskeläinen, Iiro P.; Hari, Riitta; Sams, Mikko

    2012-01-01

    Sharing others’ emotional states may facilitate understanding their intentions and actions. Here we show that networks of brain areas “tick together” in participants who are viewing similar emotional events in a movie. Participants’ brain activity was measured with functional MRI while they watched movies depicting unpleasant, neutral, and pleasant emotions. After scanning, participants watched the movies again and continuously rated their experience of pleasantness–unpleasantness (i.e., valence) and of arousal–calmness. Pearson’s correlation coefficient was used to derive multisubject voxelwise similarity measures [intersubject correlations (ISCs)] of functional MRI data. Valence and arousal time series were used to predict the moment-to-moment ISCs computed using a 17-s moving average. During movie viewing, participants' brain activity was synchronized in lower- and higher-order sensory areas and in corticolimbic emotion circuits. Negative valence was associated with increased ISC in the emotion-processing network (thalamus, ventral striatum, insula) and in the default-mode network (precuneus, temporoparietal junction, medial prefrontal cortex, posterior superior temporal sulcus). High arousal was associated with increased ISC in the somatosensory cortices and visual and dorsal attention networks comprising the visual cortex, bilateral intraparietal sulci, and frontal eye fields. Seed-voxel–based correlation analysis confirmed that these sets of regions constitute dissociable, functional networks. We propose that negative valence synchronizes individuals’ brain areas supporting emotional sensations and understanding of another’s actions, whereas high arousal directs individuals’ attention to similar features of the environment. By enhancing the synchrony of brain activity across individuals, emotions may promote social interaction and facilitate interpersonal understanding. PMID:22623534

  11. Activator protein 1 promotes the transcriptional activation of IRAK-M.

    PubMed

    Jin, Peipei; Bo, Lulong; Liu, Yongjian; Lu, Wenbin; Lin, Shengwei; Bian, Jinjun; Deng, Xiaoming

    2016-10-01

    Interleukin-1 receptor-associated kinase M (IRAK-M) is a well-known negative regulator for Toll-like receptor signaling, which can regulate immune homeostasis and tolerance in a number of pathological settings. However, the mechanism for IRAK-M regulation at transcriptional level remains largely unknown. In this study, a 1.4kb upstream sequence starting from the major IRAK-M transcriptional start site was cloned into luciferase reporter vector pGL3-basic to construct the full-length IRAK-M promoter. Luciferase reporter plasmids harboring the full-length and the deletion mutants of IRAK-M were transfected into 293T and A549 cells, and their relative luciferase activity was measured. The results demonstrated that activator protein 1(AP-1) cis-element plays a crucial role in IRAK-M constitutive gene transcription. Silencing of c-Fos and/or c-Jun expression suppressed the IRAK-M promoter activity as well as its mRNA and protein expressions. As a specific inhibitor for AP-1 activation, SP600125 also significantly suppressed the basal transcriptional activity of IRAK-M, the binding activity of c-Fos/c-Jun with IRAK-M promoter, and IRAK-M protein expression. Taken together, the result of this study highlights the importance of AP-1 in IRAK-M transcription, which offers more information on the role of IRAK-M in infectious and non-infectious diseases.

  12. Photodynamic activation as a molecular switch to promote osteoblast cell differentiation via AP-1 activation

    PubMed Central

    Kushibiki, Toshihiro; Tu, Yupeng; Abu-Yousif, Adnan O.; Hasan, Tayyaba

    2015-01-01

    In photodynamic therapy (PDT), cells are impregnated with a photosensitizing agent that is activated by light irradiation, thereby photochemically generating reactive oxygen species (ROS). The amounts of ROS produced depends on the PDT dose and the nature of the photosensitizer. Although high levels of ROS are cytotoxic, at physiological levels they play a key role as second messengers in cellular signaling pathways, pluripotency, and differentiation of stem cells. To investigate further the use of photochemically triggered manipulation of such pathways, we exposed mouse osteoblast precursor cells and rat primary mesenchymal stromal cells to low-dose PDT. Our results demonstrate that low-dose PDT can promote osteoblast differentiation via the activation of activator protein-1 (AP-1). Although PDT has been used primarily as an anti-cancer therapy, the use of light as a photochemical “molecular switch” to promote differentiation should expand the utility of this method in basic research and clinical applications. PMID:26279470

  13. Promoting physical activity: fertile ground for rehabilitation psychology.

    PubMed

    Uswatte, Gitendra

    2013-02-01

    Comments on the article by Schmacher et al. (see record 2013-06066-009). Readers of Rehabilitation Psychology might be surprised, or maybe even alarmed, to find an article on promoting physical activity in able-bodied people between the covers of their latest issue. This commentary contends that this area of research and practice might be one into which rehabilitation psychologists want to venture. Schumacher and coworkers describe a field test (N = 216) of a token system for reinforcing stair taking. The setting was an eight-story office building housing a single company in a midsized city in the southeastern United States. Schumacher et al. report an increase from 39 stair transactions per day by all study participants in the 6 months before implementation of the intervention to 301 transactions in the 6 months after the implementation of the intervention, which represents a 600% increase. The cost of the intervention was only $17 per person. Although replication of these results in a study with additional sources of control would increase confidence in the validity of the findings, the size of the gains in stair taking, the number of participants in the study, the length of the baseline and implementation periods, and the objective measurement of outcome warrant attention.

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

    PubMed Central

    Lindqvist, Anna-Karin; Kostenius, Catrine; Gard, Gunvor; Rutberg, Stina

    2015-01-01

    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. PMID:26282870

  15. Promotion of sink activity of developing rose shoots by light.

    PubMed

    Mor, Y; Halevy, A H

    1980-11-01

    Holding young rose shoots (Rosa hybrida cv. Marimba) in darkness while the rest of the plant was in light reduced the amount of (14)C assimilates recovered from the darkened shoot by half. Relative specific activity of the shoot tip grown in light was 13.5 times greater than that of the darkened one. The flower bud at the shoot tip degenerated in darkness and died. Shoots 2 to 3 centimeters long, after flower initiation, were most sensitive to the dark treatment. The degeneration is a gradual and reversible process in the first 8 days of darkness, followed by irreversible damage and atrophy. Darkening enhanced the ability of the young leaves to compete for the available assimilates over that of the darkened shoot tip. The enhancement of the mobilizing ability of the shoot tip by light is independent of photosynthesis since spraying with 3-(3,4-dichlorophenyl)-1,1-dimethylurea or holding shoots in a CO(2)-free atmosphere did not diminish the promoting effect of light on flower bud development or assimilate import. The possibility that light exerts its effect by photoproduction of ATP was also excluded inasmuch as no differences were found in ATP levels of shoot tips held in darkness and those held in light.

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

    PubMed

    Lindqvist, Anna-Karin; Kostenius, Catrine; Gard, Gunvor; Rutberg, Stina

    2015-01-01

    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.

  17. Halofuginone promotes satellite cell activation and survival in muscular dystrophies.

    PubMed

    Barzilai-Tutsch, Hila; Bodanovsky, Anna; Maimon, Hadar; Pines, Mark; Halevy, Orna

    2016-01-01

    Halofuginone is a leading agent in preventing fibrosis and inflammation in various muscular dystrophies. We hypothesized that in addition to these actions, halofuginone directly promotes the cell-cycle events of satellite cells in the mdx and dysf(-/-) mouse models of early-onset Duchenne muscular dystrophy and late-onset dysferlinopathy, respectively. In both models, addition of halofuginone to freshly prepared single gastrocnemius myofibers derived from 6-week-old mice increased BrdU incorporation at as early as 18h of incubation, as well as phospho-histone H3 (PHH3) and MyoD protein expression in the attached satellite cells, while having no apparent effect on myofibers derived from wild-type mice. BrdU incorporation was abolished by an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated protein kinase, suggesting involvement of this pathway in mediating halofuginone's effects on cell-cycle events. In cultures of myofibers and myoblasts isolated from dysf(-/-) mice, halofuginone reduced Bax and induced Bcl2 expression levels and induced Akt phosphorylation in a time-dependent manner. Addition of an inhibitor of the phosphinositide-3-kinase/Akt pathway reversed the halofuginone-induced cell survival, suggesting this pathway's involvement in mediating halofuginone's effects on survival. Thus, in addition to its known role in inhibiting fibrosis and inflammation, halofuginone plays a direct role in satellite cell activity and survival in muscular dystrophies, regardless of the mutation. These actions are of the utmost importance for improving muscle pathology and function in muscular dystrophies.

  18. Apolipoprotein A-I configuration and cell cholesterol efflux activity of discoidal lipoproteins depend on the reconstitution process.

    PubMed

    Cuellar, Luz Ángela; Prieto, Eduardo Daniel; Cabaleiro, Laura Virginia; Garda, Horacio Alberto

    2014-01-01

    Discoidal high-density lipoproteins (D-HDL) are critical intermediates in reverse cholesterol transport. Most of the present knowledge of D-HDL is based on studies with reconstituted lipoprotein complexes of apolipoprotein A-I (apoA-I) obtained by cholate dialysis (CD). D-HDL can also be generated by the direct microsolubilization (DM) of phospholipid vesicles at the gel/fluid phase transition temperature, a process mechanistically similar to the "in vivo" apoAI lipidation via ABCA1. We compared the apoA-I configuration in D-HDL reconstituted with dimyristoylphosphatidylcholine by both procedures using fluorescence resonance energy transfer measurements with apoA-I tryptophan mutants and fluorescently labeled cysteine mutants. Results indicate that apoA-I configuration in D-HDL depends on the reconstitution process and are consistent with a "double belt" molecular arrangement with different helix registry. As reported by others, a configuration with juxtaposition of helices 5 of each apoAI monomer (5/5 registry) predominates in D-HDL obtained by CD. However, a configuration with helix 5 of one monomer juxtaposed with helix 2 of the other (5/2 registry) would predominate in D-HDL generated by DM. Moreover, we also show that the kinetics of cholesterol efflux from macrophage cultures depends on the reconstitution process, suggesting that apoAI configuration is important for this HDL function.

  19. Combining Health Promotion Classroom Lessons with Health Fair Activities

    ERIC Educational Resources Information Center

    Cooper, Leslie; Eliason, Kathy; True, Alexandra

    2004-01-01

    This article focuses on the important role of the school nurse in promoting healthy lifestyle choices through networking, resource identification, and working with community partners. "Everyone Is Healthy at Northeast" was a health promotion program designed and presented in two ways: classroom lessons and a health fair. There were interactive…

  20. Core promoter specificities of the Sp1 and VP16 transcriptional activation domains.

    PubMed Central

    Emami, K H; Navarre, W W; Smale, S T

    1995-01-01

    The core promoter compositions of mammalian protein-coding genes are highly variable; some contain TATA boxes, some contain initiator (Inr) elements, and others contain both or neither of these basal elements. The underlying reason for this heterogeneity remains a mystery, as recent studies have suggested that TATA-containing and Inr-containing core promoters direct transcription initiation by similar mechanisms and respond similarly to a wide variety of upstream activators. To analyze in greater detail the influence of core promoter structure on transcriptional activation, we compared activation by GAL4-VP16 and Sp1 through synthetic core promoters containing a TATA box, an Inr, or both TATA and Inr. Striking differences were found between the two activators, most notably in the relative strengths of the TATA/Inr and Inr core promoters: the TATA/Inr promoter was much stronger than the Inr promoter when transcription was activated by GAL4-VP16, but the strengths of the two promoters were more comparable when transcription was activated by Sp1. To define the domains of Sp1 responsible for efficient activation through an Inr, several Sp1 deletion mutants were tested as GAL4 fusion proteins. The results reveal that the glutamine-rich activation domains, which previously were found to interact with Drosophila TAF110, preferentially stimulate Inr-containing core promoters. In contrast, efficient activation through TATA appears to require additional domains of Sp1. These results demonstrate that activation domains differ in their abilities to function with specific core promoters, suggesting that the core promoter structure found in a given gene may reflect a preference of the regulators of that gene. Furthermore, the core promoter preference of an activation domain may be related to a specific mechanism of action, which may provide a functional criterion for grouping activation domains into distinct classes. PMID:7565743

  1. Apolipoprotein A-I inhibits the production of interleukin-1beta and tumor necrosis factor-alpha by blocking contact-mediated activation of monocytes by T lymphocytes.

    PubMed

    Hyka, N; Dayer, J M; Modoux, C; Kohno, T; Edwards, C K; Roux-Lombard, P; Burger, D

    2001-04-15

    Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), essential components in the pathogenesis of immunoinflammatory diseases, are strongly induced in monocytes by direct contact with stimulated T lymphocytes. This study demonstrates that adult human serum (HS) but not fetal calf or cord blood serum displays inhibitory activity toward the contact-mediated activation of monocytes by stimulated T cells, decreasing the production of both TNF-alpha and IL-1beta. Fractionation of HS and N-terminal microsequencing as well as electroelution of material subjected to preparative electrophoresis revealed that apolipoprotein A-I (apo A-I), a "negative" acute-phase protein, was the inhibitory factor. Functional assays and flow cytometry analyses show that high-density lipoprotein (HDL)-associated apo A-I inhibits contact-mediated activation of monocytes by binding to stimulated T cells, thus inhibiting TNF-alpha and IL-1beta production at both protein and messenger RNA levels. Furthermore, apo A-I inhibits monocyte inflammatory functions in peripheral blood mononuclear cells activated by either specific antigens or lectins without affecting cell proliferation. These results demonstrate a new anti-inflammatory activity of HDL-associated apo A-I that might have modulating functions in nonseptic conditions. Therefore, because HDL has been shown to bind and neutralize lipopolysaccharide, HDL appears to play an important part in modulating both acute and chronic inflammation. The novel anti-inflammatory function of apo A-I reported here might lead to new therapeutic approaches in inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, and atherosclerosis.

  2. Physical activity promotion in the health care system.

    PubMed

    Vuori, Ilkka M; Lavie, Carl J; Blair, Steven N

    2013-12-01

    Physical activity (PA) and exercise training (ET) have great potential in the prevention, management, and rehabilitation of a variety of diseases, but this potential has not been fully realized in clinical practice. The health care system (HCS) could do much more to support patients in increasing their PA and ET. However, counseling on ET is not used widely by the HCS owing partly to attitudes but mainly to practical obstacles. Extensive searches of MEDLINE, the Cochrane Library, the Database of Abstracts of Reviews of Effects, and ScienceDirect for literature published between January 1, 2000, and January 31, 2013, provided data to assess the critical characteristics of ET counseling. The evidence reveals that especially brief ET counseling is an efficient, effective, and cost-effective means to increase PA and ET and to bring considerable clinical benefits to various patient groups. Furthermore, it can be practiced as part of the routine work of the HCS. However, there is a need and feasible means to increase the use and improve the quality of ET counseling. To include PA and ET promotion as important means of comprehensive health care and disease management, a fundamental change is needed. Because exercise is medicine, it should be seen and dealt with in the same ways as pharmaceuticals and other medical interventions regarding the basic and continuing education and training of health care personnel and processes to assess its needs and to prescribe and deliver it, to reimburse the services related to it, and to fund research on its efficacy, effectiveness, feasibility, and interactions and comparability with other preventive, therapeutic, and rehabilitative modalities. This change requires credible, strong, and skillful advocacy inside the medical community and the HCS.

  3. Understanding the physical activity promotion behaviours of podiatrists: a qualitative study

    PubMed Central

    2013-01-01

    Background Health professionals are encouraged to play a part in reducing the health risks of physical inactivity. Little is known of the physical activity promotion practice behaviours of podiatrists. Methods We performed 20 semi-structured interviews with purposefully selected podiatrists to explore their physical activity promotion attitudes, beliefs, knowledge and practice. Transcribed interviews were coded using an iterative thematic approach to identify major themes and salient beliefs. Results Overall, the participants had a positive attitude to physical activity promotion, considering it a normal part of their role. They saw their role as giving information, encouraging activity and making recommendations, however in practice they were less inclined to follow up on recommendations, monitor activity levels or document the process. Their approach was generally opportunistic, informal and unstructured and the content of assessment and promotion dependent upon the presenting patient’s condition. Advice tended to be tailored to the patient’s capabilities and interests. They considered there are opportunities to promote physical activity during regular consultations, however, were more likely to do so in patients with chronic diseases such as diabetes. Main barriers to physical activity promotion included unreceptive and unmotivated patients as well as a lack of time, skills and resources. Conclusions Physical activity promotion appears feasible in podiatry practice in terms of opportunity and acceptability to practitioners, but there is scope for improvement. Strategies to improve promotion need to consider the major issues, barriers and opportunities as well as provide a more structured approach to physical activity promotion by podiatrists. PMID:24016671

  4. Inhibition of apolipoprotein A-I gene expression by obesity-associated endocannabinoids.

    PubMed

    Haas, Michael J; Mazza, Angela D; Wong, Norman C W; Mooradian, Arshag D

    2012-04-01

    Obesity is associated with increased serum endocannabinoid (EC) levels and decreased high-density lipoprotein cholesterol (HDLc). Apolipoprotein A-I (apo A-I), the primary protein component of HDL is expressed primarily in the liver and small intestine. To determine whether ECs regulate apo A-I gene expression directly, the effect of the obesity-associated ECs anandamide and 2-arachidonylglycerol on apo A-I gene expression was examined in the hepatocyte cell line HepG2 and the intestinal cell line Caco-2. Apo A-I protein secretion was suppressed nearly 50% by anandamide and 2-arachidonoylglycerol in a dose-dependent manner in both cell lines. Anandamide treatment suppressed both apo A-I mRNA and apo A-I gene promoter activity in both cell lines. Studies using apo A-I promoter deletion constructs indicated that repression of apo A-I promoter activity by anandamide requires a previously identified nuclear receptor binding site designated as site A. Furthermore, anandamide-treatment inhibited protein-DNA complex formation with the site A probe. Exogenous over expression of cannabinoid receptor 1 (CBR1) in HepG2 cells suppressed apo A-I promoter activity, while in Caco-2 cells, exogenous expression of both CBR1 and CBR2 could repress apo A-I promoter activity. The suppressive effect of anandamide on apo A-I promoter activity in Hep G2 cells could be inhibited by CBR1 antagonist AM251 but not by AM630, a selective and potent CBR2 inhibitor. These results indicate that ECs directly suppress apo A-I gene expression in both hepatocytes and intestinal cells, contributing to the decrease in serum HDLc in obese individuals.

  5. Coaches' Perceptions of French Sports Clubs: Health-Promotion Activities, Aims and Coach Motivation

    ERIC Educational Resources Information Center

    Van Hoye, Aurélie; Sarrazin, Philippe; Heuzé, Jean-Philippe; Kokko, Sami

    2015-01-01

    Background: Given the benefits of participating in sport, sports clubs have been recognised as health promoting organizations. To examine health-promotion activities in Finnish sports clubs, Kokko et al. developed a set of standards for health-promoting sports clubs (HPSC). Objective: The present study extends this line of research, by (1)…

  6. Queuine promotes antioxidant defence system by activating cellular antioxidant enzyme activities in cancer.

    PubMed

    Pathak, Chandramani; Jaiswal, Yogesh K; Vinayak, Manjula

    2008-04-01

    Constant generation of Reactive oxygen species (ROS) during normal cellular metabolism of an organism is generally balanced by similar rate of consumption by antioxidants. Imbalance between ROS production and antioxidant defense results in increased level of ROS causing oxidative stress which leads to promotion of malignancy. Queuine is a hyper modified base analogue of guanine, found at first anti-codon position of Q- family of tRNAs. These tRNAs are completely modified with respect to queuosine in terminally differentiated somatic cells, however hypomodification of Q-tRNAs is close association with cell proliferation. Q-tRNA modification is essential for normal development, differentiation and cellular functions. Queuine is a nutrient factor to eukaryotes. It is found to promote cellular antioxidant defense system and inhibit tumorigenesis. The activities of antioxidant enzymes like catalase, SOD, glutathione peroxidase and glutathione reductase are found to be low in Dalton's lymphoma ascites transplanted (DLAT) mouse liver compared to normal. However, exogenous administration of queuine to DLAT mouse improves the activities of antioxidant enzymes. The results suggest that queuine promotes antioxidant defense system by increasing antioxidant enzyme activities and in turn inhibits oxidative stress and tumorigenesis.

  7. Tissue-specific activity of the pro-opiomelanocortin gene promoter

    SciTech Connect

    Jeannotte, L.; Trifiro, M.A.; Plante, R.K.; Chamberland, M.; Drouin, J.

    1987-11-01

    The pro-opiomelanocortin (POMC) gene is specifically expressed in corticotroph cells of the anterior pituitary. To define the POMC promoter sequences responsible for tissue-specific expression, we assessed POMC promoter activity by gene transfer into POMC-expressing pituitary tumor cells (AtT-20) and fibroblast L cells. The rat POMC promoter was only efficiently utilized and correctly transcribed in AtT-20 cells. 5'-End deletion analysis revealed two promoter regions for activity in AtT-20 cells. When tested by fusion to a heterologuous promoter, DNA fragments corresponding to both regions exhibited tissue-specific activity, suggesting the presence of at least two tissue-specific DNA sequence elements within the promoter. In summary, POMC promoter sequences from -480 to -34 base pairs appear sufficient to mimic the specificity of anterior pituitary expression.

  8. An MDR1 promoter allele with higher promoter activity is common in clinically isolated strains of Candida albicans

    PubMed Central

    Bruzual, Igor

    2013-01-01

    In the opportunistic fungal pathogen Candida albicans, up-regulation of MDR1, encoding an efflux transporter, leads to increased resistance to the antifungal drug fluconazole. Antifungal resistance has been linked to several types of genetic change in C. albicans, including changes in genome structure, genetic alteration of the drug target, and overexpression of transporters. High-level over-expression of MDR1 is commonly mediated by mutation in a trans-acting factor, Mrr1p. This report describes a second mechanism that contributes to up-regulation of MDR1 expression. By analyzing the sequence of the MDR1 promoter region in fluconazole-resistant and fluconazole-susceptible strains, we identified sequence polymorphisms that defined two linkage groups, corresponding to the two alleles in the diploid genome. One of the alleles conferred higher MDR1 expression compared with the other allele. Strains in which both alleles were of the higher activity type were common in collections of clinically isolated strains while strains carrying only the less active allele were rare. As increased expression of MDR1 confers higher resistance to drugs, strains with the more active MDR1 promoter allele may grow or survive longer when exposed to drugs or other selective pressures, providing greater opportunity for mutations that confer high-level drug resistance to arise. Through this mechanism, higher activity alleles of the MDR1 promoter could promote the development of drug resistance. PMID:21972105

  9. The I.A.G. / A.I.G. SEDIBUD (Sediment Budgets in Cold Environments) Programme: Current and future activities

    NASA Astrophysics Data System (ADS)

    Beylich, Achim A.; Lamoureux, Scott; Decaulne, Armelle

    2013-04-01

    Projected climate change in cold regions is expected to alter melt season duration and intensity, along with the number of extreme rainfall events, total annual precipitation and the balance between snowfall and rainfall. Similarly, changes to the thermal balance are expected to reduce the extent of permafrost and seasonal ground frost and increase active layer depths. These effects will undoubtedly change surface environments in cold regions and alter the fluxes of sediments, nutrients and solutes, but the absence of quantitative data and coordinated geomorphic process monitoring and analysis to understand the sensitivity of the Earth surface environment is acute in cold climate environments. The International Association of Geomorphologists (I.A.G. / A.I.G. ) SEDIBUD (Sediment Budgets in Cold Environments) Programme was formed in 2005 to address this existing key knowledge gap. SEDIBUD currently has about 400 members worldwide and the Steering Committee of this international programme is composed of ten scientists from eight different countries: Achim A. Beylich (Chair) (Norway), Armelle Decaulne (Secretary) (France), John C. Dixon (USA), Scott F. Lamoureux (Vice-Chair) (Canada), John F. Orwin (Canada), Jan-Christoph Otto (Austria), Irina Overeem (USA), Thorsteinn Sæmundsson (Iceland), Jeff Warburton (UK) and Zbigniew Zwolinski (Poland). The central research question of this global group of scientists is to: Assess and model the contemporary sedimentary fluxes in cold climates, with emphasis on both particulate and dissolved components. Initially formed as European Science Foundation (ESF) Network SEDIFLUX (Sedimentary Source-to-Sink Fluxes in Cold Environments) (2004 - ), SEDIBUD has further expanded to a global group of researchers with field research sites located in polar and alpine regions in the northern and southern hemisphere. Research carried out at each of the close to 50 defined SEDIBUD key test sites varies by programme, logistics and available

  10. Redesign of MST enzymes to target lyase activity instead promotes mutase and dehydratase activities.

    PubMed

    Meneely, Kathleen M; Luo, Qianyi; Lamb, Audrey L

    2013-11-01

    The isochorismate and salicylate synthases are members of the MST family of enzymes. The isochorismate synthases establish an equilibrium for the conversion chorismate to isochorismate and the reverse reaction. The salicylate synthases convert chorismate to salicylate with an isochorismate intermediate; therefore, the salicylate synthases perform isochorismate synthase and isochorismate-pyruvate lyase activities sequentially. While the active site residues are highly conserved, there are two sites that show trends for lyase-activity and lyase-deficiency. Using steady state kinetics and HPLC progress curves, we tested the "interchange" hypothesis that interconversion of the amino acids at these sites would promote lyase activity in the isochorismate synthases and remove lyase activity from the salicylate synthases. An alternative, "permute" hypothesis, that chorismate-utilizing enzymes are designed to permute the substrate into a variety of products and tampering with the active site may lead to identification of adventitious activities, is tested by more sensitive NMR time course experiments. The latter hypothesis held true. The variant enzymes predominantly catalyzed chorismate mutase-prephenate dehydratase activities, sequentially generating prephenate and phenylpyruvate, augmenting previously debated (mutase) or undocumented (dehydratase) adventitious activities.

  11. Redesign of MST enzymes to target lyase activity instead promotes mutase and dehydratase activities

    PubMed Central

    Meneely, Kathleen M.; Luo, Qianyi; Lamb, Audrey L.

    2013-01-01

    The isochorismate and salicylate synthases are members of the MST family of enzymes. The isochorismate synthases establish an equilibrium for the conversion chorismate to isochorismate and the reverse reaction. The salicylate synthases convert chorismate to salicylate with an isochorismate intermediate; therefore, the salicylate synthases perform isochorismate synthase and isochorismate-pyruvate lyase activities sequentially. While the active site residues are highly conserved, there are two sites that show trends for lyase-activity and lyase-deficiency. Using steady state kinetics and HPLC progress curves, we tested the “interchange” hypothesis that interconversion of the amino acids at these sites would promote lyase activity in the isochorismate synthases and remove lyase activity from the salicylate synthases. An alternative, “permute” hypothesis, that chorismate-utilizing enzymes are designed to permute the substrate into a variety of products and tampering with the active site may lead to identification of adventitious activities, is tested by more sensitive NMR time course experiments. The latter hypothesis held true. The variant enzymes predominantly catalyzed chorismate mutase-prephenate dehydratase activities, sequentially generating prephenate and phenylpyruvate, augmenting previously debated (mutase) or undocumented (dehydratase) adventitious activities. PMID:24055536

  12. Flying the "Active School Flag": Physical Activity Promotion through Self-Evaluation in Primary Schools in Ireland

    ERIC Educational Resources Information Center

    Chroinin, Deirdre Ni; Murtagh, Elaine; Bowles, Richard

    2012-01-01

    Primary schools are key sites where children can be active, advance their knowledge and understanding of how to participate in physical activity (PA) and develop an appreciation of its importance in their lives. This study explored the role of schools in promoting PA asking: how do primary schools approach the promotion of whole-school PA? Data…

  13. The Role of Physical Educators in Helping Classroom Teachers to Promote Physical Activity

    ERIC Educational Resources Information Center

    Russ, Laura

    2015-01-01

    Elementary classroom teachers are an increasingly important constituency in school-based physical activity promotion. This article situates the need for classroom teacher physical-activity promotion at the intersection of what we know about teacher actions, what informs those actions, and what recent research has uncovered. Recommendations are…

  14. Adapting a Community-Based Physical Activity Promotion Program for Rural, Diverse Youth

    ERIC Educational Resources Information Center

    Colquitt, Gavin; Walker, Ashley; Alfonso, Moya

    2014-01-01

    With school-aged youth spending less time in physical education, school-community-university partnerships offer potential to promote physical activity among school-aged youth. The VERB™ Summer Scorecard (VSS) program was designed in Lexington, Kentucky, to promote physical activity among "tweens" (8- to 13-year-olds). VSS since has been…

  15. Promoting Physical Activity in Secondary Schools: Growing Expectations, "Same Old" Issues?

    ERIC Educational Resources Information Center

    Cale, Lorraine; Harris, Jo; Duncombe, Rebecca

    2016-01-01

    There are growing expectations on schools to promote health and physical activity and helping schools to effectively do so is considered a priority. This paper reports on selected findings from a research project that was concerned with supporting secondary schools in the effective promotion of physical activity and establishing their needs in…

  16. Promoting Diversity through Multilevel Activism: An Organizational Approach

    ERIC Educational Resources Information Center

    McHatton, Patricia Alvarez; Shircliffe, Barbara J.; Cobb-Roberts, Deirdre

    2011-01-01

    The National Council for Accreditation of Teacher Education (NCATE) was founded in 1954 to serve as an independent body in promoting high quality teacher preparation programs. Its mission is to ensure accredited institutions produce high quality educators, administrators, and specialists able to meet the needs of all learners. Institutions seeking…

  17. Heterologous activation of the Porphyra tenera HSP70 promoter in Bangiophycean algal cells.

    PubMed

    Hirata, Ryo; Jeong, Won-Joong; Saga, Naotsune; Mikami, Koji

    2011-01-01

    Porphyra has attracted great attention for its biological and industrial importance. However, establishment of a stable nuclear transformation has not yet been achieved in these organisms, which impedes the molecular biological study and the development of a molecular breeding method for them. Toward establishing the stable transformation, we have recently developed an efficient transient gene expression system in Bangiophycean algae, in which the HSP70 promoter from P. tenera (PtHSP70 promoter) was activated heterologously in P. yezoensis cells. Since heterologous promoters are required for homologous recombination-based stable transformation, the identification of heterologously activated promoters is important in establishing a stable transformation system in individual Bangiophycean alga. We here examined the activation of the PtHSP70 promoter using the GC-rich PyGUS reporter system in additional Porphyra and Bangia species. The results indicated that this promoter drove expression of the PyGUS gene efficiently in all examined algae, whereas there was quite low expression of PyGUS by the cauliflower mosaic virus 35S promoter that is widely used as a heterologous promoter in the transformation of green land plants. Therefore, heterologous activation of the PtHSP70 promoter could promote the establishment of the stable transformation system in various kinds of Bangiophycean algae.

  18. Berberine promotes glucose consumption independently of AMP-activated protein kinase activation.

    PubMed

    Xu, Miao; Xiao, Yuanyuan; Yin, Jun; Hou, Wolin; Yu, Xueying; Shen, Li; Liu, Fang; Wei, Li; Jia, Weiping

    2014-01-01

    Berberine is a plant alkaloid with anti-diabetic action. Activation of AMP-activated protein kinase (AMPK) pathway has been proposed as mechanism for berberine's action. This study aimed to examine whether AMPK activation was necessary for berberine's glucose-lowering effect. We found that in HepG2 hepatocytes and C2C12 myotubes, berberine significantly increased glucose consumption and lactate release in a dose-dependent manner. AMPK and acetyl coenzyme A synthetase (ACC) phosphorylation were stimulated by 20 µmol/L berberine. Nevertheless, berberine was still effective on stimulating glucose utilization and lactate production, when the AMPK activation was blocked by (1) inhibition of AMPK activity by Compound C, (2) suppression of AMPKα expression by siRNA, and (3) blockade of AMPK pathway by adenoviruses containing dominant-negative forms of AMPKα1/α2. To test the effect of berberine on oxygen consumption, extracellular flux analysis was performed in Seahorse XF24 analyzer. The activity of respiratory chain complex I was almost fully blocked in C2C12 myotubes by berberine. Metformin, as a positive control, showed similar effects as berberine. These results suggest that berberine and metformin promote glucose metabolism by stimulating glycolysis, which probably results from inhibition of mitochondrial respiratory chain complex I, independent of AMPK activation.

  19. Active Kids Active Minds: A Physical Activity Intervention to Promote Learning?

    ERIC Educational Resources Information Center

    lisahunter; Abbott, Rebecca; Macdonald, Doune; Ziviani, Jennifer; Cuskelly, Monica

    2014-01-01

    This study assessed the feasibility and impact of introducing a programme of an additional 30 minutes per day of moderate physical activity within curriculum time on learning and readiness to learn in a large elementary school in south-east Queensland, Australia. The programme, Active Kids Active Minds (AKAM), involved Year 5 students (n = 107),…

  20. nifH promoter activity is regulated by DNA supercoiling in Sinorhizobium meliloti.

    PubMed

    Liu, Yan-Jie; Hu, Biao; Zhu, Jia-Bi; Shen, Shan-Jiong; Yu, Guan-Qiao

    2005-04-01

    In prokaryotes, DNA supercoiling regulates the expression of many genes; for example, the expression of Klebsiella pneumoniae nifLA operon depends on DNA negative supercoiling in anaerobically grown cells, which indicates that DNA supercoiling might play a role in gene regulation of the anaerobic response. Since the expression of the nifH promoter in Sinorhizobium meliloti is not repressed by oxygen, it is proposed that the status of DNA supercoiling may not affect the expression of the nifH promoter. We tested this hypothesis by analyzing nifH promoter activity in wild-type and gyr- Escherichia coli in the presence and absence of DNA gyrase inhibitors. Our results show that gene expression driven by the S. meliloti nifH promoter requires the presence of active DNA gyrase. Because DNA gyrase increases the number of negative superhelical turns in DNA in the presence of ATP, our data indicate that negative supercoiling is also important for nifH promoter activity. Our study also shows that the DNA supercoiling-dependent S. meliloti nifH promoter activity is related to the trans-acting factors NtrC and NifA that activate it. DNA supercoiling appeared to have a stronger effect on NtrC-activated nifH promoter activity than on NifA-activated promoter activity. Collectively, these results from the S. meliloti nifH promoter model system seem to indicate that, in addition to regulating gene expression during anaerobic signaling, DNA supercoiling may also provide a favorable topology for trans-acting factor binding and promoter activation regardless of oxygen status.

  1. Ino80 promotes cervical cancer tumorigenesis by activating Nanog expression

    PubMed Central

    Hu, Jing; Liu, Jie; Chen, Aozheng; Lyu, Jia; Ai, Guihai; Zeng, Qiongjing; Sun, Yi; Chen, Chunxia; Wang, Jinbo; Qiu, Jin; Wu, Yi; Cheng, Jiajing; Shi, Xiujuan; Song, Liwen

    2016-01-01

    Ino80 ATPase is an integral component of the INO80 ATP-dependent chromatin-remodeling complex, which regulates transcription, DNA repair and replication. We found that Ino80 was highly expressed in cervical cancer cell lines and tumor samples. Ino80 knockdown inhibited cervical cancer cell proliferation, induced G0/G1 phase cell cycle arrest in vitro and suppressed tumor growth in vivo. However, Ino80 knockdown did not affect cell apoptosis, migration or invasion in vitro. Ino80 overexpression promoted proliferation in the H8 immortalized cervical epithelial cell line, which has low endogenous Ino80 expression as compared to cervical cancer cell lines. Ino80 bound to the Nanog transcription start site (TSS) and enhanced its expression in cervical cancer cells. Nanog overexpression in Ino80 knockdown cell lines promoted cell proliferation. This study demonstrated for the first time that Ino80 was upregulated in cervical cancer and promoted cell proliferation and tumorigenesis. Our findings suggest that Ino80 may be a potential therapeutic target for the treatment of cervical cancer. PMID:27750218

  2. Crx activates opsin transcription by recruiting HAT-containing co-activators and promoting histone acetylation

    PubMed Central

    Peng, Guang-Hua; Chen, Shiming

    2008-01-01

    The homeodomain transcription factor Crx is required for expression of many photoreceptor genes in the mammalian retina. The mechanism by which Crx activates transcription remains to be determined. Using protein–protein interaction assays, Crx was found to interact with three co-activator proteins (complexes): STAGA, Cbp and p300, all of which possess histone acetyl-transferase (HAT) activity. To determine the role of Crx–HAT interactions in target gene chromatin modification and transcriptional activation, quantitative RT–PCR and chromatin immunoprecipitation were performed on Crx target genes, rod and cone opsins, in developing mouse retina. Although cone opsins are transcribed earlier than rhodopsin during development, the transcription of each gene is preceded by the same sequence of events in their promoter and enhancer regions: (i) binding of Crx, followed by (ii) binding of HATs, (iii) the acetylation of histone H3, then (iv) binding of other photoreceptor transcription factors (Nrl and Nr2e3) and RNA polymerase II. In Crx knockout mice (Crx−/−), the association of HATs and AcH3 with target promoter/enhancer regions was significantly decreased, which correlates with aberrant opsin transcription and photoreceptor dysfunction in these mice. Similar changes to the opsin chromatin were seen in Y79 retinoblastoma cells, where opsin genes are barely transcribed. These defects in Y79 cells can be reversed by expressing a recombinant Crx or applying histone deacetylase inhibitors. Altogether, these results suggest that one mechanism for Crx-mediated transcriptional activation is to recruit HATs to photoreceptor gene chromatin for histone acetylation, thereby inducing and maintaining appropriate chromatin configurations for transcription. PMID:17656371

  3. Activation of geminivirus V-sense promoters in roots is restricted to nematode feeding sites.

    PubMed

    Escobar, Carolina; García, Alejandra; Aristizábal, Fabio; Portillo, Mary; Herreros, Esther; Munoz-Martín, M Angeles; Grundler, Florian; Mullineaux, Phillip M; Fenoll, Carmen

    2010-05-01

    Obligate sedentary endoparasitic nematodes, such as the root-knot and cyst nematodes, elicit the differentiation of specialized nematode nurse or feeding cells [nematode feeding sites (NFS), giant cells and syncytia, respectively]. During NFS differentiation, marked changes in cell cycle progression occur, partly similar to those induced by some geminiviruses. In this work, we describe the activation of V-sense promoters from the Maize streak virus (MSV) and Wheat dwarf virus (WDV) in NFS formed by root-knot and cyst nematodes. Both promoters were transiently active in microinjection experiments. In tobacco and Arabidopsis transgenic lines carrying promoter-beta-glucuronidase fusions, the MSV V-sense promoter was activated in the vascular tissues of aerial plant parts, primarily leaf and cotyledon phloem tissue and some floral structures. Interestingly, in roots, promoter activation was restricted to syncytia and giant cells tested with four different nematode populations, but undetectable in the rest of the root system. As the activity of the promoter in transgenic rootstocks should be restricted to NFS only, the MSV promoter may have utility in engineering grafted crops for nematode control. Therefore, this study represents a step in the provision of some of the much needed additional data on promoters with restricted activation in NFS useful in biotechnological nematode control strategies.

  4. Promoting Physical Activity: Addressing Barriers and Moving Forward

    ERIC Educational Resources Information Center

    Beighle, Aaron; Morrow, James R.

    2014-01-01

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

  5. Using Learning Styles Inventories To Promote Active Learning.

    ERIC Educational Resources Information Center

    Fritz, Margaret

    2002-01-01

    Defines active learning as students actively involved in the learning process. Suggests that to learn actively, students need to know their learning styles and engage with the subject matter. Concludes that students who know their learning styles and are allowed to choose time management methods, note-taking systems, textbook marking methods and…

  6. International Approaches to Whole-of-School Physical Activity Promotion

    ERIC Educational Resources Information Center

    McMullen, Jaimie; Ní Chróinín, Déirdre; Tammelin, Tuija; Pogorzelska, Malgorzata; van der Mars, Hans

    2015-01-01

    Increasing physical activity opportunities in schools has emerged as a global priority among school-aged youth. As a result, many countries have designed and implemented whole-of-school physical activity initiatives that seek to increase physical activity opportunities that are available to school-aged children before, during, and after school.…

  7. Health Promotion Activity Book for Grades 4-6.

    ERIC Educational Resources Information Center

    Ohio State Dept. of Health, Columbus.

    This book of activities is designed to supplement health lessons for students in grades 4-6. Some of the activities are quite simple and require very little instruction and direction, while others are more difficult and require careful explanation prior to completion. The level of difficulty of the activities is varied in order to create both…

  8. School-Based Health Promotion Initiative Increases Children's Physical Activity

    ERIC Educational Resources Information Center

    Cluss, Patricia; Lorigan, Devin; Kinsky, Suzanne; Nikolajski, Cara; McDermott, Anne; Bhat, Kiran B.

    2016-01-01

    Background: Childhood obesity increases health risk, and modest physical activity can impact that risk. Schools have an opportunity to help children become more active. Purpose: This study implemented a program offering extra school-day activity opportunities in a rural school district where 37% of students were obese or overweight in 2005 and…

  9. National level promotion of physical activity: results from England's ACTIVE for LIFE campaign

    PubMed Central

    Hillsdon, M; Cavill, N; Nanchahal, K; Diamond, A; White, I

    2001-01-01

    STUDY OBJECTIVE—To assess the impact of a national campaign on awareness of the campaign, change in knowledge of physical activity recommendations and self reported physical activity.
DESIGN—three year prospective longitudinal survey using a multi-stage, cluster random probability design to select participants.
SETTING—England.
PARTICIPANTS—A nationally representative sample of 3189 adults aged 16-74 years.
MAIN OUTCOME MEASURES—Awareness of the advertising element of the campaign, changes in knowledge of physical activity recommendations for health and self reported physical activity.
RESULTS—38% of participants were aware of the main advertising images, assessed six to eight months after the main television advertisement. The proportion of participants knowledgeable about moderate physical activity recommendations increased by 3.0% (95% CI: 1.4%, 4.5%) between waves 1 and 2 and 3.7% (95% CI: 2.1%, 5.3%) between waves 1 and 3. The change in proportion of active people between baseline and waves 1 and 2 was
−0.02 (95% CI: −2.0 to +1.7) and between waves 1 and 3 was −9.8 (−7.9 to −11.7).
CONCLUSION—The proportion of participants who were knowledgeable about the new recommendations, increased significantly after the campaign. There was however, no significant difference in knowledge by awareness of the main campaign advertisement. There is no evidence that ACTIVE for LIFE improved physical activity, either overall or in any subgroup.


Keywords: exercise; mass media; follow up studies; health promotion; physical activity PMID:11553661

  10. Site-directed mutagenesis of the Klebsiella pneumoniae nifL and nifH promoters and in vivo analysis of promoter activity.

    PubMed Central

    Buck, M; Khan, H; Dixon, R

    1985-01-01

    The role of conserved nucleotides in nitrogen-fixation promoter function has been examined using both oligonucleotide and chemical mutagenesis to introduce base changes in the Klebsiella pneumoniae nifL and nifH promoters. Among ten mutations analysed, including six spontaneous mutations, base changes at -12, -13, -14, and -26, located in previously identified conserved sequences, perturbed the activity of the promoters, demonstrating that these sequences are required for transcription. Not all base changes produced similar strong promoter down phenotypes when the nifL and nifH promoters were compared: activation of the nifH promoter by the nifA gene product was less sensitive to base changes in conserved nucleotides than was activation of the equivalently altered nifL promoter by the nifA or ntrC products. We have found that the nifH promoter can be weakly activated by the ntrC product; this activation shows the same down response to base changes seen with ntrC activation of the nifL promoter. We present evidence that the efficient activation of the nifH promoter by nifA (but not ntrC) can be attributed to specific upstream sequences present in the nifH promoter. PMID:3906564

  11. [Evaluation of the effectiveness of home-based physical activity promotion by community health workers].

    PubMed

    Costa, Evelyn Fabiana; Andrade, Douglas Roque; Garcia, Leandro Martin Totaro; Ribeiro, Evelyn Helena Corgosinho; Santos, Taynã Ishi dos; Florindo, Alex Antonio

    2015-10-01

    This study analyzed the effectiveness of physical activity promotion by community health workers (CHW) during home visits. This was a non-randomized controlled trial that lasted six months, with one group of CHW that received training to promote physical activity during home visits among users of the Brazilian Unified National Health System (SUS) and a control group. Physical activity and stages of behavior change were evaluated in 176 adults (n = 90 in the intervention group and n = 86 in the control group) assisted by the CHW. Associations, prevalence ratios, and generalized estimate equations were conducted to verify differences between groups. No evidence of differences in physical activity and stages of behavior change were observed between the two groups. CHW from the intervention group conducted more home visits promoting physical activity among elders, those with low schooling, unemployed, and those with chronic diseases. It is important to reassess the work and priorities of CHW to expand physical activity promotion under the SUS.

  12. Chinese Tobacco Industry Promotional Activity on the Microblog Weibo

    PubMed Central

    Wang, Fan; Zheng, Pinpin; Yang, Dongyun; Freeman, Becky; Fu, Hua; Chapman, Simon

    2014-01-01

    Background Although China ratified the WHO Framework Convention on Tobacco Control [FCTC] in 2005, the partial ban on tobacco advertising does not cover the internet. Weibo is one of the most important social media channels in China, using a format similar to its global counterpart, Twitter. The Weibo homepage is a platform to present products, brands and corporate culture. There is great potential for the tobacco industry to exploit Weibo to promote products. Methods Seven tobacco industry Weibo accounts that each had more than 5000 fans were selected to examine the content of Weibos established by tobacco companies or their advertising agents. Results Of the 12073 posts found on the seven accounts, 92.3% (11143) could be classified into six main themes: traditional culture, popular culture, social and business affairs, advertisement, public relations and tobacco culture. Posts under the theme of popular culture accounted for about half of total posts (49%), followed by ‘advertisement’ and ‘tobacco culture’ (both at 12%), ‘traditional culture’ and ‘public relations’ (both at 11%), and finally ‘social and business affairs’ (5%). 33% of posts included the words ‘cigarette’ or ‘smoking’ and 53% of posts included the tobacco brand name, indicating that tobacco companies carefully construct the topic and content of posts. Conclusions Weibo is an important new online marketing tool for the Chinese tobacco industry. Tobacco industry use of Weibo to promote brands and normalize smoking subverts China's ratification of the WHO FCTC. Policy to control tobacco promotion needs reforming to address this widespread circumvention of China's tobacco advertising ban. PMID:24914739

  13. Lack of knowledge of physical activity guidelines: can physical activity promotion campaigns do better?

    PubMed Central

    Knox, Emily C L; Esliger, Dale W; Biddle, Stuart J H; Sherar, Lauren B

    2013-01-01

    . Although knowledge of physical activity guidelines appears to have increased in recent years demographic disparities are still evident. Efforts are needed to promote health information among these groups. PMID:24319271

  14. Krüppel like factor 4 promoter undergoes active demethylation during monocyte/macrophage differentiation.

    PubMed

    Karpurapu, Manjula; Ranjan, Ravi; Deng, Jing; Chung, Sangwoon; Lee, Yong Gyu; Xiao, Lei; Nirujogi, Teja Srinivas; Jacobson, Jeffrey R; Park, Gye Young; Christman, John W

    2014-01-01

    The role of different lineage specific transcription factors in directing hematopoietic cell fate towards myeloid lineage is well established but the status of epigenetic modifications has not been defined during this important developmental process. We used non proliferating, PU.1 inducible myeloid progenitor cells and differentiating bone marrow derived macrophages to study the PU.1 dependent KLF4 transcriptional regulation and its promoter demethylation during monocyte/macrophage differentiation. Expression of KLF4 was regulated by active demethylation of its promoter and PU.1 specifically bound to KLF4 promoter oligo harboring the PU.1 consensus sequence. Methylation specific quantitative PCR and Bisulfite sequencing indicated demethylation of CpG residues most proximal to the transcription start site of KLF4 promoter. Cloned KLF4 promoter in pGL3 Luciferase and CpG free pcpgf-bas vectors showed accentuated reporter activity when co-transfected with the PU.1 expression vector. In vitro methylation of both KLF4 promoter oligo and cloned KLF4 promoter vectors showed attenuated in vitro DNA binding activity and Luciferase/mouse Alkaline phosphotase reporter activity indicating the negative influence of KLF4 promoter methylation on PU.1 binding. The Cytosine deaminase, Activation Induced Cytidine Deaminase (AICDA) was found to be critical for KLF4 promoter demethylation. More importantly, knock down of AICDA resulted in blockade of KLF4 promoter demethylation, decreased F4/80 expression and other phenotypic characters of macrophage differentiation. Our data proves that AICDA mediated active demethylation of the KLF4 promoter is necessary for transcriptional regulation of KLF4 by PU.1 during monocyte/macrophage differentiation.

  15. Staff's perceptions of the use of evidence-based physical activity promotion strategies for promoting girls' physical activity at afterschool programs: a qualitative study.

    PubMed

    Dinkel, Danae; Huberty, Jennifer; Beets, Michael; Tibbits, Melissa

    2014-08-01

    There is a need to improve girls' physical activity (PA) in afterschool programs as girls' PA levels are consistently lower than boys'. An evidence-based professional development framework, the 5 Ms, has been effective in helping staff to improve PA in both girls and boys but further improvements in girls' PA are needed. Little is known about staff's perceptions of using PA promotion strategies to promote girls' PA. Therefore, the purpose of this study was to explore staff perceptions of the use of evidence-based PA promotion strategies for promoting PA in girls. Semi-structured interviews were conducted with staff from three community-based afterschool programs located within a school setting (n=18). Data were analyzed using the process of immersion/crystallization. A majority of staff had some knowledge of PA promotion strategies but few staff consistently utilized these strategies and a majority felt several strategies were unnecessary (i.e., having a PA policy). Newer staff reported depending on senior staff to promote PA in girls. Overall, findings suggest that staff's perceptions may impact their use of PA promotions strategies. The results of this study will contribute to the enhancement of an existing staff training framework (the 5 Ms) to improve girls' PA in afterschool programs.

  16. Mutational analysis of the lac regulatory region: second-site changes that activate mutant promoters.

    PubMed Central

    Rothmel, R K; LeClerc, J E

    1989-01-01

    Second-site mutations that restored activity to severe lacP1 down-promoter mutants were isolated. This was accomplished by using a bacteriophage f1 vector containing a fusion of the mutant E. coli lac promoters with the structural gene for chloramphenicol acetyltransferase (CAT), so that a system was provided for selecting phage revertants (or pseudorevertants) that conferred resistance of phage-infected cells to chloramphenicol. Among the second-site changes that relieved defects in mutant lac promoters, the only one that restored lacP1 activity was a T----G substitution at position -14, a weakly conserved site in E. coli promoters. Three other sequence changes, G----A at -2, A----T at +1, and C----A at +10, activated nascent promoters in the lac regulatory region. The nascent promoters conformed to the consensus rule, that activity is gained by sequence changes toward homology with consensus sequences at the -35 and -10 regions of the promoter. However, the relative activities of some promoters cannot be explained solely by consideration of their conserved sequence elements. Images PMID:2660105

  17. Promoting Female Students' Learning Motivation towards Science by Exercising Hands-On Activities

    ERIC Educational Resources Information Center

    Wen-jin, Kuo; Chia-ju, Liu; Shi-an, Leou

    2012-01-01

    The purpose of this study is to design different hands-on science activities and investigate which activities could better promote female students' learning motivation towards science. This study conducted three types of science activities which contains nine hands-on activities, an experience scale and a learning motivation scale for data…

  18. Barriers to physical activity promotion by general practitioners and practice nurses

    PubMed Central

    McKenna, J.; Naylor, P. J.; McDowell, N.

    1998-01-01

    OBJECTIVE: To examine the promotion of physical activity by general practitioners (GPs) and practice nurses (PNs). METHODS: A questionnaire that examined the types of barriers and the levels of their influence as well as stage of change for activity promotion and for personal behaviour was mailed to 846 subjects. RESULTS: The return rate exceeded 70% in each group with a high proportion (69%) of GPs and PNs reporting that they regularly promote physical activity with their patients. GPs were less likely to regularly promote physical activity with their patients if they indicated lack of time as a barrier (odds ratio (OR) = 0.73, 95% confidence interval (CI) 0.58 to 0.93) or lack of incentives (OR = 0.74, 95% CI 0.59 to 0.94), and more likely to promote exercise if they themselves were regular exercisers (OR = 3.19, 95% CI 1.96 to 5.18). However, for PNs longer consultation times (by 1.5 to 2 minutes) had a higher likelihood of producing regular promotion of activity (OR = 1.61, 95% CI 1.02 to 1.62). For PNs personal physical activity stage was the strongest significant predictor of promotion level, but with a stronger effect (OR = 4.77, 95% CI 1.48 to 15.35) than in the GPs. CONCLUSION: The main finding is that GPs in the action or maintenance stage of changing their own physical activity are three times more likely to regularly promote the same behaviour in their patients than those in the other stages; for PNs the same difference quadruples the likelihood of them promoting physical activity. Professional readiness to change is influenced by known system barriers in GPs, and not in PNs, but is more strongly predicted by personal physical activity behaviour in both groups. 


 PMID:9773175

  19. Promoting Healthy Lifestyle Behaviors: The Heart Smart Discussion Activity

    ERIC Educational Resources Information Center

    McCalla, Judith R.; Juarez, Cheryl L.; Williams, Lucia E.; Brown, Judy; Chipungu, Katie; Saab, Patrice G.

    2012-01-01

    The health habits of high school students affect not only their current health but also their future risk for obesity and cardiovascular disease. The "Heart Smart Discussion Activity" was developed to provide information about heart health, good nutrition, physical activity, and stress management. It encourages students to discuss…

  20. Videogames to Promote Physical Activity in Older Adults with Schizophrenia.

    PubMed

    Leutwyler, Heather; Hubbard, Erin M; Vinogradov, Sophia; Dowling, Glenna A

    2012-10-01

    Older adults with schizophrenia need physical activity interventions to improve their physical health. The purpose of this report is to describe the preliminary acceptability of a videogame-based physical activity program using the Kinect™ for Xbox 360 game system (Microsoft, Redmond, WA) in older adults with schizophrenia.

  1. Promoting Physical Activity and Exercise among Children. ERIC Digest.

    ERIC Educational Resources Information Center

    Summerfield, Liane M.

    This Digest discusses the importance of and ways to foster activity and exercise in children. Following an introduction, the Digest is organized into four sections. The first section deals with the significant health benefits of physical activity, including: reduction in chronic disease risk; lowered risk of colon cancer; increase in bone density;…

  2. Use of SPARK to Promote After-School Physical Activity

    ERIC Educational Resources Information Center

    Herrick, Heidi; Thompson, Hannah; Kinder, Jennifer; Madsen, Kristine A.

    2012-01-01

    Background: The after-school period is potentially an important venue for increasing physical activity for youth. We sought to assess the effectiveness of the Sports, Play, and Recreation for Youth (SPARK) program to increase physical activity and improve cardiorespiratory fitness and weight status among elementary students after school. Methods:…

  3. Promoting Physical Activity through Student Life and Academics

    ERIC Educational Resources Information Center

    McDaniel, Tyler; Melton, Bridget F.; Langdon, Jody

    2014-01-01

    Objective: A physical activity passport (PAP) was developed to increase student's physical activity through the collaboration of student life and academics. The purpose was to measure the effectiveness of the PAP. Design: The research design used was a quantitative, descriptive, quasi-experimental design with experimental and control groups.…

  4. A novel baculovirus-derived promoter with high activity in the baculovirus expression system

    PubMed Central

    Martínez-Solís, María; Gómez-Sebastián, Silvia; Escribano, José M.; Jakubowska, Agata K.

    2016-01-01

    The baculovirus expression vector system (BEVS) has been widely used to produce a large number of recombinant proteins, and is becoming one of the most powerful, robust, and cost-effective systems for the production of eukaryotic proteins. Nevertheless, as in any other protein expression system, it is important to improve the production capabilities of this vector. The orf46 viral gene was identified among the most highly abundant sequences in the transcriptome of Spodoptera exigua larvae infected with its native baculovirus, the S. exigua multiple nucleopolyhedrovirus (SeMNPV). Different sequences upstream of the orf46 gene were cloned, and their promoter activities were tested by the expression of the GFP reporter gene using the Autographa californica nucleopolyhedrovirus (AcMNPV) vector system in different insect cell lines (Sf21, Se301, and Hi5) and in larvae from S. exigua and Trichoplusia ni. The strongest promoter activity was defined by a 120 nt sequence upstream of the ATG start codon for the orf46 gene. On average, GFP expression under this new promoter was more than two fold higher than the expression obtained with the standard polyhedrin (polh) promoter. Additionally, the orf46 promoter was also tested in combination with the polh promoter, revealing an additive effect over the polh promoter activity. In conclusion, this new characterized promoter represents an excellent alternative to the most commonly used baculovirus promoters for the efficient expression of recombinant proteins using the BEVS. PMID:27375973

  5. Promoting Physical Activity through Hand-Held Computer Technology

    PubMed Central

    King, Abby C.; Ahn, David K.; Oliveira, Brian M.; Atienza, Audie A.; Castro, Cynthia M.; Gardner, Christopher D.

