Sample records for actively promotes initiation

  1. Tumor initiating and promoting activities of various benzo(a)pyrene metabolites in mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Slaga, T J; Bracken, W M; Viaje, A; Berry, D L; Fischer, S M; Miller, D R; Levin, W; Conney, A H; Yagi, H; Jerina, D M


    The skin tumor-initiating activities of the twelve isomeric phenols of BP revealed that 2-OHBP was as potent as BP while 11-OHBP was moderately active and the others were weak or inactive. However, 2-OHBP has not been shown to be formed from BP in the skin or any other tissue. The (-)-trans-7,8-diol of BP skin was found to be more active as a skin tumor initiator than BP suggesting that it is a proximal carcinogen. The data on carcinogenicity, mutagenicity and metabolism suggest that BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide is the ultimate carcinogenic form of BP. The skin tumor-initiating activities of the various BP metabolites correlate very well with their complete carcinogenic in mouse skin except for BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide. It was found to have skin tumor initiating activity but not complete carcinogenic activity. However, BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide was found to be a very potent complete carcinogen in newborn mice. It is possible that BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide is only a tumor initiator in which a promoting stimulus must be supplied for carcinogenic activity. A natural tumor promoting stimulus may be present in the newborn mouse. There is also a good correlation between the skin tumor initiating activities of the various BP metabolites and their mutagenic activity in the V79 mammalian cell mediated mutagenesis system.


    DEFF Research Database (Denmark)

    Gish, Liv


    In new product development a central activity is to provide new ideas. Over the last decades experiences with stimulating employee creativity and establishing idea promoting initiatives have been made in industrial practice. Such initiatives are often labeled Idea Management – a research field...... with a growing interest. In this paper I examine three different idea promoting initiatives carried out in Grundfos, a leading pump manufacturer. In the analysis I address what understandings of idea work are inscribed in the initiatives and what role these initiatives play in the organization with respect...... understandings of idea work are inscribed in the idea promoting initiatives as they to some degree have to fit with the understandings embedded in practice in order to work....

  3. Using the tax system to promote physical activity: critical analysis of Canadian initiatives. (United States)

    von Tigerstrom, Barbara; Larre, Tamara; Sauder, Joanne


    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.

  4. Core promoter-specific gene regulation: TATA box selectivity and Initiator-dependent bi-directionality of serum response factor-activated transcription. (United States)

    Xu, Muyu; Gonzalez-Hurtado, Elsie; Martinez, Ernest


    Gene-specific activation by enhancers involves their communication with the basal RNA polymerase II transcription machinery at the core promoter. Core promoters are diverse and may contain a variety of sequence elements such as the TATA box, the Initiator (INR), and the downstream promoter element (DPE) recognized, respectively, by the TATA-binding protein (TBP) and TBP-associated factors of the TFIID complex. Core promoter elements contribute to the gene selectivity of enhancers, and INR/DPE-specific enhancers and activators have been identified. Here, we identify a TATA box-selective activating sequence upstream of the human β-actin (ACTB) gene that mediates serum response factor (SRF)-induced transcription from TATA-dependent but not INR-dependent promoters and requires the TATA-binding/bending activity of TBP, which is otherwise dispensable for transcription from a TATA-less promoter. The SRF-dependent ACTB sequence is stereospecific on TATA promoters but activates in an orientation-independent manner a composite TATA/INR-containing promoter. More generally, we show that SRF-regulated genes of the actin/cytoskeleton/contractile family tend to have a TATA box. These results suggest distinct TATA-dependent and INR-dependent mechanisms of TFIID-mediated transcription in mammalian cells that are compatible with only certain stereospecific combinations of activators, and that a TBP-TATA binding mechanism is important for SRF activation of the actin/cytoskeleton-related gene family.

  5. Promoting Nature-Based Activity for People With Mental Illness Through the US "Exercise Is Medicine" Initiative. (United States)

    Maier, Julie; Jette, Shannon


    Nature-based physical activity programming (e.g., countryside walks, hiking, horseback riding) has been found to be an effective way to help improve the health of people with mental illness. Exercise referral initiatives, whereby health practitioners prescribe exercise in an attempt to prevent or treat chronic illnesses, have helped make such nature-based activities accessible to this population in the United Kingdom and Australia; however, there is a dearth of research related to the most prominent exercise referral program in the United States: Exercise is Medicine. Taking into account the barriers to physical activity faced by people with mental illness, we explore how nature-based programming for this population might be mobilized in the United States through the growing Exercise is Medicine initiative.

  6. A Gammaherpesvirus Complement Regulatory Protein Promotes Initiation of Infection by Activation of Protein Kinase Akt/PKB (United States)

    Steer, Beatrix; Adler, Barbara; Jonjic, Stipan; Stewart, James P.; Adler, Heiko


    Background Viruses have evolved to evade the host's complement system. The open reading frames 4 (ORF4) of gammaherpesviruses encode homologs of regulators of complement activation (RCA) proteins, which inhibit complement activation at the level of C3 and C4 deposition. Besides complement regulation, these proteins are involved in heparan sulfate and glycosaminoglycan binding, and in case of MHV-68, also in viral DNA synthesis in macrophages. Methodology/Principal Findings Here, we made use of MHV-68 to study the role of ORF4 during infection of fibroblasts. While attachment and penetration of virions lacking the RCA protein were not affected, we observed a delayed delivery of the viral genome to the nucleus of infected cells. Analysis of the phosphorylation status of a variety of kinases revealed a significant reduction in phosphorylation of the protein kinase Akt in cells infected with ORF4 mutant virus, when compared to cells infected with wt virus. Consistent with a role of Akt activation in initial stages of infection, inhibition of Akt signaling in wt virus infected cells resulted in a phenotype resembling the phenotype of the ORF4 mutant virus, and activation of Akt by addition of insulin partially reversed the phenotype of the ORF4 mutant virus. Importantly, the homologous ORF4 of KSHV was able to rescue the phenotype of the MHV-68 ORF4 mutant, indicating that ORF4 is functionally conserved and that ORF4 of KSHV might have a similar function in infection initiation. Conclusions/Significance In summary, our studies demonstrate that ORF4 contributes to efficient infection by activation of the protein kinase Akt and thus reveal a novel function of a gammaherpesvirus RCA protein. PMID:20657771

  7. Correlates of Initial Recall of a Multimedia Communication Campaign to Promote Physical Activity among Tweens: the WIXX Campaign. (United States)

    Bélanger-Gravel, Ariane; Cutumisu, Nicoleta; Gauvin, Lise; Lagarde, François; Laferté, Marilie


    This study examined factors associated with children's and parents' recall of a communication campaign aimed at promoting children's physical activity. A cross-sectional population-based telephone survey was conducted among 1001 children and their parents. Respondents were recruited through a random digit dialing procedure. Respondents' recall of the campaign, beliefs, sociodemographics as well as levels of physical activity and sedentary behaviors were self-reported. Logistic regression analyses were conducted for tweens and their parents separately. Girls (odds ratio [OR] = 2.1; 95%confidence interval (CI): 1.3, 3.5) were more likely to have unaided recall when compared to boys. Tweens in primary school (OR = 1.9; 95%CI: 1.0, 3.4 and OR = 2.1; 95%CI: 1.4, 3.0) and those speaking French (OR = 3.3; 95%CI: 1.4, 8.1 and OR = 2.9; 95%CI: 1.8, 4.7) were more likely to have unaided and aided recall, respectively. Among parents, tweens' unaided (OR = 12.0; 95%CI: 5.2, 28.1) and aided (OR = 3.3; 95%CI: 1.5, 7.3) recall, obesity status (OR = 2.6; 95%CI: 1.3, 5.3), and low income (OR = 5.2; 95%CI: 1.9, 14.3) were positively associated with recall. Additional beliefs were associated with tweens' and parents' recall of the campaign. The association between sex, language, and recall is in line with the branding strategy adopted and no clear evidence for communication inequalities was observed.

  8. Policy initiatives to promote healthy aging. (United States)

    Infeld, Donna Lind; Whitelaw, Nancy


    An overwhelming array of policies and programs can be used to help older people (and future older people) maintain healthy lifestyles. How can clinicians help ensure that their patients take advantage of these opportunities? How can these broad-scope policies, educational and information initiatives, and direct service programs be turned into tools to help older people maximize health and independence? First, physicians do not need to do it all themselves. They need to know where to send their patients. For example, case managers in local aging service organizations and social workers, nurses, and discharge planners in hospitals can help connect elderly patients to appropriate benefits and services. Physicians play a critical role in creating a bridge between patients and the array of programs and information that can help them change their individual patterns of behavior. A serious lack of integration exists between what is known about healthy behaviors and lifestyles and what is really happening and available to older people today. From the earlier articles in this issue we know that much can be done to prevent many types of age-related disease and disability. This article provides examples of mechanisms that can be used to broadly disseminate knowledge about effective behavior and treatment changes and create mechanisms to turn this knowledge into real and widespread client-level, practice-level, health system, and community-wide interventions. Second, physicians need to understand that they are not merely subject to these policies and initiatives. They can help formulate and shape them. This political involvement includes active participation in policy initiatives of professional associations, involvement in research and demonstration activities, keeping informed about policy proposals at the federal and state levels, and helping advance ideas for improving health behaviors by speaking up and working toward change. These changes go beyond health initiatives to

  9. A NF-κB-dependent dual promoter-enhancer initiates the lipopolysaccharide-mediated transcriptional activation of the chicken lysozyme in macrophages. (United States)

    Witham, James; Ouboussad, Lylia; Lefevre, Pascal F


    The transcriptional activation of the chicken lysozyme gene (cLys) by lipopolysaccharide (LPS) in macrophages is dependent on transcription of a LPS-Inducible Non-Coding RNA (LINoCR) triggering eviction of the CCCTC-binding factor (CTCF) from a negative regulatory element upstream of the lysozyme transcription start site. LINoCR is transcribed from a promoter originally characterized as a hormone response enhancer in the oviduct. Herein, we report the characterization of this cis-regulatory element (CRE). In activated macrophages, a 60 bp region bound by NF-κB, AP1 and C/EBPβ controls this CRE, which is strictly dependent on NF-κB binding for its activity in luciferase assays. Moreover, the serine/threonine kinase IKKα, known to be recruited by NF-κB to NF-κB-dependent genes is found at the CRE and within the transcribing regions of both cLys and LINoCR. Such repartition suggests a simultaneous promoter and enhancer activity of this CRE, initiating cLys transcriptional activation and driving CTCF eviction. This recruitment was transient despite persistence of both cLys transcription and NF-κB binding to the CRE. Finally, comparing cLys with other LPS-inducible genes indicates that IKKα detection within transcribing regions can be correlated with the presence of the elongating form of RNA polymerase II or concentrated in the 3' end of the gene.

  10. Activities for Engaging Schools in Health Promotion (United States)

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


    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…

  11. Exploring Australian health promotion and environmental sustainability initiatives. (United States)

    Patrick, Rebecca; Kingsley, Jonathan


    Issue addressed Health promotion practitioners have important roles in applying ecosystem approaches to health and actively promoting environmental sustainability within community-level practice. The present study identified the nature and scope of health promotion activities across Australia that tackle environmental sustainability. Methods A mixed-method approach was used, with 82 participants undertaking a quantitative survey and 11 undertaking a qualitative interview. Purposeful sampling strategies were used to recruit practitioners who were delivering community-level health promotion and sustainability programs in Australia. The data were analysed thematically and interpretation was guided by the principles of triangulation. Results Study participants were at various stages of linking health promotion and environmental sustainability. Initiatives focused on healthy and sustainable food, active transport, energy efficiency, contact with nature and capacity building. Conclusion Capacity building approaches were perceived as essential to strengthening this field of practice. Healthy and sustainable food and active transport were suitable platforms for simultaneously promoting community health and sustainability. There was potential for expansion of programs that emphasise contact with nature and energy issues, as well as interventions that emphasise systems thinking and interdisciplinary approaches. So what? It was promising that Australian health promotion programs have started to address complexity rather than single issues, as evidenced by explicit engagement with environmental sustainability. However, more effort is required to enable a shift towards ecosystem approaches to health.

  12. Interventions for promoting the initiation of breastfeeding

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    Lisa Dyson

    Full Text Available BACKGROUND: Despite the widely documented health advantages of breastfeeding over formula feeding, initiation rates remain relatively low in many high-income countries, particularly among women in lower income groups. OBJECTIVE : To evaluate the effectiveness of interventions which aim to encourage women to breastfeed in terms of changes in the number of women who start to breastfeed. METHODS : Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (July 2007, handsearched the Journal of Human Lactation, Health Promotion International and Health Education Quarterly from inception to 15 August 2007, and scanned reference lists of all articles obtained. Selection criteria: Randomized controlled trials, with or without blinding, of any breastfeeding promotion intervention in any population group except women and infants with a specific health problem. Data collection and analysis: One review author independently extracted data and assessed trial quality, checked by a second author. We contacted investigators to obtain missing information. MAIN RESULTS: Main results: Eleven trials were included. Statistical analyses were conducted on data from eight trials (1553 women. Five studies (582 women on low incomes in the USA with typically low breastfeeding rates showed breastfeeding education had a significant effect on increasing initiation rates compared to standard care (risk ratio (RR 1.57, 95% confidence interval (CI 1.15 to 2.15, P = 0.005. Subgroup analyses showed that one-to-one, needs-based, informal repeat education sessions and generic, formal antenatal education sessions are effective in terms of an increase in breastfeeding rates among women on low incomes regardless of ethnicity and feeding intention. Needs-based, informal peer support in the antenatal and postnatal periods was also shown to be effective in one study conducted among Latina women who were considering breastfeeding in the USA (RR 4.02, 95% CI

  13. Health Promoting Schools: Initiatives in Africa (United States)

    Macnab, Andrew J.; Stewart, Donald; Gagnon, Faith A.


    Purpose: The purpose of this paper is to describe the rationale for and potential of World Health Organization (WHO) health promoting schools (HPS) in Africa. Design/Methodology/Approach: Overview of the related literature and presentations at the 2011 Stellenbosch international colloquium on HPS relating to sub-Saharan Africa. Findings: Schools…

  14. Motility initiation in active gels

    CERN Document Server

    Recho, Pierre; Truskinovsky, Lev


    Motility initiation in crawling cells requires a symmetry breaking mechanism which transforms a symmetric state into a polarized state. Experiments on keratocytes suggest that polarization is triggered by increased contractility of motor proteins. In this paper we argue that contraction can be responsible not only for the symmetry breaking transition but also for the incipient translocation of the segment of an active gel mimicking the crawling cell. Our model suggests that when the contractility increases sufficiently far beyond the motility initiation threshold, the cell can stop and re-symmetrizes. The proposed theory reproduces the motility initiation pattern in fish keratocytes and the behavior of keratocytes prior to cell division.

  15. Regulation of Drosophila Adh promoter switching by an initiator-targeted repression mechanism. (United States)

    Ren, B; Maniatis, T


    The stage-specific expression of the Drosophila alcohol dehydrogenase (Adh) gene is achieved through the alternate activation of two tandem promoters. The proximal promoter is active primarily during late embryonic development and early larval stages, while the distal promoter is active in late third instar larvae and adults. Here, we provide evidence that this Adh promoter switch is regulated by a zinc finger repressor protein (AEF-1) that is expressed predominantly in adult flies and targets the initiator region of the proximal promoter. We propose that AEF-1 plays a critical role in Adh promoter switching by blocking interactions between a component of the general transcription machinery and the initiator region of the proximal promoter. PMID:9463385

  16. Two tobacco AP1-like gene promoters with highly specific, tightly regulated and uniquely expressed activity during floral transition, initiation and development (United States)

    Biotech engineering of agronomic traits requires an array of highly specific and tightly regulated promoters in flower or other tissues. In this study, we isolated and characterized two tobacco AP1-like promoters (termed NtAP1La and NtAP1Lb1) in transgenic plants using GUS reporter and tissue-speci...

  17. The invisibilization of health promotion in Australian public health initiatives. (United States)

    O'Hara, Lily; Taylor, Jane; Barnes, Margaret


    The field of health promotion has arguably shifted over the past thirty years from being socially proactive to biomedically defensive. In many countries this has been accompanied by a gradual decline, or in some cases the almost complete removal of health promotion designated positions within Government health departments. The language or discourse used to describe the practice and discipline of health promotion is reflective of such changes. In this study, critical discourse analysis was used to determine the representation of health promotion as a practice and a discipline within 10 Australian Government weight-related public health initiatives. The analysis revealed the invisibilization of critical health promotion in favour of an agenda described as 'preventive health'. This was achieved primarily through the textual practices of overlexicalization and lexical suppression. Excluding document titles, there were 437 uses of the terms health promotion, illness prevention, disease prevention, preventive health, preventative health in the documents analysed. The term 'health promotion' was used sparingly (16% of total terms), and in many instances was coupled with the term 'illness prevention'. Conversely, the terms 'preventive health' and 'preventative health' were used extensively, and primarily used alone. The progressive invisibilization of critical health promotion has implications for the perceptions and practice of those identifying as health promotion professionals and for people with whom we work to address the social and structural determinants of health and wellbeing. Language matters, and the language and intent of critical health promotion will struggle to survive if its speakers are professionally unidentifiable or invisible.

  18. Examination of the Physical and Social Environments and Their Effect on Health Promotion Program Participation, Self Initiated Physical Activity and Nutrition Choices among University Employees (United States)

    Leininger, Lisa Janzen


    The worksite can be an effective arena to elicit health behavior change. Worksite health promotion programs now exist in 90% of all companies with more than 50 employees. These programs have become prevalent due to the high rates of obesity and lifestyle related diseases that are present in the United States. The purpose of this study was to…

  19. Cocaine promotes both initiation and elongation phase of HIV-1 transcription by activating NF-κB and MSK1 and inducing selective epigenetic modifications at HIV-1 LTR

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    Sahu, Geetaram; Farley, Kalamo [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); El-Hage, Nazira [Virginia Commonwealth University, Richmond, VA (United States); Aiamkitsumrit, Benjamas; Fassnacht, Ryan [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); Kashanchi, Fatah [George Mason University, Manassas, VA (United States); Ochem, Alex [ICGEB, Wernher and Beit Building, Anzio Road, Observatory, 7925 Cape Town (South Africa); Simon, Gary L. [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); Karn, Jonathan [Case Western Reserve University, Cleveland, OH (United States); Hauser, Kurt F. [Virginia Commonwealth University, Richmond, VA (United States); Tyagi, Mudit, E-mail: [Division of Infectious Diseases, Department of Medicine, George Washington University, Washington, DC (United States); Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC 20037 (United States)


    Cocaine accelerates human immunodeficiency virus (HIV-1) replication by altering specific cell-signaling and epigenetic pathways. We have elucidated the underlying molecular mechanisms through which cocaine exerts its effect in myeloid cells, a major target of HIV-1 in central nervous system (CNS). We demonstrate that cocaine treatment promotes HIV-1 gene expression by activating both nuclear factor-kappa B (NF-ĸB) and mitogen- and stress-activated kinase 1 (MSK1). MSK1 subsequently catalyzes the phosphorylation of histone H3 at serine 10, and p65 subunit of NF-ĸB at 276th serine residue. These modifications enhance the interaction of NF-ĸB with P300 and promote the recruitment of the positive transcription elongation factor b (P-TEFb) to the HIV-1 LTR, supporting the development of an open/relaxed chromatin configuration, and facilitating the initiation and elongation phases of HIV-1 transcription. Results are also confirmed in primary monocyte derived macrophages (MDM). Overall, our study provides detailed insights into cocaine-driven HIV-1 transcription and replication. - Highlights: • Cocaine induces the initiation phase of HIV transcription by activating NF-ĸB. • Cocaine induced NF-ĸB phosphorylation promotes its interaction with P300. • Cocaine enhances the elongation phase of HIV transcription by stimulating MSK1. • Cocaine activated MSK1 catalyzes the phosphorylation of histone H3 at its Ser10. • Cocaine induced H3S10 phosphorylation facilitates the recruitment of P-TEFb at LTR.

  20. Brazilian physical activity guidelines as a strategy for health promotion. (United States)

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


    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.

  1. Evaluating Maori community initiatives to promote healthy eating, healthy action. (United States)

    Hamerton, Heather; Mercer, Christine; Riini, Denise; McPherson, Brighid; Morrison, Laurie


    Māori, the indigenous people of Aotearoa New Zealand, experience poorer health than non-Māori across a range of health measures. Interventions focused at an individual level have proved largely ineffective; 'bottom-up' approaches where communities determine their own priorities may be more sustainable than 'top-down' approaches where goals are determined by health authorities. The purpose of this paper is to illustrate an innovative health promotion programme aimed at improving Māori health and to discuss the importance of ownership and control of health initiatives by Māori. Evaluators conducted a comprehensive evaluation of a Healthy Eating Healthy Action programme in six small Māori health agencies, gathering information from programme managers and co-ordinators, participants and wider community members about what changes were occurring at individual, family and community levels. Effective interventions built on cultural values and practices and were delivered by Māori with close connections to the community. Changes in nutrition and physical activity made by participants also benefitted their wider families and community. The changes demonstrated subtle but important shifts in thinking about healthy eating and healthy activity that in the longer term could lead to more measurable change towards improved quality of life for people within communities.

  2. Application of the improved BALB/c 3T3 cell transformation assay to the examination of the initiating and promoting activities of chemicals: the second interlaboratory collaborative study by the non-genotoxic carcinogen study group of Japan. (United States)

    Tsuchiya, Toshiyuki; Umeda, Makoto; Tanaka, Noriho; Sakai, Ayako; Nishiyama, Hiroshi; Yoshimura, Isao; Ajimi, Syozo; Asada, Shin; Asakura, Masumi; Baba, Hiroshi; Dewa, Yasuaki; Ebe, Youji; Fushiwaki, Yuichi; Hagiwara, Yuji; Hamada, Shuichi; Hamamura, Tetsuo; Iwase, Yumiko; Kajiwara, Yoshitsugu; Kasahara, Yasushi; Kato, Yukihiko; Kawabata, Masayoshi; Kitada, Emiko; Kaneko, Kazuko; Kizaki, Yuko; Kubo, Kinya; Miura, Daisaku; Mashiko, Kaori; Mizuhashi, Fukutaro; Muramatsu, Dai; Nakajima, Madoka; Nakamura, Tetsu; Oishi, Hidetoshi; Sasaki, Toshiaki; Shimada, Sawako; Takahashi, Chitose; Takeda, Yuko; Wakuri, Sinobu; Yajima, Nobuhiro; Yajima, Satoshi; Yatsushiro, Tomoko


    The Non-genotoxic Carcinogen Study Group in the Environmental Mutagen Society of Japan organised the second step of the inter-laboratory collaborative study on one-stage and two-stage cell transformation assays employing BALB/c 3T3 cells, with the objective of confirming whether the respective laboratories could independently produce results relevant to initiation or promotion. The method was modified to use a medium consisting of DMEM/F12 supplemented with 2% fetal bovine serum and a mixture of insulin, transferrin, ethanolamine and sodium selenite, at the stationary phase of cell growth. Seventeen laboratories collaborated in this study, and each chemical was tested by three to five laboratories. Comparison between the one-stage and two-stage assays revealed that the latter method would be beneficial in the screening of chemicals. In the test for initiating activity with the two-stage assay (post-treated with 0.1microg/ml 12-O-tetradecanoylphorbol-13-acetate), the relevant test laboratories all obtained positive results for benzo[a]pyrene and methylmethane sulphonate, and negative results for phenanthrene. Of those laboratories assigned phenacetin for the initiation phase, two returned positive results and two returned negative results, where the latter laboratories tested up to one dose lower than the maximum dose used by the former laboratories. In the exploration of promoting activity with the twostage assay (pretreated with 0.2microg/ml 3-methylcholanthrene), the relevant test laboratories obtained positive results for mezerein, sodium orthovanadate and TGF-beta1, and negative results for anthralin, phenacetin and phorbol. Two results returned for phorbol 12,13-didecanoate were positive, but one result was negative - again, the maximum dose to achieve the latter result was lower than that which produced the former results. These results suggest that this modified assay method is relevant, reproducible and transferable, provided that dosing issues, such as the

  3. International energy-promotion-activities

    Energy Technology Data Exchange (ETDEWEB)



    Comprehensive promotion of energy and environmental measures are demanded in order to realize improvement in energy demand/supply structures in developing countries where increase in energy demand is anticipated. To achieve this goal, technical transfer related to energy saving technologies and clean coal as well as international energy promotion activities are implemented in China and Indonesia since fiscal 1993. In the field of energy saving, model operations are performed to improve efficiency in such energy consuming fields as steel making, power generation, and oil refining, in addition to cooperation in structuring databases and establishing master plans. In the clean coal field, model operations are conducted to reduce environmental load in coal utilizing areas, in addition to cooperation in establishing master plans for coal utilization. This paper describes feasibility studies on environmentally harmonious coal utilization systems in developing countries, assistance to introduction thereof, and joint verification operations. To rationalize international energy usage, basic surveys on energy utilization efficiency improvement and model operations are carried out mainly in the Asia-Pacific countries.

  4. Astronomy Olympiad: An Initiative To Promote Astronomy Education In Nepal (United States)

    Bhattarai, Suresh


    This paper presents National Astronomy Olympiad Program as a new initiative towards the development of astronomy education in Nepal by Nepal Astronomical Society (NASO).Innovoative components of the olympiad programs designed by NASO to engage both scince and non-science backgound people will be discussed in detail. It will discuss the first National Astronomy Olympiad 2014 and Second National Astronomy Olympiad 2015 in details. It will also present crowd funding, its effectiveness to outreach as well as collecting funds from around the world will be presented in brief. Proposed module of astronomy olympiad to promote astronnomy in the countries without formal astronomy education in high school like Nepal,will be presented in dedail. Possible strategry to strengthen such programs in developing nations and role of IAU to promote such educational program will be explored in detail.

  5. Viral promoters can initiate expression of toxin genes introduced into Escherichia coli

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    Jacob Daniela


    Full Text Available Abstract Background The expression of recombinant proteins in eukaryotic cells requires the fusion of the coding region to a promoter functional in the eukaryotic cell line. Viral promoters are very often used for this purpose. The preceding cloning procedures are usually performed in Escherichia coli and it is therefore of interest if the foreign promoter results in an expression of the gene in bacteria. In the case molecules toxic for humans are to be expressed, this knowledge is indispensable for the specification of safety measures. Results We selected five frequently used viral promoters and quantified their activity in E. coli with a reporter system. Only the promoter from the thymidine kinase gene from HSV1 showed no activity, while the polyhedrin promoter from baculovirus, the early immediate CMV promoter, the early SV40 promoter and the 5' LTR promoter from HIV-1 directed gene expression in E. coli. The determination of transcription start sites in the immediate early CMV promoter and the polyhedrin promoter confirmed the existence of bacterial -10 and -35 consensus sequences. The importance of this heterologous gene expression for safety considerations was further supported by analysing fusions between the aforementioned promoters and a promoter-less cytotoxin gene. Conclusion According to our results a high percentage of viral promoters have the ability of initiating gene expression in E. coli. The degree of such heterologous gene expression can be sufficient for the expression of toxin genes and must therefore be considered when defining safety measures for the handling of corresponding genetically modified organisms.

  6. HUD Initiated Activity Cancellation Reports (United States)

    Department of Housing and Urban Development — This monthly report displays all HOME activities automatically cancelled by IDIS. Effective January 1, 2011, and the beginning of every month thereafter, committed...


    Directory of Open Access Journals (Sweden)



    Full Text Available In the paper authors presets experience of Czestochowa University of Technology within collaboration with Czestochowa Business Incubator (CBI. In 2010, chosen staff of Czestochowa UT have been working within brand new Phare project “Promotion of employment among youth”. Because relatively high unemployment level among young people in Czestochowa city and region, the project has been implemented in order to help graduates to find their strengths and to advise in planning individual job track, to extend their job skills adequate to present and foreseen market needs, prepare them to the job interviews, prepare and help in starting own business. Authors also describes CBI’s other initiatives undertaken to increase number of new business set up by young people, especially.

  8. Assessment of Site Specific Mutational Effect on Transcription Initiation at Escherichia coli Promoter

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    S. Kannan


    Full Text Available Problem statement: It is widely accepted thought that the weak promoters control the RNA synthesis and play regulatory role in complex genetic networks in bacterial system. An experiment had been designed to address whether mutations in the -16/-17 region affect the rate of transcription at an activator-independent promoter in E. coli or not? Approach: The aim of this study was to determine whether mutations in the -16/-17 region affect the rate of expression at an activator-dependent promoter in JM109 strain of E. coli. Primers were constructed to amplify the mutant promoter genes through PCR. The amplified PCR product was checked and then inserted into the MCS region of pAA128 plasmid. Further the plasmid vector was transformed into JM109 strain of E. coli and then cloned the selected transformats. Finally, the plasmid from each mutant colony was then sequenced using the protocol supplied with the Amersham Pharmacia Biotech T7 sequencing Kit. The JM109 cultures for which the sequences were determined, then assayed for ß-galactosidase activity to assess the rate of gene expression from the altered promoters. Results: The present investigation revealed that the extended-10 promoter region has a substantial effect on the rate of transcription at weak promoter sequence and also bearing little resemblance to the consensus sequence recognized by RNA. The expression of the genetically engineered plasmid proved that the 2 bps (-16 and -17 base pair found adjacently upstream of the extended-10 promoter have an effect on the level of transcription. This was achieved by site specific base substitutions into the weak promoter of a modified lac operon lacking any activator or repressor binding sites. The results from gene expression assays of several mutants showed a distinct preference for either GG or TT located adjacently upstream of the extended promoter element. Thus the present study emphasized that

  9. Corporate responsibility for childhood physical activity promotion in the UK. (United States)

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


    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. Promoting Business Education through Student Organization Activities. (United States)

    Yelverton, Sandra


    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)

  11. Promoter activities in Vibrio cholerae ctx phi prophage. (United States)

    Fando, R; Pérez, J L; Rodriguez, B L; Campos, J; Robert, A; García, L; Silva, A; Benitez, J A


    Comparison of cholera toxin (CT) production directed by different gene constructs and S1 nuclease mapping revealed the presence of a ctxB-specific promoter within the ctxA coding sequence. Initiation of transcription in this region occurred in wild-type El Tor and classical biotype choleragenic vibrios. We propose that transcription from the ctxB-specific promoter and a stronger ribosomal binding site on the ctxB mRNA synergistically contribute to achieve the correct (5B:1A) subunit stoichiometry. Plasmid pB, a CT promoterless vector expressing only CTB, was used to detect promoter activity by restoration of A-subunit synthesis. Promoter activity expressed in vitro and in vivo was detected upstream of the zonula occludens toxin gene, suggesting that this factor could be produced in vivo to contribute to fluid accumulation. No promoter activity was detected in vitro and in vivo upstream from the accessory cholera enterotoxin gene.

  12. Promotion marketing activities in universities


    Guseva I.B.; Ledentcova E.A.


    The article discusses the need for promotion of educational services through such means of marketing communications as advertising and personal selling , able to satisfy user requests. The results of market research - questioning school graduates of Perm, which was carried out in order to create an effective advertising campaign to attract entrants. Experience can be used in the advertising campaign universities in Russia , in particular , Perm State National Research University.


    Directory of Open Access Journals (Sweden)

    Costel Iliuta Negricea


    Full Text Available The promotion as one of the components of the marketing mix, laying stress, în this regard,on its role în the deployment of the tourism companies’ activity, the structure of the promotional activity în thetouristic sector as well as the use of the promotional strategies în the attainment of the development targets ofthe tourism companies.So, în the paper there have been mentioned the three levels at which it is made the touristic promotionîn Romania, respectively nationally, by the Ministry of the Tourism, under whose subordination it is theTourism National Authority, the second level is the regional/local one, concerning the activity carried out bythe Centers/Offices of Touristic Information from a series of localities, and the last level refers to the microone, respectively at the level of the tourism companies, which promote their offer individually (the most often.The important role of the promotion în the deployment of the activity of the tourism companies isbeing highlighted by the fact that this makes the connection between the activity of an organization and itscustomers (effective or potential, and, în the touristic field, the content of the promotional activity is stronglystressed by the features of this type of services and of the system of creation and delivery, as well as of thepurchasing behaviour.

  14. Evaluation of Results from Sales Promotion Activities


    Olimpia Ban


    An essential element of the sales promotion strategy and not only is the evaluation of the results obtained from the activities performed. Due to their nature and applicability, the evaluation of the sales promotion is much easier to be achieved, but it raises some problems. Using a hypothetical example, we have tried to develop a "classic" evaluation model of the specialty literature.

  15. Promoting physical activity in socially vulnerable groups

    NARCIS (Netherlands)

    Herens, M.C.


    Background:  In the Netherlands, inequalities in physical activity behaviour go hand in hand with socioeconomic inequalities in health. To promote physical activity effectively and equitably, participatory community-based physical activity interventions seem promising and are s

  16. Promoting Active Involvement in Classrooms (United States)

    Conderman, Greg; Bresnahan, Val; Hedin, Laura


    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,…

  17. A survey of local health promotion initiatives for older people in Wales

    Directory of Open Access Journals (Sweden)

    Williams Nefyn H


    Full Text Available Abstract Background As the demographic profile of the UK changes, policy makers and practitioners have to respond to health challenges presented by a progressively ageing population. The health promotion plan for older people, aged over 50 years, in Wales included eight key areas: physical activity, healthy eating, home safety and warmth, emotional health, health protection, smoking, alcohol and sexual health. The aim of this study was to describe the extent, content and regional variation of existing health promotion initiatives for older people in Wales, provided by statutory, voluntary and private sector agencies. Method A questionnaire was sent to senior health promotion specialists employed in the 22 local authority areas in Wales to ascertain details of all projects promoting health and wellbeing in the eight key areas where the priority population was aged over 50, or the majority of users were older people. Additional information was sought from project leads and websites. Results Eighteen questionnaires were returned; not all were fully completed. Four areas did not return a questionnaire. Additional information was obtained from internet searches but this mainly concerned national initiatives rather than local projects. In all, 120 projects were included, 11 were throughout Wales. Best provision was for physical activity, with 3 national and 42 local initiatives, but local provision was patchy. Healthy eating, and home safety and warmth had far fewer initiatives, as did health protection, which comprised two national immunisation campaigns. Smoking and alcohol misuse were poorly provided for, and there was no provision for older people's sexual health. Evaluation arrangements were poorly described. Half of those who responded identified unmet training needs. Conclusion The reasons for patchy provision of services were not clear. Increased efforts to improve the coverage of interventions known to be effective should be made. Rigorous

  18. Faithful transcription initiation from a mitochondrial promoter in transgenic plastids. (United States)

    Bohne, Alexandra-Viola; Ruf, Stephanie; Börner, Thomas; Bock, Ralph


    The transcriptional machineries of plastids and mitochondria in higher plants exhibit striking similarities. All mitochondrial genes and part of the plastid genes are transcribed by related phage-type RNA polymerases. Furthermore, the majority of mitochondrial promoters and a subset of plastid promoters show a similar structural organization. We show here that the plant mitochondrial atpA promoter is recognized by plastid RNA polymerases in vitro and in vivo. The Arabidopsis phage-type RNA polymerase RpoTp, an enzyme localized exclusively to plastids, was found to recognize the mitochondrial atpA promoter in in vitro assays suggesting the possibility that mitochondrial promoters might function as well in plastids. We have, therefore, generated transplastomic tobacco plants harboring in their chloroplast genome the atpA promoter fused to the coding region of the bacterial nptII gene. The chimeric nptII gene was found to be efficiently transcribed in chloroplasts. Mapping of the 5' ends of the nptII transcripts revealed accurate recognition of the atpA promoter by the chloroplast transcription machinery. We show further that the 5' untranslated region (UTR) of the mitochondrial atpA transcript is capable of mediating translation in chloroplasts. The functional and evolutionary implications of these findings as well as possible applications in chloroplast genome engineering are discussed.

  19. Promotion of Viral IRES-Mediated Translation Initiation under Mild Hypothermia.

    Directory of Open Access Journals (Sweden)

    Maria Licursi

    Full Text Available Internal ribosome entry site (IRES-mediated translation is an essential replication step for certain viruses. As IRES-mediated translation is regulated differently from cap-dependent translation under various cellular conditions, we sought to investigate whether temperature influences efficiency of viral IRES-mediated translation initiation by using bicistronic reporter constructs containing an IRES element of encephalomyocarditis virus (EMCV, foot-and-mouth disease virus (FMDV, hepatitis C virus (HCV, human rhinovirus (HRV or poliovirus (PV. Under mild hypothermic conditions (30 and 35°C, we observed increases in the efficiency of translation initiation by HCV and HRV IRES elements compared to translation initiation at 37°C. The promotion of HRV IRES activity was observed as early as 2 hours after exposure to mild hypothermia. We also confirmed the promotion of translation initiation by HRV IRES under mild hypothermia in multiple cell lines. The expression levels and locations of polypyrimidine tract-binding protein (PTB and upstream of N-Ras (unr, the IRES trans-acting factors (ITAFs of HCV and HRV IRES elements, were not modulated by the temperature shift from 37°C to 30°C. Taken together, this study demonstrates that efficiency of translation initiation by some viral IRES elements is temperature dependent.

  20. Promotion of Viral IRES-Mediated Translation Initiation under Mild Hypothermia (United States)

    Licursi, Maria; Carmona-Martinez, Ricardo A.; Razavi, Seyd; Hirasawa, Kensuke


    Internal ribosome entry site (IRES)-mediated translation is an essential replication step for certain viruses. As IRES-mediated translation is regulated differently from cap-dependent translation under various cellular conditions, we sought to investigate whether temperature influences efficiency of viral IRES-mediated translation initiation by using bicistronic reporter constructs containing an IRES element of encephalomyocarditis virus (EMCV), foot-and-mouth disease virus (FMDV), hepatitis C virus (HCV), human rhinovirus (HRV) or poliovirus (PV). Under mild hypothermic conditions (30 and 35°C), we observed increases in the efficiency of translation initiation by HCV and HRV IRES elements compared to translation initiation at 37°C. The promotion of HRV IRES activity was observed as early as 2 hours after exposure to mild hypothermia. We also confirmed the promotion of translation initiation by HRV IRES under mild hypothermia in multiple cell lines. The expression levels and locations of polypyrimidine tract-binding protein (PTB) and upstream of N-Ras (unr), the IRES trans-acting factors (ITAFs) of HCV and HRV IRES elements, were not modulated by the temperature shift from 37°C to 30°C. Taken together, this study demonstrates that efficiency of translation initiation by some viral IRES elements is temperature dependent. PMID:25951166

  1. Exploring Opportunities for Promoting Synergies between Climate Change Adaptation and Mitigation in Forest Carbon Initiatives

    Directory of Open Access Journals (Sweden)

    Eugene L. Chia


    Full Text Available There is growing interest in designing and implementing climate change mitigation and adaptation (M + A in synergy in the forest and land use sectors. However, there is limited knowledge on how the planning and promotion of synergies between M + A can be operationalized in the current efforts to mitigate climate change through forest carbon. This paper contributes to fill this knowledge gap by exploring ways of planning and promoting M + A synergy outcomes in forest carbon initiatives. It examines eight guidelines that are widely used in designing and implementing forest carbon initiatives. Four guiding principles with a number of criteria that are relevant for planning synergy outcomes in forest carbon activities are proposed. The guidelines for developing forest carbon initiatives need to demonstrate that (1 the health of forest ecosystems is maintained or enhanced; (2 the adaptive capacity of forest-dependent communities is ensured; (3 carbon and adaptation benefits are monitored and verified; and (4 adaptation outcomes are anticipated and planned in forest carbon initiatives. The forest carbon project development guidelines can encourage the integration of adaptation in forest carbon initiatives. However, their current efforts guiding projects and programs to deliver biodiversity and environmental benefits, ecosystem services, and socioeconomic benefits are not considered explicitly as efforts towards enhancing adaptation. An approach for incentivizing and motivating project developers, guideline setters, and offset buyers is imperative in order to enable existing guidelines to make clear contributions to adaptation goals. We highlight and discuss potential ways of incentivizing and motivating the explicit planning and promotion of adaptation outcomes in forest carbon initiatives.

  2. Evaluation of Results from Sales Promotion Activities

    Directory of Open Access Journals (Sweden)

    Olimpia Ban


    Full Text Available An essential element of the sales promotion strategy and not only is the evaluation of the results obtained from the activities performed. Due to their nature and applicability, the evaluation of the sales promotion is much easier to be achieved, but it raises some problems. Using a hypothetical example, we have tried to develop a "classic" evaluation model of the specialty literature.

  3. Mesoscale architecture shapes initiation and richness of spontaneous network activity. (United States)

    Okujeni, Samora; Kandler, Steffen; Egert, Ulrich


    Spontaneous activity in the absence of external input, including propagating waves of activity, is a robust feature of neuronal networks in vivo and in vitro. The neurophysiological and anatomical requirements for initiation and persistence of such activity, however, are poorly understood, as is their role in the function of neuronal networks. Computational network studies indicate that clustered connectivity may foster the generation, maintenance and richness of spontaneous activity. Since this mesoscale architecture cannot be systematically modified in intact tissue, testing these predictions is impracticable in vivo. Here, we investigate how the mesoscale structure shapes spontaneous activity in generic networks of rat cortical neurons in vitro. In these networks, neurons spontaneously arrange into local clusters with high neurite density and form fasciculating long-range axons. We modified this structure by modulation of protein kinase C, an enzyme regulating neurite growth and cell migration. Inhibition of protein kinase C reduced neuronal aggregation and fasciculation of axons, i.e. promoted uniform architecture. Conversely, activation of protein kinase C promoted aggregation of neurons into clusters, local connectivity and bundling of long-range axons. Supporting predictions from theory, clustered networks were more spontaneously active and generated diverse activity patterns. Neurons within clusters received stronger synaptic inputs and displayed increased membrane potential fluctuations. Intensified clustering promoted the initiation of synchronous bursting events but entailed incomplete network recruitment. Moderately clustered networks appear optimal for initiation and propagation of diverse patterns of activity. Our findings support a crucial role of the mesoscale architectures in the regulation of spontaneous activity dynamics.SIGNIFICANCE STATEMENTComputational studies predict richer and persisting spatio-temporal patterns of spontaneous activity in

  4. The United Nations Human Space Technology Initiative (HSTI): Science Activities

    CERN Document Server

    Niu, A; Haubold, H J; Doi, T


    The United Nations Human Space Technology Initiative (HSTI) aims at promoting international cooperation in human spaceflight and space exploration-related activities; creating awareness among countries on the benefits of utilizing human space technology and its applications; and building capacity in microgravity education and research. HSTI has been conducting various scientific activities to promote microgravity education and research. The primary science activity is called 'Zero-gravity Instrument Distribution Project', in which one-axis clinostats will be distributed worldwide. The distribution project will provide unique opportunities for students and researchers to observe the growth of indigenous plants in their countries in a simulated microgravity condition and is expected to create a huge dataset of plant species with their responses to gravity.

  5. Promoting Global Initiatives and Cross-Cultural Understanding in China (United States)

    Brand, Susan Trostle; Snodgress, Faye


    As an "international" honor society in education, Kappa Delta Pi (KDP) recognizes the importance of encouraging and promoting education internationally in the 21st century. The challenge shared by educators in many countries is to achieve higher levels of learning for all students. Committed educators around the globe are already working…

  6. Promoting Physical Activity during Early Childhood (United States)

    Vidoni, Carla; Ignico, Arlene


    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…

  7. Parent-Implemented Script Fading to Promote Play-Based Verbal Initiations in Children with Autism (United States)

    Reagon, Kara A.; Higbee, Thomas S.


    We trained 3 mothers of children with autism to create, implement, and systematically fade scripts to promote vocal initiations during play. All 3 children's scripted and unscripted initiations increased after the introduction and fading of scripts, and unscripted initiations were maintained at the 2-week follow-up. The results indicate that…

  8. Limited in vivo bioassays on some benzodiazepines: lack of experimental initiating or promoting effect of the benzodiazepine tranquillizers diazepam, clorazepate, oxazepam and lorazepam. (United States)

    Mazue, G; Remandet, B; Gouy, D; Berthe, J; Roncucci, R; Williams, G M


    Four benzodiazepine tranquillizers were tested for their ability to initiate or promote the development of preneoplastic and neoplastic rat liver lesions. In comparison with the liver carcinogen, N-2-fluorenylacetamide, the benzodiazepines exhibited no initiating activity during a 14-week period of daily administration by gavage. To study the promoting activity, N-2-fluorenylacetamide was used to initiate altered foci and neoplastic nodules in rat liver during 8 weeks and then the benzodiazepines were administered by daily gavage for a period of 12 weeks. The liver tumor promoter phenobarbital had a substantial enhancing effect upon the persistence of nodules but none of the benzodiazepines showed a similar effect. Thus, in the process model systems used, to detect initiating or promoting potential effect, the benzodiazepine tranquillizers failed to exhibit either an initiating or a promoting action.

  9. Heavy drinking and health promotion activities. (United States)

    Ettner, Susan L; French, Michael T; Popovici, Ioana


    Empirical evidence suggests that individuals who consume relatively large amounts of alcohol are more likely to use expensive acute medical care and less likely to use preventive or ambulatory services than other individuals. The few studies that investigated the associations between heavy drinking and health promotion activities did not try to address omitted-variable biases that may confound the relationships. To fill this void in the literature, we examined the effects of heavy alcohol use on three health promotion activities (routine physical exam, flu shot, regular seatbelt use) using the US 2006 Behavioral Risk Factor Surveillance Survey. Although specification tests indicated that omitted variable bias was not present in the majority of the single-equation probit models, we cautiously interpret our findings as evidence of strong associations rather than causal effects. Among both men and women, heavy alcohol use is negatively and significantly associated with each of our three outcomes. These findings suggest that heavy drinkers may be investing less in health promotion activities relative to abstainers and other drinkers. Policy options to address the associated externalities may be warranted.

  10. Promoting the export of environmental technologies: An analysis of governmental initiatives from eight countries


    Kanda, Wisdom; Hjelm, Olof; Dugand, Santiago Mejiá


    Export represents a means for the diffusion of environmental technologies with potential socio-economic and environmental benefits. However, environmental technology providers experience export barriers which stifle export and thus several governments continue to formulate export promotion initiatives towards this sector. Although export promotion is identified as essential in the environmental technology policy literature, it is yet to receive attention as to which initiatives are available ...


    Directory of Open Access Journals (Sweden)

    Felicia Sabou


    Full Text Available The paper focused on importance and benefits of control and evaluation of marketing activities. The control of efficiency review the assessment of the resources for marketing activity, checking also the efficiency of the human resources, advertising, promotion activities and distribution activities. In the analyse of human resources the most important ratio are: the average of costumers visits on a day, the number of custom order received from 100 visits, the number of new customers from a period, the number of lost customers from a period, the marketing human expenditures from all the sales.The strategic control is made to check if the objectives and the company strategy are adapted to the marketing environment.

  12. Principles for RNA metabolism and alternative transcription initiation within closely spaced promoters

    DEFF Research Database (Denmark)

    Chen, Yun; Pai, Athma A.; Herudek, Jan;


    sites, promoters often cluster so that the divergent activity of one might impact another. Here we found that the distance between promoters strongly correlates with the expression, stability and length of their associated PROMPTs. Adjacent promoters driving divergent mRNA transcription support PROMPT...... suggest that basic building blocks of divergently transcribed core promoter pairs, in combination with the wealth of TSSs in mammalian genomes, provide a framework with which evolution shapes transcriptomes....

  13. Loyalty Card Promotional Activity in Budget Hotel


    Teng, Fei


    Loyalty card is one of the most commonly used promotional activities in business. Thus far, there are some research has been done on luxury hotel, but very few researches are on budget hotel. So, the purpose of the thesis is finding out the Swedish customers’ attitude and behavior towards budget hotel’s loyalty card; getting to know what factors influence Swedish customers’ response towards the loyalty card and budget hotels. In the thesis, the main research problem is “How do Swedish custome...

  14. PARP activation promotes nuclear AID accumulation in lymphoma cells. (United States)

    Tepper, Sandra; Jeschke, Julia; Böttcher, Katrin; Schmidt, Angelika; Davari, Kathrin; Müller, Peter; Kremmer, Elisabeth; Hemmerich, Peter; Pfeil, Ines; Jungnickel, Berit


    Activation-induced cytidine deaminase (AID) initiates immunoglobulin diversification in germinal center B cells by targeted introduction of DNA damage. As aberrant nuclear AID action contributes to the generation of B cell lymphoma, the protein's activity is tightly regulated, e.g. by nuclear/cytoplasmic shuttling and nuclear degradation. In the present study, we asked whether DNA damage may affect regulation of the AID protein. We show that exogenous DNA damage that mainly activates base excision repair leads to prevention of proteasomal degradation of AID and hence its nuclear accumulation. Inhibitor as well as knockout studies indicate that activation of poly (ADP-ribose) polymerase (PARP) by DNA damaging agents promotes both phenomena. These findings suggest that PARP inhibitors influence DNA damage dependent AID regulation, with interesting implications for the regulation of AID function and chemotherapy of lymphoma.


    Directory of Open Access Journals (Sweden)



    Full Text Available Researches in the field of the labour market has allowed the identification of certain specific mechanisms for employment promotion; at present, on the Romanian labour market we find passive policies, concretised in financial aids paid to the unemployed, along with active policies, constituting the most efficient social protection activity addressed to the unemployed (they aim at counterbalancing the inefficiencies determined by the granting of financial allowances, help population to find a job by actions of information, professional training and contributing to the encouragement of the labour force mobility. The paper refers to some theoretical considerations related to the influence factors of employment stimulation, as well as to the unemployment – correlated adequate measures synapse. The applied research comprises the analysis of statistic documents; the method used is the case study, i.e. the activity of employment stimulation carried on by the County Agency for Employment Caraş-Severin, in the period 2004-2012. The conclusions highlight the impact of the activity of the institutions involved in the system of social protection and security within the labour market.

  16. FGFR2 promotes breast tumorigenicity through maintenance of breast tumor-initiating cells.

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    Sungeun Kim

    Full Text Available Emerging evidence suggests that some cancers contain a population of stem-like TICs (tumor-initiating cells and eliminating TICs may offer a new strategy to develop successful anti-cancer therapies. As molecular mechanisms underlying the maintenance of the TIC pool are poorly understood, the development of TIC-specific therapeutics remains a major challenge. We first identified and characterized TICs and non-TICs isolated from a mouse breast cancer model. TICs displayed increased tumorigenic potential, self-renewal, heterogeneous differentiation, and bipotency. Gene expression analysis and immunostaining of TICs and non-TICs revealed that FGFR2 was preferentially expressed in TICs. Loss of FGFR2 impaired self-renewal of TICs, thus resulting in marked decreases in the TIC population and tumorigenic potential. Restoration of FGFR2 rescued the defects in TIC pool maintenance, bipotency, and breast tumor growth driven by FGFR2 knockdown. In addition, pharmacological inhibition of FGFR2 kinase activity led to a decrease in the TIC population which resulted in suppression of breast tumor growth. Moreover, human breast TICs isolated from patient tumor samples were found enriched in a FGFR2+ population that was sufficient to initiate tumor growth. Our data suggest that FGFR2 is essential in sustaining the breast TIC pool through promotion of self-renewal and maintenance of bipotent TICs, and raise the possibility of FGFR2 inhibition as a strategy for anti-cancer therapy by eradicating breast TICs.

  17. Environmental Technology Export Promotion : A study of governmental initiatives in selected countries


    Kanda, Wisdom; Hjelm, Olof; Mejia-Dugand, Santiago


    Introduction-This report is based on structured literature reviews and brainstorming sections on governmental export promotion initiatives for environmental technology in selected countries. It is intended to answer two fundamental questions: why governments intervene to promote environmental technology export and how this intervention is actually executed. These questions emerged in-light of two general challenges: 1) the lack of vivid scientific insights with robust theoretical underpinning...

  18. Governmental export promotion initiatives : awareness, participation, and perceived effectiveness among Swedish environmental technology firms


    Kanda, Wisdom; Mejiá-Dugand, Santiago; Hjelm, Olof


    Some countries rely heavily on exports as an essential component of their economic competitiveness. With the current trends in economic globalization, promoting exports has become a common strategy to boost economic growth. Exports of environmental technologies represent a new window of opportunity for economic growth and a contribution to global sustainability. With this in mind, national governments have designed initiatives that aim to promote exports within this sector. To address their o...

  19. Nutrition Education Initiative: A School-Based Program to Promote Healthy Eating Practices of Preadolescents (United States)

    Greenwood, Bonnie; Ralston, Penny A.; Young-Clark, Iris; Cornille, Tom; Brown, Linda Lockett; Davis, Kimberly E.; Salley, Tihesha J.; Goehrig, Marianne Henderson; Mullins, Amy Piper; Gaskins, Dykibra J.


