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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

    1977-01-01

    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.

  2. EXPERIENCES WITH IDEA PROMOTING INITIATIVES

    DEFF Research Database (Denmark)

    Gish, Liv

    2011-01-01

    to idea work. Furthermore I look into what makes these initiatives ‘work’ or ‘not work’. The analysis builds on an in-depth case study made in Grundfos based on 40 interviews with R&D professionals and managers. The managerial implications of the study are that managers should be aware of what......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...

  3. Core promoter-specific gene regulation: TATA box selectivity and Initiator-dependent bi-directionality of serum response factor-activated transcription.

    Science.gov (United States)

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

    2016-04-01

    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.

  4. A NF-κB-dependent dual promoter-enhancer initiates the lipopolysaccharide-mediated transcriptional activation of the chicken lysozyme in macrophages.

    Science.gov (United States)

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

    2013-01-01

    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.

  5. Hypoxia-inducible factor 1α promotes primary tumor growth and tumor-initiating cell activity in breast cancer

    OpenAIRE

    Schwab, Luciana P; Peacock, Danielle L.; Majumdar, Debeshi; Ingels, Jesse F; Jensen, Laura C; Smith, Keisha D; Cushing, Richard C; Seagroves, Tiffany N

    2012-01-01

    Introduction Overexpression of the oxygen-responsive transcription factor hypoxia-inducible factor 1α (HIF-1α) correlates with poor prognosis in breast cancer patients. The mouse mammary tumor virus polyoma virus middle T (MMTV-PyMT) mouse is a widely utilized preclinical mouse model that resembles human luminal breast cancer and is highly metastatic. Prior studies in which the PyMT model was used demonstrated that HIF-1α is essential to promoting carcinoma onset and lung metastasis, although...

  6. Exploring Australian health promotion and environmental sustainability initiatives.

    Science.gov (United States)

    Patrick, Rebecca; Kingsley, Jonathan

    2016-04-01

    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. PMID:26650394

  7. Exploring Australian health promotion and environmental sustainability initiatives.

    Science.gov (United States)

    Patrick, Rebecca; Kingsley, Jonathan

    2016-04-01

    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.

  8. Activated KRAS Cooperates with MLL-AF4 to Promote Extramedullary Engraftment and Migration of Cord Blood CD34+ HSPC But Is Insufficient to Initiate Leukemia.

    Science.gov (United States)

    Prieto, Cristina; Stam, Ronald W; Agraz-Doblas, Antonio; Ballerini, Paola; Camos, Mireia; Castaño, Julio; Marschalek, Rolf; Bursen, Aldeheid; Varela, Ignacio; Bueno, Clara; Menendez, Pablo

    2016-04-15

    The MLL-AF4 (MA4) fusion gene is the genetic hallmark of an aggressive infant pro-B-acute lymphoblastic leukemia (B-ALL). Our understanding of MA4-mediated transformation is very limited. Whole-genome sequencing studies revealed a silent mutational landscape, which contradicts the aggressive clinical outcome of this hematologic malignancy. Only RAS mutations were recurrently detected in patients and found to be associated with poorer outcome. The absence of MA4-driven B-ALL models further questions whether MA4 acts as a single oncogenic driver or requires cooperating mutations to manifest a malignant phenotype. We explored whether KRAS activation cooperates with MA4 to initiate leukemia in cord blood-derived CD34(+) hematopoietic stem/progenitor cells (HSPC). Clonogenic and differentiation/proliferation assays demonstrated that KRAS activation does not cooperate with MA4 to immortalize CD34(+) HSPCs. Intrabone marrow transplantation into immunodeficient mice further showed that MA4 and KRAS(G12V) alone or in combination enhanced hematopoietic repopulation without impairing myeloid-lymphoid differentiation, and that mutated KRAS did not cooperate with MA4 to initiate leukemia. However, KRAS activation enhanced extramedullary hematopoiesis of MA4-expressing cell lines and CD34(+) HSPCs that was associated with leukocytosis and central nervous system infiltration, both hallmarks of infant t(4;11)(+) B-ALL. Transcriptional profiling of MA4-expressing patients supported a cell migration gene signature underlying the mutant KRAS-mediated phenotype. Collectively, our findings demonstrate that KRAS affects the homeostasis of MA4-expressing HSPCs, suggesting that KRAS activation in MA4(+) B-ALL is important for tumor maintenance rather than initiation. Cancer Res; 76(8); 2478-89. ©2016 AACR. PMID:26837759

  9. Regulation of Drosophila Adh promoter switching by an initiator-targeted repression mechanism.

    Science.gov (United States)

    Ren, B; Maniatis, T

    1998-01-01

    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

  10. Two tobacco AP1-like gene promoters with highly specific, tightly regulated and uniquely expressed activity during floral transition, initiation and development

    Science.gov (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...

  11. Initial transcribed sequence mutations specifically affect promoter escape properties.

    Science.gov (United States)

    Hsu, Lilian M; Cobb, Ingrid M; Ozmore, Jillian R; Khoo, Maureen; Nahm, Grace; Xia, Lulin; Bao, Yeran; Ahn, Colette

    2006-07-25

    Promoter escape efficiency of E. coli RNA polymerase is guided by both the core promoter and the initial transcribed sequence (ITS). Here, we quantitatively examined the escape properties of 43 random initial sequence variants of the phage T5 N25 promoter. The position for promoter escape on all N25-ITS variants occurred at the +15/+16 juncture, unlike the +11/+12 juncture for the wild type N25. These variants further exhibited a 25-fold difference in escape efficiency. ITS changes favoring promoter escape showed a compositional bias that is unrelated to nucleotide substrate binding affinity for the initial positions. Comparing all variants, the natural N25 promoter emerges as having evolved an ITS optimal for promoter escape, giving a high level of productive synthesis after undergoing the shortest abortive program. We supplemented GreB to transcription reactions to better understand abortive initiation and promoter escape in vivo. GreB supplementation elevated productive RNA synthesis 2-5-fold by altering the abortive RNA pattern, decreasing the abundance of the medium (6-10 nt) to long (11-15 nt) abortive RNAs without changing the levels of short (2-5 nt) and very long abortive RNAs (16-20 nt). The GreB-refractive nature of short abortive RNA production may reflect a minimum length requirement of 4-5 bp of the RNA-DNA hybrid for maintaining the stability of initial or backtracked complexes. That the very long abortive RNAs are unaffected by GreB suggests that they are unlikely to be products of polymerase backtracking. How the ITS might influence the course of early transcription is discussed within the structural context of an initial transcribing complex. PMID:16846227

  12. 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

    Energy Technology Data Exchange (ETDEWEB)

    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: tmudit@email.gwu.edu [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)

    2015-09-15

    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.

  13. 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

    International Nuclear Information System (INIS)

    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

  14. Evaluating Maori community initiatives to promote healthy eating, healthy action.

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

    2014-03-01

    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.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Mammalian transcriptomes are complex and formed by extensive promoter activity. In addition, gene promoters are largely divergent and initiate transcription of reverse-oriented promoter upstream transcripts (PROMPTs). Although PROMPTs are commonly terminated early, influenced by polyadenylation...... 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...... formation, but owing to polyadenylation site constraints, these transcripts tend to spread into the neighboring mRNA on the same strand. This mechanism to derive new alternative mRNA transcription start sites (TSSs) is also evident at closely spaced promoters supporting convergent mRNA transcription. We...

  16. 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.

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    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

    2010-03-01

    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

  17. The Importance of the United Nations Guidelines for the Long-Term Sustainability of Space Activities and Other International Initiatives to Promote Space Sustainability

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    Laura Delgado López

    2014-12-01

    Full Text Available The long-term sustainability of space activities is an emerging issue to which actors in the global space community –including governments, agencies, and industry– are devoting increasing amounts of attention and resources. Considering the sustainability of space activities involves taking into account the present population of space debris, the size of the debris population in the most commonly-used Earth orbits in the future, and the possibility of collision events between objects in space. Addressing space debris and other threats to space sustainability involves both technological and political solutions. The United Nations Committee on the Peaceful Uses of Outer Space (copuos has led a major effort to define such solutions and has established a working group tasked with the development of non-binding long-term sustainability (lts guidelines. This article includes an overview of the concept of space sustainability, a discussion of the need, development, and current status of the lts guidelines, as well as an analysis of some of the guidelines themselves. It concludes with a broader discussion of space as an area without state sovereignty – one of the key aspects that have influenced the development of non-binding measures to address the space sustainability challenge. In this context, and given the governance questions that arise from the interaction between states and non-state actors in this domain, this discussion should be of interest to international relations scholars and practitioners.

  18. United States policy initiatives in promoting the RERTR program

    International Nuclear Information System (INIS)

    The Reduced Enrichment for Research and Test Reactors (RERTR) program has been successful in furthering efforts to reduce and eventually eliminate highly enriched uranium (HEU) from international commerce. Three key policy initiatives are underway to further promote the RERTR program. The first initiative is implementation of a new nuclear weapons nonproliferation policy concerning foreign research reactor spent nuclear fuel. Under this policy, the United States will accept over the next 13 years research reactor spent fuel from 41 countries that have converted or plan to convert to use LEU fuels. The second initiative is to pursue cooperative efforts to expand the RERTR program to new regions of the globe, including Russia and China. The third initiative is to restart the advanced LEU fuels development program at the Argonne National Laboratory in order to increase the number of reactors that can convert to use LEU without significant detriment to their performance

  19. State Initiatives to Promote Technological Innovation and Economic Growth. Postsecondary Education Research Reports.

    Science.gov (United States)

    Breslin, Janice

    Activities undertaken by 43 states including Maryland to promote technological innovation and economic growth and the impact of these activities are identified. Implications for Maryland are also noted in a brief section of recommendations. State initiatives include: sponsoring research and development at colleges and companies, improving the…

  20. International energy-promotion-activities

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-01

    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.

  1. Astronomy Olympiad: An Initiative To Promote Astronomy Education In Nepal

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    Bhattarai, Suresh

    2015-08-01

    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.

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

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    Jacob Daniela

    2005-06-01

    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.

  3. PROMOTION OF EMPLOYMENT AMONG YOUTH – REMARKS FOR NEXT INITIATIVES

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    VLADIMIR MODRAK

    2011-01-01

    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.

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

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    S. Kannan

    2009-01-01

    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

  5. Promotion marketing activities in universities

    OpenAIRE

    Guseva I.B.; Ledentcova E.A.

    2014-01-01

    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.

  6. THE PROMOTIONAL ACTIVITY IN THE TOURISTIC SECTOR

    Directory of Open Access Journals (Sweden)

    Costel Iliuta Negricea

    2008-05-01

    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.

  7. Public Relations as Promotional Activity

    Directory of Open Access Journals (Sweden)

    Almira CURRI-MEMETI

    2011-11-01

    Full Text Available Public relations give opportunity to the organization to present its image and personality to its own “public”- users, supporters, sponsors, donors, local community and other public.It is about transferring the message to the public, but that is a twoway street. You must communicate with your public, but at the same time you must give opportunity to the public to communicate easier with you. The real public relations include dialog – you should listen to the others, to see things through their perspective. This elaborate is made with the purpose to be useful for every organization, not for the sensational promotion of its achievements, but to become more critical towards its work. Seeing the organization in the way that the other see it, you can become better and sure that you are giving to your users the best service possible.

  8. Evaluation of Results from Sales Promotion Activities

    OpenAIRE

    Olimpia Ban

    2007-01-01

    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.

  9. Promoting physical activity in socially vulnerable groups

    NARCIS (Netherlands)

    Herens, M.C.

    2016-01-01

    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

  10. Promoting Physical Activity among Underserved Populations.

    Science.gov (United States)

    Mendoza-Vasconez, Andrea S; Linke, Sarah; Muñoz, Mario; Pekmezi, Dori; Ainsworth, Cole; Cano, Mayra; Williams, Victoria; Marcus, Bess H; Larsen, Britta A

    2016-01-01

    Underserved populations, including racial/ethnic minorities, individuals with low socioeconomic status, and individuals with physical disabilities, are less likely to engage in sufficient moderate to vigorous physical activity (MVPA) and are thus at increased risk of morbidity and mortality. These populations face unique challenges to engaging in MVPA. Learning how to overcome these challenges is a necessary first step in achieving health equity through health promotion research. In this review of the literature, we discuss issues and strategies that have been used to promote MVPA among individuals from underserved populations, focusing on recruitment, intervention delivery, and the use of technology in interventions. Physical activity promotion research among these vulnerable populations is scarce. Nevertheless, there is preliminary evidence of efficacy in the use of certain recruitment and intervention strategies including tailoring, cultural adaptation, incorporation of new technologies, and multilevel and community-based approaches for physical activity promotion among different underserved populations. PMID:27399827

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

    Directory of Open Access Journals (Sweden)

    Williams Nefyn H

    2008-06-01

    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

  12. Promoting physical activity in socially vulnerable groups

    OpenAIRE

    Herens, M.C.

    2016-01-01

    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 supported by the Dutch government’s policy. Although many strategies have been developed to increase physical activity levels in general and in socially vulnerable groups in particular, most evaluations show o...

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

    Science.gov (United States)

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

    2015-01-01

    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

  14. 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.

  15. Evaluation of Results from Sales Promotion Activities

    Directory of Open Access Journals (Sweden)

    Olimpia Ban

    2007-02-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Eugene L. Chia

    2016-01-01

    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.

  17. Civil Wrongs: Federal Equity Initiative Promotes Paperwork, Not Equality

    Science.gov (United States)

    Melnick, R. Shep

    2016-01-01

    In October 2014, U.S. secretary of education Arne Duncan announced the Obama administration's new "education equity initiative," explaining that the president could not "continue to wait" for Congress to act "on behalf of vulnerable children." The centerpiece of this initiative was a 37-page "Dear Colleague"…

  18. Promoting Global Initiatives and Cross-Cultural Understanding in China

    Science.gov (United States)

    Brand, Susan Trostle; Snodgress, Faye

    2012-01-01

    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 to…

  19. Promoting Physical Activity during Early Childhood

    Science.gov (United States)

    Vidoni, Carla; Ignico, Arlene

    2011-01-01

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

  20. Evaluating School Travel Initiatives and Promoting "Healthy Travel" through PSHCE

    Science.gov (United States)

    Baslington, Hazel

    2010-01-01

    The number of primary school children travelling to school by car in the UK has almost doubled from 22% to 43% in 20 years. A governmental policy response is school travel plans (STPs). This paper reports the findings of an empirical evaluation designed to measure the effectiveness of the travel initiative at three schools. Quantitative and…

  1. Promoting Arab and Israeli cooperation: peacebuilding through health initiatives.

    Science.gov (United States)

    Skinner, Harvey; Abdeen, Ziad; Abdeen, Hani; Aber, Phil; Al-Masri, Mohammad; Attias, Joseph; Avraham, Karen B; Carmi, Rivka; Chalin, Catherine; El Nasser, Ziad; Hijazi, Manaf; Jebara, Rema Othman; Kanaan, Moien; Pratt, Hillel; Raad, Firas; Roth, Yehudah; Williams, A Paul; Noyek, Arnold

    This article describes a positive experience in building Arab and Israeli cooperation through health initiatives. Over the past 10 years Israeli, Jordanian, and Palestinian health professionals have worked together through the Canada International Scientific Exchange Program (CISEPO). In the initial project, nearly 17,000 Arab and Israeli newborn babies were tested for early detection of hearing loss, an important health issue for the region. The network has grown to address additional needs, including mother-child health, nutrition, infectious diseases, and youth health. Our guiding model emphasises two goals: project-specific outcomes in health improvement, and broader effects on cross-border cooperation. Lessons learned from this experience and the model provide direction for ways that health professionals can contribute to peacebuilding. PMID:15811462

  2. Regional initiatives to promote economic development in north East Asia

    OpenAIRE

    Nijkamp, P.; Wiegmans, B.W.

    1996-01-01

    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...

  3. THE CONTROL AND EVALUATION OF PROMOTIONAL ACTIVITIES

    Directory of Open Access Journals (Sweden)

    Felicia Sabou

    2012-01-01

    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.

  4. Solar Eruptions Initiated in Sigmoidal Active Regions

    Science.gov (United States)

    Savcheva, Antonia

    2016-07-01

    active regions that have been shown to possess high probability for eruption. They present a direct evidence of the existence of flux ropes in the corona prior to the impulsive phase of eruptions. In order to gain insight into their eruptive behavior and how they get destabilized we need to know their 3D magnetic field structure. First, we review some recent observations and modeling of sigmoidal active regions as the primary hosts of solar eruptions, which can also be used as useful laboratories for studying these phenomena. Then, we concentrate on the analysis of observations and highly data-constrained non-linear force-free field (NLFFF) models over the lifetime of several sigmoidal active regions, where we have captured their magnetic field structure around the times of major flares. We present the topology analysis of a couple of sigmoidal regions pointing us to the probable sites of reconnection. A scenario for eruption is put forward by this analysis. We demonstrate the use of this topology analysis to reconcile the observed eruption features with the standard flare model. Finally, we show a glimpse of how such a NLFFF model of an erupting region can be used to initiate a CME in a global MHD code in an unprecedented realistic manner. Such simulations can show the effects of solar transients on the near-Earth environment and solar system space weather.

  5. Metabolic, autophagic, and mitophagic activities in cancer initiation and progression.

    Science.gov (United States)

    Hjelmeland, Anita; Zhang, Jianhua

    2016-04-01

    Cancer is a complex disease marked by uncontrolled cell growth and invasion. These processes are driven by the accumulation of genetic and epigenetic alterations that promote cancer initiation and progression. Contributing to genome changes are the regulation of oxidative stress and reactive species-induced damage to molecules and organelles. Redox regulation, metabolic plasticity, autophagy, and mitophagy play important and interactive roles in cancer hallmarks including sustained proliferation, activated invasion, and replicative immortality. However, the impact of these processes can differ depending on the signaling pathways altered in cancer, tumor type, tumor stage, and/or the differentiation state. Here, we highlight some of the representative studies on the impact of oxidative and nitrosative activities, mitochondrial bioenergetics, metabolism, and autophagy and mitophagy in the context of tumorigenesis. We discuss the implications of these processes for cellular activities in cancer for anti-cancer-based therapeutics. PMID:27372165

  6. Loyalty Card Promotional Activity in Budget Hotel

    OpenAIRE

    Teng, Fei

    2010-01-01

    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...

  7. Kinetics model for initiation and promotion for describing tumor prevalence from HZE radiation

    Science.gov (United States)

    Cucinotta, Francis A.; Wilson, John W.

    1994-01-01

    A kinetics model for cellular repair and misrepair for multiple radiation-induced lesions (mutation-inactivation) is coupled to a two-mutation model of initiation and promotion in tissue to provide a parametric description of tumor prevalence in the Harderian gland in a mouse. Dose-response curves are described for gamma-rays and relativistic ions. The effects of nuclear fragmentation are also considered for high-energy proton and alpha particle exposures The model described provides a parametric description of age-dependent cancer induction for a wide range of radiation fields. We also consider the two hypotheses that radiation acts either solely as an initiator or as both initiator and promoter and make model calculations for fractionation exposures from gamma-rays and relativistic Fe ions. For fractionated Fe exposures, an inverse dose-rate effect is provided by a promotion hypothesis using a mutation rate for promotion typical of single-gene mutations.

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

    OpenAIRE

    Hossein Matlabi; Abdolreza Shaghaghi; Shahriar Amiri

    2014-01-01

    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 t...

  9. PARP activation promotes nuclear AID accumulation in lymphoma cells.

    Science.gov (United States)

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

    2016-03-15

    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.

  10. PROMOTION OF ACTIVE MEASURES AND EMPLOYMENT STIMULATION

    Directory of Open Access Journals (Sweden)

    LAVINIA ELISABETA POPP

    2012-01-01

    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.

  11. The Sulfolobus initiator element is an important contributor to promoter strength.

    Science.gov (United States)

    Ao, Xiang; Li, Yingjun; Wang, Fan; Feng, Mingxia; Lin, Yanxu; Zhao, Shumiao; Liang, Yunxiang; Peng, Nan

    2013-11-01

    Basal elements in archaeal promoters, except for putative initiator elements encompassing transcription start sites, are well characterized. Here, we employed the Sulfolobus araS promoter as a model to study the function of the initiator element (Inr) in archaea. We have provided evidence for the presence of a third core promoter element, the Sulfolobus Inr, whose action depends on a TATA box and the TFB recognition element (BRE). Substitution mutations in the araS Inr did not alter the location of the transcription start site. Using systematic mutagenesis, the most functional araS Inr was defined as +1 GAGAMK +6 (where M is A/C and K is G/T). Furthermore, WebLogo analysis of a subset of promoters with coding sequences for 5' untranslated regions (UTRs) larger than 4 nucleotides (nt) in Sulfolobus solfataricus P2 identified an Inr consensus that exactly matches the functional araS Inr sequence. Moreover, mutagenesis of 3 randomly selected promoters confirmed the Inr sequences to be important for basal promoter strength in the subgroup. Importantly, the result of the araS Inr being added to the Inr-less promoters indicates that the araS Inr, the core promoter element, is able to enhance the strength of Inr-less promoters. We infer that transcription factor B (TFB) and subunits of RNA polymerase bind the Inr to enhance promoter strength. Taken together, our data suggest that the presence or absence of an Inr on basal promoters is important for global gene regulation in Sulfolobus. PMID:24039266

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

    OpenAIRE

    Eugene L. Chia; Kalame Fobissie; Markku Kanninen

    2016-01-01

    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 ex...

  13. Neutrophils Are Required for 3-Methylcholanthrene-Initiated, Butylated Hydroxytoluene-Promoted Lung Carcinogenesis

    OpenAIRE

    Vikis, Haris G.; Gelman, Andrew E.; Franklin, Andrew; Stein, Lauren; Rymaszewski, Amy; Zhu, Jihong; Liu, Pengyuan; Tichelaar, Jay W.; Krupnick, Alexander S.; You, Ming

    2011-01-01

    Multiple studies have shown a link between chronic inflammation and lung tumorigenesis. Inbred mouse strains vary in their susceptibility to methylcholanthrene (MCA)-initiated butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated whether neutrophils play a role in strain dependent differences in susceptibility to lung tumor promotion. We observed a significant elevation in homeostatic levels of neutrophils in the lungs of tumor-susceptible BALB/cByJ...

  14. Chemo-preventive effect of Star anise in N-nitrosodiethylamine initiated and phenobarbital promoted hepato-carcinogenesis.

    Science.gov (United States)

    Yadav, Amit Singh; Bhatnagar, D

    2007-09-20

    The generation of free radicals is a cause of many pathological conditions like diabetes mellitus, cancer, stroke, etc. Free radicals cause damage to cellular DNA and initiate carcinogenesis. Free radicals also bring about proliferation of cells via cell signaling. An inverse relationship between the consumption of vegetable diets and the risk of cancer has been established. In the present study, Star anise (Illicium verum), which is a commonly used condiment in Indian cuisine, was assessed for its anti-carcinogenic potential in N-nitrosodiethylamine (NDEA) initiated and phenobarbital (PB) promoted hepato-carcinogenesis. Rats were randomly selected for eight experimental groups. The carcinogenesis was induced by injecting the rats, with a single dose of NDEA (200mg/kg body weight) intraperitoneally as initiator, followed by promotion with PB (0.05%) in drinking water for 14 consecutive weeks. The treatment with NDEA increased liver weight, while Star anise (Star) treatment reduced the liver weight of rats. The treatment with Star throughout for 20 weeks or during the promotion stage (6-20 weeks) significantly reduced the nodule incidence and nodule multiplicity in the rats, while the treatment with Star at the initiation phase (first 4 weeks) only could not reduce these parameters. The treatment with Star for 20 consecutive weeks significantly reduced the nodule size and nodule volume. The treatment with Star throughout as well as at the promotion stage lowered the lipid peroxidation (LPO) in liver and erythrocytes, while the LPO was not lowered, when Star was administered during initiation stage only. The treatment with Star restored the liver and erythrocyte super-oxide dismutase (SOD) activities to normal in the carcinogenesis-induced rats. The liver catalase (CAT) activity increased in all the treated groups. The erythrocyte CAT activity increased in the rats treated with Star during initiation and promotion stage only. The liver glutathione (GSH) level

  15. Nutrition Education Initiative: A School-Based Program to Promote Healthy Eating Practices of Preadolescents

    Science.gov (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.

    2009-01-01

    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…

  16. Human mediator subunit MED15 promotes transcriptional activation.

    Science.gov (United States)

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

    2014-10-01

    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.

  17. Mechanistic aspects of initiation and promotion in C3H/10T1/2 cells.

    Science.gov (United States)

    Boreiko, C J

    1985-01-01

    The transformation of C3H/10T1/2 cells can be made to proceed through discrete stages of initiation and promotion. Studies of the effect of cell density upon focus formation in cultures treated with MNNG and TPA suggest that initiation by MNNG is due to a relatively infrequent, irreversible event induced by a single carcinogen treatment. In contrast, promotion appears to be a reversible process requiring multiple treatments with TPA over a protracted period of time. Some evidence suggests that promotion may entail the induction of phenotypic changes which impart a growth advantage to phenotypically unstable "initiated" cell populations. The actual cellular mechanism(s) for most of the phenomena observed in C3H/10T1/2 cultures have eluded precise definition and widely divergent hypotheses have been advanced to explain transformation, initiation, and promotion. Conceivably there are multiple mechanisms responsible for each of these phenomenon. Some agents may transform by a multistage mechanism whereas others may exert their effects in a more direct fashion. Some of the foci produced by promotion may be the result of simple selective processes, others the product of more complex inductive events. Variations would thus be expected between laboratories working with different protocols and agents. As demonstrated by the possible involvement of an MCA residue in transformation, it is also apparent that fundamental technical aspects of this conceptually simple cell transformation system are poorly understood. While it is natural to develop mechanistic models based on quantitative observations of transformation, a limited understanding of the basic cell culture variables which modulate both the induction and expression of transformation dictate that caution be exercised in extrapolating the significance of such models to in vivo carcinogenesis. PMID:4053071

  18. Dynamical analysis on gene activity in the presence of repressors and an interfering promoter.

    Science.gov (United States)

    Nakanishi, Hiizu; Mitarai, Namiko; Sneppen, Kim

    2008-11-01

    Transcription is regulated through interplay among transcription factors, an RNA polymerase (RNAP), and a promoter. Even for a simple repressive transcription factor that disturbs promoter activity at initial binding of RNAP, its repression level is not determined solely by the dissociation constant of transcription factor but is sensitive to timescales of processes in RNAP. We first analyze the promoter activity under strong repression by a slow binding repressor, in which case transcription events occur in bursts, followed by long quiescent periods while a repressor binds to the operator; the number of transcription events, bursting, and quiescent times are estimated by reaction rates. We then examine interference effect from an opposing promoter, using the correlation function of initiation events for a single promoter. The interference is shown to de-repress the promoter because RNAPs from the opposing promoter most likely encounter the repressor and remove it in case of strong repression. This de-repression mechanism should be especially prominent for the promoters that facilitate fast formation of open complex with the repressor whose binding rate is slower than approximately 1/s. Finally, we discuss possibility of this mechanism for high activity of promoter PR in the hyp-mutant of lambda-phage. PMID:18658208

  19. Promoting physical activity in persons with subacute spinal cord injury

    NARCIS (Netherlands)

    C.F.J. Nooijen (Carla)

    2015-01-01

    markdownabstractAbstract Introduction: After discharge from inpatient rehabilitation, physical activity levels in persons with spinal cord injury (SCI) are known to decline. Primary objective: To evaluate the added value of a behavioral intervention promoting an active lifestyle after discharge

  20. The initiatives of a library association for the promotion of grey literature

    OpenAIRE

    Alberani, V; De Castro Pietrangeli, P. (ISS); GreyNet, Grey Literature Network Service

    1994-01-01

    The main initiatives taken in Italy by the Italian Library Association (AIB) for the development and promotion of grey literature since the recommendations of the seminar of York and following the Italian adhesion to EAGLE (through the Central Library of the Italian National Research Council-CNR) are presented, i.e.: survey the main Italian producers of GL through the application and creation of international and national standards; evaluate the use of grey literature in scientific communicat...

  1. An initiation-promotion model of tumour prevalence from high-charge and energy radiations

    Science.gov (United States)

    Cucinotta, F. A.; Wilson, J. W.

    1994-01-01

    A repair/misrepair kinetic model for multiple radiation-induced lesions (mutation inactivation) is coupled to a two-mutation model of initiation-promotion in tissue to provide a parametric description of tumour prevalence in the mouse Harderian gland from high-energy and charge radiations. Track-structure effects are considered using an action-cross section model. Dose-response curves are described for gamma rays and relativistic ions, and good agreement with experiment is found. The effects of nuclear fragmentation are also considered for high-energy proton and alpha-particle exposures. The model described provides a parametric description of age-dependent cancer induction for a wide range of radiation fields. Radiosensitivity parameters found in the model for an initiation mutation (sigma 0 = 7.6 x 10(-10) cm2 and D0 = 148.0 Gy) are somewhat different than previously observed for neoplastic transformation of C3H10T1/2 cell cultures (sigma 0 = 0.7 x 10(-10) cm2 and D0 = 117.0 Gy). We consider the two hypotheses that radiation acts solely as an initiator or as both initiator and promoter and make model calculations for fractionation exposures from gamma rays and relativistic Fe ions. For fractionated Fe exposures, an inverse-dose-rate effect is provided by a promotion hypothesis with an increase of 30% or more, dependent on the dose level and fractionation schedule, using a mutation rate for promotion similar to that of single-gene mutations.

  2. Initiation-promotion model of tumor prevalence in mice from space radiation exposures.

    Science.gov (United States)

    Cucinotta, F A; Wilson, J W

    1995-08-01

    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.

  3. Initiation-promotion model of tumor prevalence in mice from space radiation exposures.

    Science.gov (United States)

    Cucinotta, F A; Wilson, J W

    1995-08-01

    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. PMID:7480628

  4. Activity-promoting gaming systems in exercise and rehabilitation.

    Science.gov (United States)

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

    2011-01-01

    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.

  5. Activity-promoting gaming systems in exercise and rehabilitation

    Directory of Open Access Journals (Sweden)

    Matthew J. D. Taylor, PhD

    2011-12-01

    Full Text Available 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 rehabilitatio

  6. Endothelial cell-initiated signaling promotes the survival and self-renewal of cancer stem cells

    Science.gov (United States)

    Krishnamurthy, Sudha; Dong, Zhihong; Vodopyanov, Dmitry; Imai, Atsushi; Helman, Joseph I.; Prince, Mark E.; Wicha, Max S.; Nör, Jacques E.

    2010-01-01

    Recent studies have demonstrated that cancer stem cells play an important role in the pathobiology of head and neck squamous cell carcinomas (HNSCC). However, little is known about functional interactions between head and neck cancer stem-like cells (CSC) and surrounding stromal cells. Here, we used Aldehyde Dehydrogenase activity and CD44 expression to sort putative stem cells from primary human HNSCC. Implantation of 1,000 CSC (ALDH+CD44+Lin−) led to tumors in 13 (out of 15) mice, while 10,000 non-cancer stem cells (NCSC; ALDH−CD44−Lin−) resulted in 2 tumors in 15 mice. These data demonstrated that ALDH and CD44 select a sub-population of cells that are highly tumorigenic. The ability to self-renew was confirmed by the observation that ALDH+CD44+Lin− cells sorted from human HNSCC formed more spheroids (orospheres) in 3-D agarose matrices or ultra-low attachment plates than controls and were serially passaged in vivo. We observed that approximately 80% of the CSC were located in close proximity (within 100-µm radius) of blood vessels in human tumors, suggesting the existence of perivascular niches in HNSCC. In vitro studies demonstrated that endothelial cell-secreted factors promoted self-renewal of CSC, as demonstrated by the upregulation of Bmi-1 expression and the increase in the number of orospheres as compared to controls. Notably, selective ablation of tumor-associated endothelial cells stably transduced with a caspase-based artificial death switch (iCaspase-9) caused a marked reduction in the fraction of CSC in xenograft tumors. Collectively, these findings indicate that endothelial cell-initiated signaling can enhance the survival and self-renewal of head and neck cancer stem cells. PMID:21098716

  7. Invariant distribution of promoter activities in Escherichia coli.

    Science.gov (United States)

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

    2009-10-01

    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.