    2009-01-01

    Background Efforts to achieve population-wide increases in walking and similar moderate-intensity physical activities potentially can be enhanced through relevant applications of state-of-the-art interactive communication technologies. Yet few systematic efforts to evaluate the efficacy of hand-held computers and similar devices for enhancing physical activity levels have occurred. The purpose of this first-generation study was to evaluate the efficacy of a hand-held computer (i.e., personal digital assistant [PDA]) for increasing moderate intensity or more vigorous (MOD+) physical activity levels over 8 weeks in mid-life and older adults relative to a standard information control arm. Design Randomized, controlled 8-week experiment. Data were collected in 2005 and analyzed in 2006-2007. Setting/Participants Community-based study of 37 healthy, initially underactive adults aged 50 years and older who were randomized and completed the 8-week study (intervention=19, control=18). Intervention Participants received an instructional session and a PDA programmed to monitor their physical activity levels twice per day and provide daily and weekly individualized feedback, goal setting, and support. Controls received standard, age-appropriate written physical activity educational materials. Main Outcome Measure Physical activity was assessed via the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire at baseline and 8 weeks. Results Relative to controls, intervention participants reported significantly greater 8-week mean estimated caloric expenditure levels and minutes per week in MOD+ activity (p<0.04). Satisfaction with the PDA was reasonably high in this largely PDA-naive sample. Conclusions Results from this first-generation study indicate that hand-held computers may be effective tools for increasing initial physical activity levels among underactive adults. PMID:18201644

  6. Promoting Physical Activity among International Students in Higher Education: A Peer-Education Approach

    ERIC Educational Resources Information Center

    Yan, Zi; Cardinal, Bradley J.

    2013-01-01

    International students have become an important and growing group in U.S. higher education. Although many universities offer various types of support to international students, little attention is given to preventive health services or health promotion efforts, such as the promotion of physical activity. This article outlines a theory-based…

  7. Collegewide Promotion of E-Learning/Active Learning and Faculty Development

    ERIC Educational Resources Information Center

    Ogawa, Nobuyuki; Shimizu, Akira

    2016-01-01

    Japanese National Institutes of Technology have revealed a plan to strongly promote e-Learning and active learning under the common schematization of education in over 50 campuses nationwide. Our e-Learning and ICT-driven education practiced for more than fifteen years were highly evaluated, and is playing a leading role in promoting e-Learning…

  8. Complement activation promotes muscle inflammation during modified muscle use

    NASA Technical Reports Server (NTRS)

    Frenette, J.; Cai, B.; Tidball, J. G.

    2000-01-01

    Modified muscle use can result in muscle inflammation that is triggered by unidentified events. In the present investigation, we tested whether the activation of the complement system is a component of muscle inflammation that results from changes in muscle loading. Modified rat hindlimb muscle loading was achieved by removing weight-bearing from the hindlimbs for 10 days followed by reloading through normal ambulation. Experimental animals were injected with the recombinant, soluble complement receptor sCR1 to inhibit complement activation. Assays for complement C4 or factor B in sera showed that sCR1 produced large reductions in the capacity for activation of the complement system through both the classical and alternative pathways. Analysis of complement C4 concentration in serum in untreated animals showed that the classical pathway was activated during the first 2 hours of reloading. Analysis of factor B concentration in untreated animals showed activation of the alternative pathway at 6 hours of reloading. Administration of sCR1 significantly attenuated the invasion of neutrophils (-49%) and ED1(+) macrophages (-52%) that occurred in nontreated animals after 6 hours of reloading. The presence of sCR1 also reduced significantly the degree of edema by 22% as compared to untreated animals. Together, these data show that increased muscle loading activated the complement system which then briefly contributes to the early recruitment of inflammatory cells during modified muscle loading.

  9. Regulatory elements involved in the bidirectional activity of an immunoglobulin promoter.

    PubMed Central

    Doyen, N; Dreyfus, M; Rougeon, F

    1989-01-01

    We show that the promoter from the mouse VH441 heavy-chain immunoglobulin gene, when present on plasmids transiently introduced into myeloma cells, promotes transcription bidirectionally, due to the presence on both strands of TATA-like sequences bracketing the highly conserved decanucleotide element. The two divergent promoters compete for the transcriptional machinery, their relative strength ultimately reflecting the likeness of the two TATA boxes to the consensus sequence. Moreover, their relative activity is also strongly influenced by certain point mutations within the distally located heavy-chain enhancer. The bearing of these results on current concepts of promoter function is discussed. Images PMID:2494644

  10. Fruit preferential activity of the tomato RIP1 gene promoter in transgenic tomato and Arabidopsis.

    PubMed

    Agarwal, Priyanka; Kumar, Rahul; Pareek, Amit; Sharma, Arun K

    2017-02-01

    Isolation and functional characterization of tissue- and stage-specific gene promoters is beneficial for genetic improvement of economically important crops. Here, we have characterized a putative promoter of a ripening-induced gene RIP1 (Ripening induced protein 1) in tomato. Quantification of the transcript level of RIP1 showed that its expression is fruit preferential, with maximum accumulation in red ripe fruits. To test the promoter activity, we made a reporter construct by cloning 1450 bp putative RIP1 promoter driving the GUS (ß-glucuronidase) gene expression and generated stable transgenic lines in tomato and Arabidopsis. Histochemical and fluorometric assays validated the fruit-specific expression of RIP1 as the highest GUS activity was found in red ripe tomatoes. Similarly, we detected high levels of GUS activity in the siliques of Arabidopsis. On the contrary, weak GUS activity was found in the flower buds in both tomato and Arabidopsis. To characterize the specific regions of the RIP1 promoter that might be essential for its maximum activity and specificity in fruits, we made stable transgenic lines of tomato and Arabidopsis with 5'-deletion constructs. Characterization of these transgenic plants showed that the full length promoter is essential for its function. Overall, we report the identification and characterization of a ripening-induced promoter of tomato, which would be useful for the controlled manipulation of the ripening-related agronomic traits in genetic manipulation studies in future.

  11. Promoting Uranium Immobilization by the Activities of Microbial Phosphatases

    SciTech Connect

    Martinez, Robert J.; Beazley, Melanie J.; Wilson, Jarad J.; Taillefert, Martial; Sobecky, Patricia A.

    2005-04-05

    The overall goal of this project is to examine the role of nonspecific phosphohydrolases present in naturally occurring subsurface microorganisms for the purpose of promoting the immobilization of radionuclides through the production of uranium [U(VI)] phosphate precipitates. Specifically, we hypothesize that the precipitation of U(VI) phosphate minerals may be promoted through the microbial release and/or accumulation of PO{sub 4}{sup 3-}. During this phase of the project we have been conducting assays to determine the effects of pH, inorganic anions and organic ligands on U(VI) mineral formation and precipitation when FRC bacterial isolates were grown in simulated groundwater medium. The molecular characterization of FRC isolates has also been undertaken during this phase of the project. Analysis of a subset of gram-positive FRC isolates cultured from FRC soils (Areas 1, 2 and 3) and background sediments have indicated a higher percentage of isolates exhibiting phosphatase phenotypes (i.e., in particular those surmised to be PO{sub 4}{sup 3-}-irrepressible) relative to isolates from the reference site. A high percentage of strains that exhibited such putatively PO{sub 4}{sup 3-}-irrepressible phosphatase phenotypes were also resistant to the heavy metals lead and cadmium. Previous work on FRC strains, including Arthrobacter, Bacillus and Rahnella spp., has demonstrated differences in tolerance to U(VI) toxicity (200 {micro}M) in the absence of organophosphate substrates. For example, Arthrobacter spp. exhibited the greatest tolerance to U(VI) while the Rahnella spp. have been shown to facilitate the precipitation of U(VI) from solution and the Bacillus spp. demonstrate the greatest sensitivity to acidic conditions and high concentrations of U(VI). PCR-based detection of FRC strains are being conducted to determine if non-specific acid phosphatases of the known molecular classes [i.e., classes A, B and C] are present in these FRC isolates. Additionally, these

  12. Nattokinase-promoted tissue plasminogen activator release from human cells.

    PubMed

    Yatagai, Chieko; Maruyama, Masugi; Kawahara, Tomoko; Sumi, Hiroyuki

    2008-01-01

    When heated to a temperature of 70 degrees C or higher, the strong fibrinolytic activity of nattokinase in a solution was deactivated. Similar results were observed in the case of using Suc-Ala-Ala-Pro-Phe-pNA and H-D-Val-Leu-Lys-pNA, which are synthetic substrates of nattokinase. In the current study, tests were conducted on the indirect fibrinolytic effects of the substances containing nattokinase that had been deactivated through heating at 121 degrees C for 15 min. Bacillus subtilis natto culture solutions made from three types of bacteria strain were heat-treated and deactivated, and it was found that these culture solutions had the ability to generate tissue plasminogen activators (tPA) from vascular endothelial cells and HeLa cells at certain concentration levels. For example, it was found that the addition of heat-treated culture solution of the Naruse strain (undiluted solution) raises the tPA activity of HeLa cells to about 20 times that of the control. Under the same conditions, tPA activity was raised to a level about 5 times higher for human vascular endothelial cells (HUVEC), and to a level about 24 times higher for nattokinase sold on the market. No change in cell count was observed for HeLa cells and HUVEC in the culture solution at these concentrations, and the level of activity was found to vary with concentration.

  13. Design of phosphorylated dendritic architectures to promote human monocyte activation.

    PubMed

    Poupot, Mary; Griffe, Laurent; Marchand, Patrice; Maraval, Alexandrine; Rolland, Olivier; Martinet, Ludovic; L'Faqihi-Olive, Fatima-Ezzahra; Turrin, Cédric-Olivier; Caminade, Anne-Marie; Fournié, Jean-Jacques; Majoral, Jean-Pierre; Poupot, Rémy

    2006-11-01

    As first defensive line, monocytes are a pivotal cell population of innate immunity. Monocyte activation can be relevant to a range of immune conditions and responses. Here we present new insights into the activation of monocytes by a series of phosphonic acid-terminated, phosphorus-containing dendrimers. Various dendritic or subdendritic structures were synthesized and tested, revealing the basic structural requirements for monocyte activation. We showed that multivalent character and phosphonic acid capping of dendrimers are crucial for monocyte targeting and activation. Confocal videomicroscopy showed that a fluorescein-tagged dendrimer binds to isolated monocytes and gets internalized within a few seconds. We also found that dendrimers follow the phagolysosomial route during internalization by monocytes. Finally, we performed fluorescence resonance energy transfer (FRET) experiments between a specifically designed fluorescent dendrimer and phycoerythrin-coupled antibodies. We showed that the typical innate Toll-like receptor (TLR)-2 is clearly involved, but not alone, in the sensing of dendrimers by monocytes. In conclusion, phosphorus-containing dendrimers appear as precisely tunable nanobiotools able to target and activate human innate immunity and thus prove to be good candidates to develop new drugs for immunotherapies.

  14. Dissemination of physical activity promotion interventions in underserved populations.

    PubMed

    Yancey, Antronette K; Ory, Marcia G; Davis, Sally M

    2006-10-01

    Achieving minimum physical activity levels of 30 or more minutes per day will require a variety of intervention strategies to engage each segment of an aging and increasingly ethnically diverse U.S. population. This article presents a focused review of the sparse literature on the diffusion of evidence-based physical activity interventions that are culturally appropriate for underserved populations. Related literature and experiential insights inform this discussion, because so few published studies report outcome data beyond the first diffusion phase of intervention development and evaluation. Three brief case studies are presented to further illustrate and exemplify key concepts and processes at several different stages in diffusing physical activity interventions. Successful engagement of underserved populations reflects a delicate balance between embracing group customs and values and recognizing the nonmonolithic nature of any sociodemographically defined group. The costs of failing to promulgate effective physical activity interventions in these groups continue to mount, in dollars, health, and lives. Researchers, practitioners, decision makers, and policymakers must partner to bridge the evidentiary gap so that the physically active lifestyle choices become the easier choices.

  15. Mobile Health Applications to Promote Active and Healthy Ageing

    PubMed Central

    Helbostad, Jorunn L.; Vereijken, Beatrix; Becker, Clemens; Todd, Chris; Taraldsen, Kristin; Pijnappels, Mirjam; Aminian, Kamiar; Mellone, Sabato

    2017-01-01

    The European population is ageing, and there is a need for health solutions that keep older adults independent longer. With increasing access to mobile technology, such as smartphones and smartwatches, the development and use of mobile health applications is rapidly growing. To meet the societal challenge of changing demography, mobile health solutions are warranted that support older adults to stay healthy and active and that can prevent or delay functional decline. This paper reviews the literature on mobile technology, in particular wearable technology, such as smartphones, smartwatches, and wristbands, presenting new ideas on how this technology can be used to encourage an active lifestyle, and discusses the way forward in order further to advance development and practice in the field of mobile technology for active, healthy ageing. PMID:28335475

  16. Mobile Health Applications to Promote Active and Healthy Ageing.

    PubMed

    Helbostad, Jorunn L; Vereijken, Beatrix; Becker, Clemens; Todd, Chris; Taraldsen, Kristin; Pijnappels, Mirjam; Aminian, Kamiar; Mellone, Sabato

    2017-03-18

    The European population is ageing, and there is a need for health solutions that keep older adults independent longer. With increasing access to mobile technology, such as smartphones and smartwatches, the development and use of mobile health applications is rapidly growing. To meet the societal challenge of changing demography, mobile health solutions are warranted that support older adults to stay healthy and active and that can prevent or delay functional decline. This paper reviews the literature on mobile technology, in particular wearable technology, such as smartphones, smartwatches, and wristbands, presenting new ideas on how this technology can be used to encourage an active lifestyle, and discusses the way forward in order further to advance development and practice in the field of mobile technology for active, healthy ageing.

  17. Endothelial Notch activity promotes angiogenesis and osteogenesis in bone.

    PubMed

    Ramasamy, Saravana K; Kusumbe, Anjali P; Wang, Lin; Adams, Ralf H

    2014-03-20

    Blood vessel growth in the skeletal system and osteogenesis seem to be coupled, suggesting the existence of molecular crosstalk between endothelial and osteoblastic cells. Understanding the nature of the mechanisms linking angiogenesis and bone formation should be of great relevance for improved fracture healing or prevention of bone mass loss. Here we show that vascular growth in bone involves a specialized, tissue-specific form of angiogenesis. Notch signalling promotes endothelial cell proliferation and vessel growth in postnatal long bone, which is the opposite of the well-established function of Notch and its ligand Dll4 in the endothelium of other organs and tumours. Endothelial-cell-specific and inducible genetic disruption of Notch signalling in mice not only impaired bone vessel morphology and growth, but also led to reduced osteogenesis, shortening of long bones, chondrocyte defects, loss of trabeculae and decreased bone mass. On the basis of a series of genetic experiments, we conclude that skeletal defects in these mutants involved defective angiocrine release of Noggin from endothelial cells, which is positively regulated by Notch. Administration of recombinant Noggin, a secreted antagonist of bone morphogenetic proteins, restored bone growth and mineralization, chondrocyte maturation, the formation of trabeculae and osteoprogenitor numbers in endothelial-cell-specific Notch pathway mutants. These findings establish a molecular framework coupling angiogenesis, angiocrine signals and osteogenesis, which may prove significant for the development of future therapeutic applications.

  18. Endothelial Notch activity promotes angiogenesis and osteogenesis in bone

    NASA Astrophysics Data System (ADS)

    Ramasamy, Saravana K.; Kusumbe, Anjali P.; Wang, Lin; Adams, Ralf H.

    2014-03-01

    Blood vessel growth in the skeletal system and osteogenesis seem to be coupled, suggesting the existence of molecular crosstalk between endothelial and osteoblastic cells. Understanding the nature of the mechanisms linking angiogenesis and bone formation should be of great relevance for improved fracture healing or prevention of bone mass loss. Here we show that vascular growth in bone involves a specialized, tissue-specific form of angiogenesis. Notch signalling promotes endothelial cell proliferation and vessel growth in postnatal long bone, which is the opposite of the well-established function of Notch and its ligand Dll4 in the endothelium of other organs and tumours. Endothelial-cell-specific and inducible genetic disruption of Notch signalling in mice not only impaired bone vessel morphology and growth, but also led to reduced osteogenesis, shortening of long bones, chondrocyte defects, loss of trabeculae and decreased bone mass. On the basis of a series of genetic experiments, we conclude that skeletal defects in these mutants involved defective angiocrine release of Noggin from endothelial cells, which is positively regulated by Notch. Administration of recombinant Noggin, a secreted antagonist of bone morphogenetic proteins, restored bone growth and mineralization, chondrocyte maturation, the formation of trabeculae and osteoprogenitor numbers in endothelial-cell-specific Notch pathway mutants. These findings establish a molecular framework coupling angiogenesis, angiocrine signals and osteogenesis, which may prove significant for the development of future therapeutic applications.

  19. Drosophila gypsy insulator and yellow enhancers regulate activity of yellow promoter through the same regulatory element.

    PubMed

    Melnikova, Larisa; Kostuchenko, Margarita; Silicheva, Margarita; Georgiev, Pavel

    2008-04-01

    There is ample evidence that the enhancers of a promoterless yellow locus in one homologous chromosome can activate the yellow promoter in the other chromosome where the enhancers are inactive or deleted, which is indicative of a high specificity of the enhancer-promoter interaction in yellow. In this paper, we have found that the yellow sequence from -100 to -69 is essential for stimulation of the heterologous eve (TATA-containing) and white (TATA-less) promoters by the yellow enhancers from a distance. However, the presence of this sequence is not required when the yellow enhancers are directly fused to the heterologous promoters or are activated by the yeast GAL4 activator. Unexpectedly, the same promoter proximal region defines previously described promoter-specific, long-distance repression of the yellow promoter by the gypsy insulator on the mod(mdg4) ( u1 ) background. These finding suggest that proteins bound to the -100 to -69 sequence are essential for communication between the yellow promoter and upstream regulatory elements.

  20. The National Blueprint for Promoting Physical Activity in the Mid-Life and Older Adult Population

    ERIC Educational Resources Information Center

    Chodzko-Zajko, Wojtek; Sheppard, Lisa; Senior, Jane; Park, Chae-Hee; Mockenhaupt, Robin; Bazzarre, Terry

    2005-01-01

    The National Blueprint: Increasing Physical Activity Among Adults Age 50 and Older was designed to develop a national strategy for the promotion of physically active lifestyles among the mid-life and older adult population. The Blueprint identifies barriers to physical activity in the areas of research, home and community programs, medical…

  1. Calcium promotes activity and confers heat stability on plant peroxidases

    PubMed Central

    Plieth, Christoph; Vollbehr, Sonja

    2012-01-01

    In this paper we demonstrate how peroxidase (PO) activities and their heat stability correlate with the availability of free Ca2+ ions. Calcium ions work as a molecular switch for PO activity and exert a protective function, rendering POs heat stable. The concentration ranges of these two activities differ markedly. POs are activated by µM Ca2+ concentration ranges, whereas heat stabilization is observed in the nM range. This suggests the existence of different Ca2+ binding sites. The heat stability of POs depends on the source plant species. Terrestrial plants have POs that exhibit higher temperature stability than those POs from limnic and marine plants. Different POs from a single species can differ in terms of heat stability. The abundance of different POs within a plant is dependent on age and developmental stage. The heat stability of a PO does not necessarily correlate with the maximum temperature the source species is usually exposed to in its natural habitat. This raises questions on the role of POs in the heat tolerance of plants. Consequently, detailed investigations are needed to identify and characterize individual POs, with regard to their genetic origin, subcellular expression, tissue abundance, developmental emergence and their functions in innate and acquired heat tolerance. PMID:22580695

  2. Promoting Physical Activity in Low-Income Preschool Children

    ERIC Educational Resources Information Center

    Spaulding, Carol; Gottlieb, Nell H.; Jensen, Jody

    2008-01-01

    Child- and family-serving programs such as the Special Supplemental Nutrition program for Women, Infants, and Children (WIC) design and conduct interventions to improve the health of their clients through better nutrition. But these programs present a significant opportunity to improve physical activity levels in the preschool population as well,…

  3. Creativity in the English Class: Activities to Promote EFL Learning

    ERIC Educational Resources Information Center

    Avila, Hernán A.

    2016-01-01

    This article introduces a pedagogical intervention that includes a set of creative activities designed to improve the oral and written production of students in the English classroom, especially those who have shown a lack of interest or attention. It was observed that participants initially seemed careless about studying the language. Eventually…

  4. Does HOPSports Promote Youth Physical Activity in Physical Education Classes?

    ERIC Educational Resources Information Center

    West, Stephanie T.; Shores, Kindal A.

    2014-01-01

    This study investigated how a technological intervention, HOPSports (HOPS), impacted youth physical activity (PA) in a physical education (PE) class. Research indicates rising levels of youth television watching and video game use, physical inactivity, and related overweight. One approach to increase youth PA is to use technology-based…

  5. Calcium promotes activity and confers heat stability on plant peroxidases.

    PubMed

    Plieth, Christoph; Vollbehr, Sonja

    2012-06-01

    In this paper we demonstrate how peroxidase (PO) activities and their heat stability correlate with the availability of free Ca(2+) ions. Calcium ions work as a molecular switch for PO activity and exert a protective function, rendering POs heat stable. The concentration ranges of these two activities differ markedly. POs are activated by µM Ca(2+) concentration ranges, whereas heat stabilization is observed in the nM range. This suggests the existence of different Ca(2+) binding sites. The heat stability of POs depends on the source plant species. Terrestrial plants have POs that exhibit higher temperature stability than those POs from limnic and marine plants. Different POs from a single species can differ in terms of heat stability. The abundance of different POs within a plant is dependent on age and developmental stage. The heat stability of a PO does not necessarily correlate with the maximum temperature the source species is usually exposed to in its natural habitat. This raises questions on the role of POs in the heat tolerance of plants. Consequently, detailed investigations are needed to identify and characterize individual POs, with regard to their genetic origin, subcellular expression, tissue abundance, developmental emergence and their functions in innate and acquired heat tolerance.

  6. Promoting Technology-Assisted Active Learning in Computer Science Education

    ERIC Educational Resources Information Center

    Gao, Jinzhu; Hargis, Jace

    2010-01-01

    This paper describes specific active learning strategies for teaching computer science, integrating both instructional technologies and non-technology-based strategies shown to be effective in the literature. The theoretical learning components addressed include an intentional method to help students build metacognitive abilities, as well as…

  7. Forming a Learning Culture to Promote Fracture Prevention Activities

    ERIC Educational Resources Information Center

    Hjalmarson, Helene V.; Strandmark, Margaretha

    2012-01-01

    Purpose: The purpose of this paper is to explore interprofessional experiences of incorporating fracture prevention activities in clinical practice inspired by an empowerment approach. Design/methodology/approach: Data collection consisted primarily of focus groups interviews, systematized and analyzed by the grounded theory method. The study took…

  8. Community Resources for Promoting Youth Nutrition and Physical Activity

    ERIC Educational Resources Information Center

    Moore, Kelly R.; McGowan, Melissa K.; Donato, Karen A.; Kollipara, Sobha; Roubideaux, Yvette

    2009-01-01

    Childhood obesity is a national public health crisis. The National Diabetes Education Program (NDEP), the National Institutes of Health and Kaiser Permanente have developed community tools and resources for children and families to lower their risk for obesity through healthier, active lifestyles. The authors describe innovative practices and…

  9. Laminar flow downregulates Notch activity to promote lymphatic sprouting.

    PubMed

    Choi, Dongwon; Park, Eunkyung; Jung, Eunson; Seong, Young Jin; Yoo, Jaehyuk; Lee, Esak; Hong, Mingu; Lee, Sunju; Ishida, Hiroaki; Burford, James; Peti-Peterdi, Janos; Adams, Ralf H; Srikanth, Sonal; Gwack, Yousang; Chen, Christopher S; Vogel, Hans J; Koh, Chester J; Wong, Alex K; Hong, Young-Kwon

    2017-04-03

    The major function of the lymphatic system is to drain interstitial fluid from tissue. Functional drainage causes increased fluid flow that triggers lymphatic expansion, which is conceptually similar to hypoxia-triggered angiogenesis. Here, we have identified a mechanotransduction pathway that translates laminar flow-induced shear stress to activation of lymphatic sprouting. While low-rate laminar flow commonly induces the classic shear stress responses in blood endothelial cells and lymphatic endothelial cells (LECs), only LECs display reduced Notch activity and increased sprouting capacity. In response to flow, the plasma membrane calcium channel ORAI1 mediates calcium influx in LECs and activates calmodulin to facilitate a physical interaction between Krüppel-like factor 2 (KLF2), the major regulator of shear responses, and PROX1, the master regulator of lymphatic development. The PROX1/KLF2 complex upregulates the expression of DTX1 and DTX3L. DTX1 and DTX3L, functioning as a heterodimeric Notch E3 ligase, concertedly downregulate NOTCH1 activity and enhance lymphatic sprouting. Notably, overexpression of the calcium reporter GCaMP3 unexpectedly inhibited lymphatic sprouting, presumably by disturbing calcium signaling. Endothelial-specific knockouts of Orai1 and Klf2 also markedly impaired lymphatic sprouting. Moreover, Dtx3l loss of function led to defective lymphatic sprouting, while Dtx3l gain of function rescued impaired sprouting in Orai1 KO embryos. Together, the data reveal a molecular mechanism underlying laminar flow-induced lymphatic sprouting.

  10. Analysis of cis-sequence of subgenomic transcript promoter from the Figwort mosaic virus and comparison of promoter activity with the cauliflower mosaic virus promoters in monocot and dicot cells.

    PubMed

    Bhattacharyya, Somnath; Dey, Nrisingha; Maiti, Indu B

    2002-12-01

    A sub-genomic transcript (Sgt) promoter was isolated from the Figwort mosaic virus (FMV) genomic clone. The FMV Sgt promoter was linked to heterologous coding sequences to form a chimeric gene construct. The 5'-3'-boundaries required for maximal activity and involvement of cis-sequences for optimal expression in plants were defined by 5'-, 3'-end deletion and internal deletion analysis of FMV Sgt promoter fragments coupled with a beta-glucuronidase reporter gene in both transient protoplast expression experiments and in transgenic plants. A 301 bp FMV Sgt promoter fragment (sequence -270 to +31 from the transcription start site; TSS) provided maximum promoter activity. The TSS of the FMV Sgt promoter was determined by primer extension analysis using total RNA from transgenic plants developed for FMV Sgt promoter: uidA fusion gene. An activator domain located upstream of the TATA box at -70 to -100 from TSS is absolutely required for promoter activity and its function is critically position-dependent with respect to TATA box. Two sequence motifs AGATTTTAAT (coordinates -100 to -91) and GTAAGCGC (coordinates -80 to -73) were found to be essential for promoter activity. The FMV Sgt promoter is less active in monocot cells; FMV Sgt promoter expression level was about 27.5-fold higher in tobacco cells compared to that in maize cells. Comparative expression analysis of FMV Sgt promoter with cauliflower mosaic virus (CaMV) 35S promoter showed that the FMV Sgt promoter is about 2-fold stronger than the CaMV 35S promoter. The FMV Sgt promoter is a constitutive promoter; expression level in seedlings was in the order: root>leaf>stem.

  11. Tumor-initiating and promoting activities of di(2-ethylhexyl) phthalate in vivo and in vitro.

    PubMed

    Ward, J M; Diwan, B A; Ohshima, M; Hu, H; Schuller, H M; Rice, J M

    1986-03-01

    The carcinogenic effects of di(2-ethylhexyl) phthalate (DEHP), including its potential as an initiator and as a promoter of carcinogenesis, were studied in mouse liver and skin and in rat liver in vivo, and in mouse epidermis-derived JB6 cells in vitro. A mouse model for liver initiation and promotion involved initiation by injection of N-nitrosodiethylamine (DEN) intraperitoneally into male B6C3F1 mice at 4 weeks of age, followed by exposure to either DEHP in the diet (3000, 6000, or 12,000 ppm) or phenobarbital in the drinking water (500 ppm), beginning 1 to 2 weeks later and continuing for periods of from 1 day to 18 months. Female F344/NCr rats were subjected to a similar protocol in which promotion continued for 14 weeks. DEHP promoted focal hepatocellular proliferative lesions (FHPL), including hyperplastic foci and neoplasms initiated by DEN in mice but not in rats. Skin-painting studies in female CD-1 or SENCAR mice involved initiation by a single topical exposure to 7,12-dimethylbenz[a]-anthracene (DMBA) applied to the dorsal skin, followed by repeated percutaneous exposure to a tumor promoter, either DEHP or 12-O-tetradecanoylphorbol-13-acetate (TPA). To test for two-stage skin tumor promotion, SENCAR mice were initiated with DMBA and then TPA was administered for only 2 weeks, after which DEHP was subsequently administered for 26 weeks. DEHP displayed very weak complete promoting activity and definite second stage promoting activity in SENCAR mouse skin, but was inactive under our conditions on CD-1 mouse skin. In vitro promoting activity of DEHP and its hydrolysis products, mono(2-ethylhexyl) phthalate (MEHP) and 2-ethylhexanol (EH), was studied by using promotable mouse epidermis-derived JB6 cells. DEHP and MEHP promoted JB6 cells to anchorage independence, while EH did not.

  12. Combining balneotherapy and health promotion to promote active and healthy ageing: the Balaruc-MACVIA-LR(®) approach.

    PubMed

    Blain, H; Bernard, P L; Canovas, G; Raffort, N; Desfour, H; Soriteau, L; Noguès, M; Camuzat, T; Mercier, J; Dupeyron, A; Quéré, I; Laffont, I; Hérisson, C; Solimene, H; Bousquet, J

    2016-12-01

    Scaling up and replication of successful innovative integrated care models for chronic diseases is one of the targets of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). MACVIA-LR(®) (MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon) is a Reference Site of the EIP on AHA. The main objective of MACVIA-LR(®) is to develop innovative solutions in order to (1) improve the care of patients affected by chronic diseases, (2) reduce avoidable hospitalization and (3) scale up the innovation to regions of Europe. The MACVIA-LR(®) project also aims to assess all possible aspects of medicine-including non-pharmacologic approaches-in order to maintain health and prevent chronic diseases. These approaches include hydrotherapy and balneotherapy which can be of great importance if health promotion strategies are considered. Balneotherapy at Balaruc-les-Bains focusses on musculoskeletal diseases and chronic venous insufficiency of the lower limbs. Each year, over 46,000 people attend an 18-day course related to a new falls prevention initiative combining balneotherapy and education. On arrival, each person receives a flyer providing information on the risk of fall and, depending on this risk, a course is proposed combining education and physical activity. A pilot study assesses the impact of the course 6 and 12 months later. This health promotion strategy for active and healthy ageing follows the FEMTEC (World Federation of Hydrotherapy and Climatotherapy) concept.

  13. NMDA Receptors Enhance Spontaneous Activity and Promote Neuronal Survival in the Developing Cochlea

    PubMed Central

    Zhang-Hooks, YingXin; Agarwal, Amit; Mishina, Masayoshi; Bergles, Dwight E.

    2016-01-01

    Summary Spontaneous bursts of activity in developing sensory pathways promote maturation of neurons, refinement of neuronal connections and assembly of appropriate functional networks. In the developing auditory system, inner hair cells (IHCs) spontaneously fire Ca2+ spikes, each of which is transformed into a mini-burst of action potentials in spiral ganglion neurons (SGNs). Here we show that NMDARs are expressed in SGN dendritic terminals and play a critical role during transmission of activity from IHCs to SGNs before hearing onset. NMDAR activation enhances glutamate-mediated Ca2+ influx at dendritic terminals, promotes repetitive firing of individual SGNs in response to each synaptic event, and enhances coincident activity of neighboring SGNs that will eventually encode similar frequencies of sound. Loss of NMDAR signaling from SGNs reduced their survival both in vivo and in vitro, revealing that spontaneous activity in the prehearing cochlea promotes maturation of auditory circuitry through periodic activation of NMDARs in SGNs. PMID:26774161

  14. Dog ownership and dog walking to promote physical activity and health in patients.

    PubMed

    Epping, Jacqueline N

    2011-07-01

    Lack of physical activity is a significant risk factor for many chronic diseases and conditions and is associated with significant medical costs. Approximately half of adults and more than a third of adolescents and youth in the United States do not achieve recommended levels of physical activity. Effective population-level strategies are needed to promote activities that are practical, accessible, and sustainable and that can reach a large proportion of the population. Dog walking may be such a strategy. Walking is popular, easy, and sustainable and has a low risk of injury. Owning dogs confers many health benefits, and dog walking, in particular, can help promote physical activity and improve health. Physicians and other health care providers can play a unique and integral role in promoting physical activity among patients by recommending dog walking both to dog owners and to non-dog owners as a purposeful, enjoyable, and sustainable form of regular physical activity.

  15. GLT-1 Promoter Activity in Astrocytes and Neurons of Mouse Hippocampus and Somatic Sensory Cortex

    PubMed Central

    de Vivo, Luisa; Melone, Marcello; Rothstein, Jeffrey D.; Conti, Fiorenzo

    2009-01-01

    GLT-1 eGFP BAC reporter transgenic adult mice were used to detect GLT-1 gene expression in individual cells of CA1, CA3 and SI, and eGFP fluorescence was measured to analyze quantitatively GLT-1 promoter activity in different cells of neocortex and hippocampus. Virtually all GFAP+ astrocytes were eGFP+; we also found that about 80% of neurons in CA3 pyramidal layer, 10–70% of neurons in I-VI layers of SI and rare neurons in all strata of CA1 and in strata oriens and radiatum of CA3 were eGFP+. Analysis of eGFP intensity showed that astrocytes had a higher GLT-1 promoter activity in SI than in CA1 and CA3, and that neurons had the highest levels of GLT-1 promoter activity in CA3 stratum pyramidale and in layer VI of SI. Finally, we observed that the intensity of GLT-1 promoter activity in neurons is 1–20% of that measured in astrocytes. These results showed that in the hippocampus and neocortex GLT-1 promoter activity is observed in astrocytes and neurons, detailed the distribution of GLT-1 expressing neurons, and indicated that GLT-1 promoter activity in both astrocytes and neurons varies in different brain regions. PMID:20161698

  16. Alternatively activated macrophages promote pancreatic fibrosis in chronic pancreatitis

    PubMed Central

    Xue, Jing; Sharma, Vishal; Hsieh, Michael H.; Chawla, Ajay; Murali, Ramachandran; Pandol, Stephen J.; Habtezion, Aida

    2015-01-01

    Chronic pancreatitis (CP) is a progressive and irreversible inflammatory and fibrotic disease with no cure. Unlike acute pancreatitis, we find that alternatively activated macrophages (AAMs) are dominant in mouse and human CP. AAMs are dependent on IL-4 and IL-13 signaling and we show that mice lacking IL-4Rα, myeloid specific IL-4Rα, and IL-4/IL-13 were less susceptible to pancreatic fibrosis. Furthermore, we demonstrate that mouse and human pancreatic stellate cells (PSCs) are a source of IL-4/IL-13. Notably, we show that pharmacologic inhibition of IL-4/IL-13 in human ex-vivo studies as well as in established mouse CP decreases pancreatic AAMs and fibrosis. We identify a critical role for macrophages in pancreatic fibrosis and in turn PSCs as important inducers of macrophage alternative activation. Our study challenges and identifies pathways involved in cross talk between macrophages and PSCs that can be targeted to reverse or halt pancreatic fibrosis progression. PMID:25981357

  17. Just-in-time automated counseling for physical activity promotion.

    PubMed

    Bickmore, Timothy; Gruber, Amanda; Intille, Stephen

    2008-11-06

    Preliminary results from a field study into the efficacy of automated health behavior counseling delivered at the moment of user decision-making compared to the same counseling delivered at the end of the day are reported. The study uses an animated PDA-based advisor with an integrated accelerometer that can engage users in dialogues about their physical activity throughout the day. Preliminary results indicate health counseling is more effective when delivered just-in-time than when delivered retrospectively.

  18. Armadillo/Pangolin regulates PCNA and DREF promoter activities.

    PubMed

    Kwon, Eunjeong; Hayashi, Yuko; Otsuki, Kyoko; Hirose, Fumiko; Nishida, Yasuyoshi; Yoo, Mi-Ae; Yamaguchi, Masamitsu

    2004-09-17

    Here we show that Armadillo and Pangolin (dTCF), downstream effectors of the Wingless (Wg) signal transduction pathway, activate transcription of the important DNA replication-related genes encoding Drosophila proliferating cell nuclear antigen (PCNA) and DNA replication-related element-binding factor (DREF). By transient luciferase expression assays and band mobility shift assays, we demonstrated the PCNA gene to be a direct target gene for the Armadillo/Pangolin complex. Using a GAL4-UAS system, stimulation of the PCNA gene by Armadillo/Pangolin was confirmed in adult females. From the published reports of an inhibitory role, we expected that Drosophila CREB-binding protein (dCBP) would interfere with activation. However, effects were only observed with the DREF but not the PCNA gene. In the latter case, as in mammals, dCBP could potentiate Armadillo-mediated activation. These results suggest that first, PCNA and DREF genes are targets of the Armadillo/Pangolin complex and second, dCBP modulates Wg signaling in a gene-specific manner.

  19. Activation of AMPK by berberine promotes adiponectin multimerization in 3T3-L1 adipocytes.

    PubMed

    Li, Yun; Wang, Pengcheng; Zhuang, Yuan; Lin, Huan; Li, Yehua; Liu, Ling; Meng, Qinghang; Cui, Ting; Liu, Jing; Li, Zhen

    2011-06-23

    Adiponectin is assembled into trimer (LMW), hexamer (MMW) and high-molecular-weight (HMW) multimer in adipocytes. The HMW adiponectin is more metabolically active and closely associated with peripheral insulin sensitivity. In this study, we reported that berberine, an isoquinoline alkaloid with insulin-sensitizing effect, inhibits the expression of adiponectin, but promotes the assembly of HMW adiponectin and increases the ratio of HMW to total adiponectin. Berberine activates AMPK. Knockdown of AMPKα1 abolishes the effect of berberine. Activation of AMPK by AICAR also increases the level of HMW adiponectin. Our study suggested that activation of AMPK by berberine promotes adiponectin multimerization.

  20. Boswellia carterii liquisolid systems with promoted anti-inflammatory activity.

    PubMed

    Mostafa, Dina Mahmoud; Ammar, Nagwa Mohammed; Abd El-Alim, Sameh Hosam; Kassem, Ahmed Alaa; Hussein, Rehab Ali; Awad, Gamal; El-Awdan, Sally Abdul-Wanees

    2015-01-01

    Boswellia carterii (BC) Birdwood oleogum resin is an ancient remedy of inflammation processes known since Ancient Egyptian time. Of boswellic acids, 3-acetyl-11-keto-β-boswellic acid (AKBA) is the most potent anti-inflammatory active principle. Liquisolid systems of the biologically active fraction of BC oleogum resin were prepared for improving dissolution properties using low dose oral delivery to achieve enhanced anti-inflammatory activity, in comparison with the standard oral anti-inflammatory; Indomethacin. AKBA was assayed, employing an accurate and sensitive HPLC method. Detection was carried out at 210 nm using UV/Vis detector. A solubility study for the bioactive fraction was conducted. Microcrystalline cellulose and Aeroperl®300 Pharma were used as carrier and coating materials. Angle of slide, liquid load factor and Carr's flow index were estimated. Six systems were prepared using polyethylene glycol 400, solvent and two drug loading concentrations; 20 and 40 %. For each concentration, three carrier: coat ratios were dispensed; 20:1, 10:1, and 5:1. Dissolution study was performed and two systems were selected for characterization and in vivo evaluation by investigating upper GIT ulcerogenic effect and anti-inflammatory efficacy in rats. Results indicate absence of ulcers and significantly higher and prolonged anti-inflammatory efficacy for formulations F1 and F2, with carrier: coat ratio, 5:1 and drug loads of 20 and 40 %, respectively, compared with standard oral indomethacin. We conclude higher efficacy of BC bioactive fraction liquisolids compared with Indomethacin with greater safety on GIT, longer duration of action and hence better patient compliance.

  1. SALSA : SAving Lives Staying Active to Promote Physical Activity and Healthy Eating.

    PubMed

    Lee, Rebecca E; Mama, Scherezade K; Medina, Ashley; Orlando Edwards, Raul; McNeill, Lorna

    2011-01-01

    Physical inactivity, poor dietary habits, and obesity are vexing problems among minorities. SAving Lives, Staying Active (SALSA) was an 8-week randomized controlled crossover design, pilot study to promote regular physical activity (PA) and fruit and vegetable (FV) consumption as a means to preventing weight gain among women of color. Participants completed measures of demographics, PA, and dietary habits. Women (N = 50; M = 42 years) who participated were overweight (MBMI = 29.7 kg/m(2); Mbody fat = 38.5%) and reported low levels of leisure time PA (M = 10.7 MET-min/wk) and FV consumption (M = 4.2 servings/day). All were randomized to a four-week (1) semiweekly Latin dance group or (2) internet-based dietary education group. All participants reported a significant increase in weekly leisure time PA from baseline (M = 10.7 MET-min/wk) to follow up (M = 34.0 MET-min/wk, P < .001), and FV consumption increased over time by group (P = .02). Data suggest that Latin dance interventions to improve PA and web-based interventions to improve dietary habits show promise for improving health among women of color.

  2. A trypanosome metacyclic VSG gene promoter with two functionally distinct, life cycle stage-specific activities.

    PubMed

    Graham, S V; Wymer, B; Barry, J D

    1998-04-15

    In the mammalian bloodstream, African trypanosomes express the variant surface glycoprotein (VSG), continual switching of which allows evasion of the host immune response. Bloodstream VSG genes are transcribed from polycistronic bloodstream expression sites with promoters which are located 45-60 kb upstream. These promoters are not exclusively stage-regulated, being active in the insect midgut stage where VSG is not expressed. However, the metacyclic VSG (M-VSG) genes, a small subset activated when VSG synthesis begins in the metacyclic stage in the tsetse fly salivary glands, are transcriptionally activated specifically in that stage from promoters <3 kb upstream. Using deletion mapping and transient transfection, we show that the entire 1.22 M-VSG gene promoter region (171 bp) is required for full activity in metacyclic-derived trypanosomes. However, a subsidiary, bloodstream stage-specific activity is present in its 5' half which directs transcription initiation very close to the initiation site used in metacyclic-derived trypanosomes. Our results imply that the M-VSG gene promoter is longer and more complex than other VSG gene promoters.

  3. Construction and evaluation of a maize (Zea mays) chimaeric promoter with activity in kernel endosperm and embryo.

    PubMed

    Shepherd, Colin T; Scott, M Paul

    2009-03-01

    Chimaeric promoters contain DNA sequences from different promoters. Chimaeric promoters are developed to increase the level of recombinant protein expression, to precisely control transgene activity or to combat homology-based gene silencing. Sets of chimaeric promoters, each containing different lengths of DNA from maize (Zea mays) 27zn (27 kDa gamma-zein) endosperm-specific promoter and the Glb1 (Globulin-1) embryo-specific promoter were created and tested in a transient expression assay of GFP (green fluorescent protein). Promoter fragments with the highest activity were combined to create the chimaeric promoter A27znGlb1. In the context of the chimaeric promoter, the selected Glb1 promoter fragment was necessary and sufficient to activate expression in embryo tissue and was functionally equivalent to the native Glb1 promoter. Similarly, the selected 27zn promoter fragment in the chimaeric promoter was necessary and sufficient to activate expression in endosperm tissue and was functionally equivalent to the native 27zn promoter. Maize transgenic plants containing the A27znGlb1 chimaeric promoter fused to GFP were produced to characterize this promoter in vivo. Quantitative reverse-transcriptase PCR was used to determine that the promoter was active in the embryo, endosperm, pericarp and immature leaf tissues. GFP activity in plants containing the chimaeric promoter was not significantly different in endosperm than the activity of GFP fused to the full-length 27zn promoter, nor was it different in embryo from the activity of GFP fused to the full-length Glb1 promoter. Transgene copy numbers were shown to be between 4 and 12 copies in different events.

  4. Notch signaling promotes osteoclast maturation and resorptive activity

    PubMed Central

    Ashley, Jason W; Ahn, Jaimo; Hankenson, Kurt D

    2015-01-01

    The role of Notch signaling in osteoclast differentiation is controversial with conflicting experimental evidence indicating both stimulatory and inhibitory roles. Differences in experimental protocols and in vivo versus in vitro models may explain the discrepancies between studies. In this study, we investigated cell autonomous roles of Notch signaling in osteoclast differentiation and function by altering Notch signaling during osteoclast differentiation using stimulation with immobilized ligands Jagged1 or Delta-like1 or by suppression with γ-secretase inhibitor DAPT or transcriptional inhibitor SAHM1. Stimulation of Notch signaling in committed osteoclast precursors resulted in larger osteoclasts with a greater number of nuclei and resorptive activity whereas suppression resulted in smaller osteoclasts with fewer nuclei and suppressed resorptive activity. Conversely, stimulation of Notch signaling in osteoclast precursors prior to induction of osteoclastogenesis resulted in fewer osteoclasts. Our data support a mechanism of context-specific Notch signaling effects wherein Notch stimulation inhibits commitment to osteoclast differentiation, but enhances the maturation and function of committed precursors. PMID:25914241

  5. CDPP activities: Promoting research and education in space physics

    NASA Astrophysics Data System (ADS)

    Genot, V. N.; Andre, N.; Cecconi, B.; Gangloff, M.; Bouchemit, M.; Dufourg, N.; Pitout, F.; Budnik, E.; Lavraud, B.; Rouillard, A. P.; Heulet, D.; Bellucci, A.; Durand, J.; Delmas, D.; Alexandrova, O.; Briand, C.; Biegun, A.

    2015-12-01

    The French Plasma Physics Data Centre (CDPP, http://cdpp.eu/) addresses for more than 15 years all issues pertaining to natural plasma data distribution and valorization. Initially established by CNES and CNRS on the ground of a solid data archive, CDPP activities diversified with the advent of broader networks and interoperability standards, and through fruitful collaborations (e.g. with NASA/PDS): providing access to remote data, designing and building science driven analysis tools then became at the forefront of CDPP developments. For instance today AMDA helps scientists all over the world accessing and analyzing data from ancient to very recent missions (from Voyager, Galileo, Geotail, ... to Maven, Rosetta, MMS, ...) as well as results from models and numerical simulations. Other tools like the Propagation Tool or 3DView allow users to put their data in context and interconnect with other databases (CDAWeb, MEDOC) and tools (Topcat). This presentation will briefly review this evolution, show technical and science use cases, and finally put CDPP activities in the perspective of ongoing collaborative projects (Europlanet H2020, HELCATS, ...) and future missions (Bepicolombo, Solar Orbiter, ...).

  6. Phosphorylation of histone H3 is functionally linked to retinoic acid receptor β promoter activation

    PubMed Central

    Lefebvre, Bruno; Ozato, Keiko; Lefebvre, Philippe

    2002-01-01

    Ligand-dependent transcriptional activation of retinoic acid receptors (RARs) is a multistep process culminating in the formation of a multimeric co-activator complex on regulated promoters. Several co-activator complexes harbor an acetyl transferase activity, which is required for retinoid-induced transcription of reporter genes. Using murine P19 embryonal carcinoma cells, we examined the relationship between histone post-translational modifications and activation of the endogenous RARβ2 promoter, which is under the control of a canonical retinoic acid response element and rapidly induced upon retinoid treatment. While histones H3 and H4 were constitutively acetylated at this promoter, retinoid agonists induced a rapid phosphorylation at Ser10 of histone H3. A retinoid antagonist, whose activity was independent of co-repressor binding to RAR, could oppose this agonist-induced H3 phosphorylation. Since such post-translational modifications were not observed at several other promoters, we conclude that histone H3 phosphorylation may be a molecular signature of the activated, retinoid-controlled mRARβ2 gene promoter. PMID:11897660

  7. Promoting physical activity for people with neurological disability: perspectives and experiences of physiotherapists.

    PubMed

    Mulligan, Hilda; Fjellman-Wiklund, Anncristine; Hale, Leigh; Thomas, David; Häger-Ross, Charlotte

    2011-08-01

    Both New Zealand and Sweden have health and disability policies that promote recreational exercise within society for people with disability. Despite these policies, levels of physical activity by people with disability in these countries are low. Physiotherapists are equipped to assist people with disabling conditions into physical activity. This qualitative study explored the perspectives and experiences of physiotherapists in New Zealand and Sweden toward promoting physically active recreation for adults with chronic neurological conditions. Nine physiotherapists who worked with adults with neurological disability in a range of long-term rehabilitation and community (home) health services were interviewed and the data analysed for themes. The physiotherapists described innovative and resourceful expertise to assist patients to be physically active. However, they perceived a lack of support for their work from within the health system and a lack of knowledge of disability issues within the recreational arena, both of which they perceived hindered their promotion of physical activity for people with neurological disability. Physiotherapists feel unable to fully support health and disability policies for the promotion of physically active recreation for people with neurological conditions, because of perceived constraints from within the recreational arena and their own health systems. If these constraints were addressed, then physiotherapists could be better agents to promote physical activity for people with neurological conditions.

  8. Testing promoter activity in the trypanosome genome: isolation of a metacyclic-type VSG promoter, and unexpected insights into RNA polymerase II transcription.

    PubMed

    McAndrew, M; Graham, S; Hartmann, C; Clayton, C

    1998-09-01

    In trypanosomes, most genes are arranged in polycistronic transcription units. Individual mRNAs are generated by 5'-trans splicing and 3' polyadenylation. Remarkably, no regulation of RNA polymerase II transcription has been detected although many RNAs are differentially expressed during kinetoplastid life cycles. Demonstration of specific class II promoters is complicated by the difficulty in distinguishing between genuine promoter activity and stimulation of trans splicing. Using vectors that were designed to allow the detection of low promoter activities in a transcriptionally silent chromosomal context, we isolated a novel trypanosome RNA polymerase I promoter. We were however unable to detect class II promoter activity in any tested DNA fragment. We also integrated genes which were preceded by a T3 promoter into the genome of cells expressing bacteriophage T3 polymerase: surprisingly, transcription was alpha-amanitin sensitive. One possible interpretation of these results is that in trypanosomes, RNA polymerase II initiation is favored by genomic accessibility and double-strand melting.

  9. Evolution of Brain Active Gene Promoters in Human Lineage Towards the Increased Plasticity of Gene Regulation.

    PubMed

    Gunbin, Konstantin V; Ponomarenko, Mikhail P; Suslov, Valentin V; Gusev, Fedor; Fedonin, Gennady G; Rogaev, Evgeny I

    2017-02-24

    Adaptability to a variety of environmental conditions is a prominent feature of Homo sapiens. We hypothesize that this feature can be explained by evolutionary changes in gene promoters active in the brain prefrontal cortex leading to a more flexible gene regulation network. The genotype-dependent range of gene expression can be broader in humans than in other higher primates. Thus, we searched for specific signatures of evolutionary changes in promoter architectures of multiple hominid genes, including the genes active in human cortical neurons that may indicate an increase of variability of gene expression rather than just changes in the level of expression, such as downregulation or upregulation of the genes. We performed a whole-genome search for genetic-based alterations that may impact gene regulation "flexibility" in a process of hominids evolution, such as (i) CpG dinucleotide content, (ii) predicted nucleosome-DNA dissociation constant, and (iii) predicted affinities for TATA-binding protein (TBP) in gene promoters. We tested all putative promoter regions across the human genome and especially gene promoters in active chromatin state in neurons of prefrontal cortex, the brain region critical for abstract thinking and social and behavioral adaptation. Our data imply that the origin of modern man has been associated with an increase of flexibility of promoter-driven gene regulation in brain. In contrast, after splitting from the ancestral lineages of H. sapiens, the evolution of ape species is characterized by reduced flexibility of gene promoter functioning, underlying reduced variability of the gene expression.

  10. Loss of the polycomb mark from bivalent promoters leads to activation of cancer-promoting genes in colorectal tumors.

    PubMed

    Hahn, Maria A; Li, Arthur X; Wu, Xiwei; Yang, Richard; Drew, David A; Rosenberg, Daniel W; Pfeifer, Gerd P

    2014-07-01

    In colon tumors, the transcription of many genes becomes deregulated by poorly defined epigenetic mechanisms that have been studied mainly in established cell lines. In this study, we used frozen human colon tissues to analyze patterns of histone modification and DNA cytosine methylation in cancer and matched normal mucosa specimens. DNA methylation is strongly targeted to bivalent H3K4me3- and H3K27me3-associated promoters, which lose both histone marks and acquire DNA methylation. However, we found that loss of the Polycomb mark H3K27me3 from bivalent promoters was accompanied often by activation of genes associated with cancer progression, including numerous stem cell regulators, oncogenes, and proliferation-associated genes. Indeed, we found many of these same genes were also activated in patients with ulcerative colitis where chronic inflammation predisposes them to colon cancer. Based on our findings, we propose that a loss of Polycomb repression at bivalent genes combined with an ensuing selection for tumor-driving events plays a major role in cancer progression.

  11. The search of the target of promotion: Phenylbenzoate esterase activities in hen peripheral nerve

    SciTech Connect

    Moretto, A. . E-mail: angelo.moretto@icps.it; Nicolli, A.; Lotti, M.

    2007-03-15

    Certain esterase inhibitors, such as carbamates, phosphinates and sulfonyl halides, do not cause neuropathy as some organophosphates, but they may exacerbate chemical or traumatic insults to axons. This phenomenon is called promotion of axonopathies. Given the biochemical and toxicological characteristics of these compounds, the hypothesis was made that the target of promotion is a phenyl valerate (PV) esterase similar to neuropathy target esterase (NTE), the target of organophosphate induced delayed polyneuropathy. However, attempts to identify a PV esterase in hen peripheral nerve have been, so far, unsuccessful. We tested several esters, other than PV, as substrates of esterases from crude homogenate of the hen peripheral nerve. The ideal substrate should be poorly hydrolysed by NTE but extensively by enzyme(s) that are insensitive to non-promoters, such as mipafox, and sensitive to promoters, such as phenyl methane sulfonyl fluoride (PMSF). When phenyl benzoate (PB) was used as substrate, about 65% of total activity was resistant to the non-promoter mipafox (up to 0.5 mM, 20 min, pH 8.0), that inhibits NTE and other esterases. More than 90% of this resistant activity was sensitive to the classical promoter PMSF (1 mM, 20 min, pH 8.0) with an IC{sub 50} of about 0.08 mM (20 min, pH 8.0). On the contrary, the non-promoter p-toluene sulfonyl fluoride caused only about 10% inhibition at 0.5 mM. Several esterase inhibitors including, paraoxon, phenyl benzyl carbamate, di-n-butyl dichlorovinyl phosphate and di-isopropyl fluorophosphate, were tested both in vitro and in vivo for inhibition of this PB activity. Mipafox-resistant PMSF-sensitive PB esterase activity(ies) was inhibited by promoters but not by non promoters and neuropathic compounds.

  12. Promoting uranium immobilization by the activities of microbial phophatases

    SciTech Connect

    Sobecky, Patricia A.

    2005-06-01

    The first objective of this project is to determine the relationship of phosphatase activity to metal resistance in subsurface strains and the role of lateral gene transfer (LGT) in dissemination of nonspecific acid phosphatase genes. Nonspecific acid phosphohydrolases are a broad group of secreted microbial phosphatases that function in acidic-to-neutral pH ranges and utilize a wide range of organophosphate substrates. We have previously shown that PO43- accumulation during growth on a model organophosphorus compound was attributable to the overproduction of alkaline phosphatase by genetically modified subsurface pseudomonads [Powers et al. (2002) FEMS Microbiol. Ecol. 41:115-123]. During this report period, we have extended these results to include indigenous metal resistant subsurface microorganisms cultivated from the Field Research Center (FRC), in Oak Ridge Tennessee.

  13. Activating Lay Health Influencers to Promote Tobacco Cessation

    PubMed Central

    Muramoto, Myra L.; Hall, John R.; Nichter, Mark; Nichter, Mimi; Aickin, Mikel; Connolly, Tim; Matthews, Eva; Campbell, Jean Z.; Lando, Harry A.