    The implementation of the Nutrition Education Initiative (NEI), a project to promote the adoption of healthy eating practices by middle school students in North Florida, included the development of the "NEI Resource Guide" and pilot study outcomes. Eight schools in North Florida participated in the pilot project. Food recall data from 331 and 768…

  20. Promotion of initial cell adhesion on trisuccinimidyl citrate-modified nickel-free high-nitrogen stainless steel. (United States)

    Sasaki, Makoto; Inoue, Motoki; Katada, Yasuyuki; Taguchi, Tetsushi


    The surface of nickel-free high-nitrogen stainless steel (HNS) was modified with a citric acid-based cross-linker, trisuccinimidyl citrate (TSC), to promote initial cell adhesion in external skeletal fixation pins. The remaining active ester groups on TSC-immobilized HNS reacted with the amino groups of serum proteins. The immobilized serum proteins formed cell recognition sites to promote the initial cell adhesion immediately after cell seeding. The amount of fibronectin, which is a typical cell adhesion protein, immobilized on the TSC-immobilized HNS surface was threefold greater than on the original HNS after only 15 min. The fibroblastic cell culture experiments showed that the initial cell adhesion was significantly enhanced on the TSC-immobilized HNS compared with the original HNS at 3 h. Furthermore, the cell adhesion activity of the TSC-immobilized HNS continued to promote cell proliferation even at 7 days. Therefore, TSC-immobilized HNS may enable the rapid integration of soft tissues through its reaction with the patient's serum proteins and extracellular proteins around the surgical site.

  1. Promoter proximal polyadenylation sites reduce transcription activity

    DEFF Research Database (Denmark)

    Andersen, Pia Kjølhede; Lykke-Andersen, Søren; Jensen, Torben Heick


    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...

  2. Mycobacterium tuberculosis 19-kDa lipoprotein promotes neutrophil activation. (United States)

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


    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.

  3. Human mediator subunit MED15 promotes transcriptional activation. (United States)

    Nakatsubo, Takuya; Nishitani, Saori; Kikuchi, Yuko; Iida, Satoshi; Yamada, Kana; Tanaka, Aki; Ohkuma, Yoshiaki


    In eukaryotes, the Mediator complex is an essential transcriptional cofactor of RNA polymerase II (Pol II). In humans, it contains up to 30 subunits and consists of four modules: head, middle, tail, and CDK/Cyclin. One of the subunits, MED15, is located in the tail module, and was initially identified as Gal11 in budding yeast, where it plays an essential role in the transcriptional regulation of galactose metabolism with the potent transcriptional activator Gal4. For this reason, we investigated the function of the human MED15 subunit (hMED15) in transcriptional activation. First, we measured the effect of hMED15 knockdown on cell growth in HeLa cells. The growth rate was greatly reduced. By immunostaining, we observed the colocalization of hMED15 with the general transcription factors TFIIE and TFIIH in the nucleus. We measured the effects of siRNA-mediated knockdown of hMED15 on transcriptional activation using two different transcriptional activators, VP16 and SREBP1a. Treatment with siRNAs reduced transcriptional activation, and this reduction could be rescued by overexpression of HA/Flag-tagged, wild-type hMED15. To investigate hMED15 localization, we treated human MCF-7 cells with the MDM2 inhibitor Nutlin-3, thus inducing p21 transcription. We found that hMED15 localized to both the p53 binding site and the p21 promoter region, along with TFIIE and TFIIH. These results indicate that hMED15 promotes transcriptional activation.

  4. Aptamers to the sigma factor mimic promoter recognition and inhibit transcription initiation by bacterial RNA polymerase. (United States)

    Miropolskaya, Nataliya; Kulbachinskiy, Andrey


    Promoter recognition by bacterial RNA polymerase (RNAP) is a multi-step process involving multiple protein-DNA interactions and several structural and kinetic intermediates which remain only partially characterized. We used single-stranded DNA aptamers containing specific promoter motifs to probe the interactions of the Thermus aquaticus RNAP σ(A) subunit with the -10 promoter element in the absence of other parts of the promoter complex. The aptamer binding decreased intrinsic fluorescence of the σ subunit, likely as a result of interactions between the -10 element and conserved tryptophan residues of the σ DNA-binding region 2. By monitoring these changes, we demonstrated that DNA binding proceeds through a single rate-limiting step resulting in formation of very stable complexes. Deletion of the N-terminal domain of the σ(A) subunit increased the rate of aptamer binding while replacement of this domain with an unrelated N-terminal region 1.1 from the Escherichia coli σ(70) subunit restored the original kinetics of σ-aptamer interactions. The results demonstrate that the key step in promoter recognition can be modelled in a simple σ-aptamer system and reveal that highly divergent N-terminal domains similarly modulate the DNA-binding properties of the σ subunit. The aptamers efficiently suppressed promoter-dependent transcription initiation by the holoenzyme of RNA polymerase, suggesting that they may be used for development of novel transcription inhibitors.

  5. Role of Libraries in Promoting E-Learning : A Review of Singapore Initiatives


    Chaudhary, Abdus Sattar


    In line with the emphasis of Singapore Government in exploiting information technology for national competitiveness, public service institutions were quick to undertake initiatives to promote e-learning among their staff. This is part of the campaign for readiness for e-governance in the country. The Library and Information sector was no exception in this national campaign. National Library Board, which had earlier won awards for use of technology and introduction of network services, took fu...

  6. Inhibition of adenovirus replication by the E1A antisense transcript initiated from hsp70 and VA-1 promoters. (United States)

    Miroshnichenko, O I; Borisenko, A S; Ponomareva, T I; Tikhonenko, T I


    The E1A region of the adenoviral genome, important for initiation of virus infection and activation of other viral genes, was chosen as a target for engineering antisense RNA (asRNA) to inhibit adenovirus 5 (Ad5) replication in COS-1 cell culture in vitro. The hsp70 promoter, taken from the appropriate heat-shock-protein gene of Drosophila melanogaster, and the VA-1 RNA promoter, derived from the Ad5 gene coding for low-molecular-mass VA-1 RNA and recognized by RNA polymerase III were used as regulatory elements of transcription. The two types of recombinant constructs contained E1A fragments of 710 bp (hsp70 constructs) or 380 or 740 bp (VA-1 RNA constructs) in reverse orientation relative to the promoter position, as well as a transcription termination signal, the SV40 ori, and the gene controlling Geneticin (antibiotic G418) resistance (G418R). After selection of transfected COS-1 cells in the presence of G418, a number of stable G418R cell lines were raised which expressed engineered asRNAs. Plating of Ad5 suspensions of known titre on monolayers of transfected COS-1 cells clearly showed strong inhibition of adenovirus replication by asRNAs: 75% with the hsp70 promoter and 90% with the VA-1 RNA promoter.

  7. Initiation-promotion model of tumor prevalence in mice from space radiation exposures. (United States)

    Cucinotta, F A; Wilson, J W


    Exposures in space consist of low-level background components from galactic cosmic rays (GCR), occasional intense-energetic solar-particle events, periodic passes through geomagnetic-trapped radiation, and exposure from possible onboard nuclear-propulsion engines. Risk models for astronaut exposure from such diverse components and modalities must be developed to assure adequate protection in future NASA missions. The low-level background exposures (GCR), including relativistic heavy ions (HZE), will be the ultimate limiting factor for astronaut career exposure. We consider herein a two-mutation, initiation-promotion, radiation-carcinogenesis model in mice in which the initiation stage is represented by a linear kinetics model of cellular repair/misrepair, including the track-structure model for heavy ion action cross-sections. The model is validated by comparison with the harderian gland tumor experiments of Alpen et al. for various ion beams. We apply the initiation-promotion model to exposures from galactic cosmic rays, using models of the cosmic-ray environment and heavy ion transport, and consider the effects of the age of the mice prior to and after the exposure and of the length of time in space on predictions of relative risk. Our results indicate that biophysical models of age-dependent radiation hazard will provide a better understanding of GCR risk than models that rely strictly on estimates of the initial slopes of these radiations.

  8. Investigating potential exogenous tumor initiating and promoting factors for Cutaneous T-Cell Lymphomas (CTCL), a rare skin malignancy

    DEFF Research Database (Denmark)

    Litvinov, Ivan V.; Shtreis, Anna; Kobayashi, Kenneth


    -Cell lymphotropic virus type 1 (HTLV1), Epstein-Barr virus (EBV), and herpes simplex virus (HSV). In this report, we review recent evidence evaluating the involvement of these agents in cancer initiation/progression. Most importantly, recent molecular experimental evidence documented for the first time that S...... are then able to activate STAT3 and STAT5 oncogenic signaling and promote cancer progression and IL-17 secretion. In light of these findings, it might be important for patients with exacerbation of their CTCL symptoms to maintain high index of suspicion and treat these individuals for S. aureus colonization and...

  9. From DDR to Security Promotion: Connecting national programs to community initiatives

    NARCIS (Netherlands)

    Verkoren, W.; Willems, R.C.; Kleingeld, J.; Rouw, H.


    Disarmament, demobilization and reintegration (DDR) is a set of activities that forms part of strategies for peacebuilding after civil war. DDR has become the standard way of addressing security threats in immediate post-conflict situations. However, DDR is designed to promote national security, rat

  10. Activity-promoting gaming systems in exercise and rehabilitation. (United States)

    Taylor, Matthew J D; McCormick, Darren; Shawis, Teshk; Impson, Rebecca; Griffin, Murray


    Commercial activity-promoting gaming systems provide a potentially attractive means to facilitate exercise and rehabilitation. The Nintendo Wii, Sony EyeToy, Dance Dance Revolution, and Xbox Kinect are examples of gaming systems that use the movement of the player to control gameplay. Activity-promoting gaming systems can be used as a tool to increase activity levels in otherwise sedentary gamers and also be an effective tool to aid rehabilitation in clinical settings. Therefore, the aim of this current work is to review the growing area of activity-promoting gaming in the context of exercise, injury, and rehabilitation.

  11. Invariant distribution of promoter activities in Escherichia coli. (United States)

    Zaslaver, Alon; Kaplan, Shai; Bren, Anat; Jinich, Adrian; Mayo, Avi; Dekel, Erez; Alon, Uri; Itzkovitz, Shalev


    Cells need to allocate their limited resources to express a wide range of genes. To understand how Escherichia coli partitions its transcriptional resources between its different promoters, we employ a robotic assay using a comprehensive reporter strain library for E. coli to measure promoter activity on a genomic scale at high-temporal resolution and accuracy. This allows continuous tracking of promoter activity as cells change their growth rate from exponential to stationary phase in different media. We find a heavy-tailed distribution of promoter activities, with promoter activities spanning several orders of magnitude. While the shape of the distribution is almost completely independent of the growth conditions, the identity of the promoters expressed at different levels does depend on them. Translation machinery genes, however, keep the same relative expression levels in the distribution across conditions, and their fractional promoter activity tracks growth rate tightly. We present a simple optimization model for resource allocation which suggests that the observed invariant distributions might maximize growth rate. These invariant features of the distribution of promoter activities may suggest design constraints that shape the allocation of transcriptional resources.

  12. Invariant distribution of promoter activities in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Alon Zaslaver


    Full Text Available Cells need to allocate their limited resources to express a wide range of genes. To understand how Escherichia coli partitions its transcriptional resources between its different promoters, we employ a robotic assay using a comprehensive reporter strain library for E. coli to measure promoter activity on a genomic scale at high-temporal resolution and accuracy. This allows continuous tracking of promoter activity as cells change their growth rate from exponential to stationary phase in different media. We find a heavy-tailed distribution of promoter activities, with promoter activities spanning several orders of magnitude. While the shape of the distribution is almost completely independent of the growth conditions, the identity of the promoters expressed at different levels does depend on them. Translation machinery genes, however, keep the same relative expression levels in the distribution across conditions, and their fractional promoter activity tracks growth rate tightly. We present a simple optimization model for resource allocation which suggests that the observed invariant distributions might maximize growth rate. These invariant features of the distribution of promoter activities may suggest design constraints that shape the allocation of transcriptional resources.

  13. Physical activity and health promotion in Italian university students

    Directory of Open Access Journals (Sweden)

    Adele Anna Teleman


    Full Text Available INTRODUCTION: Physical activity, diet plans, the mantainment of a certain Body Mass Index (BMI and the use of various types of supplementation are common elements in the search for disease prevention, health promotion and well-being. MATERIALS AND METHODS: We analyzed the data regarding Italian university students' BMI, dieting behaviour, personal body perception, exercise habits, and use of dietary supplements and of doping substances. RESULTS: 13.7% resulted being underweight, 75.1% was in the normal range, 9.8% was overweight, and 1.4% was obese. 11.0% were on a diet. 25.8% of the students reported never doing any type of physical activity. 0.9% admitted consuming doping substances. The percentage of overweight/obese students increases from 8.8% of the 18-21 year olds to 18.1% of the 25-30 year olds. Similarly, the prevalence of overweight/obesity was 18.5% among male population and 7.5% among the female one. DISCUSSION: The data deriving from this questionnaire showed that while the majority of university students has a BMI in the normal range, 11.2% of the study population is overweight/obese. Males present a higher risk of being overweight or obese. An important part of the population showed to be sedentary even though data coming from our study are aligned to further evidence. CONCLUSION: The most important concern arising from the questionnaire is represented by physical inactivity. Indeed, it is necessary to encourage and plan initiatives aimed at promoting physical activity in university students.

  14. Core Promoter Plasticity Between Maize Tissues and Genotypes Contrasts with Predominance of Sharp Transcription Initiation Sites. (United States)

    Mejía-Guerra, María Katherine; Li, Wei; Galeano, Narmer F; Vidal, Mabel; Gray, John; Doseff, Andrea I; Grotewold, Erich


    Core promoters are crucial for gene regulation, providing blueprints for the assembly of transcriptional machinery at transcription start sites (TSSs). Empirically, TSSs define the coordinates of core promoters and other regulatory sequences. Thus, experimental TSS identification provides an essential step in the characterization of promoters and their features. Here, we describe the application of CAGE (cap analysis of gene expression) to identify genome-wide TSSs used in root and shoot tissues of two maize (Zea mays) inbred lines (B73 and Mo17). Our studies indicate that most TSS clusters are sharp in maize, similar to mice, but distinct from Arabidopsis thaliana, Drosophila melanogaster, or zebra fish, in which a majority of genes have broad-shaped TSS clusters. We established that ∼38% of maize promoters are characterized by a broader TATA-motif consensus, and this motif is significantly enriched in genes with sharp TSSs. A noteworthy plasticity in TSS usage between tissues and inbreds was uncovered, with ∼1500 genes showing significantly different dominant TSSs, sometimes affecting protein sequence by providing alternate translation initiation codons. We experimentally characterized instances in which this differential TSS utilization results in protein isoforms with additional domains or targeted to distinct subcellular compartments. These results provide important insights into TSS selection and gene expression in an agronomically important crop.

  15. Relevance of the mouse skin initiation-promotion model for the classification of carcinogenic substances encountered at the workplace. (United States)

    Schwarz, Michael; Thielmann, Heinz W; Meischner, Veronika; Fartasch, Manigé


    The Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission of the Deutsche Forschungsgemeinschaft) evaluates chemical substances using scientific criteria to prevent adverse effects on health at the work place. As part of this task there is a need to evaluate tumor promoting activity of chemicals (enhancement of formation of squamous cell carcinomas via premalignant papillomas) obtained from two-stage initiation/promotion experiments using the mouse skin model. In the present communication we address this issue by comparing responses seen in mouse skin with those in humans. We conclude that tumor promotional effects seen in such animal models be carefully analyzed on a case by case basis. Substances that elicit a rather non-specific effect that is restricted to the high dose range are considered to be irrelevant to humans and thus do not require classification as carcinogens. In contrast, substances that might have both a mode of action and a potency similar to the specific effects seen with TPA (12-O-tetradecanoylphorbol-13-acetate), the prototype tumor promoter in mouse skin, which triggers receptor-mediated signal cascades in the very low dose range, have to be classified in a category for carcinogens.

  16. Reassembly of nucleosomes at the MLH1 promoter initiates resilencing following decitabine exposure.

    Directory of Open Access Journals (Sweden)

    Luke B Hesson

    Full Text Available Hypomethylating agents reactivate tumor suppressor genes that are epigenetically silenced in cancer. Inevitably these genes are resilenced, leading to drug resistance. Using the MLH1 tumor suppressor gene as a model, we showed that decitabine-induced re-expression was dependent upon demethylation and eviction of promoter nucleosomes. Following decitabine withdrawal, MLH1 was rapidly resilenced despite persistent promoter demethylation. Single molecule analysis at multiple time points showed that gene resilencing was initiated by nucleosome reassembly on demethylated DNA and only then was followed by remethylation and stable silencing. Taken together, these data establish the importance of nucleosome positioning in mediating resilencing of drug-induced gene reactivation and suggest a role for therapeutic targeting of nucleosome assembly as a mechanism to overcome drug resistance.

  17. Hyphal development in Candida albicans requires two temporally linked changes in promoter chromatin for initiation and maintenance.

    Directory of Open Access Journals (Sweden)

    Yang Lu


    Full Text Available Phenotypic plasticity is common in development. For Candida albicans, the most common cause of invasive fungal infections in humans, morphological plasticity is its defining feature and is critical for its pathogenesis. Unlike other fungal pathogens that exist primarily in either yeast or hyphal forms, C. albicans is able to switch reversibly between yeast and hyphal growth forms in response to environmental cues. Although many regulators have been found involved in hyphal development, the mechanisms of regulating hyphal development and plasticity of dimorphism remain unclear. Here we show that hyphal development involves two sequential regulations of the promoter chromatin of hypha-specific genes. Initiation requires a rapid but temporary disappearance of the Nrg1 transcriptional repressor of hyphal morphogenesis via activation of the cAMP-PKA pathway. Maintenance requires promoter recruitment of Hda1 histone deacetylase under reduced Tor1 (target of rapamycin signaling. Hda1 deacetylates a subunit of the NuA4 histone acetyltransferase module, leading to eviction of the NuA4 acetyltransferase module and blockage of Nrg1 access to promoters of hypha-specific genes. Promoter recruitment of Hda1 for hyphal maintenance happens only during the period when Nrg1 is gone. The sequential regulation of hyphal development by the activation of the cAMP-PKA pathway and reduced Tor1 signaling provides a molecular mechanism for plasticity of dimorphism and how C. albicans adapts to the varied host environments in pathogenesis. Such temporally linked regulation of promoter chromatin by different signaling pathways provides a unique mechanism for integrating multiple signals during development and cell fate specification.

  18. Releasing stimuli and aggression in crickets: octopamine promotes escalation and maintenance but not initiation

    Directory of Open Access Journals (Sweden)

    Jan eRillich


    Full Text Available Biogenic amines have widespread effects on numerous behaviors, but their natural functions are often unclear. We investigated the role of octopamine (OA, the invertebrate analogue of noradrenaline, on initiation and maintenance of aggression in male crickets of different social status. The key-releasing stimulus for aggression is antennal fencing between males, a behavior occurring naturally on initial contact. We show that mechanical antennal stimulation (AS alone is sufficient to initiate an aggressive response (mandible threat display. The efficacy of AS was augmented in winners of a previous fight, but unaffected in losers. The efficacy of AS was not, however, influenced by OA receptor (OAR agonists or antagonists, regardless of social status. Additional experiments indicate that the efficacy of AS is also not influenced by dopamine (DA or serotonin (5HT. In addition to initiating an aggressive response, prior AS enhanced aggression exhibited in subsequent fights, whereby AS with a male antenna was now necessary, indicating a role for male contact pheromones. This priming effect of male-AS on subsequent aggression was dependent on OA since it was blocked by OAR-antagonists, and enhanced by OAR-agonists. Together our data reveal that neither OA, DA nor 5HT are required for initiating aggression in crickets, nor do these amines influence the efficacy of the natural releasing stimulus to initiate aggression. OA’s natural function is restricted to promoting escalation and maintenance of aggression once initiated, and this can be invoked by numerous experiences, including prior contact with a male antenna as shown here.

  19. Automated activity-aware prompting for activity initiation. (United States)

    Holder, Lawrence B; Cook, Diane J


    Performing daily activities without assistance is important to maintaining an independent functional lifestyle. As a result, automated activity prompting systems can potentially extend the period of time that adults can age in place. In this paper we introduce AP, an algorithm to automate activity prompting based on smart home technology. AP learns prompt rules based on the time when activities are typically performed as well as the relationship between activities that normally occur in a sequence. We evaluate the AP algorithm based on smart home datasets and demonstrate its ability to operate within a physical smart environment.

  20. Parents' Perspectives of School Mental Health Promotion Initiatives Are Related to Parents' Self-Assessed Parenting Capabilities (United States)

    Askell-Williams, Helen


    Achieving broad-scale parent engagement with school initiatives has proven elusive. This article reports survey data from 287 Maltese parents about their perceptions of the quality of their child's school's initiatives for promoting students' wellbeing and mental health. Findings indicate that, on average, parents rated school initiatives highly.…

  1. Physical Activity Promotion in Call Centres: Employers' Perspectives (United States)

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


    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…

  2. The United Nations Human Space Technology Initiative (HSTI): Activity Status in 2012

    CERN Document Server

    Ochiai, M; Haubold, H J; Doi, T


    In 2010, the Human Space Technology Initiative (HSTI) was launched by the United Nations Office for Outer Space Affairs (UNOOSA) within the United Nations Programme on Space Applications. The Initiative aims at promoting international cooperation in human spaceflight and space exploration-related activities, creating awareness among countries on the benefits of utilizing human space technology and its applications, and building capacity in microgravity education and research. HSTI has conducted a series of outreach activities and expert meetings bringing together participants from around the world. HSTI will also be implementing science and educational activities in relevant areas to raise the capacities, particularly in developing countries, in pursuit of the development goals of the United Nations, thus contributing to promoting the peaceful uses of outer space.

  3. Archaeal promoter architecture and mechanism of gene activation

    DEFF Research Database (Denmark)

    Peng, Nan; Ao, Xiang; Liang, Yun Xiang;


    Sulfolobus solfataricus and Sulfolobus islandicus contain several genes exhibiting D-arabinose-inducible expression and these systems are ideal for studying mechanisms of archaeal gene expression. At sequence level, only two highly conserved cis elements are present on the promoters: a regulatory...... element named ara box directing arabinose-inducible expression and the basal promoter element TATA, serving as the binding site for the TATA-binding protein. Strikingly, these promoters possess a modular structure that allows an essentially inactive basal promoter to be strongly activated. The invoked...

  4. European Commission Initiatives to Promote Social Concern on the Market: a Counterbalance to Fiscal Discipline?

    Directory of Open Access Journals (Sweden)

    Laura Gómez Urquijo


    Full Text Available The aim of this article is to analyse the significance of recent European Commission initiatives in the face of evidence of non-compliance with the social objectives targeted in the EU 2020 Strategy. In the midst of the ongoing debate regarding austerity and growth, we stress the need to further the EU trend toward differentiated growth-friendly fiscal consolidation. Given that “conditionality” is a new keystone of economic governance and cohesion policy, the difficulties that the Member States encounter and the diversity of their social protections give a new meaning to the European coordination policies that are intended to promote social cohesion. By analysing EU proposals and official documents, we will show how the Commission’s initiatives have introduced diverse elements that are intended to address the social consequences of the economic crisis and reveal how new ideas of growth and new ways to deepen the internal market have been promoted. We will also determine whether we can consider these ideas to be a valid response to current social challenges.

  5. Benchmarking promotion and deployment activities regarding intelligent vehicle safety systems in the EU

    NARCIS (Netherlands)

    Kievit, M. de; Malone, K.M.; Zwijnenberg, H.; Arem, B. van


    This paper presents the results of a Benchmarking study performed in the European Union on Awareness and Promotion & Deployment activities related to Intelligent Vehicle Safety (IVS) systems (1). The study, commissioned by the European Commission under the Intelligent Car Initiative (a i2010 flagshi

  6. Active Agents of Health Promotion? The School's Role in Supporting the HPV Vaccination Programme (United States)

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


    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…

  7. Promoting Physical Activity through Goal Setting Strategies (United States)

    Martinez, Ray


    Physical educators are used to setting specific goals for students within a given unit. Here, the author emphasizes that they should also encourage students to set their own goals. Goal setting engages students in the learning process and allows them to develop the skills that support an active lifestyle. The author presents goal setting…

  8. The 'Practice Entrepreneur' - An Australian case study of a systems thinking inspired health promotion initiative. (United States)

    Joyce, A; Green, C; Carey, G; Malbon, E


    The potential of systems science concepts to inform approaches for addressing complex public health problems, such as obesity prevention, has been attracting significant attention over the last decade. Despite its recent popularity, there are very few studies examining the application of systems science concepts, termed systems thinking, in practice and whether (if at all) it influences the implementation of health promotion in real world settings and in what ways. Healthy Together Victoria (HTV) was based on a systems thinking approach to address obesity prevention alongside other chronic health problems and was implemented across 14 local government areas. This paper examines the experience of practitioners from one of those intervention sites. In-depth interviews with eight practitioners revealed that there was a rigidity with which they had experienced previous health promotion jobs relative to the flexibility and fluidity of HTV. While the health promotion literature does not indicate that health promotion should be overly prescriptive, the experience of these practitioners suggests it is being applied as such in real world settings. Within HTV, asking people to work with 'systems thinking', without giving a prescription about what systems thinking is, enabled practitioners to be 'practice entrepreneurs' by choosing from a variety of systems thinking methods (mapping, reflection) to engage actively in their positions. This highlights the importance of understanding how key concepts, both traditional planning approaches and systems science concepts, are interpreted and then implemented in real world settings.


    Directory of Open Access Journals (Sweden)

    Ivica Batinić


    Full Text Available Modern restaurant business, as part of a catering business, offers a variety of meals and beverages in restaurants and various related facilities. Promotional activities play a very important role in managing a restaurant and related facilities, because any serious restaurant facility must take all the necessary and effective measures in order to maintain regular guests and approach potential new guests. In this paper, I will write about conceptualizing restaurant business and elementary business systems in restaurant business. In a separate part, I will write about conceptualizing promotions and promotional activities as important factors in achieving better and more efficient communication of restaurants with regular and potential guests.

  10. HDAC Activity Is Required for Efficient Core Promoter Function at the Mouse Mammary Tumor Virus Promoter

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    Sang C. Lee


    Full Text Available Histone deacetylases (HDACs have been shown to be required for basal or inducible transcription at a variety of genes by poorly understood mechanisms. We demonstrated previously that HDAC inhibition rapidly repressed transcription from the mouse mammary tumor virus (MMTV promoter by a mechanism that does not require the binding of upstream transcription factors. In the current study, we find that HDACs work through the core promoter sequences of MMTV as well as those of several cellular genes to facilitate transcriptional initiation through deacetylation of nonhistone proteins.

  11. Exposure to Brefeldin A promotes initiation of meiosis in murine female germ cells. (United States)

    Zhang, Lian-Jun; Chen, Bo; Feng, Xin-Lei; Ma, Hua-Gang; Sun, Li-Lan; Feng, Yan-Min; Liang, Gui-Jin; Cheng, Shun-Feng; Li, Lan; Shen, Wei


    In mammals, ontogenesis starts from a fusion of spermatozoon and oocyte, which are produced by reductive nuclear division of a diploid germ cell in a specialised but complex biological process known as meiosis. However, little is known about the mechanism of meiotic initiation in germ cells, although many factors may be responsible for meiosis both in male and female gonads. In this study, 11.5 days post coitum (dpc) female fetal mouse genital ridges were cultured in vitro with exposure to Brefeldin A (BFA) for 6h, and the changes in meiosis were detected. Synaptonemal-complex analysis implied that BFA played a positive role in meiosis initiation and this hypothesis was confirmed by quantitative PCR of meiosis-specific genes: stimulated by retinoic acid gene 8 (Stra8) and deleted in a zoospermia-like (DAZL). At the same time, mRNA expression of retinoic acid synthetase (Raldh2) and retinoic acid (RA) receptors increased in female gonads with in vitro exposure to BFA. Transplanting genital ridges treated with BFA into the kidney capsule of immunodeficient mice demonstrated that the development capacity of female germ cells was normal, while formation of primordial follicles was seen to be a result of accelerated meiosis after exposure to BFA. In conclusion, the study indicated that BFA stimulated meiosis initiation partly by RA signalling and then promoted the development of follicles.

  12. Regulation of ALF promoter activity in Xenopus oocytes.

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    Dan Li

    Full Text Available BACKGROUND: In this report we evaluate the use of Xenopus laevis oocytes as a matched germ cell system for characterizing the organization and transcriptional activity of a germ cell-specific X. laevis promoter. PRINCIPAL FINDINGS: The promoter from the ALF transcription factor gene was cloned from X. laevis genomic DNA using a PCR-based genomic walking approach. The endogenous ALF gene was characterized by RACE and RT-PCR for transcription start site usage, and by sodium bisulfite sequencing to determine its methylation status in somatic and oocyte tissues. Homology between the X. laevis ALF promoter sequence and those from human, chimpanzee, macaque, mouse, rat, cow, pig, horse, dog, chicken and X. tropicalis was relatively low, making it difficult to use such comparisons to identify putative regulatory elements. However, microinjected promoter constructs were very active in oocytes and the minimal promoter could be narrowed by PCR-mediated deletion to a region as short as 63 base pairs. Additional experiments using a series of site-specific promoter mutants identified two cis-elements within the 63 base pair minimal promoter that were critical for activity. Both elements (A and B were specifically recognized by proteins present in crude oocyte extracts based on oligonucleotide competition assays. The activity of promoter constructs in oocytes and in transfected somatic Xenopus XLK-WG kidney epithelial cells was quite different, indicating that the two cell types are not functionally equivalent and are not interchangeable as assay systems. CONCLUSIONS: Overall the results provide the first detailed characterization of the organization of a germ cell-specific Xenopus promoter and demonstrate the feasibility of using immature frog oocytes as an assay system for dissecting the biochemistry of germ cell gene regulation.

  13. [Physical activity based on the new health promotion perspective: contradictions of an institutional program]. (United States)

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


    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.

  14. International Association for Promoting Geoethics (IAPG): an update on activities (United States)

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


    The International Association for Promoting Geoethics (IAPG: 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

  15. Promotion of sink activity of developing rose shoots by light. (United States)

    Mor, Y; Halevy, A H


    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. The Role of Physical Activity Assessments for School-Based Physical Activity Promotion (United States)

    Welk, Gregory J.


    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…


    Directory of Open Access Journals (Sweden)

    Pavel STANCIU


    Full Text Available The villages of Bucovina possess a particular charm, mainly through the orthodox churches with heritage value, the deep spiritual character sent both to local communities and tourists, the architecture based on wood handicraft, the manner in which traditions, local customs and crafts are still preserved, the multicultural character, and, not least, the outstanding hospitality of the hosts.Continuous improvement of performance in rural tourism refers to an integrated approach of specific elements in the destination Bucovina, online marketing becoming more present in everyday practice of small entrepreneurs in local tourism. From an empirical point of view, promotion of rural tourism on Facebook and YouTube represents an easy initiative accessible to the general public, which has the ability to create the foundation of a competitive tourism.

  18. Recent federal initiatives to promote unconventional gas: High octane delivery of just hot air?

    Energy Technology Data Exchange (ETDEWEB)

    Griff, M.T.


    This paper provides an overview of recent initiatives of the United States which promote greater use of natural gas and unconventional gas as one part of this nations`s larger response to the global warming threat. Measurable increases in greenhouse gas concentrations since the beginning of the industrial revolution have led to the belief in the existence of a global warming problem. The international community has responded to the global warming threat with the United Nations Framework Convention on Climate Change which is directed toward the stabilization of greenhouse gases in the atmosphere. The Climate Change Action Plan is the Clinton Administration`s detailed response to the global warming threat. It is designed to return United States emissions of greenhouse gases to their 1990 levels by the year 2000. The Action Plan targets all greenhouse gases and emphasizes energy efficiency. Significant regulatory reformation designed to increase the efficiency of the natural gas industry has already occurred and will be continued. Recovery of methane emissions from landfills will be encouraged through indentification of suitable sites and use of existing technology and development of new technology. Recovery of methane from coal mining operations will be promoted by targeting 50 of the gassiest mines in the United States. Even if the Action Plan is fully implemented. legitimate questions arise as to whether its goals will be achieved as a result of funding shortfalls.

  19. The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops.

    Directory of Open Access Journals (Sweden)

    Mauricio Menacho-Márquez


    Full Text Available The catalytic activity of GDP/GTP exchange factors (GEFs is considered critical to maintain the typically high activity of Rho GTPases found in cancer cells. However, the large number of them has made it difficult to pinpoint those playing proactive, nonredundant roles in tumors. In this work, we have investigated whether GEFs of the Vav subfamily exert such specific roles in skin cancer. Using genetically engineered mice, we show here that Vav2 and Vav3 favor cooperatively the initiation and promotion phases of skin tumors. Transcriptomal profiling and signaling experiments indicate such function is linked to the engagement of, and subsequent participation in, keratinocyte-based autocrine/paracrine programs that promote epidermal proliferation and recruitment of pro-inflammatory cells. This is a pathology-restricted mechanism because the loss of Vav proteins does not cause alterations in epidermal homeostasis. These results reveal a previously unknown Rho GEF-dependent pro-tumorigenic mechanism that influences the biology of cancer cells and their microenvironment. They also suggest that anti-Vav therapies may be of potential interest in skin tumor prevention and/or treatment.

  20. Promotion of nutrition and physical activity in Dutch general practice

    NARCIS (Netherlands)

    Dillen, van S.; Hiddink, G.J.; Woerkum, van C.M.J.


    Introduction: Promotion of nutrition and physical activity is important to slow down the increase of overweight. General practitioners (GPs) are in an unique position to communicate with their patients about nutrition and physical activity, because of the high referral score, high perceived expertis

  1. Promotion as a Tool in Sustaining the Destination Marketing Activities


    Ivo Mulec


    Promoting the tourism destination in the right and best possible way is today one of vital marketing activities of all Destination Management Organizations. Only successful promotion can entice and attract potential travelers to visit the destination. The number of new destinations is increasing every year and some of them are quite similar. Market segmentation is one of the starting points for devising marketing strategy. Only by presenting the destination to the right segment of potential c...

  2. Promoting Physical Activity Among Overweight Young African American Women

    Centers for Disease Control (CDC) Podcasts


    This podcast is an interview with Nefertiti Durant, MD, MPH, from the University of Alabama at Birmingham about promoting physical activity among overweight and obese young African American Women using Internet-based tools.  Created: 1/15/2014 by Preventing Chronic Disease (PCD), National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 1/15/2014.

  3. A Social Partnership Model to Promote Educators' Development in Mauritius through Formal and Informal Capacity-Building Initiatives (United States)

    Santally, Mohammad Issack; Cooshna-Naik, Dorothy; Conruyt, Noel; Wing, Caroline Koa


    This paper describes a social partnership model based on the living lab concept to promote the professional development of educators through formal and informal capacity-building initiatives. The aim is to have a broader impact on society through community outreach educational initiatives. A Living Lab is an environment for user-centered…

  4. ParticipACTION: the future challenges for physical activity promotion in Canada

    Directory of Open Access Journals (Sweden)

    Cavill Nick


    Full Text Available Abstract This commentary is the concluding piece of a series of papers about the Canadian ParticipACTION initiative. It describes the resurgence of the new ParticipACTION as a national communications initiative in Canada, and sets this in an international context. The set of ParticipACTION papers in this issue establish benchmarks and provide baseline and initial impact data for the evaluation and monitoring of ParticipACTION, using qualitative and quantiative research methods. As a set, they describe a comprehensive approach to setting up evaluations of national social marketing efforts to promote physical activity.


    Directory of Open Access Journals (Sweden)

    Byunghun Choi


    Full Text Available Chinese responsibility for reducing Greenhouse Gas or carbon dioxide emission increases continuously. Chinese government suggested two targets; Alternative Fuel Vehicle output volume 500 thousand and AFV market share 5% by the end of 2011. However any of two targets did not come true. Therefore this study accessed the question, ‘why Chinese government initiative model for AFV promotion has been so poor?’ This study reviewed the transition process for AFV policies in China and made a structural analysis for three key policies since 2009. As a result the number of articles for related industries or factor endowments was relatively more than firm strategy or demand conditions. Also this study accessed the AFV strategy of Six SOEs from the perspective of social responsibility. Six SOEs have more concentrated on electric vehicle rather than hybrid vehicle with following the government leadership. However major EV or HEV models of them mostly were made by Joint Ventures being under control of foreign makers and the JVs have actually controlled over AFV business. So the limitation of Chinese government initiative model resulted from supplier-centric approach with targeting for public transportation and institution consumer, and it caused a failure to create the demand conditions of general customers.

  6. Active Multistatic Track Initiation Cued by Passive Acoustic Detection (United States)


    REFERENCES [1] D. Grimmett and S. Coraluppi, “Multistatic Active Sonar System Inter- operability, Data Fusion and Measures of Performance,” NURC ...Technical Report NURC -FR-2006-004, 2006. [2] D. Grimmett, “Multistatic Target Tracking Using Specular Cue Initiation and Directed Data Retrieval,” Proc. of

  7. Neuronal Activity Promotes Glioma Growth through Neuroligin-3 Secretion. (United States)

    Venkatesh, Humsa S; Johung, Tessa B; Caretti, Viola; Noll, Alyssa; Tang, Yujie; Nagaraja, Surya; Gibson, Erin M; Mount, Christopher W; Polepalli, Jai; Mitra, Siddhartha S; Woo, Pamelyn J; Malenka, Robert C; Vogel, Hannes; Bredel, Markus; Mallick, Parag; Monje, Michelle


    Active neurons exert a mitogenic effect on normal neural precursor and oligodendroglial precursor cells, the putative cellular origins of high-grade glioma (HGG). By using optogenetic control of cortical neuronal activity in a patient-derived pediatric glioblastoma xenograft model, we demonstrate that active neurons similarly promote HGG proliferation and growth in vivo. Conditioned medium from optogenetically stimulated cortical slices promoted proliferation of pediatric and adult patient-derived HGG cultures, indicating secretion of activity-regulated mitogen(s). The synaptic protein neuroligin-3 (NLGN3) was identified as the leading candidate mitogen, and soluble NLGN3 was sufficient and necessary to promote robust HGG cell proliferation. NLGN3 induced PI3K-mTOR pathway activity and feedforward expression of NLGN3 in glioma cells. NLGN3 expression levels in human HGG negatively correlated with patient overall survival. These findings indicate the important role of active neurons in the brain tumor microenvironment and identify secreted NLGN3 as an unexpected mechanism promoting neuronal activity-regulated cancer growth.

  8. Promoters active in interphase are bookmarked during mitosis by ubiquitination. (United States)

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


    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.

  9. Applying Transtheoretical Model to Promote Physical Activities Among Women



    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 transtheo...

  10. Using Virtual Pets to Promote Physical Activity in Children: An Application of the Youth Physical Activity Promotion Model. (United States)

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


    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.

  11. Healthy and wellbeing activities' promotion using a Big Data approach. (United States)

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


    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.

  12. Decrease of epidermal histidase activity by tumor-promoting phorbol esters. (United States)

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


    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.

  13. Eaf1p Is Required for Recruitment of NuA4 in Targeting TFIID to the Promoters of the Ribosomal Protein Genes for Transcriptional Initiation In Vivo. (United States)

    Uprety, Bhawana; Sen, Rwik; Bhaumik, Sukesh R


    NuA4 (nucleosome acetyltransferase of H4) promotes transcriptional initiation of TFIID (a complex of TBP and TBP-associated factors [TAFs])-dependent ribosomal protein genes involved in ribosome biogenesis. However, it is not clearly understood how NuA4 regulates the transcription of ribosomal protein genes. Here, we show that NuA4 is recruited to the promoters of ribosomal protein genes, such as RPS5, RPL2B, and RPS11B, for TFIID recruitment to initiate transcription, and the recruitment of NuA4 to these promoters is impaired in the absence of its Eaf1p component. Intriguingly, impaired NuA4 recruitment in a Δeaf1 strain depletes recruitment of TFIID (a TAF-dependent form of TBP) but not the TAF-independent form of TBP to the promoters of ribosomal protein genes. However, in the absence of NuA4, SAGA (Spt-Ada-Gcn5-acetyltransferase) is involved in targeting the TAF-independent form of TBP to the promoters of ribosomal protein genes for transcriptional initiation. Thus, NuA4 plays an important role in targeting TFIID to the promoters of ribosomal protein genes for transcriptional initiation in vivo. Such a function is mediated via its targeted histone acetyltransferase activity. In the absence of NuA4, ribosomal protein genes lose TFIID dependency and become SAGA dependent for transcriptional initiation. Collectively, these results provide significant insights into the regulation of ribosomal protein gene expression and, hence, ribosome biogenesis and functions.

  14. Mushroom bodies enhance initial motor activity in Drosophila. (United States)

    Serway, Christine N; Kaufman, Rebecca R; Strauss, Roland; de Belle, J Steven


    The central body (or central complex, CCX) and the mushroom bodies (MBs) are brain structures in most insect phyla that have been shown to influence aspects of locomotion. The CCX regulates motor coordination and enhances activity while MBs have, thus far, been shown to suppress motor activity levels measured over time intervals ranging from hours to weeks. In this report, we investigate MB involvement in motor behavior during the initial stages (15 minutes) of walking in Buridan's paradigm. We measured aspects of walking in flies that had MB lesions induced by mutations in six different genes and by chemical ablation. All tested flies were later examined histologically to assess MB neuroanatomy. Mutant strains with MB structural defects were generally less active in walking than wild-type flies. Most mutants in which MBs were also ablated with hydroxyurea (HU) showed additional activity decrements. Variation in measures of velocity and orientation to landmarks among wild-type and mutant flies was attributed to pleiotropy, rather than to MB lesions. We conclude that MBs upregulate activity during the initial stages of walking, but suppress activity thereafter. An MB influence on decision making has been shown in a wide range of complex behaviors. We suggest that MBs provide appropriate contextual information to motor output systems in the brain, indirectly fine tuning walking by modifying the quantity (i.e., activity) of behavior.

  15. Asphalt fume dermal carcinogenicity potential: II. Initiation-promotion assay of Type III built-up roofing asphalt. (United States)

    Freeman, James J; Schreiner, Ceinwen A; Beazley, S; Burnett, Donald M; Clark, Charles R; Mahagaokar, Suneeta; Parker, Craig M; Stewart, Christopher W; Swanson, Mark S; Arp, Earl W


    Clark et al. (accepted for publication) reported that a sample of field-matched fume condensate from a Type III built-up roofing asphalt (BURA) resulted in a carcinogenic response in a mouse skin bioassay, with relatively few tumor-bearing animals, long tumor latency and chronic skin irritation. This mouse skin initiation/promotion study was conducted to assess possible mechanisms, i.e., genotoxic initiation vs. tumor promotion subsequent to repeated skin injury and repair. The same Type III BURA fume condensate sample was evaluated in groups of 30 male Crl:CD1® mice by skin application twice per week (total dose of 50 mg/week) for 2 weeks during the initiation phase and for 26 weeks during the promotion phase. Positive control substances were 7,12-dimethylbenz(a)anthracene (DMBA, 50 μg applied once) as an initiator and 12-O-tetradecanoyl-13-acetate (TPA, 5 μg, applied twice weekly) during the promotion phase. During the 6 months of study with the asphalt fume condensate, eight skin masses were observed when tested for initiation, five of which were confirmed microscopically to be benign squamous cell papillomas. Only two papillomas were observed when tested for promotion. There was no apparent relationship between skin irritation and tumor development in this study. These results are more indicative of genotoxicity rather than a non-genotoxic mode of action.

  16. Evaluation of the Mental Healthiness Aging Initiative: community program to promote awareness about mental health and aging issues. (United States)

    Zanjani, Faika; Kruger, Tina; Murray, Deborah


    The objective of this study is to evaluate the Mental Healthiness Aging Initiative, designed to promote community awareness and knowledge about mental health and aging issues. This study occurred during 2007-2009 in 67 of 120 counties in Kentucky. A rural region (11 counties) received the intervention, consisting of focus groups, Extension Agent training, and television-based social marketing campaign. Partial-intervention counties (29 counties) received only the television-based social marketing campaign. The control counties (27 counties) received no intervention activities. Results indicated that the intervention counties agreed more with being able to assist elder adults with a potential mental illness. Also, the intervention counties understood the risk of consuming alcohol and medications better, but had a poorer recognition of drinking problems in elder adults. These findings need to be considered within study limitations, such as measurement error, degree of intervention exposure, and regional differences across intervention groups. The study demonstrates that community interventions on mental health awareness and knowledge are feasible within majority rural regions, with Extension Agents being gatekeepers, for promoting positive messages about mental health and aging issues.

  17. BRCA1-IRIS overexpression promotes and maintains the tumor initiating phenotype: implications for triple negative breast cancer early lesions. (United States)

    Sinha, Abhilasha; Paul, Bibbin T; Sullivan, Lisa M; Sims, Hillary; El Bastawisy, Ahmed; Yousef, Hend F; Zekri, Abdel-Rahman N; Bahnassy, Abeer A; ElShamy, Wael M


    Tumor-initiating cells (TICs) are cancer cells endowed with self-renewal, multi-lineage differentiation, increased chemo-resistance, and in breast cancers the CD44+/CD24-/ALDH1+ phenotype. Triple negative breast cancers show lack of BRCA1 expression in addition to enhanced basal, epithelial-to-mesenchymal transition (EMT), and TIC phenotypes. BRCA1-IRIS (hereafter IRIS) is an oncogene produced by the alternative usage of the BRCA1 locus. IRIS is involved in induction of replication, transcription of selected oncogenes, and promoting breast cancer cells aggressiveness. Here, we demonstrate that IRIS overexpression (IRISOE) promotes TNBCs through suppressing BRCA1 expression, enhancing basal-biomarkers, EMT-inducers, and stemness-enforcers expression. IRISOE also activates the TIC phenotype in TNBC cells through elevating CD44 and ALDH1 expression/activity and preventing CD24 surface presentation by activating the internalization pathway EGFR→c-Src→cortactin. We show that the intrinsic sensitivity to an anti-CD24 cross-linking antibody-induced cell death in membranous CD24 expressing/luminal A cells could be acquired in cytoplasmic CD24 expressing IRISOE TNBC/TIC cells through IRIS silencing or inactivation. We show that fewer IRISOE TNBC/TICs cells form large tumors composed of TICs, resembling TNBCs early lesions in patients that contain metastatic precursors capable of disseminating and metastasizing at an early stage of the disease. IRIS-inhibitory peptide killed these IRISOE TNBC/TICs, in vivo and prevented their dissemination and metastasis. We propose IRIS inactivation could be pursued to prevent dissemination and metastasis from early TNBC tumor lesions in patients.

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

    Institute of Scientific and Technical Information of China (English)



    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.

  19. Promoting policy and environmental change using photovoice in the Kaiser Permanente Community Health Initiative. (United States)

    Kramer, Leila; Schwartz, Pamela; Cheadle, Allen; Borton, J Elaine; Wright, Merrick; Chase, Charlie; Lindley, Corina


    Creative ways must be found to engage both community residents and political leaders around policy and environmental solutions to public health issues. Photovoice is a community-based, participatory approach to documentary photography that provides people with training on photography, ethics, critical discussion, and policy advocacy. Photovoice projects have been implemented across the nation as part of Kaiser Permanente's Community Health Initiative-a community-based obesity prevention effort. This article focuses on the first Photovoice project implemented in three communities in Colorado. Photovoice themes related to healthy eating and active living include a lack of access to healthy food choices in stores and schools, unsafe street crossings and sidewalks, and the need to redevelop certain areas to encourage safe recreation. The involvement of policy leaders in the project combined with several dissemination activities has contributed to healthier food offerings in schools and neighborhoods and city planning efforts that emphasize walkability and access to healthy food, and park revitalization.

  20. Health Promotion Guidance Activity of Youth Sports Clubs (United States)

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


    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…

  1. Improving health through policies that promote active travel

    DEFF Research Database (Denmark)

    de Nazelle, Audrey; Nieuwenhuijsen, Mark J; Antó, Josep M;


    Substantial policy changes to control obesity, limit chronic disease, and reduce air pollution emissions, including greenhouse gasses, have been recommended. Transportation and planning policies that promote active travel by walking and cycling can contribute to these goals, potentially yielding...... further co-benefits. Little is known, however, about the interconnections among effects of policies considered, including potential unintended consequences....

  2. How do general practitioners in Denmark promote physical activity?

    DEFF Research Database (Denmark)

    Jørgensen, Tanja K; Nordentoft, Merete; Krogh, Jesper


    The primary objective of this study was to quantify the frequency of advice given on type, frequency, duration, and intensity of exercise during physical activity (PA) promoting sessions by general practitioners. Second, to find GP characteristics associated with high quality of PA counselling....

  3. Healthy and Active Ageing: Social Capital in Health Promotion (United States)

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


    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…

  4. The Role of Values in Promoting Physical Activity (United States)

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


    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…

  5. Ultraviolet irradiation initiates ectopic foot formation in regenerating hydra and promotes budding

    Indian Academy of Sciences (India)

    Saroj S Ghaskadbi; Leena Shetye; Shashi Chiplonkar; Surendra Ghaskadbi


    We have studied the effects of ultraviolet-C (UVC) and Ultraviolet-B (UVB) on growth and pattern formation in Pelmatohydra oligactis. UVC brings about a significant increase in budding in intact hydra while UVB does not exhibit such an effect. Excessive budding could be a response for survival at wavelengths that damage biological tissues. If the head or base piece of a bisected hydra is irradiated and recombined with the unirradiated missing part, regeneration proceeds normally indicating that exposure of a body part with either an intact head or foot to UVC does not influence pattern formation. Most significantly, in the middle piece, but not in the head or the base piece of a trisected hydra, UVC leads to initiation of ectopic feet formation in almost one third of the cases. Thus, UV irradiation interferes with pattern formation in regenerating hydra, possibly by changing positional values, and promotes budding in intact hydra. This is the first report on induction of ectopic feet formation by UV in regenerating hydra and opens up the possibility of using UV irradiation as a tool to understand pattern formation in the enigmatic hydra.

  6. Tumour-promoting activity of polycyclic aromatic hydrocarbons and their oxygenated or nitrated derivatives. (United States)

    Misaki, Kentaro; Takamura-Enya, Takeji; Ogawa, Hideoki; Takamori, Kenji; Yanagida, Mitsuaki


    Various types of polycyclic aromatic compounds (PACs) in diesel exhaust particles are thought to contribute to carcinogenesis in mammals. Although the carcinogenicity, mutagenicity and tumour-initiating activity of these compounds have been evaluated, their tumour-promoting activity is unclear. In the present study, to determine the tumour-inducing activity of PACs, including previously known mutagenic compounds in atmospheric environments, a transformation assay for promoting activity mediated by the release of contact inhibition was conducted for six polycyclic aromatic hydrocarbons (PAHs), seven oxygenated PAHs (oxy-PAHs) and seven nitrated PAHs (nitro-PAHs) using mouse embryonic fibroblast cells transfected with the v-Ha-ras gene (Bhas 42 cells). Of these, two PAHs [benzo[k]fluoranthene (B[k]FA) and benzo[b]fluoranthene (B[b]FA)], one oxy-PAH [6H-benzo[cd]pyren-6-one (BPO)] and two nitro-PAHs (3-nitro-7H-benz[de]anthracen-7-one and 6-nitrochrysene) were found to exhibit particularly powerful tumour-promoting activity (≥10 foci following exposure to BPO). Further, an HO-1 antioxidant response activation was observed following exposure to B[k]FA, B[b]FA and BPO, suggesting that the induction of tumour-promoting activity in these compounds is correlated with the dysfunction of signal transduction via AhR-mediated responses and/or oxidative stress responses.

  7. Mapping of RNA initiation sites by high doses of uv iradiation: evidence for three independent promoters within the left 11% of the Ad-2 genome

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, M.C.; Fraser, N.W.; Darnell, J.E. Jr.


    Cells infected with Ad-2 virus were irradiated so that uv-induced lesions were introduced every 500 to 1000 nucleotides in the genomes, consequently leading to the premature termination of RNA transcription. Such cells when labeled with (/sup 3/H)uridine accumulate labeled promoter proximal RNA. Hybridization of this RNA after size fractionation to restriction fragments of the Ad-2 genome allowed the identification of DNA sequences containing active RNA initiation sites. Early during the infectious cycle two active RNA initiation sites were found within the left 11% of the Ad-2 genome within the 0 to 3.0 and 4.4 to 8.0 restriction fragments. During late infection (15 hr) an additional uv resistant transcript was detected indicating that a newly activated RNA initiation site, presumably for protein IX, resides within the fragment 8.0 to 11.2.

  8. Analysis of promoter activity in transgenic plants by normalizing expression with a reference gene: anomalies due to the influence of the test promoter on the reference promoter

    Indian Academy of Sciences (India)

    Simran Bhullar; Suma Chakravarthy; Deepak Pental; Pradeep Kumar Burma


    Variations in transgene expression due to position effect and copy number are normalized when analysing and comparing the strengths of different promoters. In such experiments, the promoter to be tested is placed upstream to a reporter gene and a second expression cassette is introduced in a linked fashion in the same transfer DNA (T-DNA). Normalization in the activity of the test promoter is carried out by calculating the ratio of activities of the test and reference promoters. When an appropriate number of independent transgenic events are analysed, normalization facilitates assessment of the relative strengths of the test promoters being compared. In this study, using different modified versions of the Cauliflower Mosaic Virus (CaMV) 35S promoter expressing the reporter gene -glucuronidase (gus) (test cassette) linked to a chloramphenicol acetyl transferase (cat) gene under the wild-type 35S promoter (reference cassette) in transgenic tobacco lines, we observed that cat gene expression varied depending upon the strength of the modified 35S promoter expressing the gus gene. The 35S promoter in the reference cassette was found to have been upregulated in cases where the modified 35S promoter was weaker than the wild-type 35S promoter. Many studies have been carried out in different organisms to study the phenomenon of transcriptional interference, which refers to the reduced expression of the downstream promoter by a closely linked upstream promoter. However, we observed a positive interaction wherein the weakened activity of a promoter led to upregulation of a contiguous promoter. These observations suggest that, in situations where the promoters of the test and reference gene share the same transcription factors, the activity of the test promoter can influence the activity of the reference promoter in a way that the test promoter’s strength is underestimated when normalized by the reference promoter.