  8. Invariant distribution of promoter activities in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Alon Zaslaver

    2009-10-01

    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.

  9. Physical activity and health promotion in Italian university students

    Directory of Open Access Journals (Sweden)

    Adele Anna Teleman

    2015-06-01

    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.

  10. Activity-promoting gaming systems in exercise and rehabilitation

    OpenAIRE

    Matthew J. D. Taylor, PhD; Darren McCormick, BSc; Teshk Shawis, MBChB, FRCP; Rebecca Impson, MSc; Murray Griffin, PhD

    2011-01-01

    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 t...

  11. 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.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jan eRillich

    2015-04-01

    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.

  14. Improving health through policies that promote active travel

    DEFF Research Database (Denmark)

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

    2011-01-01

    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...

  15. Parents' Perspectives of School Mental Health Promotion Initiatives Are Related to Parents' Self-Assessed Parenting Capabilities

    Science.gov (United States)

    Askell-Williams, Helen

    2016-01-01

    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.…

  16. Promoter proximal polyadenylation sites reduce transcription activity

    DEFF Research Database (Denmark)

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

    2012-01-01

    Gene expression relies on the functional communication between mRNA processing and transcription. We previously described the negative impact of a point-mutated splice donor (SD) site on transcription. Here we demonstrate that this mutation activates an upstream cryptic polyadenylation (CpA) site...

  17. Promoting Physical Activity through Goal Setting Strategies

    Science.gov (United States)

    Martinez, Ray

    2004-01-01

    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…

  18. 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

    2008-01-01

    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

  19. Control of mammalian cell mutagenesis and differentiation by chemicals which initiate or promote tumor formation

    Energy Technology Data Exchange (ETDEWEB)

    Jones, C. A.; Huberman, E.

    1980-01-01

    A cell-mediated mutagenesis assay was developed to predict the potential carcinogenic hazard of some environmental chemicals. In this assay, Chinese hamster V79 cells, which are susceptible to mutagenesis, are co-cultivated with cells capable of metabolizing chemical carcinogens. Use of this assay made it possible to demonstrate a relationship between the degree of carcinogenicity and mutagenicity of a series of polycyclic hydrocarbons and nitrosamines and to study the organ specificity exhibited by some chemical carcinogens. However, most short-term in vitro assays are designed to detect mutagenic activity and therefore do not detect tumor promoting agents which are devoid of this activity. By analyzing various markers of terminal differentiation in cultured human melanoma and myeloid leukemia cells, we have established a relationship between the activity of a series of tumor promoting phorbol diesters in the mouse skin and their ability to induce terminal differentiation. We suggest that measuring alterations in the differentiation characteristics of some cultured cells may represent an approach by which environmental tumor promoting agents can be studied and detected.

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

    Directory of Open Access Journals (Sweden)

    Laura Gómez Urquijo

    2014-03-01

    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.

  1. Interleukin-10 promoter polymorphism predicts initial response of chronic hepatitis B to interferon alfa

    Directory of Open Access Journals (Sweden)

    Ma Weimin

    2011-01-01

    Full Text Available Abstract In order to examine whether variation in interleukin-10 promoter polymorphism would predict the likelihood of sustain response of chronic hepatitis B to treatment with interferon alfa (IFN-α, the inheritance of 3 biallelic polymorphisms in the IL-10 gene promoter in patients with 52 chronic hepatitis B were determined by polymerase chain reaction (PCR-bared techniques, restriction enzyme digestion or direct sequencing. The relationship to the outcome of antiviral therapy for chronic HBV infection was studied in 24 patients who had a virologically sustained response(SR and in 28 non-responder(NR to interferon alfa-2b and several IL-10 variants were more frequent among SR compared with NR. Carriage of the -592A allele, -592A/A genotype and -1082/-1819/-592 ATA haplotype was associated with SR. Our findings indicate that heterogeneity in the promoter region of the IL-10 gene has a role in determining the initial response of chronic hepatitis B to IFN-α therapy.

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

    Directory of Open Access Journals (Sweden)

    Sang C. Lee

    2011-01-01

    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.

  3. Promoter binding, initiation, and elongation by bacteriophage T7 RNA polymerase. A single-molecule view of the transcription cycle.

    Science.gov (United States)

    Skinner, Gary M; Baumann, Christoph G; Quinn, Diana M; Molloy, Justin E; Hoggett, James G

    2004-01-30

    A single-molecule transcription assay has been developed that allows, for the first time, the direct observation of promoter binding, initiation, and elongation by a single RNA polymerase (RNAP) molecule in real-time. To promote DNA binding and transcription initiation, a DNA molecule tethered between two optically trapped beads was held near a third immobile surface bead sparsely coated with RNAP. By driving the optical trap holding the upstream bead with a triangular oscillation while measuring the position of both trapped beads, we observed the onset of promoter binding, promoter escape (productive initiation), and processive elongation by individual RNAP molecules. After DNA template release, transcription re-initiation on the same DNA template is possible; thus, multiple enzymatic turnovers by an individual RNAP molecule can be observed. Using bacteriophage T7 RNAP, a commonly used RNAP paradigm, we observed the association and dissociation (k(off)= 2.9 s(-1)) of T7 RNAP and promoter DNA, the transition to the elongation mode (k(for) = 0.36 s(-1)), and the processive synthesis (k(pol) = 43 nt s(-1)) and release of a gene-length RNA transcript ( approximately 1200 nt). The transition from initiation to elongation is much longer than the mean lifetime of the binary T7 RNAP-promoter DNA complex (k(off) > k(for)), identifying a rate-limiting step between promoter DNA binding and promoter escape. PMID:14597619

  4. Development of transcriptional fusions to assess Leptospira interrogans promoter activity.

    Directory of Open Access Journals (Sweden)

    Gustavo M Cerqueira

    Full Text Available BACKGROUND: Leptospirosis is a zoonotic infectious disease that affects both humans and animals. The existing genetic tools for Leptospira spp. have improved our understanding of the biology of this spirochete as well as the interaction of pathogenic leptospires with the mammalian host. However, new tools are necessary to provide novel and useful information to the field. METHODOLOGY AND PRINCIPAL FINDINGS: A series of promoter-probe vectors carrying a reporter gene encoding green fluorescent protein (GFP were constructed for use in L. biflexa. They were tested by constructing transcriptional fusions between the lipL41, Leptospiral Immunoglobulin-like A (ligA and Sphingomyelinase 2 (sph2 promoters from L. interrogans and the reporter gene. ligA and sph2 promoters were the most active, in comparison to the lipL41 promoter and the non-induced controls. The results obtained are in agreement with LigA expression from the L. interrogans Fiocruz L1-130 strain. CONCLUSIONS: The novel vectors facilitated the in vitro evaluation of L. interrogans promoter activity under defined growth conditions which simulate the mammalian host environment. The fluorescence and rt-PCR data obtained closely reflected transcriptional regulation of the promoters, thus demonstrating the suitability of these vectors for assessing promoter activity in L. biflexa.

  5. Regulation of ALF promoter activity in Xenopus oocytes.

    Directory of Open Access Journals (Sweden)

    Dan Li

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

  6. Prediction of fine-tuned promoter activity from DNA sequence.

    Science.gov (United States)

    Siwo, Geoffrey; Rider, Andrew; Tan, Asako; Pinapati, Richard; Emrich, Scott; Chawla, Nitesh; Ferdig, Michael

    2016-01-01

    The quantitative prediction of transcriptional activity of genes using promoter sequence is fundamental to the engineering of biological systems for industrial purposes and understanding the natural variation in gene expression. To catalyze the development of new algorithms for this purpose, the Dialogue on Reverse Engineering Assessment and Methods (DREAM) organized a community challenge seeking predictive models of promoter activity given normalized promoter activity data for 90 ribosomal protein promoters driving expression of a fluorescent reporter gene. By developing an unbiased modeling approach that performs an iterative search for predictive DNA sequence features using the frequencies of various k-mers, inferred DNA mechanical properties and spatial positions of promoter sequences, we achieved the best performer status in this challenge. The specific predictive features used in the model included the frequency of the nucleotide G, the length of polymeric tracts of T and TA, the frequencies of 6 distinct trinucleotides and 12 tetranucleotides, and the predicted protein deformability of the DNA sequence. Our method accurately predicted the activity of 20 natural variants of ribosomal protein promoters (Spearman correlation r = 0.73) as compared to 33 laboratory-mutated variants of the promoters (r = 0.57) in a test set that was hidden from participants. Notably, our model differed substantially from the rest in 2 main ways: i) it did not explicitly utilize transcription factor binding information implying that subtle DNA sequence features are highly associated with gene expression, and ii) it was entirely based on features extracted exclusively from the 100 bp region upstream from the translational start site demonstrating that this region encodes much of the overall promoter activity. The findings from this study have important implications for the engineering of predictable gene expression systems and the evolution of gene expression in naturally occurring

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

    Science.gov (United States)

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

    2016-04-01

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

  8. YAP/TEAD co-activator regulated pluripotency and chemoresistance in ovarian cancer initiated cells.

    Directory of Open Access Journals (Sweden)

    Yan Xia

    Full Text Available Recent evidence suggests that some solid tumors, including ovarian cancer, contain distinct populations of stem cells that are responsible for tumor initiation, growth, chemo-resistance, and recurrence. The Hippo pathway has attracted considerable attention and some investigators have focused on YAP functions for maintaining stemness and cell differentiation. In this study, we successfully isolated the ovarian cancer initiating cells (OCICs and demonstrated YAP promoted self-renewal of ovarian cancer initiated cell (OCIC through its downstream co-activator TEAD. YAP and TEAD families were required for maintaining the expression of specific genes that may be involved in OCICs' stemness and chemoresistance. Taken together, our data first indicate that YAP/TEAD co-activator regulated ovarian cancer initiated cell pluripotency and chemo-resistance. It proposed a new mechanism on the drug resistance in cancer stem cell that Hippo-YAP signal pathway might serve as therapeutic targets for ovarian cancer treatment in clinical.

  9. Archaeal promoter architecture and mechanism of gene activation

    DEFF Research Database (Denmark)

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

    2011-01-01

    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...... mechanisms include TFB (transcription factor B) recruitment by the ara-box-binding factor to activate gene expression and modulation of TFB recruitment efficiency to yield differential gene expression....

  10. Archaeal promoter architecture and mechanism of gene activation.

    Science.gov (United States)

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

    2011-01-01

    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 mechanisms include TFB (transcription factor B) recruitment by the ara-box-binding factor to activate gene expression and modulation of TFB recruitment efficiency to yield differential gene expression. PMID:21265754

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

    NARCIS (Netherlands)

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

    2011-01-01

    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

  12. 76 FR 52845 - Establishing a Coordinated Government-Wide Initiative to Promote Diversity and Inclusion in the...

    Science.gov (United States)

    2011-08-23

    ... order to promote the Federal workplace as a model of equal opportunity, diversity, and inclusion, it is... every 4 years, focusing on workforce diversity, workplace inclusion, and agency accountability and... Initiative to Promote Diversity and Inclusion in the Federal Workforce #0; #0; #0; Presidential Documents...

  13. Promoting Physical Activity Among Overweight Young African American Women

    Centers for Disease Control (CDC) Podcasts

    2014-01-15

    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.

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

    OpenAIRE

    Ivo Mulec

    2010-01-01

    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...

  15. Evaluation of hair growth promoting activity of Phyllanthus niruri

    OpenAIRE

    Satish Patel; Vikas Sharma; Nagendra Chauhan; Mayank Thakur; Vinod Dixit

    2015-01-01

    Objective: This study was designed to investigate the potential Phyllanthus niruri (P. niruri ) extracts in promotion of hair growth. Materials and Methods: Here, we studied the hair growth promoting activity of petroleum ether extract of P. niruri following its topical administration. Alopecia was induced in albino rats by subcutaneous administration of testosterone for 21 days. Evaluation of hair loss inhibition was done by concurrent administration of extract and monitoring parameters like...

  16. "Know your CD4 campaign": 6-year outcomes from a quality improvement initiative to promote earlier initiation of antiretroviral therapy in Tanzania

    Directory of Open Access Journals (Sweden)

    Peter Memiah

    2014-07-01

    Full Text Available Background: Late initiation of treatment for illness secondary to the human immunodeficiency virus (HIV remains a major challenge in developing countries. Despite the World Health Organization (WHO recommendation that treatment be initiated early in disease management, health providers conducting quality improvement monitoring in one region of Tanzania noted that common management practice relies upon clinical signs of advanced disease alone for initiation of combination antiretroviral therapy (ART. Although Tanzanian National Treatment Guidelines followed standard WHO recommendations, few patients initiated ART based on laboratory parameters. As a potential barrier to optimal patient outcomes, further investigation of this inconsistency led to recognition of challenges reflecting patient, healthcare staff, and laboratory levels that might inhibit the use of CD4 cell counts as the entryway to care. Materials and Methods: Using a quality improvement approach, investigations were pursued for six discrete activities of HIV care delivery with before and after measures of selected indicators. With respect to patient engagement, meetings and informal educational sessions were held to promote understanding of the meaning of and need for CD4 testing. For clinic staff: (1 Qualitative interviews were conducted with providers to understand why laboratory data was not being used and (2 on-site interviews were conducted with laboratory personnel to review beliefs, methods, and practices related to measurement of CD4 cells testing. A large scale local campaign was mounted to (1 educate and empower patients to recognize a need for CD4 information in management of their own care; (2 re-educate and encourage providers to use measured, rather than clinical observation alone to initiate ART; and (3 understand and resolve clinical and laboratory challenges. Based upon findings from the interviews: (1 Meetings with hospital administrations were effected to resolve

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

    Directory of Open Access Journals (Sweden)

    Yunfei Li

    2015-01-01

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

  18. PROMOTING RURAL DESTINATION BUCOVINA VIA FACEBOOK. AN EMPIRICAL IDENTIFICATION OF SUPPORTING ONLINE MARKETING INITIATIVES

    Directory of Open Access Journals (Sweden)

    Pavel STANCIU

    2016-09-01

    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.

  19. Neuronal Activity Promotes Glioma Growth through Neuroligin-3 Secretion.

    Science.gov (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

    2015-05-01

    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.

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

    Science.gov (United States)

    Raine, Gary

    2013-11-01

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

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

    Science.gov (United States)

    Raine, Gary

    2013-11-01

    Many companies nowadays consider schools to be an important setting for marketing to children. However, important concerns can be raised from a health promotion perspective about the potential negative impact of commercial activities on the health and well-being of pupils. As this discussion paper will demonstrate, some commercial activities raise concerns in relation to physical health and obesity, not only by potentially undermining formal curriculum messages, but also through the active promotion of specific products, particularly those high in fat, sugar or salt. Nonetheless, the issues raised by commercial activities are not solely limited to effects on physical health. By allowing commercial activities, schools risk instilling in pupils consumer-orientated values. This is significant as such values have been linked to the development of poor health and well-being. Furthermore, the presence in schools of commercial activities will also militate against informed decision-making and be disempowering. There is also evidence that business-sponsored teaching materials can contain biased and misleading information. The potential negative impacts of commercial activities are inconsistent with goals in relation to the promotion of health and the principles of health-promoting schools. PMID:23135869

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

    Energy Technology Data Exchange (ETDEWEB)

    Griff, M.T.

    1995-10-01

    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.

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

    Science.gov (United States)

    Bauman, Adrian; Cavill, Nick; Brawley, Lawrence

    2009-01-01

    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. PMID:19995460

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

    Directory of Open Access Journals (Sweden)

    Cavill Nick

    2009-12-01

    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.

  5. 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

    2013-07-01

    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.

  6. Hmo1 directs pre-initiation complex assembly to an appropriate site on its target gene promoters by masking a nucleosome-free region.

    Science.gov (United States)

    Kasahara, Koji; Ohyama, Yoshifumi; Kokubo, Tetsuro

    2011-05-01

    Saccharomyces cerevisiae Hmo1 binds to the promoters of ∼ 70% of ribosomal protein genes (RPGs) at high occupancy, but is observed at lower occupancy on the remaining RPG promoters. In Δhmo1 cells, the transcription start site (TSS) of the Hmo1-enriched RPS5 promoter shifted upstream, while the TSS of the Hmo1-limited RPL10 promoter did not shift. Analyses of chimeric RPS5/RPL10 promoters revealed a region between the RPS5 upstream activating sequence (UAS) and core promoter, termed the intervening region (IVR), responsible for strong Hmo1 binding and an upstream TSS shift in Δhmo1 cells. Chromatin immunoprecipitation analyses showed that the RPS5-IVR resides within a nucleosome-free region and that pre-initiation complex (PIC) assembly occurs at a site between the IVR and a nucleosome overlapping the TSS (+1 nucleosome). The PIC assembly site was shifted upstream in Δhmo1 cells on this promoter, indicating that Hmo1 normally masks the RPS5-IVR to prevent PIC assembly at inappropriate site(s). This novel mechanism ensures accurate transcriptional initiation by delineating the 5'- and 3'-boundaries of the PIC assembly zone. PMID:21288884

  7. A STUDY ON LIMITATION OF GOVERNMENT INITIATIVE MODEL FOR ALTERNATIVE FUEL VEHICLE (AFV PROMOTION IN CHINA

    Directory of Open Access Journals (Sweden)

    Byunghun Choi

    2016-04-01

    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.

  8. Transcriptional activation of the nitrogenase promoter in vitro: adenosine nucleotides are required for inhibition of NIFA activity by NIFL.

    Science.gov (United States)

    Eydmann, T; Söderbäck, E; Jones, T; Hill, S; Austin, S; Dixon, R

    1995-03-01

    The enhancer-binding protein NIFA is required for transcriptional activation of nif promoters by the alternative holoenzyme form of RNA polymerase, which contains the sigma factor sigma 54 (sigma N). NIFA hydrolyzes nucleoside triphosphates to catalyze the isomerization of closed promoter complexes to transcriptionally competent open complexes. The activity of NIFA is antagonized by the regulatory protein NIFL in response to oxygen and fixed nitrogen in vivo. We have investigated the requirement for nucleotides in the formation and stability of open promoter complexes by NIFA and inhibition of its activity by NIFL at the Klebsiella pneumoniae nifH promoter. Open complexes formed by sigma 54-containing RNA polymerase are considerably more stable to heparin challenge in the presence of GTP than in the presence of ATP. This differential stability is most probably a consequence of GTP being the initiating nucleotide at this promoter. Adenosine nucleosides are specifically required for Azotobacter vinelandii NIFL to inhibit open complex formation by native NIFA, and the nucleoside triphosphatase activity of NIFA is strongly inhibited by NIFL under these conditions. We propose a model in which NIFL modulates the activity of NIFA via an adenosine nucleotide switch. PMID:7868590

  9. 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)

    BEREZHNOY Andrey Yu; SHCKORBATOV Yuriy G.; HISANORI Kiryu

    2006-01-01

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

  10. Eaf1p Is Required for Recruitment of NuA4 in Targeting TFIID to the Promoters of the Ribosomal Protein Genes for Transcriptional Initiation In Vivo.

    Science.gov (United States)

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

    2015-09-01

    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.

  11. Internet as a Medium of Pharmaceutical Companies Promotional Activities

    OpenAIRE

    Darko Pantelic

    2009-01-01

    Pharmaceuticals market is highly regulated, and it can be stated that prescription (legal or ethical) drugs have a status of substances in controlled circulation. Promotional activities are also under strict legislation, further burdened with ethical consideration and public scrutiny. Internet as liberal and hard to control medium brings entirely new sets of solutions and/or problems to pharmaceuticals market(ers).

  12. Health Promotion Guidance Activity of Youth Sports Clubs

    Science.gov (United States)

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

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    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....

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

    Science.gov (United States)

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

    2014-01-01

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

  15. It Takes a Virtual Community: Promoting Collaboration through Student Activities

    Science.gov (United States)

    Battista, Ludmila; Forrey, Carol; Stevenson, Carolyn

    2008-01-01

    Distance education provides many nontraditional students with the opportunity to pursue a college education not possible through traditional brick and mortar education. Although not meeting face-to-face, student activities help promote a stronger connection between the classroom and university community. This paper will discuss strategies for…

  16. Promoting Educational Equity through School Libraries: Equity Activity Book.

    Science.gov (United States)

    Arizona State Univ., Tempe.

    The activities suggested in this workbook for participants in a continuing education program for inservice school media specialists are designed to develop the trainee's skills in identifying instances of sexism and sex stereotyping in education, and in promoting sex fairness in the library. Exercises and tests on the first module are concerned…

  17. The Role of Values in Promoting Physical Activity

    Science.gov (United States)

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

    2015-01-01

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

  18. Invariant distribution of promoter activities in Escherichia coli.

    OpenAIRE

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

    2009-01-01

    Author Summary Cells respond to a changing environment by regulating the activity of genes. Here, we sought to understand how E. coli cells distribute their limited transcriptional resources among their target genes, and how this allocation varies with growth rate and growth conditions. To achieve this, we assayed the expression of a comprehensive library of transcriptional reporter strains under different conditions. High-temporal resolution measurements of promoter activities were obtained ...

  19. 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

    2009-12-01

    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.

  20. Mushroom bodies enhance initial motor activity in Drosophila.

    Science.gov (United States)

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

    2009-01-01

    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.

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

    Science.gov (United States)

    Franklin, Nina C

    2015-01-01

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

  2. cis Determinants of Promoter Threshold and Activation Timescale

    Directory of Open Access Journals (Sweden)

    Anders S. Hansen

    2015-08-01

    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.

  3. TALE factors poise promoters for activation by Hox proteins.

    Science.gov (United States)

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

    2014-01-27

    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.

  4. Tumour-promoting activity of polycyclic aromatic hydrocarbons and their oxygenated or nitrated derivatives.

    Science.gov (United States)

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

    2016-03-01

    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.

  5. Propionate induces the bovine cytosolic phosphoenolpyruvate carboxykinase promoter activity.

    Science.gov (United States)

    Zhang, Qian; Koser, Stephanie L; Donkin, Shawn S

    2016-08-01

    Cytosolic phosphoenolpyruvate carboxykinase (PCK1) is a critical enzyme within the metabolic networks for gluconeogenesis, hepatic energy metabolism, and tricarboxylic acid cycle function, and is controlled by several transcription factors including hepatic nuclear factor 4α (HNF4α). The primary objective of the present study was to determine whether propionate regulates bovine PCK1 transcription. The second objective was to determine the action of cyclic AMP (cAMP), glucocorticoids, and insulin, hormonal cues known to modulate glucose metabolism, on bovine PCK1 transcriptional activity. The proximal promoter of the bovine PCK1 gene was ligated to a Firefly luciferase reporter and transfected into H4IIE hepatoma cells. Cells were exposed to treatments for 23 h and luciferase activity was determined in cell lysates. Activity of the PCK1 promoter was linearly induced by propionate, and maximally increased 7-fold with 2.5 mM propionate, which was not muted by 100 nM insulin. Activity of the PCK1 promoter was increased 1-fold by either 1.0 mM cAMP or 5.0µM dexamethasone, and 2.2-fold by their combination. Induction by cAMP and dexamethasone was repressed 50% by 100 nM insulin. Propionate, cAMP, and dexamethasone acted synergistically to induce the PCK1 promoter activity. Propionate-responsive regions, identified by 5' deletion analysis, were located between -1,238 and -409 bp and between -85 and +221 bp. Deletions of the core sequences of the 2 putative HNF4α sites decreased the responsiveness to propionate by approximately 40%. These data indicate that propionate regulates its own metabolism through transcriptional stimulation of the bovine PCK1 gene. This induction is mediated, in part, by the 2 putative HNF4α binding sites in the bovine PCK1 promoter. PMID:27289145

  6. An upstream activation element exerting differential transcriptional activation on an archaeal promoter

    DEFF Research Database (Denmark)

    Peng, Nan; Xia, Qiu; Chen, Zhengjun;

    2009-01-01

    (UAS) ara-box activated the basal promoter by recruiting transcription factor B to its BRE. While this UAS ensured a general expression from an inactive or weak basal promoter in the presence of other tested carbon resources, it exhibited a strong arabinose-responsive transcriptional activation. To our...

  7. Promoting policy and environmental change using photovoice in the Kaiser Permanente Community Health Initiative.

    Science.gov (United States)

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

    2010-05-01

    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. PMID:19843702

  8. NOTCH1 signaling promotes human T-cell acute lymphoblastic leukemia initiating cell regeneration in supportive niches.

    Directory of Open Access Journals (Sweden)

    Wenxue Ma

    Full Text Available BACKGROUND: Leukemia initiating cells (LIC contribute to therapeutic resistance through acquisition of mutations in signaling pathways, such as NOTCH1, that promote self-renewal and survival within supportive niches. Activating mutations in NOTCH1 occur commonly in T cell acute lymphoblastic leukemia (T-ALL and have been implicated in therapeutic resistance. However, the cell type and context specific consequences of NOTCH1 activation, its role in human LIC regeneration, and sensitivity to NOTCH1 inhibition in hematopoietic microenvironments had not been elucidated. METHODOLOGY AND PRINCIPAL FINDINGS: We established humanized bioluminescent T-ALL LIC mouse models transplanted with pediatric T-ALL samples that were sequenced for NOTCH1 and other common T-ALL mutations. In this study, CD34(+ cells from NOTCH1(Mutated T-ALL samples had higher leukemic engraftment and serial transplantation capacity than NOTCH1(Wild-type CD34(+ cells in hematopoietic niches, suggesting that self-renewing LIC were enriched within the NOTCH1(Mutated CD34(+ fraction. Humanized NOTCH1 monoclonal antibody treatment reduced LIC survival and self-renewal in NOTCH1(Mutated T-ALL LIC-engrafted mice and resulted in depletion of CD34(+CD2(+CD7(+ cells that harbor serial transplantation capacity. CONCLUSIONS: These results reveal a functional hierarchy within the LIC population based on NOTCH1 activation, which renders LIC susceptible to targeted NOTCH1 inhibition and highlights the utility of NOTCH1 antibody targeting as a key component of malignant stem cell eradication strategies.

  9. 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

    2005-03-01

    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.

  10. Alterations in HIV-1 LTR promoter activity during AIDS progression

    International Nuclear Information System (INIS)

    HIV-1 variants evolving in AIDS patients frequently show increased replicative capacity compared to those present during early asymptomatic infection. It is known that late stage HIV-1 variants often show an expanded coreceptor tropism and altered Nef function. In the present study we investigated whether enhanced HIV-1 LTR promoter activity might also evolve during disease progression. Our results demonstrate increased LTR promoter activity after AIDS progression in 3 of 12 HIV-1-infected individuals studied. Further analysis revealed that multiple alterations in the U3 core-enhancer and in the transactivation-response (TAR) region seem to be responsible for the enhanced functional activity. Our findings show that in a subset of HIV-1-infected individuals enhanced LTR transcription contributes to the increased replicative potential of late stage virus isolates and might accelerate disease progression

  11. Implementing healthy lifestyle promotion in primary care: a quasi-experimental cross-sectional study evaluating a team initiative

    OpenAIRE

    Andersson, Kristin; Krevers, Barbro; Bendtsen, Preben

    2015-01-01

    Background: Non-communicable diseases are a leading cause of death and can largely be prevented by healthy lifestyles. Health care organizations are encouraged to integrate healthy lifestyle promotion in routine care. This study evaluates the impact of a team initiative on healthy lifestyle promotion in primary care. Methods: A quasi-experimental, cross-sectional design compared three intervention centres that had implemented lifestyle teams with three control centres that used a traditional ...

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

    Directory of Open Access Journals (Sweden)

    Ivo Mulec

    2010-01-01

    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.

  13. Anti-tumour promoting activity of diphenylmethyl selenocyanate against two-stage mouse skin carcinogenesis.

    Science.gov (United States)

    Das, Rajat Kumar; Bhattacharya, Sudin

    2005-01-01

    Epidemiological, clinical and experimental evidence collectively suggests that Se in different inorganic and organic forms provides a potential cancer chemopreventive agent, active against several types of cancer. It can exert preventive activity in all the three stages of cancer: initiation, promotion and progression. Literature reports revealed that organoselenocyanates have more potential as chemopreventive agents than inorganic forms due to their lower toxicity. In our previous report we showed chemopreventive efficacy of diphenylmethyl selenocyanate during the initiation and pre- plus post-initiation phases of skin and colon carcinogenesis process. The present study was undertaken to explore the anti-tumour promoting activity of diphenylmethyl selenocyanate in a 7,12-dimethylbenz (a) anthracene (DMBA)-croton oil two-stage skin carcinogenesis model. The results obtained showed significant (pliver and skin. Thus, the present data strongly suggest that diphenylmethyl selenocyanate also has the potential to act as anti-tumour promoter agent in a two-stage skin carcinogenesis mouse model, pointing to possible general efficacy. PMID:16101330

  14. Promoting Space Education and Awareness in Pakistan- Initiatives, Achievements, Challenges and Issues

    Science.gov (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

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

    Directory of Open Access Journals (Sweden)

    Luoma Pauli V

    2010-07-01

    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.

  16. Skin tumor-initiating activities of the twelve isomeric phenols of benzo(a)pyrene

    International Nuclear Information System (INIS)

    The skin tumor-initiating activities of the 12 isomeric phenols of benzo(a)pyrene (BP) were determined in mice by use of a two-stage system of tumorigenesis. 11-Hydroxybenzo(a)pyrene was moderately active, whereas 2-hydroxybenzo(a)pyrene and BP were strong tumor initiators when applied topically to CD-1 mice and followed by twice-weekly applications of the promoter 12-O-tetradecanoylphorbol-13-acetate. 1-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, and 12-hydroxybenzo(a)pyrene had less than 5% of the tumor-initiating activity of BP when the data were expressed as papillomas per mouse. After 30 weeks of promotion, the number of papillomas per mouse was 8.4, 8.5, and 2.8, respectively, for the animals treated with BP, 2-hydroxybenzo(a)pyrene, and 11-hydroxybenzo(a)pyrene. A 5-week latency period before the appearance of the first tumor was observed after the application of either 2-hydroxybenzo(a)pyrene or BP, whereas a slightly longer latency period of 7 weeks was observed following application of 11-hydroxybenzo(a)pyrene. The time required for 50% of the animals to develop tumors was 13 weeks for animals treated with BP and 15 weeks for animals treated with 2- or 11-hydroxybenzo(a)pyrene

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

    Directory of Open Access Journals (Sweden)

    Hossein Matlabi

    2014-07-01

    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.

  18. IKKβ in intestinal mesenchymal cells promotes initiation of colitis-associated cancer.

    Science.gov (United States)

    Koliaraki, Vasiliki; Pasparakis, Manolis; Kollias, George

    2015-12-14

    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.

  19. 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.