    2014-01-01

    Objective Evaluate the effect of tobacco cessation brief-intervention (BI) training for lay “health influencers,” on knowledge, self-efficacy and the proportion of participants reporting BI delivery post-training. Methods Randomized, community-based study comparing In-person or Web-based training, with mailed materials. Results In-person and Web-training groups had significant post-training cessation knowledge and self-efficacy gains. All groups increased the proportion of individuals reporting BIs at follow-up, with no significant between-group differences. Irrespective of participants’ prior intervention experience, 80–86% reported BIs within the past 90 days; 71–79% reported ≥1 in the past 30. Conclusions Web and In-person training significantly increase health influencer cessation knowledge and self-efficacy. With minimal prompting and materials, even persons without BI experience can be activated to encourage tobacco cessation. PMID:24636035

  14. C23 promotes tumorigenesis via suppressing p53 activity

    PubMed Central

    Wang, Juan; Hu, Guilin; Fang, Xing; Hu, Yamin; Tao, Tingting; Wei, Xin; Tang, Haitao; Huang, Baojun; Hu, Wanglai

    2016-01-01

    C23 is an abundant and multi-functional protein, which plays an important role in various biological processes, including ribosome biogenesis and maturation, cell cycle checkpoints and transcriptional regulation [1, 2]. However, the role of C23 in controlling tumorigenesis has not been well defined. Here we report that C23 is highly expressed in cancer cells and the elevated expression of C23 facilitates cancer cell proliferation in vitro and tumor xenograft growth in vivo. Notably, C23 binds to p53 through its GAR domain and suppresses the transcriptional activity of p53 under DNA damage and hypoxia. Moreover, the GAR domain is critical for C23-mediated tumor cell proliferation both in vitro and in vivo. Our findings reveal a novel role of C23 in tumorigenesis and suggest that C23 may represent a potential therapeutic target for treating malignancy. PMID:27506938

  15. Natural lecithin promotes neural network complexity and activity

    PubMed Central

    Latifi, Shahrzad; Tamayol, Ali; Habibey, Rouhollah; Sabzevari, Reza; Kahn, Cyril; Geny, David; Eftekharpour, Eftekhar; Annabi, Nasim; Blau, Axel; Linder, Michel; Arab-Tehrany, Elmira

    2016-01-01

    Phospholipids in the brain cell membranes contain different polyunsaturated fatty acids (PUFAs), which are critical to nervous system function and structure. In particular, brain function critically depends on the uptake of the so-called “essential” fatty acids such as omega-3 (n-3) and omega-6 (n-6) PUFAs that cannot be readily synthesized by the human body. We extracted natural lecithin rich in various PUFAs from a marine source and transformed it into nanoliposomes. These nanoliposomes increased neurite outgrowth, network complexity and neural activity of cortical rat neurons in vitro. We also observed an upregulation of synapsin I (SYN1), which supports the positive role of lecithin in synaptogenesis, synaptic development and maturation. These findings suggest that lecithin nanoliposomes enhance neuronal development, which may have an impact on devising new lecithin delivery strategies for therapeutic applications. PMID:27228907

  16. Hunger Promotes Fear Extinction by Activation of an Amygdala Microcircuit.

    PubMed

    Verma, Dilip; Wood, James; Lach, Gilliard; Herzog, Herbert; Sperk, Guenther; Tasan, Ramon

    2016-01-01

    Emotions control evolutionarily-conserved behavior that is central to survival in a natural environment. Imbalance within emotional circuitries, however, may result in malfunction and manifestation of anxiety disorders. Thus, a better understanding of emotional processes and, in particular, the interaction of the networks involved is of considerable clinical relevance. Although neurobiological substrates of emotionally controlled circuitries are increasingly evident, their mutual influences are not. To investigate interactions between hunger and fear, we performed Pavlovian fear conditioning in fasted wild-type mice and in mice with genetic modification of a feeding-related gene. Furthermore, we analyzed in these mice the electrophysiological microcircuits underlying fear extinction. Short-term fasting before fear acquisition specifically impaired long-term fear memory, whereas fasting before fear extinction facilitated extinction learning. Furthermore, genetic deletion of the Y4 receptor reduced appetite and completely impaired fear extinction, a phenomenon that was rescued by fasting. A marked increase in feed-forward inhibition between the basolateral and central amygdala has been proposed as a synaptic correlate of fear extinction and involves activation of the medial intercalated cells. This form of plasticity was lost in Y4KO mice. Fasting before extinction learning, however, resulted in specific activation of the medial intercalated neurons and re-established the enhancement of feed-forward inhibition in this amygdala microcircuit of Y4KO mice. Hence, consolidation of fear and extinction memories is differentially regulated by hunger, suggesting that fasting and modification of feeding-related genes could augment the effectiveness of exposure therapy and provide novel drug targets for treatment of anxiety disorders.

  17. Hunger Promotes Fear Extinction by Activation of an Amygdala Microcircuit

    PubMed Central

    Verma, Dilip; Wood, James; Lach, Gilliard; Herzog, Herbert; Sperk, Guenther; Tasan, Ramon

    2016-01-01

    Emotions control evolutionarily-conserved behavior that is central to survival in a natural environment. Imbalance within emotional circuitries, however, may result in malfunction and manifestation of anxiety disorders. Thus, a better understanding of emotional processes and, in particular, the interaction of the networks involved is of considerable clinical relevance. Although neurobiological substrates of emotionally controlled circuitries are increasingly evident, their mutual influences are not. To investigate interactions between hunger and fear, we performed Pavlovian fear conditioning in fasted wild-type mice and in mice with genetic modification of a feeding-related gene. Furthermore, we analyzed in these mice the electrophysiological microcircuits underlying fear extinction. Short-term fasting before fear acquisition specifically impaired long-term fear memory, whereas fasting before fear extinction facilitated extinction learning. Furthermore, genetic deletion of the Y4 receptor reduced appetite and completely impaired fear extinction, a phenomenon that was rescued by fasting. A marked increase in feed-forward inhibition between the basolateral and central amygdala has been proposed as a synaptic correlate of fear extinction and involves activation of the medial intercalated cells. This form of plasticity was lost in Y4KO mice. Fasting before extinction learning, however, resulted in specific activation of the medial intercalated neurons and re-established the enhancement of feed-forward inhibition in this amygdala microcircuit of Y4KO mice. Hence, consolidation of fear and extinction memories is differentially regulated by hunger, suggesting that fasting and modification of feeding-related genes could augment the effectiveness of exposure therapy and provide novel drug targets for treatment of anxiety disorders. PMID:26062787

  18. Stat5 Promotes Survival of Mammary Epithelial Cells through Transcriptional Activation of a Distinct Promoter in Akt1▿

    PubMed Central

    Creamer, Bradley A.; Sakamoto, Kazuhito; Schmidt, Jeffrey W.; Triplett, Aleata A.; Moriggl, Richard; Wagner, Kay-Uwe

    2010-01-01

    The signal transducer and activator of transcription 5 (Stat5) plays a pivotal role in the proliferation, secretory differentiation, and survival of mammary epithelial cells. However, there is little information about Stat5 target genes that facilitate these biological processes. We provide here experimental evidence that the prolactin-mediated phosphorylation of Stat5 regulates the transcriptional activation of the Akt1 gene. Stat5 binds to consensus sequences within the Akt1 locus in a growth factor-dependent manner to initiate transcription of a unique Akt1 mRNA from a distinct promoter, which is only active in the mammary gland. Elevating the levels of active Akt1 restores the expression of cyclin D1 and proliferation of Jak2-deficient mammary epithelial cells, which provides evidence that Akt1 acts downstream of Jak/Stat signaling. The ligand-inducible expression of Stat5 in transgenic females mediates a sustained upregulation of Akt1 in mammary epithelial cells during the onset of postlactational involution. Stat5-expressing mammary glands exhibit a delay in involution despite induction of proapoptotic signaling events. Collectively, the results of the present study elucidate an underlying mechanism by which active Stat5 mediates evasion from apoptosis and self-sufficiency in growth signals. PMID:20385773

  19. ERK5 Activation in Macrophages Promotes Efferocytosis and Inhibits Atherosclerosis

    PubMed Central

    Heo, Kyung-Sun; Cushman, Hannah J.; Akaike, Masashi; Woo, Chang-Hoon; Wang, Xin; Qiu, Xing; Fujiwara, Keigi; Abe, Jun-ichi

    2015-01-01

    Background Efferocytosis is a process by which dead and dying cells are removed by phagocytic cells. Efferocytosis by macrophages is thought to curb the progression of atherosclerosis, but the mechanistic insight of this process is lacking. Methods and Results When macrophages were fed apoptotic cells or treated with pitavastatin in vitro, efferocytosis-related signaling and phagocytic capacity were upregulated in an ERK5 activity–dependent manner. Macrophages isolated from macrophage-specific ERK5-null mice exhibited reduced efferocytosis and levels of gene and protein expression of efferocytosis-related molecules. When these mice were crossed with low-density lipoprotein receptor−/− mice and fed a high-cholesterol diet, atherosclerotic plaque formation was accelerated, and the plaques had more advanced and vulnerable morphology. Conclusions Our results demonstrate that ERK5, which is robustly activated by statins, is a hub molecule that upregulates macrophage efferocytosis, thereby suppressing atherosclerotic plaque formation. Molecules that upregulate ERK5 and its signaling in macrophages may be good drug targets for suppressing cardiovascular diseases. PMID:25001623

  20. SHADE: A Shape-Memory-Activated Device Promoting Ankle Dorsiflexion

    NASA Astrophysics Data System (ADS)

    Pittaccio, S.; Viscuso, S.; Rossini, M.; Magoni, L.; Pirovano, S.; Villa, E.; Besseghini, S.; Molteni, F.

    2009-08-01

    Acute post-stroke rehabilitation protocols include passive mobilization as a means to prevent contractures. A device (SHADE) that provides repetitive passive motion to a flaccid ankle by using shape memory alloy actuators could be of great help in providing this treatment. A suitable actuator was designed as a cartridge of approximately 150 × 20 × 15 mm, containing 2.5 m of 0.25 mm diameter NiTi wire. This actuator was activated by Joule’s effect employing a 7 s current input at 0.7 A, which provided 10 N through 76 mm displacement. Cooling and reset by natural convection took 30 s. A prototype of SHADE was assembled with two thermoplastic shells hinged together at the ankle and strapped on the shin and foot. Two actuators were fixed on the upper shell while an inextensible thread connected each NiTi wire to the foot shell. The passive ankle motion (passive range of motion, PROM) generated by SHADE was evaluated optoelectronically on three flaccid patients (58 ± 5 years old); acceptability was assessed by a questionnaire presented to further three flaccid patients (44 ± 11.5 years old) who used SHADE for 5 days, 30 min a day. SHADE was well accepted by all patients, produced good PROM, and caused no pain. The results prove that suitable limb mobilization can be produced by SMA actuators.

  1. [Physical activity based on the new health promotion perspective: contradictions of an institutional program].

    PubMed

    Ferreira, Marcos Santos; Castiel, Luis David; Cardoso, Maria Helena Cabral de Almeida

    2011-01-01

    This article aims to discuss how the ambiguity of health promotion occurs in one physical activity institutional program. Firstly, different approaches to health promotion are presented as embodiments of such ambiguities. Then, after a brief discussion about manifestations of such ambiguity in everyday media coverage, we analyze the Agita São Paulo Program, regarded by the World Health Organization as an example of health promotion initiative. The conclusion is that, in spite of being under the umbrella of the so-called new health promotion movement, the Agita São Paulo Program is based upon behavioral/conservative approaches of health promotion because it demonizes sedentarism, blames its followers and supports its strategies in terms of behavioral changes as a way of reducing epidemiologic risks, in spite of social, economic and cultural determinants.

  2. Recruiting Older Adults into a Physical Activity Promotion Program: "Active Living Every Day" Offered in a Naturally Occurring Retirement Community

    ERIC Educational Resources Information Center

    Hildebrand, Mary; Neufeld, Peggy

    2009-01-01

    Purpose: This article explores recruitment strategies based on the transtheoretical model (TTM) with older adults living in a naturally occurring retirement community (NORC) to encourage enrollment in a physical activity promotion program, "Active Living Every Day" (ALED). Reasons for participation or nonparticipation are identified. Design and…

  3. Desired features of smartphone applications promoting physical activity.

    PubMed

    Rabin, Carolyn; Bock, Beth

    2011-12-01

    Approximately one-third of adults in the United States are physically inactive. This is a significant public health concern as physical activity (PA) can influence the risk of cardiovascular disease, diabetes, and certain forms of cancer. To minimize these health risks, effective PA interventions must be developed and disseminated to the vast number of individuals who remain sedentary. Smartphone technology presents an exciting opportunity for delivering PA interventions remotely. Although a number of PA applications are currently available for smartphones, these "apps" are not based on established theories of health behavior change and most do not include evidence-based features (e.g., reinforcement and goal setting). Our aim was to collect formative data to develop a smartphone PA app that is empirically and theoretically-based and incorporates user preferences. We recruited 15 sedentary adults to test three currently available PA smartphone apps and provide qualitative and quantitative feedback. Findings indicate that users have a number of specific preferences with regard to PA app features, including that apps provide automatic tracking of PA (e.g., steps taken and calories burned), track progress toward PA goals, and integrate a music feature. Participants also preferred that PA apps be flexible enough to be used with several types of PA, and have well-documented features and user-friendly interfaces (e.g., a one-click main page). When queried by the researcher, most participants endorsed including goal-setting and problem-solving features. These findings provide a blue print for developing a smartphone PA app that incorporates evidence-based components and user preferences.

  4. Mutation of the TERT promoter, switch to active chromatin, and monoallelic TERT expression in multiple cancers

    PubMed Central

    Stern, Josh Lewis; Theodorescu, Dan; Vogelstein, Bert; Papadopoulos, Nickolas; Cech, Thomas R.

    2015-01-01

    Somatic mutations in the promoter of the gene for telomerase reverse transcriptase (TERT) are the most common noncoding mutations in cancer. They are thought to activate telomerase, contributing to proliferative immortality, but the molecular events driving TERT activation are largely unknown. We observed in multiple cancer cell lines that mutant TERT promoters exhibit the H3K4me2/3 mark of active chromatin and recruit the GABPA/B1 transcription factor, while the wild-type allele retains the H3K27me3 mark of epigenetic silencing; only the mutant promoters are transcriptionally active. These results suggest how a single-base-pair mutation can cause a dramatic epigenetic switch and monoallelic expression. PMID:26515115

  5. Anti-tumor-promoting activity of lignans from the aerial part of Saussurea medusa.

    PubMed

    Takasaki, M; Konoshima, T; Komatsu, K; Tokuda, H; Nishino, H

    2000-09-29

    In the course of our continuing search for novel cancer chemopreventive agents from natural sources, several kinds of Compositae plants were screened. Consequently, the lignans, arctiin (ARC) and arctigenin (ARC-G), were obtained from the aerial part of Saussurea medusaas active constituents. These compounds exhibited the remarkable anti-tumor-promoting effect on two-stage carcinogenesis test of mouse skin tumors induced by 7, 12-dimethylbenz[a]anthracene as an initiator and 12-O-tetradecanoyl phorbol-13-acetate as a promoter by both topical application and oral administration. Furthermore, ARC-G exhibited potent anti-tumor-promoting activity on two-stage carcinogenesis test of mouse pulmonary tumors induced by 4-nitroquinoline-N-oxide as an initiator and glycerol as a promoter.

  6. Recent Activities of the Physical Society of Japan for the Promotion of Gender Equality (abstract)

    NASA Astrophysics Data System (ADS)

    Maeda, Atsutaka; Yonenaga, Ichiro; Tajima, Setsuko; Hiyama, Emiko; Torikai, Eiko

    2009-04-01

    We present activities of the Gender Equality Promotion Committee of the Physical Society of Japan (JPS) untaken after the Second IUPAP Women in Physics Conference, Rio de Janiero, 2005. These include: (1) summer and spring classes for high school girls, (2) symposia on the promotion of gender equality at annual JPS meetings, (3) continuous cooperation with the Japan Inter-Society Liaison Association Committee for Promoting Equal Participation of Men and Women in Science and Engineering (EPMEWSE), (4) consultation for JPS members on the Restart Postdoctoral Fellowship (RPD) program conducted by the Japan Society for the Promotion of Science (JSPS), (5) publication of a series of articles in the JPS membership journal, and (6) presentation at international meetings such as the Asia Pacific Physics Conference 10 (APPC10). We report that these activities were successful.

  7. An Exploratory Study of Elementary Classroom Teachers' Physical Activity Promotion from a Social Learning Perspective

    ERIC Educational Resources Information Center

    Webster, Collin A.; Buchan, Heather; Perreault, Melanie; Doan, Rob; Doutis, Panayiotis; Weaver, Robert Glenn

    2015-01-01

    Despite its recommended use, physical activity promotion in the academic classroom (PAPAC) has received little attention in terms of the factors that help to facilitate it. In this study, a social learning perspective was adopted to examine the role of physical activity biographies in generalist classroom teachers' (CTs) PAPAC. CTs (N = 213) were…

  8. Use and Nonuse of a Rail Trail Conversion for Physical Activity: Implications for Promoting Trail Use

    ERIC Educational Resources Information Center

    Price, Anna E.; Reed, Julian A.

    2014-01-01

    Background: There is limited research examining both use and nonuse of trails for physical activity. Purpose: Such research might enable health educators to better promote physical activity on trails.Methods:We used random digit dialing methods to survey 726 respondents in 2012. Results: The majority (75.1%) of respondents reported not using the…

  9. Self-Determination in Physical Education: Designing Class Environments to Promote Active Lifestyles

    ERIC Educational Resources Information Center

    Bryan, Charity L.; Solmon, Melinda A.

    2007-01-01

    Recently, the lack of physical activity and increasing rates of childhood obesity have received a great deal of attention in the United States. One way to combat inactivity in children is to utilize physical education programs as a means to promote active lifestyles. There is not, however, a consensus concerning how physical education programs can…

  10. Promoter analysis of mouse Scn3a gene and regulation of the promoter activity by GC box and CpG methylation.

    PubMed

    Deng, Guang-Fei; Qin, Jia-Ming; Sun, Xun-Sha; Kuang, Zu-Ying; Su, Tao; Zhao, Qi-Hua; Shi, Yi-Wu; Liu, Xiao-Rong; Yu, Mei-Juan; Yi, Yong-Hong; Liao, Wei-Ping; Long, Yue-Sheng

    2011-06-01

    Voltage-gated sodium channel α-subunit type III (Na(v)1.3) is mainly expressed in the central nervous system and is associated with neurological disorders. The expression of mouse Scn3a product (Na(v)1.3) mainly occurs in embryonic and early postnatal brain but not in adult brain. Here, we report for the first time the identification and characterization of the mouse Scn3a gene promoter region and regulation of the promoter activity by GC box and CpG methylation. Luciferase assay showed that the promoter region F1.2 (nt -1,049 to +157) had significantly higher activity in PC12 cells, comparing with that in SH-SY5Y cells and HEK293 cells. A stepwise 5' truncation of the promoter region found that the minimal functional promoter located within the region nt -168 to +157. Deletion of a GC box (nt -254 to -258) in the mouse Scn3a promoter decreased the promoter activity. CpG methylation of the F1.2 without the GC box completely repressed the promoter activity, suggesting that the GC box is a critical element in the CpG-methylated Scn3a promoter. These results suggest that the GC box and CpG methylation might play important roles in regulating mouse Scn3a gene expression.

  11. Leptin activates chicken growth hormone promoter without chicken STAT3 in vitro.

    PubMed

    Murase, Daisuke; Namekawa, Shoko; Ohkubo, Takeshi

    2016-01-01

    Leptin is an adipocyte-derived hormone that not only regulates food intake and energy homeostasis but also induces growth hormone (GH) mRNA expression and release, thereby controlling growth and metabolism in mammals. The molecular mechanism of leptin-induced regulation of GH gene transcription is unclear. The current study investigated the effects of leptin on the chicken GH (cGH) promoter and the molecular mechanism underlying leptin-induced cGH gene expression in vitro. Leptin activated the cGH promoter in the presence of chPit-1α in CHO cells stably expressing the chicken leptin receptor. Promoter activation did not require STAT-binding elements in the cGH promoter or STAT3 activity. However, JAK2 activation was required for leptin-dependent activity. JAK2-dependent pathways include p42/44 MAPK and PI3K, and inhibition of these pathways partially blocked leptin-induced cGH gene transcription. Although CK2 directly activates JAK2, a CK2 inhibitor blocked leptin-dependent activation of the cGH gene without affecting JAK2 phosphorylation. The CK2 inhibitor suppressed Erk1/2 and Akt phosphorylation. Additional data implicate Src family kinases in leptin-dependent cGH gene activation. These results suggest that leptin activates the cGH gene in the presence of chPit-1α via several leptin-activated kinases. Although further study is required, we suggest that the leptin-induced JAK2/p42/44 MAPK and JAK2/PI3K cascades are activated by Src-meditated CK2, leading to CBP phosphorylation and interaction with chPit-1α, resulting in transactivation of the cGH promoter.

  12. Selection and Characterization of Conditionally Active Promoters in Lactobacillus plantarum, Using Alanine Racemase as a Promoter Probe

    PubMed Central

    Bron, Peter A.; Hoffer, Sally M.; Van Swam, Iris I.; De Vos, Willem M.; Kleerebezem, Michiel

    2004-01-01

    This paper describes the use of the alr gene, encoding alanine racemase, as a promoter-screening tool for the identification of conditional promoters in Lactobacillus plantarum. Random fragments of the L. plantarum WCFS1 genome were cloned upstream of the promoterless alr gene of Lactococcus lactis in a low-copy-number plasmid vector. The resulting plasmid library was introduced into an L. plantarum Δalr strain (MD007), and 40,000 clones were selected. The genome coverage of the library was estimated to be 98%, based on nucleotide insert sequence and restriction analyses of the inserts of randomly selected clones. The library was screened for clones that were capable of complementing the d-alanine auxotroph phenotype of MD007 in media containing up to 10, 100, or 300 μg of the competitive Alr inhibitor d-cycloserine per ml. Western blot analysis with polyclonal antibodies raised against lactococcal Alr revealed that the Alr production level required for growth increased in the presence of increasing concentrations of d-cycloserine, adding a quantitative factor to the primarily qualitative nature of the alr complementation screen. Screening of the alr complementation library for clones that could grow only in the presence of 0.8 M NaCl resulted in the identification of eight clones that upon Western blot analysis showed significantly higher Alr production under high-salt conditions than under low-salt conditions. These results established the effectiveness of the alanine racemase complementation screening method for the identification of promoters on their conditional or constitutive activity. PMID:14711657

  13. Inverse correlation between promoter strength and excision activity in class 1 integrons.

    PubMed

    Jové, Thomas; Da Re, Sandra; Denis, François; Mazel, Didier; Ploy, Marie-Cécile

    2010-01-01

    Class 1 integrons are widespread genetic elements that allow bacteria to capture and express gene cassettes that are usually promoterless. These integrons play a major role in the dissemination of antibiotic resistance among Gram-negative bacteria. They typically consist of a gene (intI) encoding an integrase (that catalyzes the gene cassette movement by site-specific recombination), a recombination site (attI1), and a promoter (Pc) responsible for the expression of inserted gene cassettes. The Pc promoter can occasionally be combined with a second promoter designated P2, and several Pc variants with different strengths have been described, although their relative distribution is not known. The Pc promoter in class 1 integrons is located within the intI1 coding sequence. The Pc polymorphism affects the amino acid sequence of IntI1 and the effect of this feature on the integrase recombination activity has not previously been investigated. We therefore conducted an extensive in silico study of class 1 integron sequences in order to assess the distribution of Pc variants. We also measured these promoters' strength by means of transcriptional reporter gene fusion experiments and estimated the excision and integration activities of the different IntI1 variants. We found that there are currently 13 Pc variants, leading to 10 IntI1 variants, that have a highly uneven distribution. There are five main Pc-P2 combinations, corresponding to five promoter strengths, and three main integrases displaying similar integration activity but very different excision efficiency. Promoter strength correlates with integrase excision activity: the weaker the promoter, the stronger the integrase. The tight relationship between the aptitude of class 1 integrons to recombine cassettes and express gene cassettes may be a key to understanding the short-term evolution of integrons. Dissemination of integron-driven drug resistance is therefore more complex than previously thought.

  14. Cruciform-extruding regulatory element controls cell-specific activity of the tyrosine hydroxylase gene promoter.

    PubMed Central

    Kim, E L; Peng, H; Esparza, F M; Maltchenko, S Z; Stachowiak, M K

    1998-01-01

    Tyrosine hydroxylase (TH) is expressed specifically in catecholaminergic cells. We have identified a novel regulatory sequence in the upstream region of the bovine TH gene promoter formed by a dyad symmetry element (DSE1;-352/-307 bp). DSE1 supports TH promoter activity in TH-expressing bovine adrenal medulla chromaffin (BAMC) cells and inhibits promoter activity in non-expressing TE671 cells. DNase I footprinting of relaxed TH promoter DNA showed weak binding of nuclear BAMC cell proteins to a short sequence in the right DSE1 arm. In BAMC cells, deletion of the right arm markedly reduced the expression of luciferase from the TH promoter. However, deletion of the left DSE1 arm or its reversed orientation (RevL) also inactivated the TH promoter. In supercoiled TH promoter, DSE1 assumes a cruciform-like conformation i.e., it binds cruciform-specific 2D3 antibody, and S1 nuclease-cleavage and OsO4-modification assays have identified an imperfect cruciform extruded by the DSE1. DNase I footprinting of supercoiled plasmid showed that cruciformed DSE1 is targeted by nuclear proteins more efficiently than the linear duplex isomer and that the protected site encompasses the left arm and center of DSE1. Our results suggest that the disruption of intrastrand base-pairing preventing cruciform formation and protein binding to DSE1 is responsible for its inactivation in DSE1 mutants. DSE1 cruciform may act as a target site for activator (BAMC cells) and repressor (TE671) proteins. Its extrusion emerges as a novel mechanism that controls cell-specific promoter activity. PMID:9512554

  15. RXRα and LXR activate two promoters in placenta- and tumor-specific expression of PLAC1

    PubMed Central

    Chen, Yaohui; Moradin, Adi; Schlessinger, David; Nagaraja, Ramaiah

    2011-01-01

    PLAC1 expression, first characterized as restricted to developing placenta among normal tissues, is also found in a wide range of tumors and transformed cell lines. To understand the basis for its unusual expression profile, we have analyzed the gene structure and its mode of transcription. We find that the gene has a hitherto unique feature, with two promoters, P1 and P2, separated by 105 kb. P2 has been described before. Here we define P1 and show that it and P2 are activated by RXRα in conjunction with LXRα or LXRβ. In placenta, P2 is the preferred promoter, whereas various tumor cell lines tend to express predominantly either one or the other promoter. Furthermore, when each promoter is fused to a luciferase reporter gene and transfected into cancer cell lines, the promoter corresponding to the more active endogenous promoter is preferentially transcribed. Joint expression of activating nuclear receptors can partially account for the restricted expression of PLAC1 in placenta, and may be co-opted for preferential P1 or P2 PLAC1 expression in various tumor cells. PMID:21937108

  16. Characterization of sequence elements from Malvastrum yellow vein betasatellite regulating promoter activity and DNA replication

    PubMed Central

    2012-01-01

    Background Many monopartite begomoviruses are associated with betasatellites, but only several promoters from which were isolated and studied. In this study, the βC1 promoter from Malvastrum yellow vein betasatellite (MYVB) was characterized and important sequence elements were identified to modulate promoter activity and replication of MYVB. Results A 991 nucleotide (nt) fragment upstream of the translation start site of the βC1 open reading frame of MYVB and a series of deletions within this fragment were constructed and fused to the β-glucuronidase (GUS) and green fluorescent protein (GFP) reporter genes, respectively. Agrobacterium-mediated transient expression assays showed that the 991 nt fragment was functional and that a 28 nt region (between −390 nt and −418 nt), which includes a 5′UTR Py-rich stretch motif, was important for promoter activity. Replication assays using Nicotiana benthamiana leaf discs and whole plants showed that deletion of the 5′UTR Py-rich stretch impaired viral satellite replication in the presence of the helper virus. Transgenic assays demonstrated that the 991 nt fragment conferred a constitutive expression pattern in transgenic tobacco plants and that a 214 nt fragment at the 3'-end of this sequence was sufficient to drive this expression pattern. Conclusion Our results showed that the βC1 promoter of MYVB displayed a constitutive expression pattern and a 5′UTR Py-rich stretch motif regulated both βC1 promoter activity and MYVB replication. PMID:23057573

  17. Promotion of beta-glucan synthase activity in corn microsomal membranes by calcium and protein phosphorylation

    NASA Technical Reports Server (NTRS)

    Paliyath, G.; Poovaiah, B. W.

    1988-01-01

    Regulation of the activity of beta-glucan synthase was studied using microsomal preparations from corn coleoptiles. The specific activity as measured by the incorporation of glucose from uridine diphospho-D-[U-14C]glucose varied between 5 to 15 pmol (mg protein)-1 min-1. Calcium promoted beta-glucan synthase activity and the promotion was observed at free calcium concentrations as low as 1 micromole. Kinetic analysis of substrate-velocity curve showed an apparent Km of 1.92 x 10(-4) M for UDPG. Calcium increased the Vmax from 5.88 x 10(-7) mol liter-1 min-1 in the absence of calcium to 9.52 x 10(-7) mol liter-1 min-1 and 1.66 x 10(-6) mol liter-1 min-1 in the presence of 0.5 mM and 1 mM calcium, respectively. The Km values remained the same under these conditions. Addition of ATP further increased the activity above the calcium-promoted level. Sodium fluoride, a phosphoprotein phosphatase inhibitor, promoted glucan synthase activity indicating that phosphorylation and dephosphorylation are involved in the regulation of the enzyme activity. Increasing the concentration of sodium fluoride from 0.25 mM to 10 mM increased glucan synthase activity five-fold over the + calcium + ATP control. Phosphorylation of membrane proteins also showed a similar increase under these conditions. Calmodulin, in the presence of calcium and ATP stimulated glucan synthase activity substantially, indicating that calmodulin could be involved in the calcium-dependent phosphorylation and promotion of beta-glucan synthase activity. The role of calcium in mediating auxin action is discussed.

  18. [Activities of voivodeship occupational medicine centers in workplace health promotion in 2008].

    PubMed

    Goszczyńska, Eliza

    2010-01-01

    The paper aims to present the activities of the largest Voivodeship Occupational Medicine Centers (VOMCs) in Poland in the area of workplace health promotion in 2008. It was compiled on the basis of written reports concerning these activities sent by the Centers to the Polish National Center for Workplace Health Promotion, Nofer Institute of Occupational Medicine, Łódź. Their analysis shows a greatly varied level of engagement in and understanding of health promotion--from simple single actions (in the field of health education and screening) to long-running programs, including various ways of influencing people the programs are addressed to. In 2008, there were 78 such programs in the country, the most popular of them were those focused on occupational voice disorders and tobacco smoke). VOMCs perceive external factors, unfavorable or indifferent attitudes towards promoting health of their employees on the part of employers as well as financial constraints, as the most common obstacles in undertaking activities in the field of workplace health promotion. At the same time, they link achievements in this field mostly with their own activities, including effective cooperation with various partners and their well qualified and experienced employees.

  19. Persistent synchronized oscillations in prolactin gene promoter activity in living pituitary cells.

    PubMed

    McFerran, D W; Stirland, J A; Norris, A J; Khan, R A; Takasuka, N; Seymour, Z C; Gill, M S; Robertson, W R; Loudon, A S; Davis, J R; White, M R

    2001-07-01

    PRL gene expression in the anterior pituitary gland responds rapidly to different hormonal signals. We have investigated the long-term timing of transcriptional activation from the PRL, GH, and cytomegalovirus promoters in response to different stimulus duration, using real-time imaging of luciferase expression in living stably transfected GH3 cells. Long-term stimulation of serum-starved cells with 50% serum induced a homogeneous rise in PRL promoter activity, with subsequent heterogeneous fluctuations in luciferase activity in individual cells. When cells were subjected to a 2-h pulse of 50% serum, followed by serum-free medium, there were long-term (approximately 50 h) synchronized, homogeneous oscillations in PRL promoter activity. This response was PRL-specific, because in GH3 cells expressing luciferase from the GH or cytomegalovirus promoters, a serum pulse elicited no oscillations in luciferase expression after an initial transient response to serum. The PRL promoter may therefore be a template for an unstable transcription complex subject to stochastic regulation, allowing an oscillatory transcriptional response to physiological signals. This suggests that precise timing and coordination of cell responses to different signal-duration may represent a novel mechanism for coordinating long-term dynamic changes in transcription in cell populations.

  20. Using the Tax System to Promote Physical Activity: Critical Analysis of Canadian Initiatives

    PubMed Central

    Larre, Tamara; Sauder, JoAnne

    2011-01-01

    In Canada, tax incentives have been recently introduced to promote physical activity and reduce rates of obesity. The most prominent of these is the federal government's Children's Fitness Tax Credit, which came into effect in 2007. We critically assess the potential benefits and limitations of using tax measures to promote physical activity. Careful design could make these measures more effective, but any tax-based measures have inherent limitations, and the costs of such programs are substantial. Therefore, it is important to consider whether public funds are better spent on other strategies that could instead provide direct public funding to address environmental and systemic factors. PMID:21680912

  1. Factors Involved in Iranian Women Heads of Household's Health Promotion Activities: A Grounded Theory Study.

    PubMed

    Rafii, Forough; Seyedfatemi, Naima; Rezaei, Mahboubeh

    2013-01-01

    We aimed to explore and describe the factors involved in Iranian women heads of household's health promotion activities. Grounded theory was used as the method. Sixteen women heads of household were recruited. Data were generated by semi structured interviews. Our findings indicated that remainder of resources (money, time and energy) alongside perceived severity of health risk were two main factors whereas women's personal and socio-economic characteristics were two contextual factors involved in these women's health promotion activities. To help these women improve their health status, we recommended that the government, non-governmental organizations and health care professionals provide them with required resources and increase their knowledge by holding training sessions.

  2. Cultivating social work leadership in health promotion and aging: strategies for active aging interventions.

    PubMed

    Marshall, Victor W; Altpeter, Mary

    2005-05-01

    The rapid growth of the population of older adults and their concomitant physical status and health needs have captured the attention, collaboration, and funding support of an array of leaders in the fields of aging and health care. To help fill the void of literature available to social workers interested in health promotion and aging, the authors provide a conceptual clarification of the meaning of health and explain how health is a resource for optimal living and not merely the absence of disease. The authors analyze frameworks of health promotion and suggest that the ecological approach provides the ideal framework for devising successful strategies in the area of aging. Finally, using the example of promoting physical activity as a healthy aging strategy, they detail eight ways that social workers can provide leadership in promoting positive health in later life.

  3. An Updated Review of Interventions that Include Promotion of Physical Activity for Adult Men.

    PubMed

    Bottorff, Joan L; Seaton, Cherisse L; Johnson, Steve T; Caperchione, Cristina M; Oliffe, John L; More, Kimberly; Jaffer-Hirji, Haleema; Tillotson, Sherri M

    2015-06-01

    The marked disparity in life expectancy between men and women suggests men are a vulnerable group requiring targeted health promotion programs. As such, there is an increasing need for health promotion strategies that effectively engage men with their health and/or illness management. Programs that promote physical activity could significantly improve the health of men. Although George et al. (Sports Med 42(3):281, 30) reviewed physical activity programs involving adult males published between 1990 and 2010, developments in men's health have prompted the emergence of new sex- and gender-specific approaches targeting men. The purpose of this review was to: (1) extend and update the review undertaken by George et al. (Sports Med 42(3):281, 30) concerning the effectiveness of physical activity programs in males, and (2) evaluate the integration of gender-specific influences in the content, design, and delivery of men's health promotion programs. A search of MEDLINE, CINAHL, ScienceDirect, Web of Science, PsycINFO, the Cochrane Library, and the SPORTDiscus databases for articles published between January 2010 and August 2014 was conducted. In total, 35 studies, involving evaluations of 31 programs, were identified. Findings revealed that a variety of techniques and modes of delivery could effectively promote physical activity among men. Though the majority of programs were offered exclusively to men, 12 programs explicitly integrated gender-related influences in male-specific programs in ways that recognized men's interests and preferences. Innovations in male-only programs that focus on masculine ideals and gender influences to engage men in increasing their physical activity hold potential for informing strategies to promote other areas of men's health.

  4. PKCε ACTIVATION PROMOTES FGF-2 EXOCYTOSIS AND INDUCES ENDOTHELIAL CELL PROLIFERATION AND SPROUTING

    PubMed Central

    Monti, Martina; Donnini, Sandra; Morbidelli, Lucia; Giachetti, Antonio; Mochly-Rosen, Daria; Mignatti, Paolo; Ziche, Marina

    2013-01-01

    Protein kinase C epsilon (PKCε) activation controls fibroblast growth factor-2 (FGF-2) angiogenic signaling. Here, we examined the effect of activating PKCε on FGF-2 dependent vascular growth and endothelial activation. ψεRACK, a selective PKCε agonist induces pro-angiogenic responses in endothelial cells, including formation of capillary like structures and cell growth. These effects are mediated by FGF-2 export to the cell membrane, as documented by biotinylation and immunofluorescence, and FGF-2/FGFR1 signaling activation, as attested by ERK1/2-STAT-3 phosphorylation and de novo FGF-2 synthesis. Similarly, vascular endothelial growth factor (VEGF) activates PKCε in endothelial cells, and promotes FGF-2 export and FGF-2/FGFR1 signaling activation. ψεRACK fails to elicit responses in FGF-2−/− endothelial cells, and in cells pretreated with methylamine (MeNH2), an exocytosis inhibitor, indicating that both intracellular FGF-2 and its export toward the membrane are required for the ψεRACK activity. In vivo ψεRACK does not induce angiogenesis in the rabbit cornea. However, ψεRACK promotes VEGF angiogenic responses, an effect sustained by endothelial FGF-2 release and synthesis, since anti-FGF-2 antibody strongly attenuates VEGF responses. The results demonstrate that PKCε stimulation promotes angiogenesis and modulates VEGF activity, by inducing FGF-2 release and autocrine signaling. PMID:23880610

  5. PKCε activation promotes FGF-2 exocytosis and induces endothelial cell proliferation and sprouting.

    PubMed

    Monti, Martina; Donnini, Sandra; Morbidelli, Lucia; Giachetti, Antonio; Mochly-Rosen, Daria; Mignatti, Paolo; Ziche, Marina

    2013-10-01

    Protein kinase C epsilon (PKCε) activation controls fibroblast growth factor-2 (FGF-2) angiogenic signaling. Here, we examined the effect of activating PKCε on FGF-2 dependent vascular growth and endothelial activation. ψεRACK, a selective PKCε agonist induces pro-angiogenic responses in endothelial cells, including formation of capillary like structures and cell growth. These effects are mediated by FGF-2 export to the cell membrane, as documented by biotinylation and immunofluorescence, and FGF-2/FGFR1 signaling activation, as attested by ERK1/2-STAT-3 phosphorylation and de novo FGF-2 synthesis. Similarly, vascular endothelial growth factor (VEGF) activates PKCε in endothelial cells, and promotes FGF-2 export and FGF-2/FGFR1 signaling activation. ψεRACK fails to elicit responses in FGF-2(-/-) endothelial cells, and in cells pretreated with methylamine (MeNH2), an exocytosis inhibitor, indicating that both intracellular FGF-2 and its export toward the membrane are required for the ψεRACK activity. In vivo ψεRACK does not induce angiogenesis in the rabbit cornea. However, ψεRACK promotes VEGF angiogenic responses, an effect sustained by endothelial FGF-2 release and synthesis, since anti-FGF-2 antibody strongly attenuates VEGF responses. The results demonstrate that PKCε stimulation promotes angiogenesis and modulates VEGF activity, by inducing FGF-2 release and autocrine signaling.

  6. Factors Predicting the Physical Activity Behavior of Female Adolescents: A Test of the Health Promotion Model

    PubMed Central

    Mohamadian, Hashem

    2014-01-01

    Objectives Physical activity behavior begins to decline during adolescence and continues to decrease throughout young adulthood. This study aims to explain factors that influence physical activity behavior in a sample of female adolescents using a health promotion model framework. Methods This cross-sectional survey was used to explore physical activity behavior among a sample of female adolescents. Participants completed measures of physical activity, perceived self-efficacy, self-esteem, social support, perceived barriers, and perceived affect. Interactions among the variables were examined using path analysis within a covariance modeling framework. Results The final model accounted for an R2 value of 0.52 for physical activity and offered a good model-data fit. The results indicated that physical activity was predicted by self-esteem (β=0.46, p<0.001), perceived self-efficacy (β=0.40, p<0.001), social support (β=0.24, p<0.001), perceived barriers (β=-0.19, p<0.001), and perceived affect (β=0.17, p<0.001). Conclusions The findings of this study showed that the health promotion model was useful to predict physical activity behavior among the Iranian female adolescents. Information related to the predictors of physical activity behavior will help researchers plan more tailored culturally relevant health promotion interventions for this population. PMID:24570808

  7. GEP oncogene promotes cell proliferation through YAP activation in ovarian cancer.

    PubMed

    Yagi, H; Asanoma, K; Ohgami, T; Ichinoe, A; Sonoda, K; Kato, K

    2016-08-25

    G-protein-coupled receptors (GPCRs) and their ligands function in the progression of human malignancies. Gα12 and Gα13, encoded by GNA12 and GNA13, respectively, are referred to as the GEP oncogene and are implicated in tumor progression. However, the molecular mechanisms by which Gα12/13 activation promotes cancer progression are not fully elucidated. Here, we demonstrate elevated expression of Gα12/13 in human ovarian cancer tissues. Gα12/13 activation did not promote cellular migration in the ovarian cancer cell lines examined. Rather, Gα12/13 activation promoted cell growth. We used a synthetic biology approach using chimeric G proteins and GPCRs activated solely by artificial ligands to selectively trigger signaling pathways downstream of specific G proteins. We found that Gα12/13 promotes proliferation of ovarian cancer cells by activating the transcriptional coactivator YAP, a critical component of the Hippo signaling pathway. Furthermore, we reveal that inhibition of YAP by short hairpin RNA or a specific inhibitor prevented the growth of ovarian cancer cells. Therefore, YAP may be a suitable therapeutic target in ovarian cancer.

  8. Impact of Environmental Factors on Bacteriocin Promoter Activity in Gut-Derived Lactobacillus salivarius

    PubMed Central

    Guinane, Caitriona M.; Piper, Clare; Draper, Lorraine A.; O'Connor, Paula M.; Hill, Colin; Ross, R. Paul

    2015-01-01

    Bacteriocin production is regarded as a desirable probiotic trait that aids in colonization and persistence in the gastrointestinal tract (GIT). Strains of Lactobacillus salivarius, a species associated with the GIT, are regarded as promising probiotic candidates and have a number of associated bacteriocins documented to date. These include multiple class IIb bacteriocins (salivaricin T, salivaricin P, and ABP-118) and the class IId bacteriocin bactofencin A, which show activity against medically important pathogens. However, the production of a bacteriocin in laboratory media does not ensure production under stressful environmental conditions, such as those encountered within the GIT. To allow this issue to be addressed, the promoter regions located upstream of the structural genes encoding the L. salivarius bacteriocins mentioned above were fused to a number of reporter proteins (green fluorescent protein [GFP], red fluorescent protein [RFP], and luciferase [Lux]). Of these, only transcriptional fusions to GFP generated signals of sufficient strength to enable the study of promoter activity in L. salivarius. While analysis of the class IIb bacteriocin promoter regions indicated relatively weak GFP expression, assessment of the promoter of the antistaphylococcal bacteriocin bactofencin A revealed a strong promoter that is most active in the absence of the antimicrobial peptide and is positively induced in the presence of mild environmental stresses, including simulated gastric fluid. Taken together, these data provide information on factors that influence bacteriocin production, which will assist in the development of strategies to optimize in vivo and in vitro production of these antimicrobials. PMID:26341205

  9. Promoting Physics Among Female Learners in the Western Cape Through Active Engagement (abstract)

    NASA Astrophysics Data System (ADS)

    Arendse, Gillian J.

    2009-04-01

    In 2006 the author organized a one-day intervention aimed at promoting physics among female learners at the University of Stellenbosch. The activities included an interactive lecture demonstration promoting active engagement, a hands-on session, and short presentations by female physicists addressing issues such as balancing family and career, breaking the stereotypes, and launching a successful career in physics. Each learner was expected to evaluate the program. In 2007 the author joined forces with Hip2B2 (Shuttleworth Foundation) to host a competition among grade-10 learners with the theme, ``promoting creativity through interactivity.'' The author was tasked by the Hip2B2-team to assist with a program for female learners planned for August 2008, coinciding with our national celebration of Women's Day. The event targeted 160 learners and took place in Durban, East London, Cape Town, and Johannesburg. The author shares some of the learners' experiences and personal triumphs.

  10. Overcoming Legal Liability Concerns for School-Based Physical Activity Promotion

    PubMed Central

    Zimmerman, Sara; Kramer, Karen

    2013-01-01

    Schools have been identified as a priority environment for physical activity promotion as a component of efforts to help prevent childhood obesity. A variety of school-based environmental and programmatic strategies have been proven effective in promoting physical activity both on-site and in the surrounding community. However, many schools are deterred by fears of increased risk of legal liability for personal injuries. We examine 3 school-based strategies for promoting physical activity—Safe Routes to School programs, joint use agreements, and playground enhancement—from a tort liability perspective, and describe how schools can substantially minimize any associated liability risk through injury prevention and other strategies. We also recommend approaches to help schools overcome their liability concerns and adopt these critically needed healthy school policies. PMID:24028226

  11. MRG15 activates the cdc2 promoter via histone acetylation in human cells

    SciTech Connect

    Pena, AndreAna N.; Tominaga, Kaoru; Pereira-Smith, Olivia M.

    2011-07-01

    Chromatin remodeling is required for transcriptional activation and repression. MRG15 (MORF4L1), a chromatin modulator, is a highly conserved protein and is present in complexes containing histone acetyltransferases (HATs) as well as histone deacetylases (HDACs). Loss of expression of MRG15 in mice and Drosophila results in embryonic lethality and fibroblast and neural stem/progenitor cells cultured from Mrg15 null mouse embryos exhibit marked proliferative defects when compared with wild type cells. To determine the role of MRG15 in cell cycle progression we performed chromatin immunoprecipitation with an antibody to MRG15 on normal human fibroblasts as they entered the cell cycle from a quiescent state, and analyzed various cell cycle gene promoters. The results demonstrated a 3-fold increase in MRG15 occupancy at the cdc2 promoter during S phase of the cell cycle and a concomitant increase in acetylated histone H4. H4 lysine 12 was acetylated at 24 h post-serum stimulation while there was no change in acetylation of lysine 16. HDAC1 and 2 were decreased at this promoter during cell cycle progression. Over-expression of MRG15 in HeLa cells activated a cdc2 promoter-reporter construct in a dose-dependent manner, whereas knockdown of MRG15 resulted in decreased promoter activity. In order to implicate HAT activity, we treated cells with the HAT inhibitor anacardic acid and determined that HAT inhibition results in loss of expression of cdc2 mRNA. Further, chromatin immunoprecipitation with Tip60 localizes the protein to the same 110 bp stretch of the cdc2 promoter pulled down by MRG15. Additionally, we determined that cotransfection of MRG15 with the known associated HAT Tip60 had a cooperative effect in activating the cdc2 promoter. These results suggest that MRG15 is acting in a HAT complex involving Tip60 to modify chromatin via acetylation of histone H4 at the cdc2 promoter to activate transcription.

  12. Evaluation of a Community-Based Intervention To Promote Physical Activity in Youth: Lessons from Active Winners.

    ERIC Educational Resources Information Center

    Pate, Russell R.; Saunders, Ruth P.; Ward, Dianne S.; Felton, Gwen; Trost, Stewart G.; Dowda, Marsha

    2003-01-01

    Tested the effectiveness of a community-based intervention designed to promote physical activity among rural fifth graders. Data on students who participated in after-school and summer programs and home, school, and community interventions indicated that the after-school and summer interventions were implemented as planned, but the home, school,…

  13. The virulence regulator Sae of Staphylococcus aureus: promoter activities and response to phagocytosis-related signals.

    PubMed

    Geiger, Tobias; Goerke, Christiane; Mainiero, Markus; Kraus, Dirk; Wolz, Christiane

    2008-05-01

    The two-component system SaeRS of Staphylococcus aureus is closely involved in the regulation of major virulence factors. However, little is known about the signals leading to saeRS activation. A total of four overlapping transcripts (T1 to T4) from three different transcription starting points are expressed in the sae operon. We used a beta-galactosidase reporter assay to characterize the putative promoter regions within the saeRS upstream region. The main transcript T2 is probably generated by endoribonucleolytic processing of the T1 transcript. Only two distinct promoter elements (P1 and P3) could be detected within the saeRS upstream region. The P3 promoter, upstream of saeRS, generates the T3 transcript, includes a cis-acting enhancer element and is repressed by saeRS. The most distal P1 promoter is strongly autoregulated, activated by agr, and repressed by sigma factor B. In strain Newman a mutation within the histidine kinase SaeS leads to a constitutively activated sae system. Evaluation of different external signals revealed that the P1 promoter in strain ISP479R and strain UAMS-1 is inhibited by low pH and high NaCl concentrations but activated by hydrogen peroxide. The most prominent induction of P1 was observed at subinhibitory concentrations of alpha-defensins in various S. aureus strains, with the exception of strain ISP479R and strain COL. P1 was not activated by the antimicrobial peptides LL37 and daptomycin. In summary, the results indicate that the sensor molecule SaeS is activated by alteration within the membrane allowing the pathogen to react to phagocytosis related effector molecules.

  14. Decrease of epidermal histidase activity by tumor-promoting phorbol esters.

    PubMed

    Colburn, N H; Lau, S; Head, R

    1975-11-01

    The potent skin tumor promoter (12-O-tetradecanoyl phorbol-13-acetate (TPA) stimulates epidermal macromolecular synthesis as well as proliferation, but little is known of specific functional aberrations produced by TPA. This report presents results of a study on the effects of TPA on epidermal histidase (L-histidine ammonia lyase), an enzyme found in normal epidermis but not in dermis or in mouse squamous cell carcinomas. Histidase activity was assayed on postmitochondrial supernatants obtained from hairless mouse epidermis after removal by keratotome. Topical TPA treatment at doses active in tumor promotion (1.7 to 17.0 nmoles/application) produced dose-dependent decreases in epidermal histidase specific activity at 19 hr posttreatment. The onset of the decrease occurred at 12 hr with recovery to control level specific activity by 5 days, showing kinetics similar to those obtained for stimulation of DNA synthesis. This decrease in histidase could not be attributed to a general inhibition of soluble protein synthesis or to the appearance of an inhibitor of histidase activity. The strong promoter TPA produced a greater histidase decrease than did the moderate promoter and mitogen 12,13-didecanoyl phorbol at equimolar dose, while phorbol, a nonpromoter and nonmitogen, produced no effects on histidase. The relationship of this histidase depression to tumor promotion and not initiation is further indicated by the finding that (a) Tween 60, a structurally unrelated tumor promotor, also produced a decrease in histidase; and (b) the tumor initiator urethan and an initiating dose of 9,10-dimethybenz(a)anthracene showed no effects on histadase activity.

  15. Seasonal variations in sexual activity and their implications for sexual health promotion.

    PubMed

    Wellings, K; Macdowall, W; Catchpole, M; Goodrich, J

    1999-02-01

    Although seasonal variations in births are observed in all human populations, the links between calendar events and sexual activity have received little attention in relation to health promotion and service provision. We have plotted various relevant data--routinely collected data for births within and outside of marriage, abortions, sexually transmitted infections, human immunodeficiency virus tests and condom sales figures--by calendar period. The trends point consistently to an increase in sexual activity and unsafe sex occurring at or around the Christmas period, and a longer but less pronounced subsidiary period of increased sexual activity and unsafe sex coinciding with the summer vacation. We conclude that seasonal patterns of sexual activity have implications for provision of sexual health services and for the timing and targeting of sexual health promotional interventions.

  16. Neurite outgrowth-promoting active constituents of the Japanese cypress (Chamaecyparis obtusa).

    PubMed

    Kuroyanagi, Masanori; Ikeda, Ryuya; Gao, Hui Yuan; Muto, Norio; Otaki, Keisuke; Sano, Toshikazu; Kawahara, Nobuo; Nakane, Takahisa

    2008-01-01

    In the screening of biologically active constituents from woody plants, the methanol extract of leaves of Chamaecyparis obtusa showed potent neurite outgrowth-promoting activity in neuronal PC12 cells. The ethyl acetate-soluble fraction of the methanol extract showed potent activity and was separated by means of various chromatographic methods to give the two new compounds 1 and 2, as well as 11 known lignan and sesquiterpene derivatives. The structures of the new compounds were determined to be 9-O-acetyldihydrosesamin (1) and 9-O-(11-hydroxyeudesman-4-yl)dihydrosesamin (2), respectively, in NMR studies including 2D-NMR experiments. Of the 13 compounds, the known compound hinokinin (5) and the new compound 2 showed potent neurite outgrowth-promoting activity in PC 12 cells.

  17. Terazosin activates Pgk1 and Hsp90 to promote stress resistance.

    PubMed

    Chen, Xinping; Zhao, Chunyue; Li, Xiaolong; Wang, Tao; Li, Yizhou; Cao, Cheng; Ding, Yuehe; Dong, Mengqiu; Finci, Lorenzo; Wang, Jia-Huai; Li, Xiaoyu; Liu, Lei

    2015-01-01

    Drugs that can protect against organ damage are urgently needed, especially for diseases such as sepsis and brain stroke. We discovered that terazosin (TZ), a widely marketed α1-adrenergic receptor antagonist, alleviated organ damage and improved survival in rodent models of stroke and sepsis. Through combined studies of enzymology and X-ray crystallography, we discovered that TZ binds a new target, phosphoglycerate kinase 1 (Pgk1), and activates its enzymatic activity, probably through 2,4-diamino-6,7-dimethoxyisoquinoline's ability to promote ATP release from Pgk1. Mechanistically, the ATP generated from Pgk1 may enhance the chaperone activity of Hsp90, an ATPase known to associate with Pgk1. Upon activation, Hsp90 promotes multistress resistance. Our studies demonstrate that TZ has a new protein target, Pgk1, and reveal its corresponding biological effect. As a clinical drug, TZ may be quickly translated into treatments for diseases including stroke and sepsis.

  18. Knowledge, Attitudes and Practices of Clinicians in Promoting Physical Activity to Prostate Cancer Survivors

    ERIC Educational Resources Information Center

    Spellman, Claire; Craike, Melinda; Livingston, Patricia M.

    2014-01-01

    Objectives: This study examined the knowledge, attitudes and practices of clinicians in promoting physical activity to prostate cancer survivors. Design: A purposeful sample was used and cross-sectional data were collected using an anonymous, self-reported online questionnaire or an identical paper-based questionnaire. Settings: Health services…

  19. Promoting Critical Racial Awareness in Teacher Education in Korea: Reflections on a Racial Discrimination Simulation Activity

    ERIC Educational Resources Information Center

    Tanghe, Shannon

    2016-01-01

    Though historically perceived as an ethnically homogenous country, rapid demographic changes in the Republic of Korea have resulted in increasing diversity. However, current multicultural education programs struggle to promote acceptance and appreciation of this diversity. This paper details one pedagogical activity, a racial discrimination…

  20. New Ideas for Promoting Physical Activity among Middle Age and Older Adults

    ERIC Educational Resources Information Center

    Godbey, Geoffrey; Burnett-Wolle, Sarah; Chow, Hsueh-Wen

    2007-01-01

    Promoting physical activity among middle age and older adults to decrease the incidence of disease and premature death and to combat the health care costs associated with a sedentary lifestyle is more important now than ever. There is now a better understanding of what "successful aging" means and of what aspects of life have the greatest…

  1. Promoting Science Outdoor Activities for Elementary School Children: Contributions from a Research Laboratory

    ERIC Educational Resources Information Center

    Boaventura, Diana; Faria, Claudia; Chagas, Isabel; Galvao, Cecilia

    2013-01-01

    The purposes of the study were to analyse the promotion of scientific literacy through practical research activities and to identify children's conceptions about scientists and how they do science. Elementary school children were engaged in two scientific experiments in a marine biology research laboratory. A total of 136 students answered a…

  2. Grounds for Movement: Green School Grounds as Sites for Promoting Physical Activity

    ERIC Educational Resources Information Center

    Dyment, J. E.; Bell, A. C.

    2008-01-01

    An environmental factor of particular importance to children's physical activity levels appears to be the presence of parks and open space. Thus, in promoting children's health, school grounds merit consideration as a potential setting for intervention. This paper explores how "green" school grounds, which contain a greater diversity of…

  3. Defining Standards and Policies for Promoting Physical Activity in Afterschool Programs

    ERIC Educational Resources Information Center

    Beets, Michael W.; Wallner, Megan; Beighle, Aaron

    2010-01-01

    Background: National guidelines exist that define "quality" afterschool programs (3-6 pm, ASP). No widely adopted national standards/policies exist, however, for ASP providers for the promotion of physical activity (PA). To address this gap, state-level ASP organizations have developed or adopted standards/policies related to PA. The extent to…

  4. Amplification of the groESL operon in Pseudomonas putida increases siderophore gene promoter activity.

    PubMed

    Venturi, V; Wolfs, K; Leong, J; Weisbeek, P J

    1994-10-17

    Pseudobactin 358 is the yellow-green fluorescent siderophore [microbial iron(III) transport agent] produced by Pseudomonas putida WCS358 under iron-limiting conditions. The genes encoding pseudobactin 358 biosynthesis are iron-regulated at the level of transcription. In this study, the molecular characterization is reported of a cosmid clone of WCS358 DNA that can stimulate, in an iron-dependent manner, the activity of a WCS358 siderophore gene promoter in the heterologous Pseudomonas strain A225. The functional region in the clone was identified by subcloning, transposon mutagenesis and DNA sequencing as the groESL operon of strain WCS358. This increase in promoter activity was not observed when the groESL genes of strain WCS358 were integrated via a transposon vector into the genome of Pseudomonas A225, indicating that multiple copies of the operon are necessary for the increase in siderophore gene promoter activity. Amplification of the Escherichia coli and WCS358 groESL genes also increased iron-regulated promoter activity in the parent strain WCS358. The groESL operon codes for the chaperone proteins GroES and GroEL, which are responsible for mediating the folding and assembly of many proteins.

  5. Active Agents of Health Promotion? The School's Role in Supporting the HPV Vaccination Programme

    ERIC Educational Resources Information Center

    Spratt, Jennifer; Shucksmith, Janet; Philip, Kate; McNaughton, Rebekah

    2013-01-01

    By providing a place in which children can be accessed, the school has long been a site for population-level health initiatives. Recent policy shifts towards health-promoting schools have however re-cast the school from passive host to active collaborator in public health. This paper examines secondary school teachers' views of their roles as…

  6. A Journal-Club-Based Class that Promotes Active and Cooperative Learning of Biology

    ERIC Educational Resources Information Center

    Kitazono, Ana A.