  9. Technology to promote and increase physical activity in heart failure. (United States)

    Franklin, Nina C


    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.

  10. cis Determinants of Promoter Threshold and Activation Timescale

    Directory of Open Access Journals (Sweden)

    Anders S. Hansen


    Full Text Available Although the relationship between DNA cis-regulatory sequences and gene expression has been extensively studied at steady state, how cis-regulatory sequences affect the dynamics of gene induction is not known. The dynamics of gene induction can be described by the promoter activation timescale (AcTime and amplitude threshold (AmpThr. Combining high-throughput microfluidics with quantitative time-lapse microscopy, we control the activation dynamics of the budding yeast transcription factor, Msn2, and reveal how cis-regulatory motifs in 20 promoter variants of the Msn2-target-gene SIP18 affect AcTime and AmpThr. By modulating Msn2 binding sites, we can decouple AmpThr from AcTime and switch the SIP18 promoter class from high AmpThr and slow AcTime to low AmpThr and either fast or slow AcTime. We present a model that quantitatively explains gene-induction dynamics on the basis of the Msn2-binding-site number, TATA box location, and promoter nucleosome organization. Overall, we elucidate the cis-regulatory logic underlying promoter decoding of TF dynamics.

  11. TALE factors poise promoters for activation by Hox proteins. (United States)

    Choe, Seong-Kyu; Ladam, Franck; Sagerström, Charles G


    Hox proteins form complexes with TALE cofactors from the Pbx and Prep/Meis families to control transcription, but it remains unclear how Hox:TALE complexes function. Examining a Hoxb1b:TALE complex that regulates zebrafish hoxb1a transcription, we find maternally deposited TALE proteins at the hoxb1a promoter already during blastula stages. These TALE factors recruit histone-modifying enzymes to promote an active chromatin profile at the hoxb1a promoter and also recruit RNA polymerase II (RNAPII) and P-TEFb. However, in the presence of TALE factors, RNAPII remains phosphorylated on serine 5 and hoxb1a transcription is inefficient. By gastrula stages, Hoxb1b binds together with TALE factors to the hoxb1a promoter. This triggers P-TEFb-mediated transitioning of RNAPII to the serine 2-phosphorylated form and efficient hoxb1a transcription. We conclude that TALE factors access promoters during early embryogenesis to poise them for activation but that Hox proteins are required to trigger efficient transcription.

  12. Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control

    DEFF Research Database (Denmark)

    Klein, Ditte Kjærsgaard; Hoffmann, Saskia; Ahlskog, Johanna K


    an important role in checkpoint control following ionizing radiation. Cyclin F-depleted cells initiate checkpoint signalling after ionizing radiation, but fail to maintain G2 phase arrest and progress into mitosis prematurely. Importantly, cyclin F suppresses the B-Myb-driven transcriptional programme...... that promotes accumulation of crucial mitosis-promoting proteins. Cyclin F interacts with B-Myb via the cyclin box domain. This interaction is important to suppress cyclin A-mediated phosphorylation of B-Myb, a key step in B-Myb activation. In summary, we uncover a regulatory mechanism linking the F-box protein...

  13. From the Paralympics to public health: increasing physical activity through legislative and policy initiatives. (United States)

    Blauwet, Cheri A; Iezzoni, Lisa I


    Individuals with disabilities experience a disproportionate rate of chronic disease and are more likely to lead sedentary lifestyles than the general population. Multiple complex factors likely contribute to these disparities, including structural, socioeconomic and attitudinal barriers that impede broad participation of individuals with disabilities in health and wellness promotion programs. Public health initiatives aimed at mitigating these health disparities emphasize improved access to physical activity and sports opportunities. Given its visibility, the Paralympic Movement provides an opportunity to transform how society conceptualizes the relationship of disability to physical fitness. The Paralympics also serve as a catalyst for public health education and program development. Already, public policies and governmental regulations are expanding grassroots sports opportunities for youth and adults with disabilities, thus promoting inclusive opportunities for participation in physical activity.

  14. Health-promoting physical activity of adults with mental retardation. (United States)

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


    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.

  15. A Pilot Physical Activity Initiative to Improve Mental Health Status amongst Iranian Institutionalized Older People

    Directory of Open Access Journals (Sweden)

    Hossein Matlabi


    Full Text Available Background: Sufficient level of physical activity may promote overall and mental health of old people. This study was carried out to investigate the practicability of a physical activity promotion initiative amongst institutionalized older people in Tabriz, Iran. Methods: Purposive sampling method was used in this semi-experimental study to recruit 31 older people living in a selected residential care in Tabriz. Moderate-intensity aerobic and muscle-strengthening activity was planned for those who had not severe baseline cognitive impairment or were not too frail to undertake the survey. The General Health Questionnaire (GHQ-28 was used to measure mental health status before and after intervention through a face-to-face interview. Descriptive statistics, Wilkcoxon rank-sum, Mann–Whitney U and Chi-Square tests were employed to analyses the data. Results: The applied intervention was significantly improved status of physical health, anxiety and insomnia, social dysfunction and severe depression. Conclusion: Incorporation of physical activity promotion programs into routines of older people residential care homes in Iran is feasible but may need training of physical activity specialists to work with older people based on their physical endurance and limitations.

  16. Promoting Space Education and Awareness in Pakistan- Initiatives, Achievements, Challenges and Issues (United States)

    Jagirani, Aisha

    With about 180 million inhabitants, Pakistan is the sixth most populous and the 34th largest country in the world in terms of area. Pakistan's economy, which is pre-dominantly based on agriculture, is the 26th largest in the world in terms of purchasing power parity and 45th largest in terms of nominal GDP. Pakistan is counted among the Next Eleven (N11) countries that have the potential to become the world's largest economies in the 21st century. Despite considerable potential to develop into a stable, moderate and democratic state, major challenges of internal security, poor agricultural productivity, inadequate infrastructure, food insecurity, insufficient health and educational facilities, depletion of natural resources, rapid environmental degradation and recurring natural disasters have burdened the country and have hampered sustainable development of Pakistan. Space technology applications offer a cost-effective means of addressing many of the above mentioned issues and have made impressive advances in the last few years in different countries in the region. Unfortunately, for various reasons, Pakistan has not been able to fully exploit the benefits of space technology and its applications to meet the challenges she faces. One of the reasons is lack of awareness and understanding by planners, decision-makers and users about the potential benefits of space technology in planning and implementation of developmental plans as well as good governance. Similarly, Pakistan's space program enjoys little public support due, primarily, to lack of awareness of the benefits space offers and the ubiquitousness of space applications in modern life. There is thus an acute need to create awareness and educate all segments of the society and stakeholders in Pakistan about the potential benefits of space technology and its applications. In the past ten years, many initiatives have been taken to promote space education and awareness for students as well as decision-makers in

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

    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


    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.

  18. An Ikaros Promoter Element with Dual Epigenetic and Transcriptional Activities. (United States)

    Perotti, Elizabeth A; Georgopoulos, Katia; Yoshida, Toshimi


    Ikaros DNA binding factor plays critical roles in lymphocyte development. Changes in Ikaros expression levels during lymphopoiesis are controlled by redundant but also unique regulatory elements of its locus that are critical for this developmental process. We have recently shown that Ikaros binds its own locus in thymocytes in vivo. Here, we evaluated the role of an Ikaros binding site within its major lympho-myeloid promoter. We identified an Ikaros/Ets binding site within a promoter sub-region that was highly conserved in mouse and human. Deletion of this binding site increased the percentage of the reporter-expressing mouse lines, indicating that its loss provided a more permissive chromatin environment. However, once transcription was established, the lack of this site decreased transcriptional activity. These findings implicate a dual role for Ikaros/Ets1 binding on Ikzf1 expression that is exerted at least through its promoter.

  19. An Ikaros Promoter Element with Dual Epigenetic and Transcriptional Activities.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Perotti

    Full Text Available Ikaros DNA binding factor plays critical roles in lymphocyte development. Changes in Ikaros expression levels during lymphopoiesis are controlled by redundant but also unique regulatory elements of its locus that are critical for this developmental process. We have recently shown that Ikaros binds its own locus in thymocytes in vivo. Here, we evaluated the role of an Ikaros binding site within its major lympho-myeloid promoter. We identified an Ikaros/Ets binding site within a promoter sub-region that was highly conserved in mouse and human. Deletion of this binding site increased the percentage of the reporter-expressing mouse lines, indicating that its loss provided a more permissive chromatin environment. However, once transcription was established, the lack of this site decreased transcriptional activity. These findings implicate a dual role for Ikaros/Ets1 binding on Ikzf1 expression that is exerted at least through its promoter.

  20. Promotion as a Tool in Sustaining the Destination Marketing Activities

    Directory of Open Access Journals (Sweden)

    Ivo Mulec


    Full Text Available Promoting the tourism destination in the right and best possible way is today one of vital marketing activities of all Destination Management Organizations. Only successful promotion can entice and attract potential travelers to visit the destination. The number of new destinations is increasing every year and some of them are quite similar. Market segmentation is one of the starting points for devising marketing strategy. Only by presenting the destination to the right segment of potential clients in the right way will a destination maximize the effectiveness of its marketing and promotion. Tourism destination marketers will continue to face considerable challenges in the future: they will have to take account of the needs, wants and expectations of more mature and knowledgeable customers, and the corresponding need for more up-to-date and reliable information upon which to base decision-making. In the future only marketing which includes collaborative dimensions will meet its objectives fully.

  1. IKKβ in intestinal mesenchymal cells promotes initiation of colitis-associated cancer. (United States)

    Koliaraki, Vasiliki; Pasparakis, Manolis; Kollias, George


    The importance of mesenchymal cells in inflammation and/or neoplastic transformation is well recognized, but their role in the initiation of these processes, particularly in the intestine, remains elusive. Using mouse models of colorectal cancer, we show that IKKβ in intestinal mesenchymal cells (IMCs) is critically involved in colitis-associated, but not spontaneous tumorigenesis. We further demonstrate that IMC-specific IKKβ is involved in the initiation of colitis-associated cancer (CAC), as in its absence mice develop reduced immune cell infiltration, epithelial cell proliferation, and dysplasia at the early stages of the disease. At the molecular level, these effects are associated with decreased early production of proinflammatory and protumorigenic mediators, including IL-6, and reduced STAT3 activation. Ex vivo IKKβ-deficient IMCs show defective responses to innate immune stimuli such as LPS, as shown by decreased NF-κB signaling and reduced expression of important NF-κB target genes. Collectively, our results reveal a hitherto unknown role of mesenchymal IKKβ in driving inflammation and enabling carcinogenesis in the intestine.

  2. Boron-10 ABUNCL Prototype Models And Initial Active Testing

    Energy Technology Data Exchange (ETDEWEB)

    Kouzes, Richard T.; Ely, James H.; Lintereur, Azaree T.; Siciliano, Edward R.


    The Department of Energy Office of Nuclear Safeguards and Security (NA-241) is supporting the project Coincidence Counting With Boron-Based Alternative Neutron Detection Technology at Pacific Northwest National Laboratory (PNNL) for the development of a 3He proportional counter alternative neutron coincidence counter. The goal of this project is to design, build and demonstrate a system based upon 10B-lined proportional tubes in a configuration typical for 3He-based coincidence counter applications. This report provides results from MCNPX model simulations and initial testing of the active mode variation of the Alternative Boron-Based Uranium Neutron Coincidence Collar (ABUNCL) design built by General Electric Reuter-Stokes. Initial experimental testing of the as-delivered passive ABUNCL was previously reported.

  3. Spontaneous initiation, promotion and progression of colorectal cancer in the novel A/J Min/+ mouse. (United States)

    Sødring, Marianne; Gunnes, Gjermund; Paulsen, Jan Erik


    The C57BL/6J multiple intestinal neoplasia (Min/+) mouse is a widely used murine model for familial adenomatous polyposis, a hereditary form of human colorectal cancer. However, it is a questionable model partly because the vast majority of tumors arise in the small intestine, and partly because the fraction of tumors that progress to invasive carcinomas is minuscule. A/J mice are typically more susceptible to carcinogen-induced colorectal cancer than C57BL/6J mice. To investigate whether the novel Min/+ mouse on the A/J genetic background could be a better model for colorectal cancer, we examined the spontaneous intestinal tumorigenesis in 81 A/J Min/+ mice ranging in age from 4 to 60 weeks. The A/J Min/+ mouse exhibited a dramatic increase in number of colonic lesions when compared to what has been reported for the conventional Min/+ mouse; however, an increase in small intestinal lesions did not occur. In addition, this novel mouse model displayed a continual development of colonic lesions highlighted by the transition from early lesions (flat ACF) to tumors over time. In mice older than 40 weeks, 13 colonic (95% CI: 8.7-16.3) and 21 small intestinal (95% CI: 18.6-24.3) tumors were recorded. Notably, a considerable proportion of those lesions progressed to carcinomas in both the colon (21%) and small intestine (51%). These findings more closely reflect aspects of human colorectal carcinogenesis. In conclusion, the novel A/J Min/+ mouse may be a relevant model for initiation, promotion and progression of colorectal cancer.

  4. Applying Transtheoretical Model to Promote Physical Activities Among Women (United States)

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


    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

  5. School health guidelines to promote healthy eating and physical activity. (United States)


    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.

  6. Gene activation regresses atherosclerosis, promotes health, and enhances longevity

    Directory of Open Access Journals (Sweden)

    Luoma Pauli V


    Full Text Available Abstract Background Lifestyle factors and pharmacological compounds activate genetic mechanisms that influence the development of atherosclerotic and other diseases. This article reviews studies on natural and pharmacological gene activation that promotes health and enhances longevity. Results Living habits including healthy diet and regular physical activity, and pharmacotherapy, upregulate genes encoding enzymes and apolipoprotein and ATP-binding cassette transporters, acting in metabolic processes that promote health and increase survival. Cytochrome P450-enzymes, physiological factors in maintaining cholesterol homeostasis, generate oxysterols for the elimination of surplus cholesterol. Hepatic CTP:phosphocholine cytidylyltransferase-α is an important regulator of plasma HDL-C level. Gene-activators produce plasma lipoprotein profile, high HDL-C, HDL2-C and HDL-C/cholesterol ratio, which is typical of low risk of atherosclerotic disease, and also of exceptional longevity together with reduced prevalence of cardiovascular, metabolic and other diseases. High HDL contributes to protection against inflammation, oxidation and thrombosis, and associates with good cognitive function in very old people. Avoiding unhealthy stress and managing it properly promotes health and increases life expectancy. Conclusions Healthy living habits and gene-activating xenobiotics upregulate mechanisms that produce lipoprotein pattern typical of very old people and enhance longevity. Lipoprotein metabolism and large HDL2 associate with the process of living a very long life. Major future goals for health promotion are the improving of commitment to both wise lifestyle choices and drug therapy, and further the developing of new and more effective and well tolerated drugs and treatments.

  7. Mental health promotion initiatives for children and youth in contexts of poverty: the case of South Africa. (United States)

    Petersen, Inge; Swartz, Leslie; Bhana, Arvin; Flisher, Alan J


    In order to achieve sustainable development and a consequent reduction in levels of poverty, a multisectoral response to development incorporating pro-poor economic policies in low- to middle-income countries (LMICs) is required. An important aspect is strengthening the human capital asset base of vulnerable populations. This should include the promotion of mental health, which can play an important role in breaking the intergenerational cycle of poverty and mental ill-health through promoting positive mental health outcomes within the context of risk. For each developmental phase of early childhood, middle childhood and adolescence, this article provides: (i) an overview of the critical risk influences and evidence of the role of mental health promotion initiatives in mediating these influences; (ii) a background to these risk influences in South Africa; and (iii) a review of mental health promotion initiatives addressing distal upstream influences at a macro-policy level in South Africa, as well as evidence-based micro- and community-level interventions that have the potential to be scaled up. From this review, strengths and gaps in existing micro- and community-level evidence-based mental health promotion interventions as well as macro-policy-level initiatives are identified, and recommendations made for South Africa that may also have applicability for other LMICs.

  8. State activities that promote fuel cell and hydrogen infrastructure development

    Energy Technology Data Exchange (ETDEWEB)

    Gangi, J. [Fuel Cells 2000, Washington, DC (United States). Breakthrough Technologies Inst.


    The fuel cell and hydrogen industry provide environmental benefits in addition to economic benefits in the form of jobs and business. This presentation outlined the initiatives, policy and partnerships that individual states are initiating to promote the commercialization of fuel cells and hydrogen fuels. Multi-state partnerships and regional organizations and initiatives were highlighted along with state programs, regulations, demonstrations and incentives that include hydrogen, fuel cells and zero emission vehicles. It was shown that 47 states and the District of Columbia (DC) are involved in the promotion of fuel cell or hydrogen legislation and funding. Breakthrough Technologies Institute, the parent organization of Fuel Cells 2000, and the U.S. Department of Energy's Hydrogen Program has launched a searchable database that catalogues all stationary installations, hydrogen fueling stations and vehicle demonstration programs in the United States, including cars, buses and specialty vehicles. The database is intended to be a guide for local, state and federal lawmakers to implement similar legislation and initiatives in their jurisdictions. The database includes regulations such as interconnection standards, renewable portfolio standards and net metering as well as legislation such as tax credits, grants, and loans. Roadmaps and funding/support for business incubators and relocation are included. The database is also an important tool for the general public who are trying to learn more about the technology. Although federal research money has mainly focused on transportation and related fuel technologies, individual states are targeting other applications and areas such as materials and components, stationary power and fuel storage.

  9. DNA Topoisomerases maintain promoters in a state competent for transcriptional activation in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Jakob Madsen Pedersen

    Full Text Available To investigate the role of DNA topoisomerases in transcription, we have studied global gene expression in Saccharomyces cerevisiae cells deficient for topoisomerases I and II and performed single-gene analyses to support our findings. The genome-wide studies show a general transcriptional down-regulation upon lack of the enzymes, which correlates with gene activity but not gene length. Furthermore, our data reveal a distinct subclass of genes with a strong requirement for topoisomerases. These genes are characterized by high transcriptional plasticity, chromatin regulation, TATA box presence, and enrichment of a nucleosome at a critical position in the promoter region, in line with a repressible/inducible mode of regulation. Single-gene studies with a range of genes belonging to this group demonstrate that topoisomerases play an important role during activation of these genes. Subsequent in-depth analysis of the inducible PHO5 gene reveals that topoisomerases are essential for binding of the Pho4p transcription factor to the PHO5 promoter, which is required for promoter nucleosome removal during activation. In contrast, topoisomerases are dispensable for constitutive transcription initiation and elongation of PHO5, as well as the nuclear entrance of Pho4p. Finally, we provide evidence that topoisomerases are required to maintain the PHO5 promoter in a superhelical state, which is competent for proper activation. In conclusion, our results reveal a hitherto unknown function of topoisomerases during transcriptional activation of genes with a repressible/inducible mode of regulation.

  10. Sustainable Professional Learning for Early Childhood Educators: Lessons from an Australia-Wide Mental Health Promotion Initiative (United States)

    Askell-Williams, Helen; Murray-Harvey, Rosalind


    New policy initiatives, such as those concerned with promoting young children's positive mental health, highlight the need for good quality professional education in the early childhood education and care sector. However, although a wealth of literature exists from the school sector, little is known about professional education in early childhood…

  11. TERT promoter mutations and monoallelic activation of TERT in cancer. (United States)

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


    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.

  12. The putative RNA helicase HELZ promotes cell proliferation, translation initiation and ribosomal protein S6 phosphorylation.

    Directory of Open Access Journals (Sweden)

    Philippe A Hasgall

    Full Text Available The hypoxia-inducible transcription factor (HIF is a key component of the cellular adaptation mechanisms to hypoxic conditions. HIFα subunits are degraded by prolyl-4-hydroxylase domain (PHD enzyme-dependent prolyl-4-hydroxylation of LxxLAP motifs that confer oxygen-dependent proteolytic degradation. Interestingly, only three non-HIFα proteins contain two conserved LxxLAP motifs, including the putative RNA helicase with a zinc finger domain HELZ. However, HELZ proteolytic regulation was found to be oxygen-independent, supporting the notion that a LxxLAP sequence motif alone is not sufficient for oxygen-dependent protein destruction. Since biochemical pathways involving RNA often require RNA helicases to modulate RNA structure and activity, we used luciferase reporter gene constructs and metabolic labeling to demonstrate that HELZ overexpression activates global protein translation whereas RNA-interference mediated HELZ suppression had the opposite effect. Although HELZ interacted with the poly(A-binding protein (PABP via its PAM2 motif, PABP was dispensable for HELZ function in protein translation. Importantly, downregulation of HELZ reduced translational initiation, resulting in the disassembly of polysomes, in a reduction of cell proliferation and hypophosphorylation of ribosomal protein S6.

  13. Has physical activity anything to do with health promotion?

    DEFF Research Database (Denmark)

    Thing, Lone Friis

    Within academic discussions of health promotion related to physical activity an Eliasian perspective is seldom used. Based on a central theoretical theme within Norbert Elias’ sociology of sport (Elias and Dunning 1986), namely the quest for excitement, this article explores the health orientatio...... issues connected to physical inactivity. References: Michie S, Atkins L, West R. (2014) The Behaviour Change Wheel: A Guide to Designing Interventions. London: Silverback Publishing.


    Energy Technology Data Exchange (ETDEWEB)

    D.A. Kalinich


    Impacts due to nearby installations and operations were determined in the Preliminary MGDS Hazards Analysis (CRWMS M&O 1996) to be potentially applicable to the proposed repository at Yucca Mountain. This determination was conservatively based on limited knowledge of the potential activities ongoing on or off the Nevada Test Site (NTS). It is intended that the Industrial/Military Activity-Initiated Accident Screening Analysis provided herein will meet the requirements of the ''Standard Review Plan for the Review of Safety Analysis Reports for Nuclear Power Plants'' (NRC 1987) in establishing whether this external event can be screened from further consideration or must be included as a design basis event (DBE) in the development of accident scenarios for the Monitored Geologic Repository (MGR). This analysis only considers issues related to preclosure radiological safety. Issues important to waste isolation as related to impact from nearby installations will be covered in the MGR performance assessment.

  15. Mannoproteins from Cryptococcus neoformans promote dendritic cell maturation and activation. (United States)

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


    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.

  16. Libraries of Synthetic TALE-Activated Promoters: Methods and Applications. (United States)

    Schreiber, T; Tissier, A


    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.

  17. The translation initiation factor DAP5 promotes IRES-driven translation of p53 mRNA. (United States)

    Weingarten-Gabbay, S; Khan, D; Liberman, N; Yoffe, Y; Bialik, S; Das, S; Oren, M; Kimchi, A


    Translational regulation of the p53 mRNA can determine the ratio between p53 and its N-terminal truncated isoforms and therefore has a significant role in determining p53-regulated signaling pathways. Although its importance in cell fate decisions has been demonstrated repeatedly, little is known about the regulatory mechanisms that determine this ratio. Two internal ribosome entry sites (IRESs) residing within the 5'UTR and the coding sequence of p53 mRNA drive the translation of full-length p53 and Δ40p53 isoform, respectively. Here, we report that DAP5, a translation initiation factor shown to positively regulate the translation of various IRES containing mRNAs, promotes IRES-driven translation of p53 mRNA. Upon DAP5 depletion, p53 and Δ40p53 protein levels were decreased, with a greater effect on the N-terminal truncated isoform. Functional analysis using bicistronic vectors driving the expression of a reporter gene from each of these two IRESs indicated that DAP5 preferentially promotes translation from the second IRES residing in the coding sequence. Furthermore, p53 mRNA expressed from a plasmid carrying this second IRES was selectively shifted to lighter polysomes upon DAP5 knockdown. Consequently, Δ40p53 protein levels and the subsequent transcriptional activation of the 14-3-3σ gene, a known target of Δ40p53, were strongly reduced. In addition, we show here that DAP5 interacts with p53 IRES elements in in vitro and in vivo binding studies, proving for the first time that DAP5 directly binds a target mRNA. Thus, through its ability to regulate IRES-dependent translation of the p53 mRNA, DAP5 may control the ratio between different p53 isoforms encoded by a single mRNA.

  18. Self-Regulation, Metacognition and Child- and Adult-Initiated Activity: Does It Matter Who Initiates the Task? (United States)

    Robson, Sue


    Debate about the balance between child- and adult-initiated activities in early childhood settings is long standing. This article reports a study of 29 children aged 4-5 years in a London state school, on the influences of child- and adult-initiated activities on children's self-regulation and metacognition. Whilst both contexts were supportive,…

  19. Mental health promotion in the health care setting: collaboration and engagement in the development of a mental health promotion capacity-building initiative. (United States)

    Horn, Michelle A; Rauscher, Alana B; Ardiles, Paola A; Griffin, Shannon L


    Health Compass is an innovative, multiphased project that aims to transform health care practice and shift organizational culture by building the capacity of Provincial Health Services Authority (PHSA) health care providers to further promote the mental health and well-being of patients and families accessing PHSA's health care services. Health Compass was developed within a health promotion framework, which involved collaboration and engagement with stakeholders across all partnering PHSA agencies. This approach led to the development of an educational and training resource that contributes to increased capacity for mental health promotion within the health care setting. Based on interviews with Health Compass' internal Project Team and findings from a Stakeholder Engagement Evaluation Report, this article outlines the participatory approach taken to develop the Health Compass Mental Health Promotion Resource and E-Learning Tool. A number of key facilitators for collaboration and engagement are discussed, which may be particularly applicable to the implementation of a mental health promotion program or initiative within a complex health care setting.

  20. Isolation and characterization of active promoters from Gluconacetobacter diazotrophicus strain PAL5 using a promoter-trapping plasmid. (United States)

    Schwab, Stefan; Pessoa, Cristiane Alves; de Lima Bergami, Amanda Aparecida; de Azevedo Figueiredo, Nathália Lima; Dos Santos Teixeira, Kátia Regina; Baldani, José Ivo


    Gluconacetobacter diazotrophicus is a nitrogen-fixing, endophytic bacterium that has the potential to promote plant growth and increase yield. Genetically modified strains might get more benefits to host plants, including through expression of useful proteins, such as Cry toxins from B. thuringiensis, or enzymes involved in phytohormone production, proteins with antagonistic activity for phytopathogens, or that improve nutrient utilization by the plant. For that, expression systems for G. diazotrophicus are needed, which requires active promoters fused to foreign (or innate) genes. This article describes the construction of a G. diazotrophicus PAL5 promoter library using a promoter-less lacZ-bearing vector, and the identification of six active promoters through β-galactosidase activity assays, sequencing and localization in the bacterial genome. The characterized promoters, which are located on distinct regions of the bacterial genome and encoding either sense or antisense transcripts, present variable expression strengths and might be used in the future for expressing useful proteins.

  1. An Initial Investigation of Active Galaxies in RESOLVE and ECO (United States)

    Norman, Dara J.; Kannappan, Sheila; Bittner, Ashley; Yarber, Aara'L.; Hoversten, Erik A.; Stark, David; RESOLVE Team


    The volume-limited REsolved Spectroscopy Of a Local VolumE (RESOLVE) survey and its complementary Environmental COntext (ECO) catalog are dominated by low mass, gas-rich galaxies, as is typical of the bulk of large-scale structure in the local universe. These surveys, therefore, provide an excellent opportunity to investigate the complete large-scale environments of low-redshift AGN and nuclear starbursts in such galaxies, in order to search for external triggering, examine activity in relation to gas supply, and investigate the role of feedback. By data-mining multi-wavelength catalogs that use varied techniques, we identify known AGN in RESOLVE and ECO, including a population of gas-dominated low-mass galaxies. We take advantage of these surveys' multi-wavelength supporting data to investigate triggering, feedback, and the roles of environment and gas supply in this initial sample of active galaxies. Because biases in standard AGN candidate selection techniques (e.g. BPT, X-ray luminosity) make them individually poor selectors of AGN activity in star-forming and low mass (<10^10 Msun) host galaxies, we also seek to improve the identification of nuclear activity in such galaxies via combined analysis of star formation and AGN signatures. RESOLVE is supported by NSF grant AST-0955368

  2. Three promoters regulate the transcriptional activity of the human holocarboxylase synthetase gene. (United States)

    Xia, Mengna; Malkaram, Sridhar A; Zempleni, Janos


    Holocarboxylase synthetase (HLCS) is the only protein biotin ligase in the human proteome. HLCS-dependent biotinylation of carboxylases plays crucial roles in macronutrient metabolism. HLCS appears to be an essential part of multiprotein complexes in the chromatin that cause gene repression and contribute toward genome stability. Consistent with these essential functions, HLCS knockdown causes strong phenotypes including shortened life span and low stress resistance in Drosophila melanogaster, and de-repression of long-terminal repeats in humans, other mammalian cell lines and Drosophila. Despite previous observations that the expression of HLCS depends on biotin status in rats and in human cell lines, little is known about the regulation of HLCS expression. The goal of this study was to identify promoters that regulate the expression of the human HLCS gene. Initially, the human HLCS locus was interrogated in silico using predictors of promoters including sequences of HLCS mRNA and expressed sequence tags, CpG islands, histone marks denoting transcriptionally poised chromatin, transcription factor binding sites and DNaseI hypersensitive regions. Our predictions revealed three putative HLCS promoters, denoted P1, P2 and P3. Promoters lacked a TATA box, which is typical for housekeeping genes. When the three promoters were cloned into a luciferase reporter plasmid, reporter gene activity was at least three times background noise in human breast, colon and kidney cell lines; activities consistently followed the pattern P1>P3>P2. Promoter activity depended on the concentration of biotin in culture media, but the effect was moderate. We conclude that we have identified promoters in the human HLCS gene.

  3. Presentation and exhibition activities for promoting theexportof transport services

    Directory of Open Access Journals (Sweden)

    Darya Vladimirovna Nesterova


    Full Text Available Development of presentation and exhibition activities is considered as an important factor in providing new competitive advantages at the strategic markets for exporting of transportation services. A specific role for exhibition activities as a factor to overcome market failures arose from imperfect information and incomplete markets is displayed. Exhibitions are considered as a true reflection of most market parameters, as a means to get correct information concerning market capacity and its borders, as an instrument to access to new markets. At the firm level presentation and branding activities should be considered as a modern technology (especially it concerns Russian companies which provide to hold up already existed markets and to conquer new ones. Presentation and branding activities are an effective technology to promote company trade-mark, competitive advantages for market demand increasing. Comparative analysis of the main exhibitions on transport and logistics issues is fulfilled on the data basecollected by authors. Data observes geographical distribution of transport exhibition and exhibition facilities development at several regions for the last years. The analyses allow to revealing a geographical structure of the exhibitions and its distribution by type of transport. The most promising and economically favorable exhibition areas for the promotion of Russian transport services are shown.

  4. Nuclear factor Y regulates ancient budgerigar hepadnavirus core promoter activity. (United States)

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


    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.

  5. Drug discovery for Duchenne muscular dystrophy via utrophin promoter activation screening.

    Directory of Open Access Journals (Sweden)

    Catherine Moorwood

    Full Text Available BACKGROUND: Duchenne muscular dystrophy (DMD is a devastating muscle wasting disease caused by mutations in dystrophin, a muscle cytoskeletal protein. Utrophin is a homologue of dystrophin that can functionally compensate for its absence when expressed at increased levels in the myofibre, as shown by studies in dystrophin-deficient mice. Utrophin upregulation is therefore a promising therapeutic approach for DMD. The use of a small, drug-like molecule to achieve utrophin upregulation offers obvious advantages in terms of delivery and bioavailability. Furthermore, much of the time and expense involved in the development of a new drug can be eliminated by screening molecules that are already approved for clinical use. METHODOLOGY/PRINCIPAL FINDINGS: We developed and validated a cell-based, high-throughput screening assay for utrophin promoter activation, and used it to screen the Prestwick Chemical Library of marketed drugs and natural compounds. Initial screening produced 20 hit molecules, 14 of which exhibited dose-dependent activation of the utrophin promoter and were confirmed as hits. Independent validation demonstrated that one of these compounds, nabumetone, is able to upregulate endogenous utrophin mRNA and protein, in C2C12 muscle cells. CONCLUSIONS/SIGNIFICANCE: We have developed a cell-based, high-throughput screening utrophin promoter assay. Using this assay, we identified and validated a utrophin promoter-activating drug, nabumetone, for which pharmacokinetics and safety in humans are already well described, and which represents a lead compound for utrophin upregulation as a therapy for DMD.

  6. Glycine Receptor α2 Subunit Activation Promotes Cortical Interneuron Migration

    Directory of Open Access Journals (Sweden)

    Ariel Avila


    Full Text Available Glycine receptors (GlyRs are detected in the developing CNS before synaptogenesis, but their function remains elusive. This study demonstrates that functional GlyRs are expressed by embryonic cortical interneurons in vivo. Furthermore, genetic disruption of these receptors leads to interneuron migration defects. We discovered that extrasynaptic activation of GlyRs containing the α2 subunit in cortical interneurons by endogenous glycine activates voltage-gated calcium channels and promotes calcium influx, which further modulates actomyosin contractility to fine-tune nuclear translocation during migration. Taken together, our data highlight the molecular events triggered by GlyR α2 activation that control cortical tangential migration during embryogenesis.

  7. Promoting Physical Activity through Hand-Held Computer Technology (United States)

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


    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

  8. Dose response for TCDD promotion of hepatocarcinogenesis in rats initiated with DEN: histologic, biochemical, and cell proliferation endpoints.


    Maronpot, R R; Foley, J F; Takahashi, K; Goldsworthy, T; Clark, G; Tritscher, A; Portier, C; Lucier, G


    The present study examines the dose-response relationship for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) promotion of histologic and biochemical parameters by using a two-stage model for hepatocarcinogenesis in female Sprague-Dawley rats initiated with a single intraperitoneal dose of 175 mg of diethylnitrosamine (DEN)/kg body weight at 70 days of age. Starting 2 weeks after initiation, treatment groups of 8-10 rats were given TCDD by gavage in corn oil once every 2 weeks for 30 weeks. Doses ...

  9. Cationic Nanocylinders Promote Angiogenic Activities of Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Jung Bok Lee


    Full Text Available Polymers have been used extensively taking forms as scaffolds, patterned surface and nanoparticle for regenerative medicine applications. Angiogenesis is an essential process for successful tissue regeneration, and endothelial cell–cell interaction plays a pivotal role in regulating their tight junction formation, a hallmark of angiogenesis. Though continuous progress has been made, strategies to promote angiogenesis still rely on small molecule delivery or nuanced scaffold fabrication. As such, the recent paradigm shift from top-down to bottom-up approaches in tissue engineering necessitates development of polymer-based modular engineering tools to control angiogenesis. Here, we developed cationic nanocylinders (NCs as inducers of cell–cell interaction and investigated their effect on angiogenic activities of human umbilical vein endothelial cells (HUVECs in vitro. Electrospun poly (l-lactic acid (PLLA fibers were aminolyzed to generate positively charged NCs. The aninolyzation time was changed to produce two different aspect ratios of NCs. When HUVECs were treated with NCs, the electrostatic interaction of cationic NCs with negatively charged plasma membranes promoted migration, permeability and tubulogenesis of HUVECs compared to no treatment. This effect was more profound when the higher aspect ratio NC was used. The results indicate these NCs can be used as a new tool for the bottom-up approach to promote angiogenesis.

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

    Directory of Open Access Journals (Sweden)

    Hernán A. Avila


    Full Text Available 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 they responded to the proposed methods positively and were more willing and motivated to participate in chain games, creative writing, and screenwriting exercises. The activities helped develop the students’ fluency in both oral and written production and improved their understanding of English grammar and structure.

  11. Effects of dietary β-carotene and selenium on initiation and promotion of pancreatic carcinogenesis in azaserine-treated rats

    NARCIS (Netherlands)

    Appel, M.J.; Woutersen, R.A.


    In the present study the effects of 0.1 or 1.0 g β-carotene/kg diet (LβC or HβC) and 1.0 mg or 2.5 mg selenium/kg diet (LSel or HSel), as well as combinations of the respective low and high concentrations of p-carotene and selenium (LMix or HMix) on the initiation/early promotion phase or on the lat

  12. Proteomic identification of an embryo-specific 1Cys-Prx promoter and analysis of its activity in transgenic rice. (United States)

    Kim, Je Hein; Jung, In Jung; Kim, Dool Yi; Fanata, Wahyu Indra; Son, Bo Hwa; Yoo, Jae Yong; Harmoko, Rikno; Ko, Ki Seong; Moon, Jeong Chan; Jang, Ho Hee; Kim, Woe Yeon; Kim, Jae-Yean; Lim, Chae Oh; Lee, Sang Yeol; Lee, Kyun Oh


    Proteomic analysis of a rice callus led to the identification of 10 abscisic acid (ABA)-induced proteins as putative products of the embryo-specific promoter candidates. 5'-flanking sequence of 1 Cys-Prx, a highly-induced protein gene, was cloned and analyzed. The transcription initiation site of 1 Cys-Prx maps 96 nucleotides upstream of the translation initiation codon and a TATA-box and putative seed-specific cis-acting elements, RYE and ABRE, are located 26, 115 and 124 bp upstream of the transcription site, respectively. β-glucuronidase (GUS) expression driven by the 1 Cys-Prx promoters was strong in the embryo and aleurone layer and the activity reached up to 24.9 ± 3.3 and 40.5 ± 2.1 pmol (4 MU/min/μg protein) in transgenic rice seeds and calluses, respectively. The activity of the 1 Cys-Prx promoters is much higher than that of the previously-identified embryo-specific promoters, and comparable to that of strong endosperm-specific promoters in rice. GUS expression driven by the 1 Cys-Prx promoters has been increased by ABA treatment and rapidly induced by wounding in callus and at the leaf of the transgenic plants, respectively. Furthermore, ectopic expression of the GUS construct in Arabidopsis suggested that the 1 Cys-Prx promoter also has strong activity in seeds of dicot plants.

  13. Bacterial lipopolysaccharide promotes profibrotic activation of intestinal fibroblasts.

    LENUS (Irish Health Repository)

    Burke, J P


    BACKGROUND: Fibroblasts play a critical role in intestinal wound healing. Lipopolysaccharide (LPS) is a cell wall component of commensal gut bacteria. The effects of LPS on intestinal fibroblast activation were characterized. METHODS: Expression of the LPS receptor, toll-like receptor (TLR) 4, was assessed in cultured primary human intestinal fibroblasts using flow cytometry and confocal microscopy. Fibroblasts were treated with LPS and\\/or transforming growth factor (TGF) beta1. Nuclear factor kappaB (NFkappaB) pathway activation was assessed by inhibitory kappaBalpha (IkappaBalpha) degradation and NFkappaB promoter activity. Fibroblast contractility was measured using a fibroblast-populated collagen lattice. Smad-7, a negative regulator of TGF-beta1 signalling, and connective tissue growth factor (CTGF) expression were assessed using reverse transcriptase-polymerase chain reaction and western blot. The NFkappaB pathway was inhibited by IkappaBalpha transfection. RESULTS: TLR-4 was present on the surface of intestinal fibroblasts. LPS treatment of fibroblasts induced IkappaBalpha degradation, enhanced NFkappaB promoter activity and increased collagen contraction. Pretreatment with LPS (before TGF-beta1) significantly increased CTGF production relative to treatment with TGF-beta1 alone. LPS reduced whereas TGF-beta1 increased smad-7 expression. Transfection with an IkappaBalpha plasmid enhanced basal smad-7 expression. CONCLUSION: Intestinal fibroblasts express TLR-4 and respond to LPS by activating NFkappaB and inducing collagen contraction. LPS acts in concert with TGF-beta1 to induce CTGF. LPS reduces the expression of the TGF-beta1 inhibitor, smad-7.

  14. Activities of E7 promoters in the human papillomavirus type 16 genome during cell differentiation

    DEFF Research Database (Denmark)

    Hansen, Christina Neigaard; Nielsen, Lone; Norrild, Bodil


    -differentiated cells and late gene-expression in more differentiated cells. We induced epithelial cells to differentiate by growth in medium with a high calcium concentration and measured the activity of different promoters thought to initiate E6 and/or E7 transcripts. The overall activity of the main promoter, P97......, situated in the long control region as well as the two promoters, P441 and P542, in the E6 ORF upstream of the E7 ORF, were decreased during differentiation. However, P441 and P542 were not down-regulated as much as P97. Therefore, we suggest that P441 and P542 regulate gene-expression in differentiated...... to deregulation of the cell cycle control. HPV-16 preferably infects the proliferating cells that will differentiate when they move upwards in the epithelium. The viral gene-expression is tightly coupled to the cellular differentiation program with early gene-expression being initiated in non- or low...

  15. Delineating active citizenship: The subjectification of citizens' initiatives

    NARCIS (Netherlands)

    Dam, van R.I.; Duineveld, M.; During, R.


    Based on three case studies on citizens' initiatives in their local governance contexts, we analyse the process of subjectification as a performative effect of the dialectical relationship between governmental organizations and citizens' initiatives. We argue that discourses produced by governmental

  16. Nonalcoholic steatohepatitis induced by a high-fat diet promotes diethylnitrosamine initiated early hepatocarcinogenesis in rats (United States)

    It has been suggested that patients with nonalcoholic steatohepatitis (NASH) are at a high risk for liver cancer. However, it is unknown whether high-fat diet induced NASH promotes hepatocarcinogenesis. In the present study, Sprague-Dawley rats were injected with a low dose of hepatic carcinogen die...

  17. Mechanism of initiation site selection promoted by the human rhinovirus 2 internal ribosome entry site. (United States)

    Kaminski, Ann; Pöyry, Tuija A A; Skene, Peter J; Jackson, Richard J


    Translation initiation site usage on the human rhinovirus 2 internal ribosome entry site (IRES) has been examined in a mixed reticulocyte lysate/HeLa cell extract system. There are two relevant AUG triplets, both in a base-paired hairpin structure (domain VI), with one on the 5' side at nucleotide (nt) 576, base paired with the other at nt 611, which is the initiation site for polyprotein synthesis. A single residue was inserted in the apical loop to put AUG-576 in frame with AUG-611, and in addition another in-frame AUG was introduced at nt 593. When most of the IRES was deleted to generate a monocistronic mRNA, the use of these AUGs conformed to the scanning ribosome model: improving the AUG-576 context increased initiation at this site and decreased initiation at downstream sites, whereas the converse was seen when AUG-576 was mutated to GUA; and AUG-593, when present, took complete precedence over AUG-611. Under IRES-dependent conditions, by contrast, much less initiation occurred at AUG-576 than in a monocistronic mRNA with the same AUG-576 context, mutation of AUG-576 decreased initiation at downstream sites by approximately 70%, and introduction of AUG-593 did not completely abrogate initiation at AUG-611, unless the apical base pairing in domain VI was destroyed by point mutations. These results indicate that ribosomes first bind at the AUG-576 site, but instead of initiating there, most of them are transferred to AUG-611, the majority by strictly linear scanning and a substantial minority by direct transfer, which is possibly facilitated by the occasional persistence of base pairing in the apical part of the domain VI stem.

  18. Activated alveolar epithelial cells initiate fibrosis through autocrine and paracrine secretion of connective tissue growth factor. (United States)

    Yang, Jibing; Velikoff, Miranda; Canalis, Ernesto; Horowitz, Jeffrey C; Kim, Kevin K


    Fibrogenesis involves a pathological accumulation of activated fibroblasts and extensive matrix remodeling. Profibrotic cytokines, such as TGF-β, stimulate fibroblasts to overexpress fibrotic matrix proteins and induce further expression of profibrotic cytokines, resulting in progressive fibrosis. Connective tissue growth factor (CTGF) is a profibrotic cytokine that is indicative of fibroblast activation. Epithelial cells are abundant in the normal lung, but their contribution to fibrogenesis remains poorly defined. Profibrotic cytokines may activate epithelial cells with protein expression and functions that overlap with the functions of active fibroblasts. We found that alveolar epithelial cells undergoing TGF-β-mediated mesenchymal transition in vitro were also capable of activating lung fibroblasts through production of CTGF. Alveolar epithelial cell expression of CTGF was dramatically reduced by inhibition of Rho signaling. CTGF reporter mice demonstrated increased CTGF promoter activity by lung epithelial cells acutely after bleomycin in vivo. Furthermore, mice with lung epithelial cell-specific deletion of CTGF had an attenuated fibrotic response to bleomycin. These studies provide direct evidence that epithelial cell activation initiates a cycle of fibrogenic effector cell activation during progressive fibrosis. Therapy targeted at epithelial cell production of CTGF offers a novel pathway for abrogating this progressive cycle and limiting tissue fibrosis.

  19. Melatonin activates the peroxidase-oxidase reaction and promotes oscillations. (United States)

    Olsen, L F; Lunding, A; Lauritsen, F R; Allegra, M


    We have studied the peroxidase-oxidase reaction with NADH and O2 as substrates and melatonin as a cofactor in a semibatch reactor. We show for the first time that melatonin is an activator of the reaction catalyzed by enzymes from both plant and animal sources. Furthermore, melatonin promotes oscillatory dynamics in the pH range from 5 to 6. The frequency of the oscillations depends on the pH such that an increase in pH was accompanied by a decrease in frequency. Conversely, an increase in the flow rate of NADH or an increase in the average concentration of NADH resulted in an increase in oscillation frequency. Complex dynamics were not observed with melatonin as a cofactor. These results are discussed in relation to observations of oscillatory dynamics and the function of melatonin and peroxidase in activated neutrophils.

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

    Directory of Open Access Journals (Sweden)

    Mariagiovanna Caprara


    Full Text Available 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.

  1. Active aging promotion: results from the vital aging program. (United States)

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


    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.

  2. The effects of tobacco sales promotion on initiation of smoking--experiences from Finland and Norway. (United States)

    Rimpelä, M K; Aarø, L E; Rimpelä, A H


    Norway and Finland were among the first countries to adopt a total ban on tobacco sales promotion. Such legislation came into force in Norway and Finland in 1975 and 1978 respectively. These two countries are sometimes referred to as illustrations that such legislation has been successfully used as a means to reduce tobacco consumption. Tobacco industry spokesmen seem to interpret available evidence in the opposite way and maintain that the prohibition has not contributed to reducing the use of tobacco. Among the publications referred to and misused by tobacco industry spokesmen are publications from the authors of the present report. The effects of a ban on advertising can only be properly examined after describing a reasonable conceptual model. Such a model has to take into account (i) other social and cultural predictors of smoking, (ii) tobacco sales promotion in the contexts of all other mass communication, (iii) control measures other than a ban, and (iv) the degree of success in implementing the ban on advertising. Like any other kind of mass communication tobacco advertising influences the individual in a rather complex way. Behaviour change may be regarded as the outcome of an interpersonal and intrapersonal process. Social science research on tobacco advertising and the effects of banning such advertising has a short history, most studies having been carried out in the late 1980s. After examining available evidence related to the effects of tobacco advertising on the smoking habits of adolescents we conclude as follows: the few scientifically valid reports available today give both theoretical and empirical evidence for a causal relationship. Tobacco sales promotion seems both to promote and to reinforce smoking among young people. The dynamic tobacco market represented by children and adolescents is probably the main target of tobacco sales promotion. In Finland, there have been few studies explicitly addressing the causal links between tobacco sales

  3. Oncogenic KRAS activates an embryonic stem cell-like program in human colon cancer initiation. (United States)

    Le Rolle, Anne-France; Chiu, Thang K; Zeng, Zhaoshi; Shia, Jinru; Weiser, Martin R; Paty, Philip B; Chiu, Vi K


    Colorectal cancer is the third most frequently diagnosed cancer worldwide. Prevention of colorectal cancer initiation represents the most effective overall strategy to reduce its associated morbidity and mortality. Activating KRAS mutation (KRASmut) is the most prevalent oncogenic driver in colorectal cancer development, and KRASmut inhibition represents an unmet clinical need. We apply a systems-level approach to study the impact of KRASmut on stem cell signaling during human colon cancer initiation by performing gene set enrichment analysis on gene expression from human colon tissues. We find that KRASmut imposes the embryonic stem cell-like program during human colon cancer initiation from colon adenoma to stage I carcinoma. Expression of miR145, an embryonic SC program inhibitor, promotes cell lineage differentiation marker expression in KRASmut colon cancer cells and significantly suppresses their tumorigenicity. Our data support an in vivo plasticity model of human colon cancer initiation that merges the intrinsic stem cell properties of aberrant colon stem cells with the embryonic stem cell-like program induced by KRASmut to optimize malignant transformation. Inhibition of the embryonic SC-like program in KRASmut colon cancer cells reveals a novel therapeutic strategy to programmatically inhibit KRASmut tumors and prevent colon cancer.

  4. The legal framework and initiatives for promoting safety in the United Arab Emirates. (United States)

    Grivna, Michal; Aw, Tar-Ching; El-Sadig, Mohamed; Loney, Tom; Sharif, Amer Ahmad; Thomsen, Jens; Mauzi, Mariam; Abu-Zidan, Fikri M


    Injury is a leading cause of morbidity and mortality in the United Arab Emirates (UAE). The UAE is a rapidly developing country with fast economic growth, demographical and environmental changes that are associated with new hazards emerging at a similar pace. The UAE as a federal entity has federal and local systems responsible for safety policy, regulations and enforcement. To set priorities for safety promotion and injury prevention, it is necessary to have data on the most frequent external causes of injury and the main individual, equipment and environmental risk factors that contribute to injury. However good quality data for injury prevention are scarce. The aim of this paper is to describe the scale of injury as a public health problem in the UAE, and the development of safety policies, regulations and promotion efforts with special emphasis on traffic, occupational and child safety.

  5. Molecular mechanism by which AMP-activated protein kinase activation promotes glycogen accumulation in muscle

    DEFF Research Database (Denmark)

    Hunter, Roger W; Treebak, Jonas Thue; Wojtaszewski, Jørgen


    OBJECTIVE During energy stress, AMP-activated protein kinase (AMPK) promotes glucose transport and glycolysis for ATP production, while it is thought to inhibit anabolic glycogen synthesis by suppressing the activity of glycogen synthase (GS) to maintain the energy balance in muscle. Paradoxically......, chronic activation of AMPK causes an increase in glycogen accumulation in skeletal and cardiac muscles, which in some cases is associated with cardiac dysfunction. The aim of this study was to elucidate the molecular mechanism by which AMPK activation promotes muscle glycogen accumulation. RESEARCH DESIGN...... AND METHODS We recently generated knock-in mice in which wild-type muscle GS was replaced by a mutant (Arg582Ala) that could not be activated by glucose-6-phosphate (G6P), but possessed full catalytic activity and could still be activated normally by dephosphorylation. Muscles from GS knock-in or transgenic...

  6. Initial Active MHD Spectroscopy Experiments on Alcator C-MOD (United States)

    Schmittdiel, D. A.; Snipes, J. A.; Granetz, R. S.; Parker, R. R.; Wolfe, S. M.; Fasoli, A.


    The Active MHD Spectroscopy system is a new diagnostic on C-MOD that will be used to study low frequency MHD modes and TAE's present at high B_tor, n_e, and Te ˜= T_i. The present system consists of two antennas, power amplifiers, and an impedance matching network. Each antenna is 15 × 25 cm with five turns, an inductance of ˜10 μH, and is covered by boron nitride tiles. The two antennas are placed at the same toroidal location, symmetrically above and below the midplane. Each antenna is driven by a ˜1 kW power amplifier in the range of 1 kHz - 1 MHz with an expected antenna current ˜10 A, which will produce a vacuum field of ˜0.5 G at the q = 1.5 surface. This diagnostic is designed to excite high n ( ˜20) stable TAE's and initial results regarding their frequency, mode structure, and damping rate will be presented. Evolution of these modes could also provide information on the q profile to compare with MSE measurements, which will be important for planned lower hybrid current drive operation in 2003.

  7. Inventory of U.S.-led International Activities on Building Energy Efficiency Initial Findings

    Energy Technology Data Exchange (ETDEWEB)

    Delgado, Alison; Evans, Meredydd


    Several U.S. Government agencies promote energy efficiency in buildings internationally. The types and scope of activities vary by agency. Those with the largest role include the U.S. Agency for International Development (USAID), the U.S. Department of State and the Environmental Protection Agency (EPA). Both USAID and the Department of State have a substantial presence overseas, which may present some complementarities with the Department of Energy’s efforts to reach out to other countries. Generally speaking, USAID focuses on capacity building and policy issues; the Department of State focuses on broad diplomatic efforts and some targeted grants in support of these efforts, and EPA has more targeted roles linked to ENERGY STAR appliances and a few other activities. Several additional agencies are also involved in trade-related efforts to promote energy efficiency in buildings. These include the Department of Commerce, the Export-Import Bank, the Overseas Private Investment Corporation and the Trade and Development Agency (TDA). This initial synthesis report is designed to summarize broad trends and activities relating to international cooperation on energy efficiency in buildings, which can help the U.S. Department of Energy (DOE) in developing its own strategy in this area. The Pacific Northwest National Laboratory will develop a more complete synthesis report later in 2010 as it populates a database on international projects on building energy efficiency.