  20. HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation.

    Science.gov (United States)

    Filbin, Megan E; Vollmar, Breanna S; Shi, Dan; Gonen, Tamir; Kieft, Jeffrey S

    2013-02-01

    The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) drives noncanonical initiation of protein synthesis necessary for viral replication. Functional studies of the HCV IRES have focused on 80S ribosome formation but have not explored its role after the 80S ribosome is poised at the start codon. Here, we report that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause only a local perturbation in IRES structure and result in conformational changes in the IRES-rabbit 40S subunit complex. Functionally, the mutations decrease IRES activity by inhibiting the first ribosomal translocation event, and modeling results suggest that this effect occurs through an interaction with a single ribosomal protein. The ability of the HCV IRES to manipulate the ribosome provides insight into how the ribosome's structure and function can be altered by bound RNAs, including those derived from cellular invaders. PMID:23262488

  1. Spontaneous initiation, promotion and progression of colorectal cancer in the novel A/J Min/+ mouse.

    Science.gov (United States)

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

    2016-04-15

    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.

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

    Science.gov (United States)

    Schreiber, T; Tissier, A

    2016-01-01

    The discovery of proteins with programmable DNA-binding specificities triggered a whole array of applications in synthetic biology, including genome editing, regulation of transcription, and epigenetic modifications. Among those, transcription activator-like effectors (TALEs) due to their natural function as transcription regulators, are especially well-suited for the development of orthogonal systems for the control of gene expression. We describe here the construction and testing of libraries of synthetic TALE-activated promoters which are under the control of a single TALE with a given DNA-binding specificity. These libraries consist of a fixed DNA-binding element for the TALE, a TATA box, and variable sequences of 19 bases upstream and 43 bases downstream of the DNA-binding element. These libraries were cloned using a Golden Gate cloning strategy making them usable as standard parts in a modular cloning system. The broad range of promoter activities detected and the versatility of these promoter libraries make them valuable tools for applications in the fine-tuning of expression in metabolic engineering projects or in the design and implementation of regulatory circuits. PMID:27480693

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

    Science.gov (United States)

    Schreiber, T; Tissier, A

    2016-01-01

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

  4. 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.

    2013-04-23

    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.

  5. Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life

    Science.gov (United States)

    Davies, Elizabeth R.; Kelly, Joanne F.C.; Howarth, Peter H.; Wilson, David I.; Holgate, Stephen T.; Davies, Donna E.; Whitsett, Jeffrey A.; Haitchi, Hans Michael

    2016-01-01

    Asthma is a chronic inflammatory airways disease that usually begins in early life and involves gene-environment interactions. Although most asthma exhibits allergic inflammation, many allergic individuals do not have asthma. Here, we report how the asthma gene a disintegrin and metalloprotease 33 (ADAM33) acts as local tissue susceptibility gene that promotes allergic asthma. We show that enzymatically active soluble ADAM33 (sADAM33) is increased in asthmatic airways and plays a role in airway remodeling, independent of inflammation. Furthermore, remodeling and inflammation are both suppressed in Adam33-null mice after allergen challenge. When induced in utero or added ex vivo, sADAM33 causes structural remodeling of the airways, which enhances postnatal airway eosinophilia and bronchial hyperresponsiveness following subthreshold challenge with an aeroallergen. This substantial gene-environment interaction helps to explain the end-organ expression of allergic asthma in genetically susceptible individuals. Finally, we show that sADAM33-induced airway remodeling is reversible, highlighting the therapeutic potential of targeting ADAM33 in asthma.

  6. Effects of high activation energies on acoustic timescale detonation initiation

    Science.gov (United States)

    Regele, J. D.; Kassoy, D. R.; Vasilyev, O. V.

    2012-08-01

    Acoustic timescale Deflagration-to-Detonation Transition (DDT) has been shown to occur through the generation of compression waves emitted by a hot spot or reaction centre where the pressure and temperature increase with little diminution of density. In order to compensate for the multi-scale nature of the physico-chemical processes, previous numerical simulations in this area have been limited to relatively small activation energies. In this work, a computational study investigates the effect of increased activation energy on the time required to form a detonation wave and the change in behaviour of each hot spot as the activation energy is increased. The simulations use a localised spatially distributed thermal power deposition of limited duration into a finite volume of reactive gas to facilitate DDT. The Adaptive Wavelet-Collocation Method is used to solve efficiently the 1-D reactive Euler equations with one-step Arrhenius kinetics. The DDT process as described in previous work is characterised by the formation of hot spots during an initial transient period, explosion of the hot spots and creation of an accelerating reaction front that reaches the lead shock and forms an overdriven detonation wave. Current results indicate that as the activation energy is raised the chemical heat release becomes more temporally distributed. Hot spots that produce an accelerating reaction front with low activation energies change behaviour with increased activation energy so that no accelerating reaction front is created. An acoustic timescale ratio is defined that characterises the change in behaviour of each hot spot.

  7. Isolation and characterization of active promoters from Gluconacetobacter diazotrophicus strain PAL5 using a promoter-trapping plasmid.

    Science.gov (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

    2016-07-01

    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. PMID:26914247

  8. A point mutation in a silencer module reduces the promoter activity for the human mercaptopyruvate sulfurtransferase.

    Science.gov (United States)

    Nagahara, Noriyuki; Sreeja, V G; Li, Qing; Shimizu, Takako; Tsuchiya, Terumasa; Fujii-Kuriyama, Yoshiaki

    2004-11-01

    A promoter region of human mercaptopyruvate sulfurtransferase (MST) [EC 2.8.1.2] is G+C-rich and TATA-less, showing features of a house-keeping gene. In the core promoter, a GC box (-284:GGGGCGTGGC:-275) and an initiator (-219:TTATATG:-225) are found. A cap site hunting analysis for human liver cDNA revealed four possible transcriptional start sites, nucleotides -223, -159, -35 and -25. Point mutagenesis and deletion studies suggest that a module of the silencer element is -394:GCTG:-391. A replacement of -391G to C lost the silencer function; on the other hand, a replacement of -394G to T or C, -393C to T or -392T to G markedly reduced the promoter activity. PMID:15507321

  9. Three promoters regulate the transcriptional activity of the human holocarboxylase synthetase gene.

    Science.gov (United States)

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

    2013-11-01

    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.

  10. Hypothermia activates adipose tissue to promote malignant lung cancer progression.

    Directory of Open Access Journals (Sweden)

    Gangjun Du

    Full Text Available Microenvironment has been increasingly recognized as a critical regulator of cancer progression. In this study, we identified early changes in the microenvironment that contribute to malignant progression. Exposure of human bronchial epithelial cells (BEAS-2B to methylnitrosourea (MNU caused a reduction in cell toxicity and an increase in clonogenic capacity when the temperature was lowered from 37°C to 28°C. Hypothermia-incubated adipocyte media promoted proliferation in A549 cells. Although a hypothermic environment could increase urethane-induced tumor counts and Lewis lung cancer (LLC metastasis in lungs of three breeds of mice, an increase in tumor size could be discerned only in obese mice housed in hypothermia. Similarly, coinjections using differentiated adipocytes and A549 cells promoted tumor development in athymic nude mice when adipocytes were cultured at 28°C. Conversely, fat removal suppressed tumor growth in obese C57BL/6 mice inoculated with LLC cells. Further studies show hypothermia promotes a MNU-induced epithelial-mesenchymal transition (EMT and protects the tumor cell against immune control by TGF-β1 upregulation. We also found that activated adipocytes trigger tumor cell proliferation by increasing either TNF-α or VEGF levels. These results suggest that hypothermia activates adipocytes to stimulate tumor boost and play critical determinant roles in malignant progression.

  11. ACTIM: an EDA initiated study on spectral active imaging

    Science.gov (United States)

    Steinvall, O.; Renhorn, I.; Ahlberg, J.; Larsson, H.; Letalick, D.; Repasi, E.; Lutzmann, P.; Anstett, G.; Hamoir, D.; Hespel, L.; Boucher, Y.

    2010-10-01

    This paper will describe ongoing work from an EDA initiated study on Active Imaging with emphasis of using multi or broadband spectral lasers and receivers. Present laser based imaging and mapping systems are mostly based on a fixed frequency lasers. On the other hand great progress has recently occurred in passive multi- and hyperspectral imaging with applications ranging from environmental monitoring and geology to mapping, military surveillance, and reconnaissance. Data bases on spectral signatures allow the possibility to discriminate between different materials in the scene. Present multi- and hyperspectral sensors mainly operate in the visible and short wavelength region (0.4-2.5 μm) and rely on the solar radiation giving shortcoming due to shadows, clouds, illumination angles and lack of night operation. Active spectral imaging however will largely overcome these difficulties by a complete control of the illumination. Active illumination enables spectral night and low-light operation beside a robust way of obtaining polarization and high resolution 2D/3D information. Recent development of broadband lasers and advanced imaging 3D focal plane arrays has led to new opportunities for advanced spectral and polarization imaging with high range resolution. Fusing the knowledge of ladar and passive spectral imaging will result in new capabilities in the field of EO-sensing to be shown in the study. We will present an overview of technology, systems and applications for active spectral imaging and propose future activities in connection with some prioritized applications.

  12. Mental health promotion in the health care setting: collaboration and engagement in the development of a mental health promotion capacity-building initiative.

    Science.gov (United States)

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

    2014-01-01

    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.

  13. Presentation and exhibition activities for promoting theexportof transport services

    Directory of Open Access Journals (Sweden)

    Darya Vladimirovna Nesterova

    2012-03-01

    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.

  14. Evaluation of hair growth promoting activity of Phyllanthus niruri

    Directory of Open Access Journals (Sweden)

    Satish Patel

    2015-10-01

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

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

    Science.gov (United States)

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

    2016-09-16

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

  16. Self-Regulation, Metacognition and Child- and Adult-Initiated Activity: Does It Matter Who Initiates the Task?

    Science.gov (United States)

    Robson, Sue

    2016-01-01

    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,…

  17. Promotion

    OpenAIRE

    Alam, Hasan B.

    2013-01-01

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

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

    Science.gov (United States)

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

    1998-09-01

    In trypanosomes, most genes are arranged in polycistronic transcription units. Individual mRNAs are generated by 5'-trans splicing and 3' polyadenylation. Remarkably, no regulation of RNA polymerase II transcription has been detected although many RNAs are differentially expressed during kinetoplastid life cycles. Demonstration of specific class II promoters is complicated by the difficulty in distinguishing between genuine promoter activity and stimulation of trans splicing. Using vectors that were designed to allow the detection of low promoter activities in a transcriptionally silent chromosomal context, we isolated a novel trypanosome RNA polymerase I promoter. We were however unable to detect class II promoter activity in any tested DNA fragment. We also integrated genes which were preceded by a T3 promoter into the genome of cells expressing bacteriophage T3 polymerase: surprisingly, transcription was alpha-amanitin sensitive. One possible interpretation of these results is that in trypanosomes, RNA polymerase II initiation is favored by genomic accessibility and double-strand melting. PMID:9709032

  19. The Impact of Chromospheric Activity on Observed Initial Mass Functions

    CERN Document Server

    Stassun, Keivan G; Dupuy, Trent; Kratter, Kaitlin

    2014-01-01

    Using recently established empirical calibrations for the impact of chromospheric activity on the radii, effective temperatures, and estimated masses of active low-mass stars and brown dwarfs, we reassess the shape of the initial mass function (IMF) across the stellar/substellar boundary in the Upper Sco star-forming region (age 5-10 Myr). We adjust the observed effective temperatures to warmer values using the observed strength of the chromospheric H$\\alpha$ emission, and redetermine the estimated masses of objects using pre--main-sequence evolutionary tracks in the H-R diagram. The effect of the activity-adjusted temperatures is to shift the objects to higher masses by 3-100%. While the slope of the resulting IMF at substellar masses is not strongly changed, the peak of the IMF does shift from ~0.06 to ~0.11 Msun. Moreover, for objects with masses ~0.2 Msun, the ratio of brown dwarfs to stars changes from ~80% to ~33%. These results suggest that activity corrections are essential for studies of the substell...

  20. Different human TFIIIB activities direct RNA polymerase III transcription from TATA-containing and TATA-less promoters

    OpenAIRE

    Schramm, Laura; Pendergrast, P. Shannon; Sun, Yuling; Hernandez, Nouria

    2000-01-01

    Transcription initiation at RNA polymerase III promoters requires transcription factor IIIB (TFIIIB), an activity that binds to RNA polymerase III promoters, generally through protein–protein contacts with DNA binding factors, and directly recruits RNA polymerase III. Saccharomyces cerevisiae TFIIIB is a complex of three subunits, TBP, the TFIIB-related factor BRF, and the more loosely associated polypeptide β″. Although human homologs for two of the TFIIIB subunits, the TATA box–binding prot...

  1. Glycine Receptor α2 Subunit Activation Promotes Cortical Interneuron Migration

    Directory of Open Access Journals (Sweden)

    Ariel Avila

    2013-08-01

    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.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Cells respond to DNA damage by activating cell cycle checkpoints to delay proliferation and facilitate DNA repair. Here, to uncover new checkpoint regulators, we perform RNA interference screening targeting genes involved in ubiquitylation processes. We show that the F-box protein cyclin F plays...... 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...

  3. Cationic Nanocylinders Promote Angiogenic Activities of Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Jung Bok Lee

    2016-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Hernán A. Avila

    2015-10-01

    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.

  5. Bacterial lipopolysaccharide promotes profibrotic activation of intestinal fibroblasts.

    LENUS (Irish Health Repository)

    Burke, J P

    2012-02-01

    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.

  6. Extravehicular Activity Systems Education and Public Outreach in Support of NASA's STEM Initiatives

    Science.gov (United States)

    Paul, Heather L.

    2011-01-01

    The exploration activities associated with NASA?s goals to return to the Moon, travel to Mars, or explore Near Earth Objects (NEOs) will involve the need for human-supported space and surface extravehicular activities (EVAs). The technology development and human element associated with these exploration missions provide fantastic content to promote science, technology, engineering, and math (STEM). As NASA Administrator Charles F. Bolden remarked on December 9, 2009, "We....need to provide the educational and experiential stepping-stones to inspire the next generation of scientists, engineers, and leaders in STEM fields." The EVA Systems Project actively supports this initiative by providing subject matter experts and hands-on, interactive presentations to educate students, educators, and the general public about the design challenges encountered as NASA develops EVA hardware for these missions. This paper summarizes these education and public efforts.

  7. 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

    2010-01-01

    -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...

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Mariagiovanna Caprara

    2013-01-01

    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.

  10. Gross and microscopic lesions in the female SENCAR mouse skin and lung in tumor initiation and promotion studies.

    OpenAIRE

    Knutsen, G L; Kovatch, R M; Robinson, M.

    1986-01-01

    The skin and lung tissues from SENCAR mice used as part of the Environmental Protection Agency's (EPA's) Carcinogenesis Testing Matrix were examined. This study included SENCAR mice used in three different short-term bioassay protocols in which the skin papilloma assay was used to identify initiators, promoters, and complete carcinogens. Also included were the pathology findings from SENCAR mice used in the combined bioassay in which the skin assay and the lung adenoma assay were conducted si...

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

    Science.gov (United States)

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

    2013-01-01

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

  12. Child and Adolescent Inpatient Restraint Reduction: A State Initiative to Promote Strength-Based Care.

    Science.gov (United States)

    LeBel, Janice; Stromberg, Nan; Duckworth, Ken; Kerzner, Joan; Goldstein, Robert; Weeks, Michael; Harper, Gordon; LaFlair, Lareina; Sudders, Marylou

    2004-01-01

    Objective: To reduce the use of restraint and seclusion with children and adolescents in psychiatric inpatient units by promoting a preventive, strength-based model of care. Method: The State Mental Health Authority used data analysis, quality improvement strategies, regulatory oversight, and technical assistance to develop and implement system…

  13. 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;

    2011-01-01

    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. Paradoxicall...... and subsequent rise in cellular [G6P]....

  14. The effects of tobacco sales promotion on initiation of smoking--experiences from Finland and Norway.

    Science.gov (United States)

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

    1993-01-01

    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

  15. Promoting moderate-vigorous physical activity in overweight minority girls.

    Science.gov (United States)

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

    2010-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Norma Olvera

    2010-01-01

    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.

  17. Breastfeeding Promotion Research: The ES/WIC Nutrition Education Initiative and Economic Considerations

    OpenAIRE

    Weimer, Jon P.

    1998-01-01

    Educating low-income women about the advantages of breastfeeding their babies increases the number who breastfeed. This report summarizes the results of four projects that focused primarily on promoting breastfeeding, which is considered to be the most healthful and beneficial feeding method for most infants. Research has shown that breastfeeding improves the general health, growth, and development of infants and significantly reduces the risk of several health problems both during early life...

  18. An artificial HSE promoter for efficient and selective detection of heat shock pathway activity.

    Science.gov (United States)

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

    2015-03-01

    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.

  19. Promoting direct interspecies electron transfer with activated carbon

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...... were attached to GAC, but did not aggregate as they do when making biological electrical connections between cells. Studies with a series of gene deletion mutants eliminated the possibility that GAC promoted electron exchange via interspecies hydrogen or formate transfer and demonstrated that DIET...... of methanogenesis might be to facilitate direct interspecies electron transfer (DIET) between bacteria and methanogens. Metabolism was substantially accelerated when GAC was added to co-cultures of Geobacter metallireducens and Geobacter sulfurreducens grown under conditions previously shown to require DIET. Cells...

  20. Activating STAT3 Alpha for Promoting Healing of Neurons

    Science.gov (United States)

    Conway, Greg

    2008-01-01

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

  1. Detailed analysis of the promoter activity of an attenuated lentivirus.

    Science.gov (United States)

    Blatti-Cardinaux, Laure; Sanjosé, Leticia; Zahno, Marie-Luise; Zanoni, Reto; Reina, Ramses; Bertoni, Giuseppe

    2016-07-01

    In spite of an eradication campaign that eliminated clinical cases of caprine arthritis encephalitis virus-induced arthritis in the Swiss goat population, seroconversions are still observed. In the affected flocks, viruses belonging mainly to the small ruminant lentivirus A4 subtype are regularly isolated. These viruses are considered attenuated, except in the mammary gland, where high viral loads and histopathological lesions have been observed. We previously characterized and sequenced such field isolates, detecting several potentially attenuating mutations in their LTR. Here we present a detailed analysis of the promoter activity of these genetic elements, which was comparable to those of virulent isolates. An AP-1 binding site was shown to be crucial for promoter activity in reporter gene assays and also in the context of a replicating molecular clone. Other sites, such as AML(vis) and a conserved E-box, appeared to be less crucial. Analysis of a unique AP-4 site showed a clear discrepancy between results obtained with reporter gene assays and those with mutated viruses. Within the limits of this in vitro study, we did not find evidence pointing to the LTR as the genetic correlate of attenuation for these viruses. Finally, the limited replication of SRLV A4 in mammary cell culture could not explain the suggested mammary tropism. In contrast, and in view of the abundance of macrophages in the mammary gland, it is the striking replication capacity of SRLV A4 in these cells, unaffected by all LTR mutations tested, which may explain the apparent mammary tropism of these viruses. PMID:27114068

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

    Science.gov (United States)

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

    2015-01-01

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

  3. 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

    2013-01-01

    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.

  4. Promoting Uranium Immobilization by the Activities of Microbial Phosphatases

    International Nuclear Information System (INIS)

    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 PO43- 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 (micro)M dissolved uranium and that Rahnella is much more efficient in precipitating U(VI) than Bacillus sp. The

  5. 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

    2007-04-19

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Delgado, Alison; Evans, Meredydd

    2010-04-01

    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.

  7. Initiatives to Promote Effective Self-Care Skills in Children and Adolescents with Diabetes Mellitus

    OpenAIRE

    Anderson, Barbara J.; Britta Svoren; Lori Laffel

    2007-01-01

    Intensive management of type 1 diabetes mellitus (T1DM) is increasingly becoming the `ideal' standard of care for pediatric patients at diabetes centers across the world. This `ideal' standard is based on two landmark studies that documented that keeping blood glucose levels as close to normal as possible and achieving this as early as possible in the disease course helps to prevent or delay the devastating long-term complications of T1DM. Simultaneously, initiatives supplemental to the medic...

  8. Effectiveness of School-Initiated Physical Activity Program on Secondary School Students' Physical Activity Participation

    Science.gov (United States)

    Gråstén, Arto; Yli-Piipari, Sami; Watt, Anthony; Jaakkola, Timo; Liukkonen, Jarmo

    2015-01-01

    Background: The promotion of physical activity and health has become a universal challenge. The Sotkamo Physical Activity as Civil Skill Program was implemented to increase students' physical activity by promoting supportive psychological and physical school environment. The aim of this study was to evaluate the effectiveness of the…

  9. Radiation promotes colorectal cancer initiation and progression by inducing senescence-associated inflammatory responses.

    Science.gov (United States)

    Kim, S B; Bozeman, R G; Kaisani, A; Kim, W; Zhang, L; Richardson, J A; Wright, W E; Shay, J W

    2016-06-30

    Proton radiotherapy is becoming more common as 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 with 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 (SIRs), 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 and induction of chronic DNA damage and TP53 mutations are increased compared with X-ray irradiation. Proton irradiation also increases the number of colonic polyps, carcinomas and invasive adenocarcinomas. Pretreatment with the non-steroidal anti-inflammatory drug, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid-ethyl amide (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

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

    Science.gov (United States)

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

    2016-10-01

    Although sonic hedgehog (SHH), an essential molecule in embryogenesis and organogenesis, stimulates proliferation of human periodontal ligament (PDL) stem cells, the effects of recombinant human SHH (rh-SHH) on osteoblastic differentiation are unclear. To reveal the role of SHH in periodontal regeneration, expression of SHH in mouse periodontal tissues and its effects on the osteoblastic/cementoblastic differentiation in human cementoblasts were investigated. SHH is immunolocalized to differentiating cementoblasts, PDL cells, and osteoblasts of the developing mouse periodontium. Addition of rh-SHH increased cell growth, ALP activity, and mineralization nodule formation, and upregulated mRNA expression of osteoblastic and cementoblastic markers. The osteoblastic/cementoblastic differentiation of rh-SHH was abolished by the SHH inhibitor cyclopamine (Cy) and the BMP antagonist noggin. rh-SHH increased the expression of BMP-2 and -4 mRNA, as well as levels of phosphorylated Akt, ERK, p38, and JNK, and of MAPK and NF-κB activation, which were reversed by noggin, Cy, and BMP-2 siRNA. Collectively, this study is the first to demonstrate that SHH can promote cell growth and cell osteoblastic/cementoblastic differentiation via BMP pathway. Thus, SHH plays important roles in the development of periodontal tissue, and might represent a new therapeutic target for periodontitis and periodontal regeneration. PMID:27289556

  11. Young Generation in Nuclear Initiative to Promote Nuclear Science and Technology

    International Nuclear Information System (INIS)

    The Kenyan Young Generation in Nuclear (KYGN) is a recently founded not to profit organization. Its mandate is to educate, inform, promote and transfer knowledge on the peaceful, safe and secure users of nuclear science and technology in Kenya. It brings on board all scientist and students with special interest in nuclear science and related fields. KYGN is an affiliate of International Youth Nuclear Congress (YNC) whose membership with IYNC whose membership is drawn from member state of United Nations. Through our membership with IYNC, KYGN members have been able to participate in different forums. In this paper, we discuss KYGN’s prime roles opportunities as well as the challenges of the organization

  12. 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

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

    Science.gov (United States)

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

    2013-12-01

    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.

  14. 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

    2012-06-01

    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.

  15. Dual-reporter in vivo imaging of transient and inducible heat-shock promoter activation.

    Science.gov (United States)

    Fortin, Pierre-Yves; Genevois, Coralie; Chapolard, Mathilde; Santalucía, Tomàs; Planas, Anna M; Couillaud, Franck

    2014-02-01

    Gene promoter activity can be studied in vivo by molecular imaging methods using reporter gene technology. Transcription of the reporter and the reported genes occurs simultaneously. However, imaging depends on reporter protein translation, stability, and cellular fate that may differ among the various proteins. A double transgenic mouse strain expressing the firefly luciferase (lucF) and fluorescent mPlum protein under the transcriptional control of the thermo-inducible heat-shock protein (Hspa1b) promoter was generated allowing to follow up the reporter proteins by different and complementary in vivo imaging technologies. These mice were used for in vivo imaging by bioluminescence and epi fluorescence reflectance imaging (BLI & FRI) and as a source of embryonic fibroblast (MEF) for in vitro approaches. LucF, mPlum and endogenous Hsp70 mRNAs were transcribed simultaneously. The increase in mRNA was transient, peaking at 3 h and then returning to the basal level about 6 h after the thermal stimulations. The bioluminescent signal was transient and initiated with a 3 h delay versus mRNA expression. The onset of mPlum fluorescence was more delayed, increasing slowly up to 30 h after heat-shock and remaining for several days. This mouse allows for both bioluminescence imaging (BLI) and fluorescence reflectance imaging (FRI) of Hsp70 promoter activation showing an early and transient lucF activity and a retrospective and persistent mPlum fluorescence. This transgenic mouse will allow following the transient local induction of Hsp-70 promoter beyond its induction time-frame and relate into subsequent dynamic biological effects of the heat-shock response. PMID:24575340

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

    KAUST Repository

    Zhao, Junpeng

    2014-03-11

    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.

  17. Will initiatives to promote hydroelectricity consumption be effective? Evidence from univariate and panel LM unit root tests with structural breaks

    International Nuclear Information System (INIS)

    This paper examines whether initiatives to promote hydroelectricity consumption are likely to be effective by applying univariate and panel Lagrange Multiplier (LM) unit root tests to hydroelectricity consumption in 55 countries over the period 1965–2011. We find that for the panel, as well as about four-fifths of individual countries, that hydroelectricity consumption is stationary. This result implies that shocks to hydroelectricity consumption in most countries will only result in temporary deviations from the long-run growth path. An important consequence of this finding is that initiatives designed to have permanent positive effects on hydroelectricity consumption, such as large-scale dam construction, are unlikely to be effective in increasing the share of hydroelectricity, relative to consumption of fossil fuels. - Highlights: • Applies unit root tests to hydroelectricity consumption. • Hydroelectricity consumption is stationary. • Shocks to hydroelectricity consumption result in temporary deviations from the long-run growth path

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

    Directory of Open Access Journals (Sweden)

    A. Voigt

    2012-12-01

    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

  19. Promoting Robust Design of Diode Lasers for Space: A National Initiative

    Science.gov (United States)

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

    2007-01-01

    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

  20. MicroRNA-31 initiates lung tumorigenesis and promotes mutant KRAS-driven lung cancer.

    Science.gov (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

    2016-01-01

    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.

  1. The Hierarchy of Transcriptional Activation: From Enhancer to Promoter.

    Science.gov (United States)

    Vernimmen, Douglas; Bickmore, Wendy A

    2015-12-01

    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.

  2. Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells

    International Nuclear Information System (INIS)

    Sox2, a master transcription factor, contributes to the generation of induced pluripotent stem cells and plays significant roles in sustaining the self-renewal of neural stem cells and glioma-initiating cells. Understanding the functional differences of Sox2 between glioma-initiating cells and normal neural stem cells would contribute to therapeutic approach for treatment of brain tumors. Here, we first demonstrated that Sox2 could contribute to the self-renewal and proliferation of glioma-initiating cells. The following experiments showed that Sox2 was activated at translational level in a subset of human glioma-initiating cells compared with the normal neural stem cells. Further investigation revealed there was a positive correlation between Sox2 and eukaryotic initiation factor 4E (eIF4E) in glioma tissues. Down-regulation of eIF4E decreased Sox2 protein level without altering its mRNA level in glioma-initiating cells, indicating that Sox2 was activated by eIF4E at translational level. Furthermore, eIF4E was presumed to regulate the expression of Sox2 by its 5' untranslated region (5' UTR) sequence. Our results suggest that the eIF4E-Sox2 axis is a novel mechanism of unregulated self-renewal of glioma-initiating cells, providing a potential therapeutic target for glioma.

  3. Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Yuqing; Zhou, Fengbiao; Chen, Hong; Cui, Chunhong; Liu, Dan [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Li, Qiuping [Zhongshan Hospital of Fudan University, Shanghai 200032 (China); Yang, Zhiyuan; Wu, Guoqiang [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Sun, Shuhui [Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Gu, Jianxin [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Institutes of Biomedical Sciences of Fudan University, Shanghai 200032 (China); Wei, Yuanyan, E-mail: yywei@fudan.edu.cn [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Jiang, Jianhai, E-mail: jianhaijiang@fudan.edu.cn [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China)

    2010-07-09

    Sox2, a master transcription factor, contributes to the generation of induced pluripotent stem cells and plays significant roles in sustaining the self-renewal of neural stem cells and glioma-initiating cells. Understanding the functional differences of Sox2 between glioma-initiating cells and normal neural stem cells would contribute to therapeutic approach for treatment of brain tumors. Here, we first demonstrated that Sox2 could contribute to the self-renewal and proliferation of glioma-initiating cells. The following experiments showed that Sox2 was activated at translational level in a subset of human glioma-initiating cells compared with the normal neural stem cells. Further investigation revealed there was a positive correlation between Sox2 and eukaryotic initiation factor 4E (eIF4E) in glioma tissues. Down-regulation of eIF4E decreased Sox2 protein level without altering its mRNA level in glioma-initiating cells, indicating that Sox2 was activated by eIF4E at translational level. Furthermore, eIF4E was presumed to regulate the expression of Sox2 by its 5' untranslated region (5' UTR) sequence. Our results suggest that the eIF4E-Sox2 axis is a novel mechanism of unregulated self-renewal of glioma-initiating cells, providing a potential therapeutic target for glioma.

  4. Tissue-specific promoters active in CD44+CD24-/low breast cancer cells.

    Science.gov (United States)

    Bauerschmitz, Gerd J; Ranki, Tuuli; Kangasniemi, Lotta; Ribacka, Camilla; Eriksson, Minna; Porten, Marius; Herrmann, Isabell; Ristimäki, Ari; Virkkunen, Pekka; Tarkkanen, Maija; Hakkarainen, Tanja; Kanerva, Anna; Rein, Daniel; Pesonen, Sari; Hemminki, Akseli

    2008-07-15

    It has been proposed that human tumors contain stem cells that have a central role in tumor initiation and posttreatment relapse. Putative breast cancer stem cells may reside in the CD44(+)CD24(-/low) population. Oncolytic adenoviruses are attractive for killing of these cells because they enter through infection and are therefore not susceptible to active and passive mechanisms that render stem cells resistant to many drugs. Although adenoviruses have been quite safe in cancer trials, preclinical work suggests that toxicity may eventually be possible with more active agents. Therefore, restriction of virus replication to target tissues with tissues-specific promoters is appealing for improving safety and can be achieved without loss of efficacy. We extracted CD44(+)CD24(-/low) cells from pleural effusions of breast cancer patients and found that modification of adenovirus type 5 tropism with the serotype 3 knob increased gene delivery to CD44(+)CD24(-/low) cells. alpha-Lactalbumin, cyclo-oxygenase 2, telomerase, and multidrug resistance protein promoters were studied for activity in CD44(+)CD24(-/low) cells, and a panel of oncolytic viruses was subsequently constructed. Each virus featured 5/3 chimerism of the fiber and a promoter controlling expression of E1A, which was also deleted in the Rb binding domain for additional tumor selectivity. Cell killing assays identified Ad5/3-cox2L-d24 and Ad5/3-mdr-d24 as the most active agents, and these viruses were able to completely eradicate CD44(+)CD24(-/low) cells in vitro. In vivo, these viruses had significant antitumor activity in CD44(+)CD24(-/low)-derived tumors. These findings may have relevance for elimination of cancer stem cells in humans. PMID:18632604

  5. 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)

    2007-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Anna-Karin Lindqvist

    2015-08-01

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

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

    Science.gov (United States)

    Uswatte, Gitendra

    2013-02-01

    Comments on the article by Schmacher et al. (see record 2013-06066-009). Readers of Rehabilitation Psychology might be surprised, or maybe even alarmed, to find an article on promoting physical activity in able-bodied people between the covers of their latest issue. This commentary contends that this area of research and practice might be one into which rehabilitation psychologists want to venture. Schumacher and coworkers describe a field test (N = 216) of a token system for reinforcing stair taking. The setting was an eight-story office building housing a single company in a midsized city in the southeastern United States. Schumacher et al. report an increase from 39 stair transactions per day by all study participants in the 6 months before implementation of the intervention to 301 transactions in the 6 months after the implementation of the intervention, which represents a 600% increase. The cost of the intervention was only $17 per person. Although replication of these results in a study with additional sources of control would increase confidence in the validity of the findings, the size of the gains in stair taking, the number of participants in the study, the length of the baseline and implementation periods, and the objective measurement of outcome warrant attention. PMID:23438004

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (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.