    2010-01-01

    A journal-club-based class has been developed to promote active and cooperative learning and expose seniors in biochemistry and cellular molecular biology to recent research in the field. Besides giving oral presentations, students also write three papers: one discussing an article of their own choosing and two, discussing articles presented by…

  7. Promoting Conceptual Change through Active Learning Using Open Source Software for Physics Simulations

    ERIC Educational Resources Information Center

    Baser, Mustafa

    2006-01-01

    This paper reports upon an active learning approach that promotes conceptual change when studying direct current electricity circuits, using free open source software, "Qucs". The study involved a total of 102 prospective mathematics teacher students. Prior to instruction, students' understanding of direct current electricity was…

  8. A Life-Course Perspective on Physical Activity Promotion: Applications and Implications

    ERIC Educational Resources Information Center

    Li, Kin-Kit; Cardinal, Bradley J.; Settersten, Richard A., Jr.

    2009-01-01

    This article illustrates how a life-course perspective can be infused more fully into the research field of physical activity promotion. A life-course perspective is particularly promising in connecting, organizing, and supplementing current knowledge and can potentially stimulate and direct future research and intervention efforts by using a…

  9. Promoting Physical Activity among Youth through Community-Based Prevention Marketing

    ERIC Educational Resources Information Center

    Bryant, Carol A.; Courtney, Anita H.; McDermott, Robert J.; Alfonso, Moya L.; Baldwin, Julie A.; Nickelson, Jen; Brown, Kelli R. McCormack; DeBate, Rita D.; Phillips, Leah M.; Thompson, Zachary; Zhu, Yiliang

    2010-01-01

    Background: Community-based prevention marketing (CBPM) is a program planning framework that blends community-organizing principles with a social marketing mind-set to design, implement, and evaluate public health interventions. A community coalition used CBPM to create a physical activity promotion program for tweens (youth 9-13 years of age)…

  10. A Holistic Approach to Promoting Physical Activity among School-Age Children

    ERIC Educational Resources Information Center

    Subramaniam, Prithwi Raj

    2011-01-01

    A holistic approach to promote physical activity should become a high priority if society is to overcome the dramatic increase in physical inactivity and kypokinetic diseases associated with it. In order to achieve this goal, a collective effort is urgently needed if everyone is serious in combating this unhealthy and dangerous trend. Schools as a…

  11. Fitness Testing in Physical Education--A Misdirected Effort in Promoting Healthy Lifestyles and Physical Activity?

    ERIC Educational Resources Information Center

    Cale, Lorraine; Harris, Jo

    2009-01-01

    Background: Physical fitness testing is commonplace within schools and the physical education (PE) curriculum, with advocates claiming one of the key purposes of testing to be the promotion of healthy lifestyles and physical activity. Despite this, much controversy has surrounded the fitness testing of young people. Purpose: This paper draws on…

  12. The Role of Out-of-School English Literacy Activities in Promoting Students' English Literacy

    ERIC Educational Resources Information Center

    Setiasih, Lilies

    2014-01-01

    This paper reports on a case study of the role of out-of-school English literacy activities in promoting students' English literacy at an elementary school in Bandung. The study is an attempt to respond to controversy among decision makers about the idea of offering English at elementary schools and the reality that at the school where the…

  13. rRNA promoter activity in the fast-growing bacterium Vibrio natriegens.

    PubMed

    Aiyar, Sarah E; Gaal, Tamas; Gourse, Richard L

    2002-03-01

    The bacterium Vibrio natriegens can double with a generation time of less than 10 min (R. G. Eagon, J. Bacteriol. 83:736-737, 1962), a growth rate that requires an extremely high rate of protein synthesis. We show here that V. natriegens' high potential for protein synthesis results from an increase in ribosome numbers with increasing growth rate, as has been found for other bacteria. We show that V. natriegens contains a large number of rRNA operons, and its rRNA promoters are extremely strong. The V. natriegens rRNA core promoters are at least as active in vitro as Escherichia coli rRNA core promoters with either E. coli RNA polymerase (RNAP) or V. natriegens RNAP, and they are activated by UP elements, as in E. coli. In addition, the E. coli transcription factor Fis activated V. natriegens rrn P1 promoters in vitro. We conclude that the high capacity for ribosome synthesis in V. natriegens results from a high capacity for rRNA transcription, and the high capacity for rRNA transcription results, at least in part, from the same factors that contribute most to high rates of rRNA transcription in E. coli, i.e., high gene dose and strong activation by UP elements and Fis.

  14. Physical Activity and Nutrition Health Promotion Interventions: What Is Working for People with Intellectual Disabilities?

    ERIC Educational Resources Information Center

    Heller, Tamar; McCubbin, Jeffrey A.; Drum, Charles; Peterson, Jana

    2011-01-01

    A scoping review of studies on physical activity and nutrition health promotion interventions for individuals with intellectual disabilities was conducted. Searches included MEDLINE, PsycINFO, and CINAHL databases from 1986 through July 2006. The final number included 11 articles comprising 12 studies. Generally, this review indicated some…

  15. Online Delivery as a Course Adjunct Promotes Active Learning and Student Success

    ERIC Educational Resources Information Center

    Lewis, J. Scott; Harrison, Marissa A.

    2012-01-01

    Chickering and Gamson's notable summary of the best practices of undergraduate teaching include promoting active learning, cooperation, and student-faculty contact. The present study hypothesized that online delivery of lecture prior to course meetings allows more in-class time to achieve these goals. Students in a control group received a…

  16. Peace Perceptions of Prospective Teachers for Promoting Peace Activities for School Settings in Pakistan

    ERIC Educational Resources Information Center

    Yousuf, Muhammad Imran; Sarwar, Muhammad; Dart, Gareth; Naseer-ud-Din, Muhmmad

    2010-01-01

    Peace has been recognized as a matter of education and to be promoted at the initial level. The present study attempts to generate a profile of activities toward peace education among prospective teachers. The Nominal Group Technique (NGT) was used by selecting fifteen prospective teachers as a Nominal Group (NG). NGT was applied under a sequence…

  17. Physical Activity Promotion in General Practices of Barcelona: A Case Study

    ERIC Educational Resources Information Center

    Puig Ribera, Anna; McKenna, Jim; Riddoch, Chris

    2006-01-01

    This case study aimed to generate explanations for the lack of integration of physical activity (PA) promotion in general practices of Barcelona, the capital of Catalonia. This explanatory study adopted a qualitative approach, based on three techniques; focus groups (n = 3), semi-structured (n = 25) and short individual interviews (n = 5). These…

  18. What Do We Know about "How" to Promote Physical Activity to Adolescents? A Mapping Review

    ERIC Educational Resources Information Center

    Bush, Paula Louise; García Bengoechea, Enrique

    2015-01-01

    To date, adolescent physical activity (PA) intervention research has focused on the school setting and suggests a need to extend interventions beyond this setting to influence teenagers' overall level of PA. But, the relative effectiveness of PA promotion strategies that can be part of such multi-setting interventions remains unknown. We completed…

  19. Association between Municipal Health Promotion Volunteers’ Health Literacy and Their Level of Outreach Activities in Japan

    PubMed Central

    Taguchi, Atsuko; Murayama, Hiroshi; Murashima, Sachiyo

    2016-01-01

    Objectives To explore the association between health literacy and levels of three types of core activities among health promotion volunteers (developing a healthy lifestyle, outreach to family, and outreach to community members). Study Design A cross-sectional, anonymous, self-administered postal survey of registered health promotion volunteers in the Konan area in Shiga Prefecture in Japan, conducted in January 2010. The study sample was 575 registered health promotion volunteers. Methods The survey collected data on health literacy, gender, age, education, self-rated health, perceptions about the volunteer organization, and perceptions of recognition in the community. The level of engagement in health promotion activities was measured by the extent to which the participants engaged in seven healthy behaviors and promoted them to family members and the community. The authors compared the health literacy level and other characteristics of the participants by core health promotion activities, using a chi-squared test, to examine the associations between demographic and other variables and the three core activities (healthy lifestyle, outreach to family, and outreach to community).Logistic regression analysis was conducted to examine the association between the degree to which the volunteers engaged in core activities (“healthy lifestyle,” “outreach to family,” “outreach to community”) and the levels of health literacy (low, medium, high) among health promotion volunteers, controlling for the effects of age, gender, health condition, education which may also have an impact on volunteers’ outreach activities. Results Four hundred and fifty-four questionnaires were returned, a 79.0% response rate. Excluding 16 cases with missing values on health literacy or the degree of health promotion activities, 438 research subjects were included in the analysis (valid response rate: 76.2%). Health literacy and a few demographic and other characteristics of the

  20. Active video games to promote physical activity in children with cancer: a randomized clinical trial with follow-up

    PubMed Central

    2014-01-01

    Background Low levels of physical activity, musculoskeletal morbidity and weight gain are commonly reported problems in children with cancer. Intensive medical treatment and a decline in physical activity may also result in reduced motor performance. Therefore, simple and inexpensive ways to promote physical activity and exercise are becoming an increasingly important part of children’s cancer treatment. Methods The aim of this study is to evaluate the effect of active video games in promotion of physical activity in children with cancer. The research is conducted as a parallel randomized clinical trial with follow-up. Patients between 3 and 16 years old, diagnosed with cancer and treated with vincristine in two specialized medical centers are asked to participate. Based on statistical estimates, the target enrollment is 40 patients. The intervention includes playing elective active video games and, in addition, education and consultations for the family. The control group will receive a general recommendation for physical activity for 30 minutes per day. The main outcomes are the amount of physical activity and sedentary behavior. Other outcomes include motor performance, fatigue and metabolic risk factors. The outcomes are examined with questionnaires, diaries, physical examinations and blood tests at baseline and at 2, 6, 12 and 30 months after the baseline. Additionally, the children’s perceptions of the most enjoyable activation methods are explored through an interview at 2 months. Discussion This trial will help to answer the question of whether playing active video games is beneficial for children with cancer. It will also provide further reasoning for physical activity promotion and training of motor skills during treatment. Trial registration ClinicalTrials.gov identifier: NCT01748058 (October 15, 2012). PMID:24708773

  1. Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance

    PubMed Central

    Stamatakis, Alice M.; Stuber, Garret D.

    2012-01-01

    Lateral habenula (LHb) projections to the ventral midbrain, including the rostromedial tegmental nucleus (RMTg) conveys negative reward-related information, but the behavioral ramifications of selective activation of this pathway remain unexplored. We found that exposure to aversive stimuli in mice increased LHb excitatory drive onto RMTg neurons. Further, optogenetic activation of this pathway promoted active, passive, and conditioned behavioral avoidance. These data demonstrate that activity of LHb efferents to the midbrain is aversive, but can also serve to negatively reinforce behavioral responding. PMID:22729176

  2. The lipid sensor GPR120 promotes brown fat activation and FGF21 release from adipocytes

    PubMed Central

    Quesada-López, Tania; Cereijo, Rubén; Turatsinze, Jean-Valery; Planavila, Anna; Cairó, Montserrat; Gavaldà-Navarro, Aleix; Peyrou, Marion; Moure, Ricardo; Iglesias, Roser; Giralt, Marta; Eizirik, Decio L.; Villarroya, Francesc

    2016-01-01

    The thermogenic activity of brown adipose tissue (BAT) and browning of white adipose tissue are important components of energy expenditure. Here we show that GPR120, a receptor for polyunsaturated fatty acids, promotes brown fat activation. Using RNA-seq to analyse mouse BAT transcriptome, we find that the gene encoding GPR120 is induced by thermogenic activation. We further show that GPR120 activation induces BAT activity and promotes the browning of white fat in mice, whereas GRP120-null mice show impaired cold-induced browning. Omega-3 polyunsaturated fatty acids induce brown and beige adipocyte differentiation and thermogenic activation, and these effects require GPR120. GPR120 activation induces the release of fibroblast growth factor-21 (FGF21) by brown and beige adipocytes, and increases blood FGF21 levels. The effects of GPR120 activation on BAT activation and browning are impaired in FGF21-null mice and cells. Thus, the lipid sensor GPR120 activates brown fat via a mechanism that involves induction of FGF21. PMID:27853148

  3. Promoting Active Species Generation by Electrochemical Activation in Alkaline Media for Efficient Electrocatalytic Oxygen Evolution in Neutral Media.

    PubMed

    Xu, Kun; Cheng, Han; Liu, Linqi; Lv, Haifeng; Wu, Xiaojun; Wu, Changzheng; Xie, Yi

    2017-01-11

    In this study, by using dicobalt phosphide nanoparticles as precatalysts, we demonstrated that electrochemical activation of metallic precatalysts in alkaline media (comparing with directly electrochemical activation in neutral media) could significantly promote the OER catalysis in neutral media, specifically realizing a 2-fold enhanced activity and meanwhile showing a greatly decreased overpotential of about 100 mV at 10 mA cm(-2). Compared directly with electrochemical activation in neutral media, the electrochemical activation in harsh alkaline media could easily break the strong Co-Co bond and promote active species generation on the surface of metallic Co2P, thus accounting for the enhancement of neutral OER activity, which is also evidenced by HRTEM and the electrochemical double-layer capacitance measurement. The activation of electrochemical oxidation of metallic precatalysts in alkaline media enhanced neutral OER catalysis could also be observed on CoP nanoparticles and Ni2P nanoparticles, suggesting this is a generic strategy. Our work highlights that the activation of electrochemical oxidation of metallic precatalysts in alkaline media would pave new avenues for the design of advanced neutral OER electrocatalysts.

  4. Activation of the Notch1/STAT3/Twist signaling axis promotes gastric cancer progression.

    PubMed

    Hsu, Kai-Wen; Hsieh, Rong-Hong; Huang, Kuo-Hung; Fen-Yau Li, Anna; Chi, Chin-Wen; Wang, Tzu-Yin; Tseng, Min-Jen; Wu, Kou-Juey; Yeh, Tien-Shun

    2012-08-01

    Gastric carcinoma is one of the most common malignancies and a lethal cancer in the world. Notch signaling and transcription factors STAT3 (signal transducer and activator of transcription 3) and Twist regulate tumor development and are critical regulators of gastric cancer progression. Herein, the relationship among Notch, STAT3 and Twist pathways in the control of gastric cancer progression was studied. We found that Twist and phosphorylated STAT3 levels were promoted by the activated Notch1 receptor in human stomach adenocarcinoma SC-M1, embryonic kidney HEK293 and erythroleukemia K562 cells. Notch1 signaling dramatically induced Twist promoter activity through a C promoter binding factor-1-independent manner and STAT3 phosphorylation. Overexpression of Notch1 receptor intracellular domain (N1IC) enhanced the interaction between nuclear STAT3 and Twist promoter in cells. Gastric cancer progression of SC-M1 cells was promoted by N1IC through STAT3 phosphorylation and Twist expression including colony formation, migration and invasion. STAT3 regulated gastric cancer progression of SC-M1 cells via Twist. N1IC also elevated the progression of other gastric cancer cells such as AGS and KATO III cells through STAT3 and Twist. The N1IC-promoted tumor growth and lung metastasis of SC-M1 cells in mice were suppressed by the STAT3 inhibitor JSI-124 and Twist knockdown. Furthermore, Notch1 and Notch ligand Jagged1 expressions were significantly associated with phosphorylated STAT3 and Twist levels in gastric cancer tissues of patients. Taken together, these results suggest that Notch1/STAT3/Twist signaling axis is involved in progression of human gastric cancer and modulation of this cascade has potential for the targeted combination therapy.

  5. NLRP1 promotes tumor growth by enhancing inflammasome activation and suppressing apoptosis in metastatic melanoma.

    PubMed

    Zhai, Z; Liu, W; Kaur, M; Luo, Y; Domenico, J; Samson, J M; Shellman, Y G; Norris, D A; Dinarello, C A; Spritz, R A; Fujita, M

    2017-03-06

    Inflammasomes are mediators of inflammation, and constitutively activated NLRP3 inflammasomes have been linked to interleukin-1β (IL-1β)-mediated tumorigenesis in human melanoma. Whereas NLRP3 regulation of caspase-1 activation requires the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD (caspase recruitment domain)), caspase-1 activation by another danger-signaling sensor NLRP1 does not require ASC because NLRP1 contains a C-terminal CARD domain that facilitates direct caspase-1 activation via CARD-CARD interaction. We hypothesized that NLRP1 has additional biological activities besides IL-1β maturation and investigated its role in melanoma tumorigenesis. NLRP1 expression in melanoma was confirmed by analysis of 216 melanoma tumors and 13 human melanoma cell lines. Unlike monocytic THP-1 cells with prominent nuclear localization of NLRP1, melanoma cells expressed NLRP1 mainly in the cytoplasm. Knocking down NLRP1 revealed a tumor-promoting property of NLRP1 both in vitro and in vivo. Mechanistic studies showed that caspase-1 activity, IL-1β production, IL-1β secretion and nuclear factor-kB activity were reduced by knocking down of NLRP1 in human metastatic melanoma cell lines 1205Lu and HS294T, indicating that NLRP1 inflammasomes are active in metastatic melanoma. However, unlike previous reports showing that NLRP1 enhances pyroptosis in macrophages, NLRP1 in melanoma behaved differently in the context of cell death. Knocking down NLRP1 increased caspase-2, -9 and -3/7 activities and promoted apoptosis in human melanoma cells. Immunoprecipitation revealed interaction of NLRP1 with CARD-containing caspase-2 and -9, whereas NLRP3 lacking a CARD motif did not interact with the caspases. Consistent with these findings, NLRP1 activation but not NLRP3 activation reduced caspase-2, -9 and -3/7 activities and provided protection against apoptosis in human melanoma cells, suggesting a suppressive role of NLRP1 in caspase-3/7 activation

  6. Osterix plays a critical role in BMP4-induced promoter activity of connexin43.

    PubMed

    Han, Younho; Cho, Dong Hyeok; Chung, Dong Jin; Lee, Kwang Youl

    2016-09-16

    Osterix is an essential transcription factor for osteogenesis and is expressed in osteoblasts. Although Osterix has been shown to be induced by bone morphogenetic protein 4, the molecular mechanism underlying Osterix function during osteoblast differentiation remains unclear. Connexin43 (Cx43) is the most abundant gap junction protein in bone cells and plays a critical role in osteoblast differentiation. However, little is known about the functional interactions between Osterix and the Cx43 promoter. In the present study, we investigated the relationship between Osterix and Cx43 in HEK293 and C2C12 cells. Cx43 expression was significantly repressed by the addition of shRNA against Osterix, whereas overexpression of Osterix resulted in enhanced Cx43 expression. Furthermore, Osterix directly occupied the promoter region of Cx43 and subsequently increased Cx43 promoter activity in a dose-dependent manner. In addition, phosphorylation of the Ser76 and Ser80 residues in Osterix were found to be critical for its activity on the Cx43 promoter. Our results suggest that Osterix plays an important role in increasing bone morphogenetic protein 4-induced Cx43 activity.

  7. Distinct promoter activation mechanisms modulate noise-driven HIV gene expression

    NASA Astrophysics Data System (ADS)

    Chavali, Arvind K.; Wong, Victor C.; Miller-Jensen, Kathryn

    2015-12-01

    Latent human immunodeficiency virus (HIV) infections occur when the virus occupies a transcriptionally silent but reversible state, presenting a major obstacle to cure. There is experimental evidence that random fluctuations in gene expression, when coupled to the strong positive feedback encoded by the HIV genetic circuit, act as a ‘molecular switch’ controlling cell fate, i.e., viral replication versus latency. Here, we implemented a stochastic computational modeling approach to explore how different promoter activation mechanisms in the presence of positive feedback would affect noise-driven activation from latency. We modeled the HIV promoter as existing in one, two, or three states that are representative of increasingly complex mechanisms of promoter repression underlying latency. We demonstrate that two-state and three-state models are associated with greater variability in noisy activation behaviors, and we find that Fano factor (defined as variance over mean) proves to be a useful noise metric to compare variability across model structures and parameter values. Finally, we show how three-state promoter models can be used to qualitatively describe complex reactivation phenotypes in response to therapeutic perturbations that we observe experimentally. Ultimately, our analysis suggests that multi-state models more accurately reflect observed heterogeneous reactivation and may be better suited to evaluate how noise affects viral clearance.

  8. Distinct promoter activation mechanisms modulate noise-driven HIV gene expression

    PubMed Central

    Chavali, Arvind K.; Wong, Victor C.; Miller-Jensen, Kathryn

    2015-01-01

    Latent human immunodeficiency virus (HIV) infections occur when the virus occupies a transcriptionally silent but reversible state, presenting a major obstacle to cure. There is experimental evidence that random fluctuations in gene expression, when coupled to the strong positive feedback encoded by the HIV genetic circuit, act as a ‘molecular switch’ controlling cell fate, i.e., viral replication versus latency. Here, we implemented a stochastic computational modeling approach to explore how different promoter activation mechanisms in the presence of positive feedback would affect noise-driven activation from latency. We modeled the HIV promoter as existing in one, two, or three states that are representative of increasingly complex mechanisms of promoter repression underlying latency. We demonstrate that two-state and three-state models are associated with greater variability in noisy activation behaviors, and we find that Fano factor (defined as variance over mean) proves to be a useful noise metric to compare variability across model structures and parameter values. Finally, we show how three-state promoter models can be used to qualitatively describe complex reactivation phenotypes in response to therapeutic perturbations that we observe experimentally. Ultimately, our analysis suggests that multi-state models more accurately reflect observed heterogeneous reactivation and may be better suited to evaluate how noise affects viral clearance. PMID:26666681

  9. Failure to activate the IFN-β promoter by a paramyxovirus lacking an interferon antagonist.

    PubMed

    Killip, M J; Young, D F; Ross, C S; Chen, S; Goodbourn, S; Randall, R E

    2011-06-20

    It is generally thought that pathogen-associated molecular patterns (PAMPs) responsible for triggering interferon (IFN) induction are produced during virus replication and, to limit the activation of the IFN response by these PAMPs, viruses encode antagonists of IFN induction. Here we have studied the induction of IFN by parainfluenza virus type 5 (PIV5) at the single-cell level, using a cell line expressing GFP under the control of the IFN-β promoter. We demonstrate that a recombinant PIV5 (termed PIV5-VΔC) that lacks a functional V protein (the viral IFN antagonist) does not activate the IFN-β promoter in the majority of infected cells. We conclude that viral PAMPs capable of activating the IFN induction cascade are not produced or exposed during the normal replication cycle of PIV5, and suggest instead that defective viruses are primarily responsible for inducing IFN during PIV5 infection in this system.

  10. An Innovative Teaching Method To Promote Active Learning: Team-Based Learning

    NASA Astrophysics Data System (ADS)

    Balasubramanian, R.

    2007-12-01

    Traditional teaching practice based on the textbook-whiteboard- lecture-homework-test paradigm is not very effective in helping students with diverse academic backgrounds achieve higher-order critical thinking skills such as analysis, synthesis, and evaluation. Consequently, there is a critical need for developing a new pedagogical approach to create a collaborative and interactive learning environment in which students with complementary academic backgrounds and learning skills can work together to enhance their learning outcomes. In this presentation, I will discuss an innovative teaching method ('Team-Based Learning (TBL)") which I recently developed at National University of Singapore to promote active learning among students in the environmental engineering program with learning abilities. I implemented this new educational activity in a graduate course. Student feedback indicates that this pedagogical approach is appealing to most students, and promotes active & interactive learning in class. Data will be presented to show that the innovative teaching method has contributed to improved student learning and achievement.

  11. Developing, implementing, and evaluating a condom promotion program targeting sexually active adolescents.

    PubMed

    Alstead, M; Campsmith, M; Halley, C S; Hartfield, K; Goldbaum, G; Wood, R W

    1999-12-01

    This article describes the development, implementation, and evaluation of the Condom Campaign, a 1995 HIV prevention program promoting condom use among sexually active adolescents in three King County, Washington, urban communities. This program employed three main strategies: (a) mobilizing all levels of the target communities to support and guide program development and implementation; (b) creating and implementing a mass media campaign targeting sexually active teenagers that promoted correct condom use and favorable attitudes toward condoms; and (c) recruiting public agencies, community organizations, and businesses to distribute condoms from bins and vending machines. We evaluated the program through a series of cross-sectional interviews conducted in the three communities chosen for their elevated levels of adolescent sexual risk behavior. Overall, 73% of target youth reported exposure to the Condom Campaign; exposure did not differ by age, gender, race, or level of sexual experience. Levels of sexual activity remained stable throughout the media campaign.

  12. Phagocyte respiratory burst activates macrophage erythropoietin signalling to promote acute inflammation resolution

    PubMed Central

    Luo, Bangwei; Wang, Jinsong; Liu, Zongwei; Shen, Zigang; Shi, Rongchen; Liu, Yu-Qi; Liu, Yu; Jiang, Man; Wu, Yuzhang; Zhang, Zhiren

    2016-01-01

    Inflammation resolution is an active process, the failure of which causes uncontrolled inflammation which underlies many chronic diseases. Therefore, endogenous pathways that regulate inflammation resolution are fundamental and of wide interest. Here, we demonstrate that phagocyte respiratory burst-induced hypoxia activates macrophage erythropoietin signalling to promote acute inflammation resolution. This signalling is activated following acute but not chronic inflammation. Pharmacological or genetical inhibition of the respiratory burst suppresses hypoxia and macrophage erythropoietin signalling. Macrophage-specific erythropoietin receptor-deficient mice and chronic granulomatous disease (CGD) mice, which lack the capacity for respiratory burst, display impaired inflammation resolution, and exogenous erythropoietin enhances this resolution in WT and CGD mice. Mechanistically, erythropoietin increases macrophage engulfment of apoptotic neutrophils via PPARγ, promotes macrophage removal of debris and enhances macrophage migration to draining lymph nodes. Together, our results provide evidences of an endogenous pathway that regulates inflammation resolution, with important implications for treating inflammatory conditions. PMID:27397585

  13. "Screw health": representations of sex as a health-promoting activity in medical and popular literature.

    PubMed

    Gupta, Kristina

    2011-06-01

    Recently, scientific and popular press articles have begun to represent sex as a health-promoting activity. A number of scientific studies have identified possible health benefits of sexual activity, including increased lifespan and decreased risk of certain types of cancers. These scientific findings have been widely reported on in the popular press. This "sex for health" discourse claims that sexual activity leads to quantifiable physical and mental health benefits in areas not directly related to sexuality. Analyzing this discourse provides an opportunity to better understand both broader health promotion discourses and current norms and anxieties about sexuality. In this article, I place this "sex for health" discourse within the context of broader health promotion discourses and within the context of a number of historical and contemporary discourses connecting health and sexuality. I argue that although the "sex for health" discourse may serve to de-stigmatize sexual activity for some, it may also increase pressure on others to be sexually active and may further pathologize sexual "dysfunction." In addition, these representations often serve to further privilege a normative form of sexual behavior - coitus in the context of a monogamous heterosexual partnership - at the expense of non-normative sexual desires, identities, and practices.

  14. PKA/CREB regulates the constitutive promoter activity of the USP22 gene.

    PubMed

    Xiong, Jianjun; Zhou, Xiaoou; Gong, Zhen; Wang, Ting; Zhang, Chao; Xu, Xiaoyuan; Liu, Jianyun; Li, Weidong

    2015-03-01

    The human ubiquitin-specific processing enzyme 22 (USP22) plays a crucial role in regulating cell cycle processes and its overexpression has been linked to tumor progression. However, the mechanisms leading to USP22 transcriptional activation in human cancer cells are still unclear. Previously, we characterized the 5'-flanking sequence of the human USP22 gene and found a potential CREB/ATF binding site within the basic promoter region. The present study found that this site was required for constitutive USP22 transcriptional activity in HeLa and HepG2 cells. Chromatin immunoprecipitation assay confirmed that CREB interacted with this site. siRNA knockdown of CREB decreased USP22 transcriptional activation and endogenous expression, whereas CREB overexpression did not affect transcriptional levels. Furthermore, USP22 promoter activity and expression were decreased by inhibiting PKA with H-89, but were not responsive to forskolin induction. All of these results demonstrate that PKA/CREB is involved in the regulation of constitutive promoter activity of the USP22 gene.

  15. SATB1 OVEREXPRESSION DRIVES TUMOR-PROMOTING ACTIVITIES IN CANCER-ASSOCIATED DENDRITIC CELLS

    PubMed Central

    Tesone, Amelia J.; Rutkowski, Melanie R.; Brencicova, Eva; Svoronos, Nikolaos; Perales-Puchalt, Alfredo; Stephen, Tom L.; Allegrezza, Michael J.; Payne, Kyle K.; Nguyen, Jenny M.; Wickramasinghe, Jayamanna; Tchou, Julia; Borowsky, Mark E.; Rabinovich, Gabriel A.; Kossenkov, Andrew V.; Conejo-Garcia, Jose R.

    2016-01-01

    SUMMARY Special AT-rich sequence-binding protein-1 (Satb1) governs genome-wide transcriptional programs. Using a conditional knockout mouse, we find that Satb1 is required for normal differentiation of conventional dendritic cells (DCs). Furthermore, Satb1 governs the differentiation of inflammatory DCs by regulating MHC-II expression through Notch1 signaling. Mechanistically, Satb1 binds to the Notch1 promoter, activating Notch expression and driving RBPJ occupancy of the H2-Ab1 promoter, which activates MHC-II transcription. However, tumor-driven, unremitting expression of Satb1 in activated Zbtb46+ inflammatory DCs that infiltrate ovarian tumors results in an immunosuppressive phenotype characterized by increased secretion of tumor-promoting Galectin-1 and IL-6. In vivo silencing of Satb1 in tumor-associated DCs reverses their tumorigenic activity and boosts protective immunity. Therefore, dynamic fluctuations in Satb1 expression govern the generation and immunostimulatory activity of steady-state and inflammatory DCs, but continuous Satb1 overexpression in differentiated DCs converts them into tolerogenic/pro-inflammatory cells that contribute to malignant progression. PMID:26876172

  16. Promotion of ovarian follicle growth following mTOR activation: synergistic effects of AKT stimulators.

    PubMed

    Cheng, Yuan; Kim, Jaehong; Li, Xiao Xiao; Hsueh, Aaron J

    2015-01-01

    Mammalian target of rapamycin (mTOR) is a serine/threonine kinase and mTOR signaling is important in regulating cell growth and proliferation. Recent studies using oocyte- and granulosa cell-specific deletion of mTOR inhibitor genes TSC1 or TSC2 demonstrated the important role of mTOR signaling in the promotion of ovarian follicle development. We now report that treatment of ovaries from juvenile mice with an mTOR activator MHY1485 stimulated mTOR, S6K1 and rpS6 phosphorylation. Culturing ovaries for 4 days with MHY1485 increased ovarian explant weights and follicle development. In vivo studies further demonstrated that pre-incubation of these ovaries with MHY1485 for 2 days, followed by allo-grafting into kidney capsules of adult ovariectomized hosts for 5 days, led to marked increases in graft weights and promotion of follicle development. Mature oocytes derived from MHY1485-activated ovarian grafts could be successfully fertilized, leading the delivery of healthy pups. We further treated ovaries with the mTOR activator together with AKT activators (PTEN inhibitor and phosphoinositol-3-kinase stimulator) before grafting and found additive enhancement of follicle growth. Our studies demonstrate the ability of an mTOR activator in promoting follicle growth, leading to a potential strategy to stimulate preantral follicle growth in infertile patients.

  17. Promotion of Ovarian Follicle Growth following mTOR Activation: Synergistic Effects of AKT Stimulators

    PubMed Central

    Cheng, Yuan; Kim, Jaehong; Li, Xiao Xiao; Hsueh, Aaron J.

    2015-01-01

    Mammalian target of rapamycin (mTOR) is a serine/threonine kinase and mTOR signaling is important in regulating cell growth and proliferation. Recent studies using oocyte- and granulosa cell-specific deletion of mTOR inhibitor genes TSC1 or TSC2 demonstrated the important role of mTOR signaling in the promotion of ovarian follicle development. We now report that treatment of ovaries from juvenile mice with an mTOR activator MHY1485 stimulated mTOR, S6K1 and rpS6 phosphorylation. Culturing ovaries for 4 days with MHY1485 increased ovarian explant weights and follicle development. In vivo studies further demonstrated that pre-incubation of these ovaries with MHY1485 for 2 days, followed by allo-grafting into kidney capsules of adult ovariectomized hosts for 5 days, led to marked increases in graft weights and promotion of follicle development. Mature oocytes derived from MHY1485-activated ovarian grafts could be successfully fertilized, leading the delivery of healthy pups. We further treated ovaries with the mTOR activator together with AKT activators (PTEN inhibitor and phosphoinositol-3-kinase stimulator) before grafting and found additive enhancement of follicle growth. Our studies demonstrate the ability of an mTOR activator in promoting follicle growth, leading to a potential strategy to stimulate preantral follicle growth in infertile patients. PMID:25710488

  18. Promoter discrimination at class I MarA regulon promoters mediated by glutamic acid 89 of the MarA transcriptional activator of Escherichia coli.

    PubMed

    Martin, Robert G; Rosner, Judah L

    2011-01-01

    Three paralogous transcriptional activators MarA, SoxS, and Rob, activate > 40 Escherichia coli promoters. To understand why MarA does not activate certain promoters as strongly as SoxS, we compared MarA, MarA mutants, and SoxS for their abilities to activate 16 promoters and to bind their cognate marbox binding sites. Replacement of the MarA glutamic acid residue 89 with alanine greatly increased the marbox binding and activation of many class I promoters. Like cells constitutive for SoxS, cells expressing the MarA with the E89A mutation were more resistant to superoxides than those harboring WT MarA. The activities of several other E89 substitutions ranked as follows: E89A > E89G > E89V > WT > E89D. Increased binding and activation occurred only at class I promoters when the 12th base of the promoter's marbox (a position at which there is no known interaction between the marbox and MarA) was not a T residue. Furthermore, WT MarA binding to a synthetic marbox in vitro was enhanced when the phosphate group between positions 12 and 13 was eliminated on one strand. The results demonstrate that relatively minor changes in a single amino acid side chain (e.g., alanine to valine or glutamic acid to aspartic acid) can strongly influence activity despite any evidence that the side chain is involved in positive interactions with either DNA or RNA polymerase. We present a model which attributes the differences in binding and activation to the interference between the β- and γ-carbons of the amino acid at position 89 and the phosphate group between positions 12 and 13.

  19. Myb and Ets proteins cooperate in transcriptional activation of the mim-1 promoter.

    PubMed Central

    Dudek, H; Tantravahi, R V; Rao, V N; Reddy, E S; Reddy, E P

    1992-01-01

    In the generation of the acutely transforming avian retrovirus E26, both myb and ets genes have been transduced, leading to the production of a Gag-Myb-Ets fusion protein. This co-occurrence of v-myb and v-ets oncogenes suggests that the two might have a functional relationship. To look for such a relationship, we tested the transcriptional activation activity of Myb alone or with coexpressed Ets-1 or Ets-2. Using the promoter of the v-Myb-inducible mim-1 gene as a target, we found that full-length c-Myb gene products were poor activators of transcription, while an oncogenic (truncated) form of this protein was a strong trans-activator. However, coexpression of Ets-2 with full-length or truncated forms of Myb greatly increased trans-activation. Coexpression of Ets-1, Fos, Jun, or Myc with Myb did not increase trans-activation of the mim-1 promoter. The ability of Myb and Ets-2 to transactivate was cooperative, since Ets-2 alone gave little or no activation. Bacterially synthesized Ets-2 protein was found to bind specifically to the mim-1 promoter, suggesting that it may be a target for both Myb and Ets proteins. Thus, Myb and Ets proteins can cooperate in transcriptional activation, and their co-occurrence in the E26 virus may reflect a functional relationship between these two oncoproteins. Truncated forms of Myb may have a reduced need for cooperating factors such as Ets-2, and this might constitute an important mechanism associated with oncogenic activation. Images PMID:1741383

  20. Microtubule-sliding activity of a kinesin-8 promotes spindle assembly and spindle-length control.

    PubMed

    Su, Xiaolei; Arellano-Santoyo, Hugo; Portran, Didier; Gaillard, Jeremie; Vantard, Marylin; Thery, Manuel; Pellman, David

    2013-08-01

    Molecular motors play critical roles in the formation of mitotic spindles, either through controlling the stability of individual microtubules, or by crosslinking and sliding microtubule arrays. Kinesin-8 motors are best known for their regulatory roles in controlling microtubule dynamics. They contain microtubule-destabilizing activities, and restrict spindle length in a wide variety of cell types and organisms. Here, we report an antiparallel microtubule-sliding activity of the budding yeast kinesin-8, Kip3. The in vivo importance of this sliding activity was established through the identification of complementary Kip3 mutants that separate the sliding activity and microtubule-destabilizing activity. In conjunction with Cin8, a kinesin-5 family member, the sliding activity of Kip3 promotes bipolar spindle assembly and the maintenance of genome stability. We propose a slide-disassemble model where the sliding and destabilizing activity of Kip3 balance during pre-anaphase. This facilitates normal spindle assembly. However, the destabilizing activity of Kip3 dominates in late anaphase, inhibiting spindle elongation and ultimately promoting spindle disassembly.

  1. BMP promotes motility and represses growth of smooth muscle cells by activation of tandem Wnt pathways

    PubMed Central

    de Jesus Perez, Vinicio A.; Ali, Ziad; Alastalo, Tero-Pekka; Ikeno, Fumiaki; Sawada, Hirofumi; Lai, Ying-Ju; Kleisli, Thomas; Spiekerkoetter, Edda; Qu, Xiumei; Rubinos, Laura H.; Ashley, Euan; Amieva, Manuel; Dedhar, Shoukat

    2011-01-01

    We present a novel cell-signaling paradigm in which bone morphogenetic protein 2 (BMP-2) consecutively and interdependently activates the wingless (Wnt)–β-catenin (βC) and Wnt–planar cell polarity (PCP) signaling pathways to facilitate vascular smooth muscle motility while simultaneously suppressing growth. We show that BMP-2, in a phospho-Akt–dependent manner, induces βC transcriptional activity to produce fibronectin, which then activates integrin-linked kinase 1 (ILK-1) via α4-integrins. ILK-1 then induces the Wnt–PCP pathway by binding a proline-rich motif in disheveled (Dvl) and consequently activating RhoA-Rac1–mediated motility. Transfection of a Dvl mutant that binds βC without activating RhoA-Rac1 not only prevents BMP-2–mediated vascular smooth muscle cell motility but promotes proliferation in association with persistent βC activity. Interfering with the Dvl-dependent Wnt–PCP activation in a murine stented aortic graft injury model promotes extensive neointima formation, as shown by optical coherence tomography and histopathology. We speculate that, in response to injury, factors that subvert BMP-2–mediated tandem activation of Wnt–βC and Wnt–PCP pathways contribute to obliterative vascular disease in both the systemic and pulmonary circulations. PMID:21220513

  2. Thiazolidinediones promote axonal growth through the activation of the JNK pathway.

    PubMed

    Quintanilla, Rodrigo A; Godoy, Juan A; Alfaro, Ivan; Cabezas, Deny; von Bernhardi, Rommy; Bronfman, Miguel; Inestrosa, Nibaldo C

    2013-01-01

    The axon is a neuronal process involved in protein transport, synaptic plasticity, and neural regeneration. It has been suggested that their structure and function are profoundly impaired in neurodegenerative diseases. Previous evidence suggest that Peroxisome Proliferator-Activated Receptors-γ (PPARγ promote neuronal differentiation on various neuronal cell types. In addition, we demonstrated that activation of PPARγby thiazolidinediones (TZDs) drugs that selectively activate PPARγ prevent neurite loss and axonal damage induced by amyloid-β (Aβ). However, the potential role of TZDs in axonal elongation and neuronal polarity has not been explored. We report here that the activation of PPARγ by TZDs promoted axon elongation in primary hippocampal neurons. Treatments with different TZDs significantly increased axonal growth and branching area, but no significant effects were observed in neurite elongation compared to untreated neurons. Treatment with PPARγ antagonist (GW 9662) prevented TZDs-induced axonal growth. Recently, it has been suggested that the c-Jun N-terminal kinase (JNK) plays an important role regulating axonal growth and neuronal polarity. Interestingly, in our studies, treatment with TZDs induced activation of the JNK pathway, and the pharmacological blockage of this pathway prevented axon elongation induced by TZDs. Altogether, these results indicate that activation of JNK induced by PPARγactivators stimulates axonal growth and accelerates neuronal polarity. These novel findings may contribute to the understanding of the effects of PPARγ on neuronal differentiation and validate the use of PPARγ activators as therapeutic agents in neurodegenerative diseases.

  3. GTPase ROP2 binds and promotes activation of target of rapamycin, TOR, in response to auxin.

    PubMed

    Schepetilnikov, Mikhail; Makarian, Joelle; Srour, Ola; Geldreich, Angèle; Yang, Zhenbiao; Chicher, Johana; Hammann, Philippe; Ryabova, Lyubov A

    2017-02-28

    Target of rapamycin (TOR) promotes reinitiation at upstream ORFs (uORFs) in genes that play important roles in stem cell regulation and organogenesis in plants. Here, we report that the small GTPase ROP2, if activated by the phytohormone auxin, promotes activation of TOR, and thus translation reinitiation of uORF-containing mRNAs. Plants with high levels of active ROP2, including those expressing constitutively active ROP2 (CA-ROP2), contain high levels of active TOR ROP2 physically interacts with and, when GTP-bound, activates TOR in vitro TOR activation in response to auxin is abolished in ROP-deficient rop2 rop6 ROP4 RNAi plants. GFP-TOR can associate with endosome-like structures in ROP2-overexpressing plants, indicating that endosomes mediate ROP2 effects on TOR activation. CA-ROP2 is efficient in loading uORF-containing mRNAs onto polysomes and stimulates translation in protoplasts, and both processes are sensitive to TOR inhibitor AZD-8055. TOR inactivation abolishes ROP2 regulation of translation reinitiation, but not its effects on cytoskeleton or intracellular trafficking. These findings imply a mode of translation control whereby, as an upstream effector of TOR, ROP2 coordinates TOR function in translation reinitiation pathways in response to auxin.

  4. Thiazolidinediones Promote Axonal Growth through the Activation of the JNK Pathway

    PubMed Central

    Quintanilla, Rodrigo A.; Godoy, Juan A.; Alfaro, Ivan; Cabezas, Deny; von Bernhardi, Rommy; Bronfman, Miguel; Inestrosa, Nibaldo C.

    2013-01-01

    The axon is a neuronal process involved in protein transport, synaptic plasticity, and neural regeneration. It has been suggested that their structure and function are profoundly impaired in neurodegenerative diseases. Previous evidence suggest that Peroxisome Proliferator-Activated Receptors-γ (PPARγ promote neuronal differentiation on various neuronal cell types. In addition, we demonstrated that activation of PPARγby thiazolidinediones (TZDs) drugs that selectively activate PPARγ prevent neurite loss and axonal damage induced by amyloid-β (Aβ). However, the potential role of TZDs in axonal elongation and neuronal polarity has not been explored. We report here that the activation of PPARγ by TZDs promoted axon elongation in primary hippocampal neurons. Treatments with different TZDs significantly increased axonal growth and branching area, but no significant effects were observed in neurite elongation compared to untreated neurons. Treatment with PPARγ antagonist (GW 9662) prevented TZDs-induced axonal growth. Recently, it has been suggested that the c-Jun N-terminal kinase (JNK) plays an important role regulating axonal growth and neuronal polarity. Interestingly, in our studies, treatment with TZDs induced activation of the JNK pathway, and the pharmacological blockage of this pathway prevented axon elongation induced by TZDs. Altogether, these results indicate that activation of JNK induced by PPARγactivators stimulates axonal growth and accelerates neuronal polarity. These novel findings may contribute to the understanding of the effects of PPARγ on neuronal differentiation and validate the use of PPARγ activators as therapeutic agents in neurodegenerative diseases. PMID:23741474

  5. Different Functional and Structural Characteristics between ApoA-I and ApoA-4 in Lipid-Free and Reconstituted HDL State: ApoA-4 Showed Less Anti-Atherogenic Activity

    PubMed Central

    Yoo, Jeong-Ah; Lee, Eun-Young; Park, Ji Yoon; Lee, Seung-Taek; Ham, Sihyun; Cho, Kyung-Hyun

    2015-01-01

    Apolipoprotein A-I and A-IV are protein constituents of high-density lipoproteins although their functional difference in lipoprotein metabolism is still unclear. To compare anti-atherogenic properties between apoA-I and apoA-4, we characterized both proteins in lipid-free and lipid-bound state. In lipid-free state, apoA4 showed two distinct bands, around 78 and 67 Å on native gel electrophoresis, while apoA-I showed scattered band pattern less than 71 Å. In reconstituted HDL (rHDL) state, apoA-4 showed three major bands around 101 Å and 113 Å, while apoA-I-rHDL showed almost single band around 98 Å size. Lipid-free apoA-I showed 2.9-fold higher phospholipid binding ability than apoA-4. In lipid-free state, BS3-crosslinking revealed that apoA-4 showed less multimerization tendency upto dimer, while apoA-I showed pentamerization. In rHDL state (95:1), apoA-4 was existed as dimer as like as apoA-I. With higher phospholipid content (255:1), five apoA-I and three apoA-4 were required to the bigger rHDL formation. Regardless of particle size, apoA-I-rHDL showed superior LCAT activation ability than apoA-4-rHDL. Uptake of acetylated LDL was inhibited by apoA-I in both lipid-free and lipid-bound state, while apoA-4 inhibited it only lipid-free state. ApoA-4 showed less anti-atherogenic activity with more sensitivity to glycation. In conclusion, apoA-4 showed inferior physiological functions in lipid-bound state, compared with those of apoA-I, to induce more pro-atherosclerotic properties. PMID:25997739

  6. Mdm2 is a novel activator of ApoCIII promoter which is antagonized by p53 and SHP inhibition

    SciTech Connect

    Yang, Zhihong; Zhang, Yuxia; Wang, Li

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer Mdm2 enhances HNF4{alpha} activation of the ApoCIII promoter via interaction with HNF4{alpha}. Black-Right-Pointing-Pointer p53 antagonizes the effect of Mdm2 activation of the ApoCIII promoter. Black-Right-Pointing-Pointer SHP strengthens p53 inhibition but abolishes Mdm2 activation of the ApoCIII promoter. Black-Right-Pointing-Pointer Mdm2 alters the enrichment of HNF4{alpha}, p53 and SHP to the ApoCIII promoter. -- Abstract: We examined the effect of Mdm2 on regulation of the ApoCIII promoter and its cross-talk with p53 and nuclear receptor SHP. Overexpression of Mdm2 markedly enhanced ApoCIII promoter activity by HNF4{alpha}. A direct association of Mdm2 protein with the HNF4{alpha} protein was observed by co-immunoprecipitation. Ectopic expression of p53 decreased HNF4{alpha} activation of the ApoCIII promoter and antagonized the effect of Mdm2. Co-expression of SHP further strengthened p53 inhibition and abolished Mdm2 activation of the ApoCIII promoter. Mdm2 inhibited p53-mediated enrichment of HNF4{alpha} to the ApoCIII promoter while simultaneously reducing p53 binding and increasing recruitment of SHP to the ApoCIII promoter. The results from this study implicate a potentially important function of Mdm2 in regulation of lipoprotein metabolism.

  7. Learning Microbiology Through Cooperation: Designing Cooperative Learning Activities that Promote Interdependence, Interaction, and Accountability

    PubMed Central

    TREMPY, JANINE E.; SKINNER, MONICA M.; SIEBOLD, WILLIAM A.

    2002-01-01

    A microbiology course and its corresponding learning activities have been structured according to the Cooperative Learning Model. This course, The World According to Microbes, integrates science, math, engineering, and technology (SMET) majors and non-SMET majors into teams of students charged with problem solving activities that are microbial in origin. In this study we describe development of learning activities that utilize key components of Cooperative Learning—positive interdependence, promotive interaction, individual accountability, teamwork skills, and group processing. Assessments and evaluations over an 8-year period demonstrate high retention of key concepts in microbiology and high student satisfaction with the course. PMID:23653547

  8. Amy as a reporter gene for promoter activity in Nocardia lactamdurans: comparison of promoters of the cephamycin cluster.

    PubMed Central

    Chary, V K; de la Fuente, J L; Liras, P; Martin, J F

    1997-01-01

    Promoter probe vectors containing the pA origin of replication and the Streptomyces griseus promoterless amy gene (encoding alpha-amylase) as reporter have been constructed to study transcription initiation regions in Nocardia lactamdurans. In some of the promoter probe vectors the phage fd terminator has been introduced to avoid readthrough expression from upstream sequences. By using these vectors, four different transcription initiation regions of the cephamycin gene cluster have been studied in N. lactamdurans. The bla gene encoding a beta-lactamase has a relatively strong promoter. Two other separate promoters corresponding to the lat and cefD genes (encoding, respectively, lysine-6-aminotransferase and isopenicillin N-epimerase) showed weak transcription initiation ability. These two promoters are arranged in a bidirectional transcription initiation region located in the center of the cephamycin gene cluster. The cmcH gene (encoding 3-hydroxymethylcephem carbamoyltransferase) upstream region did not contain a functional promoter, suggesting that cmcH is transcribed as a part of a polycistronic mRNA. The native amy promoter is used very efficiently in N. lactamdurans, resulting in secretion of high levels of extracellular alpha-amylase. PMID:9251185

  9. Direct inhibition of TNF-α promoter activity by Fanconi anemia protein FANCD2.

    PubMed

    Matsushita, Nobuko; Endo, Yujiro; Sato, Koichi; Kurumizaka, Hitoshi; Yamashita, Takayuki; Takata, Minoru; Yanagi, Shigeru

    2011-01-01

    Fanconi anemia (FA), an inherited disease, is associated with progressive bone marrow failure, predisposition to cancer, and genomic instability. Genes corresponding to 15 identified FA complementation groups have been cloned, and each gene product functions in the response to DNA damage induced by cross-linking agents and/or in protection against genome instability. Interestingly, overproduction of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and aberrant activation of NF-κB-dependent transcriptional activity have been observed in FA cells. Here we demonstrated that FANCD2 protein inhibits NF-κB activity in its monoubiquitination-dependent manner. Furthermore, we detected a specific association between FANCD2 and an NF-κB consensus element in the TNF-α promoter by electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) assay. Therefore, we propose FANCD2 deficiency promotes transcriptional activity of the TNF-α promoter and induces overproduction of TNF-which then sustains prolonged inflammatory responses. These results also suggest that artificial modulation of TNFα production could be a promising therapeutic approach to FA.

  10. EZH2-mediated repression of Dkk1 promotes hepatic stellate cell activation and hepatic fibrosis.

    PubMed

    Yang, Yang; Chen, Xiao-Xia; Li, Wan-Xia; Wu, Xiao-Qin; Huang, Cheng; Xie, Juan; Zhao, Yu-Xin; Meng, Xiao-Ming; Li, Jun

    2017-03-23

    EZH2, a histone H3 lysine-27-specific methyltransferase, is involved in diverse physiological and pathological processes including cell proliferation and differentiation. However, the role of EZH2 in liver fibrosis is largely unknown. In this study, it was identified that EZH2 promoted Wnt pathway-stimulated fibroblasts in vitro and in vivo by repressing Dkk-1, which is a Wnt pathway antagonist. The expression of EZH2 was increased in CCl4 -induced rat liver and primary HSCs as well as TGF-β1-treated HSC-T6, whereas the expression of Dkk1 was reduced. Silencing of EZH2 prevented TGF-β1-induced proliferation of HSC-T6 cells and the expression of α-SMA. In addition, knockdown of Dkk1 promoted TGF-β1-induced activation of HSCs. Moreover, silencing of EZH2 could restore the repression of Dkk-1 through trimethylation of H3K27me3 in TGF-β1-treated HSC-T6 cells. Interestingly, inhibition of EZH2 had almost no effect on the activation of HSC when Dkk1 was silenced. Collectively, EZH2-mediated repression of Dkk1 promotes the activation of Wnt/β-catenin pathway, which is an essential event for HSC activation.

  11. Wnt activation followed by Notch inhibition promotes mitotic hair cell regeneration in the postnatal mouse cochlea

    PubMed Central

    Li, Wenyan; Chen, Yan; Zhang, Shasha; Tang, Mingliang; Sun, Shan; Chai, Renjie; Li, Huawei

    2016-01-01

    Hair cell (HC) loss is the main cause of permanent hearing loss in mammals. Previous studies have reported that in neonatal mice cochleae, Wnt activation promotes supporting cell (SC) proliferation and Notch inhibition promotes the trans-differentiation of SCs into HCs. However, Wnt activation alone fails to regenerate significant amounts of new HCs, Notch inhibition alone regenerates the HCs at the cost of exhausting the SC population, which leads to the death of the newly regenerated HCs. Mitotic HC regeneration might preserve the SC number while regenerating the HCs, which could be a better approach for long-term HC regeneration. We present a two-step gene manipulation, Wnt activation followed by Notch inhibition, to accomplish mitotic regeneration of HCs while partially preserving the SC number. We show that Wnt activation followed by Notch inhibition strongly promotes the mitotic regeneration of new HCs in both normal and neomycin-damaged cochleae while partially preserving the SC number. Lineage tracing shows that the majority of the mitotically regenerated HCs are derived specifically from the Lgr5+ progenitors with or without HC damage. Our findings suggest that the co-regulation of Wnt and Notch signaling might provide a better approach to mitotically regenerate HCs from Lgr5+ progenitor cells. PMID:27564256

  12. Genetic variants in ABCA1 promoter affect transcription activity and plasma HDL level in pigs.

    PubMed

    Dang, Xiao-yong; Chu, Wei-wei; Shi, Heng-chuan; Yu, Shi-gang; Han, Hai-yin; Gu, Shu-Hua; Chen, Jie

    2015-01-25

    Excess accumulation of cholesterol in plasma may result in coronary artery disease. Numerous studies have demonstrated that ATP-binding cassette protein A1 (ABCA1) mediates the efflux of cholesterol and phospholipids to apolipoproteins, a process necessary for plasma high density lipoprotein (HDL) formation. Higher plasma levels of HDL are associated with lower risk for cardiovascular disease. Studies of human disease and animal models had shown that an increased hepatic ABCA1 activity relates to an enhanced plasma HDL level. In this study, we hypothesized that functional mutations in the ABCA1 promoter in pigs may affect gene transcription activity, and consequently the HDL level in plasma. The promoter region of ABCA1 was comparatively scanned by direct sequencing with pool DNA of high- and low-HDL groups (n=30 for each group). Two polymorphisms, c. - 608A>G and c. - 418T>A, were revealed with reverse allele distribution in the two groups. The two polymorphisms were completely linked and formed only G-A or A-T haplotypes when genotyped in a larger population (n=526). Furthermore, we found that the G-A/G-A genotype was associated with higher HDL and ABCA1 mRNA level than A-T/A-T genotype. Luciferase assay also revealed that G-A haplotype promoter had higher activity than A-T haplotype. Single-nucleotide mutant assay showed that c.-418T>A was the causal mutation for ABCA1 transcription activity alteration. Conclusively, we identified two completely linked SNPs in porcine ABCA1 promoter region which have influence on the plasma HDL level by altering ABCA1 gene transcriptional activity.

  13. Dietary cholesterol promotes AOM-induced colorectal cancer through activating the NLRP3 inflammasome.

    PubMed

    Du, Qianming; Wang, Qing; Fan, Huimin; Wang, Jianing; Liu, Xiuting; Wang, Hong; Wang, Yajing; Hu, Rong

    2016-04-01

    Prolonged ingestion of a cholesterol-enriched diet induces chronic, auto-inflammatory responses resulting in significant health problems including colorectal cancer. Inflammasomes are thought to mediate intestinal homeostasis, and their dysregulation contributes to inflammatory bowel diseases and colitis-associated cancer (CAC). However, in vitro and in vivo information regarding the inflammation-inducing and tumor-promoting effect of cholesterol is lacking. Here we show that the cholesterol promoted colon carcinogenesis in azoxymethane (AOM)-treated mice through activating the NLRP3 inflammasome. High cholesterol diet (HCD) significantly increased inflammatory responses and tumor burden. Cholesterol crystals, detected in the colon of mice fed with HCD, also promoted NLRP3 inflammasome activation in macrophages, as indicated by elevated expression of cleaved caspase-1, formation of NLRP3-ASC-caspase-1 complex assembly, and higher IL-1β secretion. Importantly, cholesterol was found to inhibit the activity of AMPKα in macrophages, leading to a significant production of mitochondrial ROS, which in turn activated the NLRP3 inflammasome. Moreover, crystal uptake and cathepsin B accounted for cholesterol crystal-induced inactivation of AMPKα. Finally, HCD-induced increase in IL-1β secretion, macrophage infiltration and tumor burden was diminished by the deletion of NLRP3 in AOM-treated mice. Taken together, our findings demonstrate that the pro-inflammatory and cancer-promoting effects of HCD are mediated by the activation of NLRP3 inflammasome. Our study extended our knowledge on how dietary choices can influence processes involved in chronic inflammatory disorders and colorectal cancer.

  14. Conservation of mouse alpha A-crystallin promoter activity in chicken lens epithelial cells.

    PubMed

    Donovan, D M; Sax, C M; Klement, J F; Li, X; Chepelinsky, A B; Piatigorsky, J

    1992-10-01

    Previous transfection experiments have shown that 162 base pairs (bp) of the 5' flanking sequence of the chicken alpha A-crystallin gene are required for promoter activity in primary chicken lens epithelial cells (PLE), while only 111 bp of the 5' flanking sequence are needed for activity of the mouse alpha A-crystallin promoter in transfected chicken PLE cells or in a SV40 T-antigen-transformed transfected mouse lens epithelial cell line (alpha TN4-1). The effect of site-directed mutations covering positions -111 to -34 of the mouse alpha A-crystallin promoter fused to the bacterial chloramphenicol acetyltransferase (CAT) gene was compared in transfected chicken PLE cells and mouse alpha TN4-1 cells; selected mutations were also examined in a nontransformed rabbit lens epithelial cell line (N/N1003A). In general, the same mutations reduced promoter activity in the transfected lens cells from all three species, although differences were noted. The mutations severely affected regions -111/-106 and -69/-40 regions in all the transfected cells examined; by contrast, mutations at positions -105/-99 and -87/-70 had a somewhat greater effect in the chicken PLE than the mouse alpha TN4-1 cells, while mutations of the -93/-88 sequence reduced expression in the alpha TN4-1 but not the PLE cells. A partial cDNA with sequence similarity to alpha A-CRYPB1 of the mouse has been isolated from a chicken lens library; mouse alpha A-CRYBP1 is a putative transcription factor which binds to the -66/-55 sequence of the mouse alpha A-crystallin promoter.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. DIXDC1 activates the Wnt signaling pathway and promotes gastric cancer cell invasion and metastasis.