  8. Promoting Active Learning: The Use of Computational Software Programs (United States)

    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.

  9. Promoting Moderate-Vigorous Physical Activity in Overweight Minority Girls

    Directory of Open Access Journals (Sweden)

    Norma Olvera


    Full Text Available There is limited research on the types of activities that are most effective for promoting MVPA in children. Purpose. To assess which types of activities elicit MVPA in overweight minority girls. Methods. Sample consisted of 31 overweight (BMI≥85th percentile Latina and African-American girls (mean age 10.3±1.2 years. Participants wore an Actical accelerometer each day for 8 hours for 15 days to assess engagement in MVPA during their participation in a three-week activity intervention that included traditional fitness, sport skills, games, dancing, and flexibility sessions. Results. On average 62% of participants met the MVPA recommended guidelines (60 min/5d/wk with an average of 68.5±14 minutes of MVPA across the three weeks. Traditional fitness sessions elicited the highest percent of MVPA (mean time spent in MVPA=32%, followed by dancing and games (mean time spent in MVPA=21%, sports skills (mean time spent in MVPA=18%, and flexibility (mean time spent in MVPA=7%. Step aerobics and rumba fitness elicited the highest proportions of MVPA. Conclusion. Traditional fitness activities were identified as the most successful in eliciting MVPA in overweight Latina and African American girls.

  10. Promoting moderate-vigorous physical activity in overweight minority girls. (United States)

    Olvera, Norma; Graham, Marilynn; McLeod, Jessica; Kellam, Stephanie F; Butte, Nancy F


    There is limited research on the types of activities that are most effective for promoting MVPA in children. Purpose. To assess which types of activities elicit MVPA in overweight minority girls. Methods. Sample consisted of 31 overweight (BMI >/= 85th percentile) Latina and African-American girls (mean age 10.3 +/- 1.2 years). Participants wore an Actical accelerometer each day for 8 hours for 15 days to assess engagement in MVPA during their participation in a three-week activity intervention that included traditional fitness, sport skills, games, dancing, and flexibility sessions. Results. On average 62% of participants met the MVPA recommended guidelines (60 min/5d/wk) with an average of 68.5 +/- 14 minutes of MVPA across the three weeks. Traditional fitness sessions elicited the highest percent of MVPA (mean time spent in MVPA = 32%), followed by dancing and games (mean time spent in MVPA = 21%), sports skills (mean time spent in MVPA = 18%), and flexibility (mean time spent in MVPA = 7%). Step aerobics and rumba fitness elicited the highest proportions of MVPA. Conclusion. Traditional fitness activities were identified as the most successful in eliciting MVPA in overweight Latina and African American girls.

  11. 7 CFR 981.441 - Credit for market promotion activities, including paid advertising. (United States)


    ... 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... expenses, or for any promotional activities that result in price discounting. (i) Paid advertising...

  12. An artificial HSE promoter for efficient and selective detection of heat shock pathway activity. (United States)

    Ortner, Viktoria; Ludwig, Alfred; Riegel, Elisabeth; Dunzinger, Sarah; Czerny, Thomas


    Detection of cellular stress is of major importance for the survival of cells. During evolution, a network of stress pathways developed, with the heat shock (HS) response playing a major role. The key transcription factor mediating HS signalling activity in mammalian cells is the HS factor HSF1. When activated it binds to the heat shock elements (HSE) in the promoters of target genes like heat shock protein (HSP) genes. They are induced by HSF1 but in addition they integrate multiple signals from different stress pathways. Here, we developed an artificial promoter consisting only of HSEs and therefore selectively reacting to HSF-mediated pathway activation. The promoter is highly inducible but has an extreme low basal level. Direct comparison with the HSPA1A promoter activity indicates that heat-dependent expression can be fully recapitulated by isolated HSEs in human cells. Using this sensitive reporter, we measured the HS response for different temperatures and exposure times. In particular, long heat induction times of 1 or 2 h were compared with short heat durations down to 1 min, conditions typical for burn injuries. We found similar responses to both long and short heat durations but at completely different temperatures. Exposure times of 2 h result in pathway activation at 41 to 44 °C, whereas heat pulses of 1 min lead to a maximum HS response between 47 and 50 °C. The results suggest that the HS response is initiated by a combination of temperature and exposure time but not by a certain threshold temperature.

  13. Activating STAT3 Alpha for Promoting Healing of Neurons (United States)

    Conway, Greg


    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.

  14. [Actively promote the development of neuro-ophthalmology in China]. (United States)

    Wei, Shi-hui; Zhao, Jia-liang


    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.

  15. Toward the assessment of psychological empowerment in health promotion: initial tests of validity and reliability. (United States)

    Rissel, C; Perry, C; Finnegan, J


    Because of the importance of empowerment in health promotion, the measurement of empowerment is a priority for health promotion research. The present study sought to develop a valid and reliable instrument to assess psychological empowerment and to resolve the theoretical question of whether psychological empowerment is a topic-specific or general construct. University of Minnesota employees (n = 160) completed two different versions of empowerment questionnaires. One of the questionnaires measured general empowerment; the other was specific to alcohol use prevention. Reasonable reliability was demonstrated in a previously developed general empowerment instrument (Cronbach's alpha coefficient of 0.84) and for an alcohol-specific instrument (Cronbach's alpha coefficient of 0.78). Construct validity for the alcohol-specific instrument was demonstrated by appropriate significant correlations between subscales and overall scores for both instruments. Predictive validity tests partially supported the concept that psychological empowerment is topic-specific, although further testing with a more representative population may be needed to resolve this question. The results suggest that the alcohol-specific psychological empowerment instrument could be used in the evaluation of community alcohol abuse prevention programmes.

  16. Regional initiatives to promote economic development in North-east Asia.


    Nijkamp, P.; Wiegmans, B.W.


    This paper addresses the economic development potential of the Asian Pacific Rim, with a particular view on north East Asia. It is argued that growth triangles are likely to be a proper way of organizing regional development forces. Next, the attention is focused on the Tumen River Area Development Programme as a potentially interesting region for joint transnational development initiatives. The opportunities and threats of this area are explored by means of scenario analysis. It is conc1uded...

  17. Promoting the export of environmental technologies : governmental initiatives in selected countries


    Kanda, Wisdom; Hjelm, Olof; Mejiá-Dugand, Santiago


    Rapid international and widespread diffusion of environmental technologies remains an essential requirement within the framework of sustainable development. Export offers a desired means for technology diffusion due to its strategic flexibility compared to other means such as foreign direct investment and aid. However, the export of environmental technologies is stifled by market failures. Among other reasons and as a response to such market failures, several governments are formulating initi...

  18. Radiation Promotes Colorectal Cancer Initiation and Progression by Inducing Senescence-Associated Inflammatory Responses (United States)

    Kim, Sang Bum; Bozeman, Ronald; Kaisani, Aadil; Kim, Wanil; Zhang, Lu; Richardson, James A.; Wright, Woodring E.; Shay, Jerry W.


    Proton radiotherapy is becoming more common since protons induce more precise DNA damage at the tumor site with reduced side effects to adjacent normal tissues. However, the long-term biological effects of proton irradiation in cancer initiation compared to conventional photon irradiation are poorly characterized. In this study, using a human familial adenomatous polyposis syndrome susceptible mouse model, we show that whole body irradiation with protons are more effective in inducing senescence-associated inflammatory responses (SIR) which are involved in colon cancer initiation and progression. After proton irradiation, a subset of SIR genes (Troy, Sox17, Opg, Faim2, Lpo, Tlr2 and Ptges) and a gene known to be involved in invasiveness (Plat), along with the senescence associated gene (P19Arf) are markedly increased. Following these changes loss of Casein kinase Iα (CKIα) and induction of chronic DNA damage and TP53 mutations are increased compared to x-ray irradiation. Proton irradiation also increases the number of colonic polyps, carcinomas and invasive adenocarcinomas. Pretreatment with the non-steroidal anti-inflammatory drug, CDDO-EA, reduces proton irradiation associated SIR and tumorigenesis. Thus, exposure to proton irradiation elicits significant changes in colorectal cancer initiation and progression that can be mitigated using CDDO-EA. PMID:26477319

  19. Ratite oils promote keratinocyte cell growth and inhibit leukocyte activation (United States)

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


    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

  20. Ratite oils promote keratinocyte cell growth and inhibit leukocyte activation. (United States)

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


    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.

  1. Stress-mediated p38 activation promotes somatic cell reprogramming

    Institute of Scientific and Technical Information of China (English)

    Xinxiu Xu; Quan Wang; Yuan Long; Ru Zhang; Xiaoyuan Wei; Mingzhe Xing; Haifeng Gu


    Environmental stress-mediated adaptation plays essential roles in the evolution of life.Cellular adaptation mechanisms usually involve the regulation of chromatin structure,transcription,mRNA stability and translation,which eventually lead to efficient changes in gene expression.Global epigenetic change is also involved in the reprogramming of somatic cells into induced pluripotent stem (iPS) cells by defined factors.Here we report that environmental stress such as hyperosmosis not only facilitates four factor-mediated reprogramming,but also enhances two or one factor-induced iPS cell generation.Hyperosmosis-induced p38 activation plays a critical role in this process.Constitutive active p38 mimics the positive effect of hyperosmosis,while dominant negative p38 and p38 inhibitor block the effect of hyperosmosis.Further study indicates stress-mediated p38 activation may promote reprogramming by reducing the global DNA methylation level and enhancing the expression of pluripotency genes.Our results demonstrate how simple environmental stress like hyperosmosis helps to alter the fate of cells via intracellular signaling and epigenetic modulation.

  2. Promoting Uranium Immobilization by the Activities of Microbial Phosphatases

    Energy Technology Data Exchange (ETDEWEB)

    Robert J. Martinez; Melanie J. Beazley; Samuel M. Webb; Martial Taillefert (co-PI); and Patricia A. Sobecky


    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

  3. Sexual experience promotes adult neurogenesis in the hippocampus despite an initial elevation in stress hormones.

    Directory of Open Access Journals (Sweden)

    Benedetta Leuner

    Full Text Available Aversive stressful experiences are typically associated with increased anxiety and a predisposition to develop mood disorders. Negative stress also suppresses adult neurogenesis and restricts dendritic architecture in the hippocampus, a brain region associated with anxiety regulation. The effects of aversive stress on hippocampal structure and function have been linked to stress-induced elevations in glucocorticoids. Normalizing corticosterone levels prevents some of the deleterious consequences of stress, including increased anxiety and suppressed structural plasticity in the hippocampus. Here we examined whether a rewarding stressor, namely sexual experience, also adversely affects hippocampal structure and function in adult rats. Adult male rats were exposed to a sexually-receptive female once (acute or once daily for 14 consecutive days (chronic and levels of circulating glucocorticoids were measured. Separate cohorts of sexually experienced rats were injected with the thymidine analog bromodeoxyuridine in order to measure cell proliferation and neurogenesis in the hippocampus. In addition, brains were processed using Golgi impregnation to assess the effects of sexual experience on dendritic spines and dendritic complexity in the hippocampus. Finally, to evaluate whether sexual experience alters hippocampal function, rats were tested on two tests of anxiety-like behavior: novelty suppressed feeding and the elevated plus maze. We found that acute sexual experience increased circulating corticosterone levels and the number of new neurons in the hippocampus. Chronic sexual experience no longer produced an increase in corticosterone levels but continued to promote adult neurogenesis and stimulate the growth of dendritic spines and dendritic architecture. Chronic sexual experience also reduced anxiety-like behavior. These findings suggest that a rewarding experience not only buffers against the deleterious actions of early elevated

  4. No Promoting Effect of Ethyl Tertiary-butyl Ether (ETBE) on Rat Urinary Bladder Carcinogenesis Initiated with N-Butyl-N-(4-hydroxybutyl)nitrosamine. (United States)

    Hagiwara, Akihiro; Imai, Norio; Doi, Yuko; Suguro, Mayuko; Kawabe, Mayumi; Furukawa, Fumio; Nagano, Kasuke; Fukushima, Shoji


    The effects of ethyl tertiary-butyl ether (ETBE) on two-stage urinary bladder carcinogenesis in male F344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were investigated at various dose levels with regard to possible promoting activity. Groups of 30 rats were given drinking water containing 500 ppm BBN, as an initiator, for 4 weeks and starting one week thereafter received ETBE by gavage (daily, 7 days/week) at dose levels of 0 (control), 100, 300, 500 or 1000 mg/kg/day until experimental week 36. No statistically significant differences in incidences of preneoplastic lesions, papillomas, and carcinomas of the urinary bladder were evident in rats treated with 100-1000 mg/kg/day ETBE as compared with control values. Furthermore, the average numbers of preneoplastic or neoplastic lesions per unit length of basement membrane in rats given 100-1000 mg/kg/day ETBE were also comparable to control values. However, papillomatosis of the urinary bladder was found in 4 out of 30 rats (13%) in the group given 1000 mg/kg/day ETBE, and soft stones in the urinary bladder were found in 3 out of these 4 rats. The results thus demonstrated that ETBE did not exert promotional activity on urinary bladder carcinogenesis. However, papillomatosis of the urinary bladder developed in small numbers of the rats given ETBE at 1000 mg/kg/day but not in rats given 500 mg/kg/day or lower doses.

  5. Phosphazene-promoted metal-free ring-opening polymerization of ethylene oxide initiated by carboxylic acid

    KAUST Repository

    Zhao, Junpeng


    The effectiveness of carboxylic acid as initiator for the anionic ring-opening polymerization of ethylene oxide was investigated with a strong phosphazene base (t-BuP4) used as promoter. Kinetic study showed an induction period, i.e., transformation of carboxylic acid to hydroxyl ester, followed by slow chain growth together with simultaneous and fast end-group transesterification, which led to poly(ethylene oxide) (PEO) consisting of monoester (monohydroxyl), diester, and dihydroxyl species. An appropriate t-BuP4/acid ratio was proven to be essential to achieve better control over the polymerization and low dispersity of PEO. This work provides important information and enriches the toolbox for macromolecular and biomolecular engineering with protic initiating sites. © 2014 American Chemical Society.

  6. Promotional tone in reviews of menopausal hormone therapy after the Women's Health Initiative: an analysis of published articles.

    Directory of Open Access Journals (Sweden)

    Adriane Fugh-Berman


    Full Text Available BACKGROUND: Even after the Women's Health Initiative (WHI found that the risks of menopausal hormone therapy (hormone therapy outweighed benefit for asymptomatic women, about half of gynecologists in the United States continued to believe that hormones benefited women's health. The pharmaceutical industry has supported publication of articles in medical journals for marketing purposes. It is unknown whether author relationships with industry affect promotional tone in articles on hormone therapy. The goal of this study was to determine whether promotional tone could be identified in narrative review articles regarding menopausal hormone therapy and whether articles identified as promotional were more likely to have been authored by those with conflicts of interest with manufacturers of menopausal hormone therapy. METHODS AND FINDINGS: We analyzed tone in opinion pieces on hormone therapy published in the four years after the estrogen-progestin arm of the WHI was stopped. First, we identified the ten authors with four or more MEDLINE-indexed reviews, editorials, comments, or letters on hormone replacement therapy or menopausal hormone therapy published between July 2002 and June 2006. Next, we conducted an additional search using the names of these authors to identify other relevant articles. Finally, after author names and affiliations were removed, 50 articles were evaluated by three readers for scientific accuracy and for tone. Scientific accuracy was assessed based on whether or not the findings of the WHI were accurately reported using two criteria: (1 Acknowledgment or lack of denial of the risk of breast cancer diagnosis associated with hormone therapy, and (2 acknowledgment that hormone therapy did not benefit cardiovascular disease endpoints. Determination of promotional tone was based on the assessment by each reader of whether the article appeared to promote hormone therapy. Analysis of inter-rater consistency found moderate agreement

  7. Promotion of adiponectin multimerization by emodin: a novel AMPK activator with PPARγ-agonist activity. (United States)

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


    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.

  8. Sea-ice dynamics strongly promote Snowball Earth initiation and destabilize tropical sea-ice margins

    Directory of Open Access Journals (Sweden)

    A. Voigt


    Full Text Available The Snowball Earth bifurcation, or runaway ice-albedo feedback, is defined for particular boundary conditions by a critical CO2 and a critical sea-ice cover (SI, both of which are essential for evaluating hypotheses related to Neoproterozoic glaciations. Previous work has shown that the Snowball Earth bifurcation, denoted as (CO2, SI*, differs greatly among climate models. Here, we study the effect of bare sea-ice albedo, sea-ice dynamics and ocean heat transport on (CO2, SI* in the atmosphere–ocean general circulation model ECHAM5/MPI-OM with Marinoan (~ 635 Ma continents and solar insolation (94% of modern. In its standard setup, ECHAM5/MPI-OM initiates a~Snowball Earth much more easily than other climate models at (CO2, SI* ≈ (500 ppm, 55%. Replacing the model's standard bare sea-ice albedo of 0.75 by a much lower value of 0.45, we find (CO2, SI* ≈ (204 ppm, 70%. This is consistent with previous work and results from net evaporation and local melting near the sea-ice margin. When we additionally disable sea-ice dynamics, we find that the Snowball Earth bifurcation can be pushed even closer to the equator and occurs at a hundred times lower CO2: (CO2, SI* ≈ (2 ppm, 85%. Therefore, the simulation of sea-ice dynamics in ECHAM5/MPI-OM is a dominant determinant of its high critical CO2 for Snowball initiation relative to other models. Ocean heat transport has no effect on the critical sea-ice cover and only slightly decreases the critical CO2. For disabled sea-ice dynamics, the state with 85% sea-ice cover is stabilized by the Jormungand mechanism and shares characteristics with the Jormungand climate states. However, there is no indication of the Jormungand bifurcation and hysteresis in ECHAM5/MPI-OM. The state with 85% sea-ice cover therefore is a soft Snowball state rather than a true

  9. Characterization of P1 promoter activity of the -galactoside 2,6-sialyltransferase I gene (siat 1) in cervical and hepatic cancer cell lines

    Indian Academy of Sciences (India)

    Lorena Milflores-Flores; Lourdes Millán-Pérez; Gerardo Santos-López; Julio Reyes-Leyva; Verónica Vallejo-Ruiz


    The level of -galactoside 2,6-sialyltransferase I (ST6Gal I) mRNA, encoded by the gene siat1, is increased in malignant tissues. Expression is regulated by different promoters – P1, P2 and P3 – generating three mRNA isoforms H, X and YZ. In cervical cancer tissue the mRNA isoform H, which results from P1 promoter activity, is increased. To study the regulation of P1 promoter, different constructs from P1 promoter were evaluated by luciferase assays in cervical and hepatic cell lines. Deletion of a fragment of 1048 bp (−89 to +24 bp) increased 5- and 3-fold the promoter activity in C33A and HepG2 cell lines, respectively. The minimal region with promoter activity was a 37 bp fragment in C33A cells. The activity of this region does not require the presence of an initiator sequence. In HepG2 cells the minimal promoter activity was detected in the 66 bp fragment. Sp1 (−32) mutation increased the promoter activity only in HepG2 cells. HNF1 mutation decreased promoter activity in HepG2 cell line but not in C33A cells. We identified a large region that plays a negative regulation role. The regulation of promoter activity is cell type specific. Our study provides new insights into the complex transcriptional regulation of siat1 gene.

  10. MicroRNA-31 initiates lung tumorigenesis and promotes mutant KRAS-driven lung cancer. (United States)

    Edmonds, Mick D; Boyd, Kelli L; Moyo, Tamara; Mitra, Ramkrishna; Duszynski, Robert; Arrate, Maria Pia; Chen, Xi; Zhao, Zhongming; Blackwell, Timothy S; Andl, Thomas; Eischen, Christine M


    MicroRNA (miR) are important regulators of gene expression, and aberrant miR expression has been linked to oncogenesis; however, little is understood about their contribution to lung tumorigenesis. Here, we determined that miR-31 is overexpressed in human lung adenocarcinoma and this overexpression independently correlates with decreased patient survival. We developed a transgenic mouse model that allows for lung-specific expression of miR-31 to test the oncogenic potential of miR-31 in the lung. Using this model, we observed that miR-31 induction results in lung hyperplasia, followed by adenoma formation and later adenocarcinoma development. Moreover, induced expression of miR-31 in mice cooperated with mutant KRAS to accelerate lung tumorigenesis. We determined that miR-31 regulates lung epithelial cell growth and identified 6 negative regulators of RAS/MAPK signaling as direct targets of miR-31. Our study distinguishes miR-31 as a driver of lung tumorigenesis that promotes mutant KRAS-mediated oncogenesis and reveals that miR-31 directly targets and reduces expression of negative regulators of RAS/MAPK signaling.

  11. Promoting Robust Design of Diode Lasers for Space: A National Initiative (United States)

    Tratt, David M.; Amzajerdian, Farzin; Kashem, Nasir B.; Shapiro, Andrew A.; Mense, Allan T.


    The Diode-laser Array Working Group (DAWG) is a national-level consumer/provider forum for discussion of engineering and manufacturing issues which influence the reliability and survivability of high-power broad-area laser diode devices in space, with an emphasis on laser diode arrays (LDAs) for optical pumping of solid-state laser media. The goals of the group are to formulate and validate standardized test and qualification protocols, operational control recommendations, and consensus manufacturing and certification standards. The group is using reliability and lifetime data collected by laser diode manufacturers and the user community to develop a set of standardized guidelines for specifying and qualifying laser diodes for long-duration operation in space, the ultimate goal being to promote an informed U.S. Government investment and procurement strategy for assuring the availability and durability of space-qualified LDAs. The group is also working to establish effective implementation of statistical design techniques at the supplier design, development, and manufacturing levels to help reduce product performance variability and improve product reliability for diodes employed in space applications

  12. Regulation of U6 Promoter Activity by Transcriptional Interference in Viral Vector-Based RNAi

    Institute of Scientific and Technical Information of China (English)

    Linghu Nie; Meghna Das Thakur; Yumei Wang; Qin Su; Yongliang Zhao; Yunfeng Feng


    The direct negative impact of the transcriptional activity of one component on the second one in c/s is referred to as transcriptional interference (TI).U6 is a type Ⅲ RNA polymerase Ⅲ promoter commonly used for driving small hairpin RNA (shRNA) expression in vector-based RNAi.In the design and construction of viral vectors,multiple transcription units may be arranged in close proximity in a space-limited vector.Determining if U6 promoter activity can be affected by TI is critical for the expression of target shRNA in gene therapy or loss-of-function studies.In this research,we designed and implemented a modified retroviral system where shRNA and exogenous gene expressions were driven by two independent transcriptional units.We arranged U6 promoter driving.shRNA expression and UbiC promoter in two promoter arrangements.In primary macrophages,we found U6 promoter activity was inhibited by UbiC promoter when in the divergent arrangement but not in tandem.In contrast,PKG promoter had no such negative impact.Instead of enhancing U6 promoter activity,CMV enhancer had significant negative impact on U6 promoter activity in the presence of UbiC promoter.Our results indicate that U6 promoter activity can be affected by TI in a proximal promoter-specific and arrangement-dependent manner.

  13. Promotion of Tumor-Initiating Cells in Primary and Recurrent Breast Tumors (United States)


    6680–6684. Gum R, Wang SW, Lengyel E, Yu D, Hung MC, Juarez J et al. (1995). Upregulation of urokinase-type plasminogen activator expression by the...induces invasion through the canonical pathway involving IKKalpha. Oncogene 2010; 8: 1238–1248. 34 Al-Hajj M, Wicha MS, Benito -Hernandez A, Morrison SJ

  14. Activator protein 1 promotes the transcriptional activation of IRAK-M. (United States)

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


    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.

  15. Initial experience at a university teaching hospital from using telemedicine to promote education through video conferencing

    Directory of Open Access Journals (Sweden)

    Bruno Monteiro Tavares Pereira

    Full Text Available CONTEXT AND OBJECTIVE: Telehealth and telemedicine services are advancing rapidly, with an increasing spectrum of information and communication technologies that can be applied broadly to the population's health, and to medical education. The aim here was to report our institution's experience from 100 videoconferencing meetings between five different countries in the Americas over a one-year period. DESIGN AND SETTING: Retrospective study at Universidade Estadual de Campinas. METHODS: Through a Microsoft Excel database, all conferences in all specialties held at our institution from September 2009 to August 2010 were analyzed retrospectively. RESULTS: A total of 647 students, physicians and professors participated in telemedicine meetings. A monthly mean of 8.3 (± 4.3 teleconferences were held over the analysis period. Excluding holidays and the month of inaugurating the telemedicine theatre, our teleconference rate reached a mean of 10.3 (± 2.7, or two teleconferences a week, on average. Trauma surgery and meetings on patient safety were by far the most common subjects discussed in our teleconference meetings, accounting for 22% and 21% of the total calls. CONCLUSION: Our experience with telemedicine meetings has increased students' interest; helped our institution to follow and discuss protocols that are already accepted worldwide; and stimulated professors to promote telemedicine-related research in their own specialties and keep up-to-date. These high-technology meetings have shortened distances in our vast country, and to other reference centers abroad. This virtual proximity has enabled discussion of international training with students and residents, to increase their overall knowledge and improve their education within this institution.

  16. Promotion of Tumor-Initiating Cells in Primary and Recurrent Breast Tumors (United States)


    Currently we have shown that NF-κB is highly active in TICs isolated from different basal-like/ triple - negative cancer cell lines. Inhibition of NF-κB...phenotype, via its regulation of RelB. FDA-approved thiordiazine may be a treatment for basal-like/ triple - negative breast cancer via its ability to...Moreover, we have demonstrated that the EMT transcription factor, Snail, is markedly upregulated in recurrent mammary tumors, and that forced expression of

  17. Cloning, sequencing and expression analysis of the NAR promoter activated during hyphal stage of Magnaporthe grisea

    Institute of Scientific and Technical Information of China (English)


    The promoter of N4R gene in Magnaporthe grisea was isolated and sequenced. The promoter sequences contained the "TATA" box, the "CAAT" box, and binding sites for fungal regulatory proteins. Programs that predict promoter sequences indicated that promoter sequence lies between locations 430 and 857 of the NAR promoter fragment. GFP expression under the NAR promoter and NAR transcript analysis revealed that this promoter is activated primarily at the mycelial stage in the rice blast fungus and could be used to express native or extrinsic genes in the mycelia of the rice blast fungus.

  18. The Hierarchy of Transcriptional Activation: From Enhancer to Promoter. (United States)

    Vernimmen, Douglas; Bickmore, Wendy A


    Regulatory elements (enhancers) that are remote from promoters play a critical role in the spatial, temporal, and physiological control of gene expression. Studies on specific loci, together with genome-wide approaches, suggest that there may be many common mechanisms involved in enhancer-promoter communication. Here, we discuss the multiprotein complexes that are recruited to enhancers and the hierarchy of events taking place between regulatory elements and promoters.

  19. Facilitators and barriers in the collaboration between the primary care and the sport sector in order to promote physical activity: A systematic literature review

    NARCIS (Netherlands)

    Leenaars, K.E.; Smit, E.; Wagemakers, A.; Molleman, G.R.; Koelen, M.A.


    INTRODUCTION: The aim of this review was to identify collaborative initiatives between the primary care and the sport sector in order to promote physical activity (PA), and barriers and facilitators in these initiatives. METHOD: Pubmed, SportDiscus, Web of Science, and SOCindex were systematically s

  20. Facilitators and barriers in the collaboration between the primary care and the sport sector in order to promote physical activity: A systematic literature review

    NARCIS (Netherlands)

    Leenaars, K.E.F.; Smit, E.; Wagemakers, A.; Molleman, G.R.M.; Koelen, M.A.


    Introduction The aim of this review was to identify collaborative initiatives between the primary care and the sport sector in order to promote physical activity (PA), and barriers and facilitators in these initiatives. Method Pubmed, SportDiscus, Web of Science, and SOCindex were systematically sea

  1. Activation of PKA leads to mesenchymal-to-epithelial transition and loss of tumor-initiating ability. (United States)

    Pattabiraman, Diwakar R; Bierie, Brian; Kober, Katharina Isabelle; Thiru, Prathapan; Krall, Jordan A; Zill, Christina; Reinhardt, Ferenc; Tam, Wai Leong; Weinberg, Robert A


    The epithelial-to-mesenchymal transition enables carcinoma cells to acquire malignancy-associated traits and the properties of tumor-initiating cells (TICs). TICs have emerged in recent years as important targets for cancer therapy, owing to their ability to drive clinical relapse and enable metastasis. Here, we propose a strategy to eliminate mesenchymal TICs by inducing their conversion to more epithelial counterparts that have lost tumor-initiating ability. We report that increases in intracellular levels of the second messenger, adenosine 3',5'-monophosphate, and the subsequent activation of protein kinase A (PKA) induce a mesenchymal-to-epithelial transition (MET) in mesenchymal human mammary epithelial cells. PKA activation triggers epigenetic reprogramming of TICs by the histone demethylase PHF2, which promotes their differentiation and loss of tumor-initiating ability. This study provides proof-of-principle for inducing an MET as differentiation therapy for TICs and uncovers a role for PKA in enforcing and maintaining the epithelial state.

  2. Where and how breastfeeding promotion initiatives should focus its attention? A study from rural Wardha

    Directory of Open Access Journals (Sweden)

    Dongre A


    Full Text Available Background: In India, the practice of breastfeeding is almost universal, but initiation of breastfeeding is generally quite late and colostrum is discarded. Integrated Management of Neonatal and Childhood Illness (IMNCI strategy recommended systematic assessment of breastfeeding and emphasized counseling of the mother on proper positioning and attachment of infant to the breast. Objective: To assess breastfeeding among mothers of below six months children in rural Wardha. Materials and Methods: The present cross-sectional study was undertaken in surrounding 23 villages of Kasturba Rural Health Training Center (KRHTC, Anji. Two Auxiliary Nurse Midwives (ANMs trained in IMNCI paid house visits to 99 mothers during the study period and undertook the assessment of breastfeeding using IMNCI assessment form for young infants. Auxiliary Nurse Midwives observed and recorded the positioning and attachment of infant to the breast as per IMNCI guidelines. The data were entered and analyzed using Epi_Info (version 6.04d software package. Results: Most of the deliveries 94 (94.9% took place in the healthcare facilities. Majority 61 (61.6% newborn babies had received breastfeeding within half an hour. About half of the mothers had any of the feeding problems like feeding less than eight times in 24 h, giving any other food or drinks or is low weight for age. Significantly more mothers with feeding problems had problems in positioning and attachment of infant to the breast as compared with those mothers who did not have any feeding problems. Conclusions: In the settings, where practice of institutional delivery is high, the staff of healthcare facility should ensure education of the mothers regarding position and attachment of infant to the breast before discharge from the healthcare facility. At the village level, Village Health Nutrition Day (VHND can be utilized for health education of future mothers and support for the breastfeeding mothers. The IMNCI

  3. Investigating ultra high-enthalpy geothermal systems: a collaborative initiative to promote scientific opportunities (United States)

    Elders, W. A.; Nielson, D.; Schiffman, P.; Schriener, A., Jr.


    Scientists, engineers, and policy makers gathered at a workshop in the San Bernardino Mountains of southern California in October 2013 to discuss the science and technology involved in developing high-enthalpy geothermal fields. A typical high-enthalpy geothermal well between 2000 and 3000 m deep produces a mixture of hot water and steam at 200-300 °C that can be used to generate about 5-10 MWe of electric power. The theme of the workshop was to explore the feasibility and economic potential of increasing the power output of geothermal wells by an order of magnitude by drilling deeper to reach much higher pressures and temperatures. Development of higher enthalpy geothermal systems for power production has obvious advantages; specifically higher temperatures yield higher power outputs per well so that fewer wells are needed, leading to smaller environmental footprints for a given size of power plant. Plans for resource assessment and drilling in such higher enthalpy areas are already underway in Iceland, New Zealand, and Japan. There is considerable potential for similar developments in other countries that already have a large production of electricity from geothermal steam, such as Mexico, the Philippines, Indonesia, Italy, and the USA. However drilling deeper involves technical and economic challenges. One approach to mitigating the cost issue is to form a consortium of industry, government and academia to share the costs and broaden the scope of investigation. An excellent example of such collaboration is the Iceland Deep Drilling Project (IDDP), which is investigating the economic feasibility of producing electricity from supercritical geothermal reservoirs, and this approach could serve as model for future developments elsewhere. A planning committee was formed to explore creating a similar initiative in the USA.

  4. CDPP activities: Promoting research and education in space physics (United States)

    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.


    The French Plasma Physics Data Centre (CDPP, 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, ...).

  5. Dose response for TCDD promotion of hepatocarcinogenesis in rats initiated with DEN: histologic, biochemical, and cell proliferation endpoints. (United States)

    Maronpot, R R; Foley, J F; Takahashi, K; Goldsworthy, T; Clark, G; Tritscher, A; Portier, C; Lucier, G


    The present study examines the dose-response relationship for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) promotion of histologic and biochemical parameters by using a two-stage model for hepatocarcinogenesis in female Sprague-Dawley rats initiated with a single intraperitoneal dose of 175 mg of diethylnitrosamine (DEN)/kg body weight at 70 days of age. Starting 2 weeks after initiation, treatment groups of 8-10 rats were given TCDD by gavage in corn oil once every 2 weeks for 30 weeks. Doses were 3.5, 10.7, 35.7, and 125 ng TCDD/kg body weight/day. A significant body weight reduction was present in the noninitiated group that received 125 ng TCDD. Relative liver weight was statistically increased in initiated rats treated with > or = 10.7 ng TCDD and in noninitiated rats treated with > or = 35.7 ng TCDD. Histopathologic evidence of cytotoxicity was dose-related in all TCDD-treated groups. There was a statistically significant dose response in the bromodeoxyuridine (BrdU) S-phase labeling index (LI) in the DEN-initiated rats (p < 0.01) and a marginally significant trend in the saline-treated rats (p = 0.10), but proliferating cell nuclear antigen S-phase LI and growth fraction within altered hepatic foci showed no increase. Among the DEN-initiated groups there was a significant increase in glutathione S-transferase altered hepatic foci stereological parameters in the 125 ng TCDD group. This study demonstrates that dose-response relationships for TCDD's effects on cell proliferation growth of altered hepatic foci are different from previously reported effects on P450 gene expression, indicating that different biological or biochemical responses may exhibit different dose-response relationships.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Mesenchymal Cancer Cell-Stroma Crosstalk Promotes Niche Activation, Epithelial Reversion, and Metastatic Colonization

    Directory of Open Access Journals (Sweden)

    Yaiza del Pozo Martin


    Full Text Available During metastatic colonization, tumor cells must establish a favorable microenvironment or niche that will sustain their growth. However, both the temporal and molecular details of this process remain poorly understood. Here, we found that metastatic initiating cells (MICs exhibit a high capacity for lung fibroblast activation as a result of Thrombospondin 2 (THBS2 expression. Importantly, inhibiting the mesenchymal phenotype of MICs by blocking the epithelial-to-mesenchymal transition (EMT-associated kinase AXL reduces THBS2 secretion, niche-activating ability, and, consequently, metastatic competence. Subsequently, disseminated metastatic cells revert to an AXL-negative, more epithelial phenotype to proliferate and decrease the phosphorylation levels of TGF-β-dependent SMAD2-3 in favor of BMP/SMAD1-5 signaling. Remarkably, newly activated fibroblasts promote this transition. In summary, our data reveal a crosstalk between cancer cells and their microenvironment whereby the EMT status initially triggers and then is regulated by niche activation during metastatic colonization.

  7. Promoting Coordinated Development of Community-Based Information Standards for Modeling in Biology: The COMBINE Initiative. (United States)

    Hucka, Michael; Nickerson, David P; Bader, Gary D; Bergmann, Frank T; Cooper, Jonathan; Demir, Emek; Garny, Alan; Golebiewski, Martin; Myers, Chris J; Schreiber, Falk; Waltemath, Dagmar; Le Novère, Nicolas


    The Computational Modeling in Biology Network (COMBINE) is a consortium of groups involved in the development of open community standards and formats used in computational modeling in biology. COMBINE's aim is to act as a coordinator, facilitator, and resource for different standardization efforts whose domains of use cover related areas of the computational biology space. In this perspective article, we summarize COMBINE, its general organization, and the community standards and other efforts involved in it. Our goals are to help guide readers toward standards that may be suitable for their research activities, as well as to direct interested readers to relevant communities where they can best expect to receive assistance in how to develop interoperable computational models.

  8. Electromagnetic activity before initial breakdown pulses of lightning (United States)

    Marshall, T.; Stolzenburg, M.; Karunarathna, N.; Karunarathne, S.


    Lightning flash initiation is studied using electric field change (E-change) measurements made in Florida. An initial E-change (IEC) was found immediately before the first initial breakdown (IB) pulse in both cloud-to-ground (CG) and intracloud (IC) flashes if the E-change sensor was within 80% of the reversal distance of the IEC. For 18 CG flashes, the IECs had an average point dipole moment of 23 C m and an average duration of 0.18 ms; these parameters for 18 IC flashes were -170 C m and 1.53 ms. The IECs of CG flashes began with a change in the slope of the E-change (with respect to time) from zero slope to a positive slope, consistent with downward motion of negative charge and/or upward motion of positive charge. For IECs of IC flashes, the beginning slope change was from zero to negative slope, consistent with upward motion of negative charge and/or downward motion of positive charge. During an IEC, the E-change monotonically increased for CG flashes and monotonically decreased for IC flashes. In 14 of 36 cases, the IEC beginning was coincident with a discrete, impulsive source of VHF radiation; another 13 cases had at least one VHF source during the IEC or the first IB pulse. Before the IECs, there were no preliminary variations detected in the 36 flashes. It is hypothesized that lightning initiation begins with an ionizing event that causes the IEC and that the IEC enhances the ambient electric field to produce the first IB pulse.

  9. [Comparative analysis of activity of different promoters for NIS gene expression in melanoma cells]. (United States)

    Kuz'mich, A I; Kopantsev, E P; Vinogradova, T V; Sverdlov, E D


    Development of targeted drug delivery system is key problem of cancer gene therapy. To ensure specific delivery of these therapeutic compounds to the tumor it is preferable for therapeutic gene expression to occur predominantly in cancer cells. Therefore, when testing drug in vivo, it is necessary to study distribution of therapeutic gene expression products in different tissues of the organism. Sodium iodide symporter (NIS) is attractive reporter because its tissue level is easily quantitatively detected by noninvasive imaging methods. Different promoters are used to direct expression of therapeutic genes in tumor cells: strong nonspecific, moderate tissue-specific and tumor-specific. Tumor-specific promoters function in wide range of tumor cells, however they are relatively weak. Relationship between promoter and sodium iodide symporter activity is unclear to date. In this report we examined activity of different promoters in two melanoma cell lines, functional activity of NIS driven by these promoters, also we compared promoter strength and NIS activity. We demonstrated that in spite of strong differences in promoter activity functional activity of NIS directed by these promoters varies weakly. Relatively weak melanoma-specific promoter directs high NIS activity in melanoma cell, however weaker cancer-specific promoters drive high NIS activity only in certain melanoma cell line.

  10. Autoactivation of proteinase A initiates activation of yeast vacuolar zymogens

    DEFF Research Database (Denmark)

    van den Hazel, H B; Kielland-Brandt, Morten; Winther, Jakob R.


    The Saccharomyces cerevisiae PEP4 gene encodes proteinase A, an aspartyl protease. pep4 mutants are defective in the activation of many vacuolar hydrolases, including proteinase B. We have expressed a pep4 mutation which directs the accumulation of pro-proteinase A with a defective active site. C...... of the mutant zymogen, owing to a strong, proteinase-B-dependent, phenotypic lag. In a proteinase-B-negative strain, processing of pro-proteinase A led to an active form of a higher molecular mass than the normal mature form....

  11. Friendship groups and physical activity: qualitative findings on how physical activity is initiated and maintained among 10–11 year old children

    Directory of Open Access Journals (Sweden)

    Page Angie S


    factor in maintaining activity participation with participating in activity with friends a key factor influencing enjoyment. Conclusion Friendship groups affect both the initiation and maintenance of youth physical activity. Children belong to several groups and engage in different activities with different groups. Simple strategies that aim to promote physical activity via the different friendship groups could be an effective means of promoting increased physical activity in young people.

  12. Coaches' Perceptions of French Sports Clubs: Health-Promotion Activities, Aims and Coach Motivation (United States)

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


    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)…

  13. 78 FR 24393 - Agency Information Collection Activities; Comment Request; Promoting Student Success in Algebra I... (United States)


    ... Agency Information Collection Activities; Comment Request; Promoting Student Success in Algebra I Project... notice will be considered public records. Title of Collection: Promoting Student Success in Algebra I... Estimated Number of Annual Burden Hours: 208. Abstract: The Promoting Student Success in Algebra I...

  14. A role for the H4 subunit of vaccinia RNA polymerase in transcription initiation at a viral early promoter. (United States)

    Deng, L; Shuman, S


    The vaccinia virus H4 gene encodes an essential subunit of the DNA-dependent RNA polymerase holoenzyme encapsidated within virus particles (Ahn, B., and Moss, B. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 3536-3540; Kane, E. M., and Shuman, S. (1992) J. Virol. 66, 5752-5762). The role of this protein in transcription of viral early genes was revealed by the effects of affinity-purified anti-H4 antibody on discrete phases of the early transcription reaction in vitro. Anti-H4 specifically prevented the synthesis of a 21-nucleotide nascent RNA chain but had no impact on elongation of the 21-mer RNA by preassembled ternary complexes. Inhibition of initiation but not elongation was also observed with affinity-purified anti-D6 antibody directed against the 70-kDa subunit of the vaccinia early transcription initiation factor (ETF). Native gel mobility-shift assays showed that anti-H4 prevented the NTP-dependent recruitment of RNA polymerase to the preinitiation complex of ETF bound at the early promoter. Two species of ternary complexes could be resolved by native gel electrophoresis. Addition of anti-H4 to preformed complexes elicited a supershift of both ternary species but not of the preinitiation complex. Supeshift by anti-D6 revealed that the more rapidly migrating species of ternary complex did not contain immunoreactive ETF. Loss of ETF from the ternary complex was time-dependent. Thus, whereas the H4 protein was a stable constituent of the elongation complex, ETF was dissociable. We suggest that H4 functions as a molecular bridge to ETF and thereby allows specific recognition of early promoters by the core RNA polymerase. H4 is unlike bacterial sigma factor in that it remains bound to polymerase after the elongation complex is established.

  15. Making Sense of Total VET Activity: An Initial Market Analysis (United States)

    National Centre for Vocational Education Research (NCVER), 2016


    Following the successful first national publication of total vocational education and training (VET) activity and presentation of various informative data products, NCVER has continued to undertake further analysis of the submitted data. This paper is the first in a suite of the National Centre for Vocational Education Research (NCVER) authored…

  16. Conserved hypothetical BB0462 protein enhances the transcription activity of oppAV promoter

    Institute of Scientific and Technical Information of China (English)


    Borrelia burgdorferi BB0462 ORF encodes an unknown functional protein with 110 amino acids.A BLAST search in protein databases and the secondary structure being predicted by the program JUFO showed that the conserved hypothetical BB0462 protein was similar to the members of the YbaB protein family in both amino acid composition and protein structure.The co-transformation of BB0462 ORF and oppA upstream regulation DNA into E.coli host cells and β-galactosidase activity assay demonstrated that the BB0462 protein enhanced the transcriptional activity of the oppAV promoter,but does not affect those of oppAⅠ,Ⅱ,Ⅲ and Ⅳ promoters.Analysis of DNA retardation and competitive repression also confirmed that the BB0462 protein bound to the 409 bp upstream regulation DNA fragment close to the initiation codon of the oppAV gene.All data in our study suggested that the BB0462 protein was involved in the transcriptional regulation of the oppAV gene

  17. Initial Implementation of an Active Prediction Capability in Bellhop (United States)


    version du Bellhop spécifiquement conçue pour offrir une capacité active. Le modèle est présentement configuré pour accepter des capteurs multiples et...capability should be examined to determine if it will be of use to the present applications of BellhopDRDC. 2.2 Enable towed array beam patterns...SECURITY CLASSIFICATION (Overall security classification of the document including special warning terms if applicable .) 3. TITLE


    Directory of Open Access Journals (Sweden)

    Hushare VJ


    Full Text Available A series of chlorosubstituted 4-aroylpyrazoles have been synthesized by refluxing of chlorosubstituted-3-aroylflavones and 3-alkoylchromone with phenylhydrazine hydrochloride in dioxane medium with 0.5 ml of piperidine. Chlorosubstituted-3-aroylflavones and chlorosubstituted-3-alkoylchromone were prepared by refluxing them separately with iodine crystal in ethanol. Initially chlorosubstituted-3-aroylflavanones and 3-alkoylchromanone have been prepared separately by the interaction of different aldehydes with 1(2-hydroxy-3,5-dichlorophenyl-3-phenyl-1,3-propanedione. Constitutions of synthesized compounds have been confirmed on the basis of elemental analysis, molecular weight determination, UV-Visible, I.R. and 1H-NMR spectral data. The titled compounds were evaluated for their growth promoting activity on some flowering plants viz. Papaver rhoeas, Dianthus chinensis, Candy tuft, Calendula officinalise, Gladiola tristis, Gaillardia.

  19. The Integration of Corporate Social Responsibility (CSR) Initiatives into Business Activities

    DEFF Research Database (Denmark)

    Knudsen, Jette Steen

    While proponents of Corporate Social Responsibility (CSR) have suggested that CSR initiatives should be integrated into mainstream business activities as ‘strategic CSR’ or ‘shared value’, research is lacking that explores how CSR initiatives are integrated in companies. This article compares CSR...... initiatives to human resource management (HRM) initiatives, which have a longer tradition of being integrated into company strategy. The focus is on gender diversity and CSR initiatives in a US multinational corporation (MNC). The MNC sees gender diversity as an integral part of business activities...

  20. Activity of heat shock genes' promoters in thermally contrasting animal species. (United States)

    Astakhova, Lyubov N; Zatsepina, Olga G; Funikov, Sergei Yu; Zelentsova, Elena S; Schostak, Natalia G; Orishchenko, Konstantin E; Evgen'ev, Michael B; Garbuz, David G


    Heat shock gene promoters represent a highly conserved and universal system for the rapid induction of transcription after various stressful stimuli. We chose pairs of mammalian and insect species that significantly differ in their thermoresistance and constitutive levels of Hsp70 to compare hsp promoter strength under normal conditions and after heat shock (HS). The first pair includes the HSPA1 gene promoter of camel (Camelus dromedarius) and humans. It was demonstrated that the camel HSPA1A and HSPA1L promoters function normally in vitro in human cell cultures and exceed the strength of orthologous human promoters under basal conditions. We used the same in vitro assay for Drosophila melanogaster Schneider-2 (S2) cells to compare the activity of the hsp70 and hsp83 promoters of the second species pair represented by Diptera, i.e., Stratiomys singularior and D. melanogaster, which dramatically differ in thermoresistance and the pattern of Hsp70 accumulation. Promoter strength was also monitored in vivo in D. melanogaster strains transformed with constructs containing the S. singularior hsp70 ORF driven either by its own promoter or an orthologous promoter from the D. melanogaster hsp70Aa gene. Analysis revealed low S. singularior hsp70 promoter activity in vitro and in vivo under basal conditions and after HS in comparison with the endogenous promoter in D. melanogaster cells, which correlates with the absence of canonical GAGA elements in the promoters of the former species. Indeed, the insertion of GAGA elements into the S. singularior hsp70 regulatory region resulted in a dramatic increase in promoter activity in vitro but only modestly enhanced the promoter strength in the larvae of the transformed strains. In contrast with hsp70 promoters, hsp83 promoters from both of the studied Diptera species demonstrated high conservation and universality.

  1. TLR4-2242 T→C variant increases transcriptional activity of its promoter

    Institute of Scientific and Technical Information of China (English)

    Wang Yongtang; Jiang Jianxin; Liu Qing; Duan Zhaoxia; Gu Wei; Zeng Ling; Chen Kehong


    Objective: To investigate the effects of-2242, -1892 and -1837 single nucleotide polymorphisms (SNPs) on toll-like receptor 4 (TLR4) promoter activity. Methods: Polymerase chain reaction (PCR) and site direct mutation technology were used to construct TLR4 basic promoter and -2242C, -1892A and -1837G mutate promoter plasmids. Dual-Luciferase Reporter assay system was used to detect the activity of constructed promoter following human embryonic kidney (HEK) 293 cells were transiently cotransfected with the constructed plasmids and the control plasmid pRL-CMV. Results: In HEK293 cells, the activity of-2242C mutate promoter was higher than -2242T promoter, and there was no significant difference when both -1892A and -1837G mutate promoter compared with -1892G and -1837A promoter, respectively. Conclusion: It is implied that -2242T→C base variation can enhance the activity of TLR4 promoter, while -1892 and -1837 SNPs have no effect on TLR4 promoter activity.

  2. Dynamic Effects of Topoisomerase I Inhibition on R-Loops and Short Transcripts at Active Promoters. (United States)

    Marinello, Jessica; Bertoncini, Stefania; Aloisi, Iris; Cristini, Agnese; Malagoli Tagliazucchi, Guidantonio; Forcato, Mattia; Sordet, Olivier; Capranico, Giovanni


    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.

  3. Dynamic Effects of Topoisomerase I Inhibition on R-Loops and Short Transcripts at Active Promoters.

    Directory of Open Access Journals (Sweden)

    Jessica Marinello

    Full Text Available 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.

  4. Extending stakeholder theory to promote resource management initiatives to key stakeholders: a case study of water transfers in Alberta, Canada. (United States)

    Lafreniere, Katherine C; Deshpande, Sameer; Bjornlund, Henning; Hunter, M Gordon


    Many attempts to implement resource management initiatives in Canadian and international communities have been resisted by stakeholders despite inclusion of their representatives in the decision-making process. Managers' failure to understand stakeholders' perspectives when proposing initiatives is a potential cause of this resistance. Our study uses marketing thought to enhance stakeholder theory by bringing in an audience-centric perspective. We attempt to understand how stakeholders perceive their interests in an organization and consequently decide how to influence that organization. By doing so, we investigate whether a disconnect exists between the perceptions of managers and those of stakeholders. Natural resource managers can utilize this knowledge to garner stakeholder support for the organization and its activities. We support this claim with findings from a water transfer plebiscite held in the Canadian province of Alberta. Sixteen personal interviews employing narrative inquiry were conducted to document voters' (i.e., irrigators') interpretations.

  5. Dynamic recruitment of active proteasomes into polyglutamine initiated inclusion bodies. (United States)

    Schipper-Krom, Sabine; Juenemann, Katrin; Jansen, Anne H; Wiemhoefer, Anne; van den Nieuwendijk, Rianne; Smith, Donna L; Hink, Mark A; Bates, Gillian P; Overkleeft, Hermen; Ovaa, Huib; Reits, Eric


    Neurodegenerative disorders such as Huntington's disease are hallmarked by neuronal intracellular inclusion body formation. Whether proteasomes are irreversibly recruited into inclusion bodies in these protein misfolding disorders is a controversial subject. In addition, it has been proposed that the proteasomes may become clogged by the aggregated protein fragments, leading to impairment of the ubiquitin-proteasome system. Here, we show by fluorescence pulse-chase experiments in living cells that proteasomes are dynamically and reversibly recruited into inclusion bodies. As these recruited proteasomes remain catalytically active and accessible to substrates, our results challenge the concept of proteasome sequestration and impairment in Huntington's disease, and support the reported absence of proteasome impairment in mouse models of Huntington's disease.

  6. Promoting Physical Activity in Secondary Schools: Growing Expectations, "Same Old" Issues? (United States)

    Cale, Lorraine; Harris, Jo; Duncombe, Rebecca


    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…

  7. The Role of Physical Educators in Helping Classroom Teachers to Promote Physical Activity (United States)

    Russ, Laura


    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…

  8. DUX4 binding to retroelements creates promoters that are active in FSHD muscle and testis.

    Directory of Open Access Journals (Sweden)

    Janet M Young


    Full Text Available The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues. Facioscapulohumeral muscular dystrophy (FSHD is caused by mutations that decrease the epigenetic repression of DUX4 in somatic tissues and result in mis-expression of this transcription factor in skeletal muscle. DUX4 binds sites in the human genome that contain a double-homeobox sequence motif, including sites in unique regions of the genome as well as many sites in repetitive elements. Using ChIP-seq and RNA-seq on myoblasts transduced with DUX4 we show that DUX4 binds and activates transcription of mammalian apparent LTR-retrotransposons (MaLRs, endogenous retrovirus (ERVL and ERVK elements, and pericentromeric satellite HSATII sequences. Some DUX4-activated MaLR and ERV elements create novel promoters for genes, long non-coding RNAs, and antisense transcripts. Many of these novel transcripts are expressed in FSHD muscle cells but not control cells, and thus might contribute to FSHD pathology. For example, HEY1, a repressor of myogenesis, is activated by DUX4 through a MaLR promoter. DUX4-bound motifs, including those in repetitive elements, show evolutionary conservation and some repeat-initiated transcripts are expressed in healthy testis, the normal expression site of DUX4, but more rarely in other somatic tissues. Testis expression patterns are known to have evolved rapidly in mammals, but the mechanisms behind this rapid change have not yet been identified: our results suggest that mobilization of MaLR and ERV elements during mammalian evolution altered germline gene expression patterns through transcriptional activation by DUX4. Our findings demonstrate a role for DUX4 and repetitive elements in mammalian germline evolution and in FSHD muscular dystrophy.