    2015-12-01

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

  10. Combining Health Promotion Classroom Lessons with Health Fair Activities

    Science.gov (United States)

    Cooper, Leslie; Eliason, Kathy; True, Alexandra

    2004-01-01

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

  11. Endothelial cell-initiated signaling promotes the survival and self-renewal of cancer stem cells

    OpenAIRE

    Krishnamurthy, Sudha; Dong, Zhihong; Vodopyanov, Dmitry; Imai, Atsushi; Helman, Joseph I.; Prince, Mark E.; Wicha, Max S.; Jacques E Nör

    2010-01-01

    Recent studies have demonstrated that cancer stem cells play an important role in the pathobiology of head and neck squamous cell carcinomas (HNSCC). However, little is known about functional interactions between head and neck cancer stem-like cells (CSC) and surrounding stromal cells. Here, we used Aldehyde Dehydrogenase activity and CD44 expression to sort putative stem cells from primary human HNSCC. Implantation of 1,000 CSC (ALDH+CD44+Lin−) led to tumors in 13 (out of 15) mice, while 10,...

  12. Activated Alveolar Epithelial Cells Initiate Fibrosis through Secretion of Mesenchymal Proteins

    OpenAIRE

    Yang, Jibing; Wheeler, Sarah E.; Velikoff, Miranda; Kleaveland, Kathryn R.; LaFemina, Michael J.; Frank, James A.; Chapman, Harold A.; Christensen, Paul J; Kim, Kevin K.

    2013-01-01

    Fibrosis is characterized by accumulation of activated fibroblasts and pathological deposition of fibrillar collagens. Activated fibroblasts overexpress matrix proteins and release factors that promote further recruitment of activated fibroblasts, leading to progressive fibrosis. The contribution of epithelial cells to this process remains unknown. Epithelium-directed injury may lead to activation of epithelial cells with phenotypes and functions similar to activated fibroblasts. Prior report...

  13. Investigating ultra high-enthalpy geothermal systems: a collaborative initiative to promote scientific opportunities

    Science.gov (United States)

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

    2014-12-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Dongre A

    2010-01-01

    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

  15. [Comparative analysis of activity of different promoters for NIS gene expression in melanoma cells].

    Science.gov (United States)

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

    2014-01-01

    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.

  16. 78 FR 24393 - Agency Information Collection Activities; Comment Request; Promoting Student Success in Algebra I...

    Science.gov (United States)

    2013-04-25

    ... 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...

  17. 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

    2009-01-01

    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.

  18. 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.

    1992-01-01

    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....

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

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    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

  20. SYNTHESIS, CHARACTERIZATION OF SOME NOVEL PYRAZOLES AND THEIR GROWTH PROMOTING ACTIVITY ON SOME FLOWERING PLANTS

    Directory of Open Access Journals (Sweden)

    Hushare VJ

    2013-01-01

    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.

  1. Activity of heat shock genes' promoters in thermally contrasting animal species.

    Science.gov (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

    2015-01-01

    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.

  2. Making Sense of Total VET Activity: An Initial Market Analysis

    Science.gov (United States)

    National Centre for Vocational Education Research (NCVER), 2016

    2016-01-01

    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…

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

    Science.gov (United States)

    Russ, Laura

    2015-01-01

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

  4. Kinetics of activation of the P4 promoter of pBR322 by the Escherichia coli cyclic AMP receptor protein.

    Science.gov (United States)

    Hoggett, J G; Brierley, I

    1992-11-01

    The activation of transcription initiation from the P4 promoter of pBR322 by the Escherichia coli cyclic AMP receptor protein (CRP) has been investigated using a fluorescence abortive initiation assay. The effect of the cyclic-AMP/CRP complex on the linear P4 promoter was to increase the initial binding (KB) of RNA polymerase to the promoter by about a factor of 10, but the rate of isomerization of closed to open complex (kf) was unaffected. One molecule of CRP per promoter was required for activation, and the concentration of cyclic AMP producing half-maximal stimulation was about 7-8 microM. Supercoiling caused a 2-3-fold increase in the rate of isomerization of the CRP-activated promoter, but weakened the initial binding of polymerase by about one order of magnitude. The unactivated supercoiled promoter was too weak to allow reliable assessment of kinetic parameters against the high background rate originating from the rest of the plasmid. PMID:1445251

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

    Science.gov (United States)

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

    2014-01-01

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

  6. 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

    2005-01-01

    In prokaryotes, DNA supercoiling regulates the expression of many genes; for example, the expression of Klebsiella pneumoniae nifLA operon depends on DNA negative supercoiling in anaerobically grown cells, which indicates that DNA supercoiling might play a role in gene regulation of the anaerobic response. Since the expression of the nifH promoter in Sinorhizobium meliloti is not repressed by oxygen, it is proposed that the status of DNA supercoiling may not affect the expression of the nifH promoter. We tested this hypothesis by analyzing nifH promoter activity in wild-type and gyr- Escherichia coli in the presence and absence of DNA gyrase inhibitors. Our results show that gene expression driven by the S.meliloti nifH promoter requires the presence of active DNA gyrase. Because DNA gyrase increases the number of negative superhelical turns in DNA in the presence of ATP, our data indicate that negative supercoiling is also important for nifH promoter activity. Our study also shows that the DNA 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.

  7. Extending stakeholder theory to promote resource management initiatives to key stakeholders: a case study of water transfers in Alberta, Canada.

    Science.gov (United States)

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

    2013-11-15

    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. PMID:23895936

  8. Initiation of non-tropical thunderstorms by solar activity

    International Nuclear Information System (INIS)

    Correlative evidence accumulating since 1926 suggests that there must be some physical coupling mechanism between solar activity and thunderstorm occurrence in middle to high latitudes. Such a link may be provided by alteration of atmospheric electric parameters through the influence of cosmic ray decreases and/or high-energy solar protons associated with active solar events. Galactic cosmic ray decreases tend to enhance the electric field at low heights. The protons produce excess ionization near and above 20 km, greatly increasing the atmospheric conductivity and possibly lowering the height of the electrosphere. Consequent effects near the solar proton cut-off latitude also lead to an enhancement of the atmospheric electric field near the surface. If appropriate meteorological conditions (warm moist air with updrafts) exist or develop during a solar event, the atmospheric electric field enhancement may be sufficient to trigger thunderstorm development. The suggested mechanism appears plausible enough to warrant a co-ordinated experimental effort involving satellite balloon and ground-based measurements of the possible forcing functions (solar protons and cosmic rays) and the responding atmospheric electrical and ionic species' characteristics. (author)

  9. Dynamic recruitment of active proteasomes into polyglutamine initiated inclusion bodies.

    Science.gov (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

    2014-01-01

    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.

  10. Extravehicular Activity Systems Education and Public Outreach in Support of NASA's STEM Initiatives in Fiscal Year 2011

    Science.gov (United States)

    Paul, Heather; Jennings, Mallory A.; Lamberth, Erika Guillory

    2012-01-01

    NASA's goals to send humans beyond low Earth orbit will involve the need for a strong engineering workforce. Research indicates that student interest in science, technology, engineering, and math (STEM) areas is on the decline. According to the Department of Education, the United States President has mandated that 100,000 educators be trained in STEM over the next decade to reduce this trend. NASA has aligned its Education and Public Outreach (EPO) initiatives to include emphasis in promoting STEM. The Extravehicular Activity (EVA) Systems Project Office at the NASA Johnson Space Center actively supports this NASA initiative by providing subject matter experts and hands-on, interactive presentations to educate students, educators, and the general public about the design challenges encountered as NASA develops EVA hardware for exploration missions. This paper summarizes the EVA Systems EPO efforts and metrics from fiscal year 2011.

  11. Initial Work Toward A Robotically Assisted Extravehicular Activity Glove

    Science.gov (United States)

    Rogers, Jonathan M.; Peters, Benjamin J.; Laske, Evans A.; McBryan, Emily R.

    2016-01-01

    The Space Suit RoboGlove (SSRG) is a glove designed to provide additional grasp strength or endurance for an Extravehicular Activity (EVA) crew member, since a pressurized space suit gloved hand performance is a fraction of what the unencumbered human hand can achieve. There have been past efforts to improve space suit gloved hand performance by employing novel materials and construction techniques to the glove design, as well as integrating powered assistance devices into the gloves. These past efforts were not completely successful and the National Aeronautics and Space Administration (NASA) decided to develop a new glove based on the NASA/General Motors RoboGlove technology. The resulting SSRG used a unique approach to integrate the robotic actuators and sensors into a Phase VI EVA glove that resulted in a space suit glove that provided grasp augmentation to the user while the augmentation is activated, and also functioned as a normal glove when the augmentation is disabled. Care was taken to avoid adding excessive bulk to the glove or affecting tactility by choosing low-profile sensors and locating the actuators at a distance from the fingers. Conduits were used to guide robotic tendons from linear actuators, across the wrist, and to the fingers. The electromechanical design, softgoods integration, control system, and early test results of the first generation SSRG are presented in this paper. These early test results showed that this sensor integration did not impact tactile feedback in the glove and that the actuators provided potential for increased grip strength and reduction in grasp fatigue over time.

  12. Has the Alberta daily physical activity initiative been successfully implemented in Calgary schools?

    NARCIS (Netherlands)

    Kennedy, Christine Diane; Cantell, Marja; Dewey, Deborah

    2010-01-01

    INTRODUCTION: In September 2005, the Alberta government introduced the daily physical activity (DPA) initiative, which requires that students from grades 1 to 9 be physically active in school for a minimum of 30 min per day. OBJECTIVE: To obtain information on whether and how the DPA initiative has

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

    NARCIS (Netherlands)

    Verhagen, E.; Engbers, L.

    2009-01-01

    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

  14. 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.

    Science.gov (United States)

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

    2007-03-01

    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.

  15. INVESTIGATION INTO CONSUMER RESPONSE TO SALES PROMOTIONAL ACTIVITIES: THE CASE OF UNILEVER GHANA LIMITED

    Directory of Open Access Journals (Sweden)

    Martin Owusu Ansah

    2013-10-01

    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.

  16. Promoting physical activity in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Berg, Machteld Heleen van den

    2007-01-01

    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

  17. Promoting Physical Activity: Addressing Barriers and Moving Forward

    Science.gov (United States)

    Beighle, Aaron; Morrow, James R.

    2014-01-01

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

  18. Strategies for Physical Activity Promotion beyond the Physical Education Classroom

    Science.gov (United States)

    Faber, Larry; Kulinna, Pamela Hodges; Darst, Paul

    2007-01-01

    The current need for physical activity has extended beyond the limited time given to students in physical education classes. In order for students to receive appropriate levels of physical activity (i.e., at least 60 minutes per day), it is necessary for physical educators to incorporate physical activity opportunities outside the traditional…

  19. Initial Teacher Education for School Health Promotion in Austria: Does It Support the Implementation of the Health-Promoting School Approach?

    Science.gov (United States)

    Flaschberger, Edith

    2013-01-01

    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…

  20. 5-azacytidine promotes microspore embryogenesis initiation by decreasing global DNA methylation, but prevents subsequent embryo development in rapeseed and barley

    Science.gov (United States)

    Solís, María-Teresa; El-Tantawy, Ahmed-Abdalla; Cano, Vanesa; Risueño, María C.; Testillano, Pilar S.

    2015-01-01

    Microspores are reprogrammed by stress in vitro toward embryogenesis. This process is an important tool in breeding to obtain double-haploid plants. DNA methylation is a major epigenetic modification that changes in differentiation and proliferation. We have shown changes in global DNA methylation during microspore reprogramming. 5-Azacytidine (AzaC) cannot be methylated and leads to DNA hypomethylation. AzaC is a useful demethylating agent to study DNA dynamics, with a potential application in microspore embryogenesis. This work analyzes the effects of short and long AzaC treatments on microspore embryogenesis initiation and progression in two species, the dicot Brassica napus and the monocot Hordeum vulgare. This involved the quantitative analyses of proembryo and embryo production, the quantification of DNA methylation, 5-methyl-deoxy-cytidine (5mdC) immunofluorescence and confocal microscopy, and the analysis of chromatin organization (condensation/decondensation) by light and electron microscopy. Four days of AzaC treatments (2.5 μM) increased embryo induction, response associated with a decrease of DNA methylation, modified 5mdC, and heterochromatin patterns compared to untreated embryos. By contrast, longer AzaC treatments diminished embryo production. Similar effects were found in both species, indicating that DNA demethylation promotes microspore reprogramming, totipotency acquisition, and embryogenesis initiation, while embryo differentiation requires de novo DNA methylation and is prevented by AzaC. This suggests a role for DNA methylation in the repression of microspore reprogramming and possibly totipotency acquisition. Results provide new insights into the role of epigenetic modifications in microspore embryogenesis and suggest a potential benefit of inhibitors, such as AzaC, to improve the process efficiency in biotechnology and breeding programs. PMID:26161085

  1. 5-azacytidine promotes microspore embryogenesis initiation by decreasing global DNA methylation, but prevents subsequent embryo development in rapeseed and barley.

    Science.gov (United States)

    Solís, María-Teresa; El-Tantawy, Ahmed-Abdalla; Cano, Vanesa; Risueño, María C; Testillano, Pilar S

    2015-01-01

    Microspores are reprogrammed by stress in vitro toward embryogenesis. This process is an important tool in breeding to obtain double-haploid plants. DNA methylation is a major epigenetic modification that changes in differentiation and proliferation. We have shown changes in global DNA methylation during microspore reprogramming. 5-Azacytidine (AzaC) cannot be methylated and leads to DNA hypomethylation. AzaC is a useful demethylating agent to study DNA dynamics, with a potential application in microspore embryogenesis. This work analyzes the effects of short and long AzaC treatments on microspore embryogenesis initiation and progression in two species, the dicot Brassica napus and the monocot Hordeum vulgare. This involved the quantitative analyses of proembryo and embryo production, the quantification of DNA methylation, 5-methyl-deoxy-cytidine (5mdC) immunofluorescence and confocal microscopy, and the analysis of chromatin organization (condensation/decondensation) by light and electron microscopy. Four days of AzaC treatments (2.5 μM) increased embryo induction, response associated with a decrease of DNA methylation, modified 5mdC, and heterochromatin patterns compared to untreated embryos. By contrast, longer AzaC treatments diminished embryo production. Similar effects were found in both species, indicating that DNA demethylation promotes microspore reprogramming, totipotency acquisition, and embryogenesis initiation, while embryo differentiation requires de novo DNA methylation and is prevented by AzaC. This suggests a role for DNA methylation in the repression of microspore reprogramming and possibly totipotency acquisition. Results provide new insights into the role of epigenetic modifications in microspore embryogenesis and suggest a potential benefit of inhibitors, such as AzaC, to improve the process efficiency in biotechnology and breeding programs. PMID:26161085

  2. 5-azacytidine promotes microspore embryogenesis initiation by decreasing global DNA methylation, but prevents subsequent embryo development in rapeseed and barley

    Directory of Open Access Journals (Sweden)

    María-Teresa eSolís

    2015-06-01

    Full Text Available Microspores are reprogrammed by stress in vitro towards embryogenesis. This process is an important tool in breeding to obtain double-haploid plants. DNA methylation is a major epigenetic modification that changes in differentiation and proliferation. We have shown changes in global DNA methylation during microspore reprogramming. 5-Azacytidine (AzaC cannot be methylated and leads to DNA hypomethylation. AzaC is a useful demethylating agent to study DNA dynamics, with a potential application in microspore embryogenesis. This work analyzes the effects of short and long AzaC treatments on microspore embryogenesis initiation and progression in two species, the dicot Brassica napus and the monocot Hordeum vulgare. This involved the quantitative analyses of proembryo and embryo production, the quantification of DNA methylation, 5mdC immunofluorescence and confocal microscopy, and the analysis of chromatin organization (condensation/ decondensation by light and electron microscopy. Four days of AzaC treatments (2.5 µM increased embryo induction, response associated with a decrease of DNA methylation, modified 5mdC and heterochromatin patterns compared to untreated embryos. By contrast, longer AzaC treatments diminished embryo production. Similar effects were found in both species, indicating that DNA demethylation promotes microspore reprogramming, totipotency acquisition and embryogenesis initiation, while embryo differentiation requires de novo DNA methylation and is prevented by AzaC. This suggests a role for DNA methylation in the repression of microspore reprogramming and possibly totipotency acquisition.Results provide new insights into the role of epigenetic modifications in microspore embryogenesis and suggest a potential benefit of inhibitors, such as AzaC, to improve the process efficiency in biotechnology and breeding programs.

  3. 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.

  4. The Southern Mariana Forearc: An Active Subduction Initiation (SI) Analogue

    Science.gov (United States)

    Stern, R. J.; Bloomer, S. H.; Brounce, M. N.; Ishii, T.; Ishizuka, O.; Kelley, K. A.; Martinez, F.; Ohara, Y.; Pujana, I.; Reagan, M. K.; Ribeiro, J.

    2014-12-01

    It is important to understand how new subduction zones form. Some subduction zones begin spontaneously, with sinking of dense oceanic lithosphere adjacent to a lithospheric weakness. The Eocene evolution of the Izu-Bonin-Mariana convergent margin is the type example of this process, with an increasingly well-documented evolution including results from IODP 352 drilling. A lack of any active examples of spontaneous SI hinders our understanding, but our studies of the evolution of the southernmost Mariana convergent margin provides important insights. Here the Mariana Trough backarc basin terminates against the Challenger Deep trench segment, where it has opened ~250 km in the past ~4 Ma. This corresponds to GPS opening rate of ~4.5cm/y at the latitude of Guam (Kato et al., 2003). This newly formed and rapidy widening margin faces the NW-converging Pacific plate and causes it to contort and tear. Pacific plate continues to move NW but the upper plate response is illustrative of a newly formed subduction zone. Slab-related earthquakes can be identified to ~200 km deep beneath this margin; with convergence rate of 3cm/yr, this may reflect no more than 7 Ma of subduction. The usual well-defined magmatic arc is missing; its position ~100 km above the subducted slab is occupied by the magma-rich (inflated) Malaguana-Gadao Ridge (MGR), and hydrous MORB-like basalts with ~2 wt. % H2O have erupted unusually close to the trench where they overly mantle peridotites ~6 km water depth. HMR-1 sonar backscatter mapping reveals a chaotic fabric that is at a high angle to the trend of the MGR to the east but is concordant to the west. This unusual spreading fabric may have formed by chaotic upper plate extension in response to rapid rollback of the short, narrow Pacific slab in a manner similar to that thought to occur during SI. Further interdisciplinary studies are needed to understand this rapidly-evolving tectono-magmatic province and what it can teach us about SI.

  5. Anthracyclines induce double-strand DNA breaks at active gene promoters.

    Science.gov (United States)

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

    2015-03-01

    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. 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.

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

    Science.gov (United States)

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

    2014-08-01

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

  8. 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

    2007-01-01

    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.

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

    Science.gov (United States)

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

    2012-01-01

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

  10. Activated Scavenger Receptor A Promotes Glial Internalization of Aβ

    OpenAIRE

    He Zhang; Ya-jing Su; Wei-wei Zhou; Shao-wei Wang; Peng-xin Xu; Xiao-lin Yu; Rui-tian Liu

    2014-01-01

    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...

  11. Considerations on the promotional activity on the DIY market in Romania

    OpenAIRE

    Mihai FÎNARU; Ioana Bianca CHIŢU

    2015-01-01

    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 technique...

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

    OpenAIRE

    Naray, Olivier; Bezençon, Valéry; Kostecki, Michel

    2015-01-01

    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...

  13. Development of an accelerometer-linked online intervention system to promote physical activity in adolescents.

    Directory of Open Access Journals (Sweden)

    Nicole Guthrie

    Full Text Available Most adolescents do not achieve the recommended levels of moderate-to-vigorous physical activity (MVPA, placing them at increased risk for a diverse array of chronic diseases in adulthood. There is a great need for scalable and effective interventions that can increase MVPA in adolescents. Here we report the results of a measurement validation study and a preliminary proof-of-concept experiment testing the impact of Zamzee, an accelerometer-linked online intervention system that combines proximal performance feedback and incentive motivation features to promote MVPA. In a calibration study that parametrically varied levels of physical activity in 31 12-14 year-old children, the Zamzee activity meter was shown to provide a valid measure of MVPA (sensitivity in detecting MVPA = 85.9%, specificity = 97.5%, and r = .94 correspondence with the benchmark RT3 accelerometer system; all p < .0001. In a subsequent randomized controlled multi-site experiment involving 182 middle school-aged children assessed for MVPA over 6 wks, intent-to-treat analyses found that those who received access to the Zamzee intervention had average MVPA levels 54% greater than those of a passive control group (p < 0.0001 and 68% greater than those of an active control group that received access to a commercially available active videogame (p < .0001. Zamzee's effects on MVPA did not diminish significantly over the course of the 6-wk study period, and were statistically significant in both females and males, and in normal- vs. high-BMI subgroups. These results provide promising initial indications that combining the Zamzee activity meter with online proximal performance feedback and incentive motivation features can positively impact MVPA levels in adolescents.

  14. 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.

  15. Changing organizational culture: using the CEO cancer gold standard policy initiatives to promote health and wellness at a school of public health

    OpenAIRE

    Towne, Samuel D.; Anderson, Kelsey E.; Smith, Matthew Lee; Dahlke, Deborah Vollmer; Kellstedt, Debra; Purcell, Ninfa Pena; Marcia G. Ory

    2015-01-01

    Background Worksite wellness initiatives for health promotion and health education have demonstrated effectiveness in improving employee health and wellness. We examined the effects of a multifaceted health promotion campaign on organizational capacity to meet requirements to become CEO Cancer Gold Standard Accredited. Methods We conducted an online survey to assess perceived organizational values and support for the five CEO Cancer Gold Standard Pillars for cancer prevention: tobacco cessati...

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

    Science.gov (United States)

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

    2012-10-01

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

  17. 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.

    2009-01-01

    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

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

    Science.gov (United States)

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

    2012-01-01

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

  19. TP0262 is a modulator of promoter activity of tpr Subfamily II genes of Treponema pallidum ssp. pallidum.

    Science.gov (United States)

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

    2009-06-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Kelly Jason R

    2009-03-01

    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

  1. 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....... 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....

  2. Spatio-Temporal Imaging of Promoter Activity in Intact Plant Tissues.

    Science.gov (United States)

    Xiong, Tou Cheu; Sanchez, Frédéric; Briat, Jean-François; Gaymard, Frédéric; Dubos, Christian

    2016-01-01

    Localization and quantification of expression levels of genes help to determine their function. Localization of gene expression is often achieved through the study of their promoter activity. Three main reporter genes β-glucuronidase (GUS), green fluorescent protein (GFP), and luciferase (LUC) have been intensively used to characterize promoter activities, each having its own specificities and advantages. Among them, the LUC reporter gene is best suitable for the analysis of the promoter activity of genes in intact living plants. Here, we describe a LUC-based method that allows to precisely localize and quantify promoter activity at the whole plant level, and to study the mechanisms that are involved in long-distance regulation of gene expression in Arabidopsis thaliana. Imaging LUC signals with a low-light CCD camera allows monitoring promoter activity in time and space in the transgenic plant harboring the promoter fused with the LUC gene. In addition, it allows quantifying change of promoter activities in plant during several hours. PMID:27557763

  3. 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.

    2007-01-01

    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

  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.

    2010-01-01

    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. Biological Activity of the Alternative Promoters of the Dictyostelium discoideum Adenylyl Cyclase A Gene.

    Science.gov (United States)

    Rodriguez-Centeno, Javier; Sastre, Leandro

    2016-01-01

    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.

  6. Complement activation promotes muscle inflammation during modified muscle use

    Science.gov (United States)

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

    2000-01-01

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

  7. 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.

    1988-05-01

    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.

  8. 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.

    2005-04-05

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

  9. AITI and GELATI - Initiatives to promote education and training for the next generation of educators and scientists during the IPY 2007/08 and beyond

    Science.gov (United States)

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

    2005-05-01

    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

  10. An MSC2 Promoter-lacZ Fusion Gene Reveals Zinc-Responsive Changes in Sites of Transcription Initiation That Occur across the Yeast Genome

    Science.gov (United States)

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

    2016-01-01

    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

  11. Loss of Ezh2 synergizes with JAK2-V617F in initiating myeloproliferative neoplasms and promoting myelofibrosis.

    Science.gov (United States)

    Shimizu, Takafumi; Kubovcakova, Lucia; Nienhold, Ronny; Zmajkovic, Jakub; Meyer, Sara C; Hao-Shen, Hui; Geier, Florian; Dirnhofer, Stephan; Guglielmelli, Paola; Vannucchi, Alessandro M; Feenstra, Jelena D Milosevic; Kralovics, Robert; Orkin, Stuart H; Skoda, Radek C

    2016-07-25

    Myeloproliferative neoplasm (MPN) patients frequently show co-occurrence of JAK2-V617F and mutations in epigenetic regulator genes, including EZH2 In this study, we show that JAK2-V617F and loss of Ezh2 in hematopoietic cells contribute synergistically to the development of MPN. The MPN phenotype induced by JAK2-V617F was accentuated in JAK2-V617F;Ezh2(-/-) mice, resulting in very high platelet and neutrophil counts, more advanced myelofibrosis, and reduced survival. These mice also displayed expansion of the stem cell and progenitor cell compartments and a shift of differentiation toward megakaryopoiesis at the expense of erythropoiesis. Single cell limiting dilution transplantation with bone marrow from JAK2-V617F;Ezh2(+/-) mice showed increased reconstitution and MPN disease initiation potential compared with JAK2-V617F alone. RNA sequencing in Ezh2-deficient hematopoietic stem cells (HSCs) and megakaryocytic erythroid progenitors identified highly up-regulated genes, including Lin28b and Hmga2, and chromatin immunoprecipitation (ChIP)-quantitative PCR (qPCR) analysis of their promoters revealed decreased H3K27me3 deposition. Forced expression of Hmga2 resulted in increased chimerism and platelet counts in recipients of retrovirally transduced HSCs. JAK2-V617F-expressing mice treated with an Ezh2 inhibitor showed higher platelet counts than vehicle controls. Our data support the proposed tumor suppressor function of EZH2 in patients with MPN and call for caution when considering using Ezh2 inhibitors in MPN. PMID:27401344

  12. 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

    2012-01-01

    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.

  13. 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.

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

    OpenAIRE

    Ahmet ÇATLI; Özlem ÇATLI

    2013-01-01

    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 promotio...

  15. Organizational Informatization and Promoting the Active Participation of Women in the Workplace (Japanese)

    OpenAIRE

    USHIO Naomi; Shimura, Kotaro

    2014-01-01

    There still has not been sufficient promotion of the active participation of women in the workplace in Japan. The main factors behind this situation are a uniform view of women and the failure to adopt a stance of inclusion. Accordingly, there is a need to establish the following systems and culture in order to promote the active participation of women in the workplace: (1) Recognize that "women" are composed of a diverse range of different individuals; and (2) Accept the diversity of women, ...

  16. Evaluation of Phytase Producing Bacteria for Their Plant Growth Promoting Activities

    OpenAIRE

    Prashant Singh; Vinod Kumar; Sanjeev Agrawal

    2014-01-01

    Bacterial inoculants are known to possess plant growth promoting abilities and have potential as liquid biofertilizer application. Four phytase producing bacterial isolates (phytase activity in the range of 0.076–0.174 U/mL), identified as Advenella species (PB-05, PB-06, and PB-10) and Cellulosimicrobium sp. PB-09, were analyzed for their plant growth promoting activities like siderophore production, IAA production, HCN production, ammonia production, phosphate solubilization, and antifungal...

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

    Science.gov (United States)

    Gao, Jinzhu; Hargis, Jace

    2010-01-01

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

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

    Science.gov (United States)

    West, Stephanie T.; Shores, Kindal A.

    2014-01-01

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

  19. Promoting Private Agribusiness Activity in Sub-Saharan Africa

    OpenAIRE

    Jaffee, Steven; Morton, John

    1995-01-01

    In a break from past policies, many countries of Sub-Saharan Africa are moving away from state-controlled agricultural marketing systems. Agricultural sector and broader economic policy reforms are being implemented, one objective of which is to enhance the incentives for private entrepreneurs and companies to undertake investments and expand and diversify agro-processing and trading activ...

  20. Bringing Nature to Schools to Promote Children's Physical Activity.

    Science.gov (United States)

    Sharma-Brymer, Vinathe; Bland, Derek

    2016-07-01

    Physical activity (PA) is essential for human health and wellbeing across all age, socioeconomic, and ethnic groups. Engagement with the natural world is a new defining criterion for enhancing the benefits of PA, particularly for children and young people. Interacting with nature benefits children's social and emotional wellbeing, develops resilience, and reduces the risk of obesity and type 2 diabetes mellitus across all population groups. Governments around the world are now recognizing the importance of children spending more active time outdoors. However, children's outdoor activities, free play, and nature-related exploration are often structured and supervised by adults due to safety concerns and risks. In this context, schools become more accessible and safe options for children to engage in PA outdoors with the presence of nature features. Research on school designs involving young children has revealed that children prefer nature-related features in school environments. Affordances in nature may increase children's interest in physically active behaviors. Given that present school campuses are designed for operational efficiency and economic reasons, there is a need to re-design schools responding to the positive role of nature on human health. If schools were re-designed to incorporate diverse natural features, children's PA and consequent health and wellbeing would likely improve markedly. PMID:26888647

  1. Community Resources for Promoting Youth Nutrition and Physical Activity

    Science.gov (United States)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2005-01-01

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

  3. AGC kinases regulate phosphorylation and activation of eukaryotic translation initiation factor 4B

    NARCIS (Netherlands)

    van Gorp, A. G. M.; van der Vos, K. E.; Brenkman, A. B.; Bremer, A.; van den Broek, N.; Zwartkruis, F.; Hershey, J. W.; Burgering, B. M. T.; Calkhoven, C. F.; Coffer, P. J.