    PubMed

    Tan, Cong; Qiao, Fan; Wei, Ping; Chi, Yayun; Wang, Weige; Ni, Shujuan; Wang, Qifeng; Chen, Tongzhen; Sheng, Weiqi; Du, Xiang; Wang, Lei

    2016-04-01

    DIXDC1 (Dishevelled-Axin domain containing 1) is a DIX (Dishevelled-Axin) domain-possessing protein that promotes colon cancer cell proliferation and increases the invasion and migration ability of non-small-cell lung cancer via the PI3K pathway. As a positive regulator of the Wnt/β-catenin pathway, the biological role of DIXDC1 in human gastric cancer and the relationship between DIXDC1 and the Wnt pathway are unclear. In the current study, the upregulation of DIXDC1 was detected in gastric cancer and was associated with advanced TNM stage cancer, lymph node metastasis, and poor prognosis. We also found that the overexpression of DIXDC1 could promote the invasion and migration of gastric cancer cells. The upregulation of MMPs and the downregulation of E-cadherin were found to be involved in the process. DIXDC1 enhanced β-catenin nuclear accumulation, which activated the Wnt pathway. Additionally, the inhibition of β-catenin in DIXDC1-overexpressing cells reversed the metastasis promotion effects of DIXDC1. These results demonstrate that the expression of DIXDC1 is associated with poor prognosis of gastric cancer patients and that DIXDC1 promotes gastric cancer invasion and metastasis through the activation of the Wnt pathway; E-cadherin and MMPs are also involved in this process. © 2015 Wiley Periodicals, Inc.

  16. AP-2{alpha} suppresses skeletal myoblast proliferation and represses fibroblast growth factor receptor 1 promoter activity

    SciTech Connect

    Mitchell, Darrion L.; DiMario, Joseph X.

    2010-01-15

    Skeletal muscle development is partly characterized by myoblast proliferation and subsequent differentiation into postmitotic muscle fibers. Developmental regulation of expression of the fibroblast growth factor receptor 1 (FGFR1) gene is required for normal myoblast proliferation and muscle formation. As a result, FGFR1 promoter activity is controlled by multiple transcriptional regulatory proteins during both proliferation and differentiation of myogenic cells. The transcription factor AP-2{alpha} is present in nuclei of skeletal muscle cells and suppresses myoblast proliferation in vitro. Since FGFR1 gene expression is tightly linked to myoblast proliferation versus differentiation, the FGFR1 promoter was examined for candidate AP-2{alpha} binding sites. Mutagenesis studies indicated that a candidate binding site located at - 1035 bp functioned as a repressor cis-regulatory element. Furthermore, mutation of this site alleviated AP-2{alpha}-mediated repression of FGFR1 promoter activity. Chromatin immunoprecipitation studies demonstrated that AP-2{alpha} interacted with the FGFR1 promoter in both proliferating myoblasts and differentiated myotubes. In total, these results indicate that AP-2{alpha} is a transcriptional repressor of FGFR1 gene expression during skeletal myogenesis.

  17. Active Gaming to Promote Physical Activity: Questions to Consider for Your School

    ERIC Educational Resources Information Center

    Meyler, Tim; Banks, Sarah; Wilson, Sandy

    2014-01-01

    The physical activity potential and physiological and motivational benefits of active gaming have been a hot topic in the past few years. It is easy to see why active games are popular among certain populations, particularly those with prior or current video game experience. Video games are fun to play and challenging, give a player total control,…

  18. Cell cycle-coupled expansion of AR activity promotes cancer progression.

    PubMed

    McNair, C; Urbanucci, A; Comstock, C E S; Augello, M A; Goodwin, J F; Launchbury, R; Zhao, S G; Schiewer, M J; Ertel, A; Karnes, J; Davicioni, E; Wang, L; Wang, Q; Mills, I G; Feng, F Y; Li, W; Carroll, J S; Knudsen, K E

    2017-03-23

    The androgen receptor (AR) is required for prostate cancer (PCa) survival and progression, and ablation of AR activity is the first line of therapeutic intervention for disseminated disease. While initially effective, recurrent tumors ultimately arise for which there is no durable cure. Despite the dependence of PCa on AR activity throughout the course of disease, delineation of the AR-dependent transcriptional network that governs disease progression remains elusive, and the function of AR in mitotically active cells is not well understood. Analyzing AR activity as a function of cell cycle revealed an unexpected and highly expanded repertoire of AR-regulated gene networks in actively cycling cells. New AR functions segregated into two major clusters: those that are specific to cycling cells and retained throughout the mitotic cell cycle ('Cell Cycle Common'), versus those that were specifically enriched in a subset of cell cycle phases ('Phase Restricted'). Further analyses identified previously unrecognized AR functions in major pathways associated with clinical PCa progression. Illustrating the impact of these unmasked AR-driven pathways, dihydroceramide desaturase 1 was identified as an AR-regulated gene in mitotically active cells that promoted pro-metastatic phenotypes, and in advanced PCa proved to be highly associated with development of metastases, recurrence after therapeutic intervention and reduced overall survival. Taken together, these findings delineate AR function in mitotically active tumor cells, thus providing critical insight into the molecular basis by which AR promotes development of lethal PCa and nominate new avenues for therapeutic intervention.

  19. The built environment: designing communities to promote physical activity in children.

    PubMed

    Tester, June M

    2009-06-01

    An estimated 32% of American children are overweight, and physical inactivity contributes to this high prevalence of overweight. This policy statement highlights how the built environment of a community affects children's opportunities for physical activity. Neighborhoods and communities can provide opportunities for recreational physical activity with parks and open spaces, and policies must support this capacity. Children can engage in physical activity as a part of their daily lives, such as on their travel to school. Factors such as school location have played a significant role in the decreased rates of walking to school, and changes in policy may help to increase the number of children who are able to walk to school. Environment modification that addresses risks associated with automobile traffic is likely to be conducive to more walking and biking among children. Actions that reduce parental perception and fear of crime may promote outdoor physical activity. Policies that promote more active lifestyles among children and adolescents will enable them to achieve the recommended 60 minutes of daily physical activity. By working with community partners, pediatricians can participate in establishing communities designed for activity and health.

  20. JAK tyrosine kinases promote hierarchical activation of Rho and Rap modules of integrin activation.

    PubMed

    Montresor, Alessio; Bolomini-Vittori, Matteo; Toffali, Lara; Rossi, Barbara; Constantin, Gabriela; Laudanna, Carlo

    2013-12-23

    Lymphocyte recruitment is regulated by signaling modules based on the activity of Rho and Rap small guanosine triphosphatases that control integrin activation by chemokines. We show that Janus kinase (JAK) protein tyrosine kinases control chemokine-induced LFA-1- and VLA-4-mediated adhesion as well as human T lymphocyte homing to secondary lymphoid organs. JAK2 and JAK3 isoforms, but not JAK1, mediate CXCL12-induced LFA-1 triggering to a high affinity state. Signal transduction analysis showed that chemokine-induced activation of the Rho module of LFA-1 affinity triggering is dependent on JAK activity, with VAV1 mediating Rho activation by JAKs in a Gαi-independent manner. Furthermore, activation of Rap1A by chemokines is also dependent on JAK2 and JAK3 activity. Importantly, activation of Rap1A by JAKs is mediated by RhoA and PLD1, thus establishing Rap1A as a downstream effector of the Rho module. Thus, JAK tyrosine kinases control integrin activation and dependent lymphocyte trafficking by bridging chemokine receptors to the concurrent and hierarchical activation of the Rho and Rap modules of integrin activation.

  1. A SURVEY OF DISPOSITION OF PHYSICIANS TOWARDS PHYSICAL ACTIVITY PROMOTION AT TWO TERTIARY HOSPITALS IN NORTH-EASTERN NIGERIA

    PubMed Central

    Oyeyemi, A.Y; Usman, R.B; Oyeyemi, A.L

    2016-01-01

    Background: A general presumption is that any advice from physicians would likely be taken seriously by patients, and patients are more likely to see their doctors in the event of any health complaints than any other health professionals. The perceptions and practice of Nigerian physicians on their role in physical activity promotion are not well known. This study aimed to determine the knowledge of physical activity message, confidence, role perceptions, barriers and feasibility of physical activity promotion among physicians in two tertiary health institutions in North-Eastern Nigeria. Method: A total of 153 (84.5% response) physicians at the University of Maiduguri Teaching Hospital and Federal Medical Center Yola completed a previously developed questionnaire that elicited information on their knowledge, barrier, feasibility, role and confidence in physical activity promotion. Results: Physicians in this study reported fairly good knowledge (mean score=14.7±2.2/20), minimal or little barrier to physical activity promotion (mean score=24.4±3.5/30), perceived physical activity promotion as their role (mean score=12.9±1.6/15), were confident in their ability to discuss and recommend exercises for physical activity promotion (mean score=7.9±1.3/ 10) and believed promoting physical activity was feasible for them (mean score=15.0±2.5/20). The physicians had good disposition to physical activity promotion (Mean score=78.5±6.7/100), but male physicians showed better disposition than their female counterparts. Conclusion: Overall these cohorts of physicians are somewhat knowledgeable on physical activity promotion and are positively disposed to promoting physical activity among their patients. These findings can be leveraged upon to optimize outcome of campaigns or interventions to change physical activity behaviour in Nigerian populace.

  2. FBI-1 enhances ETS-1 signaling activity and promotes proliferation of human colorectal carcinoma cells.

    PubMed

    Zhu, Min; Li, Mingyang; Zhang, Fan; Feng, Fan; Chen, Weihao; Yang, Yutao; Cui, Jiajun; Zhang, Dong; Linghu, Enqiang

    2014-01-01

    In this study, we investigated a potential regulatory role of FBI-1 in transcription factor activity of ETS-1. The protein interaction was identified between ETS-1 and FBI-1 in lovo cells. The accumulating data showed that FBI-1 promoted the recruitment of ETS-1 to endogenous promoter of its target genes and increase ETS-1 accumulation in the nuclear. Our work also indicated that the FBI-1 enhances ETS-1 transcription factor activity via down-regulating p53-mediated inhibition on ETS-1. Further, FBI-1 plays a role in regulation of colorectal carcinoma cells proliferation. These findings supported that FBI-1 might be a potential molecule target for treating colorectal carcinoma.

  3. Randomised controlled trials of physical activity promotion in free living populations: a review.

    PubMed Central

    Hillsdon, M; Thorogood, M; Anstiss, T; Morris, J

    1995-01-01

    OBJECTIVES--To review evidence on the effectiveness of trials of physical activity promotion in healthy, free living adults. To identify the more effective intervention programmes. METHODS--Computerised databases and references were searched. Experts were contacted and asked for information about existing work. INCLUSION CRITERIA--Randomised controlled trials of healthy, free living adult subjects, where exercise behaviour was the dependent variable were included. CONCLUSIONS--Ten trials were identified. The small number of trials limits the strength of any conclusions and highlights the need for more research. No UK based studies were found. Previously sedentary adults can increase activity levels and sustain them. Promotion of these changes requires personal instruction, continued support, and exercise of moderate intensity which does not depend on attendance at a facility. The exercise should be easily included into an existing lifestyle and should be enjoyable. Walking is the exercise most likely to fulfil these criteria. PMID:7499985

  4. FBI-1 Enhances ETS-1 Signaling Activity and Promotes Proliferation of Human Colorectal Carcinoma Cells

    PubMed Central

    Chen, Weihao; Yang, Yutao; Cui, Jiajun; Zhang, Dong; Linghu, Enqiang

    2014-01-01

    In this study, we investigated a potential regulatory role of FBI-1 in transcription factor activity of ETS-1. The protein interaction was identified between ETS-1 and FBI-1 in lovo cells. The accumulating data showed that FBI-1 promoted the recruitment of ETS-1 to endogenous promoter of its target genes and increase ETS-1 accumulation in the nuclear. Our work also indicated that the FBI-1 enhances ETS-1 transcription factor activity via down-regulating p53-mediated inhibition on ETS-1. Further, FBI-1 plays a role in regulation of colorectal carcinoma cells proliferation. These findings supported that FBI-1 might be a potential molecule target for treating colorectal carcinoma. PMID:24857950

  5. Extraction, chemical characterization and biological activity determination of broccoli health promoting compounds.

    PubMed

    Ares, Ana M; Nozal, María J; Bernal, José

    2013-10-25

    Broccoli (Brassica oleracea L. var. Italica) contains substantial amount of health-promoting compounds such as vitamins, glucosinolates, phenolic compounds, and dietary essential minerals; thus, it benefits health beyond providing just basic nutrition, and consumption of broccoli has been increasing over the years. This review gives an overview on the extraction and separation techniques, as well as the biological activity of some of the above mentioned compounds which have been published in the period January 2008 to January 2013. The work has been distributed according to the different families of health promoting compounds discussing the extraction procedures and the analytical techniques employed for their characterization. Finally, information about the different biological activities of these compounds has been also provided.

  6. Recent activities for the promotion of gender equality in the societies of physics in Japan

    NASA Astrophysics Data System (ADS)

    Mori, H.; Sasao, M.; Nemoto, K.; Tamechika, E.; Watanabe, M. O.

    2015-12-01

    Although the percentage of women members increases from 2% to 6% in the last 30 years, the ratio is still low in both the Physical Society of Japan and the Japan Society of Applied Physics. Recent activities for the promotion of gender equality in both societies, the development of the next generation of members, organizing international workshops and domestic symposiums, and so on, are introduced in this paper.

  7. Inactivation of ID4 promotes a CRPC phenotype with constitutive AR activation through FKBP52.

    PubMed

    Joshi, Jugal Bharat; Patel, Divya; Morton, Derrick J; Sharma, Pankaj; Zou, Jin; Hewa Bostanthirige, Dhanushka; Gorantla, Yamini; Nagappan, Peri; Komaragiri, Shravan Kumar; Sivils, Jeffrey C; Xie, Huan; Palaniappan, Ravi; Wang, Guangdi; Cox, Marc B; Chaudhary, Jaideep

    2016-11-27

    Castration-resistant prostate cancer (CRPC) is the emergence of prostate cancer cells that have adapted to the androgen-depleted environment of the prostate. In recent years, targeting multiple chaperones and co-chaperones (e.g., Hsp27, FKBP52) that promote androgen receptor (AR) signaling and/or novel AR regulatory mechanisms have emerged as promising alternative treatments for CRPC. We have shown that inactivation of inhibitor of differentiation 4 (ID4), a dominant-negative helix loop helix protein, promotes de novo steroidogenesis and CRPC with a gene expression signature that resembles constitutive AR activity in castrated mice. In this study, we investigated the underlying mechanism through which loss of ID4 potentiates AR signaling. Proteomic analysis between prostate cancer cell line LNCaP (L+ns) and LNCaP lacking ID4 (L(-)ID4) revealed elevated levels of Hsp27 and FKBP52, suggesting a role for these AR-associated co-chaperones in promoting constitutively active AR signaling in L(-)ID4 cells. Interestingly, protein interaction studies demonstrated a direct interaction between ID4 and the 52-kDa FK506-binding protein (FKBP52) in vitro, but not with AR. An increase in FKBP52-dependent AR transcriptional activity was observed in L(-)ID4 cells. Moreover, pharmacological inhibition of FKBP52-AR signaling, by treatment with MJC13, attenuated the tumor growth, weight, and volume in L(-)ID4 xenografts. Together, our results demonstrate that ID4 selectively regulates AR activity through direct interaction with FKBP52, and its loss, promotes CRPC through FKBP52-mediated AR signaling.

  8. Canadian Society for Exercise Physiology position stand: Benefit and risk for promoting childhood physical activity.

    PubMed

    Longmuir, Patricia E; Colley, Rachel C; Wherley, Valerie A; Tremblay, Mark S

    2014-11-01

    Current guidelines recommend children accumulate 60 min of daily physical activity; however, highly publicized sudden-death events among young athletes raise questions regarding activity safety. An expert group convened (June 2012) to consider the safety of promoting increased physical activity for children, and recommended the publication of an evidence-based statement of current knowledge regarding the benefits and risks of physical activity for children. Recommendations for encouraging physical activity while maximizing the opportunity to identify children who have been prescribed a physical activity restriction include (1) professionals and (or) researchers that encourage children to change the type of physical activity or to increase the frequency, intensity, or duration of their activity should inquire whether a child has primary healthcare provider-prescribed activity limitations before the child's activity participation changes; (2) physical activity researchers should prioritize the development of evidence regarding the benefits and risks of childhood physical activity and inactivity, particularly data on the risks of sedentary lifestyles and physical activity-associated injury risks that accounts for the amount of activity performed, and the effectiveness of current risk-management strategies and screening approaches; (3) professionals and researchers should prioritize the dissemination of information regarding the benefits of physical activity and the risks of sedentary behaviour in children; and (4) parents and professionals should encourage all children to accumulate at least 60 min of physical activity daily. The recommendations are established as a minimum acceptable standard that is applicable to all physical activity opportunities organized for children, whether those opportunities occur in a community, school, or research setting.

  9. Tumor suppressor protein C53 antagonizes checkpoint kinases to promote cyclin-dependent kinase 1 activation.

    PubMed

    Jiang, Hai; Wu, Jianchun; He, Chen; Yang, Wending; Li, Honglin

    2009-04-01

    Cyclin-dependent kinase 1 (Cdk1)/cyclin B1 complex is the driving force for mitotic entry, and its activation is tightly regulated by the G2/M checkpoint. We originally reported that a novel protein C53 (also known as Cdk5rap3 and LZAP) potentiates DNA damage-induced cell death by modulating the G2/M checkpoint. More recently, Wang et al. (2007) found that C53/LZAP may function as a tumor suppressor by way of inhibiting NF-kappaB signaling. We report here the identification of C53 protein as a novel regulator of Cdk1 activation. We found that knockdown of C53 protein causes delayed Cdk1 activation and mitotic entry. During DNA damage response, activation of checkpoint kinase 1 and 2 (Chk1 and Chk2) is partially inhibited by C53 overexpression. Intriguingly, we found that C53 interacts with Chk1 and antagonizes its function. Moreover, a portion of C53 protein is localized at the centrosome, and centrosome-targeting C53 potently promotes local Cdk1 activation. Taken together, our results strongly suggest that C53 is a novel negative regulator of checkpoint response. By counteracting Chk1, C53 promotes Cdk1 activation and mitotic entry in both unperturbed cell-cycle progression and DNA damage response.

  10. “I am active”: effects of a program to promote active aging

    PubMed Central

    Mendoza-Ruvalcaba, Neyda Ma; Arias-Merino, Elva Dolores

    2015-01-01

    Background Active aging involves a general lifestyle strategy that allows preservation of both physical and mental health during the aging process. “I am Active” is a program designed to promote active aging by increased physical activity, healthy nutritional habits, and cognitive functioning. The purpose of this study was to assess the effectiveness of this program. Methods Sixty-four healthy adults aged 60 years or older were recruited from senior centers and randomly allocated to an experimental group (n=31) or a control group (n=33). Baseline, post-test, and 6-month follow-up assessments were performed after the theoretical–practical intervention. Effect sizes were calculated. Results At the conclusion of the program, the experimental group showed significant improvement compared with the control group in the following domains: physical activity (falls risk, balance, flexibility, self-efficacy), nutrition (self-efficacy and nutritional status), cognitive performance (processing speed and self-efficacy), and quality of life (general, health and functionality, social and economic status). Although some declines were reported, improvements at follow-up remained in self-efficacy for physical activity, self-efficacy for nutrition, and processing speed, and participants had better nutritional status and quality of life overall. Conclusion Our findings show that this program promotes improvements in domains of active aging, mainly in self-efficacy beliefs as well as in quality of life in healthy elders. PMID:26005337

  11. HU0622: a small molecule promoting GAP-43 activation and neurotrophic effects.

    PubMed

    Uwabe, Ken-Ichiro; Iwakawa, Tsuneo; Matsumoto, Mitsunobu; Talkahashi, Koji; Nagata, Kiyoshi

    2006-09-01

    During the course of neuronal development or regeneration, the axonal growth cone protein growth-associated protein 43 (GAP-43) is expressed in a great majority of differentiating neurons, suggesting that the regulation of this gene is tied to important differentiation signals common to many neurons. In order to discover non-peptide molecules capable of mimicking the effects of NGF, we developed a reporter gene assay system based on measurement of light production in PC12 cells stably transfected with the luciferase reporter gene, the expression of which depends on the transcriptional activation of GAP-43. High throughput screening of the proprietary compound collection using this system revealed (E,E)-1-[5-(3,4-dihydroxyphenyl)-1-oxo-2,4-pentadienyl]piperidine (HU0622), a piperine derivative, to be an activator of GAP-43 transcription. HU0622 strongly induced neurite outgrowth and extension in PC12 and sensory neuronal cultures of chick dorsal root ganglia. The compound induced sustained extracellular signal-regulated kinase (ERK) activation that is crucial for neurite outgrowth activity without activating NGF receptor, TrkA. Furthermore, HU0622 as well as NGF promoted PC12 survival under serum-free conditions and activated Akt/protein kinase B downstream from phosphatidylinositol 3-kinase (PI3K). HU0622 also promoted survival of rat dorsal root ganglion neurons deprived of NGF. HU0622, a small non-peptidyl molecule, may be a novel promising lead compound for the stimulation of nerve regeneration.

  12. Promoting Physical Activity With Group Pictures. Affiliation-Based Visual Communication for High-Risk Populations.

    PubMed

    Reifegerste, Doreen; Rossmann, Constanze

    2017-02-01

    Past research in social and health psychology has shown that affiliation motivation is associated with health behavior, especially for high-risk populations, suggesting that targeting this motivation could be a promising strategy to promote physical activity. However, the effects that affiliation appeals (e.g., pictures depicting companionship during physical activities) and accompanying slogans have on motivating physical activity have been largely unexplored. Hence, our two studies experimentally tested the effects of exposure to affiliation-based pictures for overweight or less active people, as well as the moderating effect of affiliation motivation. The results of these two studies give some indication that group pictures (with or without an accompanying slogan) can be an effective strategy to improve high-risk populations' attitudes, self-efficacy, and intentions to engage in physical activity. Affiliation motivation as a personality trait did not interact with these effects, but was positively associated with attitudes, independent of the group picture effect.

  13. Autophagy Promotes Microglia Activation Through Beclin-1-Atg5 Pathway in Intracerebral Hemorrhage.

    PubMed

    Yuan, Bangqing; Shen, Hanchao; Lin, Li; Su, Tonggang; Zhong, Lina; Yang, Zhao

    2017-01-01

    Previous study demonstrates that intracerebral hemorrhage (ICH) promotes microglia activation and inflammation. However, the exact mechanism of microglia activation induced by ICH is not clear. In this experiment, microglia autophagy was examined using electron microscopy, conversion of light chain 3(LC3), and monodansylcadaverine (MDC) staining to detect autophagic vacuoles. We found that ICH induced microglia autophagy and activation. The suppression of autophagy using either pharmacologic inhibitors (3-methyladenine, bafilomycin A1) or RNA interference in essential autophagy genes (BECN1 and ATG5) decreased the microglia activation and inflammation in ICH. Moreover, autophagy inhibitors reduced brain damage in ICH. In conclusion, these data indicate that ICH contributes to microglia autophagic activation through BECN1 and ATG5 and provide the therapeutical strategy for ICH.

  14. Promoting physical activity and healthy eating: convergence in framing the role of industry.

    PubMed

    Dorfman, Lori; Yancey, Antronette K

    2009-10-01

    This commentary addresses a little explored aspect of prevention, namely, how public health practitioners conceptualize the roles of industries whose business interests may be at odds with physical activity and eating nutrient-rich foods. Taking their cues from successful campaigns in tobacco control, many public health advocates have framed obesity as a battle with the food industry. Such framing presents problems when it exacerbates existing tensions between practitioners in nutrition and physical activity, and alienates potential fitness industry partners. Creating healthy environments requires reframing expectations of all industries that influence physical activity and inactivity. A broader view of the influence of corporate practices on physical and social environments will help both physical activity and nutrition advocates identify what they can do together, and in partnership with the business sector, to create environments that promote activity and nutritious eating.

  15. The human papillomavirus (HPV) E6 oncoproteins promotes nuclear localization of active caspase 8

    SciTech Connect

    Manzo-Merino, Joaquin; Lizano, Marcela

    2014-02-15

    The HPV-16 E6 and E6{sup ⁎} proteins have been shown previously to be capable of regulating caspase 8 activity. We now show that the capacity of E6 to interact with caspase 8 is common to diverse HPV types, being also seen with HPV-11 E6, HPV-18 E6 and HPV-18 E6{sup ⁎}. Unlike most E6-interacting partners, caspase 8 does not appear to be a major proteasomal target of E6, but instead E6 appears able to stimulate caspase 8 activation, without affecting the overall apoptotic activity. This would appear to be mediated in part by the ability of the HPV E6 oncoproteins to recruit active caspase 8 to the nucleus. - Highlights: • Multiple HPV E6 oncoproteins interact with the caspase 8 DED domain. • HPV E6 stimulates activation of caspase 8. • HPV E6 promotes nuclear accumulation of caspase 8.

  16. Activation of the Oryza sativa non-symbiotic haemoglobin-2 promoter by the cytokinin-regulated transcription factor, ARR1.

    PubMed

    Ross, Emily J H; Stone, Julie M; Elowsky, Christian G; Arredondo-Peter, Raul; Klucas, Robert V; Sarath, Gautam

    2004-08-01

    Using in silico methods, several putative phytohormone-responsive cis-elements in the Oryza sativa non-symbiotic haemoglobin (NSHB) 1-4 and Arabidopsis thaliana NSHB1-2 promoters have been identified. An OsNSHB2 promoter::GUS reporter gene fusion shows tissue-specific expression in A. thaliana. GUS expression was observed in roots, the vasculature of young leaves, in flowers, and in the pedicel/stem junction. In transient assays, activity of the OsNSHB2 promoter was significantly up-regulated in the presence of the cytokinin, 6-benzylaminopurine (BA). Deletion analyses indicated that the full-length promoter was required for maximal trans-activation in the presence of cytokinin. Mutation of the single cytokinin-regulated ARR1-binding element abolished promoter activation in response to cytokinin. Constitutive expression of ARR1 under the control of the 35S cauliflower mosaic virus promoter enhanced wild-type OsNSHB2 promoter activity, but had no effect on the activity of the mutated promoter in the absence of cytokinin. However, overexpression of ARR1 in the presence of cytokinin resulted in super-activation of the wild-type promoter. The mutated promoter was only moderately activated in the presence of cytokinin and ARR1, indicating that the OsNSHB2 promoter can be regulated by the ARR1 protein, but requires other cytokinin-induced factors for optimal activation. This is the first report that identifies a trans-acting factor involved in the activation of a NSHB gene.

  17. Effect of environmental estrogens on IL-1beta promoter activity in a macrophage cell line.

    PubMed

    Ruh, M F; Bi, Y; Cox, L; Berk, D; Howlett, A C; Bellone, C J

    1998-10-01

    Environmental estrogens or estrogen disrupters have recently received a great deal of attention because of their potential health impact on reproductive tissues. Few, if any, studies have been made on the impact of these compounds on the immune system. We sought to determine the activities of various environmental estrogens on the modulation of the interleukin-1beta (IL-1beta) gene in a model monocytic cell line, hER + IL-1beta-CAT+. This cell line stably transfected with the human estrogen receptor, and an IL-1beta promoter construct fused to the CAT reporter gene allows us to monitor the effect of estrogenic compounds on IL-1beta promoter activity. 17beta-estradiol (E2) markedly enhanced lipopolysaccharide- (LPS) induced IL-1beta promoter-driven CAT activity in a dose-dependent manner. The mycotoxins alpha-zearalenol and zearalenone both exhibited full agonist activity, but at lower potencies, with EC50 values of 1.8 and 54 nM, respectively, compared with E2 at 0.5 nM. In addition, genistein was a very low-potency agonist, having an EC50 of 1.5 microM. Similar to the E2 response, the slope factors for alpha-zearalenol, zearalenone, and genistein were close to 3.0, suggesting positive cooperativity in the estrogenic response. The activity of the mycotoxins appeared to be mediated through the estrogen receptor, since both the antiestrogens H1285 and ICI 182,780 effectively inhibited their agonist activity in a dose-dependent manner. Representative environmental estrogenic compounds both from plant and industrial sources were also tested. Unlike the mycoestrogens, none of the compounds, with the exception of genistein, synergized with LPS to enhance IL-1beta promoter activity. When tested for antiestrogenic activity, the industrial compound 4-octylphenol was able to antagonize the response to E2; however, the response was three orders of magnitude less potent than H 1285. Naringenin, a plant flavonoid, showed little or no ability to antagonize the response to E2

  18. Promoting physical activity and reducing climate change: opportunities to replace short car trips with active transportation.

    PubMed

    Maibach, Edward; Steg, Linda; Anable, Jillian

    2009-10-01

    Automobile use is a significant contributor to climate change, local air pollution, pedestrian injuries and deaths, declines in physical activity and obesity. A significant proportion of car use is for short trips that can relatively easily be taken with active transportation options--walking or cycling--or with public transportation. In this commentary, we review a number of immediate, practical opportunities to implement policies and programs that reduce short car trips and increase active transportation.

  19. In vivo single-molecule kinetics of activation and subsequent activity of the arabinose promoter.

    PubMed

    Mäkelä, Jarno; Kandhavelu, Meenakshisundaram; Oliveira, Samuel M D; Chandraseelan, Jerome G; Lloyd-Price, Jason; Peltonen, Juha; Yli-Harja, Olli; Ribeiro, Andre S

    2013-07-01

    Using a single-RNA detection technique in live Escherichia coli cells, we measure, for each cell, the waiting time for the production of the first RNA under the control of PBAD promoter after induction by arabinose, and subsequent intervals between transcription events. We find that the kinetics of the arabinose intake system affect mean and diversity in RNA numbers, long after induction. We observed the same effect on Plac/ara-1 promoter, which is inducible by arabinose or by IPTG. Importantly, the distribution of waiting times of Plac/ara-1 is indistinguishable from that of PBAD, if and only if induced by arabinose alone. Finally, RNA production under the control of PBAD is found to be a sub-Poissonian process. We conclude that inducer-dependent waiting times affect mean and cell-to-cell diversity in RNA numbers long after induction, suggesting that intake mechanisms have non-negligible effects on the phenotypic diversity of cell populations in natural, fluctuating environments.

  20. Biocontrol and plant growth-promoting activity of rhizobacteria from Chinese fields with contaminated soils

    PubMed Central

    Wang, Xuefei; Mavrodi, Dmitri V; Ke, Linfeng; Mavrodi, Olga V; Yang, Mingming; Thomashow, Linda S; Zheng, Na; Weller, David M; Zhang, Jibin

    2015-01-01

    The aim of this study was to inventory the types of plant growth-promoting rhizobacteria (PGPR) present in the rhizosphere of plants grown in soils contaminated with heavy metals, recalcitrant organics, petroleum sewage or salinity in China. We screened 1223 isolates for antifungal activity and about 24% inhibited Rhizoctonia solani or Sclerotinia sclerotiorum. Twenty-four strains inhibitory to R. solani, Gaeumannomyces graminis var. tritici and/or S. sclerotiorum and representing the dominant morphotypes were assayed for PGPR activity. Seven strains contained phlD, prnD, pltC or phzF genes and produced the antibiotics 2,4-diacetylphloroglucinol, pyrrolnitrin, pyoluteorin and phenazines respectively. Six strains contained acdS, which encodes 1-aminocyclopropane-1-carboxylic acid deaminase. Phylogenetic analysis of 16S rDNA and phlD, phzF and acdS genes demonstrated that some strains identified as Pseudomonas were similar to model PGPR strains Pseudomonas protegens Pf-5, Pseudomonas chlororaphis subsp. aureofaciens 30–84 and P. brassicacearum Q8r1-96. Pseudomonas protegens- and P. chlororaphis-like strains had the greatest biocontrol activity against Rhizoctonia root rot and take-all of wheat. Pseudomonas protegens and P. brassicacearum-like strains showed the greatest promotion of canola growth. Our results indicate that strains from contaminated soils are similar to well-described PGPR found in agricultural soils worldwide. Growth-promoting rhizobacteria in polluted soils PMID:25219642

  1. ATPase activity tightly regulates RecA nucleofilaments to promote homologous recombination

    PubMed Central

    Zhao, Bailin; Zhang, Dapeng; Li, Chengmin; Yuan, Zheng; Yu, Fangzhi; Zhong, Shangwei; Jiang, Guibin; Yang, Yun-Gui; Le, X Chris; Weinfeld, Michael; Zhu, Ping; Wang, Hailin

    2017-01-01

    Homologous recombination (HR), catalyzed in an evolutionarily conserved manner by active RecA/Rad51 nucleofilaments, maintains genomic integrity and promotes biological evolution and diversity. The structures of RecA/Rad51 nucleofilaments provide information critical for the entire HR process. By exploiting a unique capillary electrophoresis-laser-induced fluorescence polarization assay, we have discovered an active form of RecA nucleofilament, stimulated by ATP hydrolysis, that contains mainly unbound nucleotide sites. This finding was confirmed by a nuclease protection assay and electron microscopy (EM) imaging. We further found that these RecA-unsaturated filaments promote strand exchange in vitro and HR in vivo. RecA mutants (P67D and P67E), which only form RecA-unsaturated nucleofilaments, were able to mediate HR in vitro and in vivo, but mutants favoring the formation of the saturated nucleofilaments failed to support HR. We thus present a new model for RecA-mediated HR in which RecA utilizes its intrinsic DNA binding-dependent ATPase activity to remodel the nucleofilaments to a less saturated form and thereby promote HR. PMID:28101376

  2. CD147 promotes melanoma progression through hypoxia-induced MMP2 activation.

    PubMed

    Zeng, W; Su, J; Wu, L; Yang, D; Long, T; Li, D; Kuang, Y; Li, J; Qi, M; Zhang, J; Chen, X

    2014-01-01

    Hypoxia enhances MMP2 expression and the invasion and metastatic potential of melanoma cells. CD147 has been shown to induce MMP2 in multiple cancers. To investigate the role of CD147 in hypoxiainduced MMP2 activation, we performed immunohistochemistry (IHC) staining in 206 normal and melanoma tissue samples, and analyzed the correlation between HIF1α and CD147. ChIP (chromosome Immunoprecipitation) in melanoma cell lines supports that HIF1α directly binds to CD147 promoter. Moreover, we made a series of deletion mutants of CD147 promoter, and identified a conserved HIF1α binding site. Point mutation in this site significantly decreased CD147 response to hypoxia. Importantly, knocking down CD147 attenuates MMP2 response to hypoxia in melanoma cell lines. MMP2 could not be efficiently activated by hypoxia in CD147 depletion cells. ELISA data showed that MMP2 secretion was reduced in CD147 depletion cells than control under hypoxia condition. To verify the data from cell culture model, we performed in vivo mouse xenograft experiment. IHC staining showed reduced MMP2 level in CD147 depleted xenografts compared to the control group, with the HIF1α level being comparable. Our study demonstrates a novel pathway mediated by CD147 to promote the MMP2 activation induced by hypoxia, and helps to understand the interplay between hypoxia and melanoma progression.

  3. Activation of Dopamine Receptors in the Nucleus Accumbens Promotes Sucrose-Reinforced Cued Approach Behavior

    PubMed Central

    du Hoffmann, Johann; Nicola, Saleem M.

    2016-01-01

    Dopamine receptor activation in the nucleus accumbens (NAc) promotes vigorous environmentally-cued food-seeking in hungry rats. Rats fed ad libitum, however, respond to fewer food-predictive cues, particularly when the value of food reward is low. Here, we investigated whether this difference could be due to differences in the degree of dopamine receptor activation in the NAc. First, we observed that although rats given ad libitum access to chow in their home cages approached a food receptacle in response to reward-predictive cues, the number of such approaches declined as animals accumulated food rewards. Intriguingly, cued approach to food occurred in clusters, with several cued responses followed by successive non-responses. This pattern suggested that behavior was dictated by transitions between two states, responsive and non-responsive. Injection of D1 or D2 dopamine receptor agonists into the NAc dose-dependently increased cue responding by promoting transitions to the responsive state and by preventing transitions to the non-responsive state. In contrast, antagonists of either D1 or D2 receptors promoted long bouts of non-responding by inducing transitions to the non-responsive state and by preventing transitions to the responsive state. Moreover, locomotor behavior during the inter-trial interval was correlated with the responsive state, and was also increased by dopamine receptor agonists. These results suggest that activation of NAc dopamine receptors plays an important role in regulating the probability of approach to food under conditions of normative satiety. PMID:27471453

  4. High activity of the stress promoter contributes to susceptibility to stress in the tree shrew

    PubMed Central

    Fang, Hui; Sun, Yun-Jun; Lv, Yan-Hong; Ni, Rong-Jun; Shu, Yu-Mian; Feng, Xiu-Yu; Wang, Yu; Shan, Qing-Hong; Zu, Ya-Nan; Zhou, Jiang-Ning

    2016-01-01

    Stress is increasingly present in everyday life in our fast-paced society and involved in the pathogenesis of many psychiatric diseases. Corticotrophin-releasing-hormone (CRH) plays a pivotal role in regulating the stress responses. The tree shrews are highly vulnerable to stress which makes them the promising animal models for studying stress responses. However, the mechanisms underlying their high stress-susceptibility remained unknown. Here we confirmed that cortisol was the dominate corticosteroid in tree shrew and was significantly increased after acute stress. Our study showed that the function of tree shrew CRH - hypothalamic-pituitary-adrenal (HPA) axis was nearly identical to human that contributed little to their hyper-responsiveness to stress. Using CRH transcriptional regulation analysis we discovered a peculiar active glucocorticoid receptor response element (aGRE) site within the tree shrew CRH promoter, which continued to recruit co-activators including SRC-1 (steroid receptor co-activator-1) to promote CRH transcription under basal or forskolin/dexamethasone treatment conditions. Basal CRH mRNA increased when the aGRE was knocked into the CRH promoter in human HeLa cells using CAS9/CRISPR. The aGRE functioned critically to form the “Stress promoter” that contributed to the higher CRH expression and susceptibility to stress. These findings implicated novel molecular bases of the stress-related diseases in specific populations. PMID:27125313

  5. Persistent ERK/MAPK Activation Promotes Lactotrope Differentiation and Diminishes Tumorigenic Phenotype

    PubMed Central

    Booth, Allyson; Trudeau, Tammy; Gomez, Crystal; Lucia, M. Scott

    2014-01-01

    The signaling pathways that govern the lactotrope-specific differentiated phenotype, and those that control lactotrope proliferation in both physiological and pathological lactotrope expansion, are poorly understood. Moreover, the specific role of MAPK signaling in lactotrope proliferation vs differentiation, whether activated phosphorylated MAPK is sufficient for prolactinoma tumor formation remain unknown. Given that oncogenic Ras mutations and persistently activated phosphorylated MAPK are found in human tumors, including prolactinomas and other pituitary tumors, a better understanding of the role of MAPK in lactotrope biology is required. Here we directly examined the role of persistent Ras/MAPK signaling in differentiation, proliferation, and tumorigenesis of rat pituitary somatolactotrope GH4 cells. We stimulated Ras/MAPK signaling in a persistent, long-term manner (over 6 d) in GH4 cells using two distinct approaches: 1) a doxycycline-inducible, oncogenic V12Ras expression system; and 2) continuous addition of exogenous epidermal growth factor. We find that long-term activation of the Ras/MAPK pathway over 6 days promotes differentiation of the bihormonal somatolactotrope GH4 precursor cell into a prolactin-secreting, lactotrope cell phenotype in vitro and in vivo with GH4 cell xenograft tumors. Furthermore, we show that persistent activation of the Ras/MAPK pathway not only fails to promote cell proliferation, but also diminishes tumorigenic characteristics in GH4 cells in vitro and in vivo. These data demonstrate that activated MAPK promotes differentiation and is not sufficient to drive tumorigenesis, suggesting that pituitary lactotrope tumor cells have the ability to evade the tumorigenic fate that is often associated with Ras/MAPK activation. PMID:25361391

  6. RNA Activation of the Vascular Endothelial Growth Factor Gene (VEGF) Promoter by Double-Stranded RNA and Hypoxia: Role of Noncoding VEGF Promoter Transcripts

    PubMed Central

    Wagner, Kay-Dietrich; Hofman, Paul; Van Obberghen, Emmanuel

    2016-01-01

    RNA activation (RNAa) is a gene regulation process in which promoter-targeted short double-stranded RNAs (dsRNAs) or microRNAs (miRs) induce target gene expression at the transcriptional level. Here, we investigate the presence of cryptic promoter transcripts within the VEGF promoter. Single-strand sense and antisense noncoding vascular endothelial growth factor (NcVEGF) promoter transcripts are identified, and their respective expression is studied in cells transfected with a VEGF promoter targeted dsRNA, namely, dsVEGF706, in hypoxic cells and in human malignant lung tissues. Interestingly, in dsVEGF706-transfected, as well as in hypoxic cells, NcVEGF expression levels increase coordinately with coding VEGF expression. Ago2 interaction with both sense and antisense NcVEGFs is increased in hypoxic cells, whereas in dsVEGF706-transfected cells, Ago2 and the antisense strand of the dsRNA interact specifically with the sense NcVEGF transcript. Furthermore, both dsVEGF706 and ectopic NcVEGF transcripts are able to activate the VEGF promoter endogenously present or in a reporter construct. Finally, using small interfering RNA targeting Ago2, we show that RNAa plays a role in the maintenance of increased VEGF and NcVEGF expression after hypoxia. Given the central role of VEGF in major human diseases, including cancer, this novel molecular mechanism is poised to reveal promising possibilities for therapeutic interventions. PMID:26976645

  7. Characterization of the promoter and upstream activating sequence from the Pseudomonas alcaligenes lipase gene.

    PubMed

    Cox, M; Gerritse, G; Dankmeyer, L; Quax, W J

    2001-03-09

    Pseudomonas alcaligenes secretes a lipase with a high pH optimum, which has interesting properties for application in detergents. The expression of the lipase is strongly dependent on the presence of lipids in the growth medium such as soybean oil. The promoter of the gene was characterized and found to have resemblance to sigma54 controlled promoters, which are known to be tightly regulated. The transcription start was mapped precisely downstream of a sequence with close similarity to the -12/-24 consensus sequence of sigma54 controlled promoters. Interestingly, a hyperproducer mutant strain was isolated and found to have a C to T mutation in the -12/-24 promoter consensus region. In addition an Upstream Activating Sequence (UAS) with homology to sigma54 UAS consensus sequences was identified. It was demonstrated that an increase of the distance from the UAS to the transcription start or the deletion of the UAS results in significantly lower expression levels of lipase. A systematic mutational analysis of the UAS sequence has resulted in a variant with an increased lipase expression.

  8. Behaviour change interventions to promote physical activity in rheumatoid arthritis: a systematic review.

    PubMed

    Larkin, Louise; Gallagher, Stephen; Cramp, Fiona; Brand, Charles; Fraser, Alexander; Kennedy, Norelee

    2015-10-01

    Research has shown that people who have rheumatoid arthritis (RA) do not usually participate in enough physical activity to obtain the benefits of optimal physical activity levels, including quality of life, aerobic fitness and disease-related characteristics. Behaviour change theory underpins the promotion of physical activity. The aim of this systematic review was to explore behaviour change interventions which targeted physical activity behaviour in people who have RA, focusing on the theory underpinning the interventions and the behaviour change techniques utilised using specific behaviour change taxonomy. An electronic database search was conducted via EBSCOhost, PubMed, Cochrane Central Register of Controlled Trials and Web of Science databases in August 2014, using Medical Subject Headings and keywords. A manual search of reference lists was also conducted. Randomised control trials which used behaviour change techniques and targeted physical activity behaviour in adults who have RA were included. Two reviewers independently screened studies for inclusion. Methodological quality was assessed using the Cochrane risk of bias tool. Five studies with 784 participants were included in the review. Methodological quality of the studies was mixed. The studies consisted of behaviour change interventions or combined practical physical activity and behaviour change interventions and utilised a large variety of behaviour change techniques. Four studies reported increased physical activity behaviour. All studies used subjective methods of assessing physical activity with only one study utilising an objective measure. There has been varied success of behaviour change interventions in promoting physical activity behaviour in people who have RA. Further studies are required to develop and implement the optimal behaviour change intervention in this population.

  9. NR2D-containing NMDA receptors mediate tissue plasminogen activator-promoted neuronal excitotoxicity.

    PubMed

    Baron, A; Montagne, A; Cassé, F; Launay, S; Maubert, E; Ali, C; Vivien, D

    2010-05-01

    Although the molecular bases of its actions remain debated, tissue-type plasminogen activator (tPA) is a paradoxical brain protease, as it favours some learning/memory processes, but increases excitotoxic neuronal death. Here, we show that, in cultured cortical neurons, tPA selectively promotes NR2D-containing N-methyl-D-aspartate receptor (NMDAR)-dependent activation. We show that tPA-mediated signalling and neurotoxicity through the NMDAR are blocked by co-application of an NR2D antagonist (phenanthrene derivative (2S(*), 3R(*))-1-(phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid, PPDA) or knockdown of neuronal NR2D expression. In sharp contrast with cortical neurons, hippocampal neurons do not exhibit NR2D both in vitro and in vivo and are consequently resistant to tPA-promoted NMDAR-mediated neurotoxicity. Moreover, we have shown that activation of synaptic NMDAR prevents further tPA-dependent NMDAR-mediated neurotoxicity and sensitivity to PPDA. This study shows that the earlier described pro-neurotoxic effect of tPA is mediated by NR2D-containing NMDAR-dependent extracellular signal-regulated kinase activation, a deleterious effect prevented by synaptic pre-activation.

  10. The Ska complex promotes Aurora B activity to ensure chromosome biorientation.

    PubMed

    Redli, Patrick M; Gasic, Ivana; Meraldi, Patrick; Nigg, Erich A; Santamaria, Anna

    2016-10-10

    Chromosome biorientation and accurate segregation rely on the plasticity of kinetochore-microtubule (KT-MT) attachments. Aurora B facilitates KT-MT dynamics by phosphorylating kinetochore proteins that are critical for KT-MT interactions. Among the substrates whose microtubule and kinetochore binding is curtailed by Aurora B is the spindle and kinetochore-associated (Ska) complex, a key factor for KT-MT stability. Here, we show that Ska is not only a substrate of Aurora B, but is also required for Aurora B activity. Ska-deficient cells fail to biorient and display chromosome segregation errors underlying suppressed KT-MT turnover. These defects coincide with KNL1-Mis12-Ndc80 network hypophosphorylation, reduced mitotic centromere-associated kinesin localization, and Aurora B T-loop phosphorylation at kinetochores. We further show that Ska requires its microtubule-binding capability to promote Aurora B activity in cells and stimulates Aurora B catalytic activity in vitro. Finally, we show that protein phosphatase 1 counteracts Aurora B activity to enable Ska kinetochore accumulation once biorientation is achieved. We propose that Ska promotes Aurora B activity to limit its own microtubule and kinetochore association and to ensure that KT-MT dynamics and stability fall within an optimal balance for biorientation.

  11. 12-Deoxyphorbols Promote Adult Neurogenesis by Inducing Neural Progenitor Cell Proliferation via PKC Activation

    PubMed Central

    Geribaldi-Doldán, Noelia; Flores-Giubi, Eugenia; Murillo-Carretero, Maribel; García-Bernal, Francisco; Carrasco, Manuel; Macías-Sánchez, Antonio J.; Domínguez-Riscart, Jesús; Verástegui, Cristina; Hernández-Galán, Rosario

    2016-01-01

    Background: Neuropsychiatric and neurological disorders frequently occur after brain insults associated with neuronal loss. Strategies aimed to facilitate neuronal renewal by promoting neurogenesis constitute a promising therapeutic option to treat neuronal death-associated disorders. In the adult brain, generation of new neurons occurs physiologically throughout the entire life controlled by extracellular molecules coupled to intracellular signaling cascades. Proteins participating in these cascades within neurogenic regions constitute potential pharmacological targets to promote neuronal regeneration of injured areas of the central nervous system. Methodology: We have performed in vitro and in vivo approaches to determine neural progenitor cell proliferation to understand whether activation of kinases of the protein kinase C family facilitates neurogenesis in the adult brain. Results: We have demonstrated that protein kinase C activation by phorbol-12-myristate-13-acetate induces neural progenitor cell proliferation in vitro. We also show that the nontumorogenic protein kinase C activator prostratin exerts a proliferative effect on neural progenitor cells in vitro. This effect can be reverted by addition of the protein kinase C inhibitor G06850, demonstrating that the effect of prostratin is mediated by protein kinase C activation. Additionally, we show that prostratin treatment in vivo induces proliferation of neural progenitor cells within the dentate gyrus of the hippocampus and the subventricular zone. Finally, we describe a library of diterpenes with a 12-deoxyphorbol structure similar to that of prostratin that induces a stronger effect than prostratin on neural progenitor cell proliferation both in vitro and in vivo. Conclusions: This work suggests that protein kinase C activation is a promising strategy to expand the endogenous neural progenitor cell population to promote neurogenesis and highlights the potential of 12-deoxyphorbols as pharmaceutical

  12. Promoting Physical Activity in Middle School Girls: Trial of Activity for Adolescent Girls

    PubMed Central

    Webber, Larry S.; Catellier, Diane J.; Lytle, Leslie A.; Murray, David M.; Pratt, Charlotte A.; Young, Deborah R.; Elder, John P.; Lohman, Timothy G.; Stevens, June; Jobe, Jared B.; Pate, Russell R.

    2008-01-01

    Background Physical activity is important for weight control and good health; however, activity levels decline in the adolescent years, particularly in girls. Design Group randomized controlled trial Setting/participants Middle school girls with English-speaking skills and no conditions to prevent participation in physical activity in 36 schools in six geographically diverse areas of the United States. Random, cross-sectional samples were drawn within schools: 6th graders in 2003 (n=1721) and 8th graders in 2005 (n=3504) and 2006 (n=3502). Intervention A 2-year study-directed intervention (fall 2003 to spring 2005) targeted schools, community agencies, and girls to increase opportunities, support, and incentives for increased physical activity. Components included programs linking schools and community agencies, physical education, health education, and social marketing. A third-year intervention used school and community personnel to direct intervention activities. Main outcome measures The primary outcome, daily MET-weighted minutes of moderate-to-vigorous physical activity (MET-weighted MVPA), was assessed using accelerometry. Percent body fat was assessed using anthropometry. Results After the staff-directed intervention (pre-stated primary outcome), there were no differences (mean= −0.4, 95% CI= CI= −8.2 to 7.4) in adjusted MET-weighted MVPA between 8th-grade girls in schools assigned to intervention or control. Following the Program Champion–directed intervention, girls in intervention schools were more physically active than girls in control schools (mean difference 10.9 MET-weighted minutes of MVPA, 95% CI=0.52–21.2). This difference is about 1.6 minutes of daily MVPA or 80 kcal per week. There were no differences in fitness or percent body fat at either 8th-grade timepoint. Conclusion A school-based, community-linked intervention modestly improved physical activity in girls. PMID:18312804

  13. The Satiety Signaling Neuropeptide Perisulfakinin Inhibits the Activity of Central Neurons Promoting General Activity

    PubMed Central

    Wicher, Dieter; Derst, Christian; Gautier, Hélène; Lapied, Bruno; Heinemann, Stefan H.; Agricola, Hans-Jürgen

    2007-01-01

    The metabolic state is one of the determinants of the general activity level. Satiety is related to resting or sleep whereas hunger correlates to wakefulness and activity. The counterpart to the mammalian satiety signal cholecystokinin (CCK) in insects are the sulfakinins. The aim of this study was to resolve the mechanism by which the antifeedant activity of perisulfakinin (PSK) in Periplaneta americana is mediated. We identified the sources of PSK which is used both as hormone and as paracrine messenger. PSK is found in the neurohemal organ of the brain and in nerve endings throughout the central nervous system. To correlate the distributions of PSK and its receptor (PSKR), we cloned the gene coding for PSKR and provide evidence for its expression within the nervous system. It occurs only in a few neurons, among them are the dorsal unpaired median (DUM) neurons which release octopamine thereby regulating the general level of activity. Application of PSK to DUM neurons attenuated the spiking frequency (EC50=11pM) due to reduction of a pacemaker Ca2+ current through cAMP-inhibited pTRPγ channels. PSK increased the intracellular cAMP level while decreasing the intracellular Ca2+ concentration in DUM neurons. Thus, the satiety signal conferred by PSK acts antagonistically to the hunger signal, provided by the adipokinetic hormone (AKH): PSK depresses the electrical activity of DUM neurons by inhibiting the pTRPγ channel that is activated by AKH under conditions of food shortage. PMID:18946521

  14. The Activation of Free Dipeptides Promoted by Strong Activating Agents in Water Does not Yield Diketopiperazines

    NASA Astrophysics Data System (ADS)

    Beaufils, Damien; Jepaul, Sandra; Liu, Ziwei; Boiteau, Laurent; Pascal, Robert

    2016-03-01

    The activation of dipeptides was studied in the perspective of the abiotic formation of oligopeptides of significant length as a requirement for secondary structure formation. The formation of piperazin-2,5-diones (DKP), previously considered as a dead end when activating free dipeptides, was shown in this work to be efficiently suppressed when using strong activating agents (e.g., carbodiimides). This behaviour was explained by the fast formation of a 5(4 H)-oxazolone intermediate at a rate that exceeds the time scale of the rotation of the peptide bond from the predominant trans-conformation into the cis-isomer required for DKP formation. No DKP was observed when using strong activating agents whereas phosphate mixed anhydrides or moderately activated esters were observed to predominantly yield DKP. The DKP side-reaction no longer constitutes a drawback for the C-terminus elongation of peptides. These results are considered as additional evidence that pathways involving strong activation are required to drive the emergence of living entities rather than close to equilibrium processes.

  15. The Activation of Free Dipeptides Promoted by Strong Activating Agents in Water Does not Yield Diketopiperazines.

    PubMed

    Beaufils, Damien; Jepaul, Sandra; Liu, Ziwei; Boiteau, Laurent; Pascal, Robert

    2016-03-01

    The activation of dipeptides was studied in the perspective of the abiotic formation of oligopeptides of significant length as a requirement for secondary structure formation. The formation of piperazin-2,5-diones (DKP), previously considered as a dead end when activating free dipeptides, was shown in this work to be efficiently suppressed when using strong activating agents (e.g., carbodiimides). This behaviour was explained by the fast formation of a 5(4H)-oxazolone intermediate at a rate that exceeds the time scale of the rotation of the peptide bond from the predominant trans-conformation into the cis-isomer required for DKP formation. No DKP was observed when using strong activating agents whereas phosphate mixed anhydrides or moderately activated esters were observed to predominantly yield DKP. The DKP side-reaction no longer constitutes a drawback for the C-terminus elongation of peptides. These results are considered as additional evidence that pathways involving strong activation are required to drive the emergence of living entities rather than close to equilibrium processes.

  16. Alcohol dysregulates corticotropin-releasing-hormone (CRH) promoter activity by interfering with the negative glucocorticoid response element (nGRE).

    PubMed

    Przybycien-Szymanska, Magdalena M; Mott, Natasha N; Pak, Toni R

    2011-01-01

    EtOH exposure in male rats increases corticotropin-releasing hormone (CRH) mRNA in the paraventricular nucleus of the hypothalamus (PVN), a brain region responsible for coordinating stress and anxiety responses. In this study we identified the molecular mechanisms involved in mediating these effects by examining the direct effects of EtOH on CRH promoter activity in a neuronal cell line derived from the PVN (IVB). In addition, we investigated the potential interactions of EtOH and glucocorticoids on the CRH promoter by concomitantly treating cells with EtOH and the glucocorticoid receptor (GR) antagonist RU486, and by sequentially deleting GR binding sites within glucocorticoid response element (GRE) on the CRH promoter. Cells were transiently transfected with a firefly luciferase reporter construct containing 2.5 kb of the rat wild type (WT) or mutated CRH promoter. Our results showed that EtOH treatment induced a biphasic response in CRH promoter activity. EtOH exposure for 0.5 h significantly decreased promoter activity compared to vehicle treated controls, whereas promoter activity was significantly increased after 2.0 h of EtOH exposure. Treatment with RU486, or deletion of the GR binding sites 1 and 2 within the GRE, abolished the EtOH-induced increase in the promoter activity, however did not affect EtOH-induced decrease in CRH promoter activity at an earlier time point. Overall, our data suggest that alcohol exposure directly regulates CRH promoter activity by interfering with the normal feedback mechanisms of glucocorticoids mediated by GR signaling at the GRE site of the CRH promoter.