  9. Interventions for promoting physical activity among European teenagers: a systematic review


    De Meester, Femke; van Lenthe, Frank J; Spittaels, Heleen; Lien, Nanna; De Bourdeaudhuij, Ilse


    Background: Although physical activity is considered to yield substantial health benefits, the level of physical activity among European teenagers is not sufficient. Adolescence is characterized by a decline in physical activity level. Many studies investigated the effectiveness of interventions promoting physical activity among young people, but none dealt with the available evidence specific for Europe. This review was conducted to summarize the effectiveness of interventions to promote phy...

  10. Immunomodulator CD200 promotes neurotrophic activity by interacting with and activating the fibroblast growth factor receptor

    DEFF Research Database (Denmark)

    Pankratova, Stanislava; Bjornsdottir, Halla; Christensen, Claus;


    in the suppression of microglia activation. We for the first time demonstrated that CD200 can interact with and transduce signaling through activation of the fibroblast growth factor receptor (FGFR), thereby inducing neuritogenesis and promoting neuronal survival in primary neurons. CD200-induced FGFR...... phosphorylation was abrogated by CD200R, whereas FGF2-induced FGFR activation was inhibited by CD200. We also identified a sequence motif located in the first Ig-like module of CD200, likely representing the minimal CD200 binding site for FGFR. The FGFR binding motif overlaps with the CD200R binding site......, suggesting that they can compete for CD200 binding in cells that express both receptors. We propose that CD200 in neurons functions as a ligand of FGFR....

  11. Prevalence of the initiator over the TATA box in human and yeast genes and identification of DNA motifs enriched in human TATA-less core promoters. (United States)

    Yang, Chuhu; Bolotin, Eugene; Jiang, Tao; Sladek, Frances M; Martinez, Ernest


    The core promoter of eukaryotic genes is the minimal DNA region that recruits the basal transcription machinery to direct efficient and accurate transcription initiation. The fraction of human and yeast genes that contain specific core promoter elements such as the TATA box and the initiator (INR) remains unclear and core promoter motifs specific for TATA-less genes remain to be identified. Here, we present genome-scale computational analyses indicating that approximately 76% of human core promoters lack TATA-like elements, have a high GC content, and are enriched in Sp1-binding sites. We further identify two motifs - M3 (SCGGAAGY) and M22 (TGCGCANK) - that occur preferentially in human TATA-less core promoters. About 24% of human genes have a TATA-like element and their promoters are generally AT-rich; however, only approximately 10% of these TATA-containing promoters have the canonical TATA box (TATAWAWR). In contrast, approximately 46% of human core promoters contain the consensus INR (YYANWYY) and approximately 30% are INR-containing TATA-less genes. Significantly, approximately 46% of human promoters lack both TATA-like and consensus INR elements. Surprisingly, mammalian-type INR sequences are present - and tend to cluster - in the transcription start site (TSS) region of approximately 40% of yeast core promoters and the frequency of specific core promoter types appears to be conserved in yeast and human genomes. Gene Ontology analyses reveal that TATA-less genes in humans, as in yeast, are frequently involved in basic "housekeeping" processes, while TATA-containing genes are more often highly regulated, such as by biotic or stress stimuli. These results reveal unexpected similarities in the occurrence of specific core promoter types and in their associated biological processes in yeast and humans and point to novel vertebrate-specific DNA motifs that might play a selective role in TATA-independent transcription.

  12. nifH Promoter Activity Is Regulated by DNA Supercoiling in Sinorhizobium meliloti

    Institute of Scientific and Technical Information of China (English)

    Yan-Jie LIU; Biao HU; Jia-Bi ZHU; Shan-Jiong SHEN; Guan-Qiao YU


    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 supercoilingdependent 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.

  13. Promotive effect of pyridine on indole degradation by activated sludge under anoxic conditions

    Institute of Scientific and Technical Information of China (English)

    LI Yongmei; LI Wenshu; GU Guowei


    Batch experiments were carried out to investigate the promotive effect ofpyridine on indole degradation under denitrifying conditions.The seed sludge was obtained from a local coal-coking wastewater treatment facility and was acclimated in the laboratory.Indole and pyridine were supplemented to the synthetic wastewater at different ratios.The optimum ratio of chemical oxygen demand (COD) to nitrate (C/N) was 8.4-8.9 for both denitrification and indole and pyridine degradation.At a temperature of 28℃ and pH of 7.0-7.5,the nitrate reductase activity (NRA) was in the best state.The addition of pyridine could promote NRA and the degradation of indole.When the initial concentration of indole was 150 mg/L,the concentration ratio of indole to pyridine was in the range of 1-10.Under optimum C/N conditions,the degradation of indole could be described with pseudo-zero-order kinetics.There was no accumulation of nitrite during the reaction.When the concentration ratio of pyridine to indole was less than 0.25 with an increase in the pyridine proportion,there were more significant augment rates for NRA and the degradation of indole than the situation when the concentration ratio was more than 0.25.

  14. [experience Of Adolescents In An Activity Of Health Promotion].


    Ferreira Júnior, Antonio Rodrigues; de Barros, Erineide Melo Albuquerque; Sousa, Rosalice Araújo de; Souza, Luiza Jane Eyre de


    This paper describes an experience that occurred in the municipality of Uruoca-CE, Brazil, where nurses from the Family Health Strategy involved a group of teenagers in practices of health promotion. Pregnant women were chosen as priority because of their resistance to perform dental consultation and small family participation in prenatal care. It was built up a play for the pregnant women and their families, focusing on the theme, in which the adolescents were the writers, set designers and ...

  15. Initial Teacher Education for School Health Promotion in Austria: Does It Support the Implementation of the Health-Promoting School Approach? (United States)

    Flaschberger, Edith


    Purpose: School health promotion is said to be most effective when implemented through a comprehensive, settings-based, whole-school approach. The purpose of this paper is to address the current lack of knowledge about the current state of teacher education for health promotion and its potential to further the development of settings-based…


    Directory of Open Access Journals (Sweden)

    Martin Owusu Ansah


    Full Text Available The promotional activities have become more sophisticated and an increasing number of companies are using them to ensure their survival in today’s competitive market. Essentially, the study analyzed the nature of sales promotional activities of Unilever Ghana Limited; determined factors that influence the consumption of Unilever products in Kumasi and finally examined the relationship between sales promotions and the consumption of Unilever products. Primary and secondary data sources were used to select 220 consumers of Unilever in Kumasi and an in-depth interview with the Managers of the companies in Kumasi. Convenient sampling technique was employed in the study. Cross tabulation was done on the demographics whilst a regression model was used to establish the relationship between sales promotions and consumption of products. The findings revealed that Personalities in promotions, Prices in promotions, Messages in promotions and Promotional tools have strong influence on consumption but the Medium in promotion did not have influence on consumption during promotions. It was therefore recommended for celebrities to be used in the company’s promotions.

  17. The physical therapist's role in physical activity promotion

    NARCIS (Netherlands)

    Verhagen, E.; Engbers, L.


    Clinicians are increasingly confronted with the diseases of physical inactivity. Paradoxically, a promising strategy to motivate sedentary individuals to become more active is the opportunity to encourage physical activity related behavioural change when individuals encounter health professionals. A

  18. Ethanol Does Not Promote MeIQx-initiated Rat Colon Carcinogenesis Based on Evidence from Analysis of a Colon Cancer Surrogate Marker. (United States)

    Kushida, Masahiko; Wanibuchi, Hideki; Wei, Min; Kakehashi, Anna; Ozaki, Keisuke; Sukata, Tokuo; Miyata, Kaori; Ogata, Keiko; Uwagawa, Satoshi; Fukushima, Shoji


    Epidemiological studies suggest that alcohol consumption increases the risk of developing colorectal cancer. However, the data are confounded by numerous cosegregating variables. To cast further light on the relationships between alcohol intake and colon cancer development, 21-day-old male F344/DuCrj rats were fed 200 ppm 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in their diet for 8 weeks and doses of 0, 0.1, 0.3, 1, 3, 10 and 20% of ethanol in their drinking water ad libitum for 16 weeks thereafter. The rats were sacrificed after 24 weeks of experiment, and aberrant crypt foci (ACF), surrogate lesions for colon cancer, were examined under a light microscope at low magnification. Ethanol was found not to affect the ACF formation at any dose compared with the initiated-controls. Furthermore, ethanol did not alter colon epithelial cell proliferation. These data, obtained by analysis of a colon cancer surrogate marker lesion, indicate that ethanol lacks promotion activity for MeIQx-initiated rat colon carcinogenesis.

  19. Promoting physical activity in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Berg, Machteld Heleen van den


    The aim of the thesis was to study: 1. The engagement of patients with RA in various forms of physical activity and their preferences regarding the delivery of physical activity interventions; 2. The evidence regarding the effectiveness of physical activity interventions delivered by means of the I

  20. Promoting Physical Activity: Addressing Barriers and Moving Forward (United States)

    Beighle, Aaron; Morrow, James R.


    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…

  1. Activated scavenger receptor A promotes glial internalization of aβ.

    Directory of Open Access Journals (Sweden)

    He Zhang

    Full Text Available Beta-amyloid (Aβ aggregates have a pivotal role in pathological processing of Alzheimer's disease (AD. The clearance of Aβ monomer or aggregates is a causal strategy for AD treatment. Microglia and astrocytes are the main macrophages that exert critical neuroprotective roles in the brain. They may effectively clear the toxic accumulation of Aβ at the initial stage of AD, however, their functions are attenuated because of glial overactivation. In this study, we first showed that heptapeptide XD4 activates the class A scavenger receptor (SR-A on the glia by increasing the binding of Aβ to SR-A, thereby promoting glial phagocytosis of Aβ oligomer in microglia and astrocytes and triggering intracellular mitogen-activated protein kinase (MAPK signaling cascades. Moreover, XD4 enhances the internalization of Aβ monomers to microglia and astrocytes through macropinocytosis or SR-A-mediated phagocytosis. Furthermore, XD4 significantly inhibits Aβ oligomer-induced cytotoxicity to glial cells and decreases the production of proinflammatory cytokines, such as TNF-α and IL-1β, in vitro and in vivo. Our findings may provide a novel strategy for AD treatment by activating SR-A.

  2. Chinese tobacco industry promotional activity on the microblog Weibo.

    Directory of Open Access Journals (Sweden)

    Fan Wang

    Full Text Available 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.

  3. Interacting Patients: The construction of active patientship in quality improvement initiatives

    NARCIS (Netherlands)

    F.D. Vennik (Femke)


    markdownabstractThe promotion of active patient participation in healthcare quality improvement projects is an important policy goal in the Netherlands and other Western countries. Healthcare quality improvement is no longer perceived to be an exclusive professional activity; patients, who may be ab

  4. AMP-activated protein kinase-regulated activation of the PGC-1alpha promoter in skeletal muscle cells.

    Directory of Open Access Journals (Sweden)

    Isabella Irrcher

    Full Text Available The mechanisms by which PGC-1alpha gene expression is controlled in skeletal muscle remains largely undefined. Thus, we sought to investigate the transcriptional regulation of PGC-1alpha using AICAR, an activator of AMPK, that is known to increase PGC-1alpha expression. A 2.2 kb fragment of the human PGC-1alpha promoter was cloned and sequence analysis revealed that this TATA-less sequence houses putative consensus sites including a GC-box, a CRE, several IRSs, a SRE, binding sites for GATA, MEF2, p 53, NF-kappaB, and EBox binding proteins. AMPK activation for 24 hours increased PGC-1alpha promoter activity with concomitant increases in mRNA expression. The effect of AICAR on transcriptional activation was mediated by an overlapping GATA/EBox binding site at -495 within the PGC-1alpha promoter based on gel shift analyses that revealed increases in GATA/EBox DNA binding. Mutation of the EBox within the GATA/EBox binding site in the promoter reduced basal promoter activity and completely abolished the AICAR effect. Supershift analyses identified USF-1 as a DNA binding transcription factor potentially involved in regulating PGC-1alpha promoter activity, which was confirmed in vivo by ChIP. Overexpression of either GATA-4 or USF-1 alone increased the p851 PGC-1alpha promoter activity by 1.7- and 2.0-fold respectively, while co-expression of GATA-4 and USF-1 led to an additive increase in PGC-1alpha promoter activity. The USF-1-mediated increase in PGC-1alpha promoter activation led to similar increases at the mRNA level. Our data identify a novel AMPK-mediated regulatory pathway that regulates PGC-1alpha gene expression. This could represent a potential therapeutic target to control PGC-1alpha expression in skeletal muscle.

  5. Anthracyclines induce double-strand DNA breaks at active gene promoters. (United States)

    Yang, Fan; Kemp, Christopher J; Henikoff, Steven


    Doxorubicin is a widely used chemotherapeutic drug that intercalates between DNA base-pairs and poisons Topoisomerase II, although the mechanistic basis for cell killing remains speculative. Doxorubicin and related anthracycline compounds have been shown to increase nucleosome turnover and/or eviction around promoters, which suggests that the resulting enhanced exposure of DNA might underlie cell killing. Previously, we showed that low doses of anthracyclines increase nucleosome turnover around active gene promoters, which suggests that loss of nucleosomes might contribute to cancer cell killing. Here we apply a genome-wide method to precisely map DNA double-strand breaks (DSBs) in cancer cells. We find that spontaneous DSBs occur preferentially around promoters of active genes, and that both anthracyclines and etoposide, a Topoisomerase II poison, increase DSBs around promoters, although CpG islands are conspicuously protected from DSBs. We propose that torsion-based enhancement of nucleosome turnover by anthracyclines exposes promoter DNA, ultimately causing DSBs around promoters.

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

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


    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.

  7. Optimization of reporter gene assay: several factors influencing detection of promoter activity

    Institute of Scientific and Technical Information of China (English)

    XUE Li-xiang; WENG Mo; ZHANG Zong-yu; TONG Tan-jun


    Background Promoter analysis is currently applied to detect the expression of the targeted gene in studies of signal transduction and transcriptional regulation. As a reporter gene, luciferase plays an important role and has been used widely in the promoter assay.Methods Human embryonic lung fibroblast cells (2BS), HeLa cells and MCF-7 cells were transfected with various genes embedded by lipofectamine. This study determined various factors that affect promoter activity determination,such as the selection of the reporter genes and internal references, the dose and the type of the vectors carrying the transcription factors, the host cells and the instruments.Results The sensitivity of the luciferase assay was much higher than that of enhanced green fluorescence protein (EGFP). Moreover, promoter activity is increased in a dose-related manner only in certain ranges outside of which the results may be reversed and the promoter activity is related to the expression vector which is carrying the cDNA.Otherwise, the length of the promoter, internal references and the host cell can also influence the promoter activity.Conclusions To detect the promoter activity accurately, a few factors including dose, vector, length and host cell which influence reporter gene assay aforementioned should be considered.

  8. Promoting Female Students' Learning Motivation towards Science by Exercising Hands-On Activities (United States)

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


    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…

  9. Airway epithelial NF-κB activation promotes Mycoplasma pneumoniae clearance in mice.

    Directory of Open Access Journals (Sweden)

    Di Jiang

    Full Text Available Respiratory infections including atypical bacteria Mycoplasma pneumoniae (Mp contribute to the pathobiology of asthma and chronic obstructive pulmonary disease (COPD. Mp infection mainly targets airway epithelium and activates various signaling pathways such as nuclear factor κB (NF-κB. We have shown that short palate, lung, and nasal epithelium clone 1 (SPLUNC1 serves as a novel host defense protein and is up-regulated upon Mp infection through NF-κB activation in cultured human and mouse primary airway epithelial cells. However, the in vivo role of airway epithelial NF-κB activation in host defense against Mp infection has not been investigated. In the current study, we investigated the effects of in vivo airway epithelial NF-κB activation on lung Mp clearance and its association with airway epithelial SPLUNC1 expression.Non-antimicrobial tetracycline analog 9-t-butyl doxycycline (9-TB was initially optimized in mouse primary tracheal epithelial cell culture, and then utilized to induce in vivo airway epithelial specific NF-κB activation in conditional NF-κB transgenic mice (CC10-(CAIKKβ with or without Mp infection. Lung Mp load and inflammation were evaluated, and airway epithelial SPLUNC1 protein was examined by immunohistochemistry. We found that 9-TB treatment in NF-κB transgene positive (Tg+, but not transgene negative (Tg- mice significantly reduced lung Mp load. Moreover, 9-TB increased airway epithelial SPLUNC1 protein expression in NF-κB Tg+ mice.By using the non-antimicrobial 9-TB, our study demonstrates that in vivo airway epithelial NF-κB activation promotes lung bacterial clearance, which is accompanied by increased epithelial SPLUNC1 expression.

  10. Mast cell activation and neutrophil recruitment promotes early and robust inflammation in the meninges in EAE. (United States)

    Christy, Alison L; Walker, Margaret E; Hessner, Martin J; Brown, Melissa A


    The meninges are often considered inert tissues that house the CSF and provide protection for the brain and spinal cord. Yet emerging data demonstrates that they are also active sites of immune responses. Furthermore, the blood-CSF barrier surrounding meningeal blood vessels, together with the blood-brain barrier (BBB), is postulated to serve as a gateway for the pathological infiltration of immune cells into the CNS in multiple sclerosis (MS). Our previous studies using mast cell-deficient (Kit(W/Wv)) mice demonstrated that mast cells resident in the dura mater and pia mater exacerbate experimental autoimmune encephalomyelitis (EAE), a rodent model of MS, by facilitating CNS inflammatory cell influx. Here we examined the underlying mechanisms that mediate these effects. We demonstrate that there are dramatic alterations in immune associated gene expression in the meninges in pre-clinical disease, including those associated with mast cell and neutrophil function. Meningeal mast cells are activated within 24 h of disease induction, but do not directly compromise CNS vascular integrity. Rather, through production of TNF, mast cells elicit an early influx of neutrophils, cells known to alter vascular permeability, into the meninges. These data add to the growing evidence that inflammation in the meninges precedes CNS immune cell infiltration and establish that mast cells are among the earliest participants in these disease-initiating events. We hypothesize that mast cell-dependent neutrophil recruitment and activation in the meninges promotes early breakdown of the local BBB and CSF-blood barrier allowing initial immune cell access to the CNS.

  11. An empirical analysis of the roles, activities and performance of commercial diplomats in promoting international business


    Naray, Olivier; Bezençon, Valéry; Kostecki, Michel


    Background Governments seek to promote – beyond the support for individual businesses – increased exports but also the intangible elements, such as nation branding and country positioning for inward foreign direct investment (FDI) and other economic benefits. In this context, commercial diplomats work as State representatives with diplomatic status conducting trade and business promotion activities between a home and a host country supporting directly individual business firms or promoting t...

  12. TP0262 is a modulator of promoter activity of tpr Subfamily II genes of Treponema pallidum subsp. pallidum (United States)

    Giacani, Lorenzo; Godornes, Charmie; Puray-Chavez, Maritza; Guerra-Giraldez, Cristina; Tompa, Martin; Lukehart, Sheila A.; Centurion-Lara, Arturo


    Transcriptional regulation in Treponema pallidum subsp. pallidum is poorly understood, primarily because this organism cannot be cultivated in vitro or genetically manipulated. We have recently shown a phase variation mechanism controlling transcription initiation of Subfamily II tpr (T. pallidum repeat) genes (tprE, tprG, and tprJ), a group of virulence factor candidates. Furthermore, the same study suggested that additional mechanisms might influence the level of transcription of these tprs. The T. pallidum genome sequence has revealed a few open reading frames (ORFs) with similarity to known bacterial transcription factors (TFs), including four catabolite activator protein (CAP) homologs. In this work, sequences matching the E. coli cAMP receptor protein (CRP) binding motif were identified in silico upstream of tprE, tprG, and tprJ. Using elecrophoretic mobility shift assay (EMSA) and DNaseI footprinting assay, recombinant TP0262, a T. pallidum CRP homolog, was shown to bind specifically to amplicons obtained from the tpr promoters containing putative CRP binding motifs. Using a heterologous reporter system, binding of TP0262 to these promoters was shown to either increase (tprE and tprJ) or decrease (tprG) tpr promoter activity. This is the first characterization of a T. pallidum transcriptional modulator which influences tpr promoter activity. PMID:19432808

  13. TP0262 is a modulator of promoter activity of tpr Subfamily II genes of Treponema pallidum ssp. pallidum. (United States)

    Giacani, Lorenzo; Godornes, Charmie; Puray-Chavez, Maritza; Guerra-Giraldez, Cristina; Tompa, Martin; Lukehart, Sheila A; Centurion-Lara, Arturo


    Transcriptional regulation in Treponema pallidum ssp. pallidum is poorly understood, primarily because this organism cannot be cultivated in vitro or genetically manipulated. We have recently shown a phase variation mechanism controlling transcription initiation of Subfamily II tpr (T. pallidumrepeat) genes (tprE, tprG and tprJ), a group of virulence factor candidates. Furthermore, the same study suggested that additional mechanisms might influence the level of transcription of these tprs. The T. pallidum genome sequence has revealed a few open reading frames with similarity to known bacterial transcription factors, including four catabolite activator protein homologues. In this work, sequences matching the Escherichia coli cAMP receptor protein (CRP) binding motif were identified in silico upstream of tprE, tprG and tprJ. Using elecrophoretic mobility shift assay and DNaseI footprinting assay, recombinant TP0262, a T. pallidum CRP homologue, was shown to bind specifically to amplicons obtained from the tpr promoters containing putative CRP binding motifs. Using a heterologous reporter system, binding of TP0262 to these promoters was shown to either increase (tprE and tprJ) or decrease (tprG) tpr promoter activity. This is the first characterization of a T. pallidum transcriptional modulator that influences tpr promoter activity.

  14. Events during eucaryotic rRNA transcription initiation and elongation: Conversion from the closed to the open promoter complex requires nucleotide substrates

    Energy Technology Data Exchange (ETDEWEB)

    Bateman, E.; Paule, M.R.


    Chemical footprinting and topological analysis were carried out on the Acanthamoeba castellanii rRNA transcription initiation factor (TIF) and RNA polymerase I complexes with DNA during transcription initiation and elongation. The results show that the binding of TIF and polymerase to the promoter does not alter the supercoiling of the DNA template and the template does not become sensitive to modification by diethylpyro-carbonate, which can identify melted DNA regions. Thus, in contrast to bacterial RNA polymerase, the eucaryotic RNA polymerase I-promoter complex is in a closed configuration preceding addition of nucleotides in vitro. Initiation and 3'-O-methyl CTP-limited translocation by RNA polymerase I results in separation of the polymerase-TIF footprints, leaving the TIF footprint unaltered. In contrast, initiation and translocation result in a significant change in the conformation of the polymerase-DNA complex, culminating in an unwound DNA region of at least 10 base pairs.

  15. Measuring the activity of BioBrick promoters using an in vivo reference standard

    Directory of Open Access Journals (Sweden)

    Kelly Jason R


    Full Text Available Abstract Background The engineering of many-component, synthetic biological systems is being made easier by the development of collections of reusable, standard biological parts. However, the complexity of biology makes it difficult to predict the extent to which such efforts will succeed. As a first practical example, the Registry of Standard Biological Parts started at MIT now maintains and distributes thousands of BioBrick™ standard biological parts. However, BioBrick parts are only standardized in terms of how individual parts are physically assembled into multi-component systems, and most parts remain uncharacterized. Standardized tools, techniques, and units of measurement are needed to facilitate the characterization and reuse of parts by independent researchers across many laboratories. Results We found that the absolute activity of BioBrick promoters varies across experimental conditions and measurement instruments. We choose one promoter (BBa_J23101 to serve as an in vivo reference standard for promoter activity. We demonstrated that, by measuring the activity of promoters relative to BBa_J23101, we could reduce variation in reported promoter activity due to differences in test conditions and measurement instruments by ~50%. We defined a Relative Promoter Unit (RPU in order to report promoter characterization data in compatible units and developed a measurement kit so that researchers might more easily adopt RPU as a standard unit for reporting promoter activity. We distributed a set of test promoters to multiple labs and found good agreement in the reported relative activities of promoters so measured. We also characterized the relative activities of a reference collection of BioBrick promoters in order to further support adoption of RPU-based measurement standards. Conclusion Relative activity measurements based on an in vivoreference standard enables improved measurement of promoter activity given variation in measurement

  16. Green care farms promote activity among elderly people with dementia

    NARCIS (Netherlands)

    Bruin, S.R. de; Oosting, S.J.; Kuin, Y.; Hoefnagels, E.C.M.; Blauw, Y.H.; Groot, C.P.G.M. de; Schols, J.M.G.A.


    In the Netherlands, an increasing number of green care farms are providing day care to community-dwelling elderly people with dementia. Currently, it is unknown whether activities, activity participation, and facility use of elderly people with dementia at green care farms differ from those at regul

  17. Videogames to Promote Physical Activity in Older Adults with Schizophrenia. (United States)

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


    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.

  18. Promoting Healthy Lifestyle Behaviors: The Heart Smart Discussion Activity (United States)

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


    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…

  19. AITI and GELATI - Initiatives to promote education and training for the next generation of educators and scientists during the IPY 2007/08 and beyond (United States)

    Vogel, S. W.; Bouchard, M.; Das, S.; Gillermann, J.; Greve, R.; Matsuoka, K.; Pasotti, J.; Tweedie, C.


    The fourth International Polar Year (IPY) in 2007/08 provides a unique opportunity to enhance international collaboration in research and education. Here we present an IPY-teaching initiative (AITI), which proposes to develop an interdisciplinary international short course series promoting and fostering education and training of the next generation(s) of scientists and educators interested in natural and social sciences related to Polar Regions; a short course series (GELATI) focusing on the impact of the cryosphere on the Earth system. The main goals of the short course series are to: a) provide education and training for the next generation of graduate students, science teachers, researchers in science related to Polar Regions; b) provide training for junior faculty c) integrate research and education; d) create awareness for Polar Regions related questions in class-rooms and beyond; e) create international partnerships in education and training; f) promote multidisciplinary thinking; g) increase gender diversity in science and teaching; h) encourage minority participation. To achieve these goals it is intended to develop a curriculum of specialized and interdisciplinary courses considering various aspects of science and scientific activities, which study, or are concerned with processes/developments in Polar Regions. Due to the vast dimensions and distribution of Polar Regions across international boundaries as well as the complexity of environmental studies in Polar Regions these courses will internationally pool students and instructors. Pooling of experts and students internationally will not only ensure highest standards but also foster international partnership. To allow the integration of research and teaching and to provide the best possible study environment the up to two to three weeklong, courses will be held at international field stations or will be incorporated into large research projects. To ensure training of the next generation of

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

    Directory of Open Access Journals (Sweden)

    María Martínez-Solís


    Full Text Available 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.

  1. An MSC2 Promoter-lacZ Fusion Gene Reveals Zinc-Responsive Changes in Sites of Transcription Initiation That Occur across the Yeast Genome (United States)

    Wu, Yi-Hsuan; Taggart, Janet; Song, Pamela Xiyao; MacDiarmid, Colin; Eide, David J.


    The Msc2 and Zrg17 proteins of Saccharomyces cerevisiae form a complex to transport zinc into the endoplasmic reticulum. ZRG17 is transcriptionally induced in zinc-limited cells by the Zap1 transcription factor. In this report, we show that MSC2 mRNA also increases (~1.5 fold) in zinc-limited cells. The MSC2 gene has two in-frame ATG codons at its 5’ end, ATG1 and ATG2; ATG2 is the predicted initiation codon. When the MSC2 promoter was fused at ATG2 to the lacZ gene, we found that unlike the chromosomal gene this reporter showed a 4-fold decrease in lacZ mRNA in zinc-limited cells. Surprisingly, β-galactosidase activity generated by this fusion gene increased ~7 fold during zinc deficiency suggesting the influence of post-transcriptional factors. Transcription of MSC2ATG2-lacZ was found to start upstream of ATG1 in zinc-replete cells. In zinc-limited cells, transcription initiation shifted to sites just upstream of ATG2. From the results of mutational and polysome profile analyses, we propose the following explanation for these effects. In zinc-replete cells, MSC2ATG2-lacZ mRNA with long 5’ UTRs fold into secondary structures that inhibit translation. In zinc-limited cells, transcripts with shorter unstructured 5’ UTRs are generated that are more efficiently translated. Surprisingly, chromosomal MSC2 did not show start site shifts in response to zinc status and only shorter 5’ UTRs were observed. However, the shifts that occur in the MSC2ATG2-lacZ construct led us to identify significant transcription start site changes affecting the expression of ~3% of all genes. Therefore, zinc status can profoundly alter transcription initiation across the yeast genome. PMID:27657924

  2. Targeting and timing promotional activities : An agent-based model for the takeoff of new products

    NARCIS (Netherlands)

    Delre, S. A.; Jager, W.; Bijmolt, T. H. A.; Janssen, M. A.


    Many marketing efforts focus on promotional activities that support the launch of new products. Promotional strategies may play a crucial role in the early stages of the product life cycle, and determine to a large extent the diffusion of a new product. This paper proposes an agent-based model to si

  3. Promoting Physical Activity among International Students in Higher Education: A Peer-Education Approach (United States)

    Yan, Zi; Cardinal, Bradley J.


    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…

  4. Investigating message-framing effects in the context of a tailored intervention promoting physical activity.

    NARCIS (Netherlands)

    Riet, van 't J.P.; Ruiter, R.A.C.; Werrij, M.Q.; Vries, de H.


    Health-promoting messages can be framed in terms of the gains associated with healthy behaviour or the losses associated with unhealthy behaviour. It has been argued that gain-framed messages promoting physical activity (PA) are more effective than loss-framed messages, but empirical findings are in

  5. Promoting evidence-based practice: the roles and activities of professional nurses' associations.

    NARCIS (Netherlands)

    Achterberg, T. van; Holleman, G.; Ven, M. van de; Grypdonck, M.H.; Eliens, A.; Vliet, M. van


    AIM: This paper reports a study exploring the role perceptions and current activities in evidence-based practice promotion of professional nurses' associations in the Netherlands. Background: The promotion of evidence-based practice contributes to professional standards in nursing and good quality c

  6. miR-125b can enhance skin tumor initiation and promote malignant progression by repressing differentiation and prolonging cell survival. (United States)

    Zhang, Liang; Ge, Yejing; Fuchs, Elaine


    Previously, we identified miR-125b as a key regulator of the undifferentiated state of hair follicle stem cells. Here, we show that in both mice and humans, miR-125b is abundantly expressed, particularly at early stages of malignant progression to squamous cell carcinoma (SCC), the second most prevalent cancer worldwide. Moreover, when elevated in normal murine epidermis, miR-125b promotes tumor initiation and contributes to malignant progression. We further show that miR-125b can confer "oncomiR addiction" in early stage malignant progenitors by delaying their differentiation and favoring an SCC cancer stem cell (CSC)-like transcriptional program. To understand how, we systematically identified and validated miR125b targets that are specifically associated with tumors that are dependent on miR-125b. Through molecular and genetic analysis of these targets, we uncovered new insights underlying miR-125b's oncogenic function. Specifically, we show that, on the one hand, mir-125b directly represses stress-responsive MAP kinase genes and associated signaling. On the other hand, it indirectly prolongs activated (phosphorylated) EGFR signaling by repressing Vps4b (vacuolar protein-sorting 4 homolog B), encoding a protein implicated in negatively regulating the endosomal sorting complexes that are necessary for the recycling of active EGFR. Together, these findings illuminate miR-125b as an important microRNA regulator that is shared between normal skin progenitors and their early malignant counterparts.

  7. A Novel Antihepatitis Drug, Bicyclol, Prevents Liver Carcinogenesis in Diethylnitrosamine-Initiated and Phenobarbital-Promoted Mice Tumor Model

    Directory of Open Access Journals (Sweden)

    Hua Sun


    Full Text Available Bicyclol, an antihepatitis drug developed by Chinese scientists, has been shown to prevent the malignant transformation induced by 3-methylcholanthrene and 12-O-tetradecanoylphorbol-13-acetate in WB-F344 rat liver epithelial cells. This study provides further evidence on its role as a chemopreventive agent in experimental mice with diethylnitrosamine- (DEN- initiated and phenobarbital- (PB- promoted liver carcinoma. Liver tissue and serum were collected. In the two-stage model of hepatocarcinogenesis in mice, oral administration of bicyclol (100, 200 mg/kg before DEN injection showed significant reduction in the incidence of hepatocellular foci, nodules, or carcinoma. Histopathological examination revealed that there was no hepatocellular carcinoma (HCC and hepatoma formation in the mice pretreated with bicyclol (200 mg/kg at week 20, while the mice treated with DEN/PB developed 33.3% HCC and 55.6% hepatoma. Furthermore, the serum levels of alanine aminotransferase (ALT, alkaline phosphatase (ALP, and α-fetal protein (AFP in serum significantly increased in the DEN/PB model group in comparison with the control group. Pretreatment with bicyclol showed a marked reduction in the above condition. Bicyclol also decreased the expression of AFP and proliferating cell nuclear antigen level in the liver tissue and attenuated the decrease in body weight. In this study, we also found that 10 weeks after stopping the administration of PB and drugs, the control and bicyclol-treated (200 mg/kg animals showed no HCC and hepatoma formation at the time of termination whereas DEN/PB-induced mice developed 100% hepatoma and 50% HCC. These results further indicate that bicyclol has the chemopreventive potential for liver carcinogenesis induced by carcinogens.

  8. Biological Activity of the Alternative Promoters of the Dictyostelium discoideum Adenylyl Cyclase A Gene. (United States)

    Rodriguez-Centeno, Javier; Sastre, Leandro


    Amoebae of the Dictyostelium discoideum species form multicellular fruiting bodies upon starvation. Cyclic adenosine monophosphate (cAMP) is used as intercellular signalling molecule in cell-aggregation, cell differentiation and morphogenesis. This molecule is synthesized by three adenylyl cyclases, one of which, ACA, is required for cell aggregation. The gene coding for ACA (acaA) is transcribed from three different promoters that are active at different developmental stages. Promoter 1 is active during cell-aggregation, promoters 2 and 3 are active in prespore and prestalk tip cells at subsequent developmental stages. The biological relevance of acaA expression from each of the promoters has been studied in this article. The acaA gene was expressed in acaA-mutant cells, that do not aggregate, under control of each of the three acaA promoters. acaA expression under promoter 1 control induced cell aggregation although subsequent development was delayed, very small fruiting bodies were formed and cell differentiation genes were expressed at very low levels. Promoter 2-driven acaA expression induced the formation of small aggregates and small fruiting bodies were formed at the same time as in wild-type strains and differentiation genes were also expressed at lower levels. Expression of acaA from promoter 3 induced aggregates and fruiting bodies formation and their size and the expression of differentiation genes were more similar to that of wild-type cells. Expression of acaA from promoters 1 and 2 in AX4 cells also produced smaller structures. In conclusion, the expression of acaA under control of the aggregation-specific Promoter 1 is able to induce cell aggregation in acaA-mutant strains. Expression from promoters 2 and 3 also recovered aggregation and development although promoter 3 induced a more complete recovery of fruiting body formation.

  9. Complement activation promotes muscle inflammation during modified muscle use (United States)

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


    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.

  10. Perilipin1 promotes unilocular lipid droplet formation through the activation of Fsp27 in adipocytes. (United States)

    Sun, Zhiqi; Gong, Jingyi; Wu, Han; Xu, Wenyi; Wu, Lizhen; Xu, Dijin; Gao, Jinlan; Wu, Jia-Wei; Yang, Hongyuan; Yang, Maojun; Li, Peng


    Mature white adipocytes contain a characteristic unilocular lipid droplet. However, the molecular mechanisms underlying unilocular lipid droplet formation are poorly understood. We previously showed that Fsp27, an adipocyte-specific lipid droplet-associated protein, promotes lipid droplet growth by initiating lipid exchange and transfer. Here, we identify Perilipin1 (Plin1), another adipocyte-specific lipid droplet-associated protein, as an Fsp27 activator. Plin1 interacts with the CIDE-N domain of Fsp27 and markedly increases Fsp27-mediated lipid exchange, lipid transfer and lipid droplet growth. Functional cooperation between Plin1 and Fsp27 is required for efficient lipid droplet growth in adipocytes, as depletion of either protein impairs lipid droplet growth. The CIDE-N domain of Fsp27 forms homodimers and disruption of CIDE-N homodimerization abolishes Fsp27-mediated lipid exchange and transfer. Interestingly, Plin1 can restore the activity of CIDE-N homodimerization-defective mutants of Fsp27. We thus uncover a novel mechanism underlying lipid droplet growth and unilocular lipid droplet formation that involves the cooperative action of Fsp27 and Plin1 in adipocytes.

  11. Promoting Activity of Microcystins Extracted From Waterblooms in SHE Cell Transformation Assay

    Institute of Scientific and Technical Information of China (English)



    Microcystis aeruginosa is the dominant algae in most of the eutrophicated lakes in China.It can produce cyclic heptapeptides,Known as microcystins,which can cause liver damage in wild and comestic animals.In this paper,a two-stage transformation assay for demonstrating the carcinogenic effects of the algan toxins is reported.The cell strain used in this assay was derived from embryos of Syrian golden hamter and the algal toxins were extracted from Microcystis aeruginosa,termed microcystis raw toxic(MRT).To elucidate is prooting activity,the target cells were first exposed to a low dosage of 3-methylcholanthrene(MCA)and then to MRT.The results showed that MRT significantly enhanced the MCA-initiated cell transformation,and a dose-response reltionship was observed,but it failed to induce transformation of SHE cells not pretreated by MCA.These results suggest that the MRT play an important role in the malignant transformation of SHE cells.MRT may thus be a tumor promoter,and this transformation assay with SHE cells may be used to predict tumor prompting activity of environmental chemicals before long-term in vivo two-stage carcinogenesis experiments are carried out.

  12. Fruit preferential activity of the tomato RIP1 gene promoter in transgenic tomato and Arabidopsis. (United States)

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


    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.

  13. Promoting Uranium Immobilization by the Activities of Microbial Phosphatases

    Energy Technology Data Exchange (ETDEWEB)

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


    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

  14. A survey of faith leaders concerning health promotion and the level of healthy living activities occurring in faith communities in Scotland. (United States)

    Fagan, Donna M; Kiger, Alice; van Teijlingen, Edwin


    Faith groups constitute a growing health promotion partner in North America where they help increase community capacity. However, in the United Kingdom this collaboration is seemingly far less developed. This study sought to find evidence of health promotion in faith communities and examine perceptions and attitudes concerning health promotion among faith leaders. It also sought to establish the level to which health-promoting activities currently occur in, and are organized by, places of worship in one Scottish city, Dundee. The authors distributed a self-administered questionnaire to representatives of all faith communities in Dundee (response rate 71%, n = 50). The survey identified existing, well-formed community groups, some of whom already engaged in health-promoting activities, and shared similar interests with health promotion professionals. Generally, faith leaders were positive towards the concept of health promotion and many considered health promotion to be compatible with their mission. Not all denominations were equally involved in health promotion activities, for example, some conducted annual one-off activities, while others had well-established walking groups or exercise classes. The responses suggest a degree of readiness by faith communities to engage, if invited, in health promotion programmes. These results also indicate that faith groups may constitute untapped resources, poised to contribute to local health promotion efforts. The article concludes that as the National Health Service (NHS) invests in community-based health initiatives that can have long-term sustainability, it is reasonable to make links between what is happening in North America, the interest in health promotion reported by faith leaders in this study and the possibilities for their participation in voluntary sector community health partnerships.

  15. Armodafinil promotes wakefulness and activates Fos in rat brain. (United States)

    Fiocchi, Elaine M; Lin, Yin-Guo; Aimone, Lisa; Gruner, John A; Flood, Dorothy G


    Modafinil increases waking and labeling of Fos, a marker of neuronal activation. In the present study, armodafinil, the R-enantiomer of racemic modafinil, was administered to rats at 30 or 100 mg/kg i.p. about 5 h after lights on (circadian time 5 and near the midpoint of the sleep phase of the sleep:wake cycle) to assess its effects on sleep/wake activity and Fos activation. Armodafinil at 100 mg/kg increased wakefulness for 2 h, while 30 mg/kg armodafinil only briefly increased wakefulness. Armodafinil (30 and 100 mg/kg) also increased latencies to the onset of sleep and motor activity. Armodafinil had differential effects in increasing neuronal Fos immunolabeling 2 h after administration. Armodafinil at 100 mg/kg increased numbers of Fos-labeled neurons in striatum and anterior cingulate cortex, without affecting nucleus accumbens. Armodafinil at 30 mg/kg only increased numbers of light Fos-labeled neurons in the anterior cingulate cortex. In brainstem arousal centers, 100 mg/kg armodafinil increased numbers of Fos-labeled neurons in the tuberomammillary nucleus, pedunculopontine tegmentum, laterodorsal tegmentum, locus coeruleus, and dorsal raphe nucleus. Fos activation of these brainstem arousal centers, as well as of the cortex and striatum, is consistent with the observed arousal effects of armodafinil.

  16. PKC-δ activation in neutrophils promotes fungal clearance. (United States)

    Li, Xun; Cullere, Xavier; Nishi, Hiroshi; Saggu, Gurpanna; Durand, Enrique; Mansour, Michael K; Tam, Jenny M; Song, Xiu-Yu; Lin, Xin; Vyas, Jatin M; Mayadas, Tanya


    The C-type lectin receptor dectin-1 and the integrin Mac-1 have key roles in controlling fungal infection. Here, we demonstrate that dectin-1- and Mac-1-induced activation of protein kinase Cδ in neutrophils, independent of the Card9 adaptor, is required for reactive oxygen species production and for intracellular killing upon Candida albicans uptake. Protein kinase Cδ was also required for zymosan-induced cytokine generation in neutrophils. In macrophages, protein kinase Cδ deficiency prevented fungi-induced reactive oxygen species generation but had no effect on activation of TGF-β-activated kinase-1, an effector of Card9, or nuclear factor κB activation, nor did it affect phagolysosomal maturation, autophagy, or intracellular C. albicans killing. In vivo, protein kinase Cδ-deficient mice were highly susceptible to C. albicans and Aspergillus fumigatus infection, which was partially rescued with adoptively transferred wild-type neutrophils. Thus, protein kinase Cδ activation downstream of dectin-1 and Mac-1 has an important role in neutrophil, but not macrophage, functions required for host defense against fungal pathogens.

  17. AKT1 Activation Promotes Development of Melanoma Metastases

    Directory of Open Access Journals (Sweden)

    Joseph H. Cho


    Full Text Available Metastases are the major cause of melanoma-related mortality. Previous studies implicating aberrant AKT signaling in human melanoma metastases led us to evaluate the effect of activated AKT1 expression in non-metastatic BRAFV600E/Cdkn2aNull mouse melanomas in vivo. Expression of activated AKT1 resulted in highly metastatic melanomas with lung and brain metastases in 67% and 17% of our mice, respectively. Silencing of PTEN in BRAFV600E/Cdkn2aNull melanomas cooperated with activated AKT1, resulting in decreased tumor latency and the development of lung and brain metastases in nearly 80% of tumor-bearing mice. These data demonstrate that AKT1 activation is sufficient to elicit lung and brain metastases in this context and reveal that activation of AKT1 is distinct from PTEN silencing in metastatic melanoma progression. These findings advance our knowledge of the mechanisms driving melanoma metastasis and may provide valuable insights for clinical management of this disease.

  18. Design of phosphorylated dendritic architectures to promote human monocyte activation. (United States)

    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


    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.

  19. Initial Teacher Training to Promote Health and Well-Being in Schools--A Systematic Review of Effectiveness, Barriers and Facilitators (United States)

    Shepherd, Jonathan; Pickett, Karen; Dewhirst, Sue; Byrne, Jenny; Speller, Viv; Grace, Marcus; Almond, Palo; Roderick, Paul


    Objectives: To conduct a systematic review of effectiveness, and barriers and facilitators, of initial teacher training to promote health and well-being in schools. Design: Systematic review of the literature. Method: A total of 20 bibliographic databases were searched, including MEDLINE, EMBASE and the Social Science Citation Index. Studies were…

  20. Mobile Health Applications to Promote Active and Healthy Ageing. (United States)

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


    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.

  1. Mobile Health Applications to Promote Active and Healthy Ageing (United States)

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


    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

  2. An activating Pik3ca mutation coupled with Pten loss is sufficient to initiate ovarian tumorigenesis in mice. (United States)

    Kinross, Kathryn M; Montgomery, Karen G; Kleinschmidt, Margarete; Waring, Paul; Ivetac, Ivan; Tikoo, Anjali; Saad, Mirette; Hare, Lauren; Roh, Vincent; Mantamadiotis, Theo; Sheppard, Karen E; Ryland, Georgina L; Campbell, Ian G; Gorringe, Kylie L; Christensen, James G; Cullinane, Carleen; Hicks, Rodney J; Pearson, Richard B; Johnstone, Ricky W; McArthur, Grant A; Phillips, Wayne A


    Mutations in the gene encoding the p110α subunit of PI3K (PIK3CA) that result in enhanced PI3K activity are frequently observed in human cancers. To better understand the role of mutant PIK3CA in the initiation or progression of tumorigenesis, we generated mice in which a PIK3CA mutation commonly detected in human cancers (the H1047R mutation) could be conditionally knocked into the endogenous Pik3ca locus. Activation of this mutation in the mouse ovary revealed that alone, Pik3caH1047R induced premalignant hyperplasia of the ovarian surface epithelium but no tumors. Concomitantly, we analyzed several human ovarian cancers and found PIK3CA mutations coexistent with KRAS and/or PTEN mutations, raising the possibility that a secondary defect in a co-regulator of PI3K activity may be required for mutant PIK3CA to promote transformation. Consistent with this notion, we found that Pik3caH1047R mutation plus Pten deletion in the mouse ovary led to the development of ovarian serous adenocarcinomas and granulosa cell tumors. Both mutational events were required for early, robust Akt activation. Pharmacological inhibition of PI3K/mTOR in these mice delayed tumor growth and prolonged survival. These results demonstrate that the Pik3caH1047R mutation with loss of Pten is enough to promote ovarian cell transformation and that we have developed a model system for studying possible therapies.

  3. Sox17 promotes cell cycle progression and inhibits TGF-beta/Smad3 signaling to initiate progenitor cell behavior in the respiratory epithelium.

    Directory of Open Access Journals (Sweden)

    Alexander W Lange

    Full Text Available The Sry-related high mobility group box transcription factor Sox17 is required for diverse developmental processes including endoderm formation, vascular development, and fetal hematopoietic stem cell maintenance. Expression of Sox17 in mature respiratory epithelial cells causes proliferation and lineage respecification, suggesting that Sox17 can alter adult lung progenitor cell fate. In this paper, we identify mechanisms by which Sox17 influences lung epithelial progenitor cell behavior and reprograms cell fate in the mature respiratory epithelium. Conditional expression of Sox17 in epithelial cells of the adult mouse lung demonstrated that cell cluster formation and respecification of alveolar progenitor cells toward proximal airway lineages were rapidly reversible processes. Prolonged expression of Sox17 caused the ectopic formation of bronchiolar-like structures with diverse respiratory epithelial cell characteristics in alveolar regions of lung. During initiation of progenitor cell behavior, Sox17 induced proliferation and increased the expression of the progenitor cell marker Sca-1 and genes involved in cell cycle progression. Notably, Sox17 enhanced cyclin D1 expression in vivo and activated cyclin D1 promoter activity in vitro. Sox17 decreased the expression of transforming growth factor-beta (TGF-beta-responsive cell cycle inhibitors in the adult mouse lung, including p15, p21, and p57, and inhibited TGF-beta1-mediated transcriptional responses in vitro. Further, Sox17 interacted with Smad3 and blocked Smad3 DNA binding and transcriptional activity. Together, these data show that a subset of mature respiratory epithelial cells retains remarkable phenotypic plasticity and that Sox17, a gene required for early endoderm formation, activates the cell cycle and reinitiates multipotent progenitor cell behavior in mature lung cells.

  4. Endothelial Notch activity promotes angiogenesis and osteogenesis in bone (United States)

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


    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.


    Directory of Open Access Journals (Sweden)

    Irina V. Abakumova


    Full Text Available The research in question investigates the technologies of initiating independent activity within the framework of distance learning and their psychological aspects. The authors’ classification of educational technologies of initiating students into independent cognitive activity is presented. Such technologies utilize various psychological mechanisms of exciting students’ cognitive interest, intensifying cognitive processes, developing independent activity skills, and, as a result, increase motivation for independent activity and learning on the whole. These include such types of technologies as developmental technologies, interactive technologies, technologies of information transfer, technologies of meaning-making initiation. The research of the attitude of distance learning educators to independent activity of students and the content of the academic courses were done at Moodle-based education programs. The findings show the differences in retention rate among distance learning educators whose competence in terms of initiating students into independent (self-guided activity varies. It’s emphasized that interactive lectures, videoconferences, audio-visual aids, interactive seminars, glossaries, interactive tests are considered the most efficient technologies in initiating students into independent (self-guided activity. The obtained results have made it possible to stress the developmental effect of distance learning technologies and the technologies of initiating students into independent (self-guided activity in various psychic spheres of students: cognitive, individual, emotional. We mention the changes in motivational sphere of students and their meaning-making activity. In the course of correct development of distance learning we notice the development of voluntary and nonvoluntary cognitive activity. A student starts actively participating in educational process, he becomes the creator of his own world.

  6. Drosophila gypsy insulator and yellow enhancers regulate activity of yellow promoter through the same regulatory element. (United States)

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


    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.

  7. Genetic variation in the proximal promoter of ABC and SLC superfamilies: liver and kidney specific expression and promoter activity predict variation.

    Directory of Open Access Journals (Sweden)

    Stephanie E Hesselson

    Full Text Available Membrane transporters play crucial roles in the cellular uptake and efflux of an array of small molecules including nutrients, environmental toxins, and many clinically used drugs. We hypothesized that common genetic variation in the proximal promoter regions of transporter genes contribute to observed variation in drug response. A total of 579 polymorphisms were identified in the proximal promoters (-250 to +50 bp and flanking 5' sequence of 107 transporters in the ATP Binding Cassette (ABC and Solute Carrier (SLC superfamilies in 272 DNA samples from ethnically diverse populations. Many transporter promoters contained multiple common polymorphisms. Using a sliding window analysis, we observed that, on average, nucleotide diversity (pi was lowest at approximately 300 bp upstream of the transcription start site, suggesting that this region may harbor important functional elements. The proximal promoters of transporters that were highly expressed in the liver had greater nucleotide diversity than those that were highly expressed in the kidney consistent with greater negative selective pressure on the promoters of kidney transporters. Twenty-one promoters were evaluated for activity using reporter assays. Greater nucleotide diversity was observed in promoters with strong activity compared to promoters with weak activity, suggesting that weak promoters are under more negative selective pressure than promoters with high activity. Collectively, these results suggest that the proximal promoter region of membrane transporters is rich in variation and that variants in these regions may play a role in interindividual variation in drug disposition and response.

  8. Trans activation of plasmid-borne promoters by adenovirus and several herpes group viruses.


    Everett, R D; Dunlop, M


    This paper describes experiments to test the ability of a number of viruses of the Herpes group, and also Adenovirus-2 and SV40, to activate transcription from the Herpes simplex virus-1 glycoprotein D and the rabbit beta-globin promoters. Plasmids containing these genes were transfected into HeLa cells which were then infected with various viruses. Transcriptional activation in trans of the plasmid-borne promoters was monitored by quantitative S1 nuclease analysis of total cytoplasmic RNA is...

  9. The National Blueprint for Promoting Physical Activity in the Mid-Life and Older Adult Population (United States)

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


    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…

  10. Does HOPSports Promote Youth Physical Activity in Physical Education Classes? (United States)

    West, Stephanie T.; Shores, Kindal A.


    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…

  11. Promoting Technology-Assisted Active Learning in Computer Science Education (United States)

    Gao, Jinzhu; Hargis, Jace


    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…

  12. Promoting direct interspecies electron transfer with activated carbon

    DEFF Research Database (Denmark)

    Liu, Fanghua; Rotaru, Amelia-Elena; Shrestha, Pravin M.;


    Granular activated carbon (GAC) is added to methanogenic digesters to enhance conversion of wastes to methane, but the mechanism(s) for GAC’s stimulatory effect are poorly understood. GAC has high electrical conductivity and thus it was hypothesized that one mechanism for GAC stimulation...

  13. Laminar flow downregulates Notch activity to promote lymphatic sprouting. (United States)

    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


    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.