    2009-01-01

    Eukaryotic translation initiation factor 4B (eIF4B) plays a critical role during the initiation of protein synthesis and its activity can be regulated by multiple phosphorylation events. In a search for novel protein kinase B (PKB/c-akt) substrates, we identified eIF4B as a potential target. Using a

  4. Physical activity promotion among underserved adolescents: "make it fun, easy, and popular".

    Science.gov (United States)

    Louise Bush, Paula; Laberge, Suzanne; Laforest, Sophie

    2010-05-01

    There is a paucity of studies regarding noncurricular physical activity promotion interventions among adolescents, and even less such research pertaining to underserved youth. This article describes the development and implementation of a noncurricular, school-based physical activity promotion program designed for a multiethnic, underserved population of adolescents. The program's impact on leisure-time physical activity (LTPA) and on physical activity enjoyment (PAE) is also presented. The 16-week program, named FunAction, utilizes social marketing principles. Control (n = 90) and intervention (n = 131) students are assessed pre- and postintervention for levels of LTPA and PAE. Results indicate that although the program did not contribute to an increase in LTPA or PAE among intervention group students, participation in the program was elevated. This study offers preliminary evidence that noncurricular physical activity promotion programs that apply social marketing principles can be effective in engaging multiethnic, underserved adolescents in physical activity. PMID:19168890

  5. GLT-1 promoter activity in astrocytes and neurons of mouse hippocampus and somatic sensory cortex

    Directory of Open Access Journals (Sweden)

    Luisa De Vivo

    2010-01-01

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

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

    Science.gov (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

    2004-08-01

    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.

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

    OpenAIRE

    Arora, Mansi; Jie ZHANG; Heine, George F.; Ozer, Gulcin; Liu, Hui-Wen; Huang, Kun; Parvin, Jeffrey D.

    2012-01-01

    We analyzed modification of chromatin by ubiquitination in human cells and whether this mark changes through the cell cycle. HeLa cells were synchronized at different stages and regions of the genome with ubiquitinated chromatin were identified by affinity purification coupled with next-generation sequencing. During interphase, ubiquitin marked the chromatin on the transcribed regions of ∼70% of highly active genes and deposition of this mark was sensitive to transcriptional inhibition. Promo...

  8. 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.

  9. 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

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

    OpenAIRE

    Yongyan Shi; Tianjing Liu; Lei He; Urszula Dougherty; Li Chen; Sarbani Adhikari; Lindsay Alpert; Guolin Zhou; Weicheng Liu; Jiaolong Wang; Deb, Dilip K.; John Hart; Liu, Shu Q.; John Kwon; Joel Pekow

    2016-01-01

    The renin-angiotensin system (RAS) plays pathogenic roles in renal and cardiovascular disorders, but whether it is involved in colitis is unclear. Here we show that RenTgMK mice that overexpress active renin from the liver developed more severe colitis than wild-type controls. More than 50% RenTgMK mice died whereas all wild-type mice recovered. RenTgMK mice exhibited more robust mucosal TH17 and TH1/TH17 responses and more profound colonic epithelial cell apoptosis compared to wild-type cont...

  11. Statins Activate Human PPAR Promoter and Increase PPAR mRNA Expression and Activation in HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Makoto Seo

    2008-01-01

    Full Text Available Statins increase peroxisome proliferator-activated receptor (PPAR mRNA expression, but the mechanism of this increased PPAR production remains elusive. To examine the regulation of PPAR production, we examined the effect of 7 statins (atorvastatin, cerivastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin on human PPAR promoter activity, mRNA expression, nuclear protein levels, and transcriptional activity. The main results are as follows. (1 Majority of statins enhanced PPAR promoter activity in a dose-dependent manner in HepG2 cells transfected with the human PPAR promoter. This enhancement may be mediated by statin-induced HNF-4. (2 PPAR mRNA expression was increased by statin treatment. (3 The PPAR levels in nuclear fractions were increased by statin treatment. (4 Simvastatin, pravastatin, and cerivastatin markedly enhanced transcriptional activity in 293T cells cotransfected with acyl-coenzyme A oxidase promoter and PPAR/RXR expression vectors. In summary, these data demonstrate that PPAR production and activation are upregulated through the PPAR promoter activity by statin treatment.

  12. Cloning the Horse RNA Polymerase I Promoter and Its Application to Studying Influenza Virus Polymerase Activity.

    Science.gov (United States)

    Lu, Gang; He, Dong; Wang, Zengchao; Ou, Shudan; Yuan, Rong; Li, Shoujun

    2016-01-01

    An influenza virus polymerase reconstitution assay based on the human, dog, or chicken RNA polymerase I (PolI) promoter has been developed and widely used to study the polymerase activity of the influenza virus in corresponding cell types. Although it is an important member of the influenza virus family and has been known for sixty years, no studies have been performed to clone the horse PolI promoter or to study the polymerase activity of equine influenza virus (EIV) in horse cells. In our study, the horse RNA PolI promoter was cloned from fetal equine lung cells. Using the luciferase assay, it was found that a 500 bp horse RNA PolI promoter sequence was required for efficient transcription. Then, using the developed polymerase reconstitution assay based on the horse RNA PolI promoter, the polymerase activity of two EIV strains was compared, and equine myxovirus resistance A protein was identified as having the inhibiting EIV polymerase activity function in horse cells. Our study enriches our knowledge of the RNA PolI promoter of eukaryotic species and provides a useful tool for the study of influenza virus polymerase activity in horse cells. PMID:27258298

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

    Directory of Open Access Journals (Sweden)

    Ahmet ÇATLI

    2013-06-01

    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.

  14. Cloning the Horse RNA Polymerase I Promoter and Its Application to Studying Influenza Virus Polymerase Activity

    Science.gov (United States)

    Lu, Gang; He, Dong; Wang, Zengchao; Ou, Shudan; Yuan, Rong; Li, Shoujun

    2016-01-01

    An influenza virus polymerase reconstitution assay based on the human, dog, or chicken RNA polymerase I (PolI) promoter has been developed and widely used to study the polymerase activity of the influenza virus in corresponding cell types. Although it is an important member of the influenza virus family and has been known for sixty years, no studies have been performed to clone the horse PolI promoter or to study the polymerase activity of equine influenza virus (EIV) in horse cells. In our study, the horse RNA PolI promoter was cloned from fetal equine lung cells. Using the luciferase assay, it was found that a 500 bp horse RNA PolI promoter sequence was required for efficient transcription. Then, using the developed polymerase reconstitution assay based on the horse RNA PolI promoter, the polymerase activity of two EIV strains was compared, and equine myxovirus resistance A protein was identified as having the inhibiting EIV polymerase activity function in horse cells. Our study enriches our knowledge of the RNA PolI promoter of eukaryotic species and provides a useful tool for the study of influenza virus polymerase activity in horse cells. PMID:27258298

  15. Notch signaling promotes osteoclast maturation and resorptive activity.

    Science.gov (United States)

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

    2015-11-01

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

  16. Endothelial Cells Promote Pigmentation through Endothelin Receptor B Activation.

    Science.gov (United States)

    Regazzetti, Claire; De Donatis, Gian Marco; Ghorbel, Houda Hammami; Cardot-Leccia, Nathalie; Ambrosetti, Damien; Bahadoran, Philippe; Chignon-Sicard, Bérengère; Lacour, Jean-Philippe; Ballotti, Robert; Mahns, Andre; Passeron, Thierry

    2015-12-01

    Findings of increased vascularization in melasma lesions and hyperpigmentation in acquired bilateral telangiectatic macules suggested a link between pigmentation and vascularization. Using high-magnification digital epiluminescence dermatoscopy, laser confocal microscopy, and histological examination, we showed that benign vascular lesions of the skin have restricted but significant hyperpigmentation compared with the surrounding skin. We then studied the role of microvascular endothelial cells in regulating skin pigmentation using an in vitro co-culture model using endothelial cells and melanocytes. These experiments showed that endothelin 1 released by microvascular endothelial cells induces increased melanogenesis signaling, characterized by microphthalmia-associated transcription factor phosphorylation, and increased tyrosinase and dopachrome tautomerase levels. Immunostaining for endothelin 1 in vascular lesions confirmed the increased expression on the basal layer of the epidermis above small vessels compared with perilesional skin. Endothelin acts through the activation of endothelin receptor B and the mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK)1/2, and p38, to induce melanogenesis. Finally, culturing of reconstructed skin with microvascular endothelial cells led to increased skin pigmentation that could be prevented by inhibiting EDNRB. Taken together these results demonstrated the role of underlying microvascularization in skin pigmentation, a finding that could open new fields of research for regulating physiological pigmentation and for treating pigmentation disorders such as melasma. PMID:26308584

  17. 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.

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

    Science.gov (United States)

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

    2011-08-01

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

  19. Promoting Active Learning in Electrical Engineering Basic Studies

    Directory of Open Access Journals (Sweden)

    Anu Lehtovuori

    2013-05-01

    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.

  20. Promoting uranium immobilization by the activities of microbial phophatases

    Energy Technology Data Exchange (ETDEWEB)

    Sobecky, Patricia A.

    2005-06-01

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

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

    Science.gov (United States)

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

    2009-08-01

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

  2. Developing and Testing Smartphone Game Applications for Physical Activity Promotion in Adolescents

    OpenAIRE

    Allen, Kacie Chanelle

    2013-01-01

    Though the benefits of physical activity are numerous and well-known, very few adolescents are meeting physical activity recommendations. Moreover, past research shows that physical activity declines with increasing age with this decline beginning in adolescence. One approach to promote physical activity is through mobile technology such as a mobile phone. Since mobile phone ownership is relatively high (77%) and there is no digital divide by race/ethnicity or socioeconomic status, mobile pho...

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

    OpenAIRE

    Mohamadian, Hashem; Ghannaee Arani, Mohammad

    2014-01-01

    Objectives Physical activity behavior begins to decline during adolescence and continues to decrease throughout young adulthood. This study aims to explain factors that influence physical activity behavior in a sample of female adolescents using a health promotion model framework. Methods This cross-sectional survey was used to explore physical activity behavior among a sample of female adolescents. Participants completed measures of physical activity, perceived self-efficacy, self-esteem, so...

  4. Activated Cdc42-associated kinase Ack1 promotes prostate cancer progression via androgen receptor tyrosine phosphorylation

    OpenAIRE

    Mahajan, Nupam P.; Liu, Yuanbo; Majumder, Samarpan; Warren, Maria R.; Parker, Carol E.; Mohler, James L.; Earp, H. Shelton; Whang, Young E.

    2007-01-01

    Activation of the androgen receptor (AR) may play a role in androgen-independent progression of prostate cancer. Multiple mechanisms of AR activation, including stimulation by tyrosine kinases, have been postulated. We and others have recently shown involvement of activated Cdc42-associated tyrosine kinase Ack1 in advanced human prostate cancer. Here we provide the molecular basis for interplay between Ack1 and AR in prostate cancer cells. Activated Ack1 promoted androgen-independent growth o...

  5. Desired features of smartphone applications promoting physical activity.

    Science.gov (United States)

    Rabin, Carolyn; Bock, Beth

    2011-12-01

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

  6. Two tobacco AP1-like gene promoters drive highly specific, tightly regulated and unique expression patterns during floral transition, initiation and development.

    Science.gov (United States)

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

    2014-02-01

    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.

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

    Science.gov (United States)

    Hildebrand, Mary; Neufeld, Peggy

    2009-01-01

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

  8. The Ne3LS Network, Quebec's initiative to evaluate the impact and promote a responsible and sustainable development of nanotechnology

    International Nuclear Information System (INIS)

    The spectacular progress made by nanosciences and nanotechnologies elicits as much hope and fear. Consequently, a great number of research and training initiatives on the ethical, environmental, economic, legal and social issues regarding nanotechnology development (Ne3LS) are emerging worldwide. In Quebec, Canada, a Task Force was mandated by NanoQuebec to conceive a Ne3LS research and training strategy to assess those issues. This Task Force brought together experts from universities, governments or industry working in nanosciences and nanotechnologies or in Ne3LS. Their resulting action plan, made public in November 2006, contained several recommendations, including the creation of a knowledge network (Ne3LS Network). In the following years, after consulting with numerous key players concerned with the possible impacts of nanosciences and nanotechnologies in Quebec, the Ne3LS Network was launched in January 2010 in partnership with the Fonds quebecois de la recherche sur la nature et les technologies, the Fonds quebecois de la recherche sur la societe et la culture and the Fonds de la recherche en sante du Quebec, NanoQuebec, the Institut de recherche Robert-Sauve en sante et en securite du travail as well as the University of Montreal. Its objectives are to 1) Foster the development of Ne3LS research activities (grants and fellowships); 2) Spearhead the Canadian and international Ne3LS network; 3) Take part in the training of researchers and experts; 4) Encourage the creation of interactive tools for the general public; 5) Facilitate collaboration between decision-makers and experts; 6) Involve the scientific community through a host of activities (symposium, conferences, thematic events); 7) Build multidisciplinary research teams to evaluate the impact of nanotechnology.

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

    Science.gov (United States)

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

    2015-11-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    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.

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

    Science.gov (United States)

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

    2015-01-01

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

  12. Semantic relatedness among objects promotes the activation of multiple phonological codes during object naming

    NARCIS (Netherlands)

    Oppermann, F.; Jescheniak, J.D.; Schriefers, H.J.; Görges, F.

    2010-01-01

    In a picture-word interference experiment the authors demonstrate that a semantic-categorical relation between a to-be-named target picture and a context picture promotes the phonological activation of the to-be-ignored context picture. No such phonological activation is observed if the objects are

  13. 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

    2009-01-01

    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.

  14. 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.

  15. Comparison of Trunk Activity during Gait Initiation and Walking in Humans

    Science.gov (United States)

    Azevedo, Christine; Cazalets, Jean-René

    2009-01-01

    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

  16. Situations of decontamination promotion activities. Efforts by Tokyo Electric Power Company, Fukushima Revitalization Headquarters, Decontamination Promotion Office

    International Nuclear Information System (INIS)

    As for the decontamination of the soil contaminated with radioactive materials, decontamination is on the way in compliance with the 'Act on Special Measures Concerning the Handling of Environmental Pollution by Radioactive Materials by the NPS Accident Associated with the Tohoku District - Off the Pacific Ocean' (hereinafter, the Act on Special Measures). Tokyo Electric Power Company (TEPCO), as the party concerned to the accident, is cooperating with decontamination activities conducted by countries and municipalities under the Act on Special Measures. Total number of people cooperated by the Decontamination Promotion Office amounts to about 120,000 people. The cooperation to the decontamination by countries and municipalities covers the following fields: provision of knowledge of radiation, training of site management and supervisors, and proposal such as the decontamination method suitable for the site. As cooperation to various monitoring, there is a traveling monitoring that performs radiation measurement from the vehicles. As cooperation in the farming and industrial resumption toward the reconstruction, the group has implemented support for the distribution promotion of the holdup that was stuck in distribution due to contamination with radioactive substances. As decontamination related technology, the following are performed: (1) preparation of radiation understanding promotion tool, (2) development of precise individual dose measurement technology, and (3) development and utilization of decontamination effect analysis program. In the future, this group will perform the follow-up for decontamination, and measures toward the lifting of evacuation order. It will install the basis to perform various technical analyses on decontamination, and will further intensify technical cooperation. (A.O.)

  17. Thymic Stromal Lymphopoietin Promotes Fibrosis and Activates Mitogen-Activated Protein Kinases in MRC-5 Cells.

    Science.gov (United States)

    Li, Li; Tang, Su; Tang, Xiaodong

    2016-01-01

    BACKGROUND Acute lung injury (ALI) is a life-threatening hypoxemic respiratory disorder with high incidence and mortality. ALI usually manifests as widespread inflammation and lung fibrosis with the accumulation of pro-inflammatory and pro-fibrotic factors and collagen. Thymic stromal lymphopoietin (TSLP) has a significant role in regulation of inflammation but little is known about its roles in lung fibrosis or ALI. This study aimed to define the role and possible regulatory mechanism of TSLP in lung fibrosis. MATERIAL AND METHODS We cultured human lung fibroblast MRC-5 cells and overexpressed or inhibited TSLP by the vector or small interfering RNA transfection. Then, the pro-fibrotic factors skeletal muscle actin alpha (α-SMA) and collagen I, and the 4 mitogen-activated protein kinases (MAPKs) - MAPK7, p38, extracellular signal-regulated kinase 1 (ERK1), and c-Jun N-terminal kinase 1 (JNK1) - were detected by Western blot. RESULTS Results showed that TSLP promoted the production of α-SMA and collagen I (Pmechanism of fibrosis. PMID:27385084

  18. Enhancer activity of Helitron in sericin-1 gene promoter from Bombyx mori.

    Science.gov (United States)

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

    2016-06-01

    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. PMID:27067405

  19. The IL - 6 promoter polymorphism is associated with disease activity and disability in systemic sclerosis

    OpenAIRE

    Sfrent-Cornateanu, Roxana; Mihai, Carina; Balan, Simona; Ionescu, R.; Moldoveanu, E

    2008-01-01

    Systemic sclerosis (SSc) is a rare, autoimmune disease characterized by cutaneous and visceral fibrosis. Interleukin-6 (IL-6) is involved in the pathogenesis of many immune-mediated diseases. IL-6 plays an important role in the initiation and promotion of fibrosis. The polymorphism in the position -174 (G/C) of the promoter region of the IL-6 gene (IL-6 pr) may alter the expression of the gene. Complete linkage disequilibrium was observed between the -174 and -597 alleles. The aim of this stu...

  20. Functional and Activity Analysis of Cattle UCP3 Promoter with MRFs-Related Factors

    OpenAIRE

    Wei Chen; Houqiang Xu; Xiang Chen; Zhongwei Liu; Wen Zhang; Dan Xia

    2016-01-01

    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 ...

  1. URG11 promotes gastric cancer growth and invasion by activation of β-catenin signalling pathway

    OpenAIRE

    Du, Rui; Xia, Lin; Sun, Shiren; Lian, Zhaorui; Zou, Xue; Gao, Juan; Xie, Huahong; Fan, Rui; Song, Jiugang; Li, Xiaohua; Liu, Jie; Fan, Daiming

    2008-01-01

    Abstract Upregulated gene 11 (URG11), a new gene upregulated by Heptatitis B Virus X protein (HBx), was previously shown to activate β-catenin and promote hepatocellular growth and tumourigenesis. Although the oncogenic role of URG11 in the development of hepatocellular carcinoma has been well documented, its relevance to other human malignancies and the underlying molecular mechanisms remain largely unknown. Here we reported a novel function of URG11 to promote gastric cancer growth and meta...

  2. Activity screening of plant growth promoting rhizobacteria isolated from alfalfa rhizosphere

    OpenAIRE

    shahla pashapour; Hossein besharati; Mahmoud rezazadeh; Ahmad Alimadadi; Nadergholi Ebrahimi

    2016-01-01

    Introduction: Some rhizobacteria by various mechanisms influence plant growth as they are called plant growth promoting rhizobacteria (PGPR). Scientists identified some PGPR characters involved in promoting plant growth, while all these characters are not able to study. The aim of this study was to evaluate PGP activities of bacterial isolates, (45 isolates belonged to rhizobium and 2 bacterial isolates belonged to Pseudomonas fluorescens), which were isolated from alfalfa (Medicago sativa) r...

  3. Does the private finance initiative promote innovation in health care? The case of the British National Health Service.

    Science.gov (United States)

    Petratos, Pythagoras

    2005-12-01

    The Private Finance Initiative (PFI) is a specific example of health care privatization within the British National Health Service. In this essay, I critically assess the ways in which various Private Finance Initiatives have increased health care efficiency and effectiveness, as well as encouraged medical innovation. Indeed, as the analysis will demonstrate, significant empirical evidence supports the conclusion that Private Finance Initiatives are a driving force of innovation within the British Health Care System. PMID:16396788

  4. 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.

  5. Mechanisms of transcriptional activation of the mouse claudin-5 promoter by estrogen receptor alpha and beta.

    Science.gov (United States)

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

    2014-07-01

    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.

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

    Science.gov (United States)

    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...

  7. Xeroderma Pigmentosum Group A Promotes Autophagy to Facilitate Cisplatin Resistance in Melanoma Cells through the Activation of PARP1.

    Science.gov (United States)

    Ge, Rui; Liu, Lin; Dai, Wei; Zhang, Weigang; Yang, Yuqi; Wang, Huina; Shi, Qiong; Guo, Sen; Yi, Xiuli; Wang, Gang; Gao, Tianwen; Luan, Qi; Li, Chunying

    2016-06-01

    Xeroderma pigmentosum group A (XPA), a key protein in the nucleotide excision repair pathway, has been shown to promote the resistance of tumor cells to chemotherapeutic drugs by facilitating the DNA repair process. However, the role of XPA in the resistance of melanoma to platinum-based drugs like cisplatin is largely unknown. In this study, we initially found that XPA was expressed at higher levels in cisplatin-resistant melanoma cells than in cisplatin-sensitive ones. Furthermore, the knockdown of XPA not only increased cellular apoptosis but also inhibited cisplatin-induced autophagy, which rendered the melanoma cells more sensitive to cisplatin. Moreover, we discovered that the increased XPA in resistant melanoma cells promoted poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) activation and that the inhibition of PARP1 could attenuate the cisplatin-induced autophagy. Finally, we proved that the inhibition of PARP1 and the autophagy process made resistant melanoma cells more susceptible to cisplatin treatment. Our study shows that XPA can promote cell-protective autophagy in a DNA repair-independent manner by enhancing the activation of PARP1 in melanoma cells resistant to cisplatin and that the XPA-PARP1-mediated autophagy process can be targeted to overcome cisplatin resistance in melanoma chemotherapy. PMID:26880244

  8. 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.

  9. Recommendations for Promoting Physical Activity for Children and Adolescents in Germany. A Consensus Statement

    OpenAIRE

    Graf, Christine; Beneke, Ralph; Bloch, Wilhelm; Bucksch, Jens; Dordel, Sigrid; Eiser, Stefanie; Ferrari, Nina; Koch, Benjamin; Krug, Susanne; Lawrenz, Wolfgang; Manz, Kristin; Naul, Roland; Oberhoffer, Renate; Quilling, Eike; Schulz, Henry

    2014-01-01

    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 ...

  10. Lysophosphatidic acid activates Arf6 to promote the mesenchymal malignancy of renal cancer

    OpenAIRE

    Hashimoto, Shigeru; Mikami, Shuji; Sugino, Hirokazu; Yoshikawa, Ayumu; Hashimoto, Ari; Onodera, Yasuhito; Furukawa, Shotaro; Handa, Haruka; Oikawa, Tsukasa; OKADA, YASUNORI; Oya, Mototsugu; Sabe, Hisataka

    2016-01-01

    Acquisition of mesenchymal properties by cancer cells is critical for their malignant behaviour, but regulators of the mesenchymal molecular machinery and how it is activated remain elusive. Here we show that clear cell renal cell carcinomas (ccRCCs) frequently utilize the Arf6-based mesenchymal pathway to promote invasion and metastasis, similar to breast cancers. In breast cancer cells, ligand-activated receptor tyrosine kinases employ GEP100 to activate Arf6, which then recruits AMAP1; and...

  11. Activated Notch Causes Deafness by Promoting a Supporting Cell Phenotype in Developing Auditory Hair Cells

    OpenAIRE

    Grace Savoy-Burke; Felicia A Gilels; Wei Pan; Diana Pratt; Jianwen Que; Lin Gan; White, Patricia M.; Kiernan, Amy E.

    2014-01-01

    Purpose To determine whether activated Notch can promote a supporting cell fate during sensory cell differentiation in the inner ear. Methods An activated form of the Notch1 receptor (NICD) was expressed in early differentiating hair cells using a Gfi1-Cre mouse allele. To determine the effects of activated Notch on developing hair cells, Gfi1-NICD animals and their littermate controls were assessed at 5 weeks for hearing by measuring auditory brainstem responses (ABRs) and distortion product...

  12. Cathepsin B Activity Initiates Apoptosis via Digestive Protease Activation in Pancreatic Acinar Cells and Experimental Pancreatitis.

    Science.gov (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

    2016-07-01

    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. PMID:27226576

  13. Impact Initiated Combustion of Aluminum Exposed to Mechanical Pre-Activation

    Science.gov (United States)

    Breidenich, Jennifer; Thadhani, Naresh

    2013-06-01

    The impact initiation of as-received and mechanically activated aluminum powder compacts is investigated using uniaxial stress rod-on-anvil impact experiments. The compacts reveal light emission due to combustion reaction at velocities greater than 320m/s. Mechanical pre-activation, such as that achieved via high-energy ball milling (HEBM) or high strain machining, strain hardens the starting materials, affecting their combustion initiation behavior. The starting materials are characterized by their lattice strain, hardness, and quasi-static compaction behavior. High speed imaging reveals that the ``threshold'' velocity (minimum velocity necessary for reaction initiation) changes as function of the mechanical pre-activation. Meso-scale simulations performed in CTH are used to correlate the effects of material properties within the powder compact with the crush up, deformation, and reaction behavior. Research funding provided by DTRA Grant No. HDTRA1-10-1-0038.

  14. Orchestrated activation of mGluR5 and CB1 promotes neuroprotection.

    Science.gov (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

    2016-08-20

    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.

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

    Science.gov (United States)

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

    2012-03-02

    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.

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

    Directory of Open Access Journals (Sweden)

    Fortier Michelle S

    2012-03-01

    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.

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

    DEFF Research Database (Denmark)

    Knudsen, Jette Steen

    2013-01-01

    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....

  18. Multilevel (mental) health promotion as social innovation in peripheral areas of Denmark – reflections on a local initiative targeting vulnerable young mothers

    DEFF Research Database (Denmark)

    Delica, Kristian Nagel

    This paper provides preliminary insights into an ongoing research project focused on marginalized young mothers and mental health initiatives in two peripheral islands of Denmark (Lolland and Falster). The municipalities on the Islands are struggling with a concentration of (mental) health problems...... of local welfare state services at the same time as the number of welfare clients are increasing. To grasp the complexities in understanding the local initiative this paper is grounded in a multilevel perspective on health promotion and addresses perspectives on the work done from the strategic......, bureaucratic level over the front line welfare professionals’ practices to the young mother’s experiences. The paper aligns a multilevel approach to theories of social innovation. This forms a fundament for discussing ‘horizontal’ and ‘vertical’ multilevel health promotion and analysing the interwoven...

  19. 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.

    1988-02-01

    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.

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

    Directory of Open Access Journals (Sweden)

    J.O. Timokhina

    2011-12-01

    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.

  1. 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

    2006-01-01

    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.

  2. Considerations on the promotional activity on the DIY market in Romania

    Directory of Open Access Journals (Sweden)

    Mihai FÎNARU

    2015-12-01

    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.

  3. A new era for functional labeling of neurons: activity-dependent promoters have come of age

    Directory of Open Access Journals (Sweden)

    Takashi eKawashima

    2014-04-01

    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.

  4. Neuritin: a gene induced by neural activity and neurotrophins that promotes neuritogenesis.

    Science.gov (United States)

    Naeve, G S; Ramakrishnan, M; Kramer, R; Hevroni, D; Citri, Y; Theill, L E

    1997-03-18

    Neural activity and neurotrophins induce synaptic remodeling in part by altering gene expression. A cDNA encoding a glycosylphoshatidylinositol-anchored protein was identified by screening for hippocampal genes that are induced by neural activity. This molecule, named neuritin, is expressed in postmitotic-differentiating neurons of the developing nervous system and neuronal structures associated with plasticity in the adult. Neuritin message is induced by neuronal activity and by the activity-regulated neurotrophins BDNF and NT-3. Purified recombinant neuritin promotes neurite outgrowth and arborization in primary embryonic hippocampal and cortical cultures. These data implicate neuritin as a downstream effector of activity-induced neurite outgrowth. PMID:9122250

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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

    2004-01-01

    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.

  7. Xyloglucan oligosaccharides promote growth and activate cellulase: Evidence for a role of cellulase in cell expansion

    International Nuclear Information System (INIS)

    Oligosaccharides produced by the action of fungal cellulase on xyloglucans promoted the elongation of etiolated pea (Pisum sativum L.) stem segments in a straight-growth bioassay designed for the determination of auxins. The oligosaccharides were most active at about 1 micromolar. We tested the relative growth-promoting activities of four HPLC-purified oligosaccharides which shared a common glucose4·xylose3 (XG7) core. The substituted oligosaccharides XG8 (glucose4·xylose3·galactose) and XG9n (glucose4·xylose3·galactose2) were more effective than XG7 itself and XG9 (glucose4·xylose3·galactose·fucose). The same oligosaccharides also promoted the degradation, assayed viscometrically, of xyloglucan by an acidic cellulase from bean (Phaseolus vulgaris L.) leaves. The oligosaccharides were highly active at 10-4 molar, causing up to a fourfold increase in activity, but the effect was still detectable at 1 micromolar. Those oligosaccharides (XG8 and XG9n) which best promoted growth, stimulated cellulase activity to the greatest extent. The oligosaccharides did not stimulate the action of the cellulase in an assay based on the conversion of [3H]xyloglucan to ethanol-soluble fragments. This suggests that the oligosaccharides enhanced the midchain hydrolysis of xyloglucan molecules (which would rapidly reduce the viscosity of the solution), at the expense of cleavage near the termini (which would yield ethanol-soluble products)

  8. THE ACTIVITY OF ARABIDOSPIS DLL PROMOTER IN TRANSGENIC TOBACCO PLANTS UNDER WATER STRESS CONDITIONS

    Directory of Open Access Journals (Sweden)

    Zuzana Polóniová

    2014-02-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Pena, AndreAna N., E-mail: andreana.pena@gmail.com [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)

    2011-07-01

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

  10. p38α Activates Purine Metabolism to Initiate Hematopoietic Stem/Progenitor Cell Cycling in Response to Stress.

    Science.gov (United States)

    Karigane, Daiki; Kobayashi, Hiroshi; Morikawa, Takayuki; Ootomo, Yukako; Sakai, Mashito; Nagamatsu, Go; Kubota, Yoshiaki; Goda, Nobuhito; Matsumoto, Michihiro; Nishimura, Emi K; Soga, Tomoyoshi; Otsu, Kinya; Suematsu, Makoto; Okamoto, Shinichiro; Suda, Toshio; Takubo, Keiyo

    2016-08-01

    Hematopoietic stem cells (HSCs) maintain quiescence by activating specific metabolic pathways, including glycolysis. We do not yet have a clear understanding of how this metabolic activity changes during stress hematopoiesis, such as bone marrow transplantation. Here, we report a critical role for the p38MAPK family isoform p38α in initiating hematopoietic stem and progenitor cell (HSPC) proliferation during stress hematopoiesis in mice. We found that p38MAPK is immediately phosphorylated in HSPCs after a hematological stress, preceding increased HSPC cycling. Conditional deletion of p38α led to defective recovery from hematological stress and a delay in initiation of HSPC proliferation. Mechanistically, p38α signaling increases expression of inosine-5'-monophosphate dehydrogenase 2 in HSPCs, leading to altered levels of amino acids and purine-related metabolites and changes in cell-cycle progression in vitro and in vivo. Our studies have therefore uncovered a p38α-mediated pathway that alters HSPC metabolism to respond to stress and promote recovery. PMID:27345838

  11. 77 FR 60124 - Draft Guidance for Industry on Initial Completeness Assessments for Type II Active Pharmaceutical...

    Science.gov (United States)

    2012-10-02

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Initial Completeness Assessments for Type II Active Pharmaceutical Ingredient Drug Master Files Under the Generic Drug User Fee Amendments of 2012 AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...

  12. Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation

    Directory of Open Access Journals (Sweden)

    Bonnet Amandine

    2012-09-01

    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

  13. Working mechanisms of a behavioural intervention promoting physical activity in persons with subacute spinal cord injury

    NARCIS (Netherlands)

    Nooijen, Carla F J; Stam, Henk J; Schoenmakers, Imte; Sluis, Tebbe A R; Post, Marcel W M; Twisk, Jos W R; Group, Act-Active Research; van den Berg-Emons, Rita J G

    2016-01-01

    OBJECTIVE: In order to unravel the working mechanisms that underlie the effectiveness of a behavioural intervention promoting physical activity in persons with subacute spinal cord injury, the aim of this study was to assess the mediating effects of physical and psychosocial factors on the intervent

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

    Science.gov (United States)

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

    2011-01-01

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

  15. p55PIK Transcriptionally Activated by MZF1 Promotes Colorectal Cancer Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Yu Deng

    2013-01-01

    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.