  17. Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis

    SciTech Connect

    Anastasiou, Dimitrios; Yu, Yimin; Israelsen, William J.; Jiang, Jian-Kang; Boxer, Matthew B.; Hong, Bum Soo; Tempel, Wolfram; Dimov, Svetoslav; Shen, Min; Jha, Abhishek; Yang, Hua; Mattaini, Katherine R.; Metallo, Christian M.; Fiske, Brian P.; Courtney, Kevin D.; Malstrom, Scott; Khan, Tahsin M.; Kung, Charles; Skoumbourdis, Amanda P.; Veith, Henrike; Southall, Noel; Walsh, Martin J.; Brimacombe, Kyle R.; Leister, William; Lunt, Sophia Y.; Johnson, Zachary R.; Yen, Katharine E.; Kunii, Kaiko; Davidson, Shawn M.; Christofk, Heather R.; Austin, Christopher P.; Inglese, James; Harris, Marian H.; Asara, John M.; Stephanopoulos, Gregory; Salituro, Francesco G.; Jin, Shengfang; Dang, Lenny; Auld, Douglas S.; Park, Hee-Won; Cantley, Lewis C.; Thomas, Craig J.; Vander Heiden, Matthew G.

    2012-08-26

    Cancer cells engage in a metabolic program to enhance biosynthesis and support cell proliferation. The regulatory properties of pyruvate kinase M2 (PKM2) influence altered glucose metabolism in cancer. The interaction of PKM2 with phosphotyrosine-containing proteins inhibits enzyme activity and increases the availability of glycolytic metabolites to support cell proliferation. This suggests that high pyruvate kinase activity may suppress tumor growth. We show that expression of PKM1, the pyruvate kinase isoform with high constitutive activity, or exposure to published small-molecule PKM2 activators inhibits the growth of xenograft tumors. Structural studies reveal that small-molecule activators bind PKM2 at the subunit interaction interface, a site that is distinct from that of the endogenous activator fructose-1,6-bisphosphate (FBP). However, unlike FBP, binding of activators to PKM2 promotes a constitutively active enzyme state that is resistant to inhibition by tyrosine-phosphorylated proteins. This data supports the notion that small-molecule activation of PKM2 can interfere with anabolic metabolism.

  18. Promotion and support of physical activity in elderly patients on hemodialysis: a case study.

    PubMed

    Shiota, Kotomi; Hashimoto, Toshihiko

    2016-04-01

    [Purpose] The aim of this study was to ascertain the optimum strategy for implementing a physical activity intervention in patients on hemodialysis by investigating the physical characteristics of elderly patients on hemodialysis, and their attitude to physical activity and level of daily activity. [Subjects] The Subject were 10 elderly patients on hemodialysis. [Methods] They wore a physical activity monitor for 1 week. Data obtained were analyzed for hemodialysis and non- hemodialysis days, and two-way analysis of variance was used to compare the number of steps and activity levels. A questionnaire was administered to investigate the stage of psychological preparedness for exercise and attitudes toward/awareness of exercise. [Results] There was no significant difference in the number of steps or exercise levels on hemodialysis and non- hemodialysis days. However, on both types of days, subjects spent long periods not engaged in any activity. Most of their activity was either inactivity or sedentary behavior. [Conclusion] Patients on hemodialysis with low physical activity levels are considered to have poor physical function and exercise tolerance. To maintain and improve the physical function of patients on hemodialysis, it will be necessary to reduce their time spent in inactive, and comprehensive care that covers psychosocial aspects should be provided to promote the proactive improvement of physical activity and their attitudes to exercise.

  19. Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis

    PubMed Central

    Anastasiou, Dimitrios; Yu, Yimin; Israelsen, William J.; Jiang, Jian-kang; Boxer, Matthew B.; Hong, Bum Soo; Tempel, Wolfram; Dimov, Svetoslav; Shen, Min; Jha, Abhishek; Yang, Hua; Mattaini, Katherine R.; Metallo, Christian M.; Fiske, Brian P.; Courtney, Kevin D.; Malstrom, Scott; Khan, Tahsin M.; Kung, Charles; Skoumbourdis, Amanda P.; Veith, Henrike; Southall, Noel; Walsh, Martin J.; Brimacombe, Kyle R.; Leister, William; Lunt, Sophia Y.; Johnson, Zachary R.; Yen, Katharine E.; Kunii, Kaiko; Davidson, Shawn M.; Christofk, Heather R.; Austin, Christopher P.; Inglese, James; Harris, Marian H.; Asara, John M.; Stephanopoulos, Gregory; Salituro, Francesco G.; Jin, Shengfang; Dang, Lenny; Auld, Douglas S.; Park, Hee-Won; Cantley, Lewis C.; Thomas, Craig J.; Vander Heiden, Matthew G.

    2012-01-01

    Cancer cells engage in a metabolic program to enhance biosynthesis and support cell proliferation. The regulatory properties of pyruvate kinase M2 (PKM2) influence altered glucose metabolism in cancer. PKM2 interaction with phosphotyrosine-containing proteins inhibits enzyme activity and increases availability of glycolytic metabolites to support cell proliferation. This suggests that high pyruvate kinase activity may suppress tumor growth. We show that expression of PKM1, the pyruvate kinase isoform with high constitutive activity, or exposure to published small molecule PKM2 activators inhibit growth of xenograft tumors. Structural studies reveal that small molecule activators bind PKM2 at the subunit interaction interface, a site distinct from that of the endogenous activator fructose-1,6-bisphosphate (FBP). However, unlike FBP, binding of activators to PKM2 promotes a constitutively active enzyme state that is resistant to inhibition by tyrosine-phosphorylated proteins. These data support the notion that small molecule activation of PKM2 can interfere with anabolic metabolism. PMID:22922757

  20. Promotion and support of physical activity in elderly patients on hemodialysis: a case study

    PubMed Central

    Shiota, Kotomi; Hashimoto, Toshihiko

    2016-01-01

    [Purpose] The aim of this study was to ascertain the optimum strategy for implementing a physical activity intervention in patients on hemodialysis by investigating the physical characteristics of elderly patients on hemodialysis, and their attitude to physical activity and level of daily activity. [Subjects] The Subject were 10 elderly patients on hemodialysis. [Methods] They wore a physical activity monitor for 1 week. Data obtained were analyzed for hemodialysis and non- hemodialysis days, and two-way analysis of variance was used to compare the number of steps and activity levels. A questionnaire was administered to investigate the stage of psychological preparedness for exercise and attitudes toward/awareness of exercise. [Results] There was no significant difference in the number of steps or exercise levels on hemodialysis and non- hemodialysis days. However, on both types of days, subjects spent long periods not engaged in any activity. Most of their activity was either inactivity or sedentary behavior. [Conclusion] Patients on hemodialysis with low physical activity levels are considered to have poor physical function and exercise tolerance. To maintain and improve the physical function of patients on hemodialysis, it will be necessary to reduce their time spent in inactive, and comprehensive care that covers psychosocial aspects should be provided to promote the proactive improvement of physical activity and their attitudes to exercise. PMID:27190487

  1. RNA polymerase I transcription factors in active yeast rRNA gene promoters enhance UV damage formation and inhibit repair.

    PubMed

    Meier, Andreas; Thoma, Fritz

    2005-03-01

    UV photofootprinting and repair of pyrimidine dimers by photolyase was used to investigate chromatin structure, protein-DNA interactions, and DNA repair in the spacer and promoter of Saccharomyces cerevisiae rRNA genes. Saccharomyces cerevisiae contains about 150 copies of rRNA genes separated by nontranscribed spacers. Under exponential growth conditions about half of the genes are transcribed by RNA polymerase I (RNAP-I). Initiation of transcription requires the assembly of the upstream activating factor (UAF), the core factor (CF), TATA binding protein, and RNAP-I with Rrn3p on the upstream element and core promoter. We show that UV irradiation of wild-type cells and transcription factor mutants generates photofootprints in the promoter elements. The core footprint depends on UAF, while the UAF footprint was also detected in absence of the CFs. Fractionation of active and inactive promoters showed the core footprint mainly in the active fraction and similar UAF footprints in both fractions. DNA repair by photolyase was strongly inhibited in active promoters but efficient in inactive promoters. The data suggest that UAF is present in vivo in active and inactive promoters and that recruitment of CF and RNAP-I to active promoters generates a stable complex which inhibits repair.

  2. Pregnane X receptor activation and silencing promote steatosis of human hepatic cells by distinct lipogenic mechanisms.

    PubMed

    Bitter, Andreas; Rümmele, Petra; Klein, Kathrin; Kandel, Benjamin A; Rieger, Jessica K; Nüssler, Andreas K; Zanger, Ulrich M; Trauner, Michael; Schwab, Matthias; Burk, Oliver

    2015-11-01

    In addition to its well-characterized role in the regulation of drug metabolism and transport by xenobiotics, pregnane X receptor (PXR) critically impacts on lipid homeostasis. In mice, both ligand-dependent activation and knockout of PXR were previously shown to promote hepatic steatosis. To elucidate the respective pathways in human liver, we generated clones of human hepatoma HepG2 cells exhibiting different PXR protein levels, and analyzed effects of PXR activation and knockdown on steatosis and expression of lipogenic genes. Ligand-dependent activation as well as knockdown of PXR resulted in increased steatosis in HepG2 cells. Activation of PXR induced the sterol regulatory element-binding protein (SREBP) 1-dependent lipogenic pathway via PXR-dependent induction of SREBP1a, which was confirmed in primary human hepatocytes. Inhibiting SREBP1 activity by blocking the cleavage-dependent maturation of SREBP1 protein impaired the induction of lipogenic SREBP1 target genes and triglyceride accumulation by PXR activation. On the other hand, PXR knockdown resulted in up-regulation of aldo-keto reductase (AKR) 1B10, which enhanced the acetyl-CoA carboxylase (ACC)-catalyzed reaction step of de novo lipogenesis. In a cohort of human liver samples histologically classified for non-alcoholic fatty liver disease, AKR1B10, SREBP1a and SREBP1 lipogenic target genes proved to be up-regulated in steatohepatitis, while PXR protein was reduced. In summary, our data suggest that activation and knockdown of PXR in human hepatic cells promote de novo lipogenesis and steatosis by induction of the SREBP1 pathway and AKR1B10-mediated increase of ACC activity, respectively, thus providing mechanistic explanations for a putative dual role of PXR in the pathogenesis of steatohepatitis.

  3. Organization of human ACAT-2 gene and its cell-type-specific promoter activity.

    PubMed

    Song, B L; Qi, W; Yang, X Y; Chang, C C; Zhu, J Q; Chang, T Y; Li, B L

    2001-03-30

    Acyl-CoA:cholesterol acyltransferase (ACAT) plays important roles in cellular cholesterol homeostasis. Two ACAT genes exist in mammals. We report here the genomic organization of human ACAT-2 gene and analysis of its promoter activity in various cell lines. The human ACAT-2 gene spans over 18 kb and contains 15 exons. Three transcription start sites and one poly(A) site are identified by the 5'/3'-RACE. In addition, the human ACAT-2 gene is linked to the insulin-like growth factor binding protein 6 (IGFBP-6) gene in a head-to-tail manner with a small intergenic region of about 1.2 kb. The 5'-flanking region of human ACAT-2 gene contains many potential cis-acting elements for multiple transcriptional regulatory factors but lacks TATA and CCAAT boxes. Using promoter-luciferase reporter assays, we demonstrate the transcriptional activity of ACAT-2 gene promoter is high in Caco-2 cells, especially after these cells become postconfluent and behave as intestinal enterocytes.

  4. Aly/ REF, a factor for mRNA transport, activates RH gene promoter function.

    PubMed

    Suganuma, Hiroshi; Kumada, Maki; Omi, Toshinori; Gotoh, Takaya; Lkhagvasuren, Munkhtulga; Okuda, Hiroshi; Kamesaki, Toyomi; Kajii, Eiji; Iwamoto, Sadahiko

    2005-06-01

    The rhesus (Rh) blood group antigens are of considerable importance in transfusion medicine as well as in newborn or autoimmune hemolytic diseases due to their high antigenicity. We identified a major DNaseI hypersensitive site at the 5' flanking regions of both RHD and RHCE exon 1. A 34 bp fragment located at -191 to -158 from a translation start position, and containing the TCCCCTCCC sequence, was involved in enhancing promoter activity, which was assessed by luciferase reporter gene assay. A biotin-labelled 34 bp probe isolated an mRNA transporter protein, Aly/REF. The specific binding of Aly/REF to RH promoter in erythroid was confirmed by chromatin immunoprecipitation assay. The silencing of Aly/REF by siRNA reduced not only the RH promoter activity of the reporter gene but also transcription from the native genome. These facts provide second proof of Aly/REF as a transcription coactivator, initially identified as a coactivator for the TCRalpha enhancer function. Aly/REF might be a novel transcription cofactor for erythroid-specific genes.

  5. Induction of megakaryocytic colony-stimulating activity in mouse skin by inflammatory agents and tumor promoters

    SciTech Connect

    Clark, D.A.; Dessypris, E.N.; Koury, M.J.

    1987-03-01

    The production of megakaryocytic colony-stimulating activity (MEG-CSA) was assayed in acetic acid extracts of skin from mice topically treated with inflammatory and tumor-promoting agents. A rapid induction of MEG-CSA was found in skin treated both with phorbol 12-myristate 13-acetate (PMA), a strong tumor promoter, and with mezerein, a weak tumor promoter, but no induction was found in untreated skin. The time course of induction of MEG-CSA following treatment of skin with PMA or mezerein was very similar to that previously demonstrated for the induction of granulocyte-macrophage colony-stimulating activity in mouse skin by these agents. The induced MEG-CSA was found in both the epidermis and the dermis. Pretreatment of the skin with US -methasone abrogated the MEG-CSA induction. The cell number response curve suggests that the MEG-CSA acts directly on the progenitor cells of the megakaryocyte colonies. That topical administration of diterpene esters results in the rapid, local induction of MEG-CSA which can be blocked by US -methasone pretreatment suggests a mechanism for the thrombocytosis associated with some inflammatory states. The indirect action in which diterpene esters induce in certain cells the production or release of growth regulatory factors for other cell types may also aid in understanding their carcinogenic properties.

  6. Nerve Growth Factor Promoter Activity Revealed in Mice Expressing Enhanced Green Fluorescent Protein

    PubMed Central

    Kawaja, Michael D.; Smithson, Laura J.; Elliott, Janet; Trinh, Gina; Crotty, Anne-Marie; Michalski, Bernadeta; Fahnestock, Margaret

    2012-01-01

    Nerve growth factor (NGF) and its precursor proNGF are perhaps the best described growth factors of the mammalian nervous system. There remains, however, a paucity of information regarding the precise cellular sites of proNGF/NGF synthesis. Here we report the generation of transgenic mice in which the NGF promoter controls the ectopic synthesis of enhanced green fluorescent protein (EGFP). These transgenic mice provide an unprecedented resolution of both neural cells (e.g., neocortical and hippocampal neurons) and non-neural cells (e.g., renal interstitial cells and thymic reticular cells) that display NGF promoter activity from postnatal development to adulthood. Moreover, the transgene is inducible by injury. At 2 days after sciatic nerve ligation, a robust population of EGFP-positive cells is seen in the proximal nerve stump. These transgenic mice offer novel insights into the cellular sites of NGF promoter activity and can be used as models for investigating the regulation of proNGF/NGF expression after injury. PMID:21456011

  7. Dynein axonemal heavy chain 8 promotes androgen receptor activity and associates with prostate cancer progression

    PubMed Central

    Wang, Yu; Ledet, Russell J.; Imberg-Kazdan, Keren; Logan, Susan K.; Garabedian, Michael J.

    2016-01-01

    To gain insight into cellular factors regulating AR action that could promote castration resistant prostate cancer (CRPC), we performed a genome-wide RNAi screen for factors that promote ligand-independent AR transcriptional activity and integrated clinical databases for candidate genes that are positively associated with prostate cancer metastasis and recurrence. From this analysis, we identified Dynein Axonemal Heavy Chain 8 (DNAH8) as an AR regulator that displayed higher mRNA expression in metastatic than in primary tumors, and showed high expression in patients with poor prognosis. Axonemal dyneins function in cellular motility, but the function of DNAH8 in prostate cancer or other cell types has not been reported. DNAH8 is on chromosome 6q21.2, a cancer-associated amplicon, and is primarily expressed in prostate and testis. Its expression is higher in primary tumors compared to normal prostate, and is further increased in metastatic prostate cancers. Patients expressing high levels of DNAH8 have a greater risk of relapse and a poor prognosis after prostatectomy. Depletion of DNAH8 in prostate cancer cells suppressed AR transcriptional activity and proliferation. Androgen treatment increased DNAH8 mRNA expression, and AR bound the DNAH8 promoter sequence indicating DNAH8 is an AR target gene. Thus, DNAH8 is a new regulator of AR associated with metastatic tumors and poor prognosis. PMID:27363033

  8. Harnessing neural activity to promote repair of the damaged corticospinal system after spinal cord injury

    PubMed Central

    Martin, John H.

    2016-01-01

    As most spinal cord injuries (SCIs) are incomplete, an important target for promoting neural repair and recovery of lost motor function is to promote the connections of spared descending spinal pathways with spinal motor circuits. Among the pathways, the corticospinal tract (CST) is most associated with skilled voluntary functions in humans and many animals. CST loss, whether at its origin in the motor cortex or in the white matter tracts subcortically and in the spinal cord, leads to movement impairments and paralysis. To restore motor function after injury will require repair of the damaged CST. In this review, I discuss how knowledge of activity-dependent development of the CST—which establishes connectional specificity through axon pruning, axon outgrowth, and synaptic competition among CST terminals—informed a novel activity-based therapy for promoting sprouting of spared CST axons after injur in mature animals. This therapy, which comprises motor cortex electrical stimulation with and without concurrent trans-spinal direct current stimulation, leads to an increase in the gray matter axon length of spared CST axons in the rat spinal cord and, after a pyramidal tract lesion, restoration of skilled locomotor movements. I discuss how this approach is now being applied to a C4 contusion rat model. PMID:27857728

  9. A negative element in the downstream region of the Rice tungro bacilliform virus promoter is orientation- and position-independent and is active with heterologous promoters.

    PubMed

    Purkayastha, Arunima; Sharma, Shweta; Dasgupta, Indranil

    2010-10-01

    The promoter of an Indian isolate of the pararetrovirus Rice tungro bacilliform virus (RTBV-WB) contains a negative element downstream of the transcription start site (TSS), between nucleotide residues +58 and +195 (Mathur and Dasgupta, 2007). To further characterize the element, we show, by using transient gus reporter gene assays in the cells of onion peel, rice calli and Arabidopsis leaves, that it down-regulates heterologous promoters CaMV35S and Maize ubiquitin. Quantitative measurements of transient GUS activity indicated more than 90% inhibition of reporter gene expression by the negative element. We also show, by reversing the orientation of the element downstream and by placing it in a position upstream to a constitutively expressing RTBV promoter, that the negative element is orientation- and position-independent, pointing towards its activity at the transcriptional and not post-transcriptional level.

  10. Harnessing Technology and Citizen Science to Support Neighborhoods that Promote Active Living in Mexico.

    PubMed

    Rosas, Lisa G; Salvo, Deborah; Winter, Sandra J; Cortes, David; Rivera, Juan; Rodriguez, Nicole M; King, Abby C

    2016-12-01

    Middle- and low-income countries bear 80 % of the global chronic disease burden. Population-level, multi-sectoral approaches to promoting healthful lifestyles that take into local physical, socioeconomic, and sociocultural characteristics of both the environment and the population are needed. The "Nuestra Voz (Our Voice)" is one such approach that involves neighborhood residents acting as "citizen scientists" to systematically gather information on the barriers and facilitators of physical activity in their neighborhoods and then use their data to collectively advocate for local environmental- and policy-level changes to support active living. We pilot tested this approach in Cuernavaca, Mexico with adults and adolescents. This community-engaged and participatory approach is driven by residents, who utilize a GPS-enabled electronic tablet-based application with simple audio-based instructions to take photographs and record audio narratives of facets of their neighborhood that promote or hinder active living. After collecting these data, the citizen scientists come together in a community meeting and use their data to prioritize realistic, multi-level changes for promoting active living in their neighborhoods. A survey assessed participants' acceptability of the approach. Participating citizen scientists included 32 adults and 9 adolescents. The citizen scientists rated the acceptability of five of the nine acceptability survey items with an average of 4.0 or higher out of 5.0, indicating they thought it was "fun," were comfortable carrying the tablet, were likely to use it again, and would recommend it to friends and family. Items with average scores of less than 4 were all related to safety concerns. The most common barriers reported by citizen scientists using the tablet were poor sidewalk quality, presence of trash, negative characteristics of the streets, unpleasant aesthetics (e.g., graffiti), and presence of parks and recreational facilities. The Our Voice

  11. Supporting public health priorities: recommendations for physical education and physical activity promotion in schools.

    PubMed

    Hills, Andrew P; Dengel, Donald R; Lubans, David R

    2015-01-01

    Physical activity (PA) provides numerous physiological and psychosocial benefits. However, lifestyle changes, including reduced PA opportunities in multiple settings, have resulted in an escalation of overweight and obesity and related health problems. Poor physical and mental health, including metabolic and cardiovascular problems is seen in progressively younger ages, and the systematic decline in school PA has contributed to this trend. Of note, the crowded school curriculum with an intense focus on academic achievement, lack of school leadership support, funding and resources, plus poor quality teaching are barriers to PA promotion in schools. The school setting and physical educators in particular, must embrace their role in public health by adopting a comprehensive school PA program. We provide an overview of key issues and challenges in the area plus best bets and recommendations for physical education and PA promotion in the school system moving forward.

  12. Cortactin promotes colorectal cancer cell proliferation by activating the EGFR-MAPK pathway

    PubMed Central

    Zhang, Tao; Wang, Zhenlei; Qin, Xuan; Jing, Xiaoqian; Wu, Haoxuan; Ji, Xiaopin; He, Yonggang; Zhao, Ren

    2017-01-01

    Cortactin (CTTN) is overexpressed in various tumors, including head and neck squamous cell carcinoma and colorectal cancer (CRC), and can serve as a biomarker of cancer metastasis. We observed that CTTN promotes cancer cell proliferation in vitro and increases CRC tumor xenograft growth in vivo. CTTN expression increases EGFR protein levels and enhances the activation of the MAPK signaling pathway. CTTN expression also inhibits the ubiquitin-mediated degradation of EGFR by suppressing the coupling of c-Cbl with EGFR. CoIP experiments indicate CTTN can interact with c-Cbl in CRC cells. These results demonstrate that CTTN promotes the proliferation of CRC cells and suppresses the degradation of EGFR. PMID:27903975

  13. Kappa opioid receptor activation alleviates experimental autoimmune encephalomyelitis and promotes oligodendrocyte-mediated remyelination.

    PubMed

    Du, Changsheng; Duan, Yanhui; Wei, Wei; Cai, Yingying; Chai, Hui; Lv, Jie; Du, Xiling; Zhu, Jian; Xie, Xin

    2016-04-04

    Multiple sclerosis (MS) is characterized by autoimmune damage to the central nervous system. All the current drugs for MS target the immune system. Although effective in reducing new lesions, they have limited effects in preventing the progression of disability. Promoting oligodendrocyte-mediated remyelination and recovery of neurons are the new directions of MS therapy. The endogenous opioid system, consisting of MOR, DOR, KOR and their ligands, has been suggested to participate in the pathogenesis of MS. However, the exact receptor and mechanism remain elusive. Here we show that genetic deletion of KOR exacerbates experimental autoimmune encephalomyelitis, whereas activating KOR with agonists alleviates the symptoms. KOR does not affect immune cell differentiation and function. Instead, it promotes oligodendrocyte differentiation and myelination both in vitro and in vivo. Our study suggests that targeting KOR might be an intriguing way to develop new MS therapies that may complement the existing immunosuppressive approaches.

  14. Muévete Bogotá: promoting physical activity with a network of partner companies.

    PubMed

    Gámez, Rocío; Parra, Diana; Pratt, Michael; Schmid, Thomas L

    2006-01-01

    In 1998 the mayor's office and the District Institute for Sports and Recreation created Muévete Bogotá, a physical activity and health promotion programme for the capital city of Colombia. Muévete means to move or to be active, and this campaign to promote physical activity was designed to improve the health and quality of life of the citizens of Bogotá through regular physical activity. The programme is based on the 1995 recommendations on physical activity of the U.S. Centers for Disease Control and Prevention and the American College of Sports Medicine (Pate el al, 1995), and was developed in close consultation with the Agita São Paulo programme in Brazil (Matsudo el al., 2003). Muévete Bogotá couples a mass media campaign with programmes targeted to change physical activity behaviour. The interventions, which are conducted at work sites, schools, health care centers and in community settings rely on partnerships created among professionals in areas of education and health, business officials and personnel, and community members, to deliver the programmes in each of these settings and populations. Like many developing countries, Colombia suffers from a growing epidemic of chronic diseases. In 1993 35.7% of total mortality in the city of Bogotá was due to chronic diseases (Espinosa, 1993). In 2002 cardiovascular diseases accounted for 40.3% of mortality among the population aged 60 years or older and 26.8% for persons 45 to 59 years of age. (Cardona, 2002) Bogotá has implemented extensive physical and social environmental changes over the last decade, which has increased opportunities for physical activity, but sedentary lifestyle continues to be a significant public health problem in the city. Programmes such as Muévete Bogotá that educate and motivate the population to become more physically active appear to be needed to complement the underlying environmental and policy changes. Muévete Bogotá provides an example of successful implementation of a

  15. A model for promoting physical activity among rural South African adolescent girls

    PubMed Central

    Kinsman, John; Norris, Shane A.; Kahn, Kathleen; Twine, Rhian; Riggle, Kari; Edin, Kerstin; Mathebula, Jennifer; Ngobeni, Sizzy; Monareng, Nester; Micklesfield, Lisa K.

    2015-01-01

    Background In South Africa, the expanding epidemic of non-communicable diseases is partly fuelled by high levels of physical inactivity and sedentary behaviour. Women especially are at high risk, and interventions promoting physical activity are urgently needed for girls in their adolescence, as this is the time when many girls adopt unhealthy lifestyles. Objective This qualitative study aimed to identify and describe facilitating factors and barriers that are associated with physical activity among adolescent girls in rural, north-eastern South Africa and, based on these, to develop a model for promoting leisure-time physical activity within this population. Design The study was conducted in and around three secondary schools. Six focus group discussions were conducted with adolescent girls from the schools, and seven qualitative interviews were held with sports teachers and youth leaders. The data were subjected to thematic analysis. Results Seven thematic areas were identified, each of which was associated with the girls’ self-reported levels of physical activity. The thematic areas are 1) poverty, 2) body image ideals, 3) gender, 4) parents and home life, 5) demographic factors, 6) perceived health effects of physical activity, and 7) human and infrastructural resources. More barriers to physical activity were reported than facilitating factors. Conclusions Analysis of the barriers found in the different themes indicated potential remedial actions that could be taken, and these were synthesised into a model for promoting physical activity among South African adolescent girls in resource-poor environments. The model presents a series of action points, seen both from the ‘supply-side’ perspective (such as the provision of resources and training for the individuals, schools, and organisations which facilitate the activities) and from the ‘demand-side’ perspective (such as the development of empowering messages about body image for teenage girls, and

  16. [Community vegetable gardens as a health promotion activity: an experience in Primary Healthcare Units].

    PubMed

    Costa, Christiane Gasparini Araújo; Garcia, Mariana Tarricone; Ribeiro, Silvana Maria; Salandini, Marcia Fernanda de Sousa; Bógus, Cláudia Maria

    2015-10-01

    Urban and peri-urban agriculture (UPA) is being practiced in different settings, contributing to the improvement of health in communities and healthier environments. In order to identify the meanings and implications of the practice of UPA in Primary Healthcare Units (PHU) as an activity of health promotion (HP), and to what extent its therapeutic dimension characterizes it as an activity aligned with complementary and integrative practices (CIP), a qualitative cross-sectional study was performed in Embu das Artes, State of São Paulo. From the analysis, the following main themes arose: health concept, health outcomes, the return to traditional practices and habits and the reorientation of health services. It was possible to identify the close link between the cultivation of vegetable gardens and HP guidelines and fields of action, such as creating healthier environments, boosting community actions, developing personal skills, stimulating autonomy and empowerment and demands for the reorientation of services. The garden activities, set up in PHU areas, proved to be an implementation strategy of CIP. The conclusion reached is that vegetable gardening activities in community gardens are seen to be health promotion practices that integrate key elements of CIP.

  17. Grounds for movement: green school grounds as sites for promoting physical activity.

    PubMed

    Dyment, J E; Bell, A C

    2008-12-01

    An environmental factor of particular importance to children's physical activity levels appears to be the presence of parks and open space. Thus, in promoting children's health, school grounds merit consideration as a potential setting for intervention. This paper explores how 'green' school grounds, which contain a greater diversity of landscaping and design features, affect the quantity and quality of physical activity among elementary school children. Teachers, parents and administrators associated with 59 schools across Canada completed questionnaires (n = 105). Analysis reveals that through greening, school grounds diversify the play repertoire, creating opportunities for boys and girls of all ages, interests and abilities to be more physically active. Complementing the rule-bound, competitive games supported by asphalt and turf playing fields, green school grounds invite children to jump, climb, dig, lift, rake, build, role play and generally get moving in ways that nurture all aspects of their health and development. Of particular significance is the potential to encourage moderate and light levels of physical activity by increasing the range of enjoyable, non-competitive, open-ended forms of play at school. Seen in this light, green school grounds stand to be an important intervention to be included in school health promotion initiatives.

  18. Inhibitory effects promoted by 5'-nucleotides on the ecto-3'-nucleotidase activity of Leishmania amazonensis.

    PubMed

    Freitas-Mesquita, Anita Leocadio; Gomes, Marta T; Vieira, Danielle P; Paes-Vieira, Lisvane; Nascimento, Michelle T C; Lopes, Angela H C S; Meyer-Fernandes, José Roberto

    2016-10-01

    The protozoan parasite Leishmania amazonensis is the etiological agent of cutaneous leishmaniasis. During its life cycle, the flagellated metacyclic promastigote forms are transmitted to vertebrate hosts by sandfly bites, and they develop into amastigotes inside macrophages, where they multiply. L. amazonensis possesses a bifunctional enzyme, called 3'-nucleotidase/nuclease (3'NT/NU), which is able to hydrolyze extracellular 3'-monophosphorylated nucleosides and nucleic acids. 3'NT/NU plays an important role in the generation of extracellular adenosine and has been described as a key enzyme in the acquisition of purines by trypanosomatids. Furthermore, it has been observed that 3'NT/NU also plays a valuable role in the establishment of parasitic infection. In this context, this study aimed to investigate the modulation of the 3'-nucleotidase (3'NT) activity of L. amazonensis by several nucleotides. It was observed that 3'NT activity is inhibited by micromolar concentrations of guanosine and guanine nucleotides. The inhibition promoted by 5'-GMP on the 3'NT activity of L. amazonensis is reversible and uncompetitive because the addition of the inhibitor decreased the kinetic parameters Km and Vmax. Finally, we found that the addition of 5'-GMP is able to reverse the stimulation promoted by 3'-AMP in a macrophage-parasite interaction assay. The determination of compounds that can inhibit the 3'NT activity of Leishmania is very important because this enzyme does not occur in mammals, making it a potential therapeutic target.

  19. Terminal Uridyltransferase Enzyme Zcchc11 Promotes Cell Proliferation Independent of Its Uridyltransferase Activity*

    PubMed Central

    Blahna, Matthew T.; Jones, Matthew R.; Quinton, Lee J.; Matsuura, Kori Y.; Mizgerd, Joseph P.

    2011-01-01

    Zcchc11 is a uridyltransferase protein with enzymatic activity directed against diverse RNA species. On the basis of its known uridylation targets, we hypothesized that Zcchc11 might regulate cell proliferation. Confirming this, loss-of-function and complementary gain-of-function experiments consistently revealed that Zcchc11 promotes the transition from G1 to S phase of the cell cycle. This activity takes place through both Rb-dependent and Rb-independent mechanisms by promoting the expression of multiple G1-associated proteins, including cyclins D1 and A and CDK4. Surprisingly, a Zcchc11 construct with point mutations inactivating the uridyltransferase domain enhanced cell proliferation as effectively as wild-type Zcchc11. Furthermore, truncated mutant constructs revealed that the cell cycle effects of Zcchc11 were driven by the N-terminal region of the protein that lacks the RNA-binding domains and uridyltransferase activity of the full protein. Therefore, the N-terminal portion of Zcchc11, which lacks nucleotidyltransferase capabilities, is biologically active and mediates a previously unrecognized role for Zcchc11 in facilitating cell proliferation. PMID:22006926

  20. Terazosin activated Pgk1 and Hsp90 to promote stress resistance

    PubMed Central

    Chen, Xinping; Zhao, Chunyue; Li, Xiaolong; Wang, Tao; Li, Yizhou; Cao, Cheng; Ding, Yuehe; Dong, Mengqiu; Finci, Lorenzo; Wang, Jia-huai; Li, Xiaoyu; Liu, Lei

    2015-01-01

    Drugs that can protect against organ damage are urgently needed, especially for diseases such as sepsis and brain stroke. We have discovered that terazosin (TZ), a widely marketed alpha1-adrenergic receptor agonist, alleviated organ damage and improved survival in rodent models of stroke and sepsis. Through combined studies of enzymology and X-ray crystallography, we have discovered that TZ binds to a novel target, phosphoglycerate kinase 1 (Pgk1) and activates its enzymatic activity, probably through 1,3-diamino-6,7-dimethoxyisoquinoline's ability to promote ATP release from Pgk1. Mechanistically, the ATP generated from Pgk1 may enhance the chaperone activity of Hsp90, an ATPase known to associate with Pgk1. Upon activation, Hsp90 promotes multi-stress resistance. Our studies have demonstrated that TZ has a novel protein target, Pgk1, and has revealed its corresponding biological effect. As a clinical drug, TZ may be quickly translated into treatment of devastating diseases including stroke and sepsis. PMID:25383758

  1. MBD3L2 promotes Tet2 enzymatic activity for mediating 5-methylcytosine oxidation.

    PubMed

    Peng, Lina; Li, Yan; Xi, Yanping; Li, Wei; Li, Jin; Lv, Ruitu; Zhang, Lei; Zou, Qingping; Dong, Shihua; Luo, Huaibing; Wu, Feizhen; Yu, Wenqiang

    2016-03-01

    Ten-eleven translocation (Tet) proteins are key players involved in the dynamic regulation of cytosine methylation and demethylation. Inactivating mutations of Tet2 are frequently found in human malignancies, highlighting the essential role of Tet2 in cellular transformation. However, the factors that control Tet enzymatic activity remain largely unknown. Here, we found that methyl-CpG-binding domain protein 3 (MBD3) and its homolog MBD3-like 2 (MBD3L2) can specifically modulate the enzymatic activity of Tet2 protein, but not Tet1 and Tet3 proteins, in converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Moreover, MBD3L2 is more effective than MBD3 in promoting Tet2 enzymatic activity through strengthening the binding affinity between Tet2 and the methylated DNA target. Further analysis revealed pronounced decreases in 5mC levels at MBD3L2 and Tet2 co-occupied genomic regions, most of which are promoter elements associated with either cancer-related genes or genes involved in the regulation of cellular metabolic processes. Our data add new insights into the regulation of Tet2 activity by MBD3 and MBD3L2, and into how that affects Tet2-mediated modulation of its target genes in cancer development. Thus, they have important applications in understanding how dysregulation of Tet2 might contribute to human malignancy.

  2. Activated mTORC1 promotes long-term cone survival in retinitis pigmentosa mice

    PubMed Central

    Venkatesh, Aditya; Ma, Shan; Le, Yun Z.; Hall, Michael N.; Rüegg, Markus A.; Punzo, Claudio

    2015-01-01

    Retinitis pigmentosa (RP) is an inherited photoreceptor degenerative disorder that results in blindness. The disease is often caused by mutations in genes that are specific to rod photoreceptors; however, blindness results from the secondary loss of cones by a still unknown mechanism. Here, we demonstrated that the mammalian target of rapamycin complex 1 (mTORC1) is required to slow the progression of cone death during disease and that constitutive activation of mTORC1 in cones is sufficient to maintain cone function and promote long-term cone survival. Activation of mTORC1 in cones enhanced glucose uptake, retention, and utilization, leading to increased levels of the key metabolite NADPH. Moreover, cone death was delayed in the absence of the NADPH-sensitive cell death protease caspase 2, supporting the contribution of reduced NADPH in promoting cone death. Constitutive activation of mTORC1 preserved cones in 2 mouse models of RP, suggesting that the secondary loss of cones is caused mainly by metabolic deficits and is independent of a specific rod-associated mutation. Together, the results of this study address a longstanding question in the field and suggest that activating mTORC1 in cones has therapeutic potential to prolong vision in RP. PMID:25798619

  3. BCL-3 expression promotes colorectal tumorigenesis through activation of AKT signalling

    PubMed Central

    Urban, Bettina C; Collard, Tracey J; Eagle, Catherine J; Southern, Samantha L; Greenhough, Alexander; Hamdollah-Zadeh, Maryam; Ghosh, Anil; Paraskeva, Christos; Silver, Andrew; Williams, Ann C

    2016-01-01

    Objective Colorectal cancer remains the fourth most common cause of cancer-related mortality worldwide. Here we investigate the role of nuclear factor-κB (NF-κB) co-factor B-cell CLL/lymphoma 3 (BCL-3) in promoting colorectal tumour cell survival. Design Immunohistochemistry was carried out on 47 tumour samples and normal tissue from resection margins. The role of BCL-3/NF-κB complexes on cell growth was studied in vivo and in vitro using an siRNA approach and exogenous BCL-3 expression in colorectal adenoma and carcinoma cells. The question whether BCL-3 activated the AKT/protein kinase B (PKB) pathway in colorectal tumour cells was addressed by western blotting and confocal microscopy, and the ability of 5-aminosalicylic acid (5-ASA) to suppress BCL-3 expression was also investigated. Results We report increased BCL-3 expression in human colorectal cancers and demonstrate that BCL-3 expression promotes tumour cell survival in vitro and tumour growth in mouse xenografts in vivo, dependent on interaction with NF-κB p50 or p52 homodimers. We show that BCL-3 promotes cell survival under conditions relevant to the tumour microenvironment, protecting both colorectal adenoma and carcinoma cells from apoptosis via activation of the AKT survival pathway: AKT activation is mediated via both PI3K and mammalian target of rapamycin (mTOR) pathways, leading to phosphorylation of downstream targets GSK-3β and FoxO1/3a. Treatment with 5-ASA suppressed BCL-3 expression in colorectal cancer cells. Conclusions Our study helps to unravel the mechanism by which BCL-3 is linked to poor prognosis in colorectal cancer; we suggest that targeting BCL-3 activity represents an exciting therapeutic opportunity potentially increasing the sensitivity of tumour cells to conventional therapy. PMID:26033966

  4. Upregulation of Glutaredoxin-1 Activates Microglia and Promotes Neurodegeneration: Implications for Parkinson's Disease

    PubMed Central

    Gorelenkova Miller, Olga; Behring, Jessica Belle; Siedlak, Sandra L.; Jiang, Sirui; Matsui, Reiko; Bachschmid, Markus M.; Zhu, Xiongwei

    2016-01-01

    Abstract Aims: Neuroinflammation and redox dysfunction are recognized factors in Parkinson's disease (PD) pathogenesis, and diabetes is implicated as a potentially predisposing condition. Remarkably, upregulation of glutaredoxin-1 (Grx1) is implicated in regulation of inflammatory responses in various disease contexts, including diabetes. In this study, we investigated the potential impact of Grx1 upregulation in the central nervous system on dopaminergic (DA) viability. Results: Increased GLRX copy number in PD patients was associated with earlier PD onset, and Grx1 levels correlated with levels of proinflammatory tumor necrosis factor-alpha (TNF-α) in mouse and human brain samples, prompting mechanistic in vitro studies. Grx1 content/activity in microglia was upregulated by lipopolysaccharide (LPS), or TNF-α, treatment. Adenoviral overexpression of Grx1, matching the extent of induction by LPS, increased microglial activation; Grx1 silencing diminished activation. Selective inhibitors/probes of nuclear factor κB (NF-κB) activation revealed glrx1 induction to be mediated by the Nurr1/NF-κB axis. Upregulation of Grx1 in microglia corresponded to increased death of neuronal cells in coculture. With a mouse diabetes model of diet-induced insulin resistance, we found upregulation of Grx1 in brain was associated with DA loss (decreased tyrosine hydroxylase [TH]; diminished TH-positive striatal axonal terminals); these effects were not seen with Grx1-knockout mice. Innovation: Our results indicate that Grx1 upregulation promotes neuroinflammation and consequent neuronal cell death in vitro, and synergizes with proinflammatory insults to promote DA loss in vivo. Our findings also suggest a genetic link between elevated Grx1 and PD development. Conclusion: In vitro and in vivo data suggest Grx1 upregulation promotes neurotoxic neuroinflammation, potentially contributing to PD. Antioxid. Redox Signal. 25, 967–982. PMID:27224303

  5. RFPL3 and CBP synergistically upregulate hTERT activity and promote lung cancer growth

    PubMed Central

    Yu, Wendan; Cai, Xin; Dai, Meng; Xu, Tingting; Huang, Wenlin; Guo, Wei; Deng, Wuguo; Wu, Taihua

    2015-01-01

    hTERT is the key component of telomerase and its overactivation contributes to maintaining telomere length and cell immortalization. Previously, we identified RFPL3 as a new transcription activator of hTERT in lung cancers. However, the exact mechanism of RFPL3 in mediating hTERT activation and its associated signal regulatory network remain unclear. In this study, we found that RFPL3 colocalized and interacted directly with CBP in the nucleus of lung cancer cells. Immunohistochemical analysis of tissue microarrays of lung cancers revealed the simultaneous overexpression of both RFPL3 and CBP predicted relatively poor prognosis. Furthermore, we confirmed their synergistic stimulation on hTERT expression and tumor cell growth. The binding of RFPL3 to hTERT promoter was reduced markedly when CBP was knocked down by its specific siRNA or suppressed by its inhibitor in lung cancer cells with stable overexpression of RFPL3. When one of the two proteins RFPL3 and CBP was upregulated or downregulated, whereas the another remains unchanged, hTERT expression and telomerase activity were activated or repressed accordingly. In the meantime, the growth of lung cancer cells was also promoted or attenuated accordingly. Furthermore, we also found that RFPL3 coordinated with CBP to upregulate hTERT through the CBP-induced acetylation of RFPL3 protein and their co-anchoring at hTERT promoter region. Collectively, our results reveal a new mechanism of hTERT regulation in lung cancer cells and suggest the RFPL3/CBP/hTERT signaling pathway may be a new targets for lung cancer treatment. PMID:26318425

  6. Genetic dissection of independent and cooperative transcriptional activation by the LysR-type activator ThnR at close divergent promoters.

    PubMed

    Rivas-Marín, Elena; Floriano, Belén; Santero, Eduardo

    2016-04-18

    Regulation of tetralin biodegradation operons is one of the examples of unconventional LysR-type mediated transcriptional regulation. ThnR activates transcription from two divergent and closely located promoters PB and PC. Although ThnR activates each promoter independently, transcription from each one increases when both promoters are together. Mutational analysis of the intergenic region shows that cooperative transcription is achieved through formation of a ThnR complex when bound to its respective sites at each promoter, via formation of a DNA loop. Mutations also defined ThnR contact sites that are important for independent transcriptional activation at each promoter. A mutation at the PB promoter region, which abolishes its independent transcription, does not affect at all PB transcription in the presence of the divergent promoter PC, thus indicating that the complex formed via DNA loop can compensate for the deficiencies in the correct protein-DNA interaction at one of the promoters. Combination of mutations in both promoters identifies a region at PC that is not important for its independent transcription but it is essential for cooperative transcription from both promoters. This work provides new insights into the diversity and complexity of activation mechanisms used by the most abundant type of bacterial transcriptional regulators.

  7. MBD3 Localizes at Promoters, Gene Bodies and Enhancers of Active Genes

    PubMed Central

    Shimbo, Takashi; Du, Ying; Grimm, Sara A.; Dhasarathy, Archana; Mav, Deepak; Shah, Ruchir R.; Shi, Huidong; Wade, Paul A.

    2013-01-01

    The Mi-2/nucleosome remodeling and histone deacetylase (NuRD) complex is a multiprotein machine proposed to regulate chromatin structure by nucleosome remodeling and histone deacetylation activities. Recent reports describing localization of NuRD provide new insights that question previous models on NuRD action, but are not in complete agreement. Here, we provide location analysis of endogenous MBD3, a component of NuRD complex, in two human breast cancer cell lines (MCF-7 and MDA-MB-231) using two independent genomic techniques: DNA adenine methyltransferase identification (DamID) and ChIP-seq. We observed concordance of the resulting genomic localization, suggesting that these studies are converging on a robust map for NuRD in the cancer cell genome. MBD3 preferentially associated with CpG rich promoters marked by H3K4me3 and showed cell-type specific localization across gene bodies, peaking around the transcription start site. A subset of sites bound by MBD3 was enriched in H3K27ac and was in physical proximity to promoters in three-dimensional space, suggesting function as enhancers. MBD3 enrichment was also noted at promoters modified by H3K27me3. Functional analysis of chromatin indicated that MBD3 regulates nucleosome occupancy near promoters and in gene bodies. These data suggest that MBD3, and by extension the NuRD complex, may have multiple roles in fine tuning expression for both active and silent genes, representing an important step in defining regulatory mechanisms by which NuRD complex controls chromatin structure and modification status. PMID:24385926

  8. Transgenic Activation of Ras in Neurons Promotes Hypertrophy and Protects from Lesion-Induced Degeneration

    PubMed Central

    Heumann, Rolf; Goemans, Christoph; Bartsch, Daniela; Lingenhöhl, Kurt; Waldmeier, Peter C.; Hengerer, Bastian; Allegrini, Peter R.; Schellander, Karl; Wagner, Erwin F.; Arendt, Thomas; Kamdem, Rigobert H.; Obst-Pernberg, Kirstin; Narz, Frank; Wahle, Petra; Berns, Hartmut

    2000-01-01

    Ras is a universal eukaryotic intracellular protein integrating extracellular signals from multiple receptor types. To investigate its role in the adult central nervous system, constitutively activated V12-Ha-Ras was expressed selectively in neurons of transgenic mice via a synapsin promoter. Ras-transgene protein expression increased postnatally, reaching a four- to fivefold elevation at day 40 and persisting at this level, thereafter. Neuronal Ras was constitutively active and a corresponding activating phosphorylation of mitogen-activated kinase was observed, but there were no changes in the activity of phosphoinositide 3-kinase, the phosphorylation of its target kinase Akt/PKB, or expression of the anti-apoptotic proteins Bcl-2 or Bcl-XL. Neuronal Ras activation did not alter the total number of neurons, but induced cell soma hypertrophy, which resulted in a 14.5% increase of total brain volume. Choline acetyltransferase and tyrosine hydroxylase activities were increased, as well as neuropeptide Y expression. Degeneration of motorneurons was completely prevented after facial nerve lesion in Ras-transgenic mice. Furthermore, neurotoxin-induced degeneration of dopaminergic substantia nigra neurons and their striatal projections was greatly attenuated. Thus, the Ras signaling pathway mimics neurotrophic effects and triggers neuroprotective mechanisms in adult mice. Neuronal Ras activation might become a tool to stabilize donor neurons for neural transplantation and to protect neuronal populations in neurodegenerative diseases. PMID:11134081

  9. Why and How Physical Activity Promotes Experience-Induced Brain Plasticity

    PubMed Central

    Kempermann, Gerd; Fabel, Klaus; Ehninger, Dan; Babu, Harish; Leal-Galicia, Perla; Garthe, Alexander; Wolf, Susanne A.

    2010-01-01

    Adult hippocampal neurogenesis is an unusual case of brain plasticity, since new neurons (and not just neurites and synapses) are added to the network in an activity-dependent way. At the behavioral level the plasticity-inducing stimuli include both physical and cognitive activity. In reductionistic animal studies these types of activity can be studied separately in paradigms like voluntary wheel running and environmental enrichment. In both of these, adult neurogenesis is increased but the net effect is primarily due to different mechanisms at the cellular level. Locomotion appears to stimulate the precursor cells, from which adult neurogenesis originates, to increased proliferation and maintenance over time, whereas environmental enrichment, as well as learning, predominantly promotes survival of immature neurons, that is the progeny of the proliferating precursor cells. Surprisingly, these effects are additive: boosting the potential for adult neurogenesis by physical activity increases the recruitment of cells following cognitive stimulation in an enriched environment. Why is that? We argue that locomotion actually serves as an intrinsic feedback mechanism, signaling to the brain, including its neural precursor cells, increasing the likelihood of cognitive challenges. In the wild (other than in front of a TV), no separation of physical and cognitive activity occurs. Physical activity might thus be much more than a generally healthy garnish to leading “an active life” but an evolutionarily fundamental aspect of “activity,” which is needed to provide the brain and its systems of plastic adaptation with the appropriate regulatory input and feedback. PMID:21151782

  10. TIFA activates IkappaB kinase (IKK) by promoting oligomerization and ubiquitination of TRAF6.

    PubMed

    Ea, Chee-Kwee; Sun, Lijun; Inoue, Jun-Ichiro; Chen, Zhijian J

    2004-10-26

    TRAF6 (tumor necrosis factor receptor-associated factor 6) is a RING (really interesting new gene) domain ubiquitin (Ub) ligase that mediates the activation of protein kinases, such as transforming growth factor beta-activated kinase (TAK1) and IkappaB kinase (IKK), by catalyzing the formation of a unique polyubiquitin chain linked through Lys-63 of Ub. Here, we present evidence that TIFA (TRAF-interacting protein with a forkhead-associated domain, also known as T2BP) activates IKK by promoting the oligomerization and Ub ligase activity of TRAF6. We show that recombinant TIFA protein, but not TRAF6-binding-defective mutant, can activate IKK in crude cytosolic extracts. Furthermore, TIFA activates IKK in an in vitro reconstitution system consisting of purified proteins, including TRAF6, the TAK1 kinase complex, and Ub-conjugating enzyme complex Ubc13-Uev1A. Interestingly, a fraction of recombinant TIFA protein exists as high-molecular-weight oligomers, and only these oligomeric forms of TIFA can activate IKK. Importantly, TIFA induces the oligomerization and polyubiquitination of TRAF6, which leads to the activation of TAK1 and IKK through a proteasome-independent mechanism.

  11. Stem cell factor-mediated activation pathways promote murine eosinophil CCL6 production and survival.

    PubMed

    Dolgachev, Vladislav; Thomas, Molly; Berlin, Aaron; Lukacs, Nicholas W

    2007-04-01

    Eosinophil activation during allergic diseases has a detrimental role in the generation of pathophysiologic responses. Stem cell factor (SCF) has recently shown an inflammatory, gene-activating role on eosinophils and contributes to the generation of pathophysiologic changes in the airways during allergic responses. The data in the present study outline the signal transduction events that are induced by SCF in eosinophils and further demonstrate that MEK-mediated signaling pathways are crucial for SCF-induced CCL6 chemokine activation and eosinophil survival. SCF-mediated eosinophil activation was demonstrated to include PI-3K activation as well as MEK/MAPK phosphorylation pathways. Subsequent analysis of CCL6 gene activation and production induced by SCF in the presence or absence of rather specific inhibitors for certain pathways demonstrated that the MEK/MAPK pathway but not the PI-3K pathway was crucial for the SCF-induced CCL6 gene activation. These same signaling pathways were shown to initiate antiapoptotic events and promote eosinophil survival, including up-regulation of BCL2 and BCL3. Altogether, SCF appears to be a potent eosinophil activation and survival factor.

  12. Cell-cycle coupled expansion of AR activity promotes cancer progression

    PubMed Central

    McNair, Christopher; Urbanucci, Alfonso; Comstock, Clay E.S.; Augello, Michael A.; Goodwin, Jonathan F.; Launchbury, Rosalind; Zhao, Shuang; Schiewer, Mathew J.; Ertel, Adam; Karnes, Jeffrey; Davicioni, Elai; Wang, Liguo; Wang, Qianben; Mills, Ian G.; Feng, Felix Y.; Li, Wei; Carroll, Jason S.; Knudsen, Karen E.

    2016-01-01

    The androgen receptor (AR) is required for prostate cancer (PCa) survival and progression, and ablation of AR activity is the first line of therapeutic intervention for disseminated disease. While initially effective, recurrent tumors ultimately arise for which there is no durable cure. Despite the dependence of PCa on AR activity throughout the course of disease, delineation of the AR-dependent transcriptional network that governs disease progression remains elusive, and the function of AR in mitotically active cells is not well understood. Analyzing AR activity as a function of cell cycle revealed an unexpected and highly expanded repertoire of AR-regulated gene networks in actively cycling cells. New AR functions segregated into two major clusters: those that are specific to cycling cells and retained throughout the mitotic cell cycle (“Cell Cycle Common”), versus those that were specifically enriched in a subset of cell cycle phases (“Phase Restricted”). Further analyses identified previously unrecognized AR functions in major pathways associated with clinical PCa progression. Illustrating the impact of these unmasked AR-driven pathways, dihydroceramide-desaturase 1 (DEGS1) was identified as an AR regulated gene in mitotically active cells that promoted pro-metastatic phenotypes, and in advanced PCa proved to be highly associated with development of metastases, recurrence after therapeutic intervention, and reduced overall survival. Taken together, these findings delineate AR function in mitotically active tumor cells, thus providing critical insight into the molecular basis by which AR promotes development of lethal PCa and nominate new avenues for therapeutic intervention. PMID:27669432

  13. 20S proteasome activation promotes life span extension and resistance to proteotoxicity in Caenorhabditis elegans

    PubMed Central

    Chondrogianni, Niki; Georgila, Konstantina; Kourtis, Nikos; Tavernarakis, Nektarios; Gonos, Efstathios S.

    2015-01-01

    Protein homeostasis (proteostasis) is one of the nodal points that need to be preserved to retain physiologic cellular/organismal balance. The ubiquitin-proteasome system (UPS) is responsible for the removal of both normal and damaged proteins, with the proteasome being the downstream effector. The proteasome is the major cellular protease with progressive impairment of function during aging and senescence. Despite the documented age-retarding properties of proteasome activation in various cellular models, simultaneous enhancement of the 20S core proteasome content, assembly, and function have never been reported in any multicellular organism. Consequently, the possible effects of the core proteasome modulation on organismal life span are elusive. In this study, we have achieved activation of the 20S proteasome at organismal level. We demonstrate enhancement of proteasome levels, assembly, and activity in the nematode Caenorhabditis elegans, resulting in life span extension and increased resistance to stress. We also provide evidence that the observed life span extension is dependent on the transcriptional activity of Dauer formation abnormal/Forkhead box class O (DAF-16/FOXO), skinhead-1 (SKN-1), and heat shock factor-1 (HSF-1) factors through regulation of downstream longevity genes. We further show that the reported beneficial effects are not ubiquitous but they are dependent on the genetic context. Finally, we provide evidence that proteasome core activation might be a potential strategy to minimize protein homeostasis deficiencies underlying aggregation-related diseases, such as Alzheimer’s disease (AD) or Huntington’s disease (HD). In summary, this is the first report demonstrating that 20S core proteasome up-regulation in terms of both content and activity is feasible in a multicellular eukaryotic organism and that in turn this modulation promotes extension of organismal health span and life span.—Chondrogianni, N., Georgila, K., Kourtis, N

  14. Active Commuting: Workplace Health Promotion for Improved Employee Well-Being and Organizational Behavior.

    PubMed

    Page, Nadine C; Nilsson, Viktor O

    2016-01-01

    Objective: This paper describes a behavior change intervention that encourages active commuting using electrically assisted bikes (e-bikes) for health promotion in the workplace. This paper presents the preliminary findings of the intervention's impact on improving employee well-being and organizational behavior, as an indicator of potential business success. Method: Employees of a UK-based organization participated in a workplace travel behavior change intervention and used e-bikes as an active commuting mode; this was a change to their usual passive commuting behavior. The purpose of the intervention was to develop employee well-being and organizational behavior for improved business success. We explored the personal benefits and organizational co-benefits of active commuting and compared these to a travel-as-usual group of employees who did not change their behavior and continued taking non-active commutes. Results: Employees who changed their behavior to active commuting reported more positive affect, better physical health and more productive organizational behavior outcomes compared with passive commuters. In addition, there was an interactive effect of commuting mode and commuting distance: a more frequent active commute was positively associated with more productive organizational behavior and stronger overall positive employee well-being whereas a longer passive commute was associated with poorer well-being, although there was no impact on organizational behavior. Conclusion: This research provides emerging evidence of the value of an innovative workplace health promotion initiative focused on active commuting in protecting and improving employee well-being and organizational behavior for stronger business performance. It considers the significant opportunities for organizations pursuing improved workforce well-being, both in terms of employee health, and for improved organizational behavior and business success.

  15. Active Commuting: Workplace Health Promotion for Improved Employee Well-Being and Organizational Behavior

    PubMed Central

    Page, Nadine C.; Nilsson, Viktor O.