  14. Community Resources for Promoting Youth Nutrition and Physical Activity (United States)

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


    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…

  15. Tissue specificity of enhancer and promoter activities of a HERV-K(HML-2) LTR. (United States)

    Ruda, V M; Akopov, S B; Trubetskoy, D O; Manuylov, N L; Vetchinova, A S; Zavalova, L L; Nikolaev, L G; Sverdlov, E D


    Transient expression of a luciferase reporter gene was used to evaluate tissue-specific promoter and enhancer activities of a solitary extraviral long terminal repeat (LTR) of the human endogenous retrovirus K (HERV-K) in several human and CHO cell lines. The promoter activity of the LTR varied from virtually not detectable (GS and Jurkat cells) to as high as that of the SV40 early promoter (Tera-1 human testicular embryonal carcinoma cells). The negative regulatory element (NRE) of the LTR retained its activity in all cell lines where the LTR could act as a promoter, and was also capable of binding host cell nuclear proteins. The enhancer activity of the LTR towards the SV40 early promoter was detected only in Tera-1 cells and was not observed in a closely related human testicular embryonal carcinoma cell line of different origin, NT2/D1. A comparison of proteins bound to central part of the LTR in nuclear extracts from Tera-1 and NT2/D1 by electrophoretic mobility shift assay revealed striking differences that could be determined by different LTR enhancer activities in these cells. Tissue specificity of the SV40 early promoter activity was also revealed.

  16. Change in sexual activity 12 months after ART initiation among HIV-positive Mozambicans. (United States)

    Pearson, Cynthia R; Cassels, Susan; Kurth, Ann E; Montoya, Pablo; Micek, Mark A; Gloyd, Stephen S


    We assessed sexual behaviors before and 12-months after ART initiation among 277 Mozambicans attending an HIV clinic. Measured behaviors included the number of sexual partners, condom use, concurrent relationships, disclosure of HIV status, alcohol use, and partners' serostatus. Compared to before ART initiation, increases were seen 12 months after ART in the proportion of participants who were sexually active (48% vs. 64% respondents, P initiation. Although reported correct and consist condom use increased, the number of unprotected sexual relationships remained the same (n = 45). Non-disclosure of HIV-serostatus to sexual partners was the only significant predictor of practicing unprotected sex with partners of HIV-negative or unknown serostatus. Sexual activity among HIV-positive persons on ART increased 12 months after ART initiation. Ongoing secondary transmission prevention programs addressing sexual activity with multiple partners, disclosure to partners and consistent condom use with serodisconcordant partners must be incorporated throughout HIV care programs.

  17. Activation of AMPK by berberine promotes adiponectin multimerization in 3T3-L1 adipocytes. (United States)

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


    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.

  18. Activity monitor intervention to promote physical activity of physicians-in-training: randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Anne N Thorndike

    Full Text Available BACKGROUND: Physicians are expected to serve as role models for healthy lifestyles, but long work hours reduce time for healthy behaviors. A hospital-based physical activity intervention could improve physician health and increase counseling about exercise. METHODS: We conducted a two-phase intervention among 104 medical residents at a large hospital in Boston, Massachusetts. Phase 1 was a 6-week randomized controlled trial comparing daily steps of residents assigned to an activity monitor displaying feedback about steps and energy consumed (intervention or to a blinded monitor (control. Phase 2 immediately followed and was a 6-week non-randomized team steps competition in which all participants wore monitors with feedback. Phase 1 outcomes were: 1 median steps/day and 2 proportion of days activity monitor worn. The Phase 2 outcome was mean steps/day on days monitor worn (≥500 steps/day. Physiologic measurements were collected at baseline and study end. Median steps/day were compared using Wilcoxon rank-sum tests. Mean steps were compared using repeated measures regression analyses. RESULTS: In Phase 1, intervention and control groups had similar activity (6369 vs. 6063 steps/day, p = 0.16 and compliance with wearing the monitor (77% vs. 77% of days, p = 0.73. In Phase 2 (team competition, residents recorded more steps/day than during Phase 1 (CONTROL: 7,971 vs. 7,567, p = 0.002; INTERVENTION: 7,832 vs. 7,739, p = 0.13. Mean compliance with wearing the activity monitor decreased for both groups during Phase 2 compared to Phase 1 (60% vs. 77%, p<0.001. Mean systolic blood pressure decreased (p = 0.004 and HDL cholesterol increased (p<0.001 among all participants at end of study compared to baseline. CONCLUSIONS: Although the activity monitor intervention did not have a major impact on activity or health, the high participation rates of busy residents and modest changes in steps, blood pressure, and HDL suggest that more

  19. Boswellia carterii liquisolid systems with promoted anti-inflammatory activity. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Rebecca E. Lee


    Full Text Available 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 (=50;=42 years who participated were overweight (BMI=29.7 kg/m2; bodyfat=38.5% and reported low levels of leisure time PA (=10.7 MET-min/wk and FV consumption (=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 (=10.7 MET-min/wk to follow up (=34.0 MET-min/wk, <.001, and FV consumption increased over time by group (=.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.

  1. SIRT1 promotes DNA repair activity in response to radiation

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jae-Min; Lee, Kee-Ho [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)


    Human SIRT1 controls various physiological responses including cell fate, stress, and aging, through deacetylation of its specific substrate protein. In processing DNA damage signaling, SIRT1 attenuates a cellular apoptotic response by deacetylation of p53 tumor suppressor. Ectopically over-expressed SIRT1 resulted in the increase of repair of DNA strand breakages produced by radiation. On the other hand, repression of endogenous SIRT1 expression by SIRT1 siRNA led to the decrease of this repair activity, indicating that SIRT1 can regulate DNA repair capacity of cells with DNA strand breaks.

  2. Online communication predicts Belgian adolescents’ initiation of romantic and sexual activity

    NARCIS (Netherlands)

    Vandenbosch, L.; Beyens, I.; Vangeel, L.; Eggermont, S.


    Online communication is associated with offline romantic and sexual activity among college students. Yet, it is unknown whether online communication is associated with the initiation of romantic and sexual activity among adolescents. This two-wave panel study investigated whether chatting, visiting

  3. Perceiving Promotion Activities İn Politic Marketing By Gazi University’ Students

    Directory of Open Access Journals (Sweden)

    Ahmet ÇATLI


    Full Text Available Political parties determine the marketing strategies about affecting electors, who have customer property. What, when and how do they want? After they can meet these wantings, needs and can subordinate other parties. Promotion activities also can be defined as election drive, is an mix of marketing. But as the seen changing of electors' wantings also in politic marketing, kinds and variations of promotion activities, especially in our technological age are more important than classic promotions. With this project inquiry work that consists of 9 parts also has done to know about how the university students are affected and which promotion activities affect the students more. İnquiry appliers are students in University of Gazi TTEF. In the inquiry, questioned to students that students' gender, incomes, the place they live, their enroling in political parties, being affected by promotion activities, if they are affected, by which promotion activity and how much they are affected, advertsement, public relations,personal marketing and marketing development.

  4. Activation of TGF-β1-CD147 positive feedback loop in hepatic stellate cells promotes liver fibrosis. (United States)

    Li, Hai-Yan; Ju, Di; Zhang, Da-Wei; Li, Hao; Kong, Ling-Min; Guo, Yanhai; Li, Can; Wang, Xi-Long; Chen, Zhi-Nan; Bian, Huijie


    Activation of hepatic stellate cells (HSCs) by transforming growth factor-β1 (TGF-β1) initiates HBV-associated fibrogenesis. The mechanism of TGF-β1 modulating HSC activation is not fully uncovered. We hypothesized a positive feedback signaling loop of TGF-β1-CD147 promoting liver fibrogenesis by activation of HSCs. Human HSC cell line LX-2 and spontaneous liver fibrosis model derived from HBV transgenic mice were used to evaluate the activation of molecules in the signaling loop. Wound healing and cell contraction assay were performed to detect the CD147-overexpressed HSC migration and contraction. The transcriptional regulation of CD147 by TGF-β1/Smad4 was determined using dual-luciferase reporter assay and chromatin immunoprecipitation. We found that a positive reciprocal regulation between TGF-β1 and CD147 mediated HSC activation. CD147 over-expression promoted HSC migration and accelerated TGF-β1-induced cell contraction. Phosphorylation of Smad2 and Smad3 in cooperation with Smad4 mediated the TGF-β1-regulated CD147 expression. Smad4 activated the transcription by direct interaction with CD147 promoter. Meanwhile, CD147 modulated the activated phenotype of HSCs through the ERK1/2 and Sp1 which up-regulated α-SMA, collagen I, and TGF-β1 synthesis. These findings indicate that TGF-β1-CD147 loop plays a key role in regulating the HSC activation and combination of TGF-β receptor inhibitor and anti-CD147 antibody might be promised to reverse fibrogenesis.

  5. Comparison of Trunk Activity during Gait Initiation and Walking in Humans (United States)

    Azevedo, Christine; Cazalets, Jean-René


    To understand the role of trunk muscles in maintenance of dynamic postural equilibrium we investigate trunk movements during gait initiation and walking, performing trunk kinematics analysis, Erector spinae muscle (ES) recordings and dynamic analysis. ES muscle expressed a metachronal descending pattern of activity during walking and gait initiation. In the frontal and horizontal planes, lateroflexion and rotation occur before in the upper trunk and after in the lower trunk. Comparison of ES muscle EMGs and trunk kinematics showed that trunk muscle activity precedes corresponding kinematics activity, indicating that the ES drive trunk movement during locomotion and thereby allowing a better pelvis mobilization. EMG data showed that ES activity anticipates propulsive phases in walking with a repetitive pattern, suggesting a programmed control by a central pattern generator. Our findings also suggest that the programs for gait initiation and walking overlap with the latter beginning before the first has ended. PMID:19997606

  6. Comparison of trunk activity during gait initiation and walking in humans.

    Directory of Open Access Journals (Sweden)

    Jean-Charles Ceccato

    Full Text Available To understand the role of trunk muscles in maintenance of dynamic postural equilibrium we investigate trunk movements during gait initiation and walking, performing trunk kinematics analysis, Erector spinae muscle (ES recordings and dynamic analysis. ES muscle expressed a metachronal descending pattern of activity during walking and gait initiation. In the frontal and horizontal planes, lateroflexion and rotation occur before in the upper trunk and after in the lower trunk. Comparison of ES muscle EMGs and trunk kinematics showed that trunk muscle activity precedes corresponding kinematics activity, indicating that the ES drive trunk movement during locomotion and thereby allowing a better pelvis mobilization. EMG data showed that ES activity anticipates propulsive phases in walking with a repetitive pattern, suggesting a programmed control by a central pattern generator. Our findings also suggest that the programs for gait initiation and walking overlap with the latter beginning before the first has ended.

  7. MAGEB2 is activated by promoter demethylation in head and neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Kavita M Pattani

    Full Text Available PURPOSE: Although promoter hypermethylation has been an accepted means of tumor suppressor gene inactivation, activation of otherwise normally repressed proto-oncogenes by promoter demethylation has been infrequently documented. EXPERIMENTAL DESIGN: In this study we performed an integrative, whole-genome analysis for discovery of epigenetically activated proto-oncogenes in head and neck cancer tumors. We used the 47K GeneChip U133 Plus 2.0 Affymetrix expression microarray platform to obtain re-expression data from 5-aza treated normal cell line and expression data from primary head and neck squamous cell carcinoma (HNSCC tumor tissues and normal mucosa tissues. We then investigated candidate genes by screening promoter regions for CpG islands and bisulfite sequencing followed by QUMSP and RT PCR for the best candidate genes. Finally, functional studies were performed on the top candidate gene. RESULTS: From the top 178 screened candidates 96 had CpG islands in their promoter region. Seven candidate genes showed promoter region methylation in normal mucosa samples and promoter demethylation in a small cohort of primary HNSCC tissues. We then studied the demethylation of the top 3 candidate genes in an expanded cohort of 76 HNSCC tissue samples and 17 normal mucosa samples. We identified MAGEB2 as having significant promoter demethylation in primary head and neck squamous cell carcinoma tissues. We then found significantly higher expression of MAGEB2 in tumors in a separate cohort of 73 primary HNSCC tissues and 31 normal tissues. Finally, we found that MAGEB2 has growth promoting effects on minimally transformed oral keratinocyte cell lines but not a definite effect on HNSCC cell lines. CONCLUSION: In conclusion, we identified MAGEB2 as activated by promoter demethylation in HNSCCand demonstrates growth promoting effects in a minimally transformed oral keratinocyte cell line. More studies are needed to evaluate MAGBE2's exact role in HNSCC.

  8. Promoting physical activity for people with neurological disability: perspectives and experiences of physiotherapists. (United States)

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


    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.

  9. Two tobacco AP1-like gene promoters drive highly specific, tightly regulated and unique expression patterns during floral transition, initiation and development. (United States)

    Zhang, Jinjin; Yan, Guohua; Wen, Zhifeng; An, Young-Qiang; Singer, Stacy D; Liu, Zongrang


    The genetic engineering of agronomic traits requires an array of highly specific and tightly regulated promoters that drive expression in floral tissues. In this study, we isolated and characterized two tobacco APETALA1-like (AP1-like) promoters (termed NtAP1La and NtAP1Lb1) in transgenic plants using the GUS reporter system, along with tissue-specific ablation analyses. Our results demonstrated that the two promoters are active in floral inflorescences but not in vegetative apical meristems or other vegetative tissues, as reflected by strong GUS staining and DT-A-mediated ablation of apical shoot tips during reproductive but not vegetative growth. We also showed that the NtAP1Lb1 promoter was more active than NtAP1La in inflorescences, as the former yielded higher frequencies and greater phenotypic evidence of tissue ablation compared to the latter. We further revealed that both promoters were uniformly expressed in the meristems of stage 1 and 2 floral buds, but were differentially expressed in floral organs later during development. While NtAP1La was found to be active in stage 4-5 carpels, later becoming confined to ovary tissue from stage 9 onwards, NtAP1Lb1 activity was apparent in all floral organs from stages 3 to 7, becoming completely absent in all floral organs from stage 11 onward. Therefore, it seems that the two tobacco promoters have acquired similar but distinct inflorescence-, floral meristem- and floral organ-specific and development-dependent regulatory features without any leaky activity in vegetative tissues. These features are novel and have rarely been observed in other flower-specific promoters characterized to date. The potential application of these promoters for engineering sterility, increasing biomass production and modifying flower architecture, as well as their putative use in flower-specific transgene excision, will be discussed.

  10. Promoting uranium immobilization by the activities of microbial phophatases

    Energy Technology Data Exchange (ETDEWEB)

    Sobecky, Patricia A.


    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.

  11. Promoting Active Learning in Electrical Engineering Basic Studies

    Directory of Open Access Journals (Sweden)

    Anu Lehtovuori


    Full Text Available Active learning, project-based teaching, and student collaboration are current trends in engineering education. Incorporating these have also been the goal of the basic studies development project EPOP started at the Aalto University School of Electrical Engineering in 2011. In the project, two obligatory basic courses in circuit analysis and electromagnetic field theory have been taught using interactive engagement during the spring of 2012. This paper presents the implementation of the teaching, including methods and evaluation with several concrete examples. As a result of the novel teaching, motivation and the engagement of students were at a high level during the whole course and learning results were better than those of the students participating the traditional lecture course.

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


    Kauhanen, Lotta; Järvelä, Liisa; Lähteenmäki, Päivi M.; Arola, Mikko; Olli J Heinonen; Axelin, Anna; Lilius, Johan; Vahlberg, Tero; Salanterä, Sanna


    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 promotio...

  13. Human gene encoding prostacyclin synthase (PTGIS): Genomic organization, chromosomal localization, and promoter activity

    Energy Technology Data Exchange (ETDEWEB)

    Yokoyama, Chieko; Yabuki, Tomoko; Inoue, Hiroyasu [National Cardiovascular Center Research Institute, Osaka (Japan)] [and others


    The prostacyclin synthase gene isolated from human genomic libraries (PTGIS) consists of 10 exons spanning approximately 60 kb. All the splice donor and acceptor sites conform to the GT/AG rule. Genomic Southern blot and fluorescence in situ hybridization analyses revealed that the human prostacyclin synthase gene is present as a single copy per haploid genome and is localized on chromosome 20q13.11-q13.13. The 1.5-kb sequence of the 5{prime} of the translational initiation site contained both GC-rich and pyrimidine-rich regions and consensus sequences of the transcription factor recognition sites such as Sp1, AP-2, the interferon-{gamma} response element, GATA, NF-{kappa}B, the CACCC box, and the glucocorticoid response element. The core binding sequence (GAGACC) of the shear stress responsive element was also found in the 5{prime}-flanking region of the gene. The major product of the primer extension analysis suggested that the transcription of the gene started from the positions around 49 bp upstream of the translational initiation codon. Transient transfection experiments using human aortic and bovine arterial endothelial cells demonstrated that the GC-rich region (positions -145 to -10) possessed a significant promoter activity. The 6-kb downstream sequence of the translational termination codon contained multiple polyadenylation signals, Alu repeat sequences, and the consensus sequence of the primate-repetitive DNA element, MER1. Two sizes of the prostacyclin synthase mRNAs (approximately 6 and 3.3 kb) were detected with the human aorta and lung. RNA blot hybridization analysis using the 3{prime}-untranslated region as probe indicated that the sizes of the 3{prime}-flanking regions were different in the major 6-kb and minor 3.3-kb mRNAs. 54 refs., 7 figs.

  14. Activation of initiation factor 2 by ligands and mutations for rapid docking of ribosomal subunits (United States)

    Pavlov, Michael Y; Zorzet, Anna; Andersson, Dan I; Ehrenberg, Måns


    We previously identified mutations in the GTPase initiation factor 2 (IF2), located outside its tRNA-binding domain, compensating strongly (A-type) or weakly (B-type) for initiator tRNA formylation deficiency. We show here that rapid docking of 30S with 50S subunits in initiation of translation depends on switching 30S subunit-bound IF2 from its inactive to active form. Activation of wild-type IF2 requires GTP and formylated initiator tRNA (fMet-tRNAi). In contrast, extensive activation of A-type IF2 occurs with only GTP or with GDP and fMet-tRNAi, implying a passive role for initiator tRNA as activator of IF2 in subunit docking. The theory of conditional switching of GTPases quantitatively accounts for all our experimental data. We find that GTP, GDP, fMet-tRNAi and A-type mutations multiplicatively increase the equilibrium ratio, K, between active and inactive forms of IF2 from a value of 4 × 10−4 for wild-type apo-IF2 by factors of 300, 8, 80 and 20, respectively. Functional characterization of the A-type mutations provides keys to structural interpretation of conditional switching of IF2 and other multidomain GTPases. PMID:21151095

  15. Isolation of Endophytic Plant Growth-Promoting Bacteria Associated with the Halophyte Salicornia europaea and Evaluation of their Promoting Activity Under Salt Stress. (United States)

    Zhao, Shuai; Zhou, Na; Zhao, Zheng-Yong; Zhang, Ke; Wu, Guo-Hua; Tian, Chang-Yan


    Several reports have highlighted that many plant growth-promoting endophytic bacteria (PGPE) can assist their host plants in coping with various biotic and abiotic stresses. However, information about the PGPE colonizing in the halophytes is still scarce. This study was designed to isolate and characterize PGPE from salt-accumulating halophyte Salicornia europaea grown under extreme salinity and to evaluate in vitro the bacterial mechanisms related to plant growth promotion. A total of 105 isolates were obtained from the surface-sterilized roots, stems, and assimilation twigs of S. europaea. Thirty-two isolates were initially selected for their ability to produce 1-aminocyclopropane-1-carboxylate deaminase as well as other properties such as production of indole-3-acetic acid and phosphate-solubilizing activities. The 16S rRNA gene-sequencing analysis revealed that these isolates belong to 13 different genera and 19 bacterial species. For these 32 strains, seed germination and seedling growth in axenically grown S. europaea seedlings at different NaCl concentrations (50-500 mM) were quantified. Five isolates possessing significant stimulation of the host plant growth were obtained. The five isolates were identified as Bacillus endophyticus, Bacillus tequilensis, Planococcus rifietoensis, Variovorax paradoxus, and Arthrobacter agilis. All the five strains could colonize and can be reisolated from the host plant interior tissues. These results demonstrate that habitat-adapted PGPE isolated from halophyte could enhance plant growth under saline stress conditions.

  16. Promotion of Sink Activity of Developing Rose Shoots by Light 1 (United States)

    Mor, Yoram; Halevy, Abraham H.


    Holding young rose shoots (Rosa hybrida cv. Marimba) in darkness while the rest of the plant was in light reduced the amount of 14C 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 CO2-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. PMID:16661566

  17. Interventions for promoting physical activity among European teenagers: a systematic review


    Lien Nanna; Spittaels Heleen; van Lenthe Frank J; De Meester Femke; De Bourdeaudhuij Ilse


    Abstract Background Although physical activity is considered to yield substantial health benefits, the level of physical activity among European teenagers is not sufficient. Adolescence is characterized by a decline in physical activity level. Many studies investigated the effectiveness of interventions promoting physical activity among young people, but none dealt with the available evidence specific for Europe. This review was conducted to summarize the effectiveness of interventions to pro...

  18. Interventions for promoting physical activity among European teenagers: a systematic review


    De Meester, Femke; van Lenthe, Frank J; Spittaels, Heleen; Lien, Nanna; De Bourdeaudhuij, Ilse


    Background Although physical activity is considered to yield substantial health benefits, the level of physical activity among European teenagers is not sufficient. Adolescence is characterized by a decline in physical activity level. Many studies investigated the effectiveness of interventions promoting physical activity among young people, but none dealt with the available evidence specific for Europe. This review was conducted to summarize the effectiveness of interventi...

  19. SHADE: A Shape-Memory-Activated Device Promoting Ankle Dorsiflexion (United States)

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


    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.

  20. On the determination of activation energy in thermoluminescence by the initial rise method

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Th.S.C.; Mazumdar, P.S.; Gartia, R.K.


    Expressions are derived which estimate the systematic error involved in the determination of activation energy (E) by the initial rise method. It is shown that the initial rise method does depend on the order of kinetics, if one takes the value of E thus determined in a quantitative sense. The applicability of these expressions has not only been discussed but also tested for some experimental peaks.

  1. Recruiting Older Adults into a Physical Activity Promotion Program: "Active Living Every Day" Offered in a Naturally Occurring Retirement Community (United States)

    Hildebrand, Mary; Neufeld, Peggy


    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…

  2. Desired features of smartphone applications promoting physical activity. (United States)

    Rabin, Carolyn; Bock, Beth


    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.

  3. Recent Activities of the Physical Society of Japan for the Promotion of Gender Equality (abstract) (United States)

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


    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.

  4. Efficient LEC2 activation of OLEOSIN expression requires two neighboring RY elements on its promoter

    Institute of Scientific and Technical Information of China (English)

    CHE NanYing; YANG Yang; LI YanDong; WANG LiLi; HUANG Ping; GAO Yin; An ChengCai


    As the main structural protein of oil body, OLEOSIN is highly expressed only during seed development. OLEOSIN promoter is a very useful tool for seed-specific gene engineering and seed bioreactor designing. The B3 domain transcription factor leafy cotyledon2 (LEC2) plays an important role in regulating seed development and seed-specific gene expression. Here, we first report how seed-specific B3 domain transcription factor leafy cotyledon2 (LEC2) efficiently activates OLEOSIN expression. The central promoter region of OLEOSIN, responsible for seed specificity and LEC2 activation, was determined by 5'-deletion analysis. Binding experiments in yeast cells and electrophoretic mobility shift assays showed that LEC2 specifically bound to two conserved RY elements in this region, in transient expression assays, mutation in either RY element dramatically reduced LEC2 activation of OLEOSIN promoter activity, while double mutation abolished it. Analysis of the distribution of RY elements in seed-specific genes activated by LEC2 also supported the idea that genes containing neighboring RY elements responded strongly to LEC2 activation. Therefore, we conclude that two neighboring RY elements are essential for efficient LEC2 activation of OLEOSIN expression. These findings will help us better utilize seed-specific promoter activity.

  5. Efficient LEC2 activation of OLEOSIN expression requires two neighboring RY elements on its promoter

    Institute of Scientific and Technical Information of China (English)


    As the main structural protein of oil body,OLEOSIN is highly expressed only during seed development. OLEOSIN promoter is a very useful tool for seed-specific gene engineering and seed bioreactor designing. The B3 domain transcription factor leafy cotyledon2 (LEC2) plays an important role in regulating seed development and seed-specific gene expression. Here,we first report how seed-specific B3 domain transcription factor leafy cotyledon2 (LEC2) efficiently activates OLEOSIN expression. The central promoter region of OLEOSIN,responsible for seed specificity and LEC2 activation,was determined by 5’-deletion analysis. Binding experiments in yeast cells and electrophoretic mobility shift assays showed that LEC2 specifically bound to two conserved RY elements in this region. In transient expression assays,mutation in either RY element dramatically reduced LEC2 activation of OLEOSIN promoter activity,while double mutation abolished it. Analysis of the distribution of RY elements in seed-specific genes activated by LEC2 also supported the idea that genes containing neighboring RY elements responded strongly to LEC2 activation. Therefore,we conclude that two neighboring RY elements are essential for efficient LEC2 activation of OLEOSIN expression. These findings will help us better utilize seed-specific promoter activity.

  6. Leptin activates chicken growth hormone promoter without chicken STAT3 in vitro. (United States)

    Murase, Daisuke; Namekawa, Shoko; Ohkubo, Takeshi


    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.

  7. Enhancer activity of Helitron in sericin-1 gene promoter from Bombyx mori. (United States)

    Huang, Ke; Li, Chun-Feng; Wu, Jie; Wei, Jun-Hong; Zou, Yong; Han, Min-Jin; Zhou, Ze-Yang


    Sericin is a kind of water-soluble protein expressed specifically in the middle silk gland of Bombyx mori. When the sericin-1 gene promoter was cloned and a transgenic vector was constructed to express a foreign protein, a specific Helitron, Bmhel-8, was identified in the sericin-1 gene promoter sequence in some genotypes of Bombyx mori and Bombyx mandarina. Given that the Bmhel-8 Helitron transposon was present only in some genotypes, it could be the source of allelic variation in the sericin-1 promoter. The length of the sericin-1 promoter sequence is approximately 1063 or 643 bp. The larger size of the sequence or allele is ascribed to the presence of Bmhel-8. Silkworm genotypes can be homozygous for either the shorter or larger promoter sequence or heterozygous, containing both alleles. Bmhel-8 in the sericin-1 promoter exhibits enhancer activity, as demonstrated by a dual-luciferase reporter system in BmE cell lines. Furthermore, Bmhel-8 displays enhancer activity in a sericin-1 promoter-driven gene expression system but does not regulate the tissue-specific expression of sericin-1.

  8. The integration of corporate social responsibility (CSR) initiatives into business activities

    DEFF Research Database (Denmark)

    Knudsen, Jette Steen


    While proponents of corporate social responsibility (CSR) have suggested that CSR initiatives should be integrated into mainstream business activities as 'strategic CSR' or 'shared value', research is lacking that explores how CSR programmes are integrated in companies. This paper compares CSR...... initiatives with human resource management (HRM) activities, which have a longer tradition of being integrated into company strategy. The focus is on gender diversity and CSR in a US multinational corporation (MNC). The MNC sees gender diversity as an integral part of business activities. In contrast, the MNC...... lacks a clear justification for the much broader CSR agenda, CSR activities seem not to reflect an overall set of values or purpose, integration into business activities is unclear, and targets are lacking....

  9. Cathepsin B Activity Initiates Apoptosis via Digestive Protease Activation in Pancreatic Acinar Cells and Experimental Pancreatitis. (United States)

    Sendler, Matthias; Maertin, Sandrina; John, Daniel; Persike, Maria; Weiss, F Ulrich; Krüger, Burkhard; Wartmann, Thomas; Wagh, Preshit; Halangk, Walter; Schaschke, Norbert; Mayerle, Julia; Lerch, Markus M


    Pancreatitis is associated with premature activation of digestive proteases in the pancreas. The lysosomal hydrolase cathepsin B (CTSB) is a known activator of trypsinogen, and its deletion reduces disease severity in experimental pancreatitis. Here we studied the activation mechanism and subcellular compartment in which CTSB regulates protease activation and cellular injury. Cholecystokinin (CCK) increased the activity of CTSB, cathepsin L, trypsin, chymotrypsin, and caspase 3 in vivo and in vitro and induced redistribution of CTSB to a secretory vesicle-enriched fraction. Neither CTSB protein nor activity redistributed to the cytosol, where the CTSB inhibitors cystatin-B/C were abundantly present. Deletion of CTSB reduced and deletion of cathepsin L increased intracellular trypsin activation. CTSB deletion also abolished CCK-induced caspase 3 activation, apoptosis-inducing factor, as well as X-linked inhibitor of apoptosis protein degradation, but these depended on trypsinogen activation via CTSB. Raising the vesicular pH, but not trypsin inhibition, reduced CTSB activity. Trypsin inhibition did not affect apoptosis in hepatocytes. Deletion of CTSB affected apoptotic but not necrotic acinar cell death. In summary, CTSB in pancreatitis undergoes activation in a secretory, vesicular, and acidic compartment where it activates trypsinogen. Its deletion or inhibition regulates acinar cell apoptosis but not necrosis in two models of pancreatitis. Caspase 3-mediated apoptosis depends on intravesicular trypsinogen activation induced by CTSB, not CTSB activity directly, and this mechanism is pancreas-specific.

  10. The Insect Neuropeptide PTTH Activates Receptor Tyrosine Kinase Torso to Initiate Metamorphosis

    DEFF Research Database (Denmark)

    Rewitz, Kim; Yamanaka, Naoki; Gilbert, Lawrence;


    Holometabolous insects undergo complete metamorphosis to become sexually mature adults. Metamorphosis is initiated by brain-derived prothoracicotropic hormone (PTTH), which stimulates the production of the molting hormone ecdysone via an incompletely defined signaling pathway. Here we demonstrate...... in the prothoracic gland (PG), and its loss phenocopies the removal of PTTH. The activation of Torso by PTTH stimulates extracellular signal–regulated kinase (ERK) phosphorylation, and the loss of ERK in the PG phenocopies the loss of PTTH and Torso. We conclude that PTTH initiates metamorphosis by activation...

  11. Interaction of the transcription start site core region and transcription factor YY1 determine ascorbate transporter SVCT2 exon 1a promoter activity.

    Directory of Open Access Journals (Sweden)

    Huan Qiao

    Full Text Available Transcription of the ascorbate transporter, SVCT2, is driven by two distinct promoters in exon 1 of the transporter sequence. The exon 1a promoter lacks a classical transcription start site and little is known about regulation of promoter activity in the transcription start site core (TSSC region. Here we present evidence that the TSSC binds the multifunctional initiator-binding protein YY1. Electrophoresis shift assays using YY1 antibody showed that YY1 is present as one of two major complexes that specifically bind to the TSSC. The other complex contains the transcription factor NF-Y. Mutations in the TSSC that decreased YY1 binding also impaired the exon 1a promoter activity despite the presence of an upstream activating NF-Y/USF complex, suggesting that YY1 is involved in the regulation of the exon 1a transcription. Furthermore, YY1 interaction with NF-Y and/or USF synergistically enhanced the exon 1a promoter activity in transient transfections and co-activator p300 enhanced their synergistic activation. We propose that the TSSC plays a vital role in the exon 1a transcription and that this function is partially carried out by the transcription factor YY1. Moreover, co-activator p300 might be able to synergistically enhance the TSSC function via a "bridge" mechanism with upstream sequences.

  12. Activated T cell exosomes promote tumor invasion via Fas signaling pathway. (United States)

    Cai, Zhijian; Yang, Fei; Yu, Lei; Yu, Zhou; Jiang, Lingling; Wang, Qingqing; Yang, Yunshan; Wang, Lie; Cao, Xuetao; Wang, Jianli


    Activated T cells release bioactive Fas ligand (FasL) in exosomes, which subsequently induce self-apoptosis of T cells. However, their potential effects on cell apoptosis in tumors are still unknown. In this study, we purified exosomes expressing FasL from activated CD8(+) T cell from OT-I mice and found that activated T cell exosomes had little effect on apoptosis and proliferation of tumor cells but promoted the invasion of B16 and 3LL cancer cells in vitro via the Fas/FasL pathway. Activated T cell exosomes increased the amount of cellular FLICE inhibitory proteins and subsequently activated the ERK and NF-κB pathways, which subsequently increased MMP9 expression in the B16 murine melanoma cells. In a tumor-invasive model in vivo, we observed that the activated T cell exosomes promoted the migration of B16 tumor cells to lung. Interestingly, pretreatment with FasL mAb significantly reduced the migration of B16 tumor cells to lung. Furthermore, CD8 and FasL double-positive exosomes from tumor mice, but not normal mice, also increased the expression of MMP9 and promoted the invasive ability of B16 murine melanoma and 3LL lung cancer cells. In conclusion, our results indicate that activated T cell exosomes promote melanoma and lung cancer cell metastasis by increasing the expression of MMP9 via Fas signaling, revealing a new mechanism of tumor immune escape.

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


    Buck, M; Khan, H.; Dixon, R


    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 a...

  14. Effects of single-base substitutions within the acanthamoeba castellanii rRNA promoter on transcription and on binding of transcription initiation factor and RNA polymerase I

    Energy Technology Data Exchange (ETDEWEB)

    Kownin, P.; Bateman, E.; Paule, M.R.


    Single-point mutations were introduced into the promoter region of the Acanthamoeba castellanii rRNA gene by chemical mutagen treatment of a single-stranded clone in vitro, followed by reverse transcription and cloning of the altered fragment. The promoter mutants were tested for transcription initiation factor (TIF) binding by a template commitment assay plus DNase I footprinting and for transcription by an in vitro runoff assay. Point mutations within the previously identified TIF interaction region (between -20 and -47, motifs A and B) indicated that TIF interacts most strongly with a sequence centered at -29 and less tightly with sequences upstream and downstream. Some alterations of the base sequence closer to the transcription start site (and outside the TIF-protected site) also significantly decrease specific RNA synthesis in vitro. These were within the region which is protected from DNAse I digestion by polymerase I, but these mutations did not detectably affect the binding of polymerase to the promoter.

  15. Choline deficient diet enhances the initiating and promoting effects of methapyrilene hydrochloride in rat liver as assayed by the induction of gamma-glutamyltranspeptidase-positive hepatocyte foci. (United States)

    Perera, M. I.; Katyal, S. L.; Shinozuka, H.


    Earlier we demonstrated that short-term feeding of methapyrilene hydrochloride (MPH) and of a choline deficient (CD) diet to rats induced peroxidative damage of microsomal membrane lipids of liver cells. In the present study, we investigated whether a CD diet modifies the extent of MPH-induced lipid peroxidation and whether the modifications lead to changes in the initiating and promoting action of these agents using assays of the induction of gamma-glutamyltranspeptidase (GGT)-positive hepatocyte foci. Addition of 0.1% MPH to a CD diet enhanced the extent of microsomal lipid peroxidation induced by a CD diet alone. Feeding a choline supplemented (CS) or a CD diet containing 0.1% MPH for 2 weeks followed by 7 weeks promotion by a CD diet plus phenobarbital was ineffective in inducing GGT-positive foci. Feeding MPH in a CS or a CD diet for 4 weeks, however, resulted in the development of substantial numbers of GGT-positive foci. There was a 3 fold increase in the number of foci in rats initiated with a CD + MPH diet over that in rats initiated with a CS + MPH diet. 0.1% MPH in a CS diet or a CD diet exerted significant promotional effects on the induction of GGT-positive foci in rats initiated with a single injection of diethylnitrosamine. Addition of MPH to a CD diet was additive in inducing GGT-positive foci. The results suggest that lipid peroxidation of the liver may be involved in the carcinogenic and/or promoting effects of MPH and a CD diet. PMID:2893639

  16. Mechanisms of transcriptional activation of the mouse claudin-5 promoter by estrogen receptor alpha and beta. (United States)

    Burek, Malgorzata; Steinberg, Katrin; Förster, Carola Y


    Claudin-5 is an integral membrane protein and a critical component of endothelial tight junctions that control paracellular permeability. Claudin-5 is expressed at high levels in the brain vascular endothelium. Estrogens have multiple effects on vascular physiology and function. The biological actions of estrogens are mediated by two different estrogen receptor (ER) subtypes, ER alpha and ER beta. Estrogens have beneficial effects in several vascular disorders. Recently we have cloned and characterized a murine claudin-5 promoter and demonstrated 17beta-estradiol (E2)-mediated regulation of claudin-5 in brain and heart microvascular endothelium on promoter, mRNA and protein level. Sequence analysis revealed a putative estrogen response element (ERE) and a putative Sp1 transcription factor binding site in the claudin-5 promoter. The aim of the present study was to further characterize the estrogen-responsive elements of claudin-5 promoter. First, we introduced point mutations in ERE or Sp1 site in -500/+111 or in Sp1 site of -268/+111 claudin-5 promoter construct, respectively. Basal and E2-mediated transcriptional activation of mutated constructs was abrogated in the luciferase reporter gene assay. Next, we examined whether estrogen receptor subtypes bind to the claudin-5 promoter region. For this purpose we performed chromatin immunoprecipitation assays using anti-estrogen receptor antibodies and cellular lysates of E2-treated endothelial cells followed by quantitative PCR analysis. We show enrichment of claudin-5 promoter fragments containing the ERE- and Sp1-binding site in immunoprecipitates after E2 treatment. Finally, in a gel mobility shift assay, we demonstrated DNA-protein interaction of both ER subtypes at ERE. In summary, this study provides evidence that both a non-consensus ERE and a Sp1 site in the claudin-5 promoter are functional and necessary for the basal and E2-mediated activation of the promoter.

  17. Moco biosynthesis and the ATAC acetyltransferase engage translation initiation by inhibiting latent PKR activity. (United States)

    Suganuma, Tamaki; Swanson, Selene K; Florens, Laurence; Washburn, Michael P; Workman, Jerry L


    Molybdenum cofactor (Moco) biosynthesis is linked to c-Jun N-terminal kinase (JNK) signaling in Drosophila through MoaE, a molybdopterin (MPT) synthase subunit that is also a component of the Ada Two A containing (ATAC) acetyltransferase complex. Here, we show that human MPT synthase and ATAC inhibited PKR, a double-stranded RNA-dependent protein kinase, to facilitate translation initiation of iron-responsive mRNA. MPT synthase and ATAC directly interacted with PKR and suppressed latent autophosphorylation of PKR and its downstream phosphorylation of JNK and eukaryotic initiation factor 2α (eIF2α). The suppression of eIF2α phosphorylation via MPT synthase and ATAC prevented sequestration of the guanine nucleotide exchange factor eIF2B, which recycles eIF2-GDP to eIF2-GTP, resulting in the promotion of translation initiation. Indeed, translation of the iron storage protein, ferritin, was reduced in the absence of MPT synthase or ATAC subunits. Thus, MPT synthase and ATAC regulate latent PKR signaling and link transcription and translation initiation.

  18. [Activities of voivodeship occupational medicine centers in workplace health promotion in 2008]. (United States)

    Goszczyńska, Eliza


    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. hypoxia-inducible factors activate CD133 promoter through ETS family transcription factors.

    Directory of Open Access Journals (Sweden)

    Shunsuke Ohnishi

    Full Text Available CD133 is a cellular surface protein that has been reported to be a cancer stem cell marker, and thus it is considered to be a potential target for cancer treatment. However, the mechanism regulating CD133 expression is not yet understood. In this study, we analyzed the activity of five putative promoters (P1-P5 of CD133 in human embryonic kidney (HEK 293 cells and colon cancer cell line WiDr, and found that the activity of promoters, particularly of P5, is elevated by overexpression of hypoxia-inducible factors (HIF-1α and HIF-2α. Deletion and mutation analysis identified one of the two E-twenty six (ETS binding sites (EBSs in the P5 region as being essential for its promoter activity induced by HIF-1α and HIF-2α. In addition, a chromatin imunoprecipitation assay demonstrated that HIF-1α and HIF-2α bind to the proximal P5 promoter at the EBSs. The immunoprecipitation assay showed that HIF-1α physically interacts with Elk1; however, HIF-2α did not bind to Elk1 or ETS1. Furthermore, knockdown of both HIF-1α and HIF-2α resulted in a reduction of CD133 expression in WiDr. Taken together, our results revealed that HIF-1α and HIF-2α activate CD133 promoter through ETS proteins.

  20. Phytohormonal networks promote differentiation of fiber initials on pre-anthesis cotton ovules grown in vitro and in planta.

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    Hee Jin Kim

    Full Text Available The number of cotton (Gossypium sp. ovule epidermal cells differentiating into fiber initials is an important factor affecting cotton yield and fiber quality. Despite extensive efforts in determining the molecular mechanisms regulating fiber initial differentiation, only a few genes responsible for fiber initial differentiation have been discovered. To identify putative genes directly involved in the fiber initiation process, we used a cotton ovule culture technique that controls the timing of fiber initial differentiation by exogenous phytohormone application in combination with comparative expression analyses between wild type and three fiberless mutants. The addition of exogenous auxin and gibberellins to pre-anthesis wild type ovules that did not have visible fiber initials increased the expression of genes affecting auxin, ethylene, ABA and jasmonic acid signaling pathways within 1 h after treatment. Most transcripts expressed differentially by the phytohormone treatment in vitro were also differentially expressed in the ovules of wild type and fiberless mutants that were grown in planta. In addition to MYB25-like, a gene that was previously shown to be associated with the differentiation of fiber initials, several other differentially expressed genes, including auxin/indole-3-acetic acid (AUX/IAA involved in auxin signaling, ACC oxidase involved in ethylene biosynthesis, and abscisic acid (ABA 8'-hydroxylase an enzyme that controls the rate of ABA catabolism, were co-regulated in the pre-anthesis ovules of both wild type and fiberless mutants. These results support the hypothesis that phytohormonal signaling networks regulate the temporal expression of genes responsible for differentiation of cotton fiber initials in vitro and in planta.

  1. Orchestrated activation of mGluR5 and CB1 promotes neuroprotection. (United States)

    Batista, Edleusa M L; Doria, Juliana G; Ferreira-Vieira, Talita H; Alves-Silva, Juliana; Ferguson, Stephen S G; Moreira, Fabricio A; Ribeiro, Fabiola M


    The metabotropic glutamate receptor 5 (mGluR5) and the cannabinoid receptor 1 (CB1) exhibit a functional interaction, as CB1 regulates pre-synaptic glutamate release and mGluR5 activation increases endocannabinoid synthesis at the post-synaptic site. Since both mGluR5 and CB1 promote neuroprotection, we delineated experiments to investigate a possible link between CB1 and mGluR5 activation in the induction of neuroprotection using primary cultured corticostriatal neurons. We find that either the pharmacological blockade or the genetic ablation of either mGluR5 or CB1 can abrogate both CB1- and mGluR5-mediated neuroprotection against glutamate insult. Interestingly, decreased glutamate release and diminished intracellular Ca(2+) do not appear to play a role in CB1 and mGluR5-mediated neuroprotection. Rather, these two receptors work cooperatively to trigger the activation of cell signaling pathways to promote neuronal survival, which involves MEK/ERK1/2 and PI3K/AKT activation. Interestingly, although mGluR5 activation protects postsynaptic terminals and CB1 the presynaptic site, intact signaling of both receptors is required to effectively promote neuronal survival. In conclusion, mGluR5 and CB1 act in concert to activate neuroprotective cell signaling pathways and promote neuronal survival.

  2. Promoting physical activity: development and testing of self-determination theory-based interventions. (United States)

    Fortier, Michelle S; Duda, Joan L; Guerin, Eva; Teixeira, Pedro J


    A growing number of studies have pulled from Deci and Ryan's Self-Determination Theory to design interventions targeting health behavior change. More recently, researchers have begun using SDT to promote the adoption and maintenance of an active lifestyle. In this review, we aim to highlight how researchers and practitioners can draw from the SDT framework to develop, implement, and evaluate intervention efforts centered on increasing physical activity levels in different contexts and different populations. In the present paper, the rationale for using SDT to foster physical activity engagement is briefly reviewed before particular attention is given to three recent randomized controlled trials, the Canadian Physical Activity Counseling (PAC) Trial, the Empower trial from the UK, and the Portuguese PESO (Promotion of Health and Exercise in Obesity) trial, each of which focused on promoting physical activity behavior. The SDT-based intervention components, procedures, and participants are highlighted, and the key findings that have emanated from these three trials are presented. Lastly, we outline some of the limitations of the work conducted to date in this area and we acknowledge the challenges that arise when attempting to design, deliver, and test SDT-grounded interventions in the context of physical activity promotion.

  3. Promoting physical activity: development and testing of self-determination theory-based interventions

    Directory of Open Access Journals (Sweden)

    Fortier Michelle S


    Full Text Available Abstract A growing number of studies have pulled from Deci and Ryan's Self-Determination Theory to design interventions targeting health behavior change. More recently, researchers have begun using SDT to promote the adoption and maintenance of an active lifestyle. In this review, we aim to highlight how researchers and practitioners can draw from the SDT framework to develop, implement, and evaluate intervention efforts centered on increasing physical activity levels in different contexts and different populations. In the present paper, the rationale for using SDT to foster physical activity engagement is briefly reviewed before particular attention is given to three recent randomized controlled trials, the Canadian Physical Activity Counseling (PAC Trial, the Empower trial from the UK, and the Portuguese PESO (Promotion of Health and Exercise in Obesity trial, each of which focused on promoting physical activity behavior. The SDT-based intervention components, procedures, and participants are highlighted, and the key findings that have emanated from these three trials are presented. Lastly, we outline some of the limitations of the work conducted to date in this area and we acknowledge the challenges that arise when attempting to design, deliver, and test SDT-grounded interventions in the context of physical activity promotion.

  4. Ctk1 Function Is Necessary for Full Translation Initiation Activity in Saccharomyces cerevisiae (United States)

    Coordes, Britta; Brünger, Katharina M.; Burger, Kaspar; Soufi, Boumediene; Horenk, Juliane; Eick, Dirk; Olsen, Jesper V.


    Translation is a fundamental and highly regulated cellular process. Previously, we reported that the kinase and transcription elongation factor Ctk1 increases fidelity during translation elongation in Saccharomyces cerevisiae. Here, we show that loss of Ctk1 function also affects the initiation step of translation. Translation active extracts from Ctk1-depleted cells show impaired translation activity of capped mRNA, but not mRNA reporters containing the cricket paralysis virus (CrPV) internal ribosome entry site (IRES). Furthermore, the formation of 80S initiation complexes is decreased, which is probably due to reduced subunit joining. In addition, we determined the changes in the phosphorylation pattern of a ribosome enriched fraction after depletion of Ctk1. Thus, we provide a catalogue of phosphoproteomic changes dependent on Ctk1. Taken together, our data suggest a stimulatory function of Ctk1 in 80S formation during translation initiation. PMID:25416238

  5. Development of complex sales promotion of educational services in the specialty «Management of innovation activities»

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    J.O. Timokhina


    Full Text Available In this article describes the complex of sales promotion of educational services in the specialty "Management of innovation activity" and proposed plan of decision to boost sales promotion for a new specialty in the Ukrainian education market.

  6. HNF1 alpha activates the aminopeptidase N promoter in intestinal (Caco-2) cells

    DEFF Research Database (Denmark)

    Olsen, Jørgen; Laustsen, Lotte; Troelsen, J


    The importance of HNF1 binding proteins for intestinal aminopeptidase N expression was investigated using the Caco-2 cell-line. Aminopeptidase N promoter activity in Caco-2 cells depends on the HNF1 element (positions -85 to -58) and co-transfection with an HNF1 alpha expression vector demonstrates...... a direct activation of the promoter by HNF1 alpha through this element. Electrophoretic mobility shift assays using nuclear extracts from Caco-2 cells show the presence of high amounts of HNF1 binding proteins irrespective of their state of differentiation....

  7. Factors Involved in Iranian Women Heads of Household's Health Promotion Activities: A Grounded Theory Study. (United States)

    Rafii, Forough; Seyedfatemi, Naima; Rezaei, Mahboubeh


    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.

  8. Protein C activation during the initial phase of experimental acute pancreatitis in the rabbit

    DEFF Research Database (Denmark)

    Ottesen, L H; Bladbjerg, E-M; Osman, M;


    BACKGROUND: Disturbances of coagulation and fibrinolysis are well-known systemic effects of acute necrotising pancreatitis (ANP). The purpose of this experimental study was to evaluate the initial events in the haemostatic activation during ANP in an animal model with relevance to the human...

  9. An Initial Description and Pilot of Group Behavioral Activation Therapy for Anxious and Depressed Youth (United States)

    Chu, Brian C.; Colognori, Daniela; Weissman, Adam S.; Bannon, Katie


    Transdiagnostic approaches for treating multiple problems within a single protocol are novel but gaining support. This report describes initial efforts to adapt reconceptualized behavioral activation (e.g., Jacobson, Martell, & Dimidjian, 2001) to a group format suitable for young adolescents, plus add a powerful exposure component to accommodate…

  10. Transcription Activity of Ectogenic Human Carcinoembryonic Antigen Promoter in Lung Adenocarcinoma Cells A549

    Institute of Scientific and Technical Information of China (English)

    XIONG Weining; FANG Huijuan; XU Yongjian; XIONG Shendao; CAO Yong; SONG Qingfeng; ZENG Daxiong; ZHANG Huilan


    The transcription activity of ectogenic human carcinoembryonic antigen (CEA) promoter in lung adenocarcinoma cells A549 was investigated for the further gene-targeting therapy. The reporter gene green fluorescent protein (GFP) driven by CEA promoter and human cytomegalovirus (CMV) promoter were relatively constructed and named plasmid pCEA-EGFP and pCMV-GFP respectively. The intensity of fluorescence was detected by fluorescence microscope and flow cytometry analysis after the pCEA-GFP and pSNAV-GFP plasmids were transfected into A549 cells through liposome respectively. The results showed (4.08±0.63) % of the A549 cells transfected with pCEA-AFP plasmid expressed, significantly lower than that of the A549 cells transfected with pCMV-GFP [(43.27±3.54) %]. It was suggested that ectogenic human CEA promoter in lung adenocarcinoma cells A549 was weakly expressed. The distinct specificity of CEA promoter in CEA high expression cells was regarded as a tool in selective gene therapy, but the transcription activity of ectogenic human CEA promoter was needed to increase in the future.

  11. Identification of a type 1 diabetes-associated CD4 promoter haplotype with high constitutive activity

    DEFF Research Database (Denmark)

    Kristiansen, O P; Karlsen, A E; Larsen, Z M;


    CD4 is a candidate gene in autoimmune diseases, including Type 1 diabetes mellitus (T1DM), because the CD4 receptor is crucial for appropriate antigen responses of CD4(+) T cells. We previously found linkage between a CD4-1188(TTTTC)(5-14) promoter polymorphism and T1DM. In the present study, we...... screened the human CD4 promoter for mutations and identified three frequent single nucleotide polymorphisms (SNPs): CD4-181C/G, CD4-521C/G and CD4-1050T/C. The SNPs are in strong linkage disequilibrium (LD) and association with the CD4-1188(TTTTC)(5-14) alleles, and we observed nine CD4 promoter haplotypes...... promoter activity and (2) the CD4-181G variant encodes higher stimulated promoter activity than the CD4-181C variant. This difference is in part neutralized in the frequently occurring CD4 promoter haplotypes by the more upstream genetic variants. Thus, we report functional impact of a novel CD4-181C/G SNP...

  12. Considerations on the promotional activity on the DIY market in Romania

    Directory of Open Access Journals (Sweden)

    Mihai FÎNARU


    Full Text Available Communication is a component of the marketing mix of great importance for the success of companies on the market. Currently the promotional activity of companies is experiencing a variety of manifestations, the manufacturers and the distributors are always interested in finding ways to promote themselves differently, moreover to draw the attention of consumers and to produce the desired behavior among them. DIY market is a highly competitive market and the promotional techniques used by the companies in this field are very diverse. In this context, this paper aims at presenting a series of promotional aspects of the techniques used by two of the largest DIY companies on the Romanian market Dedeman and Praktiker.

  13. A new era for functional labeling of neurons: activity-dependent promoters have come of age

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    Takashi eKawashima


    Full Text Available Genetic labeling of neurons with a specific response feature is an emerging technology for precise dissection of brain circuits that are functionally heterogeneous at the single-cell level. While immediate early gene mapping has been widely used for decades to identify brain regions which are activated by external stimuli, recent characterization of the promoter and enhancer elements responsible for neuronal activity-dependent transcription have opened new avenues for live imaging of active neurons. Indeed, these advancements provided the basis for a growing repertoire of novel experiments to address the role of active neuronal networks in cognitive behaviors. In this review, we summarize the current literature on the usage and development of activity-dependent promoters and discuss the future directions of this expanding new field.