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

    Science.gov (United States)

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

    2007-01-01

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

  17. The Role of Biographical Characteristics in Preservice Classroom Teachers' School Physical Activity Promotion Attitudes

    Science.gov (United States)

    Webster, Collin A.; Monsma, Eva; Erwin, Heather E.

    2010-01-01

    Recommendations for increasing children's daily physical activity (PA) call on classroom teachers to assume an activist role at school. This study examined relationships among preservice classroom teachers' (PCT; n = 247) biographical characteristics, perceptions and attitudes regarding school PA promotion (SPAP). Results indicated participants…

  18. Design of cAMP-CRP-activated promoters in Escherichia coli

    DEFF Research Database (Denmark)

    Valentin-Hansen, P; Holst, B; Søgaard-Andersen, L;

    1991-01-01

    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...

  19. A telecare programme for self-management of COPD exacerbations and promotion of an active lifestyle

    NARCIS (Netherlands)

    Tabak, Monique; Brusse-Keizer, Marjolein; Ommeren, Clara; Kotte, Hayke; Weltevreden, Paul; Hermens, Hermie; Vollenbroek-Hutten, Miriam

    2013-01-01

    Objective: The Condition Coach (CoCo) is a technology-supported care programme for self-management of COPD exacerbations and for promotion of an active lifestyle. The objective is to investigate the added value of the telecare programme in terms of clinical changes compared to usual care, and in add

  20. A new starting point for powerful lignin promotion : Eurolignin and linked activities

    NARCIS (Netherlands)

    Abaecherli, A.; Gosselink, R.J.A.; Jong, de E.; Guran, B.

    2004-01-01

    The International Lignin Institute (ILI) was created in 1991 as a new platform for promotion of lignin utilisations. For a few years, the activity was based on informal information exchange, such as Newsletters, international conferences (Forums) and Workshops, as well as in the proceedings of these

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

    Science.gov (United States)

    Cale, Lorraine; Harris, Jo

    2009-01-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

  3. Cdc6 ATPase activity disengages Cdc6 from the pre-replicative complex to promote DNA replication.

    Science.gov (United States)

    Chang, FuJung; Riera, Alberto; Evrin, Cecile; Sun, Jingchuan; Li, Huilin; Speck, Christian; Weinreich, Michael

    2015-08-25

    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.

  4. School Health Promotion to Increase Empowerment, Gender Equality and Pupil Participation: A Focus Group Study of a Swedish Elementary School Initiative

    Science.gov (United States)

    Gadin, Katja Gillander; Weiner, Gaby; Ahlgren, Christina

    2013-01-01

    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…

  5. Complement C1q Activates Canonical Wnt Signaling and Promotes Aging-Related Phenotypes

    OpenAIRE

    Atsuhiko T. Naito; Sumida, Tomokazu; Nomura, Seitaro; Liu, Mei-Lan; Higo, Tomoaki; NAKAGAWA, AKITO; Okada, Katsuki; Sakai, Taku; Hashimoto, Akihito; Hara, Yurina; Shimizu, Ippei; Zhu, Weidong; Toko, Haruhiro; Katada, Akemi; Akazawa, Hiroshi

    2012-01-01

    Wnt signaling plays critical roles in development of various organs and pathogenesis of many diseases, and augmented Wnt signaling has recently been implicated in mammalian aging and aging-related phenotypes. We here report that complement C1q activates canonical Wnt signaling and promotes aging-associated decline in tissue regeneration. Serum C1q concentration is increased with aging, and Wnt signaling activity is augmented during aging in the serum and in multiple tissues of wild-type mice,...

  6. Involving postgraduate's students in undergraduate small group teaching promotes active learning in both

    OpenAIRE

    Kalra, Ruchi; Modi, Jyoti Nath; Vyas, Rashmi

    2015-01-01

    Background: Lecture is a common traditional method for teaching, but it may not stimulate higher order thinking and students may also be hesitant to express and interact. The postgraduate (PG) students are less involved with undergraduate (UG) teaching. Team based small group active learning method can contribute to better learning experience. Aim: To-promote active learning skills among the UG students using small group teaching methods involving PG students as facilitators to impart hands-o...

  7. Variants of the cell recognition site of fibronectin that retain attachment-promoting activity

    OpenAIRE

    1985-01-01

    A tetrapeptide sequence, Arg-Gly-Asp-Ser, is the minimal structure recognized by cells in the large, adhesive glycoprotein fibronectin. We now have defined the structural requirements for this cell recognition site by testing several synthetic variants of the active tetrapeptide sequence. The conservative substitutions of lysine for arginine, alanine for glycine, or glutamic acid for aspartic acid each resulted in abrogation of the cell attachment-promoting activity characteristic of the natu...

  8. Evaluation methods for physical activity-promoting mobile technologies: an interdisciplinary scoping review

    OpenAIRE

    Claire McCallum; John Rooksby

    2015-01-01

    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 activ...

  9. Analysis of the effects of depression associated polymorphisms on the activity of the BICC1 promoter in amygdala neurones.

    Science.gov (United States)

    Davidson, S; Shanley, L; Cowie, P; Lear, M; McGuffin, P; Quinn, J P; Barrett, P; MacKenzie, A

    2016-08-01

    The Bicaudal C Homolog 1 (BICC1) gene, which encodes an RNA binding protein, has been identified by genome wide association studies (GWAS) as a candidate gene associated with major depressive disorder (MDD). We explored the hypothesis that MDD associated single-nucleotide polymorphisms (SNPs) affected the ability of cis-regulatory elements within intron 3 of the BICC1 gene to modulate the activity of the BICC1 promoter region. We initially established that the BICC1 promoter drove BICC1 mRNA expression in amygdala, hippocampus and hypothalamus. Intriguingly, we provide evidence that MDD associated polymorphisms alter the ability of the BICC1 promoter to respond to PKA signalling within amygdala neurones. Considering the known role of amygdala PKA pathways in fear learning and mood these observations suggest a possible mechanism through which allelic changes in the regulation of the BICC1 gene in amygdala neurones may contribute to mood disorders. Our findings also suggest a novel direction for the identification of novel drug targets and the design of future personalised therapeutics.The Pharmacogenomics Journal advance online publication, 6 October 2015; doi:10.1038/tpj.2015.62. PMID:26440730

  10. In Vitro and In Vivo Plant Growth Promoting Activities and DNA Fingerprinting of Antagonistic Endophytic Actinomycetes Associates with Medicinal Plants

    OpenAIRE

    Ajit Kumar Passari; Vineet Kumar Mishra; Vijai Kumar Gupta; Mukesh Kumar Yadav; Ratul Saikia; Bhim Pratap Singh

    2015-01-01

    Endophytic actinomycetes have shown unique plant growth promoting as well as antagonistic activity against fungal phytopathogens. In the present study forty-two endophytic actinomycetes recovered from medicinal plants were evaluated for their antagonistic potential and plant growth-promoting abilities. Twenty-two isolates which showed the inhibitory activity against at least one pathogen were subsequently tested for their plant-growth promoting activities and were compared genotypically using...

  11. Cloning and Transcriptional Activity of the Mouse Omi/HtrA2 Gene Promoter

    Directory of Open Access Journals (Sweden)

    Dan Liu

    2016-01-01

    Full Text Available 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 (SP1sites, 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.

  12. p21-activated Kinase1(PAK1) can promote ERK activation in a kinase independent manner

    DEFF Research Database (Denmark)

    Wang, Zhipeng; Fu, Meng; Wang, Lifeng;

    2013-01-01

    PAK1 plays an important role in proliferation and tumorigenesis, at least partially by promoting Erk phosphorylation of c-Raf (Ser 338) or Mek1 (Ser 298). We observed now that overexpression of a kinase-dead mutant form of PAK1 increased phosphorylation of Mek1/2 (Ser 217/221) and Erk (Thr 202/Tyr...

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

    Science.gov (United States)

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

    2015-12-01

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

  14. A synthetic isoflavone, DCMF, promotes human keratinocyte migration by activating Src/FAK signaling pathway.

    Science.gov (United States)

    Sophors, Phorl; Kim, Young Mee; Seo, Ga Young; Huh, Jung-Sik; Lim, Yoongho; Koh, Dong Soo; Cho, Moonjae

    2016-04-01

    Flavonoids are plant secondary compounds with various pharmacological properties. We previously showed that one flavonoid, trimethoxyisoflavone (TMF), could promote wound healing by inducing keratinocyte migration. Here, we screened TMF derivatives for enhanced activity and identified one compound, 2',6 Dichloro-7-methoxyisoflavone (DCMF), as most effective at promoting migration in a scratch wound assay. Using the HaCaT keratinocyte cell line, we found DCMF treatment induced phosphorylation of both FAK and Src, and increased keratinocyte migration. DCMF-induced Src kinase could promote activation of ERK, AKT, and p38 signaling pathways, and DCMF-induced secretion of matrix metalloproteinase (MMP)-2 and MMP-9 and partial epithelial-mesenchymal transition (EMT), whereas Src inhibition abolished DCMF-induced EMT. Using an in vivo excisional wound model, we observed improved wound closure and re-epithelialization in DCMF-treated mice, as compared to controls. Collectively, our data demonstrate that DCMF induces cell migration and promotes wound healing through activation of Src/FAK, ERK, AKT, and p38 MAPK signaling. PMID:26923073

  15. A downstream CpG island controls transcript initiation and elongation and the methylation state of the imprinted Airn macro ncRNA promoter.

    Directory of Open Access Journals (Sweden)

    Martha V Koerner

    Full Text Available A CpG island (CGI lies at the 5' end of the Airn macro non-protein-coding (nc RNA that represses the flanking Igf2r promoter in cis on paternally inherited chromosomes. In addition to being modified on maternally inherited chromosomes by a DNA methylation imprint, the Airn CGI shows two unusual organization features: its position immediately downstream of the Airn promoter and transcription start site and a series of tandem direct repeats (TDRs occupying its second half. The physical separation of the Airn promoter from the CGI provides a model to investigate if the CGI plays distinct transcriptional and epigenetic roles. We used homologous recombination to generate embryonic stem cells carrying deletions at the endogenous locus of the entire CGI or just the TDRs. The deleted Airn alleles were analyzed by using an ES cell imprinting model that recapitulates the onset of Igf2r imprinted expression in embryonic development or by using knock-out mice. The results show that the CGI is required for efficient Airn initiation and to maintain the unmethylated state of the Airn promoter, which are both necessary for Igf2r repression on the paternal chromosome. The TDRs occupying the second half of the CGI play a minor role in Airn transcriptional elongation or processivity, but are essential for methylation on the maternal Airn promoter that is necessary for Igf2r to be expressed from this chromosome. Together the data indicate the existence of a class of regulatory CGIs in the mammalian genome that act downstream of the promoter and transcription start.

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

    Science.gov (United States)

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

    2016-01-01

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

  17. Classroom Activities to Engage Students and Promote Critical Thinking about Genetic Regulation of Bacterial Quorum Sensing

    Directory of Open Access Journals (Sweden)

    Kimberly Aebli

    2016-05-01

    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.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    Balasubramanian, R.

    2007-12-01

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

  20. Mitochondrial Oxidative Stress due to Complex I Dysfunction Promotes Fibroblast Activation and Melanoma Cell Invasiveness

    Directory of Open Access Journals (Sweden)

    Maria Letizia Taddei

    2012-01-01

    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.

  1. T-cell activation promotes tumorigenesis in inflammation-associated cancer

    Directory of Open Access Journals (Sweden)

    Lairmore Michael

    2009-12-01

    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.

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

    Science.gov (United States)

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

    2016-01-01

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

  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

    2013-02-01

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

  4. Deepening the impact of initiatives to promote teamwork and workplace health: a perspective from the NEKTA study.

    Science.gov (United States)

    Leiter, Michael P

    2007-01-01

    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. 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.

    Science.gov (United States)

    Li, Tianlu; De Clercq, Nikki; Medina, Daniel A; Garre, Elena; Sunnerhagen, Per; Pérez-Ortín, José E; Alepuz, Paula

    2016-02-01

    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.

  6. Oncogenic and tumor-promoting Spermatophytes and Pteridophytes and their active principles.

    Science.gov (United States)

    Farnsworth, N R; Bingel, A S; Fong, H H; Saleh, A A; Christenson, G M; Saufferer, S M

    1976-08-01

    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.

  7. 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

    2013-12-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Rodrigo A Quintanilla

    Full Text Available 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.

  9. 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

  10. Anti-tumor promoting activity of bufadienolides from Kalanchoe pinnata and K. daigremontiana x tubiflora.

    Science.gov (United States)

    Supratman, U; Fujita, T; Akiyama, K; Hayashi, H; Murakami, A; Sakai, H; Koshimizu, K; Ohigashi, H

    2001-04-01

    Five bufadienolides (1-5) isolated from the leaves of Kalanchoe pinnata and K. daigremontiana x tubiflora (Crassulaceae) were examined for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation in Raji cells induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate. All bufadienolides showed inhibitory activity, and bryophyllin A (1) exhibited the most marked inhibition (IC50 = 0.4 microM) among the tested compounds. Bryophyllin C (2), a reduction analogue of 1, and bersaldegenin-3-acetate (3) lacking the orthoacetate moiety were less active. These results strongly suggest that bufadienolides are potential cancer chemopreventive agents. PMID:11388478

  11. Using Paid Radio Advertisements to Promote Physical Activity Among Arkansas Tweens

    Directory of Open Access Journals (Sweden)

    Appathurai Balamurugan, MD, MPH

    2005-11-01

    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

  12. Promoting social skills of mexican high school students through virtual activities in the Moodle platform

    Directory of Open Access Journals (Sweden)

    Laura Yolanda RODRÍGUEZ MATAMOROS

    2014-11-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Janine E. Trempy

    2009-12-01

    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. Functional and Activity Analysis of Cattle UCP3 Promoter with MRFs-Related Factors

    Directory of Open Access Journals (Sweden)

    Wei Chen

    2016-05-01

    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.

  15. Functional and Activity Analysis of Cattle UCP3 Promoter with MRFs-Related Factors

    Science.gov (United States)

    Chen, Wei; Xu, Houqiang; Chen, Xiang; Liu, Zhongwei; Zhang, Wen; Xia, Dan

    2016-01-01

    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. PMID:27164086

  16. Liver segmentation with new supervised method to create initial curve for active contour.

    Science.gov (United States)

    Zareei, Abouzar; Karimi, Abbas

    2016-08-01

    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. PMID:27286186

  17. 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

    2006-03-01

    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

  18. Union Activities to promote cooperative activities at enterprise level: workplace assesment

    DEFF Research Database (Denmark)

    Jensen, Per Langå; Høy, Jette

    1996-01-01

    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...

  19. Evaluation methods for physical activity-promoting mobile technologies: an interdisciplinary scoping review

    Directory of Open Access Journals (Sweden)

    Claire McCallum

    2015-10-01

    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.

  20. 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

    2005-01-01

    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.

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

    Science.gov (United States)

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

    2015-01-25

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

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

    Science.gov (United States)

    Meyler, Tim; Banks, Sarah; Wilson, Sandy

    2014-01-01

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

  3. Using formative research to develop CHANGE!: a curriculum-based physical activity promoting intervention

    Directory of Open Access Journals (Sweden)

    Knowles Zoe R

    2011-10-01

    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

  4. Fiscal Year 2014 Annual Report on BNLs Next Generation Safeguards Initiative Human Capital Development Activities

    Energy Technology Data Exchange (ETDEWEB)

    Pepper S. E.

    2014-10-10

    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.

  5. Oncogenic KRAS activates an embryonic stem cell-like program in human colon cancer initiation

    OpenAIRE

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

    2016-01-01

    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...

  6. Initial Free Recall Data Characterized and Explained By Activation Theory of Short Term Memory

    OpenAIRE

    Tarnow, Dr. Eugen

    2011-01-01

    The initial recall distribution in a free recall experiment is shown to be predictably different from the overall free recall distribution including an offset which can cause the least remembered items to be almost completely absent from the first recall. Using the overall free recall distribution as input and a single parameter describing the probability of simultaneous reactivated items per number of items in the presented list, activation theory not only qualitatively but quantitatively d...

  7. Epac Activation Initiates Associative Odor Preference Memories in the Rat Pup

    Science.gov (United States)

    Grimes, Matthew T.; Powell, Maria; Gutierrez, Sandra Mohammed; Darby-King, Andrea; Harley, Carolyn W.; McLean, John H.

    2015-01-01

    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…

  8. Feasibility, acceptability, and initial efficacy of an online sexual health promotion program for LGBT youth: the Queer Sex Ed intervention.

    Science.gov (United States)

    Mustanski, Brian; Greene, George J; Ryan, Daniel; Whitton, Sarah W

    2015-01-01

    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 < .05). Effect sizes ranged from small for sexual orientation (e.g., internalized homophobia) and relationship variables (e.g., communication skills) to moderate for safer sex (e.g., contraceptive knowledge) outcomes. This study demonstrated the feasibility, acceptability, and initial efficacy of QSE, an innovative online comprehensive sexual health program for LGBT youth. PMID:24588408

  9. Inducible and Constitutive Activation of Two Polymorphic Promoter Alleles of the Candida albicans Multidrug Efflux Pump MDR1

    OpenAIRE

    Sasse, Christoph; Schillig, Rebecca; Reimund, Alexandra; Merk, Julia; Morschhäuser, Joachim

    2012-01-01

    Overexpression of the multidrug efflux pump MDR1 confers resistance to the antifungal drug fluconazole on Candida albicans. It has been reported that two types of MDR1 promoters exist in C. albicans and that homozygosity for the allele with higher activity may promote fluconazole resistance. We found that the two MDR1 promoter alleles in strain SC5314 were equally well activated by inducing chemicals or hyperactive forms of the transcription factors Mrr1 and Cap1, which control MDR1 expressio...

  10. Flavonoids promoting HaCaT migration: I. Hologram quantitative structure-activity relationships.

    Science.gov (United States)

    Cho, Moonjae; Yoon, Hyuk; Park, Mijoo; Kim, Young Hwa; Lim, Yoongho

    2014-03-15

    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.

  11. 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.

  12. 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

    2006-03-01

    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

  13. 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;

    2015-01-01

    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

  14. The effectiveness of active travel initiatives in Irish provincial towns: an evaluation of a quasi-experimental natural experiment

    OpenAIRE

    Lambe, Barry

    2015-01-01

    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...

  15. Youth, Caregiver, and Staff Perspectives on an Initiative to Promote Success of Emerging Adults with Emotional and Behavioral Disabilities.

    Science.gov (United States)

    Stein, Kathleen F; Connors, Elizabeth H; Chambers, Kerri L; Thomas, Charmaine L; Stephan, Sharon H

    2014-07-01

    Transitioning to adulthood is more challenging for youth with emotional and behavioral disorders (EBD) as compared to youth with other disability types and typically-developing peers. Outcomes for emerging adults with EBD as a group are particularly concerning in the domains of unemployment, educational dropout rates, and interactions with the judicial system including incarceration, early parenting, homelessness, substance abuse, mental health problems, and suicide. The current study presents qualitative program evaluation data for one of seven grantee states awarded 5-year cooperative agreements by the Substance Abuse Mental Health Services Administration (SAMHSA) to build developmentally-appropriate and effective youth-guided local systems of care for transition age youth, ages 16-25 years, to promote positive transition outcomes. Findings, obtained from focus groups of 25 participating transition age youth, caregivers, staff, and supervisors, include strategies for maintaining and expanding on the strengths of program, as well as for improving specific program areas. Also, consistent with the goals of the program, this process provided an opportunity for the youth and caregivers to voice their opinions and perspectives regarding their services. Implications for research and practice on effectively serving the unique needs of young adults experiencing EBD and their families in areas such as navigating special education, providing emotional and behavioral supports, and leveraging interagency collaboration are discussed. PMID:25005428

  16. Role Modeling Attitudes, Physical Activity and Fitness Promoting Behaviors of Prospective Physical Education Specialists and Non-Specialists.

    Science.gov (United States)

    Cardinal, Bradley J.; Cardinal, Marita K.

    2002-01-01

    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…

  17. The physical education teacher as a physical activity promoter: Current developments

    OpenAIRE

    Cloes, Marc

    2014-01-01

    The current society needs to fight against the growing of sedentary lifestyles among the population all around the world. The school environment is identified as a pillar of the multisectorial approach that should be implemented to avoid that children who born today do not live less longer than their parents. The presentation will focus on four topics: (1) The role of school in physical activity (PA) promotion; (2) The dimensions of PA at school; (3) The action that physical education (PE) te...

  18. Hair growth-promoting activity of hot water extract of Thuja orientalis

    OpenAIRE

    Zhang, Nan-Nan; Park, Dong Ki; Park, Hye-Jin

    2013-01-01

    Background Thuja orientalis has been traditionally used to treat patients who suffer from baldness and hair loss in East Asia. The present study sought to investigate the hair growth-promoting activity of T. orientalis hot water extract and the underlying mechanism of action. Methods After T. orientalis extract was topically applied to the shaved dorsal skin of telogenic C57BL/6 N mice, the histomorphometric analysis was employed to study induction of the hair follicle cycle. To determine the...

  19. Recent activities for the promotion of gender equality in the societies of physics in Japan

    Science.gov (United States)

    Mori, H.; Sasao, M.; Nemoto, K.; Tamechika, E.; Watanabe, M. O.

    2015-12-01

    Although the percentage of women members increases from 2% to 6% in the last 30 years, the ratio is still low in both the Physical Society of Japan and the Japan Society of Applied Physics. Recent activities for the promotion of gender equality in both societies, the development of the next generation of members, organizing international workshops and domestic symposiums, and so on, are introduced in this paper.

  20. The Use of Promotional Activities in the Tourism Industry : The Case of Bangladesh

    OpenAIRE

    Jakir, Hossain Md.

    2006-01-01

    Abstract This thesis is an attempt to investigate how the use of promotional activities can help to develop the tourism industry by giving a special concentration to the case of Bangladesh. The investigation was conducted from both a theoretical and an empirical point of view. The contribution of the same industry to the world economy is considerable. Many countries are now dependent on this sector for foreign currency earnings. Every destination country is trying to achieve more gain by deve...

  1. Biocontrol and plant growth-promoting activity of rhizobacteria from Chinese fields with contaminated soils

    OpenAIRE

    WANG, XUEFEI; Mavrodi, Dmitri V.; Ke, Linfeng; Mavrodi, Olga V; Yang, Mingming; Thomashow, Linda S.; Zheng, Na; Weller, David M; Zhang, Jibin

    2014-01-01

    The aim of this study was to inventory the types of plant growth-promoting rhizobacteria (PGPR) present in the rhizosphere of plants grown in soils contaminated with heavy metals, recalcitrant organics, petroleum sewage or salinity in China. We screened 1223 isolates for antifungal activity and about 24% inhibited R hizoctonia solani or S clerotinia sclerotiorum. Twenty-four strains inhibitory to R . solani, G aeumannomyces graminis var. tritici and/or S . sclerotiorum and representing the do...

  2. A magnetic resonance spectroscopy driven initialization scheme for active shape model based prostate segmentation.

    Science.gov (United States)

    Toth, Robert; Tiwari, Pallavi; Rosen, Mark; Reed, Galen; Kurhanewicz, John; Kalyanpur, Arjun; Pungavkar, Sona; Madabhushi, Anant

    2011-04-01

    Segmentation of the prostate boundary on clinical images is useful in a large number of applications including calculation of prostate volume pre- and post-treatment, to detect extra-capsular spread, and for creating patient-specific anatomical models. Manual segmentation of the prostate boundary is, however, time consuming and subject to inter- and intra-reader variability. T2-weighted (T2-w) magnetic resonance (MR) structural imaging (MRI) and MR spectroscopy (MRS) have recently emerged as promising modalities for detection of prostate cancer in vivo. MRS data consists of spectral signals measuring relative metabolic concentrations, and the metavoxels near the prostate have distinct spectral signals from metavoxels outside the prostate. Active Shape Models (ASM's) have become very popular segmentation methods for biomedical imagery. However, ASMs require careful initialization and are extremely sensitive to model initialization. The primary contribution of this paper is a scheme to automatically initialize an ASM for prostate segmentation on endorectal in vivo multi-protocol MRI via automated identification of MR spectra that lie within the prostate. A replicated clustering scheme is employed to distinguish prostatic from extra-prostatic MR spectra in the midgland. The spatial locations of the prostate spectra so identified are used as the initial ROI for a 2D ASM. The midgland initializations are used to define a ROI that is then scaled in 3D to cover the base and apex of the prostate. A multi-feature ASM employing statistical texture features is then used to drive the edge detection instead of just image intensity information alone. Quantitative comparison with another recent ASM initialization method by Cosio showed that our scheme resulted in a superior average segmentation performance on a total of 388 2D MRI sections obtained from 32 3D endorectal in vivo patient studies. Initialization of a 2D ASM via our MRS-based clustering scheme resulted in an average

  3. KNL1 facilitates phosphorylation of outer kinetochore proteins by promoting Aurora B kinase activity.

    Science.gov (United States)

    Caldas, Gina V; DeLuca, Keith F; DeLuca, Jennifer G

    2013-12-23

    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.

  4. 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

    2009-01-01

    Cyclin-dependent kinase 1 (Cdk1)/cyclin B1 complex is the driving force for mitotic entry, and its activation is tightly regulated by the G2/M checkpoint. We originally reported that a novel protein C53 (also known as Cdk5rap3 and LZAP) potentiates DNA damage-induced cell death by modulating the G2/M checkpoint. More recently, Wang et al. (2007) found that C53/LZAP may function as a tumor suppressor by way of inhibiting NF-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.

  5. Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain.

    Science.gov (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

    2014-05-01

    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.

  6. The human papillomavirus (HPV) E6 oncoproteins promotes nuclear localization of active caspase 8

    International Nuclear Information System (INIS)

    The HPV-16 E6 and E6⁎ 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⁎. 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

  7. 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: lizanosoberon@gmail.com [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: banks@icgeb.org [International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34149 Trieste (Italy)

    2014-02-15

    The HPV-16 E6 and E6{sup ⁎} proteins have been shown previously to be capable of regulating caspase 8 activity. We now show that the capacity of E6 to interact with caspase 8 is common to diverse HPV types, being also seen with HPV-11 E6, HPV-18 E6 and HPV-18 E6{sup ⁎}. Unlike most E6-interacting partners, caspase 8 does not appear to be a major proteasomal target of E6, but instead E6 appears able to stimulate caspase 8 activation, without affecting the overall apoptotic activity. This would appear to be mediated in part by the ability of the HPV E6 oncoproteins to recruit active caspase 8 to the nucleus. - Highlights: • Multiple HPV E6 oncoproteins interact with the caspase 8 DED domain. • HPV E6 stimulates activation of caspase 8. • HPV E6 promotes nuclear accumulation of caspase 8.

  8. Berberine Promotes Glucose Consumption Independently of AMP-Activated Protein Kinase Activation

    OpenAIRE

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

    2014-01-01

    Berberine is a plant alkaloid with anti-diabetic action. Activation of AMP-activated protein kinase (AMPK) pathway has been proposed as mechanism for berberine's action. This study aimed to examine whether AMPK activation was necessary for berberine's glucose-lowering effect. We found that in HepG2 hepatocytes and C2C12 myotubes, berberine significantly increased glucose consumption and lactate release in a dose-dependent manner. AMPK and acetyl coenzyme A synthetase (ACC) phosphorylation wer...

  9. Peer-delivered physical activity interventions: an overlooked opportunity for physical activity promotion

    OpenAIRE

    Ginis, Kathleen A Martin; Nigg, Claudio R; Smith, Alan L.

    2013-01-01

    The purpose of this systematic review was to catalogue and synthesize published studies that have examined the effects of peer-delivered physical activity interventions on physical activity behavior. Ten published studies were identified that met the inclusion criteria. The following information was extracted from each study: study design and duration; characteristics of the sample, peers, and interventions; and physical activity outcomes. In all articles reporting within-groups analyses, pee...

  10. LncSox4 promotes the self-renewal of liver tumour-initiating cells through Stat3-mediated Sox4 expression

    Science.gov (United States)

    Chen, Zhen-zhen; Huang, Lan; Wu, Ya-hong; Zhai, Wen-jie; Zhu, Ping-ping; Gao, Yan-feng

    2016-01-01

    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

  11. Farnesoid X receptor activation promotes cell proliferation via PDK4-controlled metabolic reprogramming

    Science.gov (United States)

    Xie, Yang; Wang, Hong; Cheng, Xuefang; Wu, Yuzheng; Cao, Lijuan; Wu, Mengqiu; Xie, Wen; Wang, Guangji; Hao, Haiping

    2016-01-01

    Farnesoid X receptor (FXR) plays a pivotal role in the regulation of various metabolic pathways as well as liver regeneration. However, the casual link between cell proliferative effects during liver regeneration and metabolic regulation of FXR was elusive. In this study, we found that FXR activation significantly promotes HepG2 cell proliferation accompanied with metabolic switch towards the excessive accumulation of aerobic glycolytic intermediates including lactic acid, pyruvate and the subsequently increased biosynthesis of glycine. This FXR-induced metabolic switch was found dependent on an up-regulation of pyruvate dehydrogenate kinase 4 (PDK4), a FXR target gene. FXR agonists were found to promote liver regeneration in the murine model of APAP induced liver injury, which was associated with a metabolic switch favoring the accumulation of glycolytic intermediates as precursors for generation of biomass. However, FXR activation has little effect on the glycolytic metabolism in healthy primary hepatocytes in vitro and the liver of healthy mice in vivo. Therefore, we conclude that FXR may promote the proliferation of tumor cells and the hepatocytes in the process of liver regeneration by activating the PDK4-mediated metabolic reprogramming to generate glycolytic intermediates essential for rapid biomass generation, establishing a mechanistic link between cell proliferation and metabolic switch. PMID:26728993

  12. Activation of Dopamine Receptors in the Nucleus Accumbens Promotes Sucrose-Reinforced Cued Approach Behavior

    Science.gov (United States)

    du Hoffmann, Johann; Nicola, Saleem M.