    2017-01-01

    Objective: This paper describes a behavior change intervention that encourages active commuting using electrically assisted bikes (e-bikes) for health promotion in the workplace. This paper presents the preliminary findings of the intervention’s impact on improving employee well-being and organizational behavior, as an indicator of potential business success. Method: Employees of a UK-based organization participated in a workplace travel behavior change intervention and used e-bikes as an active commuting mode; this was a change to their usual passive commuting behavior. The purpose of the intervention was to develop employee well-being and organizational behavior for improved business success. We explored the personal benefits and organizational co-benefits of active commuting and compared these to a travel-as-usual group of employees who did not change their behavior and continued taking non-active commutes. Results: Employees who changed their behavior to active commuting reported more positive affect, better physical health and more productive organizational behavior outcomes compared with passive commuters. In addition, there was an interactive effect of commuting mode and commuting distance: a more frequent active commute was positively associated with more productive organizational behavior and stronger overall positive employee well-being whereas a longer passive commute was associated with poorer well-being, although there was no impact on organizational behavior. Conclusion: This research provides emerging evidence of the value of an innovative workplace health promotion initiative focused on active commuting in protecting and improving employee well-being and organizational behavior for stronger business performance. It considers the significant opportunities for organizations pursuing improved workforce well-being, both in terms of employee health, and for improved organizational behavior and business success. PMID:28119640

  16. Acanthamoeba protease activity promotes allergic airway inflammation via protease-activated receptor 2.

    PubMed

    Park, Mi Kyung; Cho, Min Kyoung; Kang, Shin Ae; Park, Hye-Kyung; Kim, Dong-Hee; Yu, Hak Sun

    2014-01-01

    Acanthamoeba is a free-living amoeba commonly present in the environment and often found in human airway cavities. Acanthamoeba possesses strong proteases that can elicit allergic airway inflammation. To our knowledge, the aeroallergenicity of Acanthamoeba has not been reported. We repeatedly inoculated mice with Acanthamoeba trophozoites or excretory-secretory (ES) proteins intra-nasally and evaluated symptoms and airway immune responses. Acanthamoeba trophozoites or ES proteins elicited immune responses in mice that resembled allergic airway inflammation. ES proteins had strong protease activity and activated the expression of several chemokine genes (CCL11, CCL17, CCL22, TSLP, and IL-25) in mouse lung epithelial cells. The serine protease inhibitor phenyl-methane-sulfonyl fluoride (PMSF) inhibited ES protein activity. ES proteins also stimulated dendritic cells and enhanced the differentiation of naive T cells into IL-4-secreting T cells. After repeated inoculation of the protease-activated receptor 2 knockout mouse with ES proteins, airway inflammation and Th2 immune responses were markedly reduced, but not to basal levels. Furthermore, asthma patients had higher Acanthamoeba-specific IgE titers than healthy controls and we found Acanthamoeba specific antigen from house dust in typical living room. Our findings suggest that Acanthamoeba elicits allergic airway symptoms in mice via a protease allergen. In addition, it is possible that Acanthamoeba may be one of the triggers human airway allergic disease.

  17. Promoting Children's Physical Activity in Physical Education: The Role of Active Video Gaming

    ERIC Educational Resources Information Center

    Zhang, Tao; Moore, William; Gu, Xiangli; Chu, Tsz Lun; Gao, Zan

    2016-01-01

    Approximately half of the children in the United States do not meet the global physical activity guidelines, and many children adopt sedentary lifestyles. Given the fact about two-thirds children are classified as overweight or obese, traditional video games have been blamed as a major contributor to children's sedentary behavior and excessive…

  18. A community-organizing approach to promoting physical activity in older adults: the southeast senior physical activity network.

    PubMed

    Cheadle, Allen; Egger, Ruth; LoGerfo, James P; Walwick, Julie; Schwartz, Sheryl

    2010-03-01

    This article describes a community organizing approach to promoting physical activity among underserved older adults in southeast Seattle: the Southeast Senior Physical Activity Network (SESPAN). The organizing strategy involves networking with a variety of community-based organizations, with two broad objectives: (a) program objective-to make connections between two (or more) community-based organizations to create senior physical activity programs where none existed before; and (b) coalition objective-to build a broader network or coalition of groups and organizations to assist in making larger scale environmental and policy changes. Networking among organizations led to the creation of a number of potentially sustainable walking and exercise programs that are reaching previously underserved communities within Southeast Seattle. In addition, a major community event led to the establishment of a health coalition that has the potential to continue to generate new broad-based programs and larger scale environmental changes.

  19. Effectiveness of the Vital Aging program to promote active aging in Mexican older adults

    PubMed Central

    Mendoza-Ruvalcaba, Neyda Ma; Fernández-Ballesteros, Rocío

    2016-01-01

    Introduction Aging is not only a population phenomenon but also an experience and an individual reality. Vital Aging® is a program that considers active aging as the lifelong adaptation process of maximizing health and independence, physical and cognitive functioning, positive affect regulation and control, and social engagement. Through its different versions and editions, it has demonstrated being an effective program to promote active aging. The aim of this study is to determine the effectiveness of the “face-to-face” and “combined” versions of the program to promote active aging in Mexican older adults trial. Methods Seventy-six older adults aged 60 years and over participated in a quasi-experimental study and were recruited in a senior center to participate in the two experimental conditions: Vital Aging face-to-face (VA-FF) (n=35) and Vital Aging combined (VA-C; multimedia/face-to-face) (n=15), and the remaining 26 adults were assigned to a control group. Pretest and posttest assessments were performed after the theoretical–practical intervention. Mean differences and size effects were calculated for estimating the effect of the program. Results At the end of the study, participants showed improvements in the active aging outcome measures. Positive effects were observed in the frequency of intellectual, cultural – artistic, and social activities, perceptions of aging, satisfaction with social relationships, and self-efficacy for aging. Additionally, those who participated in VA-FF showed better memory performance, meta-memory, and a trend to report less memory problems, while older persons in VA-C showed a trend to have better life satisfaction. No effects were observed in physical activity, frequency of social relationships, and subjective health. Conclusion Findings show that the Vital Aging program in face-to-face and combined versions encourages active aging in Mexican older persons. These results are in general similar to those found in

  20. Residential summer camp: a new venue for nutrition education and physical activity promotion

    PubMed Central

    2013-01-01

    Background Millions of children attend residential summer camps each year. However, few studies have examined the potential of camps for obesity prevention efforts. Research in the domain of positive youth development has shown that camp programs as short as one week have both short- and long-term positive effects on self-esteem, self-efficacy and other youth outcomes. The objective of the present study was to highlight the potential of resident camps as promising venues for the promotion of healthy eating and physical activity behaviors in the children who attend. Methods Data for this study came from the American Camp Association 2007 Emerging Issues Survey. This survey assessed camp professionals’ perspectives on a diverse array of issues, including the healthy eating and physical activity of children. Data analysis focused on responses from 247 camp professionals whose camps offered resident camp programs. Results Descriptive and Chi-square statistics were calculated. Ninety-two percent of camp professionals reported that the healthy eating and physical activity of campers was an “important” or “very important” issue for camps. The majority of camps reported offering vegetarian options, healthy snacks and salad bars, and allergen-free options. Additionally, 86% of camp professionals indicated that they had implemented one or more strategies to address concerns related to the unhealthy eating behaviors of children, with top strategies including increasing the availability of fruits and vegetables, increasing the availability of healthy drink options, and improving the nutritional quality of menus. Fewer camp professionals (50%) indicated they had implemented strategies to increase children’s physical activity levels, but many professionals indicated that their camp programs were inherently active and additional strategies to promote physical activity were not necessary. Associations were found between camp affiliation and food options available to

  1. Promoter Methylation Pattern Controls Corticotropin Releasing Hormone Gene Activity in Human Trophoblasts

    PubMed Central

    Pan, Xin; Bowman, Maria; Scott, Rodney J.; Fitter, John; Smith, Roger

    2017-01-01

    Placental CRH production increases with advancing pregnancy in women and its course predicts gestational length. We hypothesized that CRH gene expression in the placenta is epigenetically controlled setting gestational trajectories characteristic of normal and pathological pregnancies. Here we determined histone modification and DNA methylation levels and DNA methylation patterns at the CRH promoter in primary trophoblast cultures by chromatin immunoprecipitation combined with clonal bisulfite sequencing and identified the transcriptionally active epialleles that associate with particular histone modifications and transcription factors during syncytialisation and cAMP-stimulation. CRH gene expression increased during syncytial differentiation and cAMP stimulation, which was associated with increased activating and decreased repressive histone modification levels at the promoter. DNA methylation levels remained unchanged. The nine CpGs of the CRH proximal promoter were partially and allele-independently methylated displaying many (>100) epialleles. RNA-polymerase-II (Pol-II) bound only to three particular epialleles in cAMP-stimulated cells, while phospho-cAMP response element-binding protein (pCREB) bound to only one epiallele, which was different from those selected by Pol-II. Binding of TATA-binding protein increased during syncytial differentiation preferentially at epialleles compatible with Pol-II and pCREB binding. Histone-3 acetylation was detected only at epialleles targeted by Pol-II and pCREB, while gene activating histone-4 acetylation and histone-3-lysine-4 trimethylation occurred at CRH epialleles not associated with Pol-II or pCREB. The suppressive histone-3-lysine-27 trimethyl and–lysine-9 trimethyl modifications showed little or no epiallele preference. The epiallele selectivity of activating histone modifications and transcription factor binding demonstrates the epigenetic and functional diversity of the CRH gene in trophoblasts, which is

  2. Dissociation of tumor promoter-stimulated ornithine decarboxylase activity and DNA synthesis in mouse epidermis in vivo and in vitro by fluocinolone acetonide, a tumor-promotion inhibitor.

    PubMed Central

    Lichti, U; Slaga, T J; Ben, T; Patterson, E; Hennings, H; Yuspa, S H

    1977-01-01

    12-O-Tetradecanoyl phorbol-13-acetate (TPA), a tumor promoter, stimulates DNA synthesis in mouse epidermal cells in vivo and in vitro. This response appears to be mediated through polyamine metabolism because ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17)activity is markedly increased shortly after promoter exposure and this induction varies in magnitude according to dose and promoter potency of a series of phorbol esters. In vitro, exogenous putrescine (0.01-10 mM) results in a dose-related increase and prolongation of promoter-stimulated DNA DNA synthesis, a phenomenon noted in other systems of polyamine-mediated growth stimulation. The anti-inflammatory steroid fluocinolone acetonide (FA), an inhibitor of tumor promotion, prevents TPA stimulation of epidermal proliferation in vivo and in vitro. In vitro, FA most effectively prevents stimulation of DNA synthesis when applied is not required. Paradoxially, FA potentiates the increase in ornithine decarboxylase activity after TPA administeration both in vivo and in vitro. Furthermore, the inhibition of TPA-stimulated DNA synthesis by FA in vitro can be reversed by exogenous putrescine. These results suggestthat FA exerts its antipromotion effect by reducing the sensitivity of the cell to polyamines or by reducing intracellular polyamine levels. PMID:269443

  3. Synergistic transcriptional enhancement does not depend on the number of acidic activation domains bound to the promoter.

    PubMed Central

    Oliviero, S; Struhl, K

    1991-01-01

    Many eukaryotic transcriptional activator proteins contain a DNA-binding domain that interacts with specific promoter sequences and an acidic activation region that is required to stimulate transcription. Transcriptional enhancement by such activator proteins is often synergistic and promiscuous; promoters containing multiple binding sites for an individual protein or even for unrelated proteins can be 10-100 times more active than promoters with single sites. It has been suggested that such synergy reflects a nonlinear response of the basic transcription machinery to the number and/or quality of acidic activation regions. Here, we determine the transcriptional activity of Jun-Fos heterodimers containing one or two GCN4 acidic activation regions on promoters containing one or two Ap-1 target sites. Surprisingly, heterodimers with one or two acidic regions activate transcription with similar efficiency and are equally synergistic (10- to 15-fold) on promoters containing two target sites. Thus, transcriptional synergy does not depend on the number of acidic activation regions but rather on the number of proteins bound to the promoter. This suggests that synergy is mediated either by cooperative DNA binding or by alternative mechanisms in which the DNA-binding domain plays a more direct role in transcription (e.g., changes in DNA structure, nucleosome displacement, or direct interactions with the transcriptional machinery). Images PMID:1898773

  4. Line active molecules promote inhomogeneous structures in membranes: theory, simulations and experiments.

    PubMed

    Palmieri, Benoit; Yamamoto, Tetsuya; Brewster, Robert C; Safran, Samuel A

    2014-06-01

    We review recent theoretical efforts that predict how line-active molecules can promote lateral heterogeneities (or domains) in model membranes. This fundamental understanding may be relevant to membrane composition in living cells, where it is thought that small domains, called lipid rafts, are necessary for the cells to be functional. The theoretical work reviewed here ranges in scale from coarse grained continuum models to nearly atomistic models. The effect of line active molecules on domain sizes and shapes in the phase separated regime or on fluctuation length scales and lifetimes in the single phase, mixed regime, of the membrane is discussed. Recent experimental studies on model membranes that include line active molecules are also presented together with some comparisons with the theoretical predictions.

  5. Activation of the beta interferon promoter by paramyxoviruses in the absence of virus protein synthesis.

    PubMed

    Killip, M J; Young, D F; Precious, B L; Goodbourn, S; Randall, R E

    2012-02-01

    Conflicting reports exist regarding the requirement for virus replication in interferon (IFN) induction by paramyxoviruses. Our previous work has demonstrated that pathogen-associated molecular patterns capable of activating the IFN-induction cascade are not normally generated during virus replication, but are associated instead with the presence of defective interfering (DI) viruses. We demonstrate here that DIs of paramyxoviruses, including parainfluenza virus 5, mumps virus and Sendai virus, can activate the IFN-induction cascade and the IFN-β promoter in the absence of virus protein synthesis. As virus protein synthesis is an absolute requirement for paramyxovirus genome replication, our results indicate that these DI viruses do not require replication to activate the IFN-induction cascade.

  6. Activation of peroxisome proliferators-activated receptor δ (PPARδ) promotes blastocyst hatching in mice.

    PubMed

    Kang, Hee Jung; Hwang, Soo Jin; Yoon, Jung Ah; Jun, Jin Hyun; Lim, Hyunjung Jade; Yoon, Tae Ki; Song, Haengseok

    2011-10-01

    Prostaglandins participate in a variety of female reproductive processes, including ovulation, fertilization, embryo implantation and parturition. In particular, maternal prostacyclin (PGI(2)) is critical for embryo implantation and the action of PGI(2) is not mediated via its G-protein-coupled membrane receptor, IP, but its nuclear receptor, peroxisome-proliferator-activated receptor δ (PPARδ). Recently, several studies have shown that PGI(2) enhances blastocyst development and/or hatching rate in vitro, and subsequently implantation and live birth rates in mice. However, the mechanism by which PGI(2) improves preimplantation embryo development in vitro remains unclear. Using molecular, pharmacologic and genetic approaches, we show that PGI(2)-induced PPARδ activation accelerates blastocyst hatching in mice. mRNAs for PPARδ, retinoid X receptor (heterodimeric partners of PPARδ) and PGI(2) synthase (PGIS) are temporally induced after zygotic gene activation, and their expression reaches maximum levels at the blastocyst stage, suggesting that functional complex of PPARδ can be formed in the blastocyst. Carbaprostacyclin (a stable analogue of PGI(2)) and GW501516 (a PPARδ selective agonist) significantly accelerated blastocyst hatching but did not increase total cell number of cultured blastocysts. Whereas U51605 (a PGIS inhibitor) interfered with blastocyst hatching, GW501516 restored U51605-induced retarded hatching. In contrast to the improvement of blastocyst hatching by PPARδ agonists, PPAR antagonists significantly inhibited blastocyst hatching. Furthermore, deletion of PPARδ at early stages of preimplantation mouse embryos caused delay of blastocyst hatching, but did not impair blastocyst development. Taken together, PGI(2)-induced PPARδ activation accelerates blastocyst hatching in mice.

  7. Protease induced plasticity: matrix metalloproteinase-1 promotes neurostructural changes through activation of protease activated receptor 1

    PubMed Central

    Allen, Megan; Ghosh, Suhasini; Ahern, Gerard P.; Villapol, Sonia; Maguire-Zeiss, Kathleen A.; Conant, Katherine

    2016-01-01

    Matrix metalloproteinases (MMPs) are a family of secreted endopeptidases expressed by neurons and glia. Regulated MMP activity contributes to physiological synaptic plasticity, while dysregulated activity can stimulate injury. Disentangling the role individual MMPs play in synaptic plasticity is difficult due to overlapping structure and function as well as cell-type specific expression. Here, we develop a novel system to investigate the selective overexpression of a single MMP driven by GFAP expressing cells in vivo. We show that MMP-1 induces cellular and behavioral phenotypes consistent with enhanced signaling through the G-protein coupled protease activated receptor 1 (PAR1). Application of exogenous MMP-1, in vitro, stimulates PAR1 dependent increases in intracellular Ca2+ concentration and dendritic arborization. Overexpression of MMP-1, in vivo, increases dendritic complexity and induces biochemical and behavioral endpoints consistent with increased GPCR signaling. These data are exciting because we demonstrate that an astrocyte-derived protease can influence neuronal plasticity through an extracellular matrix independent mechanism. PMID:27762280

  8. Vacancy associates promoting solar-driven photocatalytic activity of ultrathin bismuth oxychloride nanosheets.

    PubMed

    Guan, Meili; Xiao, Chong; Zhang, Jie; Fan, Shaojuan; An, Ran; Cheng, Qingmei; Xie, Junfeng; Zhou, Min; Ye, Bangjiao; Xie, Yi

    2013-07-17

    Crystal facet engineering of semiconductors is of growing interest and an important strategy for fine-tuning solar-driven photocatalytic activity. However, the primary factor in the exposed active facets that determines the photocatalytic property is still elusive. Herein, we have experimentally achieved high solar photocatalytic activity in ultrathin BiOCl nanosheets with almost fully exposed active {001} facets and provide some new and deep-seated insights into how the defects in the exposed active facets affect the solar-driven photocatalytic property. As the thickness of the nanosheets reduces to atomic scale, the predominant defects change from isolated defects V(Bi)‴ to triple vacancy associates V(Bi)‴V(O)••V(Bi)‴, which is unambiguously confirmed by the positron annihilation spectra. By virtue of the synergic advantages of enhanced adsorption capability, effective separation of electron–hole pairs and more reductive photoexcited electrons benefited from the V(Bi)‴V(O)••V(Bi)‴ vacancy associates, the ultrathin BiOCl nanosheets show significantly promoted solar-driven photocatalytic activity, even with extremely low photocatalyst loading. The finding of the existence of distinct defects (different from those in bulks) in ultrathin nanosheets undoubtedly leads to new possibilities for photocatalyst design using quasi-two-dimensional materials with high solar-driven photocatalytic activity.

  9. Finding of the Low Molecular Weight Inhibitors of Resuscitation Promoting Factor Enzymatic and Resuscitation Activity

    PubMed Central

    Demina, Galina R.; Makarov, Vadim A.; Nikitushkin, Vadim D.; Ryabova, Olga B.; Vostroknutova, Galina N.; Salina, Elena G.; Shleeva, Margarita O.; Goncharenko, Anna V.; Kaprelyants, Arseny S.

    2009-01-01

    Background Resuscitation promoting factors (RPF) are secreted proteins involved in reactivation of dormant actinobacteria, including Mycobacterium tuberculosis. They have been considered as prospective targets for the development of new anti-tuberculosis drugs preventing reactivation of dormant tubercle bacilli, generally associated with latent tuberculosis. However, no inhibitors of Rpf activity have been reported so far. The goal of this study was to find low molecular weight compounds inhibiting the enzymatic and biological activities of Rpfs. Methodology/Principal Findings Here we describe a novel class of 2-nitrophenylthiocyanates (NPT) compounds that inhibit muralytic activity of Rpfs with IC50 1–7 µg/ml. Fluorescence studies revealed interaction of active NPTs with the internal regions of the Rpf molecule. Candidate inhibitors of Rpf enzymatic activity showed a bacteriostatic effect on growth of Micrococcus luteus (in which Rpf is essential for growth protein) at concentrations close to IC50. The candidate compounds suppressed resuscitation of dormant (“non-culturable”) cells of M. smegmatis at 1 µg/ml or delayed resuscitation of dormant M. tuberculosis obtained in laboratory conditions at 10 µg/ml. However, they did not inhibit growth of active mycobacteria under these concentrations. Conclusions/Significance NPT are the first example of low molecular weight compounds that inhibit the enzymatic and biological activities of Rpf proteins. PMID:20016836

  10. Critical narrative review to identify educational strategies promoting physical activity in preschool.

    PubMed

    Kreichauf, S; Wildgruber, A; Krombholz, H; Gibson, E L; Vögele, C; Nixon, C A; Douthwaite, W; Moore, H J; Manios, Y; Summerbell, C D

    2012-03-01

    The aim of this narrative review is critically to evaluate educational strategies promoting physical activity that are used in the preschool setting in the context of obesity prevention programmes. Literature search was conducted between April and August 2010 in English and German databases (PubMED, PsychINFO, PSYNDEX, ERIC, FIS Bildung). Outcomes considered were time and intensity of physical activity, motor skills or measures of body composition. A total of 19 studies were included. Ten studies added physical activity lessons into their curriculum, one study provided more time for free play, eight studies focused on the social and play environment. Studies reporting positive outcomes implemented physical activity sessions that lasted at least 30 min d(-1). Several studies showed that children are most active in the first 10-15 min. The existence or installation of playground markings or fixed play equipment had no effect, whereas the presence or addition of portable play equipment was positively correlated with moderate-to-vigorous physical activity. Teacher training may be a key element for successful interventions. To overcome time constraints, a suggested solution is to integrate physical activity into daily routines and other areas of the preschool curriculum.

  11. Yeast homologous recombination-based promoter engineering for the activation of silent natural product biosynthetic gene clusters.

    PubMed

    Montiel, Daniel; Kang, Hahk-Soo; Chang, Fang-Yuan; Charlop-Powers, Zachary; Brady, Sean F

    2015-07-21

    Large-scale sequencing of prokaryotic (meta)genomic DNA suggests that most bacterial natural product gene clusters are not expressed under common laboratory culture conditions. Silent gene clusters represent a promising resource for natural product discovery and the development of a new generation of therapeutics. Unfortunately, the characterization of molecules encoded by these clusters is hampered owing to our inability to express these gene clusters in the laboratory. To address this bottleneck, we have developed a promoter-engineering platform to transcriptionally activate silent gene clusters in a model heterologous host. Our approach uses yeast homologous recombination, an auxotrophy complementation-based yeast selection system and sequence orthogonal promoter cassettes to exchange all native promoters in silent gene clusters with constitutively active promoters. As part of this platform, we constructed and validated a set of bidirectional promoter cassettes consisting of orthogonal promoter sequences, Streptomyces ribosome binding sites, and yeast selectable marker genes. Using these tools we demonstrate the ability to simultaneously insert multiple promoter cassettes into a gene cluster, thereby expediting the reengineering process. We apply this method to model active and silent gene clusters (rebeccamycin and tetarimycin) and to the silent, cryptic pseudogene-containing, environmental DNA-derived Lzr gene cluster. Complete promoter refactoring and targeted gene exchange in this "dead" cluster led to the discovery of potent indolotryptoline antiproliferative agents, lazarimides A and B. This potentially scalable and cost-effective promoter reengineering platform should streamline the discovery of natural products from silent natural product biosynthetic gene clusters.

  12. Structural and functional analysis of myostatin-2 promoter alleles from the marine fish Sparus aurata: evidence for strong muscle-specific promoter activity and post-transcriptional regulation.

    PubMed

    Nadjar-Boger, Elisabeth; Hinits, Yaniv; Funkenstein, Bruria

    2012-09-25

    Myostatin (MSTN) is a negative regulator of skeletal muscle growth. In contrast to mammals, fish possess at least two paralogs of MSTN: MSTN-1 and MSTN-2. In this study, we analyzed the structural-functional features of the four variants of Sparus aurata MSTN-2 5'-flanking region: saMSTN-2a, saMSTN-2as, saMSTN-2b and saMSTN-2c. In silico analysis revealed numerous putative cis regulatory elements including several E-boxes known as binding sites to myogenic transcription factors. Transient transfection experiments using non-muscle and muscle cell lines showed surprisingly high transcriptional activity in muscle cells, suggesting the presence of regulatory elements unique to differentiated myotubes. These observations were confirmed by in situ intramuscular injections of promoter DNA followed by reporter gene assays. Moreover, high promoter activity was found in differentiated neural cell, in agreement with MSTN-2 expression in brain. Progressive 5'-deletion analysis, using reporter gene assays, showed that the core promoter is located within the first -127 bp upstream of the ATG, and suggested the presence of regulatory elements that either repress or induce transcriptional activity. Transient transgenic zebrafish provided evidence for saMSTN-2 promoter ability to direct GFP expression to myofibers. Finally, our data shows that although no mature saMSTN-2 mRNA is observed in muscle; unspliced forms accumulate, confirming high level of transcription. In conclusion, our study shows for the first time that MSTN-2 promoter is a very robust promoter, especially in muscle cells.

  13. First functional polymorphism in CFTR promoter that results in decreased transcriptional activity and Sp1/USF binding

    SciTech Connect

    Taulan, M. Lopez, E.; Guittard, C.; Rene, C.; Baux, D.; Altieri, J.P.; DesGeorges, M.; Claustres, M.; Romey, M.C.

    2007-09-28

    Growing evidences show that functionally relevant polymorphisms in various promoters alter both transcriptional activity and affinities of existing protein-DNA interactions, and thus influence disease progression in humans. We previously reported the -94G>T CFTR promoter variant in a female CF patient in whom any known disease-causing mutation has been detected. To investigate whether the -94G>T could be a regulatory variant, we have proceeded to in silico analyses and functional studies including EMSA and reporter gene assays. Our data indicate that the promoter variant decreases basal CFTR transcriptional activity in different epithelial cells and alters binding affinities of both Sp1 and USF nuclear proteins to the CFTR promoter. The present report provides evidence for the first functional polymorphism that negatively affects the CFTR transcriptional activity and demonstrates a cooperative role of Sp1 and USF transcription factors in transactivation of the CFTR gene promoter.

  14. Therapeutic intraspinal stimulation to generate activity and promote long-term recovery

    PubMed Central

    Mondello, Sarah E.; Kasten, Michael R.; Horner, Philip J.; Moritz, Chet T.

    2014-01-01

    Neuroprosthetic approaches have tremendous potential for the treatment of injuries to the brain and spinal cord by inducing appropriate neural activity in otherwise disordered circuits. Substantial work has demonstrated that stimulation applied to both the central and peripheral nervous system leads to immediate and in some cases sustained benefits after injury. Here we focus on cervical intraspinal microstimulation (ISMS) as a promising method of activating the spinal cord distal to an injury site, either to directly produce movements or more intriguingly to improve subsequent volitional control of the paretic extremities. Incomplete injuries to the spinal cord are the most commonly observed in human patients, and these injuries spare neural tissue bypassing the lesion that could be influenced by neural devices to promote recovery of function. In fact, recent results have demonstrated that therapeutic ISMS leads to modest but sustained improvements in forelimb function after an incomplete spinal cord injury (SCI). This therapeutic spinal stimulation may promote long-term recovery of function by providing the necessary electrical activity needed for neuron survival, axon growth, and synaptic stability. PMID:24578680

  15. Attitudes of women in midlife to web-based interventions for promoting physical activity.

    PubMed

    Im, Eun-Ok; Chang, Sun Ju; Chee, Wonshik; Chee, Eunice

    2012-10-01

    We explored the attitudes of women at midlife to web-based interventions for promoting physical activity. 145 women volunteered to participate in one of four online forums. The forums were for four major racial/ethnic groups. 90 volunteers were recruited for the online forums (29 Whites, 23 Hispanics, 21 African Americans, and 17 Asians). Two sets of topics on attitudes to physical activity and racial/ethnic contexts were used. Each topic had some introductory questions and related prompts, and these were posted on the online forum sites in a serial fashion during the six-month period. We used a thematic analysis. Four major themes emerged: (1) 'a matter of the source of the information'; (2) 'I can pace myself'; (3) 'lack of interpersonal interactions'; and (4) 'culture-specificity and low cost.' The women in all ethnic groups thought that the source of the information was much more important than the medium of the information (e.g. web-based, booklet or face-to-face). They liked the self-controllability in web-based interventions. They preferred web-based interventions to other types of interventions because of easy accessibility, but they were concerned about lack of interpersonal interaction. None of the White or African American women indicated the need for culture-specificity in web-based interventions, but Hispanic and Asian women indicated that culture-specific interventions should be provided. Web-based interventions appear to have several advantages over conventional approaches to promoting physical activity.

  16. Phosphatidylinositol 3-Kinase Promotes Activation and Vacuolar Acidification and Delays Methyl Jasmonate-Induced Leaf Senescence.

    PubMed

    Liu, Jian; Ji, Yingbin; Zhou, Jun; Xing, Da

    2016-03-01

    PI3K and its product PI3P are both involved in plant development and stress responses. In this study, the down-regulation of PI3K activity accelerated leaf senescence induced by methyl jasmonate (MeJA) and suppressed the activation of vacuolar H(+)-ATPase (V-ATPase). Yeast two-hybrid analyses indicated that PI3K bound to the V-ATPase B subunit (VHA-B). Analysis of bimolecular fluorescence complementation in tobacco guard cells showed that PI3K interacted with VHA-B2 in the tonoplasts. Through the use of pharmacological and genetic tools, we found that PI3K and V-ATPase promoted vacuolar acidification and stomatal closure during leaf senescence. Vacuolar acidification was suppressed by the PIKfyve inhibitor in 35S:AtVPS34-YFP Arabidopsis during MeJA-induced leaf senescence, but the decrease was lower than that in YFP-labeled Arabidopsis. These results suggest that PI3K promotes V-ATPase activation and consequently induces vacuolar acidification and stomatal closure, thereby delaying MeJA-induced leaf senescence.

  17. Strategies to Increase After-School Program Staff Skills to Promote Healthy Eating and Physical Activity.

    PubMed

    Weaver, R Glenn; Beets, Michael W; Beighle, Aaron; Webster, Collin; Huberty, Jennifer; Moore, Justin B

    2016-01-01

    Standards targeting children's healthy eating and physical activity (HEPA) in after-school programs call for staff to display or refrain from HEPA-promoting or -discouraging behaviors that are linked to children's HEPA. This study evaluated strategies to align staff behaviors with HEPA Standards. Staff at four after-school programs serving approximately 500 children participated in professional development training from January 2012 to May 2013. Site leaders also attended workshops and received technical support during the same time frame. Changes in staff behaviors were evaluated using the System for Observing Staff Promotion of Activity and Nutrition in a pre- (fall 2011) multiple-post (spring 2012, fall 2012, and spring 2013), no-control group study design. A total of 8,949 scans were completed across the four measurement periods. Of the 19 behaviors measured, 14 changed in the appropriate direction. For example, staff engaging in physical activity with children increased from 27% to 40% of scans and staff eating unhealthy foods decreased from 56% to 14% of days. Ongoing training and technical assistance can have a measureable impact on staff behaviors linked to child-level HEPA outcomes. Future research should explore the feasibility of disseminating ongoing trainings to after-school program staff on a large scale.

  18. Epidermal keratinocyte-derived basophil promoting activity. Role of interleukin 3 and soluble CD23.

    PubMed Central

    Dalloul, A H; Arock, M; Fourcade, C; Béranger, J Y; Jaffray, P; Debré, P; Mossalayi, M D

    1992-01-01

    Human epidermal keratinocytes (EK) secrete factors able to sustain the proliferation of early myeloid cells and, in particular, the generation of basophils. This activity was previously attributed to IL-3, although no definitive in situ demonstration of this cytokine was provided. In regard to the possible physiological relevance of these data, we investigated herein the nature of EK-derived factors responsible for basophil promotion. Our data show that EK-derived supernatants (EK-sup) contain IL-3 as well as soluble CD23 (sCD23), both known for their colony stimulating activity. Messenger RNA for IL-3 and CD23 were also detected in EK. Blocking experiments using specific neutralizing monoclonal antibodies (mAb) further indicate that EK-derived basophil promoting activity is mainly due to the presence of IL-3 and sCD23 in EK-sup. Furthermore, by contrast to IL-3, sCD23 secretion by EK is cortisone sensitive and highly enhanced by IL-4, suggesting distinct regulatory mechanisms for their production. Images PMID:1401061

  19. Hedgehog-regulated atypical PKC promotes phosphorylation and activation of Smoothened and Cubitus interruptus in Drosophila

    PubMed Central

    Jiang, Kai; Liu, Yajuan; Fan, Junkai; Epperly, Garretson; Gao, Tianyan; Jiang, Jin; Jia, Jianhang

    2014-01-01

    Smoothened (Smo) is essential for transduction of the Hedgehog (Hh) signal in both insects and vertebrates. Cell surface/cilium accumulation of Smo is thought to play an important role in Hh signaling, but how the localization of Smo is controlled remains poorly understood. In this study, we demonstrate that atypical PKC (aPKC) regulates Smo phosphorylation and basolateral accumulation in Drosophila wings. Inactivation of aPKC by either RNAi or a mutation inhibits Smo basolateral accumulation and attenuates Hh target gene expression. In contrast, expression of constitutively active aPKC elevates basolateral accumulation of Smo and promotes Hh signaling. The aPKC-mediated phosphorylation of Smo at Ser680 promotes Ser683 phosphorylation by casein kinase 1 (CK1), and these phosphorylation events elevate Smo activity in vivo. Moreover, aPKC has an additional positive role in Hh signaling by regulating the activity of Cubitus interruptus (Ci) through phosphorylation of the Zn finger DNA-binding domain. Finally, the expression of aPKC is up-regulated by Hh signaling in a Ci-dependent manner. Our findings indicate a direct involvement of aPKC in Hh signaling beyond its role in cell polarity. PMID:25349414

  20. Characterization of human erythroid burst-promoting activity derived from bone marrow conditioned media

    SciTech Connect

    Porter, P.N.; Ogawa, M.

    1982-06-01

    Bone marrow conditioned media (BMCM) increases burst number and the incorporation of /sup 59/Fe into heme by bursts when peripheral blood or bone marrow cells are cultured at limiting serum concentrations. Burst-promoting activity (BPA) has now been purified approximately 300-fold from this source by ion-exchange chromatography on DEAE-Sephadex and absorption chromatography on hydroxyapatite agarose gel. Marrow BPA increased burst number and hemoglobin (Hb) synthesis in a dose-dependent manner. A larger increase in Hb synthesis than in burst number was consistently observed, which was probably a consequence of the increase in the number of cells per burst that occurs in the presence of BPA. The role of BPA in culture could be distinguished from erythropoietin (Ep), since no bursts grew in the absence of Ep, whether or not BPA was present, and since it had no effect on the growth of erythroid colonies scored at day 5 of culture. Our purified fraction did not support the growth of CFU-C in culture. Activity was stable at temperatures of 70 degrees C or lower for 10 min; exposure to 80 degrees C resulted in approximately 50% loss of activity. BPA was completely inactivated by treatment at 100 degrees C for 10 min. Thus, human bone marrow cells produce a heat-sensitive factor that specifically promotes the growth of early erythroid progenitors in culture.

  1. Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T-lymphocytes

    PubMed Central

    Caruana, Ignazio; Savoldo, Barbara; Hoyos, Valentina; Weber, Gerrit; Liu, Hao; Kim, Eugene S.; Ittmann, Michael M.; Marchetti, Dario; Dotti, Gianpietro

    2015-01-01

    Adoptive transfer of chimeric antigen receptor (CAR)-redirected T lymphocytes (CAR-T cells) has had less striking effects in solid tumors1–3 than in lymphoid malignancies4, 5. Although active tumor-mediated immunosuppression may play a role in limiting efficacy6, functional changes in T lymphocytes following their ex vivo manipulation may also account for cultured CAR-T cells’ reduced ability to penetrate stroma-rich solid tumors. We therefore studied the capacity of human in vitro-cultured CAR-T cells to degrade components of the extracellular matrix (ECM). In contrast to freshly isolated T lymphocytes, we found that in vitro-cultured T lymphocytes lack expression of the enzyme heparanase (HPSE) that degrades heparan sulphate proteoglycans, which are main components of ECM. We found that HPSE mRNA is down regulated in in vitro-expanded T cells, which may be a consequence of p53 binding to the HPSE gene promoter. We therefore engineered CAR-T cells to express HPSE and showed improved capacity to degrade ECM, which promoted tumor T-cell infiltration and antitumor activity. Employing this strategy may enhance the activity of CAR-T cells in individuals with stroma-rich solid tumors. PMID:25849134

  2. FGF23 promotes myocardial fibrosis in mice through activation of β-catenin

    PubMed Central

    Lin, Hairuo; Chen, Zhenhuan; Xie, Jiahe; Xuan, Wanling; Liao, Wangjun; Bin, Jianping; Huang, Xiaobo; Kitakaze, Masafumi; Liao, Yulin

    2016-01-01

    Fibroblast growth factor 23 (FGF23) has been reported to induce left ventricular hypertrophy, but it remains unclear whether FGF23 plays a role in cardiac fibrosis. This study is attempted to investigate the role of FGF23 in post-infarct myocardial fibrosis in mice. We noted that myocardial and plasma FGF23 and FGF receptor 4 were increased in mice with heart failure as well as in cultured adult mouse cardiac fibroblasts (AMCFs) exposed to angiotensin II, phenylephrine, soluble fractalkine. Recombinant FGF23 protein increased active β-catenin , procollagen I and procollagen III expression in cultured AMCFs. Furthermore, intra-myocardial injection of adeno-associated virus-FGF23 in mice significantly increased left ventricular end-diastolic pressure and myocardial fibrosis, and markedly upregulated active β-catenin, transforming growth factor β (TGF-β), procollagen I and procollagen III in both myocardial infarction (MI) and ischemia/reperfusion (IR) mice, while β-catenin inhibitor or silencing of β-catenin antagonized the FGF23-promoted myocardial fibrosis in vitro and in vivo. These findings indicate that FGF23 promotes myocardial fibrosis and exacerbates diastolic dysfunction induced by MI or IR, which is associated with the upregulation of active β-catenin and TGF-β. PMID:27579618

  3. Proteolytic activation of receptor-bound anthrax protective antigen on macrophages promotes its internalization.

    PubMed

    Beauregard, K E; Collier, R J; Swanson, J A

    2000-06-01

    Immunofluorescence and other methods have been used to probe the self-assembly and internalization of the binary toxin, anthrax lethal toxin (LeTx), in primary murine macrophages. Proteolytic activation of protective antigen (PA; 83 kDa, the B moiety of the toxin) by furin was the rate-limiting step in internalization of LeTx and promoted clearance of PA from the cell surface. A furin-resistant form of PA remained at the cell surface for at least 90 min. Oligomerization of receptor-bound PA63, the 63 kDa active fragment of PA, was manifested by its conversion to a pronase-resistant state, characteristic of the heptameric prepore form in solution. That oligomerization of PA63 triggers toxin internalization is supported by the observation that PA20, the complementary 20 kDa fragment of PA, inhibited clearance of nicked PA. The PA63 prepore, with or without lethal factor (LF), cleared slowly from the cell surface. These studies show that proteolytic cleavage of PA, in addition to permitting oligomerization and LF binding, also promotes internalization of the protein. The relatively long period of activation and internalization of PA at the cell surface may reflect adaptation of this binary toxin that maximizes self-assembly.

  4. ANALYSIS OF 2,3,7,8-TCDD TUMOR PROMOTION ACTIVITY ...

    EPA Pesticide Factsheets

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has a high estimated cancer potency in animals which has been reasoned to imply that TCDD might be carcinogenic to man. The animal cancer data show that TCDD can act in a solitary manner causing tumors without the participation of other known factors. owever, there exist animal cancer data indicating that TCDD can act as a tumor-promoting compound. This analysis examines which type of carcinogen and which mechanism best characterize TCDD cancer activity. It is suggested that TCDD acts by a hormonal mechanism to cause cancer in solitary manner, at low doses, in two species, and in a number of different organs, including rare sites. These observations in toto characterize TCDD as a complete carcinogen, which by definition encompasses both initiation and promotion carcinogenic activities. This analysis examines which type of carcinogen and which mechanism best characterize TCDD cancer activity. It is suggested that TCDD acts by a hormonal mechanism to cause cancer in solitary manner, at low doses, in two species, and in a number of different organs, including rare sites

  5. Promoting Science Outdoor Activities for Elementary School Children: Contributions from a research laboratory

    NASA Astrophysics Data System (ADS)

    Boaventura, Diana; Faria, Cláudia; Chagas, Isabel; Galvão, Cecília

    2013-03-01

    The purposes of the study were to analyse the promotion of scientific literacy through practical research activities and to identify children's conceptions about scientists and how they do science. Elementary school children were engaged in two scientific experiments in a marine biology research laboratory. A total of 136 students answered a questionnaire about their previous habits towards science and carried out the following actions: (1) a guided visit to the laboratory, (2) a brief presentation of the research theme, (3) the development of two experiments, and (4) a questionnaire about the experiments and science conceptions. The research methods included observation, document analysis, and content analysis of the answers to the questionnaires. Additionally, each visit was video recorded in order to design learning materials. The results revealed that most of the pupils were able to follow every stage of experimentation. However, some of them misinterpreted results and conclusions. One implication of the study is that this type of outdoor activity is extremely important to promote meaningful science learning in children, but more care should be taken in practical science activities so that children can overcome some common difficulties when performing scientific inquiry.

  6. Polycystin-1 promotes PKC{alpha}-mediated NF-{kappa}B activation in kidney cells

    SciTech Connect

    Banzi, Manuela; Aguiari, Gianluca; Trimi, Viky; Mangolini, Alessandra; Pinton, Paolo; Witzgall, Ralph; Rizzuto, Rosario; Senno, Laura del . E-mail: sen@unife.it

    2006-11-17

    Polycystin-1 (PC1), the PKD1 gene product, is a membrane receptor which regulates many cell functions, including cell proliferation and apoptosis, both typically increased in cyst lining cells in autosomal dominant polycystic kidney disease. Here we show that PC1 upregulates the NF-{kappa}B signalling pathway in kidney cells to prevent cell death. Human embryonic kidney cell lines (HEK293{sup CTT}), stably expressing a PC1 cytoplasmic terminal tail (CTT), presented increased NF-{kappa}B nuclear levels and NF-{kappa}B-mediated luciferase promoter activity. This, consistently, was reduced in HEK293 cells in which the endogenous PC1 was depleted by RNA interference. CTT-dependent NF-{kappa}B promoter activation was mediated by PKC{alpha} because it was blocked by its specific inhibitor Ro-320432. Furthermore, it was observed that apoptosis, which was increased in PC1-depleted cells, was reduced in HEK293{sup CTT} cells and in porcine kidney LtTA cells expressing a doxycycline-regulated CTT. Staurosporine, a PKC inhibitor, and parthenolide, a NF-{kappa}B inhibitor, significantly reduced the CTT-dependent antiapoptotic effect. These data reveal, therefore, a novel pathway by which polycystin-1 activates a PKC{alpha}-mediated NF-{kappa}B signalling and cell survival.

  7. Biocontrol and plant growth-promoting activity of rhizobacteria from Chinese fields with contaminated soils.

    PubMed

    Wang, Xuefei; Mavrodi, Dmitri V; Ke, Linfeng; Mavrodi, Olga V; Yang, Mingming; Thomashow, Linda S; Zheng, Na; Weller, David M; Zhang, Jibin

    2015-05-01

    The aim of this study was to inventory the types of plant growth-promoting rhizobacteria (PGPR) present in the rhizosphere of plants grown in soils contaminated with heavy metals, recalcitrant organics, petroleum sewage or salinity in China. We screened 1223 isolates for antifungal activity and about 24% inhibited Rhizoctonia solani or Sclerotinia sclerotiorum. Twenty-four strains inhibitory to R. solani, Gaeumannomyces graminis var. tritici and/or S. sclerotiorum and representing the dominant morphotypes were assayed for PGPR activity. Seven strains contained phlD, prnD, pltC or phzF genes and produced the antibiotics 2,4-diacetylphloroglucinol, pyrrolnitrin, pyoluteorin and phenazines respectively. Six strains contained acdS, which encodes 1-aminocyclopropane-1-carboxylic acid deaminase. Phylogenetic analysis of 16S rDNA and phlD, phzF and acdS genes demonstrated that some strains identified as Pseudomonas were similar to model PGPR strains Pseudomonas protegens Pf-5, Pseudomonas chlororaphis subsp. aureofaciens 30-84 and P. brassicacearum Q8r1-96. Pseudomonas protegens- and P. chlororaphis-like strains had the greatest biocontrol activity against Rhizoctonia root rot and take-all of wheat. Pseudomonas protegens and P. brassicacearum-like strains showed the greatest promotion of canola growth. Our results indicate that strains from contaminated soils are similar to well-described PGPR found in agricultural soils worldwide.

  8. Microfilament regulatory protein MENA increases activity of RhoA and promotes metastasis of hepatocellular carcinoma.

    PubMed

    Lin, Ling; Yang, Xiao-Mei; Li, Jun; Zhang, Yan-Li; Qin, Wenxin; Zhang, Zhi-Gang

    2014-09-10

    Mammalian enabled (MENA), usually known as a direct regulator of microfilament polymerization and bundling, promotes metastasis in various cancers. Here we focus on the role of MENA in hepatocellular carcinoma (HCC) metastasis and the relevant mechanism from the view of RhoA activity regulation. By HCC tissue microarray analysis, we found that MENA expression was positively associated with satellite lesions (P<0.01) and vascular invasion (P<0.01). Cases with membrane reinforcement of MENA staining in HCC tissues had significantly higher rates of early recurrence in the intermediate MENA expression group. Knockdown of MENA significantly suppressed HCC cell migration and invasion in vitro, as well as their intrahepatic and distant metastasis in vivo. Knockdown of MENA also decreased filopodia and stress fibers in SMMC-7721 cells. Furthermore, a decrease of RhoA activity was detected by a pull-down assay in SMMC-7721-shMENA cells. The ROCK inhibitor, Y-27632, suppressed migration of both MENA knockdown SMMC-7721 cells and control cells, but diminished their difference. Thus, our findings suggest that MENA promotes HCC cell motility by activating RhoA.

  9. A Novel Pyrimidin-Like Plant Activator Stimulates Plant Disease Resistance and Promotes Growth

    PubMed Central

    Sun, Tie-Jun; Lu, Yun; Narusaka, Mari; Shi, Chao; Yang, Yu-Bing; Wu, Jian-Xin; Zeng, Hong-Yun; Narusaka, Yoshihiro; Yao, Nan

    2015-01-01

    Plant activators are chemicals that induce plant defense responses to a broad spectrum of pathogens. Here, we identified a new potential plant activator, 5-(cyclopropylmethyl)-6-methyl-2-(2-pyridyl)pyrimidin-4-ol, named PPA (pyrimidin-type plant activator). Compared with benzothiadiazole S-methyl ester (BTH), a functional analog of salicylic acid (SA), PPA was fully soluble in water and increased fresh weight of rice (Oryza sativa) and Arabidopsis plants at low concentrations. In addition, PPA also promoted lateral root development. Microarray data and real-time PCR revealed that PPA-treated leaves not challenged with pathogen showed up-regulation of genes related to reactive oxygen species (ROS), defenses and SA. During bacterial infection, Arabidopsis plants pretreated with PPA showed dramatically decreased disease symptoms and an earlier and stronger ROS burst, compared with plants pretreated with BTH. Microscopy revealed that H2O2 accumulated in the cytosol, plasma membrane and cell wall around intracellular bacteria, and also on the bacterial cell wall, indicating that H2O2 was directly involved in killing bacteria. The increase in ROS-related gene expression also supported this observation. Our results indicate that PPA enhances plant defenses against pathogen invasion through the plant redox system, and as a water-soluble compound that can promote plant growth, has broad potential applications in agriculture. PMID:25849038

  10. Mechanism for the catastrophe-promoting activity of the microtubule destabilizer Op18/stathmin.

    PubMed

    Gupta, Kamlesh K; Li, Chunlei; Duan, Aranda; Alberico, Emily O; Kim, Oleg V; Alber, Mark S; Goodson, Holly V

    2013-12-17

    Regulation of microtubule dynamic instability is crucial for cellular processes, ranging from mitosis to membrane transport. Stathmin (also known as oncoprotein 18/Op18) is a prominent microtubule destabilizer that acts preferentially on microtubule minus ends. Stathmin has been studied intensively because of its association with multiple types of cancer, but its mechanism of action remains controversial. Two models have been proposed. One model is that stathmin promotes microtubule catastrophe indirectly, and does so by sequestering tubulin; the other holds that stathmin alters microtubule dynamics by directly destabilizing growing microtubules. Stathmin's sequestration activity is well established, but the mechanism of any direct action is mysterious because stathmin binds to microtubules very weakly. To address these issues, we have studied interactions between stathmin and varied tubulin polymers. We show that stathmin binds tightly to Dolastatin-10 tubulin rings, which mimic curved tubulin protofilaments, and that stathmin depolymerizes stabilized protofilament-rich polymers. These observations lead us to propose that stathmin promotes catastrophe by binding to and acting upon protofilaments exposed at the tips of growing microtubules. Moreover, we suggest that stathmin's minus-end preference results from interactions between stathmin's N terminus and the surface of α-tubulin that is exposed only at the minus end. Using computational modeling of microtubule dynamics, we show that these mechanisms could account for stathmin's observed activities in vitro, but that both the direct and sequestering activities are likely to be relevant in a cellular context. Taken together, our results suggest that stathmin can promote catastrophe by direct action on protofilament structure and interactions.

  11. Activities for the Promotion of Gender Equality in Japan—Japan Society of Applied Physics

    NASA Astrophysics Data System (ADS)

    Kodate, Kashiko; Tanaka, Kazuo

    2005-10-01

    Since 1946, the Japan Society of Applied Physics (JSAP) has strived to promote research and development in applied physics for benefits beyond national boundaries. Activities of JSAP involve multidisciplinary fields, from physics and engineering to life sciences. Of its 23,000 members, 48% are from industry, 29% from academia, and about 7% from semi-autonomous national research laboratories. Its large industrial membership is one of the distinctive features of JSAP. In preparation for the First IUPAP International Conference on Women in Physics (Paris, 2002), JSAP members took the first step under the strong leadership of then-JSAP President Toshio Goto, setting up the Committee for the Promotion Equal Participation of Men and Women in Science and Technology. Equality rather than women's advancement is highlighted to further development in science and technology. Attention is also paid to balancing the number of researchers from different age groups and affiliations. The committee has 22 members: 12 female and 10 male; 7 from corporations, 12 from universities, and 3 from semi-autonomous national research institutes. Its main activities are to organize symposia and meetings, conduct surveys among JSAP members, and provide child-care facilities at meetings and conferences. In 2002 the Japan Physics Society and the Chemical Society of Japan jointly created the Japan Inter-Society Liaison Association for the Promotion of Equal Participation of Men and Women in Science and Engineering. Membership has grown to 44 societies (of which 19 are observers) ranging from mathematics, information, and life sciences to civil engineering. Joint activities across sectors and empower the whole. The Gender Equality Bureau in the Cabinet Office recently launched a large-scale project called "Challenge Campaign" to encourage girls to major in natural science and engineering, which JSAP is co-sponsoring.

  12. Nuclease activity of Legionella pneumophila Cas2 promotes intracellular infection of amoebal host cells.

    PubMed

    Gunderson, Felizza F; Mallama, Celeste A; Fairbairn, Stephanie G; Cianciotto, Nicholas P

    2015-03-01

    Legionella pneumophila, the primary agent of Legionnaires' disease, flourishes in both natural and man-made environments by growing in a wide variety of aquatic amoebae. Recently, we determined that the Cas2 protein of L. pneumophila promotes intracellular infection of Acanthamoeba castellanii and Hartmannella vermiformis, the two amoebae most commonly linked to cases of disease. The Cas2 family of proteins is best known for its role in the bacterial and archeal clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein (Cas) system that constitutes a form of adaptive immunity against phage and plasmid. However, the infection event mediated by L. pneumophila Cas2 appeared to be distinct from this function, because cas2 mutants exhibited infectivity defects in the absence of added phage or plasmid and since mutants lacking the CRISPR array or any one of the other cas genes were not impaired in infection ability. We now report that the Cas2 protein of L. pneumophila has both RNase and DNase activities, with the RNase activity being more pronounced. By characterizing a catalytically deficient version of Cas2, we determined that nuclease activity is critical for promoting infection of amoebae. Also, introduction of Cas2, but not its catalytic mutant form, into a strain of L. pneumophila that naturally lacks a CRISPR-Cas locus caused that strain to be 40- to 80-fold more infective for amoebae, unequivocally demonstrating that Cas2 facilitates the infection process independently of any other component encoded within the CRISPR-Cas locus. Finally, a cas2 mutant was impaired for infection of Willaertia magna but not Naegleria lovaniensis, suggesting that Cas2 promotes infection of most but not all amoebal hosts.

  13. Nuclease Activity of Legionella pneumophila Cas2 Promotes Intracellular Infection of Amoebal Host Cells

    PubMed Central

    Gunderson, Felizza F.; Mallama, Celeste A.; Fairbairn, Stephanie G.

    2014-01-01

    Legionella pneumophila, the primary agent of Legionnaires' disease, flourishes in both natural and man-made environments by growing in a wide variety of aquatic amoebae. Recently, we determined that the Cas2 protein of L. pneumophila promotes intracellular infection of Acanthamoeba castellanii and Hartmannella vermiformis, the two amoebae most commonly linked to cases of disease. The Cas2 family of proteins is best known for its role in the bacterial and archeal clustered regularly interspaced short palindromic repeat (CRISPR)–CRISPR-associated protein (Cas) system that constitutes a form of adaptive immunity against phage and plasmid. However, the infection event mediated by L. pneumophila Cas2 appeared to be distinct from this function, because cas2 mutants exhibited infectivity defects in the absence of added phage or plasmid and since mutants lacking the CRISPR array or any one of the other cas genes were not impaired in infection ability. We now report that the Cas2 protein of L. pneumophila has both RNase and DNase activities, with the RNase activity being more pronounced. By characterizing a catalytically deficient version of Cas2, we determined that nuclease activity is critical for promoting infection of amoebae. Also, introduction of Cas2, but not its catalytic mutant form, into a strain of L. pneumophila that naturally lacks a CRISPR-Cas locus caused that strain to be 40- to 80-fold more infective for amoebae, unequivocally demonstrating that Cas2 facilitates the infection process independently of any other component encoded within the CRISPR-Cas locus. Finally, a cas2 mutant was impaired for infection of Willaertia magna but not Naegleria lovaniensis, suggesting that Cas2 promotes infection of most but not all amoebal hosts. PMID:25547789

  14. Hair growth promoting activity of cedrol isolated from the leaves of Platycladus orientalis.

    PubMed

    Zhang, Yan; Han, Ling; Chen, Shan-Shan; Guan, Jian; Qu, Fan-Zhi; Zhao, Yu-Qing

    2016-10-01

    Platycladus orientalis (L.) Franco is traditionally known to potentiate hair growth promotion. However, there has been no report on its main active ingredient responsible for the hair growth activity. In the current work, cedrol as a major constituent from P. orientalis was evaluated for its potential on hair growth in vivo. Different concentrations of cedrol (10, 20 and 30mg/mL) were applied topically over the shaved skin of C57BL/6 mice and monitored for 21days. Results indicated that cedrol significantly promoted hair growth in a dose-dependent manner, particularly for the female mice. Both male and female mice groups treated with 30mg/mL cedrol required shorter time than the blank control and 2% minoxidil groups at different growth stages. Compared with the blank control (8.87mm) and 2% minoxidil (9.94mm) groups at 21days, the hair length of female mice treated with 30mg/mL cedrol showed a remarkable increase with the value of 11.07mm. Hair in male and female mice groups treated with 30mg/mL cedrol was heavier than the 2% minoxidil (38.2 and 35.9mg, respectively) groups with the weight of 42.6 and 45.2mg, respectively. Further observation of the hair follicle demonstrated that cedrol exerted a remarkable effect on the hair follicle length. These findings suggested that cedrol may be the main active ingredient of P. orientalis and have the potential of becoming a new hair growth promoter.

  15. The ERF11 Transcription Factor Promotes Internode Elongation by Activating Gibberellin Biosynthesis and Signaling1[OPEN

    PubMed Central

    Zhou, Xin; Zhang, Zhong-Lin; Tyler, Ludmila; Yusuke, Jikumaru; Qiu, Kai; Lumba, Shelley; Desveaux, Darrell; McCourt, Peter; Sun, Tai-ping

    2016-01-01

    The phytohormone gibberellin (GA) plays a key role in promoting stem elongation in plants. Previous studies show that GA activates its signaling pathway by inducing rapid degradation of DELLA proteins, GA signaling repressors. Using an activation-tagging screen in a reduced-GA mutant ga1-6 background, we identified AtERF11 to be a novel positive regulator of both GA biosynthesis and GA signaling for internode elongation. Overexpression of AtERF11 partially rescued the dwarf phenotype of ga1-6. AtERF11 is a member of the ERF (ETHYLENE RESPONSE FACTOR) subfamily VIII-B-1a of ERF/AP2 transcription factors in Arabidopsis (Arabidopsis thaliana). Overexpression of AtERF11 resulted in elevated bioactive GA levels by up-regulating expression of GA3ox1 and GA20ox genes. Hypocotyl elongation assays further showed that overexpression of AtERF11 conferred elevated GA response, whereas loss-of-function erf11 and erf11 erf4 mutants displayed reduced GA response. In addition, yeast two-hybrid, coimmunoprecipitation, and transient expression assays showed that AtERF11 enhances GA signaling by antagonizing the function of DELLA proteins via direct protein-protein interaction. Interestingly, AtERF11 overexpression also caused a reduction in the levels of another phytohormone ethylene in the growing stem, consistent with recent finding showing that AtERF11 represses transcription of ethylene biosynthesis ACS genes. The effect of AtERF11 on promoting GA biosynthesis gene expression is likely via its repressive function on ethylene biosynthesis. These results suggest that AtERF11 plays a dual role in promoting internode elongation by inhibiting ethylene biosynthesis and activating GA biosynthesis and signaling pathways. PMID:27255484

  16. Enhancer and promoter elements directing activation and glucocorticoid repression of the. cap alpha. /sub 1/-fetoprotein gene in hepatocytes

    SciTech Connect

    Guertin, M.; La Rue, H.; Bernier, D.; Wrange, O.; Chevrette, M.; Gingras, M.C.; Belanger, L.