  14. Evaluation of physical activity in the health promotion for brazilian teenagers: a systematic review

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    Alvaro Adolfo Duarte Alberto


    Full Text Available Objective: To analyze the methodological designs of national studies that assessed the level of physical activity for promoting adolescent health. Methods: a systematic literature review of original researches and publications of MEDLINE, LILACS, SCOPUS and ADOLEC electronic databases. It focused on determinant aspects of physical activity for health promotion using the following keywords: physical activity, physical fitness, physical activity, physical exercise, motor activity, sedentary and sedentariness, adolescent, adolescence, young, youth, teenager, and teenage, Brazil, Brazilian, South America, Low-middle income and country(ies. Data analysis covered the period from 2005 to 2011. First, 449 studies were identified. After analyzing the titles of the manuscripts, 130 articles were eligible for abstract evaluation and subsequent full text analysis. In the end, 31 articles met all inclusion criteria. Results: A total of 93.6% (n=29 of the evaluated studies used cross-sectional design, with samples ranging from 92 to 5028 subjects, and all of them used questionnaires for measuring physical activity. The main analysis of the studies was based on the association between physical activity, biodemographic data (age, gender and socioeconomic data (income, social class and parental education. Conclusion: The national studies assessing the level of physical activity for promoting adolescent health appear with great methodological variability since there is no standardization in the methodological design, instrument and definition of variables, highlighting the need for longitudinal studies in this area. doi:10.5020/18061230.2013.p426


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


    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


    Directory of Open Access Journals (Sweden)

    Zuzana Polóniová


    Full Text Available In this work we used the Cre/loxP recombination system to study the activity of the Arabidopsis DLL promoter under water stress treatment. For this, the T-DNA containing the Cre/loxP self-excision recombination cassette was introduced into tobacco genome via A. tumefaciens LBA 4404. The expression of the cre gene was regulated by the DLL promoter. On activity of the DLL the Cre recombinase was expected to remove Cre/loxP cassette. Transgenic nature of regenerated transgenic T0 tobacco plantlets was proved by GUS and PCR analyses. The selected 10 transgenic T0 plants were subjected to the water stress analyses under in vitro as well as under in vivo conditions. The osmotic stress experiments were performed with 10 % PEG and 100 mmol.l-1 mannitol (individually. The activity of the DLL was evaluated after 24 hours. For drought stress experiments, the watering was withheld for 10 days. The activity of the DLL was monitored using PCR approach. Under given abiotic stress conditions, no activity of the DLL was observed. The DLL promoter remained stable. It points out the DLL as the promoter with precise control of the gene expression with wide usability in plant biotechnology.

  17. Harpinxoo and Its Functional Domains Activate Pathogen-inducible Plant Promoters in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    PENGJian-Ling; BAOZhi-Long; LIPing; CHENGuang-Yong; WANGJin-Sheng; DONGHan-Song


    Harpins are bacterial proteins that can enhance plant growth and defense against pathogens and insects. To elaborate whether harpins perform the diverse functions in coordination with the activation of specific promoters that contain particular elements, we cloned pathogen-inducible plant promoters PPP1, PPP2, and PPP3 from tobacco and investigated their responses to harpinxoo or its truncated fragments DEG, DIR, and DPR (domains for enhancing plant growth, insect resistance and pathogen resistance). PPP1 contains an internal repeat composed of two tandem 111bp fragments; 111bp in the repeat was deleted in PPP2. PPP3 contains a bacteria-inducible element; PPP1 and PPP2 additionally contain TAC-1 and Eli boxes inducible correspondingly by salicylic acid (SA) and elicitors. Function of cloned PPPs was confirmed based on their activation in transgenic Arabidopsis plants by Ralstonia solanacearum (Ralston) or SA. Harpinxoo, DEG, DIR, or DPR activated PPP1 and PPP2 but not PPP3, consistent with the presence of Eli boxes in promoters. PPP1 was ca. 3-fold more active than PPP2, suggesting that the internal repeat affects levels of the promoter activation.

  18. School Health Promotion to Increase Empowerment, Gender Equality and Pupil Participation: A Focus Group Study of a Swedish Elementary School Initiative (United States)

    Gadin, Katja Gillander; Weiner, Gaby; Ahlgren, Christina


    A school health promotion project was carried out in an elementary school in Sweden where active participation, gender equality, and empowerment were leading principles. The objective of the study was to understand challenges and to identify social processes of importance for such a project. Focus group interviews were conducted with 6 single-sex…

  19. Gyrase-dependent stabilization of pSC101 plasmid inheritance by transcriptionally active promoters. (United States)

    Beaucage, S L; Miller, C A; Cohen, S N


    The pSC101 plasmid encodes a cis-acting genetic locus termed par that ensures the stable inheritance of plasmids in a population of dividing cells. In the absence of selection, par-defective plasmids are lost rapidly from the bacterial population. We report here that the stability of par-deleted pSC101 derivatives is restored by introducing certain adventitious bacterial promoters onto the plasmid. Stabilization requires active transcription from the inserted promoter and is affected by the site and orientation of the insertion, the length of the nascent transcript and DNA gyrase activity. While a promotor-associated overall increase in negative superhelicity of plasmid DNA was observed, stabilized inheritance appeared to be dependent on localized rather than generalized supercoiling. Our demonstration that promoter-induced DNA supercoiling can mimic the effects of the pSC101 par locus provides evidence that the previously reported superhelicity-generating effects of par are intrinsic to its function.

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

    Arendse, Gillian J.


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Pena, AndreAna N., E-mail: [Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX (United States); Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX (United States); Tominaga, Kaoru; Pereira-Smith, Olivia M. [Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX (United States); Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX (United States)


    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.

  2. hTERT promoter activity and CpG methylation in HPV-induced carcinogenesis

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    Snijders Peter JF


    Full Text Available Abstract Background Activation of telomerase resulting from deregulated hTERT expression is a key event during high-risk human papillomavirus (hrHPV-induced cervical carcinogenesis. In the present study we examined hTERT promoter activity and its relation to DNA methylation as one of the potential mechanisms underlying deregulated hTERT transcription in hrHPV-transformed cells. Methods Using luciferase reporter assays we analyzed hTERT promoter activity in primary keratinocytes, HPV16- and HPV18-immortalized keratinocyte cell lines and cervical cancer cell lines. In the same cells as well as cervical specimens we determined hTERT methylation by bisulfite sequencing analysis of the region spanning -442 to +566 (relative to the ATG and quantitative methylation specific PCR (qMSP analysis of two regions flanking the hTERT core promoter. Results We found that in most telomerase positive cells increased hTERT core promoter activity coincided with increased hTERT mRNA expression. On the other hand basal hTERT promoter activity was also detected in telomerase negative cells with no or strongly reduced hTERT mRNA expression levels. In both telomerase positive and negative cells regulatory sequences flanking both ends of the core promoter markedly repressed exogenous promoter activity. By extensive bisulfite sequencing a strong increase in CpG methylation was detected in hTERT positive cells compared to cells with no or strongly reduced hTERT expression. Subsequent qMSP analysis of a larger set of cervical tissue specimens revealed methylation of both regions analyzed in 100% of cervical carcinomas and 38% of the high-grade precursor lesions, compared to 9% of low grade precursor lesions and 5% of normal controls. Conclusions Methylation of transcriptionally repressive sequences in the hTERT promoter and proximal exonic sequences is correlated to deregulated hTERT transcription in HPV-immortalized cells and cervical cancer cells. The detection of DNA

  3. Effectiveness of Video Self-Modeling to Promote Social Initiations by 3-Year-Olds with Autism Spectrum Disorders (United States)

    Buggey, Tom


    Video Self-Modeling (VSM) provides individuals the opportunity to view themselves performing a task beyond their present functioning level through the careful editing of videos. In this study, a single-case multiple-baseline design was used to determine whether VSM would facilitate social initiations across three young children (M = 3 years 10…

  4. The virulence regulator Sae of Staphylococcus aureus: promoter activities and response to phagocytosis-related signals. (United States)

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


    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.

  5. Cdc6 ATPase activity disengages Cdc6 from the pre-replicative complex to promote DNA replication. (United States)

    Chang, FuJung; Riera, Alberto; Evrin, Cecile; Sun, Jingchuan; Li, Huilin; Speck, Christian; Weinreich, Michael


    To initiate DNA replication, cells first load an MCM helicase double hexamer at origins in a reaction requiring ORC, Cdc6, and Cdt1, also called pre-replicative complex (pre-RC) assembly. The essential mechanistic role of Cdc6 ATP hydrolysis in this reaction is still incompletely understood. Here, we show that although Cdc6 ATP hydrolysis is essential to initiate DNA replication, it is not essential for MCM loading. Using purified proteins, an ATPase-defective Cdc6 mutant 'Cdc6-E224Q' promoted MCM loading on DNA. Cdc6-E224Q also promoted MCM binding at origins in vivo but cells remained blocked in G1-phase. If after loading MCM, Cdc6-E224Q was degraded, cells entered an apparently normal S-phase and replicated DNA, a phenotype seen with two additional Cdc6 ATPase-defective mutants. Cdc6 ATP hydrolysis is therefore required for Cdc6 disengagement from the pre-RC after helicase loading to advance subsequent steps in helicase activation in vivo.

  6. Ontogenic timing mechanism initiates the expression of rat intestinal sucrase activity

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, K.Y.; Holt, P.R.


    Morphologic and enzymic differentiation occurs in rat small intestinal epithelium during 16-20 days of postnatal life. This change is considered to be initiated by an ontogenic timing mechanism and is modulated by extrinsic systemic and luminal factors. The importance of the ontogenic timing was tested directly using a transplantation technique in which jejunal isografts from newborn (day 0) and 5-day-old (day 5) rats were implanted under the skin of newborn (day 0) hosts. Isografts showing cryptvillus architecture were obtained in 44% and 21% of transplants, respectively. Day 0 isografts and host intestine expressed sucrase activity at about 16-18 days of age and showed similar crypt cell labeling and epithelial migration after (3H)thymidine injection. Day 5 isografts expressed sucrase activity when the hosts were 13 days of age, whereas host intestine showed no detectable sucrase activity. Isograft lactase activities in both experimental transplant models were significantly higher than host intestinal lactase up to 28 days of age, suggesting that luminal factors are important in modulating lactase activity during the first 4 wk of postnatal life. It is concluded that (a) no systemic factors at day 13 inhibit the expression of sucrase activity and (b) an ontogenic timing mechanism in the jejunum initiates the expression of sucrase activity.

  7. Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation

    Directory of Open Access Journals (Sweden)

    Bonnet Amandine


    Full Text Available Abstract Background The Tax protein encoded by Human T-lymphotropic virus type 1 (HTLV-1 is a powerful activator of the NF-κB pathway, a property critical for HTLV-1-induced immortalization of CD4+ T lymphocytes. Tax permanently stimulates this pathway at a cytoplasmic level by activating the IκB kinase (IKK complex and at a nuclear level by enhancing the binding of the NF-κB factor RelA to its cognate promoters and by forming nuclear bodies, believed to represent transcriptionally active structures. In previous studies, we reported that Tax ubiquitination and SUMOylation play a critical role in Tax localization and NF-κB activation. Indeed, analysis of lysine Tax mutants fused or not to ubiquitin or SUMO led us to propose a two-step model in which Tax ubiquitination first intervenes to activate IKK while Tax SUMOylation is subsequently required for promoter activation within Tax nuclear bodies. However, recent studies showing that ubiquitin or SUMO can modulate Tax activities in either the nucleus or the cytoplasm and that SUMOylated Tax can serve as substrate for ubiquitination suggested that Tax ubiquitination and SUMOylation may mediate redundant rather than successive functions. Results In this study, we analyzed the properties of a new Tax mutant that is properly ubiquitinated, but defective for both nuclear body formation and SUMOylation. We report that reducing Tax SUMOylation and nuclear body formation do not alter the ability of Tax to activate IKK, induce RelA nuclear translocation, and trigger gene expression from a NF-κB promoter. Importantly, potent NF-κB promoter activation by Tax despite low SUMOylation and nuclear body formation is also observed in T cells, including CD4+ primary T lymphocytes. Moreover, we show that Tax nuclear bodies are hardly observed in HTLV-1-infected T cells. Finally, we provide direct evidence that the degree of NF-κB activation by Tax correlates with the level of Tax ubiquitination, but not

  8. Neurite outgrowth-promoting active constituents of the Japanese cypress (Chamaecyparis obtusa). (United States)

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


    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.

  9. Terazosin activates Pgk1 and Hsp90 to promote stress resistance. (United States)

    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


    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.

  10. A Highly Active and Selective Manganese Oxide Promoted Cobalt-on-Silica Fischer-Tropsch Catalyst

    NARCIS (Netherlands)

    den Breejen, Johan P.; Frey, Anne M.; Yang, Jia; Holmen, Anders; van Schooneveld, Matti M.; de Groot, Frank M. F.; Stephan, Odile; Bitter, Johannes H.; de Jong, Krijn P.


    A highly active and selective manganese oxide-promoted silica-supported cobalt catalyst for the Fischer-Tropsch reaction is reported. Co/MnO/SiO2 catalysts were prepared via impregnation of a cobalt nitrate and manganese nitrate precursor, followed by drying and calcination in an NO/He flow. The cat

  11. p55PIK Transcriptionally Activated by MZF1 Promotes Colorectal Cancer Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Yu Deng


    Full Text Available p55PIK, regulatory subunit of class IA phosphatidylinositol 3-kinase (PI3K, plays a crucial role in cell cycle progression by interaction with tumor repressor retinoblastoma (Rb protein. A recent study showed that Rb protein can localize to the mitochondria in proliferative cells. Aberrant p55PIK expression may contribute to mitochondrial dysfunction in cancer progression. To reveal the mechanisms of p55PIK transcriptional regulation, the p55PIK promoter characteristics were analyzed. The data show that myeloid zinc finger 1, MZF1, is necessary for p55PIK gene transcription activation. ChIP (Chromatin immuno-precipitation assay shows that MZF1 binds to the cis-element “TGGGGA” in p55PIK promoter. In MZF1 overexpressed cells, the promoter activity, expression of p55PIK, and cell proliferation rate were observed to be significantly enhanced. Whereas in MZF1-silenced cells, the promoter activity and expression of p55PIK and cell proliferation level was statistically decreased. In CRC tissues, MZF1 and p55PIK mRNA expression were increased (P=0.046, P=0.047, resp.. A strong positive correlation (Rs=0.94 between MZF1 and p55PIK mRNA expression was observed. Taken together, we concluded that p55PIK is transcriptionally activated by MZF1, resulting in increased proliferation of colorectal cancer cells.

  12. Design of cAMP-CRP-activated promoters in Escherichia coli

    DEFF Research Database (Denmark)

    Valentin-Hansen, P; Holst, B; Søgaard-Andersen, L


    We have studied the deoP2 promoter of Escherichia coli to define features that are required for optimal activation by the complex of adenosine 3',5' monophosphate (cAMP) and the cAMP receptor protein (CRP). Systematic mutagenesis of deoP2 shows that the distance between the CRP site and the -10...

  13. Promoting Science Outdoor Activities for Elementary School Children: Contributions from a Research Laboratory (United States)

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


    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…

  14. New Ideas for Promoting Physical Activity among Middle Age and Older Adults (United States)

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


    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…

  15. Tailored interventions to promote Active Ageing using mobile technology: a feasibility study

    NARCIS (Netherlands)

    Cabrita, M.; Melenk, J.; El Menshawy, N.; Tabak, M.; Vollenbroek-Hutten, M.


    Introduction: Mobile technologies facilitate innovative and ubiquitous interventions to promote Active Ageing in daily life. To ensure adoption, such interventions must be designed in co-operation with older adults. This work presents the results of a feasibility study of a system that monitors phys

  16. What Do We Know about "How" to Promote Physical Activity to Adolescents? A Mapping Review (United States)

    Bush, Paula Louise; García Bengoechea, Enrique


    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…

  17. Neutrophil myeloperoxidase activity and the influence of two single-nucleotide promoter polymorphisms

    NARCIS (Netherlands)

    Rutgers, Abraham; Heeringa, Peter; Giesen, Joyce E H M; Theunissen, Ruud T; Jacobs, Heinz; Tervaert, Jan Willem Cohen


    Myeloperoxidase (MPO) catalyses the formation of hypochlorous acid and is involved in many (patho)physiological processes. The present study was designed to determine the effect of two MPO promoter polymorphisms (463G/A and 129G/A) on enzyme activity. In 243 healthy controls, genotypes were determin

  18. Promotion of physical activity in the European region: content analysis of 27 national policy documents

    DEFF Research Database (Denmark)

    Daugbjerg, Signe B; Kahlmeier, Sonja; Racioppi, Francesca;


    search methods, 49 national policy documents on physical activity promotion were identified. An analysis grid covering key features was developed for the analysis of the 27 documents published in English. RESULTS: Analysis showed that many general recommendations for policy developments are being...

  19. Knowledge, Attitudes and Practices of Clinicians in Promoting Physical Activity to Prostate Cancer Survivors (United States)

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


    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…

  20. Fitness Testing in Physical Education--A Misdirected Effort in Promoting Healthy Lifestyles and Physical Activity? (United States)

    Cale, Lorraine; Harris, Jo


    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…

  1. A Journal-Club-Based Class that Promotes Active and Cooperative Learning of Biology (United States)

    Kitazono, Ana A.


    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…

  2. Adding effect sizes to a systematic review on interventions for promoting physical activity among European teenagers


    Crutzen Rik


    Abstract This commentary adds effect sizes to the recently published systematic review by De Meester and colleagues and provides a more detailed insight into the effectiveness of interventions to promote physical activity among European teenagers. The main findings based on this evidence were: (1) school-based interventions generally lead to short term improvement in physical activity levels, but there were large differences between interventions with regard to effect sizes; (2) a multi-compo...

  3. Mechanistical studies on gap junctions and their role in tumour promotion : Structure-activity relationships of polychlorinated biphelyls


    Bager, Yvonne


    Chemically induced carcinogenesis is a multi-stage process that can be divided into at least three major stages, initiation, promotion and progression. The promotion stage involves clonal expansion of genetically altered cells (i.e. initiated cells). The final stage, progression, includes a karyotypic instability of cells that may result in malignancy. Several lines of evidence support the theory that inhibition of gap junctional intercellular communication plays a sig...

  4. Deepening the impact of initiatives to promote teamwork and workplace health: a perspective from the NEKTA study. (United States)

    Leiter, Michael P


    Evaluations of major policy initiatives on workplace health and teamwork have found significant progress on some issues and inertia on others. This article explores the applicability of a model describing employees' psychological relationships with work as a framework for considering workplace health initiatives. The Mediation Model contributes a way of focusing on experiences that are integral to staff nurses' day-to-day work life. As such, the model provides direction for developing and evaluating strategies for enhancing the quality of work life, especially pertaining to workplace health. The commentary considers a few key findings from the Nursing Environments: Knowledge to Action (NETKA) study that reviewed the applicability of national policy documents on the healthcare systems of Atlantic Canada. The discussion considers implications of staff nurses' participation in sharing and using new knowledge about workplace health.

  5. Systems biology of coagulation initiation: kinetics of thrombin generation in resting and activated human blood.

    Directory of Open Access Journals (Sweden)

    Manash S Chatterjee

    Full Text Available Blood function defines bleeding and clotting risks and dictates approaches for clinical intervention. Independent of adding exogenous tissue factor (TF, human blood treated in vitro with corn trypsin inhibitor (CTI, to block Factor XIIa will generate thrombin after an initiation time (T(i of 1 to 2 hours (depending on donor, while activation of platelets with the GPVI-activator convulxin reduces T(i to ∼20 minutes. Since current kinetic models fail to generate thrombin in the absence of added TF, we implemented a Platelet-Plasma ODE model accounting for: the Hockin-Mann protease reaction network, thrombin-dependent display of platelet phosphatidylserine, VIIa function on activated platelets, XIIa and XIa generation and function, competitive thrombin substrates (fluorogenic detector and fibrinogen, and thrombin consumption during fibrin polymerization. The kinetic model consisting of 76 ordinary differential equations (76 species, 57 reactions, 105 kinetic parameters predicted the clotting of resting and convulxin-activated human blood as well as predicted T(i of human blood under 50 different initial conditions that titrated increasing levels of TF, Xa, Va, XIa, IXa, and VIIa. Experiments with combined anti-XI and anti-XII antibodies prevented thrombin production, demonstrating that a leak of XIIa past saturating amounts of CTI (and not "blood-borne TF" alone was responsible for in vitro initiation without added TF. Clotting was not blocked by antibodies used individually against TF, VII/VIIa, P-selectin, GPIb, protein disulfide isomerase, cathepsin G, nor blocked by the ribosome inhibitor puromycin, the Clk1 kinase inhibitor Tg003, or inhibited VIIa (VIIai. This is the first model to predict the observed behavior of CTI-treated human blood, either resting or stimulated with platelet activators. CTI-treated human blood will clot in vitro due to the combined activity of XIIa and XIa, a process enhanced by platelet activators and which proceeds

  6. The pancreatitis-associated protein VMP1, a key regulator of inducible autophagy, promotes KrasG12D-mediated pancreatic cancer initiation (United States)

    Loncle, C; Molejon, M I; Lac, S; Tellechea, J I; Lomberk, G; Gramatica, L; Fernandez Zapico, M F; Dusetti, N; Urrutia, R; Iovanna, J L


    Both clinical and experimental evidence have firmly established that chronic pancreatitis, in particular in the context of Kras oncogenic mutations, predisposes to pancreatic ductal adenocarcinoma (PDAC). However, the repertoire of molecular mediators of pancreatitis involved in Kras-mediated initiation of pancreatic carcinogenesis remains to be fully defined. In this study we demonstrate a novel role for vacuole membrane protein 1 (VMP1), a pancreatitis-associated protein critical for inducible autophagy, in the regulation of Kras-induced PDAC initiation. Using a newly developed genetically engineered model, we demonstrate that VMP1 increases the ability of Kras to give rise to preneoplastic lesions, pancreatic intraepithelial neoplasias (PanINs). This promoting effect of VMP1 on PanIN formation is due, at least in part, by an increase in cell proliferation combined with a decrease in apoptosis. Using chloroquine, an inhibitor of autophagy, we show that this drug antagonizes the effect of VMP1 on PanIN formation. Thus, we conclude that VMP1-mediated autophagy cooperate with Kras to promote PDAC initiation. These findings are of significant medical relevance, molecules targeting autophagy are currently being tested along chemotherapeutic agents to treat PDAC and other tumors in human trials. PMID:27415425

  7. Adult stem cell theory of the multi-stage, multi-mechanism theory of carcinogenesis: role of inflammation on the promotion of initiated stem cells. (United States)

    Trosko, James E; Tai, Mei-Hui


    Inflammation, induced by microbial agents, radiation, endogenous or exogenous chemicals, has been associated with chronic diseases, including cancer. Since carcinogenesis has been characterized as consisting of the 'initiation', 'promotion' and 'progression' phases, the inflammatory process could affect any or all three phases. The stem cell theory of carcinogenesis has been given a revival, in that isolated human adult stem cells have been isolated and shown to be 'targets' for neoplastic transformation. Oct4, a transcription factor, has been associated with adult stem cells, as well as their immortalized and tumorigenic derivatives, but not with the normal differentiated daughters. These data are consistent with the stem cell theory of carcinogenesis. In addition, Gap Junctional Intercellular Communication (GJIC) seems to play a major role in cell growth. Inhibition of GJIC by non-genotoxic chemicals or various oncogenes seems to be the mechanism for the tumor promotion and progression phases of carcinogenesis. Many of the toxins, synthetic non-genotoxicants, and endogenous inflammatory factors have been shown to inhibit GJIC and act as tumor promoters. The inhibition of GJIC might be the mechanism by which the inflammatory process affects cancer and that to intervene during tumor promotion with anti-inflammatory factors might be the most efficacious anti-cancer strategy.

  8. Promoting Active Species Generation by Electrochemical Activation in Alkaline Media for Efficient Electrocatalytic Oxygen Evolution in Neutral Media. (United States)

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


    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.

  9. Cloning and Transcriptional Activity of the Mouse Omi/HtrA2 Gene Promoter. (United States)

    Liu, Dan; Liu, Xin; Wu, Ye; Wang, Wen; Ma, Xinliang; Liu, Huirong


    HtrA serine peptidase 2 (HtrA2), also named Omi, is a pro-apoptotic protein that exhibits dramatic changes in expression levels in a variety of disorders, including ischemia/reperfusion injury, cancer, and neurodegeneration. In our study, Omi/HtrA2 protein levels were high in the heart, brain, kidney and liver, with elevated heart/brain expression in aging mice. A similar expression pattern was observed at the mRNA level, which suggests that the regulation of Omi/HtrA2 is predominately transcriptional. Promoter binding by transcription factors is the main influencing factor of transcription, and to identify specific promoter elements that contribute to the differential expression of mouse Omi/HtrA2, we constructed truncated Omi/HtrA2 promoter/luciferase reporter vectors and analyzed their relative luciferase activity; it was greatest in the promoter regions at -1205~-838 bp and -146~+93 bp, with the -838~-649 bp region exhibiting negative regulatory activity. Bioinformatics analysis suggested that the Omi/HtrA2 gene promoter contains a CpG island at -709~+37 bp, and eight heat shock transcription factor 1 (HSF1) sites, two Sp1 transcription factor (SP1)sites, one activator protein (AP) site, seven p53 sites, and four YY1 transcription factor(YY1) sites were predicted in the core areas. Furthermore, we found that p53 and HSF1 specifically binds to the Omi/HtrA2 promoter using chromatin immunoprecipitation analysis. These results provide a foundation for understanding Omi/HtrA2 regulatory mechanisms, which could further understanding of HtrA-associated diseases.

  10. An upstream activation element exerting differential transcriptional activation on an archaeal promoter

    DEFF Research Database (Denmark)

    Peng, Nan; Xia, Qiu; Chen, Zhengjun


    Summary Microorganisms can utilize different sugars as energy and carbon sources and the genes involved in sugar metabolism often exhibit highly regulated expression. To study cis-acting elements controlling arabinose-responsive expression in archaea, the promoter of the Sulfolobus solfataricus a...

  11. Liver segmentation with new supervised method to create initial curve for active contour. (United States)

    Zareei, Abouzar; Karimi, Abbas


    The liver performs a critical task in the human body; therefore, detecting liver diseases and preparing a robust plan for treating them are both crucial. Liver diseases kill nearly 25,000 Americans every year. A variety of image segmentation methods are available to determine the liver's position and to detect possible liver tumors. Among these is the Active Contour Model (ACM), a framework which has proven very sensitive to initial contour delineation and control parameters. In the proposed method based on image energy, we attempted to obtain an initial segmentation close to the liver's boundary, and then implemented an ACM to improve the initial segmentation. The ACM used in this work incorporates gradient vector flow (GVF) and balloon energy in order to overcome ACM limitations, such as local minima entrapment and initial contour dependency. Additionally, in order to adjust active contour control parameters, we applied a genetic algorithm to produce a proper parameter set close to the optimal solution. The pre-processing method has a better ability to segment the liver tissue during a short time with respect to other mentioned methods in this paper. The proposed method was performed using Sliver CT image datasets. The results show high accuracy, precision, sensitivity, specificity and low overlap error, MSD and runtime with few ACM iterations.

  12. Distinct promoter activation mechanisms modulate noise-driven HIV gene expression (United States)

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


    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.

  13. The mRNA cap-binding protein Cbc1 is required for high and timely expression of genes by promoting the accumulation of gene-specific activators at promoters. (United States)

    Li, Tianlu; De Clercq, Nikki; Medina, Daniel A; Garre, Elena; Sunnerhagen, Per; Pérez-Ortín, José E; Alepuz, Paula


    The highly conserved Saccharomyces cerevisiae cap-binding protein Cbc1/Sto1 binds mRNA co-transcriptionally and acts as a key coordinator of mRNA fate. Recently, Cbc1 has also been implicated in transcription elongation and pre-initiation complex (PIC) formation. Previously, we described Cbc1 to be required for cell growth under osmotic stress and to mediate osmostress-induced translation reprogramming. Here, we observe delayed global transcription kinetics in cbc1Δ during osmotic stress that correlates with delayed recruitment of TBP and RNA polymerase II to osmo-induced promoters. Interestingly, we detect an interaction between Cbc1 and the MAPK Hog1, which controls most gene expression changes during osmostress, and observe that deletion of CBC1 delays the accumulation of the activator complex Hot1-Hog1 at osmostress promoters. Additionally, CBC1 deletion specifically reduces transcription rates of highly transcribed genes under non-stress conditions, such as ribosomal protein (RP) genes, while having low impact on transcription of weakly expressed genes. For RP genes, we show that recruitment of the specific activator Rap1, and subsequently TBP, to promoters is Cbc1-dependent. Altogether, our results indicate that binding of Cbc1 to the capped mRNAs is necessary for the accumulation of specific activators as well as PIC components at the promoters of genes whose expression requires high and rapid transcription.

  14. The translation initiation factor 3f (eIF3f exhibits a deubiquitinase activity regulating Notch activation.

    Directory of Open Access Journals (Sweden)

    Julien Moretti

    Full Text Available Activation of the mammalian Notch receptor after ligand binding relies on a succession of events including metalloprotease-cleavage, endocytosis, monoubiquitination, and eventually processing by the gamma-secretase, giving rise to a soluble, transcriptionally active molecule. The Notch1 receptor was proposed to be monoubiquitinated before its gamma-secretase cleavage; the targeted lysine has been localized to its submembrane domain. Investigating how this step might be regulated by a deubiquitinase (DUB activity will provide new insight for understanding Notch receptor activation and downstream signaling. An immunofluorescence-based screening of an shRNA library allowed us to identify eIF3f, previously known as one of the subunits of the translation initiation factor eIF3, as a DUB targeting the activated Notch receptor. We show that eIF3f has an intrinsic DUB activity. Knocking down eIF3f leads to an accumulation of monoubiquitinated forms of activated Notch, an effect counteracted by murine WT eIF3f but not by a catalytically inactive mutant. We also show that eIF3f is recruited to activated Notch on endocytic vesicles by the putative E3 ubiquitin ligase Deltex1, which serves as a bridging factor. Finally, catalytically inactive forms of eIF3f as well as shRNAs targeting eIF3f repress Notch activation in a coculture assay, showing that eIF3f is a new positive regulator of the Notch pathway. Our results support two new and provocative conclusions: (1 The activated form of Notch needs to be deubiquitinated before being processed by the gamma-secretase activity and entering the nucleus, where it fulfills its transcriptional function. (2 The enzyme accounting for this deubiquitinase activity is eIF3f, known so far as a translation initiation factor. These data improve our knowledge of Notch signaling but also open new avenues of research on the Zomes family and the translation initiation factors.

  15. Oncogenic KRAS activates an embryonic stem cell-like program in human colon cancer initiation


    Le Rolle, Anne-France; Chiu, Thang K; ZENG, ZHAOSHI; Shia, Jinru; Weiser, Martin R; Paty, Philip B.; Chiu, Vi K


    Colorectal cancer is the third most frequently diagnosed cancer worldwide. Prevention of colorectal cancer initiation represents the most effective overall strategy to reduce its associated morbidity and mortality. Activating KRAS mutation (KRASmut ) is the most prevalent oncogenic driver in colorectal cancer development, and KRASmut inhibition represents an unmet clinical need. We apply a systems-level approach to study the impact of KRASmut on stem cell signaling during human colon cancer i...

  16. Fiscal Year 2014 Annual Report on BNLs Next Generation Safeguards Initiative Human Capital Development Activities

    Energy Technology Data Exchange (ETDEWEB)

    Pepper, Susan E. [Brookhaven National Lab. (BNL), Upton, NY (United States)


    Brookhaven National Laboratory’s (BNL’s) Nonproliferation and National Security Department contributes to the National Nuclear Security Administration Office of Nonproliferation and International Security Next Generation Safeguards Initiative (NGSI) through university engagement, safeguards internships, safeguards courses, professional development, recruitment, and other activities aimed at ensuring the next generation of international safeguards professionals is adequately prepared to support the U.S. safeguards mission. This report is a summary of BNL s work under the NGSI program in Fiscal Year 2014.

  17. Epac Activation Initiates Associative Odor Preference Memories in the Rat Pup (United States)

    Grimes, Matthew T.; Powell, Maria; Gutierrez, Sandra Mohammed; Darby-King, Andrea; Harley, Carolyn W.; McLean, John H.


    Here we examine the role of the exchange protein directly activated by cAMP (Epac) in ß-adrenergic-dependent associative odor preference learning in rat pups. Bulbar Epac agonist (8-pCPT-2-O-Me-cAMP, or 8-pCPT) infusions, paired with odor, initiated preference learning, which was selective for the paired odor. Interestingly, pairing odor with Epac…

  18. Mitochondrial Oxidative Stress due to Complex I Dysfunction Promotes Fibroblast Activation and Melanoma Cell Invasiveness

    Directory of Open Access Journals (Sweden)

    Maria Letizia Taddei


    Full Text Available Increased ROS (cellular reactive oxygen species are characteristic of both fibrosis and tumour development. ROS induce the trans-differentiation to myofibroblasts, the activated form of fibroblasts able to promote cancer progression. Here, we report the role of ROS produced in response to dysfunctions of mitochondrial complex I, in fibroblast activation and in tumour progression. We studied human fibroblasts with mitochondrial dysfunctions of complex I, leading to hyperproduction of ROS. We demonstrated that ROS level produced by the mutated fibroblasts correlates with their activation. The increase of ROS in these cells provides a greater ability to remodel the extracellular matrix leading to an increased motility and invasiveness. Furthermore, we evidentiated that in hypoxic conditions these fibroblasts cause HIF-1α stabilization and promote a proinvasive phenotype of human melanoma cells through secretion of cytokines. These data suggest a possible role of deregulated mitochondrial ROS production in fibrosis evolution as well as in cancer progression and invasion.

  19. Activation of the Notch signaling pathway promotes neurovascular repair after traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Qi-shan Ran; Yun-hu Yu; Xiao-hong Fu; Yuan-chao Wen


    The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after traumatic brain injury. Therefore, in the present study, we controlled the Notch signaling path-way using overexpression and knockdown constructs. Activation of the Notch signaling pathway by Notch1 or Jagged1 overexpression enhanced the migration, invasiveness and angiogenic ability of endothelial progenitor cells. Suppression of the Notch signaling pathway with Notch1 or Jagged1 siRNAs reduced the migratory capacity, invasiveness and angiogenic ability of endo-thelial progenitor cells. Activation of the Notch signaling pathwayin vivo in a rat model of mild traumatic brain injury promoted neurovascular repair. These ifndings suggest that the activation of the Notch signaling pathway promotes blood vessel formation and tissue repair after brain trauma.

  20. Classroom Activities to Engage Students and Promote Critical Thinking about Genetic Regulation of Bacterial Quorum Sensing

    Directory of Open Access Journals (Sweden)

    Kimberly Aebli


    Full Text Available We developed an interactive activity to mimic bacterial quorum sensing, and a classroom worksheet to promote critical thinking about genetic regulation of the lux operon. The interactive quorum sensing activity engages students and provides a direct visualization of how population density functions to influence light production in bacteria. The worksheet activity consists of practice problems that require students to apply basic knowledge of the lux operon in order to make predictions about genetic complementation experiments, and students must evaluate how genetic mutations in the lux operon affect gene expression and overall phenotype. The worksheet promotes critical thinking and problem solving skills, and emphasizes the roles of diffusible signaling molecules, regulatory proteins, and structural proteins in quorum sensing.

  1. Policies to promote on physical activity and healthy eating in kindergartens from theory to practice

    DEFF Research Database (Denmark)

    Mikkelsen, Bent Egberg


    Accumulating evidence shows that there seems to be a relation between the existence of a policy and at least some health behaviours of children. The purpose of this paper is to give a brief account of the value of policy as a tool that can be used at local level to guide action to promote healthy...... lifestyle in kindergartens. A policy can be defi ned as a set of adopted principles that guide the work of an organization and aim to achieve a well defi ned goal, but only policies that rely on the active participation and involvement of concerned actors will be effi cient. A number of studies suggest...... that local level policy on nutrition and on physical activity seems to have the potential to work as a good frame for the organizational efforts that the kindergarten undertakes in order to promote healthy eating and physical activity among children in kindergarten. However, kindergartens need to make...

  2. T-cell activation promotes tumorigenesis in inflammation-associated cancer

    Directory of Open Access Journals (Sweden)

    Lairmore Michael


    Full Text Available Abstract Chronic inflammation has long been associated with a wide range of malignancies, is now widely accepted as a risk factor for development of cancer, and has been implicated as a promoter of a variety of cancers including hematopoietic malignancies. We have described a mouse model uniquely suited to examine the link between inflammation and lymphoma in which the Tax oncogene, expressed in activated T and NK cells, perpetuates chronic inflammation that begins as microscopic intraepithelial lesions and develops into inflammatory nodules, subcutaneous tumors, and large granular lymphocytic leukemia. The use of bioluminescent imaging in these mice has expanded our ability to interrogate aspects of inflammation and tumorigenesis non-invasively. Here we demonstrate that bioluminescence induction in these mice correlated with inflammation resulting from wounding, T cell activation, and exposure to chemical agents. In experiments in which long-term effects of inflammation on disease outcome were monitored, the development of lymphoma was promoted by an inflammatory stimulus. Finally we demonstrated that activation of T-cells in T-cell receptor (TCR transgenic TAX-LUC animals dramatically exacerbated the development of subcutaneous TCR- CD16+ LGL tumors. The role of activated T-cells and acquired immunity in inflammation-associated cancers is broadly applicable to hematopoietic malignancies, and we propose these mice will be of use in dissecting mechanisms by which activated T-cells promote lymphomagenesis in vivo.

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

    Directory of Open Access Journals (Sweden)

    Geense Wytske W


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

  4. Promoter discrimination at class I MarA regulon promoters mediated by glutamic acid 89 of the MarA transcriptional activator of Escherichia coli. (United States)

    Martin, Robert G; Rosner, Judah L


    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.

  5. Oncogenic and tumor-promoting Spermatophytes and Pteridophytes and their active principles. (United States)

    Farnsworth, N R; Bingel, A S; Fong, H H; Saleh, A A; Christenson, G M; Saufferer, S M


    A survey and discussion are presented of plants classified as Spermatophyta and Pteridophyta, extracts of which have been shown to be oncogenic or tumor-promoting in animals. The active oncogenic and tumor-promoting principles, where known, have been identified. They represent tannins; pyrrolizidine, indole, tropolone, quinoline, purine, and benzophenanthridine alkaloids; nitroso compounds; triterpene glycosides; lignans; isoflavans; allyl benzenoids; simple (nu-pyrenes; and carbocyclic hydroxy acids. A total of 28 compounds of known structure have been identified as oncogens and several phorbol esters as tumor-promoters. Plants known to contain any of the 28 oncogens (excluding shikimic acid and caffeine) have been tabulated; they represent at least 454 species, 110 genera, and 34 families of Spermatophyta and Pteridophyta.

  6. Swimming Upstream: Faculty and Staff Members From Urban Middle Schools in Low-Income Communities Describe Their Experience Implementing Nutrition and Physical Activity Initiatives

    Directory of Open Access Journals (Sweden)

    Katherine W. Bauer, SM


    Full Text Available Introduction Addressing childhood overweight has become a top priority in the United States. Modification of school policies and practices has been used in an attempt to address the overweight epidemic among children and adolescents. Culturally diverse urban schools in low-income communities attempting to improve nutrition and increase physical activity may face unique challenges in the school environment. A better understanding is needed about school environments and how they may affect the implementation, efficacy, and sustainability of initiatives designed to improve nutrition and physical activity. Methods We carried out a qualitative study in five urban middle schools in low-income communities that had recently implemented Planet Health, a nutrition and physical activity intervention, to assess which aspects of the schools’ physical, social, and policy environments were facilitating or impeding the implementation of health promotion initiatives. Thirty-five faculty and staff members participated. We conducted one focus group per school, with an average of seven participants per group. We analyzed focus group transcripts using the thematic analysis technique to identify key concepts, categories, and themes. Results Teachers and staff members in our study identified many school-related environmental barriers to successful implementation of nutrition and physical activity initiatives in their schools. School personnel recommended that classroom-based nutrition interventions such as Planet Health be coordinated with school food services so that the healthy messages taught in the classroom are reinforced by the availability of healthy, culturally appropriate cafeteria food. They identified household food insufficiency and overly restrictive eligibility criteria of the federally subsidized meal program as critical barriers to healthy nutritional behaviors. They also identified weight-related teasing and bullying and unhealthy weight

  7. Physical activity and capacity at initiation of antiretroviral treatment in HIV patients in Ethiopia

    DEFF Research Database (Denmark)

    Olsen, Mette Frahm; Kæstel, Pernille; Tesfaye, M


    SUMMARY We described levels of habitual physical activity and physical capacity in HIV patients initiating antiretroviral treatment in Ethiopia and assessed the role of HIV and nutritional indicators on these outcomes. Physical activity energy expenditure (PAEE) and activity levels were measured...... with combined heart rate and movement sensors. Physical capacity was assessed by grip strength, sleeping heart rate and heart rate economy. Grip strength data was also available from a sex- and age-matched HIV-negative reference group. Median PAEE was 27·9 (interquartile range 17·4-39·8) kJ/kg per day and mean......±s.d. grip strength was 23·6 ± 6·7 kg. Advanced HIV disease predicted reduced levels of both physical activity and capacity; e.g. each unit viral load [log(1+copies/ml)] was associated with -15% PAEE (P

  8. Interventions to promote physical activity in older people with type 2 diabetes mellitus: A systematic review

    Directory of Open Access Journals (Sweden)

    Sazlina eShariff-Ghazali


    Full Text Available Introduction: Type 2 diabetes mellitus (T2DM among people aged 60 years and above is a growing public health problem. Regular physical activity is one of the key elements in the management of T2DM. Recommendations suggest that older people with T2DM will benefit from regular physical activity for better disease control and delaying complications. Despite the known benefits, many remain sedentary. Hence, this review assessed interventions for promoting physical activity in persons aged 65 years and older with type 2 diabetes mellitus. Methods: A literature search was conducted using OvidMEDLINE, PubMed, EMBASE, SPORTDiscus and CINAHL databases to retrieve articles published between January 2000 and December 2012. Randomised controlled trials and quasi-experimental designs comparing different strategies to increase physical activity level in persons aged 65 years and older with T2DM were included. The methodological quality of studies was assessed.Results: Twenty-one eligible studies were reviewed, only six studies were rated as good quality and only one study specifically targeted persons aged 65 years and older. Personalised coaching, goal setting, peer support groups, use of technology and physical activity monitors were proven to increase the level of physical activity. Incorporation of health behaviour theories and follow-up supports also were successful strategies. However, the methodological quality and type of interventions promoting physical activity of the included studies in this review varied widely across the eligible studies.Conclusion: Strategies that increased level of physical activity in persons with T2DM are evident but most studies focused on middle-aged persons and there was a lack of well-designed trials. Hence, more studies of satisfactory methodological quality with interventions promoting physical activity in older people are required.

  9. The effectiveness of active travel initiatives in Irish provincial towns: an evaluation of a quasi-experimental natural experiment


    Lambe, Barry


    Ireland is a car dependent country with low levels of active travel and also low levels of total physical activity. There is a paucity of studies, internationally, that have evaluated active travel initiatives in a real world setting. This thesis contributes new knowledge to the evidence base on the implementation, effectiveness and design of active travel initiatives at the community level and their impact on physical activity. This thesis is comprised of a series of quasi-experimental de...

  10. Sympathetic nervous system promotes hepatocarcinogenesis by modulating inflammation through activation of alpha1-adrenergic receptors of Kupffer cells. (United States)

    Huan, Hong-Bo; Wen, Xu-Dong; Chen, Xue-Jiao; Wu, Lin; Wu, Li-Li; Zhang, Liang; Yang, Da-Peng; Zhang, Xia; Bie, Ping; Qian, Cheng; Xia, Feng


    The sympathetic nervous system (SNS) is known to play a significant role in tumor initiation and metastasis. Hepatocellular carcinoma (HCC) frequently occurs in cirrhotic livers after chronic inflammation, and the SNS is hyperactive in advanced liver cirrhosis. However, it remains unclear whether the SNS promotes hepatocarcinogenesis by modulating chronic liver inflammation. In this study, a retrospective pathological analysis and quantification of sympathetic nerve fiber densities (tyrosine hydroxylase, TH(+)) in HCC patients, and diethylnitrosamine (DEN)-induced hepatocarcinogenesis in rats were performed. Our data showed that high density of sympathetic nerve fibers and α1-adrenergic receptors (ARs) of Kupffer cells (KCs) were associated with a poor prognosis of HCC. Sympathetic denervation or blocking of α1-ARs decreased DEN-induced HCC incidence and tumor development. In addition, synergistic effects of interleukin-6 (IL-6) and transforming growth factor-beta (TGF-β) in hepatocarcinogenesis were observed. The suppression of the SNS reduced IL-6 and TGF-β expression, which suppressed hepatocarcinogenesis, and KCs play a key role in this process. After the ablation of KCs, IL-6 and TGF-β expression and the development of HCC were inhibited. This study demonstrates that sympathetic innervation is crucial for hepatocarcinogenesis and that the SNS promotes hepatocarcinogenesis by activating α1-ARs of KCs to boost the activation of KCs and to maintain the inflammatory microenvironment. These results indicate that sympathetic denervation or α1-ARs blockage may represent novel treatment approaches for HCC.

  11. Thiazolidinediones Promote Axonal Growth through the Activation of the JNK Pathway (United States)

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


    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

  12. Using Paid Radio Advertisements to Promote Physical Activity Among Arkansas Tweens

    Directory of Open Access Journals (Sweden)

    Appathurai Balamurugan, MD, MPH


    Full Text Available Introduction The level of physical activity among children is a growing concern. Evidence shows that many children aged 9 to 13 years (tweens do not participate in any organized physical activity during their nonschool hours, and some do not engage in any free-time physical activity. Physical inactivity is associated with a host of chronic diseases such as diabetes and cardiovascular disease. Paid media advertisements have been an effective method of promoting physical activity. Methods From March 10, 2003, through June 29, 2003, we aired paid radio advertisements in six major Arkansas metropolitan areas to promote physical activity among tweens. In September 2003, we surveyed 295 Arkansas tweens by telephone to assess their exposure to the advertisements and the impact of the advertisements on their intent to participate in physical activity. In the same telephone survey, we also asked questions about the respondents’ physical activity level. The data were weighted so that the results would be representative of the areas surveyed. The statistical analysis was performed using SPSS, version 11.5 (SPSS Inc, Chicago, Ill. Results Of the tweens surveyed, 56.4% (95% confidence interval [CI], 50.7%–62.1% reported hearing the radio advertisements. Of the tweens who heard the advertisement messages, 76.1% (95% CI, 69.4%–82.8% said the messages made them more likely to get involved in physical activity. Younger tweens (aged 9 and 10 years were less likely to have heard the advertisements than older tweens (aged 11 to 13 years. However, the advertisements were more likely to cause younger tweens to want to get involved in physical activity (odds ratio [OR] = 6.89, P = .003 than older tweens. Of the tweens surveyed, 74.9% (95% CI, 70.0%–79.8% reported that they were involved in nonschool-sponsored sports, and 45.3% (95% CI, 39.6%–51.0% were involved in school-sponsored sports. Conclusion Paid media advertisements may be an effective way to

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

    Directory of Open Access Journals (Sweden)

    Janine E. Trempy


    Full Text Available 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.

  14. Promoting social skills of mexican high school students through virtual activities in the Moodle platform

    Directory of Open Access Journals (Sweden)



    Full Text Available With the intention of promoting social skills of Mexican high school students based on the graduate profile of this level, virtual activities were implemented in the Moodle platform to 169 students of second year, adopting the proposed Goldstein social skills. In order to establish the impact of these activities to a pretest-postest a one group design was used. The results show that the activities had a positive and significant impact in beginning social skills, advanced social skills, skills for dealing with feeling, social alternatives skills of the participants according to the results obtained by skills scale social Goldstein.

  15. Functional and Activity Analysis of Cattle UCP3 Promoter with MRFs-Related Factors

    Directory of Open Access Journals (Sweden)

    Wei Chen


    Full Text Available Uncoupling protein 3 (UCP3 is mainly expressed in muscle. It plays an important role in muscle, but less research on the regulation of cattle UCP3 has been performed. In order to elucidate whether cattle UCP3 can be regulated by muscle-related factors, deletion of cattle UCP3 promoter was amplified and cloned into pGL3-basic, pGL3-promoter and PEGFP-N3 vector, respectively, then transfected into C2C12 myoblasts cells and UCP3 promoter activity was measured using the dual-Luciferase reporter assay system. The results showed that there is some negative-regulatory element from −620 to −433 bp, and there is some positive-regulatory element between −433 and −385 bp. The fragment (1.08 kb of UCP3 promoter was cotransfected with muscle-related transcription factor myogenic regulatory factors (MRFs and myocyte-specific enhancer factor 2A (MEF2A. We found that UCP3 promoter could be upregulated by Myf5, Myf6 and MyoD and downregulated by MyoG and MEF2A.

  16. SfDredd, a Novel Initiator Caspase Possessing Activity on Effector Caspase Substrates in Spodoptera frugiperda. (United States)

    Yang, Zhouning; Zhou, Ke; Liu, Hao; Wu, Andong; Mei, Long; Liu, Qingzhen


    Sf9, a cell line derived from Spodoptera frugiperda, is an ideal model organism for studying insect apoptosis. The first notable study that attempted to identify the apoptotic pathway in Sf9 was performed in 1997 and included the discovery of Sf-caspase-1, an effector caspase of Sf9. However, it was not until 2013 that the first initiator caspase in Sf9, SfDronc, was discovered, and the apoptotic pathway in Sf9 became clearer. In this study, we report another caspase of Sf9, SfDredd. SfDredd is highly similar to insect initiator caspase Dredd homologs. Experimentally, recombinant SfDredd underwent autocleavage and exhibited different efficiencies in cleavage of synthetic caspase substrates. This was attributed to its caspase activity for the predicted active site mutation blocked the above autocleavage and synthetic caspase substrates cleavage activity. SfDredd was capable of not only cleaving Sf-caspase-1 in vitro but also cleaving Sf-caspase-1 and inducing apoptosis when it was co-expressed with Sf-caspase-1 in Sf9 cells. The protein level of SfDredd was increased when Sf9 cells were treated by Actinomycin D, whereas silencing of SfDredd reduced apoptosis and Sf-caspase-1 cleavage induced by Actinomycin D treatment. These results clearly indicate that SfDredd functioned as an apoptotic initiator caspase. Apoptosis induced in Sf9 cells by overexpression of SfDredd alone was not as obvious as that induced by SfDronc alone, and the cleavage sites of Sf-caspase-1 for SfDredd and SfDronc are different. In addition, despite sharing a sequence homology with initiator caspases and possessing weak activity on initiator caspase substrates, SfDredd showed strong activity on effector caspase substrates, making it the only insect caspase reported so far functioning similar to human caspase-2 in this aspect. We believe that the discovery of SfDredd, and its different properties from SfDronc, will improve the understanding of apoptosis pathway in Sf9 cells.

  17. SfDredd, a Novel Initiator Caspase Possessing Activity on Effector Caspase Substrates in Spodoptera frugiperda.

    Directory of Open Access Journals (Sweden)

    Zhouning Yang

    Full Text Available Sf9, a cell line derived from Spodoptera frugiperda, is an ideal model organism for studying insect apoptosis. The first notable study that attempted to identify the apoptotic pathway in Sf9 was performed in 1997 and included the discovery of Sf-caspase-1, an effector caspase of Sf9. However, it was not until 2013 that the first initiator caspase in Sf9, SfDronc, was discovered, and the apoptotic pathway in Sf9 became clearer. In this study, we report another caspase of Sf9, SfDredd. SfDredd is highly similar to insect initiator caspase Dredd homologs. Experimentally, recombinant SfDredd underwent autocleavage and exhibited different efficiencies in cleavage of synthetic caspase substrates. This was attributed to its caspase activity for the predicted active site mutation blocked the above autocleavage and synthetic caspase substrates cleavage activity. SfDredd was capable of not only cleaving Sf-caspase-1 in vitro but also cleaving Sf-caspase-1 and inducing apoptosis when it was co-expressed with Sf-caspase-1 in Sf9 cells. The protein level of SfDredd was increased when Sf9 cells were treated by Actinomycin D, whereas silencing of SfDredd reduced apoptosis and Sf-caspase-1 cleavage induced by Actinomycin D treatment. These results clearly indicate that SfDredd functioned as an apoptotic initiator caspase. Apoptosis induced in Sf9 cells by overexpression of SfDredd alone was not as obvious as that induced by SfDronc alone, and the cleavage sites of Sf-caspase-1 for SfDredd and SfDronc are different. In addition, despite sharing a sequence homology with initiator caspases and possessing weak activity on initiator caspase substrates, SfDredd showed strong activity on effector caspase substrates, making it the only insect caspase reported so far functioning similar to human caspase-2 in this aspect. We believe that the discovery of SfDredd, and its different properties from SfDronc, will improve the understanding of apoptosis pathway in Sf9 cells.

  18. Diffusing a Research-based Physical Activity Promotion Program for Seniors Into Diverse Communities: CHAMPS III

    Directory of Open Access Journals (Sweden)

    Anita L. Stewart, PhD


    Full Text Available Introduction Increasing the physical activity levels of older adults through diffusion of successful research-based programs into community settings is challenging because of differences between research and real-world settings. This project diffused the Community Healthy Activities Model Program for Seniors (CHAMPS II, an individual-level research-based physical activity promotion program, through three community organizations to reach lower-income and minority (primarily Hispanic or Latino and African American seniors. Methods Through an academic–community partnership, university staff worked with each organization to adapt the program to be appealing and effective, enable their staff and volunteers to provide the program, increase participants’ physical activity, and leave sustainable programs in place. Evaluation was based on methods recommended by the Centers for Disease Control and Prevention. Results The adapted programs, referred to as CHAMPS III, differed from the original program and among organizations. Group-based components and resource guides were included and new features were added; however, individualized components were not offered because of limited resources. A total of 321 people enrolled among three organizations; there was a trend toward increased physical activity at two organizations (an estimated increase of 481 kcal/week [P = .08] and 437 kcal/week [P = .06] expended in physical activity. Evaluation revealed challenges and unexpected community-level benefits. All organizations are continuing efforts to promote physical activity for older adults. Conclusion This project enabled community organizations to implement physical activity promotion programs. The overarching challenge was to retain original program features within each organization’s resources yet be sustainable. Although the programs differed from the original research program, they were a catalyst for numerous community-level changes. Our findings can

  19. Union Activities to promote cooperative activities at enterprise level: workplace assesment

    DEFF Research Database (Denmark)

    Jensen, Per Langå; Høy, Jette


    An analysis of the information activities on workplace assessment from a major Danish confederation......An analysis of the information activities on workplace assessment from a major Danish confederation...