    2016-01-01

    Dopamine receptor activation in the nucleus accumbens (NAc) promotes vigorous environmentally-cued food-seeking in hungry rats. Rats fed ad libitum, however, respond to fewer food-predictive cues, particularly when the value of food reward is low. Here, we investigated whether this difference could be due to differences in the degree of dopamine receptor activation in the NAc. First, we observed that although rats given ad libitum access to chow in their home cages approached a food receptacle in response to reward-predictive cues, the number of such approaches declined as animals accumulated food rewards. Intriguingly, cued approach to food occurred in clusters, with several cued responses followed by successive non-responses. This pattern suggested that behavior was dictated by transitions between two states, responsive and non-responsive. Injection of D1 or D2 dopamine receptor agonists into the NAc dose-dependently increased cue responding by promoting transitions to the responsive state and by preventing transitions to the non-responsive state. In contrast, antagonists of either D1 or D2 receptors promoted long bouts of non-responding by inducing transitions to the non-responsive state and by preventing transitions to the responsive state. Moreover, locomotor behavior during the inter-trial interval was correlated with the responsive state, and was also increased by dopamine receptor agonists. These results suggest that activation of NAc dopamine receptors plays an important role in regulating the probability of approach to food under conditions of normative satiety. PMID:27471453

  13. The Role of Culture, Environment, and Religion in the Promotion of Physical Activity Among Arab Israelis

    Directory of Open Access Journals (Sweden)

    David L. Katz, MD, MPH

    2008-07-01

    Full Text Available IntroductionDespite low levels of physical activity among Arabs in Israel, interventions designed to increase physical activity in this population have been scarce. To improve our understanding of the cultural, religious, and environmental barriers and enablers to physical activity, we conducted a qualitative study among Arab Israeli college students in Israel.MethodsA total of 45 students participated in 8 focus groups. Purposeful sampling was used to capture the diverse characteristics of participants. Two researchers analyzed the data independently guided by grounded theory. Peer-debriefing sessions were held to group preliminary categories into larger themes. Generally, consensus between researchers was high, and minor differences were resolved.ResultsParticipants recognized the importance of physical activity in chronic disease prevention, yet most were not regularly physically active. This contradiction could be explained by the fact that many participants lived in an extended-family setting that deemphasized the importance of physical activity. Women often found themselves exercising at odd hours so that they would not be noticed by neighbors. Religion, in comparison, was considered a facilitating factor because the scriptures supported physical activity. Furthermore, an urban environment was an enabling factor because it provided exercise facilities, sidewalks, and a socially acceptable venue for activity. Participants felt resources were not allocated by the government to accommodate physical activity.ConclusionIncreasing Arab Israelis’ access to safe and culturally appropriate exercise facilities should become a priority. Thus, policy changes in allocating appropriate funds to promote physical activity must be considered, along with using multiple health promotion strategies.

  14. Peroxisome proliferator-activated receptor gamma recruits the positive transcription elongation factor b complex to activate transcription and promote adipogenesis

    DEFF Research Database (Denmark)

    Iankova, Irena; Petersen, Rasmus K; Annicotte, Jean-Sébastien;

    2006-01-01

    in adipogenesis. In this study we show that the expression of the cdk9 p55 isoform is highly regulated during 3T3-L1 adipocyte differentiation at RNA and protein levels. Furthermore, cdk9, as well as cyclin T1 and cyclin T2, shows differences in nuclear localization at distinct stages of adipogenesis...... with and phosphorylation of peroxisome proliferator-activated receptor gamma (PPARgamma), which is the master regulator of this process, on the promoter of PPARgamma target genes. PPARgamma-cdk9 interaction results in increased transcriptional activity of PPARgamma and therefore increased adipogenesis....

  15. Testing multi-theory model (MTM) in predicting initiation and sustenance of physical activity behavior among college students

    Science.gov (United States)

    Nahar, Vinayak K.; Sharma, Manoj; Catalano, Hannah Priest; Ickes, Melinda J.; Johnson, Paul; Ford, M. Allison

    2016-01-01

    Background: Most college students do not adequately participate in enough physical activity (PA) to attain health benefits. A theory-based approach is critical in developing effective interventions to promote PA. The purpose of this study was to examine the utility of the newly proposed multi-theory model (MTM) of health behavior change in predicting initiation and sustenance of PA among college students. Methods: Using a cross-sectional design, a valid and reliable survey was administered in October 2015 electronically to students enrolled at a large Southern US University. The internal consistency Cronbach alphas of the subscales were acceptable (0.65-0.92). Only those who did not engage in more than 150 minutes of moderate to vigorous intensity aerobic PA during the past week were included in this study. Results: Of the 495 respondents, 190 met the inclusion criteria of which 141 completed the survey. The majority of participants were females (72.3%) and Caucasians (70.9%). Findings of the confirmatory factor analysis (CFA) confirmed construct validity of subscales (initiation model: χ2 = 253.92 [df = 143], P < 0.001, CFI = 0.91, RMSEA = 0.07, SRMR = 0.07; sustenance model: χ2= 19.40 [df = 22], P < 0.001, CFI = 1.00, RMSEA = 0.00, SRMR = 0.03). Multivariate regression analysis showed that 26% of the variance in the PA initiation was explained by advantages outweighing disadvantages, behavioral confidence, work status, and changes in physical environment. Additionally, 29.7% of the variance in PA sustenance was explained by emotional transformation, practice for change, and changes in social environment. Conclusion: Based on this study’s findings, MTM appears to be a robust theoretical framework for predicting PA behavior change. Future research directions and development of suitable intervention strategies are discussed. PMID:27386419

  16. CARE Coordinated Accelerator Research in Europe: integrating activity implemented as integrated infrastructure initiative

    CERN Document Server

    Aleksan, R

    2009-01-01

    The main objective of the CARE project was to generate a structured and integrated European area in the field of accelerator research and related R&D. A set of integrating activities involving the largest European infrastructure laboratories and their user communities “active in accelerator R&D”, including industrial partners was established with the following general objectives: 1) To optimise the use of existing infrastructures for improving the European knowledge on accelerator physics  By promoting a coherent and coordinated utilization and development of infrastructures and to facilitate the access to accelerators and test facilities for carrying accelerator studies  By understanding accelerator operation and reliability issues 2) To tackle new or state-of-the-art technologies in a more co-ordinated and collaborative approach  By developing a coherent and coordinated accelerator R&D program in Europe and carrying out joint R&D projects allowing one to enhance the existing (or...

  17. MoveU? Assessing a Social Marketing Campaign to Promote Physical Activity

    Science.gov (United States)

    Scarapicchia, Tanya M. F.; Sabiston, Catherine M. F.; Brownrigg, Michelle; Blackburn-Evans, Althea; Cressy, Jill; Robb, Janine; Faulkner, Guy E. J.

    2015-01-01

    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:…

  18. Quality of Life Assessment for Physical Activity and Health Promotion: Further Psychometrics and Comparison of Measures

    Science.gov (United States)

    Gill, Diane L.; Reifsteck, Erin J.; Adams, Melanie M.; Shang, Ya-Ting

    2015-01-01

    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)…

  19. Harnessing different motivational frames via mobile phones to promote daily physical activity and reduce sedentary behavior in aging adults.

    Science.gov (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

    2013-01-01

    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

  20. Harnessing different motivational frames via mobile phones to promote daily physical activity and reduce sedentary behavior in aging adults.

    Science.gov (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

    2013-01-01

    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

  1. 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

  2. Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling.

    Science.gov (United States)

    Le Gall, Sylvain M; Szabo, Roman; Lee, Melody; Kirchhofer, Daniel; Craik, Charles S; Bugge, Thomas H; Camerer, Eric

    2016-06-23

    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. PMID:27114461

  3. 非洲推动传统医学发展的举措与进展%African initiatives and progress in promoting the development of traditional medicine

    Institute of Scientific and Technical Information of China (English)

    黄睿; 潘艳丽; 柳长华

    2014-01-01

    To study the initiatives and progress of African nations in promoting the development of traditional medicine to determine if these measures can be applied to the protection of traditional Chinese medicine knowledge. Information research methods were used to collect and analyze relevant literature. The development of African traditional medicine has been effectively promoted through various measures taken by African organizations and governments. In recent years, Africa has achieved remarkable results in promoting the development of traditional medicine. Many other countries will benefit from studying their examples and adopting similar measures.%本文采用信息研究的方法收集和分析相关文献,重点研究了非洲推动传统医学发展的举措与进展,为中医药传统知识保护提供思路。结果表明,非洲各组织和各国家政府采取多种措施,有力地促进了非洲传统医学发展,其成效值得其他国家推广和借鉴。

  4. 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;

    2009-01-01

    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....... Population groups most in need such as people with low levels of physical activity were rarely specifically targeted. Most policies emphasized the importance of an evaluation. However, only about half of them indicated a related intention or requirement. CONCLUSION: In recent years there has been...

  5. Depletion of Retinoic Acid Receptors Initiates a Novel Positive Feedback Mechanism that Promotes Teratogenic Increases in Retinoic Acid

    OpenAIRE

    Enrico D'Aniello; Rydeen, Ariel B.; Jane L Anderson; Amrita Mandal; Waxman, Joshua S.

    2013-01-01

    Author Summary Retinoic acid (RA) is the most active metabolic product of Vitamin A. Appropriate levels of RA are required for proper embryonic development and tissue maintenance in all vertebrates. Inappropriate levels of RA in human embryos can cause congenital defects that affect many organs, including the heart and limbs, and lead to numerous types of cancers. Understanding how animals maintain appropriate RA levels and the consequences of inappropriate RA signaling will therefore provide...

  6. ORM Promotes Skeletal Muscle Glycogen Accumulation via CCR5-Activated AMPK Pathway in Mice

    Science.gov (United States)

    Qin, Zhen; Wan, Jing-Jing; Sun, Yang; Wang, Peng-Yuan; Su, Ding-Feng; Lei, Hong; Liu, Xia

    2016-01-01

    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

  7. Feasibility, acceptability, and initial efficacy of an online sexual health promotion program for LGBT youth: the Queer Sex Ed intervention.

    Science.gov (United States)

    Mustanski, Brian; Greene, George J; Ryan, Daniel; Whitton, Sarah W

    2015-01-01

    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.

  8. Eukaryotic Translation Initiation Factor 3a (eIF3a) Promotes Cell Proliferation and Motility in Pancreatic Cancer.

    Science.gov (United States)

    Wang, Shu Qian; Liu, Yu; Yao, Min Ya; Jin, Jing

    2016-10-01

    Identifying a target molecule that is crucially involved in pancreatic tumor growth and metastasis is necessary in developing an effective treatment. The study aimed to investigate the role of the eukaryotic translation initiation factor 3a (eIF3a) in the cell proliferation and motility in pancreatic cancer. Our data showed that the expression of eIF3a was upregulated in pancreatic ductal adenocarcinoma as compared with its expression in normal pancreatic tissues. Knockdown of eIF3a by a specific shRNA caused significant decreases in cell proliferation and clonogenic abilities in pancreatic cancer SW1990 and Capan-1 cells. Consistently, the pancreatic cancer cell growth rates were also impaired in xenotransplanted mice. Moreover, wound-healing assay showed that depletion of eIF3a significantly slowed down the wound recovery processes in SW1990 and Capan-1 cells. Transwell migration and invasion assays further showed that cell migration and invasion abilities were significantly inhibited by knockdown of eIF3a in SW1990 and Capan-1 cells. Statistical analysis of eIF3a expression in 140 cases of pancreatic ductal adenocarcinoma samples revealed that eIF3a expression was significantly associated with tumor metastasis and TNM staging. These analyses suggest that eIF3a contributes to cell proliferation and motility in pancreatic ductal adenocarcinoma. PMID:27550487

  9. NASA safety program activities in support of the Space Exploration Initiatives Nuclear Propulsion program

    Science.gov (United States)

    Sawyer, J. C., Jr.

    1993-01-01

    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.

  10. Physical Activity in Medellín: a Challenge for Health Promotion

    Directory of Open Access Journals (Sweden)

    Frank Éuler Sepúlveda

    2008-06-01

    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.

  11. Recommendations for Promoting Physical Activity for Children and Adolescents in Germany. A Consensus Statement

    Directory of Open Access Journals (Sweden)

    Christine Graf

    2014-05-01

    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.

  12. Irisin promotes osteoblast proliferation and differentiation via activating the MAP kinase signaling pathways.

    Science.gov (United States)

    Qiao, Xiaoyong; Yong Qiao, Xiao; Nie, Ying; Ma, Yaxian; Xian Ma, Ya; Chen, Yan; Cheng, Ran; Yin, Weiyao; Yao Yinrg, Wei; Hu, Ying; Xu, Wenming; Ming Xu, Wen; Xu, Liangzhi; Zhi Xu, Liang

    2016-01-01

    Physical exercise is able to improve skeletal health. However, the mechanisms are poorly known. Irisin, a novel exercise-induced myokine, secreted by skeletal muscle in response to exercise, have been shown to mediate beneficial effects of exercise in many disorders. In the current study, we demonstrated that irisin promotes osteoblast proliferation, and increases the expression of osteoblastic transcription regulators, such as Runt-related transcription factor-2, osterix/sp7; and osteoblast differentiation markers, including alkaline phosphatase, collagen type 1 alpha-1, osteocalcin, and osteopontin in vitro. Irisin also increase ALP activity and calcium deposition in cultured osteoblast. These osteogenic effects were mediated by activating the p38 mitogen-activated protein kinase (p-p38 MAPK) and extracellular signal-regulated kinase (ERK). Inhibition of p38 MAPK by SB023580 or pERK by U0126 abolished the proliferation and up-regulatory effects of irisin on Runx2 expression and ALP activity. Together our observation suggest that irisin directly targets osteoblast, promoting osteoblast proliferation and differentiation via activating P38/ERK MAP kinase signaling cascades in vitro. Whether irisin can be utilized as the therapeutic agents for osteopenia and osteoporosis is worth to be further pursued. PMID:26738434

  13. The regulation of the SARK promoter activity by hormones and environmental signals.

    Science.gov (United States)

    Delatorre, Carla A; Cohen, Yuval; Liu, Li; Peleg, Zvi; Blumwald, Eduardo

    2012-09-01

    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.

  14. 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)

    2002-01-01

    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.

  15. Direct interaction of Sox10 with the promoter of murine Dopachrome Tautomerase (Dct) and synergistic activation of Dct expression with Mitf.

    Science.gov (United States)

    Jiao, Zhongxian; Mollaaghababa, Ramin; Pavan, William J; Antonellis, Anthony; Green, Eric D; Hornyak, Thomas J

    2004-08-01

    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.

  16. The satiety signaling neuropeptide perisulfakinin inhibits the activity of central neurons promoting general activity

    Directory of Open Access Journals (Sweden)

    Dieter Wicher

    2007-12-01

    Full Text Available The metabolic state is one of the determinants of the general activity level. Satiety is related to resting or sleep whereas hunger correlates to wakefulness and activity. The counterpart to the mammalian satiety signal cholecystokinin (CCK in insects are the sulfakinins. The aim of this study was to resolve the mechanism by which the antifeedant activity of perisulfakinin (PSK in Periplaneta americana is mediated. We identified the sources of PSK which is used both as hormone and as paracrine messenger. PSK is found in the neurohemal organ of the brain and in nerve endings throughout the central nervous system. To correlate the distributions of PSK and its receptor (PSKR, we cloned the gene coding for PSKR and provide evidence for its expression within the nervous system. It occurs only in a few neurons, among them are the dorsal unpaired median (DUM neurons which release octopamine thereby regulating the general level of activity. Application of PSK to DUM neurons attenuated the spiking frequency (EC50=11pM due to reduction of a pacemaker Ca2+ current through cAMP-inhibited pTRPγ channels. PSK increased the intracellular cAMP level while decreasing the intracellular Ca2+ concentration in DUM neurons. Thus, the satiety signal conferred by PSK acts antagonistically to the hunger signal, provided by the adipokinetic hormone (AKH: PSK depresses the electrical activity of DUM neurons by inhibiting the pTRPγ channel that is activated by AKH under conditions of food shortage.

  17. The satiety signaling neuropeptide perisulfakinin inhibits the activity of central neurons promoting general activity.

    Science.gov (United States)

    Wicher, Dieter; Derst, Christian; Gautier, Hélène; Lapied, Bruno; Heinemann, Stefan H; Agricola, Hans-Jürgen

    2007-01-01

    The metabolic state is one of the determinants of the general activity level. Satiety is related to resting or sleep whereas hunger correlates to wakefulness and activity. The counterpart to the mammalian satiety signal cholecystokinin (CCK) in insects are the sulfakinins. The aim of this study was to resolve the mechanism by which the antifeedant activity of perisulfakinin (PSK) in Periplaneta americana is mediated. We identified the sources of PSK which is used both as hormone and as paracrine messenger. PSK is found in the neurohemal organ of the brain and in nerve endings throughout the central nervous system. To correlate the distributions of PSK and its receptor (PSKR), we cloned the gene coding for PSKR and provide evidence for its expression within the nervous system. It occurs only in a few neurons, among them are the dorsal unpaired median (DUM) neurons which release octopamine thereby regulating the general level of activity. Application of PSK to DUM neurons attenuated the spiking frequency (EC(50)=11pM) due to reduction of a pacemaker Ca(2+) current through cAMP-inhibited pTRPgamma channels. PSK increased the intracellular cAMP level while decreasing the intracellular Ca(2+) concentration in DUM neurons. Thus, the satiety signal conferred by PSK acts antagonistically to the hunger signal, provided by the adipokinetic hormone (AKH): PSK depresses the electrical activity of DUM neurons by inhibiting the pTRPgamma channel that is activated by AKH under conditions of food shortage. PMID:18946521

  18. The Activation of Free Dipeptides Promoted by Strong Activating Agents in Water Does not Yield Diketopiperazines.

    Science.gov (United States)

    Beaufils, Damien; Jepaul, Sandra; Liu, Ziwei; Boiteau, Laurent; Pascal, Robert

    2016-03-01

    The activation of dipeptides was studied in the perspective of the abiotic formation of oligopeptides of significant length as a requirement for secondary structure formation. The formation of piperazin-2,5-diones (DKP), previously considered as a dead end when activating free dipeptides, was shown in this work to be efficiently suppressed when using strong activating agents (e.g., carbodiimides). This behaviour was explained by the fast formation of a 5(4H)-oxazolone intermediate at a rate that exceeds the time scale of the rotation of the peptide bond from the predominant trans-conformation into the cis-isomer required for DKP formation. No DKP was observed when using strong activating agents whereas phosphate mixed anhydrides or moderately activated esters were observed to predominantly yield DKP. The DKP side-reaction no longer constitutes a drawback for the C-terminus elongation of peptides. These results are considered as additional evidence that pathways involving strong activation are required to drive the emergence of living entities rather than close to equilibrium processes.

  19. The Activation of Free Dipeptides Promoted by Strong Activating Agents in Water Does not Yield Diketopiperazines

    Science.gov (United States)

    Beaufils, Damien; Jepaul, Sandra; Liu, Ziwei; Boiteau, Laurent; Pascal, Robert

    2016-03-01

    The activation of dipeptides was studied in the perspective of the abiotic formation of oligopeptides of significant length as a requirement for secondary structure formation. The formation of piperazin-2,5-diones (DKP), previously considered as a dead end when activating free dipeptides, was shown in this work to be efficiently suppressed when using strong activating agents (e.g., carbodiimides). This behaviour was explained by the fast formation of a 5(4 H)-oxazolone intermediate at a rate that exceeds the time scale of the rotation of the peptide bond from the predominant trans-conformation into the cis-isomer required for DKP formation. No DKP was observed when using strong activating agents whereas phosphate mixed anhydrides or moderately activated esters were observed to predominantly yield DKP. The DKP side-reaction no longer constitutes a drawback for the C-terminus elongation of peptides. These results are considered as additional evidence that pathways involving strong activation are required to drive the emergence of living entities rather than close to equilibrium processes.

  20. Policies to promote on physical activity and healthy eating in kindergartens from theory to practice

    DEFF Research Database (Denmark)

    Mikkelsen, Bent Egberg

    2011-01-01

    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...... the policy tool an active vehicle for an improvement of children ’ s lifestyle behaviour and thus a dynamic instrument....

  1. Radiation protection survey of research and development activities initiated after the Chernobyl accident. Review report

    International Nuclear Information System (INIS)

    The compilation of research and development activities in the various fields of radiation protection in OECD Member countries which have been undertaken or planned specifically to address open questions arising from the Chernobyl reactor accident experience shows a potential for international cooperative arrangements and/or coordination between national programmes. Both the preliminary review of the answers, which only cover a part of the relevant activities in OECD Member countries, and a computerized literature search indicate that the multidisciplinarity of the research area under consideration will call for special efforts to efficiently implement new models and new quantitative findings from the different fields of activity to provide an improved basis for emergency management and risk assessment. Further improvements could also be achieved by efforts to initiate new activities to close gaps in the programmes under way, to enhance international cooperation, and to coordinate the evaluation of the results. This preliminary review of the answers of 17 Member countries to the questionnaire on research and development activities initiated after the Chernobyl accident is not sufficient as a basis for a balanced decision on those research areas most in need for international cooperation and coordination. It may however serve as a guide for the exploration of the potential for international cooperative arrangements and/or coordination between national programmes by the CRPPH. Even at this preliminary stage, several specific activities are proposed to the NEA/OECD by Member countries. Whole body counting and the intercomparison of national data bases on the behaviour of radionuclides in the environment did attract most calls for international cooperation sponsored by the NEA

  2. 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

    2000-01-01

    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.

  3. 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.

  4. Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Anastasiou, Dimitrios; Yu, Yimin; Israelsen, William J.; Jiang, Jian-Kang; Boxer, Matthew B.; Hong, Bum Soo; Tempel, Wolfram; Dimov, Svetoslav; Shen, Min; Jha, Abhishek; Yang, Hua; Mattaini, Katherine R.; Metallo, Christian M.; Fiske, Brian P.; Courtney, Kevin D.; Malstrom, Scott; Khan, Tahsin M.; Kung, Charles; Skoumbourdis, Amanda P.; Veith, Henrike; Southall, Noel; Walsh, Martin J.; Brimacombe, Kyle R.; Leister, William; Lunt, Sophia Y.; Johnson, Zachary R.; Yen, Katharine E.; Kunii, Kaiko; Davidson, Shawn M.; Christofk, Heather R.; Austin, Christopher P.; Inglese, James; Harris, Marian H.; Asara, John M.; Stephanopoulos, Gregory; Salituro, Francesco G.; Jin, Shengfang; Dang, Lenny; Auld, Douglas S.; Park, Hee-Won; Cantley, Lewis C.; Thomas, Craig J.; Vander Heiden, Matthew G.

    2012-08-26

    Cancer cells engage in a metabolic program to enhance biosynthesis and support cell proliferation. The regulatory properties of pyruvate kinase M2 (PKM2) influence altered glucose metabolism in cancer. The interaction of PKM2 with phosphotyrosine-containing proteins inhibits enzyme activity and increases the availability of glycolytic metabolites to support cell proliferation. This suggests that high pyruvate kinase activity may suppress tumor growth. We show that expression of PKM1, the pyruvate kinase isoform with high constitutive activity, or exposure to published small-molecule PKM2 activators inhibits the growth of xenograft tumors. Structural studies reveal that small-molecule activators bind PKM2 at the subunit interaction interface, a site that is distinct from that of the endogenous activator fructose-1,6-bisphosphate (FBP). However, unlike FBP, binding of activators to PKM2 promotes a constitutively active enzyme state that is resistant to inhibition by tyrosine-phosphorylated proteins. This data supports the notion that small-molecule activation of PKM2 can interfere with anabolic metabolism.

  5. Promotion and support of physical activity in elderly patients on hemodialysis: a case study.

    Science.gov (United States)

    Shiota, Kotomi; Hashimoto, Toshihiko

    2016-04-01

    [Purpose] The aim of this study was to ascertain the optimum strategy for implementing a physical activity intervention in patients on hemodialysis by investigating the physical characteristics of elderly patients on hemodialysis, and their attitude to physical activity and level of daily activity. [Subjects] The Subject were 10 elderly patients on hemodialysis. [Methods] They wore a physical activity monitor for 1 week. Data obtained were analyzed for hemodialysis and non- hemodialysis days, and two-way analysis of variance was used to compare the number of steps and activity levels. A questionnaire was administered to investigate the stage of psychological preparedness for exercise and attitudes toward/awareness of exercise. [Results] There was no significant difference in the number of steps or exercise levels on hemodialysis and non- hemodialysis days. However, on both types of days, subjects spent long periods not engaged in any activity. Most of their activity was either inactivity or sedentary behavior. [Conclusion] Patients on hemodialysis with low physical activity levels are considered to have poor physical function and exercise tolerance. To maintain and improve the physical function of patients on hemodialysis, it will be necessary to reduce their time spent in inactive, and comprehensive care that covers psychosocial aspects should be provided to promote the proactive improvement of physical activity and their attitudes to exercise. PMID:27190487

  6. Community Vision and Interagency Alignment: A Community Planning Process to Promote Active Transportation.

    Science.gov (United States)

    DeGregory, Sarah Timmins; Chaudhury, Nupur; Kennedy, Patrick; Noyes, Philip; Maybank, Aletha

    2016-04-01

    In 2010, the Brooklyn Active Transportation Community Planning Initiative launched in 2 New York City neighborhoods. Over a 2-year planning period, residents participated in surveys, school and community forums, neighborhood street assessments, and activation events-activities that highlighted the need for safer streets locally. Consensus among residents and key multisectoral stakeholders, including city agencies and community-based organizations, was garnered in support of a planned expansion of bicycling infrastructure. The process of building on community assets and applying a collective impact approach yielded changes in the built environment, attracted new partners and resources, and helped to restore a sense of power among residents. PMID:26959270

  7. Community Vision and Interagency Alignment: A Community Planning Process to Promote Active Transportation.

    Science.gov (United States)

    DeGregory, Sarah Timmins; Chaudhury, Nupur; Kennedy, Patrick; Noyes, Philip; Maybank, Aletha

    2016-04-01

    In 2010, the Brooklyn Active Transportation Community Planning Initiative launched in 2 New York City neighborhoods. Over a 2-year planning period, residents participated in surveys, school and community forums, neighborhood street assessments, and activation events-activities that highlighted the need for safer streets locally. Consensus among residents and key multisectoral stakeholders, including city agencies and community-based organizations, was garnered in support of a planned expansion of bicycling infrastructure. The process of building on community assets and applying a collective impact approach yielded changes in the built environment, attracted new partners and resources, and helped to restore a sense of power among residents.

  8. Guidelines for youth sports clubs to develop, implement, and assess health promotion within its activities.

    Science.gov (United States)

    Kokko, Sami

    2014-05-01

    The settings approach to health promotion is a world-known concept concerning settings like city, hospital, school, and workplace. The concept has also been used in some regionally specific settings, such as island, prison, or university. However, there are still many, often noninstitutional, settings that have a lot of potential but have not yet been recognized. One of the newcomers is the youth sports club, which has the potential to reach a lot of children and adolescents and is effective, via its casual educational nature based on voluntary participation. According to research, health is an important aim for most youth sports clubs, but it has not been converted into practical actions. Indeed, the clubs often recognize the importance of healthy lifestyles, but there is a lack of understanding of what to do to reinforce it within one's activities. That is why, on the basis of the results of the Health Promoting Sports Club survey in Finland, guidelines for clubs to enhance health promotion as a part of their activities were created. The aim of this article is to present the guidelines, theirs rationale, and practical examples. PMID:24357861

  9. Induction of megakaryocytic colony-stimulating activity in mouse skin by inflammatory agents and tumor promoters

    Energy Technology Data Exchange (ETDEWEB)

    Clark, D.A.; Dessypris, E.N.; Koury, M.J.

    1987-03-01

    The production of megakaryocytic colony-stimulating activity (MEG-CSA) was assayed in acetic acid extracts of skin from mice topically treated with inflammatory and tumor-promoting agents. A rapid induction of MEG-CSA was found in skin treated both with phorbol 12-myristate 13-acetate (PMA), a strong tumor promoter, and with mezerein, a weak tumor promoter, but no induction was found in untreated skin. The time course of induction of MEG-CSA following treatment of skin with PMA or mezerein was very similar to that previously demonstrated for the induction of granulocyte-macrophage colony-stimulating activity in mouse skin by these agents. The induced MEG-CSA was found in both the epidermis and the dermis. Pretreatment of the skin with US -methasone abrogated the MEG-CSA induction. The cell number response curve suggests that the MEG-CSA acts directly on the progenitor cells of the megakaryocyte colonies. That topical administration of diterpene esters results in the rapid, local induction of MEG-CSA which can be blocked by US -methasone pretreatment suggests a mechanism for the thrombocytosis associated with some inflammatory states. The indirect action in which diterpene esters induce in certain cells the production or release of growth regulatory factors for other cell types may also aid in understanding their carcinogenic properties.

  10. Activity Analysis and Preliminary Inducer Screening of the Chicken DAZL Gene Promoter

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2015-03-01

    Full Text Available This study was aimed at identifying the active control area of chicken DAZL gene core promoter, to screen optimum inducers of the DAZL gene, thus to enhance the differentiation of embryonic stem cells into spermatogonial stem cells. Fragments of chicken DAZL gene promoter were cloned into fluorescent reporter plasmids and transfected into DF-1 cells. Then Dual-Luciferase® Reporter Assay System was used to identify the activity of the DAZL gene under different inducers. Our studies showed that the DAZL core promoter region for the Suqin yellow chicken was −383 to −39 bp. The dual-luciferase® reporter showed that all-trans retinoic acid (ATRA, a retinoic acid receptor alpha agonist (tamibarotene/Am80, or estradiol (E2 could significantly enhance DAZL transcription. The in vitro inductive culture of chicken ESCs demonstrated that, with ATRA treatment, DAZL transcription peaked at 6 days and then decreased slowly; whereas, DAZL transcription was continuous and peaked at 10 days with Am80 treatment. E2 treatment significantly increased DAZL expression after 8 days. All three treatments were associated with the appearance of male germ cell (MGC-like cells on day 10. These results provide the optimum inducer screening of the DAZL gene and lay the foundation for further screening of compounds that can induce the differentiation of ESCs into MGCs in vitro.

  11. Activity analysis and preliminary inducer screening of the chicken DAZL gene promoter.

    Science.gov (United States)

    Zhang, Lei; Zhu, Rui; Zuo, Qisheng; Li, Dong; Lian, Chao; Tang, Beibei; Xiao, Tianrong; Zhang, Yani; Li, Bichun

    2015-01-01

    This study was aimed at identifying the active control area of chicken DAZL gene core promoter, to screen optimum inducers of the DAZL gene, thus to enhance the differentiation of embryonic stem cells into spermatogonial stem cells. Fragments of chicken DAZL gene promoter were cloned into fluorescent reporter plasmids and transfected into DF-1 cells. Then Dual-Luciferase® Reporter Assay System was used to identify the activity of the DAZL gene under different inducers. Our studies showed that the DAZL core promoter region for the Suqin yellow chicken was -383 to -39 bp. The dual-luciferase® reporter showed that all-trans retinoic acid (ATRA), a retinoic acid receptor alpha agonist (tamibarotene/Am80), or estradiol (E2) could significantly enhance DAZL transcription. The in vitro inductive culture of chicken ESCs demonstrated that, with ATRA treatment, DAZL transcription peaked at 6 days and then decreased slowly; whereas, DAZL transcription was continuous and peaked at 10 days with Am80 treatment. E2 treatment significantly increased DAZL expression after 8 days. All three treatments were associated with the appearance of male germ cell (MGC)-like cells on day 10. These results provide the optimum inducer screening of the DAZL gene and lay the foundation for further screening of compounds that can induce the differentiation of ESCs into MGCs in vitro. PMID:25807265

  12. 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

    2008-01-01

    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.

  13. Using Competency-Based Digital Open Learning Activities to Facilitate and Promote Health Professions Education (OLAmeD): A Proposal

    Science.gov (United States)

    Barman, Linda

    2016-01-01

    Background Traditional learning in medical education has been transformed with the advent of information technology. We have recently seen global initiatives to produce online activities in an effort to scale up learning opportunities through learning management systems and massive open online courses for both undergraduate and continued professional education. Despite the positive impact of such efforts, factors such as cost, time, resources, and the specificity of educational contexts restrict the design and exchange of online medical educational activities. Objective The goal is to address the stated issues within the health professions education context while promoting learning by proposing the Online Learning Activities for Medical Education (OLAmeD) concept which builds on unified competency frameworks and generic technical standards for education. Methods We outline how frameworks used to describe a set of competencies for a specific topic in medical education across medical schools in the United States and Europe can be compared to identify commonalities that could result in a unified set of competencies representing both contexts adequately. Further, we examine how technical standards could be used to allow standardization, seamless sharing, and reusability of educational content. Results The entire process of developing and sharing OLAmeD is structured and presented in a set of steps using as example Urology as a part of clinical surgery specialization. Conclusions Beyond supporting the development, sharing, and repurposing of educational content, we expect OLAmeD to work as a tool that promotes learning and sets a base for a community of medical educational content developers across different educational contexts. PMID:27390226

  14. eIF2B promotes eIF5 dissociation from eIF2•GDP to facilitate guanine nucleotide exchange for translation initiation

    OpenAIRE

    Jennings, Martin D.; Zhou, Yu; Mohammad-Qureshi, Sarah S.; Bennett, David; Pavitt, Graham D.