    1988-04-01

    Mutations were introduced in 7 kilobases of 5'-flanking rat ..cap alpha../sub 1/-fetoprotein (AFP) genomic DNA, linked to the chloramphenicol acetyltransferase gene. AFP promoter activity and its repression by a glucocorticoid hormone were assessed by stable and transient expression assays. Stable transfection assays were more sensitive and accurate than transient expression assays in a Morris 7777 rat hepatoma recipient (Hepa7.6), selected for its strong AFP repression by dexamethasone. The segment of DNA encompassing a hepatocyte-constitutive chromatin DNase I-hypersensitive site at -3.7 kilobases and a liver developmental stage-specific site at -2.5 kilobases contains interacting enhancer elements sufficient for high AFP promoter activity in Hepa7.6 or HepG2 cells. Deletions and point mutations define an upstream promoter domain of AFP gene activation, operating with at least three distinct promoter-activating elements, PEI at -65 base pairs, PEII at -120 base pairs, and DE at -160 base pairs. PEI and PEII share homologies with albumin promoter sequences, PEII is a near-consensus nuclear factor I recognition sequence, and DE overlaps a glucocorticoid receptor recognition sequence. An element conferring glucocorticoid repression of AFP gene activity is located in the upstream AFP promoter domain. Receptor-binding assays indicate that this element is the glucocorticoid receptor recognition sequence which overlaps with promoter-activating element DE.

  17. Community Health Workers promoting physical activity: Targeting multiple levels of the Social Ecological Model

    PubMed Central

    Haughton, Jessica; Ayala, Guadalupe X.; Burke, Kari Herzog; Elder, John P.; Montañez, Jacqueline; Arredondo, Elva M.

    2015-01-01

    The effectiveness of Community Health Workers (CHWs) as health educators and health promoters among Latino populations is widely recognized. The Affordable Care Act created important opportunities to increase the role of CHWs in preventive health. This article describes the implementation of CHW-led, culturally specific, faith-based program to increase physical activity (PA) among churchgoing Latinas. The current study augments previous research by describing the recruitment, selection, training, and evaluation of CHWs for a PA intervention targeting multiple levels of the Social Ecological Model. PMID:26280587

  18. The artificial zinc finger coding gene 'Jazz' binds the utrophin promoter and activates transcription.

    PubMed

    Corbi, N; Libri, V; Fanciulli, M; Tinsley, J M; Davies, K E; Passananti, C

    2000-06-01

    Up-regulation of utrophin gene expression is recognized as a plausible therapeutic approach in the treatment of Duchenne muscular dystrophy (DMD). We have designed and engineered new zinc finger-based transcription factors capable of binding and activating transcription from the promoter of the dystrophin-related gene, utrophin. Using the recognition 'code' that proposes specific rules between zinc finger primary structure and potential DNA binding sites, we engineered a new gene named 'Jazz' that encodes for a three-zinc finger peptide. Jazz belongs to the Cys2-His2 zinc finger type and was engineered to target the nine base pair DNA sequence: 5'-GCT-GCT-GCG-3', present in the promoter region of both the human and mouse utrophin gene. The entire zinc finger alpha-helix region, containing the amino acid positions that are crucial for DNA binding, was specifically chosen on the basis of the contacts more frequently represented in the available list of the 'code'. Here we demonstrate that Jazz protein binds specifically to the double-stranded DNA target, with a dissociation constant of about 32 nM. Band shift and super-shift experiments confirmed the high affinity and specificity of Jazz protein for its DNA target. Moreover, we show that chimeric proteins, named Gal4-Jazz and Sp1-Jazz, are able to drive the transcription of a test gene from the human utrophin promoter.

  19. Epigenomic Modifications Predict Active Promoters and Gene Structure in Toxoplasma gondii

    PubMed Central

    Gissot, Mathieu; Kelly, Krystyna A; Ajioka, James W; Greally, John M; Kim, Kami

    2007-01-01

    Mechanisms of gene regulation are poorly understood in Apicomplexa, a phylum that encompasses deadly human pathogens like Plasmodium and Toxoplasma. Initial studies suggest that epigenetic phenomena, including histone modifications and chromatin remodeling, have a profound effect upon gene expression and expression of virulence traits. Using the model organism Toxoplasma gondii, we characterized the epigenetic organization and transcription patterns of a contiguous 1% of the T. gondii genome using custom oligonucleotide microarrays. We show that methylation and acetylation of histones H3 and H4 are landmarks of active promoters in T. gondii that allow us to deduce the position and directionality of gene promoters with >95% accuracy. These histone methylation and acetylation “activation” marks are strongly associated with gene expression. We also demonstrate that the pattern of histone H3 arginine methylation distinguishes certain promoters, illustrating the complexity of the histone modification machinery in Toxoplasma. By integrating epigenetic data, gene prediction analysis, and gene expression data from the tachyzoite stage, we illustrate feasibility of creating an epigenomic map of T. gondii tachyzoite gene expression. Further, we illustrate the utility of the epigenomic map to empirically and biologically annotate the genome and show that this approach enables identification of previously unknown genes. Thus, our epigenomics approach provides novel insights into regulation of gene expression in the Apicomplexa. In addition, with its compact genome, genetic tractability, and discrete life cycle stages, T. gondii provides an important new model to study the evolutionarily conserved components of the histone code. PMID:17559302

  20. Promoting Physical Activity among Children: The “Great Live and Move Challenge”

    PubMed

    Mourgues, Marion; Gourlan, Mathieu; Coste, Olivier; Fregeac, Bruno; Mora, Lucile; Cousson-Gélie, Florence

    2016-06-08

    Objective: The “Great Live and Move Challenge” (GLMC) is an intervention designed to promote physical activity (PA) in schools and the community among 6- to 11-year-old schoolchildren and their families.Method: This project, implemented in the Montpellier and Pays Coeur d’Hérault regions since 2013, encourages children to quantify their daily PA level by illustrating each 15 minutes of exercise by an “energy cube”. Based on collaboration between pilots, teachers and policymakers, this project is implemented over a 6-week period in schools, municipalities and recreation centres. “Great Challenge” events are organized to promote PA. The GLMC is also a theory-based intervention based on the tenets of the planned behaviour theory.Results: Since the 2014-2015 edition, 2,243 children have taken part in the GLMC and have accumulated 391,102 “energy cubes”. In addition, more than 30 “Great Challenge” events have been organized. Since its launch during the 2012-2013 school year, the numbers of children who have taken part in the GLMC have been multiplied by 5.58. The mean number of daily “energy cubes” accumulated by children has increased from 4.04 in the first year to 6.22 in 2014-2015.Conclusion: The “energy cube” can provide a measure of the commitment of children and their surrounding community in a comprehensive approach to PA promotion.

  1. The transcriptionally-active MMTV promoter is depleted of histone H1.

    PubMed Central

    Bresnick, E H; Bustin, M; Marsaud, V; Richard-Foy, H; Hager, G L

    1992-01-01

    We have used an ultraviolet light cross-linking and immunoadsorption assay to demonstrate that histones H1 and H2B are bound to the repressed MMTV promoter. Hormone activation results in reduced H1 content with little or no change in H2B. High resolution analysis of the glucocorticoid-inducible DNaseI hypersensitive region demonstrates an NF-1 footprint as well as specific sites of enhanced cleavage on nucleosome B and in the nucleosome B/nucleosome A linker. These results are consistent with a model in which binding of the glucocorticoid receptor to glucocorticoid regulatory elements on the surface of nucleosome B induces a chromatin transition that is necessary for transcription factor (NF-1 and TFIID) recruitment to the MMTV promoter. We hypothesize that association of histone H1 with important cis-elements on the promoter masks these sites, and glucocorticoid-induced displacement of H1 is necessary to expose factor binding sites at the 3' edge of nucleosome B, in the nucleosome B/nucleosome A linker and at the 5' edge of nucleosome A. Images PMID:1311071

  2. Thrombomodulin promotes focal adhesion kinase activation and contributes to angiogenesis by binding to fibronectin

    PubMed Central

    Hsu, Yun-Yan; Shi, Guey-Yueh; Wang, Kuan-Chieh; Ma, Chih-Yuan; Cheng, Tsung-Lin; Wu, Hua-Lin

    2016-01-01

    Angiogenesis promotes tumor growth and metastasis. Cell adhesion molecules interact with the extracellular matrix (ECM) and increase cell adhesion and migration during angiogenesis. Thrombomodulin (TM) is a cell surface transmembrane glycoprotein expressed in endothelial cells. However, the function and significance of TM in cell-matrix interactions and angiogenesis remain unclear. Here, we first demonstrated that recombinant lectin-like domain of TM interacts with an ECM protein, fibronectin, and identified the N-terminal 70-kDa domain of fibronectin as the TM-binding site. Exogenous expression of TM in TM-deficient A2058 melanoma cells enhanced cell adhesion and migration on fibronectin and invasion on Matrigel. In addition, TM increased focal adhesion kinase (FAK) phosphorylation and matrix metalloproteinase-9 production. In mice bearing subcutaneous B16F10 melanoma tumors, immunofluorescence analysis indicated that TM was highly expressed and co-localized with fibronectin on the tumor vasculature. The interaction between TM and fibronectin in tumor blood vessels was also validated by the proximity ligation assay. In human umbilical vein endothelial cells, up-regulation of TM by vascular endothelial growth factor (VEGF), a tumor angiogenic factor, promoted cell adhesion and tube formation, whereas TM knockdown by RNA interference attenuated VEGF-induced cell adhesion and tube formation. In summary, TM promotes angiogenesis by enhancing cell adhesion, migration, and FAK activation through interaction with fibronectin. TM may represent a novel target for inhibiting tumor angiogenesis. PMID:27602495

  3. The c-Jun kinase signaling cascade promotes glial engulfment activity through activation of draper and phagocytic function.

    PubMed

    Macdonald, J M; Doherty, J; Hackett, R; Freeman, M R

    2013-09-01

    After neuronal injury or death glial cells become reactive, exhibiting dramatic changes in morphology and patterns of gene expression and ultimately engulfing neuronal debris. Rapid clearance of degenerating neuronal material is thought to be crucial for suppression of inflammation and promotion of functional recovery. Here we demonstrate that Drosophila c-Jun N-terminal kinase (dJNK) signaling is a critical in vivo mediator of glial engulfment activity. In response to axotomy, we find glial dJNK signals through a cascade involving the upstream mitogen-activated protein kinase kinase kinases Slipper and Tak1, the mitogen-activated protein kinase kinase MKK4, and ultimately the Drosophila activator protein 1 (AP-1) transcriptional complex composed of Jra and Kayak to initiate glial phagocytosis of degenerating axons. Interestingly, loss of dJNK also blocked injury-induced upregulation of Draper levels in glia, and glial-specific overexpression of Draper was sufficient to rescue engulfment defects associated with loss of dJNK signaling. This work identifies that the dJNK pathway is a novel mediator of glial engulfment activity and a primary role for the glial Slipper/Tak1 →MKK4 →dJNK →dAP-1 signaling cascade appears to be activation of draper expression after axon injury.

  4. Active form Notch4 promotes the proliferation and differentiation of 3T3-L1 preadipocytes

    SciTech Connect

    Lai, Peng-Yeh; Tsai, Chong-Bin; Tseng, Min-Jen

    2013-01-18

    Highlights: ► Notch4IC modulates the ERK pathway and cell cycle to promote 3T3-L1 proliferation. ► Notch4IC facilitates 3T3-L1 differentiation by up-regulating proadipogenic genes. ► Notch4IC promotes proliferation during the early stage of 3T3-L1 adipogenesis. ► Notch4IC enhances differentiation during subsequent stages of 3T3-L1 adipogenesis. -- Abstract: Adipose tissue is composed of adipocytes, which differentiate from precursor cells in a process called adipogenesis. Many signal molecules are involved in the transcriptional control of adipogenesis, including the Notch pathway. Previous adipogenic studies of Notch have focused on Notch1 and HES1; however, the role of other Notch receptors in adipogenesis remains unclear. Q-RT-PCR analyses showed that the augmentation of Notch4 expression during the differentiation of 3T3-L1 preadipocytes was comparable to that of Notch1. To elucidate the role of Notch4 in adipogenesis, the human active form Notch4 (N4IC) was transiently transfected into 3T3-L1 cells. The expression of HES1, Hey1, C/EBPδ and PPARγ was up-regulated, and the expression of Pref-1, an adipogenic inhibitor, was down-regulated. To further characterize the effect of N4IC in adipogenesis, stable cells expressing human N4IC were established. The expression of N4IC promoted proliferation and enhanced differentiation of 3T3-L1 cells compared with those of control cells. These data suggest that N4IC promoted proliferation through modulating the ERK pathway and the cell cycle during the early stage of 3T3-L1 adipogenesis and facilitated differentiation through up-regulating adipogenic genes such as C/EBPα, PPARγ, aP2, LPL and HSL during the middle and late stages of 3T3-L1 adipogenesis.

  5. The human glucokinase gene beta-cell-type promoter: an essential role of insulin promoter factor 1/PDX-1 in its activation in HIT-T15 cells.

    PubMed

    Watada, H; Kajimoto, Y; Umayahara, Y; Matsuoka, T; Kaneto, H; Fujitani, Y; Kamada, T; Kawamori, R; Yamasaki, Y

    1996-11-01

    The glycolytic enzyme glucokinase plays a primary role in the glucose-responsive secretion of insulin, and defects of this enzyme can cause NIDDM. As a step toward understanding the molecular basis of glucokinase (GK) gene regulation, we assessed the structure and regulation of the human GK gene beta-cell-type promoter. The results of reporter gene analyses using HIT-T15 cells revealed that the gene promoter was comprised of multiple cis-acting elements, including two primarily important cis-motifs: a palindrome structure, hPal-1, and the insulin gene cis-motif A element-like hUPE3. While both elements were bound specifically by nuclear proteins, it was the homeodomain-containing transcription factor insulin promoter factor 1 (IPF1)/STF-1/PDX-1 that bound to the hUPE3 site: IPF1, when expressed in CHO-K1 cells, became bound to the hUPE3 site and activated transcription. An anti-IPF1 antiserum used in gel-mobility shift analysis supershifted the DNA protein complex formed with the hUPE3 probe and nuclear extracts from HIT-T15 cells, thus supporting the involvement of IPF1 in GK gene activation in HIT-T15 cells. In contrast to the insulin gene, however, neither the synergistic effect of the Pan1 expression on the IPF1-induced promoter activation nor the glucose responsiveness of the activity was observed for the GK gene promoter. These results revealed some conservative but unique features for the transcriptional regulation of the beta-cell-specific genes in humans. Being implicated in insulin and GK gene regulations as a common transcription factor, IPF1/STF-1/PDX-1 is likely to play an essential role in maintaining normal beta-cell functions.

  6. Health promotion activities of sports clubs and coaches, and health and health behaviours in youth participating in sports clubs: the Health Promoting Sports Club study

    PubMed Central

    Kokko, Sami; Selänne, Harri; Alanko, Lauri; Heinonen, Olli J; Korpelainen, Raija; Savonen, Kai; Vasankari, Tommi; Kannas, Lasse; Kujala, Urho M; Aira, Tuula; Villberg, Jari; Parkkari, Jari

    2015-01-01

    Introduction Sports clubs form a potential setting for health promotion, but the research is limited. The aim of the Health Promoting Sports Club (HPSC) study was to elucidate the current health promotion activities of youth sports clubs and coaches, and to investigate the health behaviours and health status of youth participating in sports clubs compared to non-participants. Methods and analysis The study design employs cross-sectional multilevel and multimethod research with aspirations to a prospective cohort study in the next phase. The setting-based variables at sports clubs and coaching levels, and health behaviour variables at the individual level, are investigated using surveys; and total levels of physical activity are assessed using objective accelerometer measurements. Health status variables will be measured by preparticipation screening. The health promotion activity of sports clubs (n=154) is evaluated by club officials (n=313) and coaches (n=281). Coaches and young athletes aged 14–16 (n=759) years evaluate the coaches’ health promotion activity. The survey of the adolescents’ health behaviours consist of two data sets—the first is on their health behaviours and the second is on musculoskeletal complaints and injuries. Data are collected via sports clubs (759 participants) and schools 1650 (665 participants and 983 non-participants). 591 (418 athletes and 173 non-athletes) youth, have already participated in preparticipation screening. Screening consists of detailed personal medical history, electrocardiography, flow-volume spirometry, basic laboratory analyses and health status screening, including posture, muscle balance, and static and dynamic postural control tests, conducted by sports and exercise medicine specialists. Ethics and dissemination The HPSC study is carried out conforming with the declaration of Helsinki. Ethical approval was received from the Ethics Committee of Health Care District of Central Finland. The HPSC study is

  7. Leucine induced dephosphorylation of Sestrin2 promotes mTORC1 activation.

    PubMed

    Kimball, Scot R; Gordon, Bradley S; Moyer, Jenna E; Dennis, Michael D; Jefferson, Leonard S

    2016-08-01

    The studies described herein were designed to explore the role of Sestrin2 in mediating the selective action of leucine to activate mTORC1. The results demonstrate that Sestrin2 is a phosphoprotein and that its phosphorylation state is responsive to the availability of leucine, but not other essential amino acids. Moreover, leucine availability-induced alterations in Sestrin2 phosphorylation correlated temporally and dose dependently with the activation state of mTORC1, there being a reciprocal relationship between the degree of phosphorylation of Sestrin2 and the extent of repression of mTORC1. With leucine deprivation, Sestrin2 became more highly phosphorylated and interacted more strongly with proteins of the GATOR2 complex. Notably, in cells lacking the protein kinase ULK1, the activation state of mTORC1 was elevated in leucine-deficient medium, such that the effect of re-addition of the amino acid was blunted. In contrast, overexpression of ULK1 led to hyperphosphorylation of Sestrin2 and enhanced its interaction with GATOR2. Neither rapamycin nor Torin2 had any effect on Sestrin2 phosphorylation, suggesting that leucine deprivation-induced repression of mTORC1 was not responsible for the action of ULK1 on Sestrin2. Mass spectrometry analysis of Sestrin2 revealed three phosphorylation sites that are conserved across mammalian species. Mutation of the three sites to phospho-mimetic amino acids in exogenously expressed Sestrin2 promoted its interaction with GATOR2 and dramatically repressed mTORC1 even in the presence of leucine. Overall, the results support a model in which leucine selectively promotes dephosphorylation of Sestrin2, causing it to dissociate from and thereby activate GATOR2, leading to activation of mTORC1.

  8. Optically-Induced Neuronal Activity Is Sufficient to Promote Functional Motor Axon Regeneration In Vivo

    PubMed Central

    Ward, Patricia J.; Jones, Laura N.; Mulligan, Amanda; Goolsby, William; Wilhelm, Jennifer C.; English, Arthur W.

    2016-01-01

    Peripheral nerve injuries are common, and functional recovery is very poor. Beyond surgical repair of the nerve, there are currently no treatment options for these patients. In experimental models of nerve injury, interventions (such as exercise and electrical stimulation) that increase neuronal activity of the injured neurons effectively enhance axon regeneration. Here, we utilized optogenetics to determine whether increased activity alone is sufficient to promote motor axon regeneration. In thy-1-ChR2/YFP transgenic mice in which a subset of motoneurons express the light-sensitive cation channel, channelrhodopsin (ChR2), we activated axons in the sciatic nerve using blue light immediately prior to transection and surgical repair of the sciatic nerve. At four weeks post-injury, direct muscle EMG responses evoked with both optical and electrical stimuli as well as the ratio of these optical/electrical evoked EMG responses were significantly greater in mice that received optical treatment. Thus, significantly more ChR2+ axons successfully re-innervated the gastrocnemius muscle in mice that received optical treatment. Sections of the gastrocnemius muscles were reacted with antibodies to Synaptic Vesicle Protein 2 (SV2) to quantify the number of re-occupied motor endplates. The number of SV2+ endplates was greater in mice that received optical treatment. The number of retrogradely-labeled motoneurons following intramuscular injection of cholera toxin subunit B (conjugated to Alexa Fluor 555) was greater in mice that received optical treatment. Thus, the acute (1 hour), one-time optical treatment resulted in robust, long-lasting effects compared to untreated animals as well as untreated axons (ChR2-). We conclude that neuronal activation is sufficient to promote motor axon regeneration, and this regenerative effect is specific to the activated neurons. PMID:27152611

  9. CTGF Promotes Inflammatory Cell Infiltration of the Renal Interstitium by Activating NF-κB

    PubMed Central

    Sánchez-López, Elsa; Rayego, Sandra; Rodrigues-Díez, Raquel; Rodriguez, Javier Sánchez; Rodrigues-Díez, Raúl; Rodríguez-Vita, Juan; Carvajal, Gisselle; Aroeira, Luiz Stark; Selgas, Rafael; Mezzano, Sergio A.; Ortiz, Alberto; Egido, Jesús; Ruiz-Ortega, Marta

    2009-01-01

    Connective tissue growth factor (CTGF) is an important profibrotic factor in kidney diseases. Blockade of endogenous CTGF ameliorates experimental renal damage and inhibits synthesis of extracellular matrix in cultured renal cells. CTGF regulates several cellular responses, including adhesion, migration, proliferation, and synthesis of proinflammatory factors. Here, we investigated whether CTGF participates in the inflammatory process in the kidney by evaluating the nuclear factor-kappa B (NF-κB) pathway, a key signaling system that controls inflammation and immune responses. Systemic administration of CTGF to mice for 24 h induced marked infiltration of inflammatory cells in the renal interstitium (T lymphocytes and monocytes/macrophages) and led to elevated renal NF-κB activity. Administration of CTGF increased renal expression of chemokines (MCP-1 and RANTES) and cytokines (INF-γ, IL-6, and IL-4) that recruit immune cells and promote inflammation. Treatment with a NF-κB inhibitor, parthenolide, inhibited CTGF-induced renal inflammatory responses, including the up-regulation of chemokines and cytokines. In cultured murine tubuloepithelial cells, CTGF rapidly activated the NF-κB pathway and the cascade of mitogen-activated protein kinases, demonstrating crosstalk between these signaling pathways. CTGF, via mitogen-activated protein kinase and NF-κB activation, increased proinflammatory gene expression. These data show that in addition to its profibrotic properties, CTGF contributes to the recruitment of inflammatory cells in the kidney by activating the NF-κB pathway. PMID:19423687

  10. Messages to promote physical activity: Are descriptors of required duration and intensity related to intentions to be more active?

    PubMed Central

    Knox, Emily C. L.; Biddle, Stuart J. H.; Taylor, Ian M.; Latimer-Cheung, Amy E.; Webb, Oliver J.; Sherar, Lauren B.

    2015-01-01

    Introduction: Mass-media campaigns such as, “Change4Life’ in the UK and “get active America” in the US, promote physical activity (PA) recommendations of at least 150 min/week of moderate-to-vigorous PA (MVPA). We investigated whether different messages used in MVPA campaigns were associated with intention to engage in more MVPA. Materials and Methods: Theory of planned behavior (TPB) constructs; subjective norms, affective attitudes, instrumental attitudes and perceived behavioral control (PBC) were applied to explain the associations between campaign messages and intentions to engage in more MVPA. Results: A total of 1412 UK adults completed an online survey on MVPA and TPB. The sample was 70% female and 93% white with 23% reporting meeting PA guidelines. Participants received one of three messages: A walking message either with or without the 150 min/week threshold (WalkT; WalkNT); a physiological description of MVPA with the 150 min/week threshold (PhysT). ANCOVA examined group differences in intention. Path analysis evaluated mediation by TPB variables. ANCOVA identified lower intentions to increase MVPA in group PhysT relative to WalkT and WalkNT (P < 0.001). PBC mediated this relationship in WalkT (β = 0.014, 95% confidence interval [CI] = 0.004–0.028) whereas affective attitudes mediated this relationship in WalkNT (β = 0.059, 95% CI = 0.006–0.113). Conclusions: Campaigns promoting MVPA guidelines need to choose their messages carefully. Messages which exemplified MVPA through walking were associated with higher intentions to increase MVPA than messages using a physiological description. Further, PBC was enhanced when the 150 min/week threshold was promoted alongside the walking exemplar. Future exemplars should be investigated to inform adults how to meet MVPA guidelines. PMID:27462619

  11. Immunization promotion activities: are they effective in encouraging mothers to immunize their children?

    PubMed

    Pérez-Cuevas, R; Reyes, H; Pego, U; Tomé, P; Ceja, K; Flores, S; Gutiérrez, G

    1999-10-01

    Mass media communication is an important strategy for increasing parental uptake and to promote community participation when large-scale immunization activities are carried out. In Mexico, the National Vaccination Council (CONAVA) launches three immunization campaigns every year accompanied by three vaccination promotion campaigns. This study was conducted to assess whether communication activities to promote CONAVA's Second National Health Week (SNHW) were effective in providing information to mothers about the importance of immunizing their children under five years of age and in prompting them to seek immunization services. A probability sample of mothers living in the metropolitan area of Mexico City and having at least one child under five years old was selected for the study. Four outcome variables were defined as measuring the impact of the campaign: (1) mothers' knowledge about the SNHW; (2) mothers' comprehension indicating how well they understood the campaign messages (aware, partly aware and unaware); (3) mothers' motivation, i.e. whether or not they sought out immunizations for their children under the age of five and (4) mothers' opinion of how well they liked the messages. A total of 935 mothers were interviewed; 88.2% knew about the SNHW, 64.3% were aware that the campaign aimed to provide immunizations, and most held a favorable opinion about the messages. Among aware mothers, 87.5% of their children received immunizations. In this group 72.1% were prompted by the information in the campaign to seek immunizations for their children while 27.9% had to be personally invited to participate in the campaign. The latter occurred either when health workers or volunteers visited mothers in their homes or by soliciting mothers' participation as they visited or passed by immunization health posts. In the unaware mothers group, 72.7% of their children received immunizations; 62.5% of the mothers took their children because of information they received through

  12. Trait-associated sequence variation in the bovine growth hormone receptor 1A promoter does not affect promoter activity in vitro.

    PubMed

    Zhou, Y; Jiang, H

    2005-04-01

    Growth hormone (GH) plays a central role in growth and metabolism in cattle by binding to growth hormone receptor (GHR) and stimulating production of insulin-like growth factor 1 (IGF1). Two sequence variations in the promoter transcribing a major GHR mRNA variant, GHR 1A mRNA, have been reported to be associated with quantitative differences in growth rate or blood concentration of IGF1 in cattle. One such variation is in the length of a TG-repeat, being 11 or 16-20; the other variation is in the nucleotide 155 bp upstream from the transcription start site, being G or A. In this study, we determined whether these sequence variations would affect the activity of GHR 1A promoter. We cloned GHR 1A promoters bearing different sequence variations and linked each of them to a reporter gene. Transient transfection analyses revealed that these promoter-reporter constructs did not differ in reporter gene expression. Cotransfection analyses demonstrated that they also did not differ in activation by hepatocyte nuclear factor 4alpha, hepatocyte nuclear factor 4gamma and nuclear receptor subfamily 2 group F member 2, known transcription factors for bovine GHR 1A promoter. These in vitro results, together with a previous observation that neither the nucleotide 155 bp upstream from the transcription start site nor the TG-repeat was part of the GHR 1A promoter region interacting with nuclear proteins from bovine liver, do not support a cause-effect relationship between the reported sequence variations and the associated changes in growth rate or blood IGF1 concentration in cattle.

  13. Ketosis may promote brain macroautophagy by activating Sirt1 and hypoxia-inducible factor-1.

    PubMed

    McCarty, Mark F; DiNicolantonio, James J; O'Keefe, James H

    2015-11-01

    Ketogenic diets are markedly neuroprotective, but the basis of this effect is still poorly understood. Recent studies demonstrate that ketone bodies increase neuronal levels of hypoxia-inducible factor-1α (HIF-1α), possibly owing to succinate-mediated inhibition of prolyl hydroxylase activity. Moreover, there is reason to suspect that ketones can activate Sirt1 in neurons, in part by increasing cytoplasmic and nuclear levels of Sirt1's obligate cofactor NAD(+). Another recent study has observed reduced activity of mTORC1 in the hippocampus of rats fed a ketogenic diet - an effect plausibly attributable to Sirt1 activation. Increased activities of HIF-1 and Sirt1, and a decrease in mTORC1 activity, could be expected to collaborate in the induction of neuronal macroautophagy. Considerable evidence points to moderate up-regulation of neuronal autophagy as a rational strategy for prevention of neurodegenerative disorders; elimination of damaged mitochondria that overproduce superoxide, as well as clearance of protein aggregates that mediate neurodegeneration, presumably contribute to this protection. Hence, autophagy may mediate some of the neuroprotective benefits of ketogenic diets. Brain-permeable agents which activate AMP-activated kinase, such as metformin and berberine, as well as the Sirt1 activator nicotinamide riboside, can also boost neuronal autophagy, and may have potential for amplifying the impact of ketogenesis on this process. Since it might not be practical for most people to adhere to ketogenic diets continuously, alternative strategies are needed to harness the brain-protective potential of ketone bodies. These may include ingestion of medium-chain triglycerides or coconut oil, intermittent ketogenic dieting, and possibly the use of supplements that promote hepatic ketogenesis - notably carnitine and hydroxycitrate - in conjunction with dietary regimens characterized by long daily episodes of fasting or carbohydrate avoidance.

  14. Endothelial cells microparticle-associated protein disulfide isomerase promotes platelet activation in metabolic syndrome

    PubMed Central

    Li, Yi-hui; Song, Dai-jun; Chen, Tong-shuai; Zhang, Wei; Zhong, Ming; Zhang, Yun; Xing, Yan-qiu; Wang, Zhi-hao

    2016-01-01

    Background Metabolic syndrome (MetS) is a common challenge in the world, and the platelet activation is enhanced in MetS patients. However, the fundamental mechanism that underlies platelet activation in MetS remains incompletely understood. Endothelial cells are damaged seriously in MetS patients, then they release more endothelial microparticles (EMPs). After all, whether the EMPs participate in platelet activation is still obscure. If they were, how did they work? Results We demonstrated that the levels of EMPs, PMPs (platelet derived microparticles) and microparticle-carried-PDI activity increased in MetS patients. IR endothelial cells released more EMPs, the EMP-PDI was more activated. EMPs can enhance the activation of CD62P, GPIIb/IIIa and platelet aggregation and this process can be partly inhibited by PDI inhibitor such as RL90 and rutin. Activated platelets stimulated by EMPs expressed more PDI on cytoplasm and released more PMPs. Materials and Methods We obtained plasma from 23 MetS patients and 8 normal healthy controls. First we built insulin resistance (IR) model of human umbilical vein endothelial cells (HUVECs), and then we separated EMPs from HUVECs culture medium and used these EMPs to stimulate platelets. Levels of microparticles, P-selectin(CD62P), Glycoprotein IIb/IIIa (GPIIb/IIIa) were detected by flow cytometry and levels of EMPs were detected by enzyme-linked immunosorbent assay (ELISA). The protein disulfide isomerase (PDI) activity was detected by insulin transhydrogenase assay. Platelet aggregation was assessed by turbidimetry. Conclusion EMPs can promote the activation of GPIIb/IIIa in platelets and platelet aggregation by the PDI which is carried on the surface of EMPs. PMID:27825126

  15. Dynamic Effects of Topoisomerase I Inhibition on R-Loops and Short Transcripts at Active Promoters.

    PubMed

    Marinello, Jessica; Bertoncini, Stefania; Aloisi, Iris; Cristini, Agnese; Malagoli Tagliazucchi, Guidantonio; Forcato, Mattia; Sordet, Olivier; Capranico, Giovanni

    2016-01-01

    Topoisomerase I-DNA-cleavage complexes (Top1cc) stabilized by camptothecin (CPT) have specific effects at transcriptional levels. We recently reported that Top1cc increase antisense transcript (aRNAs) levels at divergent CpG-island promoters and, transiently, DNA/RNA hybrids (R-loop) in nuclear and mitochondrial genomes of colon cancer HCT116 cells. However, the relationship between R-loops and aRNAs was not established. Here, we show that aRNAs can form R-loops in N-TERA-2 cells under physiological conditions, and that promoter-associated R-loops are somewhat increased and extended in length immediately upon cell exposure to CPT. In contrast, persistent Top1ccs reduce the majority of R-loops suggesting that CPT-accumulated aRNAs are not commonly involved in R-loops. The enhancement of aRNAs by Top1ccs is present both in human colon cancer HCT116 cells and WI38 fibroblasts suggesting a common response of cancer and normal cells. Although Top1ccs lead to DSB and DDR kinases activation, we do not detect a dependence of aRNA accumulation on ATM or DNA-PK activation. However, we showed that the cell response to persistent Top1ccs can involve an impairment of aRNA turnover rather than a higher synthesis rate. Finally, a genome-wide analysis shows that persistent Top1ccs also determine an accumulation of sense transcripts at 5'-end gene regions suggesting an increased occurrence of truncated transcripts. Taken together, the results indicate that Top1 may regulate transcription initiation by modulating RNA polymerase-generated negative supercoils, which can in turn favor R-loop formation at promoters, and that transcript accumulation at TSS is a response to persistent transcriptional stress by Top1 poisoning.

  16. Thyroid hormone and vitamin D regulate VGF expression and promoter activity

    PubMed Central

    Lewis, Jo E; Brameld, John M; Hill, Phil; Wilson, Dana; Barrett, Perry; Ebling, Francis J P; Jethwa, Preeti H

    2016-01-01

    The Siberian hamster (Phodopus sungorus) survives winter by decreasing food intake and catabolizing abdominal fat reserves, resulting in a sustained, profound loss of body weight. Hypothalamic tanycytes are pivotal for this process. In these cells, short-winter photoperiods upregulate deiodinase 3, an enzyme that regulates thyroid hormone availability, and downregulate genes encoding components of retinoic acid (RA) uptake and signaling. The aim of the current studies was to identify mechanisms by which seasonal changes in thyroid hormone and RA signaling from tanycytes might ultimately regulate appetite and energy expenditure. proVGF is one of the most abundant peptides in the mammalian brain, and studies have suggested a role for VGF-derived peptides in the photoperiodic regulation of body weight in the Siberian hamster. In silico studies identified possible thyroid and vitamin D response elements in the VGF promoter. Using the human neuroblastoma SH-SY5Y cell line, we demonstrate that RA increases endogenous VGF expression (P<0.05) and VGF promoter activity (P<0.0001). Similarly, treatment with 1,25-dihydroxyvitamin D3 increased endogenous VGF mRNA expression (P<0.05) and VGF promoter activity (P<0.0001), whereas triiodothyronine (T3) decreased both (P<0.01 and P<0.0001). Finally, intra-hypothalamic administration of T3 blocked the short day-induced increase in VGF expression in the dorsomedial posterior arcuate nucleus of Siberian hamsters. Thus, we conclude that VGF expression is a likely target of photoperiod-induced changes in tanycyte-derived signals and is potentially a regulator of seasonal changes in appetite and energy expenditure. PMID:26643910

  17. Ligand structural motifs can decouple glucocorticoid receptor transcriptional activation from target promoter occupancy.

    PubMed

    Blind, Raymond D; Pineda-Torra, Inés; Xu, Yong; Xu, H Eric; Garabedian, Michael J

    2012-04-20

    Glucocorticoid (GC) induction of the tyrosine aminotransferase (TAT) gene by the glucocorticoid receptor (GR) is a classic model used to investigate steroid-regulated gene expression. Classic studies analyzing GC-induction of the TAT gene demonstrated that despite having very high affinity for GR, some steroids cannot induce maximal TAT enzyme activity, but the molecular basis for this phenomenon is unknown. Here, we used RT-PCR and chromatin immunoprecipitation to determine TAT mRNA accumulation and GR recruitment to the TAT promoter (TAT-GRE) in rat hepatoma cells induced by seven GR ligands: dexamethasone (DEX), cortisol (CRT), corticosterone (CCS), 11-deoxycorticosterone (DOC), aldosterone (ALD), progesterone (PRG) and 17-hydroxyprogesterone (17P). As expected, DEX, CRT, CCS and ALD all induced both TAT mRNA and GR recruitment to the TAT-GRE, while PRG and 17P did not. However, while DOC could not induce significant TAT mRNA, it did induce robust GR occupancy of the TAT-GRE. DOC also induced recruitment of the histone acetyltransferase p300 to the TAT-GRE as efficiently as DEX. These DOC-induced effects recapitulated at another GR target gene (sulfonyltransferase 1A1), and DOC also failed to promote the multiple changes in gene expression required for glucocorticoid-dependent 3T3-L1 adipocyte differentiation. Structural simulations and protease sensitivity assays suggest that DOC and DEX induce different conformations in GR. Thus, although steroids that bind GR with high affinity can induce GR and p300 occupancy of target promoters, they may not induce a conformation of GR capable of activating transcription.

  18. The metastasis-promoting phosphatase PRL-3 shows activity toward phosphoinositides.

    PubMed

    McParland, Victoria; Varsano, Giulia; Li, Xun; Thornton, Janet; Baby, Jancy; Aravind, Ajay; Meyer, Christoph; Pavic, Karolina; Rios, Pablo; Köhn, Maja

    2011-09-06

    Phosphatase of regenerating liver 3 (PRL-3) is suggested as a biomarker and therapeutic target in several cancers. It has a well-established causative role in cancer metastasis. However, little is known about its natural substrates, pathways, and biological functions, and only a few protein substrates have been suggested so far. To improve our understanding of the substrate specificity and molecular determinants of PRL-3 activity, the wild-type (WT) protein, two supposedly catalytically inactive mutants D72A and C104S, and the reported hyperactive mutant A111S were tested in vitro for substrate specificity and activity toward phosphopeptides and phosphoinositides (PIPs), their structural stability, and their ability to promote cell migration using stable HEK293 cell lines. We discovered that WT PRL-3 does not dephosphorylate the tested phosphopeptides in vitro. However, as shown by two complementary biochemical assays, PRL-3 is active toward the phosphoinositide PI(4,5)P(2). Our experimental results substantiated by molecular docking studies suggest that PRL-3 is a phosphatidylinositol 5-phosphatase. The C104S variant was shown to be not only catalytically inactive but also structurally destabilized and unable to promote cell migration, whereas WT PRL-3 promotes cell migration. The D72A mutant is structurally stable and does not dephosphorylate the unnatural substrate 3-O-methylfluorescein phosphate (OMFP). However, we observed residual in vitro activity of D72A against PI(4,5)P(2), and in accordance with this, it exhibits the same cellular phenotype as WT PRL-3. Our analysis of the A111S variant shows that the hyperactivity toward the unnatural OMFP substrate is not apparent in dephosphorylation assays with phosphoinositides: the mutant is completely inactive against PIPs. We observed significant structural destabilization of this variant. The cellular phenotype of this mutant equals that of the catalytically inactive C104S mutant. These results provide a possible

  19. Pim1 promotes human prostate cancer cell tumorigenicity and c-MYC transcriptional activity

    PubMed Central

    2010-01-01

    Background The serine/threonine kinase PIM1 has been implicated as an oncogene in various human cancers including lymphomas, gastric, colorectal and prostate carcinomas. In mouse models, Pim1 is known to cooperate with c-Myc to promote tumorigenicity. However, there has been limited analysis of the tumorigenic potential of Pim1 overexpression in benign and malignant human prostate cancer cells in vivo. Methods We overexpressed Pim1 in three human prostate cell lines representing different disease stages including benign (RWPE1), androgen-dependent cancer (LNCaP) and androgen-independent cancer (DU145). We then analyzed in vitro and in vivo tumorigenicity as well as the effect of Pim1 overexpression on c-MYC transcriptional activity by reporter assays and gene expression profiling using an inducible MYC-ER system. To validate that Pim1 induces tumorigenicity and target gene expression by modulating c-MYC transcriptional activity, we inhibited c-MYC using a small molecule inhibitor (10058-F4) or RNA interference. Results Overexpression of Pim1 alone was not sufficient to convert the benign RWPE1 cell to malignancy although it enhanced their proliferation rates when grown as xenografts in vivo. However, Pim1 expression enhanced the in vitro and in vivo tumorigenic potentials of the human prostate cancer cell lines LNCaP and DU145. Reporter assays revealed increased c-MYC transcriptional activity in Pim1-expressing cells and mRNA expression profiling demonstrated that a large fraction of c-MYC target genes were also regulated by Pim1 expression. The c-MYC inhibitor 10058-F4 suppressed the tumorigenicity of Pim1-expressing prostate cancer cells. Interestingly, 10058-F4 treatment also led to a reduction of Pim1 protein but not mRNA. Knocking-down c-MYC using short hairpin RNA reversed the effects of Pim1 on Pim1/MYC target genes. Conclusion Our results suggest an in vivo role of Pim1 in promoting prostate tumorigenesis although it displayed distinct oncogenic activities

  20. Purified Kinesin Promotes Vesicle Motility and Induces Active Sliding Between Microtubules In vitro

    NASA Astrophysics Data System (ADS)

    Urrutia, Raul; McNiven, Mark A.; Albanesi, Joseph P.; Murphy, Douglas B.; Kachar, Bechara

    1991-08-01

    We examined the ability of kinesin to support the movement of adrenal medullary chromaffin granules on microtubules in a defined in vitro system. We found that kinesin and ATP are all that is required to support efficient (33% vesicle motility) and rapid (0.4-0.6 μ m/s) translocation of secretory granule membranes on microtubules in the presence of a low-salt motility buffer. Kinesin also induced the formation of microtubule asters in this buffer, with the plus ends of microtubules located at the center of each aster. This observation indicates that kinesin is capable of promoting active sliding between microtubules toward their respective plus ends, a movement analogous to that of anaphase b in the mitotic spindle. The fact that vesicle translocation, microtubule sliding, and microtubule-dependent kinesin ATPase activities are all enhanced in low-salt buffer establishes a functional parallel between this translocator and other motility ATPases, myosin, and dynein.

  1. Strong and coverage-independent promotion of catalytic activity of a noble metal by subsurface vanadium

    NASA Astrophysics Data System (ADS)

    Reichl, Wolfgang; Hayek, Konrad

    2003-07-01

    While common bimetallic surfaces have a variable composition, the stable subsurface alloys of V/Rh and V/Pd are characterised by a purely noble metal-terminated surface and the second metal positioned in near-surface layers. The uniform composition of the topmost surface layer excludes conventional ensemble effects in catalysis, and the activity of the surface can be controlled by the metal loading and by the temperature of annealing. For example, the activity of a polycrystalline Rh surface in CO hydrogenation is significantly increased by promotion with subsurface vanadium. The modification of the subsurface layer with a different metal must be considered a promising approach to improve the catalytic properties of a metal surface.

  2. Epsin2 promotes polarity establishment and meiotic division through activating Cdc42 in mouse oocyte

    PubMed Central

    Zhang, Jiaqi; Liu, Xiaohui; Ma, Rujun; Hou, Xiaojing; Ge, Juan; Wang, Qiang

    2016-01-01

    Epsins are a conserved family of endocytic adaptors essential for diverse biological events. However, its role in oocytes remains completely unknown. Here, we report that specific depletion of Epsin2 in mouse oocytes significantly disrupts meiotic progression. Confocal microscopy reveals that Epsin2 knockdown results in the failure of actin cap formation and polar body extrusion during meiosis, indicative of the importance of Epsin2 in polarity establishment and cytokinesis. In addition, spindle defects and chromosome misalignment are readily observed in oocytes depleted of Epsin2. Moreover, we find that Epsin2 knockdown markedly decreases the activity of Cdc42 in oocytes and importantly, that the dominant-positive mutant of Cdc42 (Cdc42Q61L) is capable of partially rescuing the deficient phenotypes of Epsin2-knockdown oocytes. Together, our data identify Epsin2 as a novel player in regulating oocyte maturation, and demonstrate that Epsin2 promotes polarity establishment and meiotic division via activating Cdc42. PMID:27463009

  3. Retinoic Acid Can Exacerbate T Cell Intrinsic TLR2 Activation to Promote Tolerance

    PubMed Central

    Nguyen, Vivien; Pearson, Kandyce; Kim, Jee-Hyun; Kamdar, Karishma; DePaolo, R. William

    2015-01-01

    The contribution of vitamin A to immune health has been well established. However, recent evidence indicates that its active metabolite, retinoic acid (RA), has the ability to promote both tolerogenic and inflammatory responses. While the outcome of RA-mediated immunity is dependent upon the immunological status of the tissue, the contribution of specific innate signals influencing this response have yet to be delineated. Here, we found that treatment with RA can dampen inflammation during intestinal injury. Importantly, we report a novel and unexpected requirement for TLR2 in RA-mediated suppression. Our data demonstrate that RA treatment enhances TLR2-dependent IL-10 production from T cells and this, in turn, potentiates T regulatory cell (TREG) generation without the need for activation of antigen presenting cells. These data also suggest that combinatorial therapy using RA and TLR2 ligands may be advantageous in the design of therapies to treat autoimmune or inflammatory disease. PMID:25826367

  4. Ran-dependent TPX2 activation promotes acentrosomal microtubule nucleation in neurons

    PubMed Central

    Chen, Wen-Shin; Chen, Yi-Ju; Huang, Yung-An; Hsieh, Bing-Yuan; Chiu, Ho-Chieh; Kao, Pei-Ying; Chao, Chih-Yuan; Hwang, Eric

    2017-01-01

    The microtubule (MT) cytoskeleton is essential for the formation of morphologically appropriate neurons. The existence of the acentrosomal MT organizing center in neurons has been proposed but its identity remained elusive. Here we provide evidence showing that TPX2 is an important component of this acentrosomal MT organizing center. First, neurite elongation is compromised in TPX2-depleted neurons. In addition, TPX2 localizes to the centrosome and along the neurite shaft bound to MTs. Depleting TPX2 decreases MT formation frequency specifically at the tip and the base of the neurite, and these correlate precisely with the regions where active GTP-bound Ran proteins are enriched. Furthermore, overexpressing the downstream effector of Ran, importin, compromises MT formation and neuronal morphogenesis. Finally, applying a Ran-importin signaling interfering compound phenocopies the effect of TPX2 depletion on MT dynamics. Together, these data suggest a model in which Ran-dependent TPX2 activation promotes acentrosomal MT nucleation in neurons. PMID:28205572

  5. Terpenoids with neurite outgrowth-promoting activity from the branches and leaves of Illicium merrillianum.

    PubMed

    Tian, Xin-Hui; Yue, Rong-Cai; Fang, Xin; Zhang, Jian-Ping; Wang, Guo-Wei; Shan, Lei; Zhang, Wei-Dong; Shen, Yun-Heng

    2016-05-01

    Eighteen terpenoids (1-18) were isolated from Illicium merrillianum. Compound 1 was identified as new compound, and its structure was established by comprehensive spectroscopic analysis and single-crystal X-ray diffraction. All compounds were evaluated for nerve growth factor (NGF)-mediated neurite outgrowth activity using rat pheochromocytoma (PC12) cells as a model system of neuronal differentiation. Compounds 1, 3, 18 showed significant neurite outgrowth-promoting activity in the presence of 20 ng/ml NGF in a dose-dependent manner at concentrations of 1-100 μM after 24-h treatment. Subtle difference of functional groups at C-2 position in hopane-type triterpene resulted in enormous bioactivity difference, compound 1 was neurotrophic but 2 was cytotoxic.

  6. Promotion of haematopoietic activity in embryonic stem cells by the aorta-gonad-mesonephros microenvironment

    SciTech Connect

    Krassowska, Anna; Gordon-Keylock, Sabrina; Samuel, Kay; Gilchrist, Derek; Dzierzak, Elaine; Oostendorp, Robert; Forrester, Lesley M. . E-mail: l.forrester@ed.ac.uk; Ansell, John D.

    2006-11-01

    We investigated whether the in vitro differentiation of ES cells into haematopoietic progenitors could be enhanced by exposure to the aorta-gonadal-mesonephros (AGM) microenvironment that is involved in the generation of haematopoietic stem cells (HSC) during embryonic development. We established a co-culture system that combines the requirements for primary organ culture and differentiating ES cells and showed that exposure of differentiating ES cells to the primary AGM region results in a significant increase in the number of ES-derived haematopoietic progenitors. Co-culture of ES cells on the AM20-1B4 stromal cell line derived from the AGM region also increases haematopoietic activity. We conclude that factors promoting the haematopoietic activity of differentiating ES cells present in primary AGM explants are partially retained in the AM20.1B4 stromal cell line and that these factors are likely to be different to those required for adult HSC maintenance.

  7. Fischer-Tropsch activity for non-promoted cobalt-on-alumina catalysts

    DOEpatents

    Singleton, Alan H.; Oukaci, Rachid; Goodwin, James G.

    2001-01-01

    Cobalt catalysts, and processes employing these inventive catalysts, for hydrocarbon synthesis. The inventive catalyst comprises cobalt on an alumina support and is not promoted with any noble or near noble metals. In one aspect of the invention, the alumina support preferably includes a dopant in an amount effective for increasing the activity of the inventive catalyst. The dopant is preferably a titanium dopant. In another aspect of the invention, the cobalt catalyst is preferably reduced in the presence of hydrogen at a water vapor partial pressure effective to increase the activity of the cobalt catalyst for hydrocarbon synthesis. The water vapor partial pressure is preferably in the range of from 0 to about 0.1 atmospheres.

  8. Axl Phosphorylates Elmo Scaffold Proteins To Promote Rac Activation and Cell Invasion

    PubMed Central

    Abu-Thuraia, Afnan; Gauthier, Rosemarie; Chidiac, Rony; Fukui, Yoshinori; Screaton, Robert A.; Gratton, Jean-Philippe

    2014-01-01

    The receptor tyrosine kinase Axl contributes to cell migration and invasion. Expression of Axl correlates with metastatic progression in cancer patients, yet the specific signaling events promoting invasion downstream of Axl are poorly defined. Herein, we report Elmo scaffolds to be direct substrates and binding partners of Axl. Elmo proteins are established to interact with Dock family guanine nucleotide exchange factors to control Rac-mediated cytoskeletal dynamics. Proteomics and mutagenesis studies reveal that Axl phosphorylates Elmo1/2 on a conserved carboxyl-terminal tyrosine residue. Upon Gas6-dependent activation of Axl, endogenous Elmo2 becomes phosphorylated on Tyr-713 and enters into a physical complex with Axl in breast cancer cells. Interfering with Elmo2 expression prevented Gas6-induced Rac1 activation in breast cancer cells. Similarly to blocking of Axl, Elmo2 knockdown or pharmacological inhibition of Dock1 abolishes breast cancer cell invasion. Interestingly, Axl or Elmo2 knockdown diminishes breast cancer cell proliferation. Rescue of Elmo2 knockdown cells with the wild-type protein but not with Elmo2 harboring Tyr-713-Phe mutations restores cell invasion and cell proliferation. These results define a new mechanism by which Axl promotes cell proliferation and invasion and identifies inhibition of the Elmo-Dock pathway as a potential therapeutic target to stop Axl-induced metastases. PMID:25332238

  9. Acute DNA damage activates the tumour suppressor p53 to promote radiation-induced lymphoma

    PubMed Central

    Lee, Chang-Lung; Castle, Katherine D.; Moding, Everett J.; Blum, Jordan M.; Williams, Nerissa; Luo, Lixia; Ma, Yan; Borst, Luke B.; Kim, Yongbaek; Kirsch, David G.

    2015-01-01

    Genotoxic cancer therapies, such as chemoradiation, cause haematological toxicity primarily by activating the tumour suppressor p53. While inhibiting p53-mediated cell death during cancer therapy ameliorates haematologic toxicity, whether it also impacts carcinogenesis remains unclear. Here we utilize a mouse model of inducible p53 short hairpin RNA (shRNA) to show that temporarily blocking p53 during total-body irradiation (TBI) not only ameliorates acute toxicity, but also improves long-term survival by preventing lymphoma development. Using KrasLA1 mice, we show that TBI promotes the expansion of a rare population of thymocytes that express oncogenic KrasG12D. However, blocking p53 during TBI significantly suppresses the expansion of KrasG12D-expressing thymocytes. Mechanistically, bone marrow transplant experiments demonstrate that TBI activates p53 to decrease the ability of bone marrow cells to suppress lymphoma development through a non-cell-autonomous mechanism. Together, our results demonstrate that the p53 response to acute DNA damage promotes the development of radiation-induced lymphoma. PMID:26399548

  10. Anti-DKK1 antibody promotes bone fracture healing through activation of β-catenin signaling.

    PubMed

    Jin, Hongting; Wang, Baoli; Li, Jia; Xie, Wanqing; Mao, Qiang; Li, Shan; Dong, Fuqiang; Sun, Yan; Ke, Hua-Zhu; Babij, Philip; Tong, Peijian; Chen, Di

    2015-02-01

    In this study we investigated if Wnt/β-catenin signaling in mesenchymal progenitor cells plays a role in bone fracture repair and if DKK1-Ab promotes fracture healing through activation of β-catenin signaling. Unilateral open transverse tibial fractures were created in CD1 mice and in β-catenin(Prx1ER) conditional knockout (KO) and Cre-negative control mice (C57BL/6 background). Bone fracture callus tissues were collected and analyzed by radiography, micro-CT (μCT), histology, biomechanical testing and gene expression analysis. The results demonstrated that treatment with DKK1-Ab promoted bone callus formation and increased mechanical strength during the fracture healing process in CD1 mice. DKK1-Ab enhanced fracture repair by activation of endochondral ossification. The normal rate of bone repair was delayed when the β-catenin gene was conditionally deleted in mesenchymal progenitor cells during the early stages of fracture healing. DKK1-Ab appeared to act through β-catenin signaling to enhance bone repair since the beneficial effect of DKK1-Ab was abrogated in β-catenin(Prx1ER) conditional KO mice. Further understanding of the signaling mechanism of DKK1-Ab in bone formation and bone regeneration may facilitate the clinical translation of this anabolic agent into therapeutic intervention.

  11. Activation of Notch1 synergizes with multiple pathways in promoting castration-resistant prostate cancer

    PubMed Central

    Stoyanova, Tanya; Riedinger, Mireille; Lin, Shu; Faltermeier, Claire M.; Smith, Bryan A.; Zhang, Kelvin X.; Going, Catherine C.; Goldstein, Andrew S.; Lee, John K.; Drake, Justin M.; Rice, Meghan A.; Hsu, En-Chi; Nowroozizadeh, Behdokht; Castor, Brandon; Orellana, Sandra Y.; Blum, Steven M.; Cheng, Donghui; Pienta, Kenneth J.; Reiter, Robert E.; Pitteri, Sharon J.; Huang, Jiaoti; Witte, Owen N.

    2016-01-01

    Metastatic castration-resistant prostate cancer (CRPC) is the primary cause of prostate cancer-specific mortality. Defining new mechanisms that can predict recurrence and drive lethal CRPC is critical. Here, we demonstrate that localized high-risk prostate cancer and metastatic CRPC, but not benign prostate tissues or low/intermediate-risk prostate cancer, express high levels of nuclear Notch homolog 1, translocation-associated (Notch1) receptor intracellular domain. Chronic activation of Notch1 synergizes with multiple oncogenic pathways altered in early disease to promote the development of prostate adenocarcinoma. These tumors display features of epithelial-to-mesenchymal transition, a cellular state associated with increased tumor aggressiveness. Consistent with its activation in clinical CRPC, tumors driven by Notch1 intracellular domain in combination with multiple pathways altered in prostate cancer are metastatic and resistant to androgen deprivation. Our study provides functional evidence that the Notch1 signaling axis synergizes with alternative pathways in promoting metastatic CRPC and may represent a new therapeutic target for advanced prostate cancer. PMID:27694579

  12. Activation of GLP-1 Receptor Promotes Bone Marrow Stromal Cell Osteogenic Differentiation through β-Catenin

    PubMed Central

    Meng, Jingru; Ma, Xue; Wang, Ning; Jia, Min; Bi, Long; Wang, Yunying; Li, Mingkai; Zhang, Huinan; Xue, Xiaoyan; Hou, Zheng; Zhou, Ying; Yu, Zhibin; He, Gonghao; Luo, Xiaoxing

    2016-01-01

    Summary Glucagon-like peptide 1 (GLP-1) plays an important role in regulating bone remodeling, and GLP-1 receptor agonist shows a positive relationship with osteoblast activity. However, GLP-1 receptor is not found in osteoblast, and the mechanism of GLP-1 receptor agonist on regulating bone remodeling is unclear. Here, we show that the GLP-1 receptor agonist exendin-4 (Ex-4) promoted bone formation and increased bone mass and quality in a rat unloading-induced bone loss model. These functions were accompanied by an increase in osteoblast number and serum bone formation markers, while the adipocyte number was decreased. Furthermore, GLP-1 receptor was detected in bone marrow stromal cells (BMSCs), but not in osteoblast. Activation of GLP-1 receptor by Ex-4 promoted the osteogenic differentiation and inhibited BMSC adipogenic differentiation through regulating PKA/β-catenin and PKA/PI3K/AKT/GSK3β signaling. These findings reveal that GLP-1 receptor regulates BMSC osteogenic differentiation and provide a molecular basis for therapeutic potential of GLP-1 against osteoporosis. PMID:26947974

  13. Cyclin F suppresses B-Myb