  20. Evaluation methods for physical activity-promoting mobile technologies: an interdisciplinary scoping review

    Directory of Open Access Journals (Sweden)

    Claire McCallum


    Full Text Available There are many thousands of mobile apps, wearables and other technologies available to support and promote physical activity. However, the rapidly evolving nature of these technologies means that the methodologies traditionally used to evaluate the effectiveness of behaviour change interventions (such as the randomised controlled trial may not be appropriate to evaluate their effectiveness. A scoping review was conducted to identify the methods currently being used to evaluate physical activity-promoting mobile technologies across health and computing science disciplines. In addition to the range of methods used, the review explored their strengths and weaknesses. The results improve understandings of when and why to use existing methods from health and computing science. Opportunities for combining and hybridising methods across the two disciplines are also identified. The review will be used to inform the development and piloting of novel, ‘fit-for-purpose’ research designs that will allow rigorous evaluation of the effectiveness of rapidly-evolving physical activity-promoting mobile technologies and their ‘active ingredients’ to build an evidence base of what works, why and for whom.

  1. Engagement of membrane immunoglobulin enhances Id3 promoter activity in WEHI-231 B lymphoma cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-jun LI; Kikumi HATA; Junichiro MIZUGUCHI


    Aim: We have recently shown that engagement of membrane immunoglobulin (mIg) induced upregulation of inhibitor of differentiation 3 (Id3) mRNA, resulting in growth arrest at G1 phase in WEHI-231 cells. In the present study, we examined whether engagement of mIg will affect promoter activity of the Id3 gene in WEHI231 cells. Methods: DNA fragments corresponding to the 5′-flanking region of mId3 gene were amplified by polymerase chain reaction (PCR) using genomic DNA as the template. Three DNA fragments upstream of the transcription start site (+ 1) of the mId3 gene were subcloned into the luciferase reporter vector PGVB2. The recombinant constructs were transiently transfected into WEHI-231 cells by an electroporation method. After incubation for 24 h, WEHI-231 cells were stimulated with 10 mg/L anti-IgM or irradiated CD40L-expressing NIH3T3 cells or control NIH3T3 cells for further 24 h, followed by assay for luciferase activity. Results: The luciferase analysis demonstrated that basal promoter activity of the Id3 gene was found in the region between -200 and +54. The Id3 promoter activity was increased 2-fold following stimulation with anti-IgM, but not CD40L, compared with medium alone. Conclusion: The mIg-mediated upregulation of Id3 expression is controlled, at least in part, through transcriptional regulation, as assessed by luciferase assay.

  2. TLR4 activation promotes podocyte injury and interstitial fibrosis in diabetic nephropathy.

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    Jin Ma

    Full Text Available Toll like receptor (TLR 4 has been reported to promote inflammation in diabetic nephropathy. However the role of TLR4 in the complicated pathophysiology of diabetic nephropathy is not understood. In this study, we report elevated expression of TLR4, its endogenous ligands and downstream cytokines, chemokines and fibrogenic genes in diabetic nephropathy in WT mice with streptozotocin (STZ diabetes. Subsequently, we demonstrated that TLR4-/- mice were protected against the development of diabetic nephropathy, exhibiting less albuminuria, inflammation, glomerular hypertrophy and hypercellularity, podocyte and tubular injury as compared to diabetic wild-type controls. Marked reductions in interstitial collagen deposition, myofibroblast activation (α-SMA and expression of fibrogenic genes (TGF-β and fibronectin were also evident in TLR4 deficient mice. Consistent with our in vivo results, high glucose directly promoted TLR4 activation in podocytes and tubular epithelial cells in vitro, resulting in NF-κB activation and consequent inflammatory and fibrogenic responses. Our data indicate that TLR4 activation may promote inflammation, podocyte and tubular epithelial cell injury and interstitial fibrosis, suggesting TLR4 is a potential therapeutic target for diabetic nephropathy.

  3. Dietary cholesterol promotes AOM-induced colorectal cancer through activating the NLRP3 inflammasome. (United States)

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


    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.

  4. Genetic variants in ABCA1 promoter affect transcription activity and plasma HDL level in pigs. (United States)

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


    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.

  5. LncSox4 promotes the self-renewal of liver tumour-initiating cells through Stat3-mediated Sox4 expression (United States)

    Chen, Zhen-zhen; Huang, Lan; Wu, Ya-hong; Zhai, Wen-jie; Zhu, Ping-ping; Gao, Yan-feng


    Liver cancer has a tendency to develop asymptomatically in patients, so most patients are diagnosed at a later stage. Accumulating evidence implicates that liver tumour-initiating cells (TICs) as being responsible for liver cancer initiation and recurrence. However, the molecular mechanism of liver TIC self-renewal is poorly understood. Here we discover that a long noncoding RNA (lncRNA) termed LncSox4 is highly expressed in hepatocellular carcinoma (HCC) tissues and in liver TICs. We find that LncSox4 is required for liver TIC self-renewal and tumour initiation. LncSox4 interacts with and recruits Stat3 to the Sox4 promoter to initiate the expression of Sox4, which is highly expressed in liver TICs and required for liver TIC self-renewal. The expression level of Sox4 correlates with HCC development, clinical severity and prognosis of patients. Altogether, we find that LncSox4 is highly expressed in liver TICs and is required for their self-renewal. PMID:27553854

  6. DIXDC1 activates the Wnt signaling pathway and promotes gastric cancer cell invasion and metastasis. (United States)

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


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, Darrion L. [Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064 (United States); DiMario, Joseph X., E-mail: [Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064 (United States)


    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.

  8. Using formative research to develop CHANGE!: a curriculum-based physical activity promoting intervention

    Directory of Open Access Journals (Sweden)

    Knowles Zoe R


    Full Text Available Abstract Background Low childhood physical activity levels are currently one of the most pressing public health concerns. Numerous school-based physical activity interventions have been conducted with varied success. Identifying effective child-based physical activity interventions are warranted. The purpose of this formative study was to elicit subjective views of children, their parents, and teachers about physical activity to inform the design of the CHANGE! (Children's Health, Activity, and Nutrition: Get Educated! intervention programme. Methods Semi-structured mixed-gender interviews (group and individual were conducted in 11 primary schools, stratified by socioeconomic status, with 60 children aged 9-10 years (24 boys, 36 girls, 33 parents (4 male, 29 female and 10 teachers (4 male, 6 female. Questions for interviews were structured around the PRECEDE stage of the PRECEDE-PROCEDE model and addressed knowledge, attitudes and beliefs towards physical activity, as well as views on barriers to participation. All data were transcribed verbatim. Pen profiles were constructed from the transcripts in a deductive manner using the Youth Physical Activity Promotion Model framework. The profiles represented analysis outcomes via a diagram of key emergent themes. Results Analyses revealed an understanding of the relationship between physical activity and health, although some children had limited understanding of what constitutes physical activity. Views elicited by children and parents were generally consistent. Fun, enjoyment and social support were important predictors of physical activity participation, though several barriers such as lack of parental support were identified across all group interviews. The perception of family invested time was positively linked to physical activity engagement. Conclusions Families have a powerful and important role in promoting health-enhancing behaviours. Involvement of parents and the whole family is a

  9. p21-activated Kinase1(PAK1) can promote ERK activation in a kinase independent manner

    DEFF Research Database (Denmark)

    Wang, Zhipeng; Fu, Meng; Wang, Lifeng


    204) although phosphorylation of b-Raf (Ser445) and c-Raf (Ser 338) remained unchanged. Furthermore, increased activation of the PAK1 activator Rac1 induced the formation of a triple complex of Rac1, PAK1 and Mek1, independent of the kinase activity of PAK1. These data suggest that PAK1 can stimulate...

  10. Active Gaming to Promote Physical Activity: Questions to Consider for Your School (United States)

    Meyler, Tim; Banks, Sarah; Wilson, Sandy


    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,…

  11. Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling. (United States)

    Le Gall, Sylvain M; Szabo, Roman; Lee, Melody; Kirchhofer, Daniel; Craik, Charles S; Bugge, Thomas H; Camerer, Eric


    The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.

  12. Impact of the initial tropospheric zenith path delay on precise point positioning convergence during active conditions (United States)

    Kalita, J. Z.; Rzepecka, Z.


    Tropospheric delay is one of the key factors that influence the convergence time of the precise point positioning (PPP) method. Current models do not allow for the fixing of the zenith path delay tropospheric parameter, leaving the difference between nominal and final value to the estimation process. Here, we present an analysis of several PPP result-sets using the tropospheric parameter’s nominal value adopted from models: VMF1, GPT2w, MOPS, and ZERO-WET. The last variant assumes a zero value for the initial wet part of the zenith delay. The PPP results are subtracted from a solution based on the final tropospheric product from the International GNSS Service (IGS). Several days exhibiting the most active tropospheric conditions were selected for each of the 7 stations located in the mid-latitude Central European region. During the active days, application of the VMF1 model increases the resulting height component’s quality by about 33–36% when compared to the GPT2w and MOPS. The respective improvement in VMF1 latitude and longitude components is 27% and 15%. The average relative deterioration in the result standard deviations between active and calm tropospheric conditions reaches about 20–30% of the former. We discuss the impact of the initial tropospheric parameter’s variance and bias on positioning. In addition, we compare the results with those of other studies over the impact of active tropospheric conditions on the PPP method.

  13. The H4 subunit of vaccinia virus RNA polymerase is not required for transcription initiation at a viral late promoter.


    Wright, C F; Coroneos, A M


    Chromatography of RNA polymerase purified from vaccinia virions and from vaccinia virus-infected HeLa cells resulted in the separation of populations active for early and late transcription. An RNA polymerase population immunodepleted for the vaccinia virus H4 gene peptide could support late transcription.

  14. Automatic brain cropping enhancement using active contours initialized by a PCNN (United States)

    Swathanthira Kumar, Murali Murugavel; Sullivan, John M., Jr.


    Active contours are a popular medical image segmentation strategy. However in practice, its accuracy is dependent on the initialization of the process. The PCNN (Pulse Coupled Neural Network) algorithm developed by Eckhorn to model the observed synchronization of neural assemblies in small mammals such as cats allows for segmenting regions of similar intensity but it lacks a convergence criterion. In this paper we report a novel PCNN based strategy to initialize the zero level contour for automatic brain cropping of T2 weighted MRI image volumes of Long-Evans rats. Individual 2D anatomy slices of the rat brain volume were processed by means of a PCNN and a surrogate image 'signature' was constructed for each slice. By employing a previously trained artificial neural network (ANN) an approximate PCNN iteration (binary mask) was selected. This mask was then used to initialize a region based active contour model to crop the brain region. We tested this hybrid algorithm on 30 rat brain (256*256*12) volumes and compared the results against manually cropped gold standard. The Dice and Jaccard similarity indices were used for numerical evaluation of the proposed hybrid model. The highly successful system yielded an average of 0.97 and 0.94 respectively.

  15. NASA safety program activities in support of the Space Exploration Initiatives Nuclear Propulsion program (United States)

    Sawyer, J. C., Jr.


    The activities of the joint NASA/DOE/DOD Nuclear Propulsion Program Technical Panels have been used as the basis for the current development of safety policies and requirements for the Space Exploration Initiatives (SEI) Nuclear Propulsion Technology development program. The Safety Division of the NASA Office of Safety and Mission Quality has initiated efforts to develop policies for the safe use of nuclear propulsion in space through involvement in the joint agency Nuclear Safety Policy Working Group (NSPWG), encouraged expansion of the initial policy development into proposed programmatic requirements, and suggested further expansion into the overall risk assessment and risk management process for the NASA Exploration Program. Similar efforts are underway within the Department of Energy to ensure the safe development and testing of nuclear propulsion systems on Earth. This paper describes the NASA safety policy related to requirements for the design of systems that may operate where Earth re-entry is a possibility. The expected plan of action is to support and oversee activities related to the technology development of nuclear propulsion in space, and support the overall safety and risk management program being developed for the NASA Exploration Program.

  16. Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island.

    Directory of Open Access Journals (Sweden)

    Heather M O'Hagan


    Full Text Available Chronic exposure to inducers of DNA base oxidation and single and double strand breaks contribute to tumorigenesis. In addition to the genetic changes caused by this DNA damage, such tumors often contain epigenetically silenced genes with aberrant promoter region CpG island DNA hypermethylation. We herein explore the relationships between such DNA damage and epigenetic gene silencing using an experimental model in which we induce a defined double strand break in an exogenous promoter construct of the E-cadherin CpG island, which is frequently aberrantly DNA hypermethylated in epithelial cancers. Following the onset of repair of the break, we observe recruitment to the site of damage of key proteins involved in establishing and maintaining transcriptional repression, namely SIRT1, EZH2, DNMT1, and DNMT3B, and the appearance of the silencing histone modifications, hypoacetyl H4K16, H3K9me2 and me3, and H3K27me3. Although in most cells selected after the break, DNA repair occurs faithfully with preservation of activity of the promoter, a small percentage of the plated cells demonstrate induction of heritable silencing. The chromatin around the break site in such a silent clone is enriched for most of the above silent chromatin proteins and histone marks, and the region harbors the appearance of increasing DNA methylation in the CpG island of the promoter. During the acute break, SIRT1 appears to be required for the transient recruitment of DNMT3B and subsequent methylation of the promoter in the silent clones. Taken together, our data suggest that normal repair of a DNA break can occasionally cause heritable silencing of a CpG island-containing promoter by recruitment of proteins involved in silencing. Furthermore, with contribution of the stress-related protein SIRT1, the break can lead to the onset of aberrant CpG island DNA methylation, which is frequently associated with tight gene silencing in cancer.

  17. FBI-1 enhances ETS-1 signaling activity and promotes proliferation of human colorectal carcinoma cells. (United States)

    Zhu, Min; Li, Mingyang; Zhang, Fan; Feng, Fan; Chen, Weihao; Yang, Yutao; Cui, Jiajun; Zhang, Dong; Linghu, Enqiang


    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.

  18. Flavonoids promoting HaCaT migration: I. Hologram quantitative structure-activity relationships. (United States)

    Cho, Moonjae; Yoon, Hyuk; Park, Mijoo; Kim, Young Hwa; Lim, Yoongho


    Cell migration plays an important role in multicellular development and preservation. Because wound healing requires cell migration, compounds promoting cell migration can be used for wound repair therapy. Several plant-derived polyphenols are known to promote cell migration, which improves wound healing. Previous studies of flavonoids on cell lines have focused on their inhibitory effects and not on wound healing. In addition, studies of flavonoids on wound healing have been performed using mixtures. In this study, individual flavonoids were used for cellular migration measurements. Relationships between the cell migration effects of flavonoids and their structural properties have never been reported. Here, we investigated the migration of keratinocytes caused by 100 flavonoids and examined their relationships using hologram quantitative structure-activity relationships. The structural conditions responsible for efficient cell migration on keratinocyte cell lines determined from the current study will facilitate the design of flavonoids with improved activity.

  19. FBI-1 enhances ETS-1 signaling activity and promotes proliferation of human colorectal carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Min Zhu

    Full Text Available 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.

  20. Race to the Top: evaluation of a novel performance-based financing initiative to promote healthcare delivery in rural Rwanda

    Directory of Open Access Journals (Sweden)

    Evrard Nahimana


    Full Text Available Background: Performance-based financing (PBF has demonstrated a range of successes and failures in improving health outcomes across low- and middle-income countries. Evidence indicates that the success of PBF depends, in large part, on the model selected, in relation to a variety of contextual factors. Objective: Partners In Health∣Inshuti Mu Buzima aimed to evaluate health outcomes associated with a novel capacity-building model of PBF at health centers throughout Kirehe district, Rwanda. Design: Thirteen health centers in Kirehe district, which provide healthcare to a population of over 300,000 people, agreed to participate in a PBF initiative scheme that integrated data feedback, quality improvement coaching, peer-to-peer learning, and district-level priority setting. Health centers’ progress toward collectively agreed upon site-specific health targets was assessed every 6 months for 18 months. Incentives were awarded only when health centers met goals on all three priorities health centers had collectively agreed upon: 90% coverage of community-based health insurance, 70% contraceptive prevalence rate, and zero acute severe malnutrition cases. Improvement across all four time points and facilities was measured using mixed-effects linear regression. Findings: At 6-month follow-up, 4 of 13 health centers had met 1 target. At 12-month follow-up, 7 centers had met 1 target, and by 18-month follow-up, 6 centers had met 2 targets and 2 centers had met all 3. Average health center performance had improved significantly across the district for all three targets: mean insurance coverage increased from 68% at baseline to 93% (p<0.001; mean number of acute malnutrition cases in the previous 6 months declined from 24 to 5 per facility (p<0.001; and contraceptive prevalence increased from 42 to 59% (p<0.001. A number of innovative improvement initiatives were identified. Conclusion: The combining of PBF, district engagement/support, and peer

  1. 主动结点启动的可靠多播通信%Active-Node-Initiated Reliable Multicast

    Institute of Scientific and Technical Information of China (English)

    蔡洪斌; 周明天; 杨国纬


    Sender-initiated and receiver-initiated reliable multicast protocols can suffer performance degradation as increasing the number of receivers. New technology and new service of active network would resolve the problem of the scalable and reliable multicast. The paper presents an Active-Node-Initiated Reliable Multicast (ANIRM)protocol. The protocol, which guarantees the data packet to transport correctly form active node to active node,shifts the burden of providing reliable data transfer to active nodes and receivers. Theoretical analysis shows that ANIRM proposed here is,comparing with the traditional network protocol,better for bandwidth and data recovery delay.

  2. Role Modeling Attitudes, Physical Activity and Fitness Promoting Behaviors of Prospective Physical Education Specialists and Non-Specialists. (United States)

    Cardinal, Bradley J.; Cardinal, Marita K.


    Compared the role modeling attitudes and physical activity and fitness promoting behaviors of undergraduate students majoring in physical education and in elementary education. Student teacher surveys indicated that physical education majors had more positive attitudes toward role modeling physical activity and fitness promoting behaviors and…

  3. Pleiotropic β-Agonist–Promoted Receptor Conformations and Signals Independent of Intrinsic Activity



    β-Agonists used for treatment of obstructive lung disease have a variety of different structures but are typically classified by their intrinsic activities for stimulation of cAMP, and predictions are made concerning other downstream signals based on such a classification. We generated modified β2-adrenergic receptors with insertions of energy donor and acceptor moieties to monitor agonist-promoted conformational changes of the receptor using intramolecular bioluminescence resonance energy tr...

  4. The effectiveness of an intervention promoting physical activity in elemantary school children


    Verstraete, S


    Regular physical activity (PA) is an important component of a healthfully lifestyle in children and adolescents. The main purpose of this dissertation was to evaluate the effectiveness of a comprehensive PA promotion intervention in elementary school children. Furthermore, the effectiveness of some of the intervention components was evaluated. Sixteen elementary schools participated in the intervention study. They were randomly assigned to the intervention (n = 8) and control condition (n = 8...

  5. Feasibility, acceptability, and initial efficacy of an online sexual health promotion program for LGBT youth: the Queer Sex Ed intervention. (United States)

    Mustanski, Brian; Greene, George J; Ryan, Daniel; Whitton, Sarah W


    Lesbian, gay, bisexual, and transgender (LGBT) youth experience multiple sexual health inequities driven, in part, by deficits in parental and peer support, school-based sex education programs, and community services. Research suggests that the Internet may be an important resource in the development of sexual health among LGBT youth. We examined the feasibility of recruiting youth in same-sex relationships into an online sexual health intervention, evaluated intervention acceptability, and obtained initial estimates of intervention efficacy. LGBT youth (16 to 20 years old) completed Queer Sex Ed (QSE), an online, multimedia sexual health intervention consisting of five modules. The final sample (N = 202) completed the pretest, intervention, and posttest assessments. The primary study outcomes were sexual orientation identity and self-acceptance (e.g., coming-out self-efficacy), sexual health knowledge (e.g., sexual functioning), relationship variables (e.g., communication skills), and safer sex (e.g., sexual assertiveness). Analyses indicated that 15 of the 17 outcomes were found to be significant (p LGBT youth.

  6. Canadian Society for Exercise Physiology position stand: Benefit and risk for promoting childhood physical activity. (United States)

    Longmuir, Patricia E; Colley, Rachel C; Wherley, Valerie A; Tremblay, Mark S


    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.

  7. KNL1 facilitates phosphorylation of outer kinetochore proteins by promoting Aurora B kinase activity. (United States)

    Caldas, Gina V; DeLuca, Keith F; DeLuca, Jennifer G


    Aurora B kinase phosphorylates kinetochore proteins during early mitosis, increasing kinetochore–microtubule (MT) turnover and preventing premature stabilization of kinetochore–MT attachments. Phosphorylation of kinetochore proteins during late mitosis is low, promoting attachment stabilization, which is required for anaphase onset. The kinetochore protein KNL1 recruits Aurora B–counteracting phosphatases and the Aurora B–targeting factor Bub1, yet the consequences of KNL1 depletion on Aurora B phospho-regulation remain unknown. Here, we demonstrate that the KNL1 N terminus is essential for Aurora B activity at kinetochores. This region of KNL1 is also required for Bub1 kinase activity at kinetochores, suggesting that KNL1 promotes Aurora B activity through Bub1-mediated Aurora B targeting. However, ectopic targeting of Aurora B to kinetochores does not fully rescue Aurora B activity in KNL1-depleted cells, suggesting KNL1 influences Aurora B activity through an additional pathway. Our findings establish KNL1 as a requirement for Aurora B activity at kinetochores and for wild-type kinetochore–MT attachment dynamics.

  8. Tumor suppressor protein C53 antagonizes checkpoint kinases to promote cyclin-dependent kinase 1 activation. (United States)

    Jiang, Hai; Wu, Jianchun; He, Chen; Yang, Wending; Li, Honglin


    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.

  9. Tumor suppressor protein C53 antagonizes checkpoint kinases to promote cyclin-dependent kinase 1 activation

    Institute of Scientific and Technical Information of China (English)

    Hai Jiang; Jianchun Wu; Chen He; Wending Yang; Honglin Li


    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-kB 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 Cdkl 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 Chkl 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. Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain. (United States)

    Gibson, Erin M; Purger, David; Mount, Christopher W; Goldstein, Andrea K; Lin, Grant L; Wood, Lauren S; Inema, Ingrid; Miller, Sarah E; Bieri, Gregor; Zuchero, J Bradley; Barres, Ben A; Woo, Pamelyn J; Vogel, Hannes; Monje, Michelle


    Myelination of the central nervous system requires the generation of functionally mature oligodendrocytes from oligodendrocyte precursor cells (OPCs). Electrically active neurons may influence OPC function and selectively instruct myelination of an active neural circuit. In this work, we use optogenetic stimulation of the premotor cortex in awake, behaving mice to demonstrate that neuronal activity elicits a mitogenic response of neural progenitor cells and OPCs, promotes oligodendrogenesis, and increases myelination within the deep layers of the premotor cortex and subcortical white matter. We further show that this neuronal activity-regulated oligodendrogenesis and myelination is associated with improved motor function of the corresponding limb. Oligodendrogenesis and myelination appear necessary for the observed functional improvement, as epigenetic blockade of oligodendrocyte differentiation and myelin changes prevents the activity-regulated behavioral improvement.

  11. Promoting Physical Activity With Group Pictures. Affiliation-Based Visual Communication for High-Risk Populations. (United States)

    Reifegerste, Doreen; Rossmann, Constanze


    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.

  12. The human papillomavirus (HPV) E6 oncoproteins promotes nuclear localization of active caspase 8

    Energy Technology Data Exchange (ETDEWEB)

    Manzo-Merino, Joaquin [Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, México/Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México. Av. San Fernando No. 22, Col. Sección XVI, Tlalpan 14080 (Mexico); Massimi, Paola [International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34149 Trieste (Italy); Lizano, Marcela, E-mail: [Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, México/Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México. Av. San Fernando No. 22, Col. Sección XVI, Tlalpan 14080 (Mexico); Banks, Lawrence, E-mail: [International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34149 Trieste (Italy)


    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.

  13. Effect of environmental estrogens on IL-1beta promoter activity in a macrophage cell line. (United States)

    Ruh, M F; Bi, Y; Cox, L; Berk, D; Howlett, A C; Bellone, C J


    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

  14. Identification of a small molecule activator of novel PKCs for promoting glucose-dependent insulin secretion

    Institute of Scientific and Technical Information of China (English)

    Shuai Han; Heling Pan; Jianhua Zhang; Li Tan; Dawei Ma; Junying Yuan; Jia-Rui Wu


    Using an image-based screen for small molecules that can affect Golgi morphology, we identify a small molecule,Sioc145, which can enlarge the Golgi compartments and promote protein secretion. More importantly, Siocl45 potentiates insulin secretion in a glucose-dependent manner. We show that Sioc145 selectively activates novel protein kinase Cs (nPKCs; δ and ε) but not conventional PKCs;cPKCs; a, βI and βll) in INS-1E insulinoma cells. In contrast, PMA, a non-selective activator of cPKCs and nPKCs, promotes insulin secretion independent of glucose concentrations. Furthermore, we demonstrate that Sioc145 and PMA show differential abilities in depolarizing the cell membrane, and suggest that Sioc145 promotes insulin secretion in the amplifying pathway downstream of K ATp channels. In pancreatic islets, the treatment with Sioc145 enhances the second phase of insulin secretion. Increased insulin granules close to the plasma membrane are observed after Sioc145 treatment. Finally, the administration of Sioc145 to diabetic GK rats increases their serum insulin levels and improves glucose tolerance. Collectively, our studies identify Sioc145 as a novel glucose-dependent insulinotropic compound via selectively activating nPKCs.

  15. Sevoflurane preconditioning induced endogenous neurogenesis against ischemic brain injury by promoting microglial activation. (United States)

    Li, Li; Saiyin, Hexige; Xie, Jingmo; Ma, Lixiang; Xue, Lei; Wang, Wei; Liang, Weimin; Yu, Qiong


    Brain ischemia causes irreversible damage to functional neurons in cases of infarct. Promoting endogenous neurogenesis to replace necrotic neurons is a promising therapeutic strategy for ischemia patients. The neuroprotective role of sevoflurane preconditioning implies that it might also enhance endogenous neurogenesis and functional restoration in the infarct region. By using a transient middle cerebral artery occlusion (tMCAO) model, we discovered that endogenous neurogenesis was enhanced by sevoflurane preconditioning. This enhancement process is characterized by the promotion of neuroblast proliferation within the subventricular zone (SVZ), migration and differentiation into neurons, and the presence of astrocytes and oligodendrocytes at the site of infarct. The newborn neurons in the sevoflurane preconditioning group showed miniature excitatory postsynaptic currents (mEPSCs), increased synaptophysin and PSD95 staining density, indicating normal neuronal function. Furthermore, long-term behavioral improvement was observed in the sevoflurane preconditioning group consistent with endogenous neurogenesis. Further histological analyses showed that sevoflurane preconditioning accelerated microglial activation, including migration, phagocytosis and secretion of brain-derived neurotrophic factor (BDNF). Intraperitoneal injection of minocycline, a microglial inhibitor, suppressed microglial activation and reversed neurogenesis. Our data showed that sevoflurane preconditioning promoted microglial activities, created a favorable microenvironment for endogenous neurogenesis and accelerated functional reconstruction in the infarct region.

  16. ATPase activity tightly regulates RecA nucleofilaments to promote homologous recombination (United States)

    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


    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

  17. CD147 promotes melanoma progression through hypoxia-induced MMP2 activation. (United States)

    Zeng, W; Su, J; Wu, L; Yang, D; Long, T; Li, D; Kuang, Y; Li, J; Qi, M; Zhang, J; Chen, X


    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.

  18. Partnering with School Nutrition Professionals to Promote Fruit and Vegetable Intake through Taste-Testing Activities (United States)

    Cirignano, Sherri M.; Hughes, Luanne J.; Wu-Jung, Corey J.; Morgan, Kathleen; Grenci, Alexandra; Savoca, LeeAnne


    The Healthy, Hunger-Free Kids Act (HHFKA) of 2010 sets new nutrition standards for schools, requiring them to serve a greater variety and quantity of fruits and vegetables. Extension educators in New Jersey partnered with school nutrition professionals to implement a school wellness initiative that included taste-testing activities to support…

  19. Quality of Life Assessment for Physical Activity and Health Promotion: Further Psychometrics and Comparison of Measures (United States)

    Gill, Diane L.; Reifsteck, Erin J.; Adams, Melanie M.; Shang, Ya-Ting


    Despite the clear relationship between physical activity and quality of life, few sound, relevant quality of life measures exist. Gill and colleagues developed a 32-item quality of life survey, and provided initial psychometric evidence. This study further examined that quality of life survey in comparison with the widely used short form (SF-36)…

  20. MoveU? Assessing a Social Marketing Campaign to Promote Physical Activity (United States)

    Scarapicchia, Tanya M. F.; Sabiston, Catherine M. F.; Brownrigg, Michelle; Blackburn-Evans, Althea; Cressy, Jill; Robb, Janine; Faulkner, Guy E. J.


    Objective: MoveU is a social marketing initiative aimed at increasing moderate-to-vigorous physical activity (MVPA) among undergraduate students. Using the Hierarchy of Effects model (HOEM), this study identified awareness of MoveU and examined associations between awareness, outcome expectations, self-efficacy, intentions, and MVPA. Participants:…

  1. The Effect of Dietary Glycine on the Hepatic Tumor Promoting Activity of Polychlorinated Biphenyls (PCBs) in Rats


    Bunaciu, Rodica Petruta; Tharappel, Job C.; Lehmler, Hans-Joachim; Korwel, Izabela; Robertson, Larry W.; Srinivasan, Cidambi; Spear, Brett T.; Glauert, Howard P.


    Polychlorinated biphenyls (PCBs) are ubiquitious lipophilic environmental pollutants. Some of the PCB congeners and mixtures of congeners have tumor promoting activity in rat liver. The mechanism of their activity is not fully understood and is likely to be multifactorial. The aim of this study was to investigate if the resident liver macrophages, Kupffer cells, are important in the promoting activity of PCBs. The hypothesis of this study was that the inhibition of Kupffer cell activity would...

  2. Harnessing different motivational frames via mobile phones to promote daily physical activity and reduce sedentary behavior in aging adults. (United States)

    King, Abby C; Hekler, Eric B; Grieco, Lauren A; Winter, Sandra J; Sheats, Jylana L; Buman, Matthew P; Banerjee, Banny; Robinson, Thomas N; Cirimele, Jesse


    Mobile devices are a promising channel for delivering just-in-time guidance and support for improving key daily health behaviors. Despite an explosion of mobile phone applications aimed at physical activity and other health behaviors, few have been based on theoretically derived constructs and empirical evidence. Eighty adults ages 45 years and older who were insufficiently physically active, engaged in prolonged daily sitting, and were new to smartphone technology, participated in iterative design development and feasibility testing of three daily activity smartphone applications based on motivational frames drawn from behavioral science theory and evidence. An "analytically" framed custom application focused on personalized goal setting, self-monitoring, and active problem solving around barriers to behavior change. A "socially" framed custom application focused on social comparisons, norms, and support. An "affectively" framed custom application focused on operant conditioning principles of reinforcement scheduling and emotional transference to an avatar, whose movements and behaviors reflected the physical activity and sedentary levels of the user. To explore the applications' initial efficacy in changing regular physical activity and leisure-time sitting, behavioral changes were assessed across eight weeks in 68 participants using the CHAMPS physical activity questionnaire and the Australian sedentary behavior questionnaire. User acceptability of and satisfaction with the applications was explored via a post-intervention user survey. The results indicated that the three applications were sufficiently robust to significantly improve regular moderate-to-vigorous intensity physical activity and decrease leisure-time sitting during the 8-week behavioral adoption period. Acceptability of the applications was confirmed in the post-intervention surveys for this sample of midlife and older adults new to smartphone technology. Preliminary data exploring sustained use

  3. Harnessing different motivational frames via mobile phones to promote daily physical activity and reduce sedentary behavior in aging adults.

    Directory of Open Access Journals (Sweden)

    Abby C King

    Full Text Available Mobile devices are a promising channel for delivering just-in-time guidance and support for improving key daily health behaviors. Despite an explosion of mobile phone applications aimed at physical activity and other health behaviors, few have been based on theoretically derived constructs and empirical evidence. Eighty adults ages 45 years and older who were insufficiently physically active, engaged in prolonged daily sitting, and were new to smartphone technology, participated in iterative design development and feasibility testing of three daily activity smartphone applications based on motivational frames drawn from behavioral science theory and evidence. An "analytically" framed custom application focused on personalized goal setting, self-monitoring, and active problem solving around barriers to behavior change. A "socially" framed custom application focused on social comparisons, norms, and support. An "affectively" framed custom application focused on operant conditioning principles of reinforcement scheduling and emotional transference to an avatar, whose movements and behaviors reflected the physical activity and sedentary levels of the user. To explore the applications' initial efficacy in changing regular physical activity and leisure-time sitting, behavioral changes were assessed across eight weeks in 68 participants using the CHAMPS physical activity questionnaire and the Australian sedentary behavior questionnaire. User acceptability of and satisfaction with the applications was explored via a post-intervention user survey. The results indicated that the three applications were sufficiently robust to significantly improve regular moderate-to-vigorous intensity physical activity and decrease leisure-time sitting during the 8-week behavioral adoption period. Acceptability of the applications was confirmed in the post-intervention surveys for this sample of midlife and older adults new to smartphone technology. Preliminary data

  4. A cell-autonomous molecular cascade initiated by AMP-activated protein kinase represses steroidogenesis. (United States)

    Abdou, Houssein S; Bergeron, Francis; Tremblay, Jacques J


    Steroid hormones regulate essential physiological processes, and inadequate levels are associated with various pathological conditions. In testosterone-producing Leydig cells, steroidogenesis is strongly stimulated by luteinizing hormone (LH) via its receptor leading to increased cyclic AMP (cAMP) production and expression of the steroidogenic acute regulatory (STAR) protein, which is essential for the initiation of steroidogenesis. Steroidogenesis then passively decreases with the degradation of cAMP into AMP by phosphodiesterases. In this study, we show that AMP-activated protein kinase (AMPK) is activated following cAMP-to-AMP breakdown in MA-10 and MLTC-1 Leydig cells. Activated AMPK then actively inhibits cAMP-induced steroidogenesis by repressing the expression of key regulators of steroidogenesis, including Star and Nr4a1. Similar results were obtained in Y-1 adrenal cells and in the constitutively steroidogenic R2C cells. We have also determined that maximum AMPK activation following stimulation of steroidogenesis in MA-10 Leydig cells occurs when steroid hormone production has reached a plateau. Our data identify AMPK as a molecular rheostat that actively represses steroid hormone biosynthesis to preserve cellular energy homeostasis and prevent excess steroid production.

  5. Recent evidence for activity-dependent initiation of sympathetic sprouting and neuropathic pain

    Institute of Scientific and Technical Information of China (English)

    Jun-Ming ZHANG; Judith A. Strong


    Traumatic injury or inflammatory irritation of the peripheral nervous system often leads to persistent pathophysiological pain states. It has been well-documented that, after peripheral nerve injury or inflammation, functional and anatomical alterations sweep over the entire peripheral nervous system including the peripheral nerve endings, the injured or inflamed afferent fibers, the dorsal root ganglion (DRG), and the central afferent terminals in the spinal cord. Among all the changes, ectopic discharge or spontaneous activity of primary sensory neurons is of great clinical interest, as such discharges doubtless contribute to the develop-ment of pathological pain states such as neuropathic pain. Two key sources of abnormal spontaneous activity have been identified following peripheral nerve injury: the injured afferent fibers (neuroma) leading to the DRG, and the DRG somata. The purpose of this review is to provide a global account of the abnormal spontaneous activity in various animal models of pain. Particular attention is focused on the consequence of peripheral nerve injury and localized inflammation. Further, mechanisms involved in the generation of spontaneous activity are also reviewed; evidence of spontaneous activity in contributing to abnormal sympathetic sprouting in the axotomized DRG and to the initiation of neuropathic pain based on new findings from our research group are discussed. An improved understanding of the causes of spontaneous activity and the origins of neuropathic pain should facilitate the development of novel strategies for effective treatment of pathological pain.

  6. Notch pathway activation targets AML-initiating cell homeostasis and differentiation. (United States)

    Lobry, Camille; Ntziachristos, Panagiotis; Ndiaye-Lobry, Delphine; Oh, Philmo; Cimmino, Luisa; Zhu, Nan; Araldi, Elisa; Hu, Wenhuo; Freund, Jacquelyn; Abdel-Wahab, Omar; Ibrahim, Sherif; Skokos, Dimitris; Armstrong, Scott A; Levine, Ross L; Park, Christopher Y; Aifantis, Iannis


    Notch signaling pathway activation is known to contribute to the pathogenesis of a spectrum of human malignancies, including T cell leukemia. However, recent studies have implicated the Notch pathway as a tumor suppressor in myeloproliferative neoplasms and several solid tumors. Here we report a novel tumor suppressor role for Notch signaling in acute myeloid leukemia (AML) and demonstrate that Notch pathway activation could represent a therapeutic strategy in this disease. We show that Notch signaling is silenced in human AML samples, as well as in AML-initiating cells in an animal model of the disease. In vivo activation of Notch signaling using genetic Notch gain of function models or in vitro using synthetic Notch ligand induces rapid cell cycle arrest, differentiation, and apoptosis of AML-initiating cells. Moreover, we demonstrate that Notch inactivation cooperates in vivo with loss of the myeloid tumor suppressor Tet2 to induce AML-like disease. These data demonstrate a novel tumor suppressor role for Notch signaling in AML and elucidate the potential therapeutic use of Notch receptor agonists in the treatment of this devastating leukemia.

  7. Interventions for promoting physical activity among European teenagers: a systematic review

    Directory of Open Access Journals (Sweden)

    Lien Nanna


    Full Text Available Abstract Background Although physical activity is considered to yield substantial health benefits, the level of physical activity among European teenagers is not sufficient. Adolescence is characterized by a decline in physical activity level. Many studies investigated the effectiveness of interventions promoting physical activity among young people, but none dealt with the available evidence specific for Europe. This review was conducted to summarize the effectiveness of interventions to promote physical activity among European teenagers. Methods A systematic review was conducted to identify European intervention studies published in the scientific literature since 1995. Four databases were searched, reference lists were scanned and the publication lists of the authors of the retrieved articles were checked. The ANGELO framework was used to categorise the included studies by setting and by intervention components. Results The literature search identified 20 relevant studies. Fifteen interventions were delivered through the school setting, of which three included a family component and another three a family and community component. One intervention was conducted within a community setting, three were delivered in primary care and one was delivered through the internet. Ten interventions included only an individual component, whereas the other ten used a multi-component approach. None of the interventions included only an environmental component. Main findings of the review were: (1 school-based interventions generally lead to short term improvements in physical activity levels; (2 improvements in physical activity levels by school-based interventions were limited to school related physical activity with no conclusive transfer to leisure time physical activity; (3 including parents appeared to enhance school-based interventions; (4 the support of peers and the influence of direct environmental changes increased the physical activity level of

  8. Androgen signaling promotes translation of TMEFF2 in prostate cancer cells via phosphorylation of the α subunit of the translation initiation factor 2.

    Directory of Open Access Journals (Sweden)

    Ryan F Overcash

    Full Text Available The type I transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2, is expressed mainly in brain and prostate. Expression of TMEFF2 is deregulated in prostate cancer, suggesting a role in this disease, but the molecular mechanism(s involved in this effect are not clear. Although androgens promote tmeff2 transcription, androgen delivery to castrated animals carrying CWR22 xenografts increases TMEFF2 protein levels in the absence of mRNA changes, suggesting that TMEFF2 may also be post-transcriptionally regulated. Here we show that translation of TMEFF2 is regulated by androgens. Addition of physiological concentrations of dihydrotestosterone (DHT to prostate cancer cell lines increases translation of endogenous TMEFF2 or transfected TMEFF2-Luciferase fusions, and this effect requires the presence of upstream open reading frames (uORFs in the 5'-untranslated region (5'-UTR of TMEFF2. Using chemical and siRNA inhibition of the androgen receptor (AR, we show that the androgen effect on TMEFF2 translation is mediated by the AR. Importantly, DHT also promotes phosphorylation of the α subunit of the translation initiation factor 2 (eIF2α in an AR-dependent manner, paralleling the effect on TMEFF2 translation. Moreover, endoplasmic reticulum (ER stress conditions, which promote eIF2α phosphorylation, also stimulate TMEFF2 translation. These results indicate that androgen signaling promotes eIF2α phosphorylation and subsequent translation of TMEFF2 via a mechanism that requires uORFs in the 5'-UTR of TMEFF2.

  9. Activity of the truncated promoter of pollen-specific G9 gene of cotton and the transgenic recessive nuclei-sterile tobacco

    Institute of Scientific and Technical Information of China (English)


    A 557 bp fragment from the translation initiation site of the G9 gene expressed in maturing pollens of cotton was isolated from genomic DNA of upland cotton (Gossypium hirsutum L.) cv. “Zhongkang 17”, and two expression vectors for plant transformation were constructed via fusing this fragment with β-glucuronidase gene (Gus) and cytotoxin gene Barnase. The promoter activity of this fragment was demonstrated via transient expression of Gus gene in cotton and by the integrated expression of Barnase gene in tobacco. This promoter can initiate the expression of exogenous gene specifically and efficiently in plant pollen. The transgenic tobacco plant containing G9-Barnase fusion gene showed the characteristics of recessive nuclei-sterility.

  10. Endogenous activation of adenosine A1 receptors promotes post-ischemic electrocortical burst suppression

    DEFF Research Database (Denmark)

    Ilie, A; Ciocan, D; Constantinescu, A O


    . Several lines of evidence suggest that BS reflects an impairment of neocortical connectivity. Here we tested in vivo whether synaptic depression by adenosine A1 receptor (A1R) activation contributes to BS patterns following GCI. Male Wistar rats were subjected to 1, 5 or 10 min of GCI using a "four...... of post-ischemic BS patterns following brief ischemic episodes. It is likely that synaptic depression by post-ischemic A1R activation functionally disrupts the connectivity within the cortical networks to an extent that promotes BS patterns....

  11. Promoting Active Learning in Calculus and General Physics through Interactive and Media-Enhanced Lectures

    Directory of Open Access Journals (Sweden)

    Guoqing Tang


    Full Text Available In this paper we present an approach of incorporating interactive and media-enhanced lectures to promote active learning in Calculus and General Physics courses. The pedagogical practice of using interactive techniques in lectures to require "heads-on" and "hands-on" learning, and involve students more as active participants than passive receivers is a part of academic curricular reform efforts undertaken currently by the mathematics, physics and chemistry departments at North Carolina A&T State University under the NSF funded project "Talent-21: Gateway for Advancing Science and Mathematics Talents."

  12. ORM Promotes Skeletal Muscle Glycogen Accumulation via CCR5-Activated AMPK Pathway in Mice (United States)

    Qin, Zhen; Wan, Jing-Jing; Sun, Yang; Wang, Peng-Yuan; Su, Ding-Feng; Lei, Hong; Liu, Xia


    We found previously that acute phase protein orosomucoid reacts to fatigue and activates C-C chemokine receptor type 5 to increase muscle glycogen storage and enhance muscle endurance (Lei et al., 2016). To explore the underlying molecular mechanisms, we investigated the role of AMP-activated protein kinase, a critical fuel sensor in skeletal muscle, in C-C chemokine receptor type 5-mediated orosomucoid action. It was found orosomucoid increased skeletal muscle AMP-activated protein kinase activation in a time- and dose- dependent manner, which was largely prevented by pharmacological blocking or knockout of C-C chemokine receptor type 5. Administration of orosomucoid also significantly increased the de-phosphorylation and activity of muscle glycogen synthase, the rate-limiting enzyme for glycogen synthesis. The effect was largely absent in mice deficient in C-C chemokine receptor type 5−/− or AMP-activated protein kinase α2−/−, the predominant isoform in skeletal muscle. Moreover, deletion of AMP-activated protein kinase α2 abolished the effect of orosomucoid on fatigue and muscle glycogen. These findings indicate that orosomucoid may promote glycogen storage and enhance muscle function through C-C chemokine receptor type 5-mdiated activation of AMP-activated protein kinase, which in turn activates glycogen synthase and increases muscle glycogen. PMID:27679573

  13. Behaviour change interventions to promote physical activity in rheumatoid arthritis: a systematic review. (United States)

    Larkin, Louise; Gallagher, Stephen; Cramp, Fiona; Brand, Charles; Fraser, Alexander; Kennedy, Norelee


    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.

  14. Effectiveness of a grant program's efforts to promote synergy within its funded initiatives: perceptions of participants of the Southern Rural Access Program

    Directory of Open Access Journals (Sweden)

    Weiner Bryan J


    Full Text Available Abstract Background Foundations and public agencies commonly fund focused initiatives for individual grantees. These discrete, stand-alone initiatives can risk failure by being carried out in isolation. Fostering synergy among grantees' initiatives is one strategy proposed for promoting the success and impact of grant programs. We evaluate an explicit strategy to build synergy within the Robert Wood Johnson Foundation's Southern Rural Access Program (SRAP, which awarded grants to collaboratives within eight southeastern U.S. states to strengthen basic health care services in targeted rural counties. Methods We interviewed 39 key participants of the SRAP, including the program director within each state and the principal subcontractors heading the program's funded initiatives that supported heath professionals' recruitment, retention and training, made loans to health care providers, and built networks among providers. Interews were recorded and transcribed. Two investigators independently coded the transcripts and a third investigator distilled the main points. Results Participants generally perceived that the SRAP yielded more synergies than other grant programs in which they had participated and that these synergies added to the program's impact. The synergies most often noted were achieved through relationship building among grantees and with outside agencies, sharing information and know-how, sharing resources, combining efforts to yield greater capacity, joining voices to advocate for common goals, and spotting gaps in services offered and then filling these gaps. The SRAP's strategies that participants felt fostered synergy included targeting funding to culturally and geographically similar states, supporting complementary types of initiatives, promoting opportunities to network through semi-annual meetings and regular conference calls, and the advocacy efforts of the program's leadership. Participants noted that synergies were sometimes

  15. Physical Activity in Medellín: a Challenge for Health Promotion

    Directory of Open Access Journals (Sweden)

    Frank Éuler Sepúlveda


    Full Text Available Objective: chronic diseases generate high economical and social costs to humankind. The lack of physical activity has been considered as a determinant factor in the epidemics of chronic diseases nowadays. It is mandatory to explore this kind of behavior in order to outline appropriate actions for prevention and health promotion. Method: a survey on 3.979 representative people of both sexes from Medellín, Colombia was carried out evaluating attitudes and practices related to physical activity and its associated factors. The analysis included the description of proportions with their respective tests of statistical significance and different crossings with sociodemographic variables. Results: only one out of five people (21.2% performs enough physical activity in order to protect its health. Physical activity is higher among men and is positively associated to social-economic levels and education status. The sedentary behavior is usually adopted in early stages of youth and is kept throughout lifespan. Physical activity, on the contrary, is usually associated to a better balance in body composition. Conclusion: the high prevalence of sedentary behaviors in the population is probably becoming a significant factor in the increase of chronic diseases. This condition should be included as a priority in the design of strategies for the intervention in public health; furthermore, the promotion of healthy lifestyles among people becomes a big challenge to health professionals who should face it with creativity and optimism.

  16. NR2D-containing NMDA receptors mediate tissue plasminogen activator-promoted neuronal excitotoxicity. (United States)

    Baron, A; Montagne, A; Cassé, F; Launay, S; Maubert, E; Ali, C; Vivien, D


    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.

  17. Recommendations for Promoting Physical Activity for Children and Adolescents in Germany. A Consensus Statement

    Directory of Open Access Journals (Sweden)

    Christine Graf


    Full Text Available Increasing physical activity and reduction of sedentary behaviour play important roles in health promotion and prevention of lifestyle-related diseases in children and adolescents. However, the question of how much physical activity is useful for which target group is still a matter of debate. International guidelines (World Health Organization; European Association for the Study of Obesity, which are mainly based on expert opinions, recommend 60 min of physical activity every day. Age- and sex-specific features and regional differences are not taken into account. Therefore, expert consensus recommendations for promoting physical activity of children and adolescents in Germany were developed with special respect to national data, but also with respect to aspects of specific target groups, e.g., children with a lower socio-economic status (SES or with migration background. They propose 90 min/day of physical activity, or at least 12,000 steps daily. Additionally, lifestyle factors, especially restriction of media consumption, were integrated. The recommendations provide orientation for parents and caregivers, for institutions such as schools and kindergartens as well as for communities and stakeholders.

  18. The regulation of the SARK promoter activity by hormones and environmental signals. (United States)

    Delatorre, Carla A; Cohen, Yuval; Liu, Li; Peleg, Zvi; Blumwald, Eduardo


    The Senescence Associated Receptor Protein Kinase (P(SARK)) promoter, fused to isopentenyltransferase (IPT) gene has been shown to promote drought tolerance in crops. We dissected P(SARK) in order to understand the various elements associated with its activation and suppression. The activity of P(SARK) was higher in mature and early senescing leaves, and abiotic stress induced its activity in mature leaves. Bioinformatics analysis suggests the interactions of multiple cis-acting elements in the control of P(SARK) activity. In vitro gel shift assays and yeast one hybrid system revealed interactions of P(SARK) with transcription factors related to abscisic acid and cytokinin response. Deletion analysis of P(SARK), fused to GUS-reporter gene was used to identify specific regions regulating transcription under senescence or during drought stress. Effects of exogenous hormonal treatments were characterized in entire plants and in leaf disk assays, and regions responsive to various hormones were defined. Our results indicate a complex interaction of plant hormones and additional factors modulating P(SARK) activity under stress resulting in a transient induction of expression.

  19. Direct interaction of Sox10 with the promoter of murine Dopachrome Tautomerase (Dct) and synergistic activation of Dct expression with Mitf. (United States)

    Jiao, Zhongxian; Mollaaghababa, Ramin; Pavan, William J; Antonellis, Anthony; Green, Eric D; Hornyak, Thomas J


    The murine dopachrome tautomerase (Dct) gene is expressed early in melanocyte development during embryogenesis, prior to other members of the tyrosinase gene family important for regulating pigmentation. We have used deletion mutants of the Dct promoter, transfections with developmentally relevant transcription factors, and gel shift assays to define transcriptional determinants of Dct expression. Deletion mutagenesis studies show that sequences within the proximal 459 nucleotides are critical for high level expression in melanocytic cells. This region of the promoter contains candidate binding sites for the transcription factors Sox10 and Mitf. Transfections into 293T and NIH3T3 cells show that Sox10 and Mitf independently activate Dct expression, and, when co-transfected, synergistically activate Dct expression. To support the notion that Sox10 acts directly upon the Dct promoter to activate gene expression, direct interaction of Sox10 was demonstrated using gel shifts of oligonucleotide probes derived from promoter sequences within the region required for Sox10-dependent induction. These results suggest that a combinatorial transcription factor interaction is important for expression of Dct in neural crest-derived melanocytes, and support a model for sequential gene activation in melanocyte development whereby Mitf, a Sox10-dependent transcription factor, is expressed initially before an early melanocyte differentiation gene, Dct, is expressed.

  20. Antibiofilm activity of Bacillus pumilus SW9 against initial biofouling on microfiltration membranes. (United States)

    Zhang, Ying; Yu, Xin; Gong, Song; Ye, Chengsong; Fan, Zihong; Lin, Huirong


    Membrane biofouling, resulting from biofilm formation on the membrane, has become the main obstacle hindering wider application of membrane technology. Initial biofouling proves to be crucial which involves early stages of microbial adhesion and biofilm formation. Biological control of microbial attachment seems to be a promising strategy due to its high efficiency and eco-friendliness. The present study investigated the effects of a bacterium Bacillus pumilus SW9 on controlling the initial fouling formed by four target bacterial strains which were pioneer species responsible for biofouling in membrane bioreactors, using microfiltration membranes as the abiotic surfaces. The results suggested that strain SW9 exhibited excellent antibiofilm activity by decreasing the attached biomass of target strains. The production of extracellular polysaccharides and proteins by four target strains was also reduced. A distinct improvement of permeate flux in dead-end filtration systems was achieved when introducing strain SW9 to microfiltration experiments. Scanning electron microscopy and confocal laser scanning microscopy were performed to further ascertain significant changes of the biofouling layers. A link between biofilm inhibition and initial biofouling mitigation was thus provided, suggesting an alternatively potential way to control membrane biofouling through bacterial interactions.