    2013-01-01

    Protein synthesis factor eIF2 delivers initiator tRNA to the ribosome. Two proteins regulate its G-protein cycle: eIF5 has both GTPase-activating protein (GAP) and GDP dissociation inhibitor (GDI) functions, and eIF2B is the guanine nucleotide exchange factor (GEF). Jennings et al. now establish a second activity for eIF2B (as a GDI displacement factor [GDF]) and demonstrate that this function is independent of its GEF activity. This study suggests that eIF2B is a bifunctional protein and def...

  15. A library of synthetic transcription activator-like effector-activated promoters for coordinated orthogonal gene expression in plants.

    Science.gov (United States)

    Brückner, Kathleen; Schäfer, Petra; Weber, Ernst; Grützner, Ramona; Marillonnet, Sylvestre; Tissier, Alain

    2015-05-01

    A library of synthetic promoters containing the binding site of a single designer transcription activator-like effector (dTALE) was constructed. The promoters contain a constant sequence, consisting of an 18-base long dTALE-binding site and a TATA box, flanked by degenerate sequences of 49 bases downstream and 19 bases upstream. Forty-three of these promoters were sequenced and tested in transient assays in Nicotiana benthamiana using a GUS reporter gene. The strength of expression of the promoters ranged from around 5% to almost 100% of the viral 35S promoter activity. We then demonstrated the utility of these promoters for metabolic engineering by transiently expressing three genes for the production of a plant diterpenoid in N. benthamiana. The simplicity of the promoter structure shows great promise for the development of genetic circuits, with wide potential applications in plant synthetic biology and metabolic engineering.

  16. Relation of intracellular signal levels and promoter activities in the gal regulon of Escherichia coli.

    Science.gov (United States)

    Krishna, Sandeep; Orosz, László; Sneppen, Kim; Adhya, Sankar; Semsey, Szabolcs

    2009-08-28

    Transcription of many genes is regulated by combinations of multiple signals. In Escherichia coli, combinatorial control is typical in the case of operons related to utilization of different sugars in the absence of glucose. To understand regulation of the transport and metabolic pathways in the galactose system, we measured activities of the six gal regulon promoters simultaneously, using an in vitro transcription system containing purified components. Input functions were computed on the basis of the experimental measurements. We observed four different shapes of input functions. From the results, we can conclude that the structure of the regulatory network is insufficient for the determination of signal integration. It is the actual structure of the promoter and regulatory region, the mechanism of transcription regulation, and the interplay between transcription factors that shape the input function to be suitable for adaptation. PMID:19559028

  17. Supporting public health priorities: recommendations for physical education and physical activity promotion in schools.

    Science.gov (United States)

    Hills, Andrew P; Dengel, Donald R; Lubans, David R

    2015-01-01

    Physical activity (PA) provides numerous physiological and psychosocial benefits. However, lifestyle changes, including reduced PA opportunities in multiple settings, have resulted in an escalation of overweight and obesity and related health problems. Poor physical and mental health, including metabolic and cardiovascular problems is seen in progressively younger ages, and the systematic decline in school PA has contributed to this trend. Of note, the crowded school curriculum with an intense focus on academic achievement, lack of school leadership support, funding and resources, plus poor quality teaching are barriers to PA promotion in schools. The school setting and physical educators in particular, must embrace their role in public health by adopting a comprehensive school PA program. We provide an overview of key issues and challenges in the area plus best bets and recommendations for physical education and PA promotion in the school system moving forward. PMID:25269062

  18. FOXR2 Interacts with MYC to Promote Its Transcriptional Activities and Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Xu Li

    2016-07-01

    Full Text Available By combining the results of a large-scale proteomic analysis of the human transcription factor interaction network with knowledge databases, we identified FOXR2 as one of the top-ranked candidate proto-oncogenes. Here, we show that FOXR2 forms a stable complex with MYC and MAX and subsequently regulates cell proliferation by promoting MYC’s transcriptional activities. We demonstrate that FOXR2 is highly expressed in several breast, lung, and liver cancer cell lines and related patient tumor samples, while reduction of FOXR2 expression in a xenograft model inhibits tumor growth. These results indicate that FOXR2 acts with MYC to promote cancer cell proliferation, which is a potential tumor-specific target for therapeutic intervention against MYC-driven cancers.

  19. A model for promoting physical activity among rural South African adolescent girls

    Directory of Open Access Journals (Sweden)

    John Kinsman

    2015-12-01

    Full Text Available Background: In South Africa, the expanding epidemic of non-communicable diseases is partly fuelled by high levels of physical inactivity and sedentary behaviour. Women especially are at high risk, and interventions promoting physical activity are urgently needed for girls in their adolescence, as this is the time when many girls adopt unhealthy lifestyles. Objective: This qualitative study aimed to identify and describe facilitating factors and barriers that are associated with physical activity among adolescent girls in rural, north-eastern South Africa and, based on these, to develop a model for promoting leisure-time physical activity within this population. Design: The study was conducted in and around three secondary schools. Six focus group discussions were conducted with adolescent girls from the schools, and seven qualitative interviews were held with sports teachers and youth leaders. The data were subjected to thematic analysis. Results: Seven thematic areas were identified, each of which was associated with the girls’ self-reported levels of physical activity. The thematic areas are 1 poverty, 2 body image ideals, 3 gender, 4 parents and home life, 5 demographic factors, 6 perceived health effects of physical activity, and 7 human and infrastructural resources. More barriers to physical activity were reported than facilitating factors. Conclusions: Analysis of the barriers found in the different themes indicated potential remedial actions that could be taken, and these were synthesised into a model for promoting physical activity among South African adolescent girls in resource-poor environments. The model presents a series of action points, seen both from the ‘supply-side’ perspective (such as the provision of resources and training for the individuals, schools, and organisations which facilitate the activities and from the ‘demand-side’ perspective (such as the development of empowering messages about body image for

  20. GPS2/KDM4A Pioneering Activity Regulates Promoter-Specific Recruitment of PPARγ

    Directory of Open Access Journals (Sweden)

    M. Dafne Cardamone

    2014-07-01

    Full Text Available Timely and selective recruitment of transcription factors to their appropriate DNA-binding sites represents a critical step in regulating gene activation; however, the regulatory strategies underlying each factor’s effective recruitment to specific promoter and/or enhancer regions are not fully understood. Here, we identify an unexpected regulatory mechanism by which promoter-specific binding, and therefore function, of peroxisome proliferator-activator receptor γ (PPARγ in adipocytes requires G protein suppressor 2 (GPS2 to prime the local chromatin environment via inhibition of the ubiquitin ligase RNF8 and stabilization of the H3K9 histone demethylase KDM4A/JMJD2. Integration of genome-wide profiling data indicates that the pioneering activity of GPS2/KDM4A is required for PPARγ-mediated regulation of a specific transcriptional program, including the lipolytic enzymes adipose triglyceride lipase (ATGL and hormone-sensitive lipase (HSL. Hence, our findings reveal that GPS2 exerts a biologically important function in adipose tissue lipid mobilization by directly regulating ubiquitin signaling and indirectly modulating chromatin remodeling to prime selected genes for activation.

  1. [Community vegetable gardens as a health promotion activity: an experience in Primary Healthcare Units].

    Science.gov (United States)

    Costa, Christiane Gasparini Araújo; Garcia, Mariana Tarricone; Ribeiro, Silvana Maria; Salandini, Marcia Fernanda de Sousa; Bógus, Cláudia Maria

    2015-10-01

    Urban and peri-urban agriculture (UPA) is being practiced in different settings, contributing to the improvement of health in communities and healthier environments. In order to identify the meanings and implications of the practice of UPA in Primary Healthcare Units (PHU) as an activity of health promotion (HP), and to what extent its therapeutic dimension characterizes it as an activity aligned with complementary and integrative practices (CIP), a qualitative cross-sectional study was performed in Embu das Artes, State of São Paulo. From the analysis, the following main themes arose: health concept, health outcomes, the return to traditional practices and habits and the reorientation of health services. It was possible to identify the close link between the cultivation of vegetable gardens and HP guidelines and fields of action, such as creating healthier environments, boosting community actions, developing personal skills, stimulating autonomy and empowerment and demands for the reorientation of services. The garden activities, set up in PHU areas, proved to be an implementation strategy of CIP. The conclusion reached is that vegetable gardening activities in community gardens are seen to be health promotion practices that integrate key elements of CIP. PMID:26465852

  2. Policies to promote on physical activity and healthy eating in kindergartens from theory to practice.

    Science.gov (United States)

    Mikkelsen, Bent Egberg

    2011-10-01

    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 defined as a set of adopted principles that guide the work of an organization and aim to achieve a well defined goal, but only policies that rely on the active participation and involvement of concerned actors will be efficient. 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 the policy tool an active vehicle for an improvement of children's lifestyle behaviour and thus a dynamic instrument.

  3. Lysophosphatidic acid activates Arf6 to promote the mesenchymal malignancy of renal cancer.

    Science.gov (United States)

    Hashimoto, Shigeru; Mikami, Shuji; Sugino, Hirokazu; Yoshikawa, Ayumu; Hashimoto, Ari; Onodera, Yasuhito; Furukawa, Shotaro; Handa, Haruka; Oikawa, Tsukasa; Okada, Yasunori; Oya, Mototsugu; Sabe, Hisataka

    2016-01-01

    Acquisition of mesenchymal properties by cancer cells is critical for their malignant behaviour, but regulators of the mesenchymal molecular machinery and how it is activated remain elusive. Here we show that clear cell renal cell carcinomas (ccRCCs) frequently utilize the Arf6-based mesenchymal pathway to promote invasion and metastasis, similar to breast cancers. In breast cancer cells, ligand-activated receptor tyrosine kinases employ GEP100 to activate Arf6, which then recruits AMAP1; and AMAP1 then binds to the mesenchymal-specific protein EPB41L5, which promotes epithelial-mesenchymal transition and focal adhesion dynamics. In renal cancer cells, lysophosphatidic acid (LPA) activates Arf6 via its G-protein-coupled receptors, in which GTP-Gα12 binds to EFA6. The Arf6-based pathway may also contribute to drug resistance. Our results identify a specific mesenchymal molecular machinery of primary ccRCCs, which is triggered by a product of autotaxin and it is associated with poor outcome of patients. PMID:26854204

  4. Inhibitory effects promoted by 5'-nucleotides on the ecto-3'-nucleotidase activity of Leishmania amazonensis.

    Science.gov (United States)

    Freitas-Mesquita, Anita Leocadio; Gomes, Marta T; Vieira, Danielle P; Paes-Vieira, Lisvane; Nascimento, Michelle T C; Lopes, Angela H C S; Meyer-Fernandes, José Roberto

    2016-10-01

    The protozoan parasite Leishmania amazonensis is the etiological agent of cutaneous leishmaniasis. During its life cycle, the flagellated metacyclic promastigote forms are transmitted to vertebrate hosts by sandfly bites, and they develop into amastigotes inside macrophages, where they multiply. L. amazonensis possesses a bifunctional enzyme, called 3'-nucleotidase/nuclease (3'NT/NU), which is able to hydrolyze extracellular 3'-monophosphorylated nucleosides and nucleic acids. 3'NT/NU plays an important role in the generation of extracellular adenosine and has been described as a key enzyme in the acquisition of purines by trypanosomatids. Furthermore, it has been observed that 3'NT/NU also plays a valuable role in the establishment of parasitic infection. In this context, this study aimed to investigate the modulation of the 3'-nucleotidase (3'NT) activity of L. amazonensis by several nucleotides. It was observed that 3'NT activity is inhibited by micromolar concentrations of guanosine and guanine nucleotides. The inhibition promoted by 5'-GMP on the 3'NT activity of L. amazonensis is reversible and uncompetitive because the addition of the inhibitor decreased the kinetic parameters Km and Vmax. Finally, we found that the addition of 5'-GMP is able to reverse the stimulation promoted by 3'-AMP in a macrophage-parasite interaction assay. The determination of compounds that can inhibit the 3'NT activity of Leishmania is very important because this enzyme does not occur in mammals, making it a potential therapeutic target. PMID:27531705

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

    OpenAIRE

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

    2001-01-01

    STUDY OBJECTIVE—To assess the impact of a national campaign on awareness of the campaign, change in knowledge of physical activity recommendations and self reported physical activity.
DESIGN—three year prospective longitudinal survey using a multi-stage, cluster random probability design to select participants.
SETTING—England.
PARTICIPANTS—A nationally representative sample of 3189 adults aged 16-74 years.
MAIN OUTCOME MEASURES—Awareness of the advertising element of the campaign, changes in...

  6. TAF4 inactivation reveals the 3 dimensional growth promoting activities of collagen 6A3.

    Directory of Open Access Journals (Sweden)

    Igor Martianov

    Full Text Available Collagen 6A3 (Col6a3, a component of extracellular matrix, is often up-regulated in tumours and is believed to play a pro-oncogenic role. However the mechanisms of its tumorigenic activity are poorly understood. We show here that Col6a3 is highly expressed in densely growing mouse embryonic fibroblasts (MEFs. In MEFs where the TAF4 subunit of general transcription factor IID (TFIID has been inactivated, elevated Col6a3 expression prevents contact inhibition promoting their 3 dimensional growth as foci and fibrospheres. Analyses of gene expression in densely growing Taf4(-/- MEFs revealed repression of the Hippo pathway and activation of Wnt signalling. The Hippo activator Kibra/Wwc1 is repressed under dense conditions in Taf4(-/- MEFs, leading to nuclear accumulation of the proliferation factor YAP1 in the cells forming 3D foci. At the same time, Wnt9a is activated and the Sfrp2 antagonist of Wnt signalling is repressed. Surprisingly, treatment of Taf4(-/- MEFs with all-trans retinoic acid (ATRA restores contact inhibition suppressing 3D growth. ATRA represses Col6a3 expression independently of TAF4 expression and Col6a3 silencing is sufficient to restore contact inhibition in Taf4(-/- MEFs and to suppress 3D growth by reactivating Kibra expression to induce Hippo signalling and by inducing Sfrp2 expression to antagonize Wnt signalling. All together, these results reveal a critical role for Col6a3 in regulating both Hippo and Wnt signalling to promote 3D growth, and show that the TFIID subunit TAF4 is essential to restrain the growth promoting properties of Col6a3. Our data provide new insight into the role of extra cellular matrix components in regulating cell growth.

  7. RFPL3 and CBP synergistically upregulate hTERT activity and promote lung cancer growth.

    Science.gov (United States)

    Qin, Yu; Chen, Wangbing; Xiao, Yao; Yu, Wendan; Cai, Xin; Dai, Meng; Xu, Tingting; Huang, Wenlin; Guo, Wei; Deng, Wuguo; Wu, Taihua

    2015-09-29

    hTERT is the key component of telomerase and its overactivation contributes to maintaining telomere length and cell immortalization. Previously, we identified RFPL3 as a new transcription activator of hTERT in lung cancers. However, the exact mechanism of RFPL3 in mediating hTERT activation and its associated signal regulatory network remain unclear. In this study, we found that RFPL3 colocalized and interacted directly with CBP in the nucleus of lung cancer cells. Immunohistochemical analysis of tissue microarrays of lung cancers revealed the simultaneous overexpression of both RFPL3 and CBP predicted relatively poor prognosis. Furthermore, we confirmed their synergistic stimulation on hTERT expression and tumor cell growth. The binding of RFPL3 to hTERT promoter was reduced markedly when CBP was knocked down by its specific siRNA or suppressed by its inhibitor in lung cancer cells with stable overexpression of RFPL3. When one of the two proteins RFPL3 and CBP was upregulated or downregulated, whereas the another remains unchanged, hTERT expression and telomerase activity were activated or repressed accordingly. In the meantime, the growth of lung cancer cells was also promoted or attenuated accordingly. Furthermore, we also found that RFPL3 coordinated with CBP to upregulate hTERT through the CBP-induced acetylation of RFPL3 protein and their co-anchoring at hTERT promoter region. Collectively, our results reveal a new mechanism of hTERT regulation in lung cancer cells and suggest the RFPL3/CBP/hTERT signaling pathway may be a new targets for lung cancer treatment.

  8. MBD3 localizes at promoters, gene bodies and enhancers of active genes.

    Science.gov (United States)

    Shimbo, Takashi; Du, Ying; Grimm, Sara A; Dhasarathy, Archana; Mav, Deepak; Shah, Ruchir R; Shi, Huidong; Wade, Paul A

    2013-01-01

    The Mi-2/nucleosome remodeling and histone deacetylase (NuRD) complex is a multiprotein machine proposed to regulate chromatin structure by nucleosome remodeling and histone deacetylation activities. Recent reports describing localization of NuRD provide new insights that question previous models on NuRD action, but are not in complete agreement. Here, we provide location analysis of endogenous MBD3, a component of NuRD complex, in two human breast cancer cell lines (MCF-7 and MDA-MB-231) using two independent genomic techniques: DNA adenine methyltransferase identification (DamID) and ChIP-seq. We observed concordance of the resulting genomic localization, suggesting that these studies are converging on a robust map for NuRD in the cancer cell genome. MBD3 preferentially associated with CpG rich promoters marked by H3K4me3 and showed cell-type specific localization across gene bodies, peaking around the transcription start site. A subset of sites bound by MBD3 was enriched in H3K27ac and was in physical proximity to promoters in three-dimensional space, suggesting function as enhancers. MBD3 enrichment was also noted at promoters modified by H3K27me3. Functional analysis of chromatin indicated that MBD3 regulates nucleosome occupancy near promoters and in gene bodies. These data suggest that MBD3, and by extension the NuRD complex, may have multiple roles in fine tuning expression for both active and silent genes, representing an important step in defining regulatory mechanisms by which NuRD complex controls chromatin structure and modification status.

  9. Why and how physical activity promotes experience-induced brain plasticity

    Directory of Open Access Journals (Sweden)

    Gerd eKempermann

    2010-12-01

    Full Text Available Adult hippocampal neurogenesis is an unusual case of brain plasticity, since new neurons (and not just neurites and synapses are added to the network in an activity-dependent way. At the behavioral level the plasticity-inducing stimuli include both physical and cognitive activity. In reductionistic animal studies these types of activity can be studied separately in paradigms like voluntary wheel running and environmental enrichment. In both of these, adult neurogenesis is increased but the net effect is primarily due to different mechanisms at the cellular level. Locomotion appears to stimulate the precursor cells, from which adult neurogenesis originates, to increased proliferation and maintenance over time, whereas environmental enrichment, as well as learning, predominantly promotes survival of immature neurons, that is the progeny of the proliferating precursor cells. Surprisingly, these effects are additive: boosting the potential for adult neurogenesis by physical activity increases the recruitment of cells following cognitive stimulation in an enriched environment. Why is that? We argue that locomotion actually serves as an intrinsic feedback mechanism, signaling to the brain, including its neural precursor cells, that the likelihood of cognitive challenges increases. In the wild (other than in front of a TV, no separation of physical and cognitive activity occurs. Physical activity might thus be much more than a generally healthy garnish to leading an active life but an evolutionarily fundamental aspect of activity, which is needed to provide the brain and its systems of plastic adaptation with the appropriate regulatory input and feedback.

  10. “I am active”: effects of a program to promote active aging

    Directory of Open Access Journals (Sweden)

    Mendoza-Ruvalcaba NM

    2015-05-01

    Full Text Available Neyda Ma Mendoza-Ruvalcaba,1 Elva Dolores Arias-Merino2 1Health Sciences Department, University of Guadalajara, University Center of Tonala Guadalajara, Jalisco, Mexico; 2Public Health Department, University of Guadalajara, University Center of Health Sciences, Guadalajara, Jalisco, Mexico Background: Active aging involves a general lifestyle strategy that allows preservation of both physical and mental health during the aging process. “I am Active” is a program designed to promote active aging by increased physical activity, healthy nutritional habits, and cognitive functioning. The purpose of this study was to assess the effectiveness of this program. Methods: Sixty-four healthy adults aged 60 years or older were recruited from senior centers and randomly allocated to an experimental group (n=31 or a control group (n=33. Baseline, post-test, and 6-month follow-up assessments were performed after the theoretical–practical intervention. Effect sizes were calculated. Results: At the conclusion of the program, the experimental group showed significant improvement compared with the control group in the following domains: physical activity (falls risk, balance, flexibility, self-efficacy, nutrition (self-efficacy and nutritional status, cognitive performance (processing speed and self-efficacy, and quality of life (general, health and functionality, social and economic status. Although some declines were reported, improvements at follow-up remained in self-efficacy for physical activity, self-efficacy for nutrition, and processing speed, and participants had better nutritional status and quality of life overall. Conclusion: Our findings show that this program promotes improvements in domains of active aging, mainly in self-efficacy beliefs as well as in quality of life in healthy elders. Keywords: active aging, successful aging, intervention program, randomized controlled trial

  11. Acanthamoeba protease activity promotes allergic airway inflammation via protease-activated receptor 2.

    Directory of Open Access Journals (Sweden)

    Mi Kyung Park

    Full Text Available Acanthamoeba is a free-living amoeba commonly present in the environment and often found in human airway cavities. Acanthamoeba possesses strong proteases that can elicit allergic airway inflammation. To our knowledge, the aeroallergenicity of Acanthamoeba has not been reported. We repeatedly inoculated mice with Acanthamoeba trophozoites or excretory-secretory (ES proteins intra-nasally and evaluated symptoms and airway immune responses. Acanthamoeba trophozoites or ES proteins elicited immune responses in mice that resembled allergic airway inflammation. ES proteins had strong protease activity and activated the expression of several chemokine genes (CCL11, CCL17, CCL22, TSLP, and IL-25 in mouse lung epithelial cells. The serine protease inhibitor phenyl-methane-sulfonyl fluoride (PMSF inhibited ES protein activity. ES proteins also stimulated dendritic cells and enhanced the differentiation of naive T cells into IL-4-secreting T cells. After repeated inoculation of the protease-activated receptor 2 knockout mouse with ES proteins, airway inflammation and Th2 immune responses were markedly reduced, but not to basal levels. Furthermore, asthma patients had higher Acanthamoeba-specific IgE titers than healthy controls and we found Acanthamoeba specific antigen from house dust in typical living room. Our findings suggest that Acanthamoeba elicits allergic airway symptoms in mice via a protease allergen. In addition, it is possible that Acanthamoeba may be one of the triggers human airway allergic disease.

  12. Promoting Children's Physical Activity in Physical Education: The Role of Active Video Gaming

    Science.gov (United States)

    Zhang, Tao; Moore, William; Gu, Xiangli; Chu, Tsz Lun; Gao, Zan

    2016-01-01

    Approximately half of the children in the United States do not meet the global physical activity guidelines, and many children adopt sedentary lifestyles. Given the fact about two-thirds children are classified as overweight or obese, traditional video games have been blamed as a major contributor to children's sedentary behavior and excessive…

  13. Activation of serotonin receptors promotes microglial injury-induced motility but attenuates phagocytic activity

    NARCIS (Netherlands)

    Krabbe, Grietje; Matyash, Vitali; Pannasch, Ulrike; Mamer, Lauren; Boddeke, Hendrikus W. G. M.; Kettenmann, Helmut

    2012-01-01

    Microglia, the brain immune cell, express several neurotransmitter receptors which modulate microglial functions. In this project we studied the impact of serotonin receptor activation on distinct microglial properties as serotonin deficiency not only has been linked to a number of psychiatric disea

  14. TNF-{alpha} promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Cheng-hu; Cao, Guo-Fan [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Jiang, Qin, E-mail: Jqin710@vip.sina.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Yao, Jin, E-mail: dryaojin@yahoo.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} induces MMP-9 expression and secretion to promote RPE cell migration. Black-Right-Pointing-Pointer MAPK activation is not critical for TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer Akt and mTORC1 signaling mediate TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer SIN1 knockdown showed no significant effect on MMP-9 expression by TNF-{alpha}. -- Abstract: Tumor necrosis factor-alpha (TNF-{alpha}) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-{alpha} promotes human RPE cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression. Inhibition of MMP-9 by its inhibitor or its neutralizing antibody inhibited TNF-{alpha}-induced in vitro RPE cell migration. Reversely, exogenously-added active MMP-9 promoted RPE cell migration. Suppression Akt/mTOR complex 1(mTORC1) activation by LY 294002 and rapamycin inhibited TNF-{alpha}-mediated MMP-9 expression. To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. RNA interference (RNAi)-mediated silencing of SIN1, a key component of mTOR complex 2 (mTORC2), had no effect on MMP-9 expression or secretion. In conclusion, this study suggest that TNF-{alpha} promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling.

  15. NUMERICAL MODELING OF THE INITIATION OF CORONAL MASS EJECTIONS IN ACTIVE REGION NOAA 9415

    International Nuclear Information System (INIS)

    Coronal mass ejections (CMEs) and solar flares are the main drivers of weather in space. Understanding how these events occur and what conditions might lead to eruptive events is of crucial importance for up to date and reliable space weather forecasting. The aim of this paper is to present a numerical magnetohydrodynamic (MHD) data-inspired model suitable for the simulation of the CME initiation and their early evolution. Starting from a potential magnetic field extrapolation of the active region (AR) NOAA 9415, we solve the full set of ideal MHD equations in a non-zero plasma-β environment. As a consequence of the applied twisting motions, a force-free-magnetic field configuration is obtained, which has the same chirality as the investigated AR. We investigate the response of the solar corona when photospheric motions resembling the ones observed for AR 9415 are applied at the inner boundary. As a response to the converging shearing motions, a flux rope is formed that quickly propagates outward, carrying away the plasma confined inside the flux rope against the gravitational attraction by the Sun. Moreover, a compressed leading edge propagating at a speed of about 550 km s–1 and preceding the CME is formed. The presented simulation shows that both the initial magnetic field configuration and the plasma-magnetic-field interaction are relevant for a more comprehensive understanding of the CME initiation and early evolution phenomenon.

  16. Antibiofilm activity of Bacillus pumilus SW9 against initial biofouling on microfiltration membranes.

    Science.gov (United States)

    Zhang, Ying; Yu, Xin; Gong, Song; Ye, Chengsong; Fan, Zihong; Lin, Huirong

    2014-02-01

    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.

  17. Metal-Induced Stabilization and Activation of Plasmid Replication Initiator RepB

    Science.gov (United States)

    Ruiz-Masó, José A.; Bordanaba-Ruiseco, Lorena; Sanz, Marta; Menéndez, Margarita; del Solar, Gloria

    2016-01-01

    Initiation of plasmid rolling circle replication (RCR) is catalyzed by a plasmid-encoded Rep protein that performs a Tyr- and metal-dependent site-specific cleavage of one DNA strand within the double-strand origin (dso) of replication. The crystal structure of RepB, the initiator protein of the streptococcal plasmid pMV158, constitutes the first example of a Rep protein structure from RCR plasmids. It forms a toroidal homohexameric ring where each RepB protomer consists of two domains: the C-terminal domain involved in oligomerization and the N-terminal domain containing the DNA-binding and endonuclease activities. Binding of Mn2+ to the active site is essential for the catalytic activity of RepB. In this work, we have studied the effects of metal binding on the structure and thermostability of full-length hexameric RepB and each of its separate domains by using different biophysical approaches. The analysis of the temperature-induced changes in RepB shows that the first thermal transition, which occurs at a range of temperatures physiologically relevant for the pMV158 pneumococcal host, represents an irreversible conformational change that affects the secondary and tertiary structure of the protein, which becomes prone to self-associate. This transition, which is also shown to result in loss of DNA binding capacity and catalytic activity of RepB, is confined to its N-terminal domain. Mn2+ protects the protein from undergoing this detrimental conformational change and the observed protection correlates well with the high-affinity binding of the cation to the active site, as substituting one of the metal-ligands at this site impairs both the protein affinity for Mn2+and the Mn2+-driven thermostabilization effect. The level of catalytic activity of the protein, especially in the case of full-length RepB, cannot be explained based only on the high-affinity binding of Mn2+ at the active site and suggests the existence of additional, lower-affinity metal binding site

  18. Physical Activity Promotion in the Preschool Years: A Critical Period to Intervene

    Directory of Open Access Journals (Sweden)

    Gary S. Goldfield

    2012-04-01

    Full Text Available The primary aim of this paper is to provide a rationale for the necessity of intervening with a physical activity intervention in the preschool years and why the daycare environment is amenable to such intervention. We also review the prevalence of physical activity, sedentary behaviour and obesity in the preschool population and the impact that these lifestyle behaviours and conditions have on the health of preschool aged children, as secondary objectives. Moreover we discuss implications for intervention and research using a “lessons learned” model based on our research team’s experience of conducting a randomized controlled trial aimed at increasing physical activity, reducing sedentary behaviour and improving motor skill development and body composition in preschoolers. Lastly, we make conclusions based on the literature and highlight issues and directions that need to be addressed in future research in order to maximize health promotion and chronic disease prevention in the pediatric population.

  19. Health-Promoting Physical Activity of Children Who Use Assistive Mobility Devices: A Scoping Review.

    Science.gov (United States)

    Jirikowic, Tracy L; Kerfeld, Cheryl I

    2016-01-01

    Children with physical disabilities who use assistive mobility devices (AMDs) are at risk for obesity and other secondary health conditions. Habitual physical activity is one lifestyle factor that may prevent obesity and contribute to overall health, and an active lifestyle in childhood improves prospects for lifelong healthy behaviors. Child, family, and environmental facilitators and barriers influence health-promoting physical activity (HPPA) for children without disabilities, but comparable models and levels of understanding for children who use AMDs are lacking. In this scoping review, we identified a similar set of child, family, and environmental facilitators and barriers relevant to HPPA participation among children who use AMDs. Noted gaps in the literature included limited reporting of AMD use, inconsistent HPPA definitions, and inadequate measurement tools for children who are nonambulatory. The identified child, family, and environmental factors provide a framework for occupational therapy practitioners and interprofessional teams to develop HPPA opportunities and interventions for an underserved population. PMID:27548861

  20. Striatal Reward Activity and Antipsychotic-Associated Weight Change in Patients With Schizophrenia Undergoing Initial Treatment

    DEFF Research Database (Denmark)

    Nielsen, Mette Ødegaard; Rostrup, Egill; Wulff, Sanne;

    2016-01-01

    anticipation is associated with amisulpride-induced weight change in antipsychotic-naive patients with schizophrenia undergoing initial treatment and to examine the association between weight change and changes in reward anticipation activity after treatment. Design, Setting, and Participants: Sixty......-nine antipsychotic-naive inpatients and outpatients with schizophrenia were included in a multimodal longitudinal cohort study from December 16, 2008, to December 11, 2013. Fifty-eight patients underwent functional magnetic resonance imaging (fMRI) while performing a monetary reward task. After 6 weeks of treatment......Importance: Weight gain is a common and serious adverse effect of antipsychotic treatment. A variable individual predisposition to development of metabolic disturbances calls for predictive biological markers. Objectives: To investigate whether attenuated striatal activity during reward...